title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series. | Conventional insertion of implantable cardioverter-defibrillator (ICD) includes an evaluation of the defibrillation threshold (DFT). Implanting an ancillary defibrillation lead in the azygos vein has been introduced as a therapeutic option in patients with "high" DFT. This study reports the efficacy and stability of azygos defibrillation coils implanted for elevated DFTs. This is a retrospective review of seven consecutive patients with right and left pectoral, single- and dual-chamber, and biventricular ICDs and elevated DFTs, in whom an azygos defibrillation coil was introduced. Addition of an azygos defibrillator lead achieved a satisfactory safety margin during single energy defibrillation efficacy testing in four out of seven patients, with success at maximum device output in two patients. No satisfactory safety margin was achieved in the remaining patient, despite the further addition of a subcutaneous defibrillation coil. No change in lead position was observed over a mean radiographic follow-up of 8 months. No complications were noted during a mean follow-up of 14 months, including no deaths, and no ICD shocks. Implanting a defibrillation coil into the azygos vein is feasible and safe. In a majority of patients with failed defibrillation efficacy testing, adding an azygos coil achieves success on repeat testing. Therefore, this technique is one option for lowering the defibrillation threshold in patients who fail DFT testing of their ICD. | 18,950,297 |
Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy. | Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT. Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 +/- 9.7 years, ejection fraction 29.9 +/- 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment. Nondiabetic patients were 366 (79.6%), noninsulin-treated diabetic patients 62 (13.9%), insulin-treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients-year in the nondiabetic group, 8.63 in noninsulin-treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin-treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6-minute walking test (6MWT) (P = 0.018). Insulin-treated diabetes is associated with a worse functional recovery and a higher mortality in patients with advanced heart failure after CRT. While cardiac death accounts for the majority of deaths in nondiabetic patients, a relevant proportion of the mortality in diabetic patients seem to result from noncardiac causes. | 18,950,300 |
A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results. | Adaptive rate sensors used in permanent pacemakers incorporate an accelerometer (XL) to increase heart rate with activity. Limited data exists regarding the relative benefit of a blended sensor (BS) (XL and minute ventilation) versus XL alone in restoring chronotropic response (CR) in chronotropically incompetent (CI) patients. One thousand five hundred thirty-eight patients from the limiting chronotropic incompetence for pacemaker recipients (LIFE) study were implanted with a pacemaker and 1,256 patients had data collected at 1 month. Patients performed a treadmill test 1-month postimplant while programmed in nonrate responsive mode (DDD-60) to determine CI. Only patients who completed at least three exercise stages and achieved a peak perceived exertion >or=16 were included in the analyses. The metabolic chronotropic relationship (MCR) slope was used to evaluate CR in 547 patients. Patients were randomized to XL or BS with a conservative fixed rate response factor (XL = 8, MV = 4). CI patients performed a follow-up 6-month treadmill test. CI prevalence in this patient population (n = 547) was 34%. No differences in baseline characteristics existed between groups. Although both groups showed significant within-group improvements in MCR slope from 1 to 6 months (both P < 0.001), the BS group had a significantly higher MCR slope at 6 months compared to the XL group (P = 0.011). Improvement in quality of life (QOL) did not differ between groups. In this general pacemaker population with CI, a BS programmed empirically restores CR more favorably than an XL sensor programmed nominally. Further studies are needed to determine if individual sensor optimization would lead to improvement in functional capacity, higher MCR slopes, and QOL. | 18,950,301 |
Three-dimensional motion analysis - an exploratory study. Part 2: reproducibility of facial movement. | To investigate the reproducibility of using spoken word as a measure of facial movement. Experimental study. Department of Dental Health and Biological Sciences, University Dental Hospital, Cardiff. 22 normal subjects. Subjects were asked to say the word 'puppy' in a normal, relaxed manner twice within a 10-second time interval. The sequence was recorded using a non-invasive, three-dimensional motion analysis image capture system (3DMDface Dynamic System) at 48 frames per second. Corresponding frames between the two utterances were aligned three-dimensionally using best fit on non-moveable points on the upper half of the face. Reproducibility was measured as the percentage point deviation between +/- 0.5 mm between two corresponding frames. Mean intrasessional reproducibility (SD) for the group was recorded at 86.2% (5.8). The reproducibility ranged from a minimum of 66.8% to a maximum of 97.5%. When the utterance was split into its two separate viseme segments (/p//u//p/ and /p//y/), the second part of the utterance was seen to be more reproducible than the first. The male group were more reproducible than the female group. Intrasessional reproducibility of the utterance 'puppy' shows high intra- and intersubject variability in this group of normal subjects and therefore further research needs to be conducted before being able to confidently use this word as a reproducible measure of facial movement. | 18,950,319 |
Temporomandibular joint adaptations following two-phase therapy: an MRI study. | To document the alterations within the condyle-glenoid fossa (C-GF) complex and the positional changes of the glenoid fossa in the cranium after removable functional appliance therapy and after the completion of fixed appliance therapy. The Department of Orthodontics, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India. The study sample consisted of 12 growing children (eight girls and four boys) between 10 and 14 years of age with skeletal Class II division 1 malocclusion selected on well defined criteria. All patients were treated with either the Twin Block or the Bionator appliance followed by fixed appliances. Mean total treatment duration was 28 months. The changes in and around the C-GF complex were evaluated using MRI at pre-treatment stage, after functional appliance therapy and at the completion of fixed mechanotherapy. Forward condylar position within the glenoid fossa and articular disc retrusion with respect to the condylar head were statistically significant after functional appliance therapy. However, the condyles had a relatively concentric position within the glenoid fossa, while the articular disc resumed its pre-treatment position at the end of the treatment. Linear measurements from the centre of the external auditory meatus to the post-glenoid spine revealed a 1.3-mm forward relocation of the post-glenoid spine along the Frankfurt Horizontal plane. Forward relocation of the C-GF complex seems to be one of the mechanisms of action of functional appliances, while the internal anatomic arrangement within the temporomandibular joint (TMJ) complex normalizes to its pre-treatment position. | 18,950,321 |
Anesthetic management of gastrochisis--a review of our practice over the past 5 years. | Surgical closure of gastrochisis has traditionally been performed under general anesthesia followed by admission to intensive care and postoperative ventilation. We reviewed the management of these neonates in our hospital over the past 5 years to identify changes in practice and possible factors which affect the perioperative course. We retrospectively identified cases of gastrochisis undergoing repair from June 2002 to May 2007. Details of the demographic data, preoperative factors, intraoperative anesthetic and surgical management and postoperative care were collected from the anesthetic chart, operative record and patient notes. Forty-eight self-ventilating neonates underwent operative repair in theatre. A neuraxial local anesthetic block was performed as part of the anesthetic technique in 22 patients. There was a significant difference in the need for postoperative ventilation in this group (23%) when compared with a traditional opioid-based method of providing analgesia (88%, P < 0.05). This difference was seen in both term and preterm babies. Conclusions are difficult when analyzing retrospective data in patients with a variety of factors. The results suggest that anesthesia which includes a regional technique is a valid method in these cases. Traditional opioid analgesia when compared to regional techniques may be associated with increased need for postoperative ventilation. | 18,950,329 |
The hemodynamic effects of newborn caudal anesthesia assessed by transthoracic echocardiography: a randomized, double-blind, controlled study. | Caudal anesthesia has been increasingly used in abdominal, urinary tract, and lower extremity surgery of infants. However, little was known about the hemodynamic effects of caudal anesthesia in them, especially in neonates. The purpose of this prospective study was designed to investigate the hemodynamic alterations by transthoracic echocardiography in newborn baby after caudal anesthesia with plain Bupivacaine or with epinephrine added Bupivacaine. Thirty full-term newborn infants scheduled for lower abdominal or urinary tract surgery were randomly allocated into three groups (n = 10 each) as follows: (i) GA group: general anesthesia with sevoflurane; (ii) GA+CP group: GA with sevoflurane, combined with caudal anesthesia of plain Bupivacaine (1.25 ml x kg(-1) of 0.2%); (iii) GA+CA group: sevoflurane GA combined with caudal anesthesia of epinephrine-added Bupivacaine (1.25 ml x kg(-1) of 0.2% Bupivacaine plus 1/200,000 epinephrine). Cardiac output (CO), arterial blood pressure, and heart rate were measured before (T-5) and 5(T5), 10(T10), 15(T15) min after performance of caudal anesthesia. In GA group, no significant hemodynamic alteration was observed in comparison with T-5, except HR, which decreased by 7% at T15; In GA+CP group, compared with T-5, HR decreased significantly at T5, T10 and T15, respectively, by 6%, 7% and 10%. And also CO decreased significantly at T15 by 8% compared with T-5; In GA+CA group, no significant hemodynamic alteration was observed expect diastolic arterial blood, which decreased significantly at T15 by 10% compared with T-5; At T15, the larger decrease of systolic arterial blood in GA+CP group and GA+CA group vs (GA) group (P < 0.05). The study shows the stability of hemodynamic variables during caudal anesthesia with Bupivacaine and with epinephrine-added Bupivacaine in newborn infants. | 18,950,332 |
Factors impacting on psychological distress and recovery after the 2004 Niigata-Chuetsu earthquake, Japan: community-based study. | This study was undertaken 5 months after the 2004 Niigata-Chuetsu earthquake in Japan to assess factors that impacted on psychological distress and its recovery. Three thousand and twenty-six adult victims who lived in temporary shelter and in seriously damaged areas were evaluated by questionnaire. The questionnaire queried subject profile, degree of house damage, health status, and psychological distress using a 5-point scale before, immediately and 5 months after the earthquake. Immediately after the earthquake, 59.3% of the subjects had psychological distress. At 5 months after the earthquake, however, this percentage decreased to 21.8%. The psychological distress immediately after the earthquake was significantly serious in victims who: (i) were female; (ii) felt stronger fear of the earthquake and the aftershocks; (iii) lived at home or office after the earthquake; and (iv) were injured due to the earthquake or suffered from sickness after the earthquake. In contrast, the factors impairing psychological recovery 5 months after the earthquake were as follows: (i) being with unfamiliar member(s) during the night after the earthquake; (ii) serious house damage; (iii) living in temporary shelter or at a relative's home after the earthquake; and (iv) physical illness after the earthquake. Despite differences between disasters, these results were consistent with those in some previous studies and may be useful for long-term mental care support. | 18,950,368 |
Exploring the burden of the primary family caregivers of schizophrenia patients in Taiwan. | The purpose of the present study was to investigate the burden of the primary family caregivers of schizophrenia patients and the factors that affect caregiver burden. A total of 126 pairs of patients and their primary family caregivers were recruited from the day care and acute wards of two teaching general hospitals. Demographic information was collected. All patients went through an interview with a senior psychiatrist using the Brief Psychiatric Rating Scale (BPRS). The Caregiver Burden Inventory-Brief Version and the Chinese Health Questionnaire (CHQ) were used to assess the caregiver burden and the caregivers' health condition. One-way analysis of variance and Pearson correlation were used to analyze the relationship between demographic factors and caregiver burden. Multiple regression was used to analyze predictors of burden of caregivers. Statistical significance in this study was defined as P <or= 0.05. The caregiver burden scores (25.9 +/- 10.7; range, 3-61) indicated a moderate burden level. Among the five dimensions of burden, caregiver anxiety (2.13 +/- 0.86) was the highest, followed by dependency of the patient (1.85 +/- 1.02), feeling shame and guilt (1.56 +/- 1.02), and family interference (1.43 +/- 0.83). The burden level of stigmata (1.32 +/- 1.24) was the lowest. The first three rankings of burden were 'I worry about his/her safety when he/she is alone' (2.26 +/- 1.15), 'I worry that she/he will become sick at any time' (2.23 +/- 1.10), and 'I feel he/she depends on me very much' (2.02 +/- 1.29). Patient satisfaction with medical staff support (P = 0.00), CHQ scores of the caregivers (P = 0.00), and the BPRS scores of the patients (P = 0.01) were significantly associated with the caregiver burden scores. The physical and mental health condition of the primary family caregiver of schizophrenia patients was the most important factor determining the caregiver burden level. Comprehensive multidisciplinary care of chronic schizophrenia patients is needed, care that supports the needs and improves the psychiatric symptoms of the patients, helps to decrease the caregiver burden level, and facilitates family participation in treatment. | 18,950,369 |
Family needs and related factors in caring for a family member with mental illness: adopting assertive community treatment in Japan where family caregivers play a large role in community care. | In Japan the family plays a large role in community care for persons with mental illness; therefore the aim of the present study was to describe the needs of family caregivers related to assertive community treatment (ACT) and to analyze the relationship of these needs to underlying factors. Participants were recruited from the membership of three family associations of persons with mental illness. Of the 224 family members, 152 (67.9%) completed a self-report questionnaire consisting of the following measures: demographic variables, family life difficulty scale, global burden, general life satisfaction, subjective health status, family rejection scale, quantity of supportive behaviors, and needs for ACT. More than 70% of participants reported that service components of ACT would be beneficial, especially in the future. Functions that helped maintain the ordinary routine of family life were significantly correlated with current needs for ACT. When a person has chronic mental illness the family has many needs related to ACT. When functions that maintained the ordinary routine of family life were disturbed, the need for ACT support increased. Elderly parents or siblings were also concerned about the future, when caring for the member with mental illness would become more difficult. | 18,950,379 |
Plasma amitriptyline level after acute administration, and driving performance in healthy volunteers. | Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions. In this double-blinded study, 17 healthy male volunteers were given an acute, single, 25-mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high-performance liquid chromatography. A significant positive correlation was observed between the plasma amitriptyline concentration and road-tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence. Amitriptyline produces a concentration-related impairment on road-tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving. | 18,950,383 |
Microphthalmia with linear skin defects: a case report and review. | Microphthalmia with linear skin defects syndrome is an X-linked dominant disorder characterized by microphthalmia and other ocular anomalies as well as linear, jagged skin defects typically involving the scalp, face, neck, and upper trunk. Other associated characteristics include short stature, developmental delay, congenital heart defects, diaphragmatic hernia, agenesis of the corpus callosum, anencephaly, hydrocephalus, and seizures. Microphthalmia with linear skin defects syndrome is now known to be associated with a deletion of the X chromosome at Xp22. This is an area that has been found to include the HCCS gene, which encodes a holocytochrome c-type synthase believed to be critical in the regulation of apoptosis. We present a patient with classic clinical and genetic findings of MLS syndrome and discuss the primary characteristics and management of this disorder. | 18,950,397 |
Enhanced response of childhood psoriasis to narrow-band UV-B phototherapy with preirradiation use of mineral oil. | Studies in adults show that pretreatment with an optimal emollient may improve transmission of ultraviolet-B. In our study, we evaluated whether the preirradiation use of mineral oil enhanced the efficacy of narrow-band ultraviolet-B phototherapy in childhood psoriasis. Twenty children, aged 5 to 14 years with widespread, symmetrical psoriasis involving >20% body surface area were enrolled in a prospective, single-blind, controlled study. Mineral oil was applied prior to irradiation over one half of the body and the other half was emollient-free control. Narrow-band ultraviolet-B phototherapy was administered to whole body twice a week on nonconsecutive days with initial dose of 50 mJ/cm(2) and increment of 10% at each session. Clinical response was evaluated as grades of erythema, scaling and induration, area of involvement and modified psoriasis area severity index score on each side at baseline, 3, 6, 9, and 12 weeks. Two patients dropped out, 18 patients completed the study. Significantly greater improvement (p < 0.05) in scaling, induration, area of involvement, and modified psoriasis area severity index score was seen on the mineral oil pretreated side as early as 3 weeks and was maintained throughout the study. Difference in erythema was noticed later at 6 weeks. The cumulative dose for clearance was significantly lower on the emollient pretreated side. No adverse effects were observed with mineral oil or narrow-band ultraviolet-B phototherapy. We conclude that preirradiation use of mineral oil enhances the therapeutic efficacy of narrow-band ultraviolet-B phototherapy in children with widespread psoriasis. | 18,950,402 |
Female reproductive output in a Mediterranean shrub: effects from inflorescence to population. | Inflorescence effects have been poorly studied, in spite of the functional relevance of the inflorescence in fruit and seed ecology. The present study focused on the effects of inflorescence size and phenology, and flower position within the inflorescence, in relation to fruit and seed production of the Mediterranean shrub Ononis fruticosa. Variability in fruit and seed production, seed weight and germination were estimated and modelled. Results confirmed that the most important predictors in seed production were inflorescence flowering time and flower position within the inflorescence. Thus, the number of mature seeds per fruit was higher in earlier inflorescences and in basal positions. On the other hand, predation was higher in fruits in basal positions. In fact, seed predation seemed to be the most important factor controlling final seed production. Models at the plant level suggested a negative incidence of geitonogamous pollination and resource limitation, which were also observed at the fruit level. This study confirmed the relevance of inflorescence effects on the reproductive output of O. fruticosa. Although the underlying processes could not be identified, our results provide several hypotheses for future experimental studies. | 18,950,424 |
The phospholipase A inhibitor, aristolochic acid, disrupts cortical microtubule arrays and root growth in Arabidopsis. | The role of phospholipase A(2) in Arabidopsis root growth and microtubule organisation was investigated using a specific inhibitor, aristolochic acid. At 0.5-1.5 microm concentrations, this inhibitor reduced root elongation and caused radial swelling of the root tip. The normally transverse cortical microtubules in root tip cells became progressively more disorganised with increasing concentrations of the inhibitor. Microtubule disorganisation also occurred in leaf epidermal cells of Allium porrum. We propose that phospholipase A(2) is involved in microtubule organisation and anisotropic growth in a manner similar to that reported previously for phospholipase D, thus broadening the significance of phospholipid signalling in microtubule organisation in plants. | 18,950,430 |
Combination therapy with flupirtine and opioid: studies in rat pain models. | Flupirtine is an established clinical analgesic for mild to moderate musculoskeletal pain states. It has recently been shown to be a KCNQ2-3 potassium channel opener. These experiments were performed to see if this property could be useful in treating pain states characterized by central sensitization with the drug either given alone or in combination with morphine. Experiments were performed in rats in an observer-blinded fashion with vehicle controls. Nonsedating doses of flupirtine, morphine, and combinations containing both drugs were defined using the rotarod test and open-field activity monitoring. Dose-response relationships were determined for nonsedating doses of both drugs given alone and together in combination in causing antinociception in two nociception paradigms: carrageenan paw inflammation and streptozotocin-induced diabetic neuropathy. Flupirtine and morphine, when given alone at the highest nonsedating doses, caused slight to moderate antinociception in both paradigms. Flupirtine also caused significant increases in morphine antinociception in both models. In carrageenan paw inflammation, complete reversal of carrageenan-induced hyperalgesia was caused by 10 mg/kg flupirtine in combination with 0.4 mg/kg morphine. These doses of the two drugs were ineffective when given alone, but the combination caused complete antinociception in this model of inflammatory pain. In the diabetic neuropathy model, morphine 3.2 mg/kg given alone caused no significant antinociception. However, a lower dose of morphine (1.6 mg/kg shown to be ineffective when it was given alone) given in combination with flupirtine 10 mg/kg caused highly significant antinociceptive effects causing complete reversal of hyperalgesia caused by diabetic neuropathy (P < 0.001, one-way analysis of variance). This combination of drugs was not sedating. Flupirtine increases morphine antinociception without causing an increase in sedation. Flupirtine should be investigated as an adjunct analgesic with opioids for the management of patients with pain states involving central sensitization. | 18,950,446 |
Facial pain: a possible therapy with stellate ganglion block. | The goal of the present study is to verify the efficacy of stellate ganglion block (SGB) in the treatment of facial pain that can be found in different pathological syndromes, and also to examine whether the efficacy is dependent upon when this therapy is administered. Fifty patients (divided into two randomized groups) with facial pain caused by traumas, iatrogenic issues, herpes zoster, or neurological pathologies participated in this study. The first group (N = 25) was treated with SGB produced by 10 administrations of 10 mg of levobupivacaine given every other day, followed by one administration per month for 6 months thereafter. The second group was treated with the drugs tramadol 100 mg/day and gabapentin 1800 mg/day orally for 6 months; during the 7th month they were given SGB therapy using the same methodology as that described for the first group. Before treatment, the mean visual analog scale (VAS) pain score for the first group was 8.89; after the 10th block treatment it was just 0.2, and it remained at that reduced level for the 6th and 12th months. Before treatment, the mean VAS pain score for the second group was 8.83; after the 20th day on medication it was reduced to 4.1, after 6 months it was 5.7 and after 12 months it was 4.9. Our results indicate that patients must be treated with SGB therapy precociously to receive its full benefits. | 18,950,449 |
Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation. | Killer immunoglobulin-like receptor (KIR)-ligand mismatched natural killer (NK) cells play a key role in achieving durable remission after haplo-identical transplantation for acute myeloid leukaemia. We investigated the feasibility of transfusing haplo-identical, T-cell depleted, KIR-ligand mismatched NK cells, after conditioning therapy with melphalan and fludarabine, to patients with advanced multiple myeloma (MM) followed by delayed rescue with autologous stem cells. No graft-versus-host disease or failure of autologous stem cells to engraft was observed. There was significant variation in the number of allo-reactive NK cells transfused. However, all NK products containing allo-reactive NK cells killed the NK cell target K562, the MM cell line U266, and recipient MM cells when available. Post NK cell infusion there was a rise in endogenous interleukin-15 accompanied by increasing donor chimaerism. Donor chimaerism was eventually lost, which correlated with the emergence of potent host anti-donor responses indicating that the immunosuppressive properties of the conditioning regimen require further optimization. Further, blocking of inhibitory KIR-ligands with anti-human leucocyte antigen antibody substantially enhanced killing of MM cells thus highlighting the potential for modulating NK/MM cell interaction. Encouragingly, 50% of patients achieved (near) complete remission. These data set the stage for future studies of KIR-ligand mismatched NK cell therapy in the autologous setting. | 18,950,462 |
Benchmarking and reducing length of stay in Dutch hospitals. | To assess the development of and variation in lengths of stay in Dutch hospitals and to determine the potential reduction in hospital days if all Dutch hospitals would have an average length of stay equal to that of benchmark hospitals. The potential reduction was calculated using data obtained from 69 hospitals that participated in the National Medical Registration (LMR). For each hospital, the average length of stay was adjusted for differences in type of admission (clinical or day-care admission) and case mix (age, diagnosis and procedure). We calculated the number of hospital days that theoretically could be saved by (i) counting unnecessary clinical admissions as day cases whenever possible, and (ii) treating all remaining clinical patients with a length of stay equal to the benchmark (15th percentile length of stay hospital). The average (mean) length of stay in Dutch hospitals decreased from 14 days in 1980 to 7 days in 2006. In 2006 more than 80% of all hospitals reached an average length of stay shorter than the 15th percentile hospital in the year 2000. In 2006 the mean length of stay ranged from 5.1 to 8.7 days. If the average length of stay of the 15th percentile hospital in 2006 is identified as the standard that other hospitals can achieve, a 14% reduction of hospital days can be attained. This percentage varied substantially across medical specialties. Extrapolating the potential reduction of hospital days of the 69 hospitals to all 98 Dutch hospitals yielded a total savings of 1.8 million hospital days (2006). The average length of stay in Dutch hospitals if all hospitals were able to treat their patients as the 15th percentile hospital would be 6 days and the number of day cases would increase by 13%. Hospitals in the Netherlands vary substantially in case mix adjusted length of stay. Benchmarking--using the method presented--shows the potential for efficiency improvement which can be realized by decreasing inputs (e.g. available beds for inpatient care). Future research should focus on the effect of length of stay reduction programs on outputs such as quality of care. | 18,950,476 |
Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans. | Invasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis. However, not all C. albicans strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the in vitro phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence. In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion in vitro. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an in vitro invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, in vitro transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal in vitro growth conditions. Our data suggest that the reason for differential virulence of C. albicans strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes. | 18,950,481 |
Trends in malaria morbidity following the introduction of artesunate plus amodiaquine combination in M'lomp village dispensary, south-western Senegal. | In Thailand, South Africa and Zanzibar, a decrease in malaria morbidity was observed following the introduction of artemisinin-based combination therapy (ACT). In Senegal, therapeutic trials supervised the in vivo efficacy of artesunate plus amodiaquine from 1999 to 2005 at the M'lomp village dispensary. The trends in malaria morbidity in this village were evaluated from 2000 to 2002. Each year, between July and December inclusive, fevers treated with antimalarials and slide-proven, uncomplicated malaria cases were collected from dispensary health records. Data were also collected in 1998, just prior to ACT introduction. Pearson's chi square tests and Student tests were used to compare two percentages or two means respectively (alpha = 0.05). Between 1998 and 2002, the total number of fevers treated with antimalarials and their repetitiveness progressively decreased: From 2824 to 945 fevers and from 17.6% to 9.7% (RR1998-2002 = 0.55; [0.44-0.69]; p < 0.0001) respectively. Considering uncomplicated malaria cases only, a decrease was observed in their total number between 2001 and 2002, from 953 to 570 cases. The incidence rate and repetitiveness also decreased. The incidence rate fell from 46.1% in 2001 to 37.5% in 2002 (p < 0.0001) and the repetitiveness decreased from 13.0% in 2000 to 6.6% in 2002 (RR2000-2002 = 0.51; [0.35-0.72]; p = 0.0001). The percentage of uncomplicated malaria cases treated with ACT increased, from 18.9% in 2000 to 64.0% in 2002, making it tempting to conclude an impact on malaria morbidity. Nonetheless, the decline in incidence rate of uncomplicated malaria was slight and a lower recorded rainfall was reported in 2002 which could also explain this decline. The context in which ACT is introduced affects the impact on malaria morbidity. In M'lomp, in contrast to studies in Thailand, South Africa and Zanzibar, ACT coverage of malaria cases was low and no vector control measure was deployed. Moreover, the malaria transmission level is higher. In sub-Saharan countries, in order to optimize the impact on malaria morbidity, ACT deployment must be supported, on the one hand, by a strengthening of public health system to ensure a high ACT coverage and, on the other hand, by others measures, such vector control measures. | 18,950,485 |
Evolutionary history of histone demethylase families: distinct evolutionary patterns suggest functional divergence. | Histone methylation can dramatically affect chromatin structure and gene expression and was considered irreversible until recent discoveries of two families of histone demethylases, the KDM1 (previously LSD1) and JmjC domain-containing proteins. These two types of proteins have different functional domains and distinct substrate specificities. Although more and more KDM1 and JmjC proteins have been shown to have histone demethylase activity, our knowledge about their evolution history is limited. We performed systematic phylogenetic analysis of these histone demethylase families and uncovered different evolutionary patterns. The KDM1 genes have been maintained with a stable low copy number in most organisms except for a few duplication events in flowering plants. In contrast, multiple genes for JmjC proteins with distinct domain architectures were present before the split of major eukaryotic groups, and experienced subsequent birth-and-death evolution. In addition, distinct evolutionary patterns can also be observed between animal and plant histone demethylases in both families. Furthermore, our results showed that some JmjC subfamilies contain only animal genes with specific demethylase activities, but do not have plant members. Our study improves the understanding about the evolutionary history of KDM1 and JmjC genes and provides valuable insights into their functions. Based on the phylogenetic relationship, we discussed possible histone demethylase activities for several plant JmjC proteins. Finally, we proposed that the observed differences in evolutionary pattern imply functional divergence between animal and plant histone demethylases. | 18,950,507 |
A user-friendly Matlab program and GUI for the pseudorotation analysis of saturated five-membered ring systems based on scalar coupling constants. | The advent of combinatorial chemistry has revived the interest in five-membered heterocyclic rings as scaffolds in pharmaceutical research. They are also the target of modifications in nucleic acid chemistry. Hence, the characterization of their conformational features is of considerable interest. This can be accomplished from the analysis of the 3J(HH) scalar coupling constants. A freely available program including an easy-to-use graphical user interface (GUI) has been developed for the calculation of five-membered ring conformations from scalar coupling constant data. A variety of operational modes and parameterizations can be selected by the user, and the coupling constants and electronegativity parameters can be defined interactively. Furthermore, the possibility of generating high-quality graphical output of the conformational space accessible to the molecule under study facilitates the interpretation of the results. These features are illustrated via the conformational analysis of two 4'-thio-2'-deoxynucleoside analogs. Results are discussed and compared with those obtained using the original PSEUROT program. A user-friendly Matlab interface has been developed and tested. This should considerably improve the accessibility of this kind of calculations to the chemical community. | 18,950,513 |
A novel approach to glaucoma screening and education in Nepal. | Glaucoma is a major cause of blindness worldwide and an increasingly significant global health problem. Glaucoma prevention and management efforts have been challenging due to inherent difficulty in developing a simple and cost-effective screening plan, limited access to health care and educational resources, poverty, and inadequate knowledge of the disease, particularly in developing countries. Starting in 2004 the Tilganga Eye Centre in Kathmandu, Nepal has provided targeted glaucoma screening, treatment, and education through a combination of clinical outreach programs and educational activities for patients. A simple, age-based glaucoma screening algorithm was incorporated into three one-day cataract screening clinics. Using this algorithm, patients who were newly diagnosed with glaucoma were referred to TEC, where medication and surgery were provided free of charge through private donor funding. In addition, we describe two ongoing educational programs for increasing glaucoma awareness: an annual Glaucoma Awareness Week (which includes free screening, treatment, and counseling), and a repeating lecture series which generates new counselors. From 2004 to 2007 screening at the annual Glaucoma Awareness Week resulted in the diagnosis of 120 individuals with glaucoma, or 7.6% of total registrants. Attendance increased annually with a trend toward an increasing number of returning patients but a decreasing percentage of newly diagnosed patients, though the absolute numbers have remained relatively stable (range 21 to 38). Data from the three one-day screening clinics in 2006 show that approximately 2 to 4% of patients 50 years of age or older per clinic were newly diagnosed with POAG. This multi-faceted approach appears to successfully identify individuals with glaucoma and provide treatment to those who would otherwise not be able to afford it. While more data is needed to validate this model, specifically regarding the effectiveness of educational activities, long-term visual outcomes, and medication compliance, it may serve as a useful framework for other developing countries with similarly limited resources. | 18,950,530 |
History of malaria control in Tajikistan and rapid malaria appraisal in an agro-ecological setting. | Reported malaria cases in rice growing areas in western Tajikistan were at the root of a rapid appraisal of the local malaria situation in a selected agro-ecological setting where only scarce information was available. The rapid appraisal was complemented by a review of the epidemiology and control of malaria in Tajikistan and Central Asia from 1920 until today. Following a resurgence in the 1990s, malaria transmission has been reduced considerably in Tajikistan as a result of concerted efforts by the government and international agencies. The goal for 2015 is transmission interruption, with control interventions and surveillance currently concentrated in the South, where foci of Plasmodium vivax and Plasmodium falciparum persist. The rapid malaria appraisal was carried out in six communities of irrigated rice cultivation during the peak of malaria transmission (August/September 2007) in western Tajikistan. In a cross-sectional survey, blood samples were taken from 363 schoolchildren and examined for Plasmodium under a light microscope. A total of 56 farmers were interviewed about agricultural activities and malaria. Potential Anopheles breeding sites were characterized using standardized procedures. A literature review on the epidemiology and control of malaria in Tajikistan was conducted. One case of P. vivax was detected among the 363 schoolchildren examined (0.28%). The interviewees reported to protect themselves against mosquito bites and used their own concepts on fever conditions, which do not distinguish between malaria and other diseases. Three potential malaria vectors were identified, i.e. Anopheles superpictus, Anopheles pulcherrimus and Anopheles hyrcanus in 58 of the 73 breeding sites examined (79.5%). Rice paddies, natural creeks and man-made ponds were the most important Anopheles habitats. The presence of malaria vectors and parasite reservoirs, low awareness of, and protection against malaria in the face of population movements and inadequate surveillance may render local communities vulnerable to potential epidemics. To attain malaria transmission interruption in Tajikistan by 2015, there is a need for rigorous surveillance along with strengthening of primary health care facilities for effective case management, and possibly a more differentiated vector control strategy based on additional local evidence. | 18,950,536 |
Are we getting closer to a Nobel prize for unraveling preeclampsia? | Preeclampsia is the major cause of maternal and fetal morbidity and mortality, involving 15% to 20% of pregnancies in developed countries and even more in less developed parts of the world. Superficial placentation driven by immune maladaptation, with subsequently reduced concentrations of angiogenic growth factors and increased placental debris in the maternal circulation, are likely responsible. Recent advances suggest that antiangiogenic factors (soluble fms-like tyrosine receptor kinase and soluble endoglin), altered relaxin-mediated mechanisms leading to impaired nitric oxide production through asymmetrical dimethylarginine production, and activating antibodies directed at the angiotensin II type 1 receptor may be responsible. The field of preeclampsia research is enjoying a well-deserved blossoming of novel ideas and approaches. We hope the activity will lead to much earlier diagnostic capacities and novel prophylactic treatments. The prize will go to the affected women and their afflicted children. For the investigators in the area, such a prize would be welcome. | 18,950,552 |
Genetic diversity of transmission blocking vaccine candidate (Pvs25 and Pvs28) antigen in Plasmodium vivax clinical isolates from Iran. | The leading candidates for a Transmission Blocking Vaccine (TBV) in Plasmodium vivax parasite are the ookinete surface protein 25 (Pvs25) and Pvs28, which their phase I clinical trial is ongoing. Therefore, we carried out survey of polymorphisms of the pvs25 and pvs28 genes in P. vivax populations that are circulating in the two malaria areas of contrasting endemicity in Iran, before field application of the TBV. To characterize the polymorphisms of pvs25 and pvs28 genes, 50 isolates were analyzed by sequencing method and their gene structure was compared with parasite populations from India, Bangladesh, Indonesia, Thailand, Mexico and Brazil. Three mutations were detected in pvs25 and pvs28 including Q87K, E97Q, I130T and M52L, T65K, T140S with two and four distinct haplotypes, in comparison with the Sal I sequence type, respectively. Both haplotypes of Pvs25 were found among northern and southern P. vivax isolates; however, only two and three of the Pvs28 variants were observed among the northern and southern isolates, respectively. In conclusion, the present results show the limited sequence polymorphism of the pvs25 and pvs28 genes among field P. vivax population in Iran. These results highly encourage with respect to applicability of Pvs25 and Pvs28-based vaccine against P. vivax infection in the region, where these parasites are prevalent, whether these occur in the temperate or tropical zones. | 18,950,597 |
Biosensor plates detect mitochondrial physiological regulators and mutations in vivo. | The measurement of mitochondrial activity in living cells is usually not straightforward, even though it is quite important in physiological and pathophysiological processes. We describe a high-throughput method for measurement of mitochondrial oxygen consumption in living cells, based on the Becton-Dickinson Biosensor plates. | 18,950,600 |
Effects of hemolysis and lipemia on the COBAS salicylate and acetaminophen assays compared to GDS assays. | We compared the COBAS(R) acetaminophen and salicylate assays (Roche Diagnostics) with the Stanbio GDS assays (Stanbio Laboratories) that are currently used in our laboratory with respect to interferences from hemolysis and lipemia. Acetaminophen and salicylate were added into human serum with varying concentrations of hemoglobin or Intralipid to generate a range of acetaminophen and salicylate concentrations. Then the COBAS and GDS assays were used to measure the apparent drug concentrations; the H and L indices were measured to determine the extent of hemolysis and lipemia present in each specimen. Both hemolysis and lipemia have less effect on the COBAS(R) acetaminophen and salicylate assays than on the GDS assays. The COBAS assays for acetaminophen and salicylate are preferable to the current GDS assays in clinical toxicology laboratories. | 18,950,612 |
Experimental study of intracellular ice growth in human umbilical vein endothelial cells. | Study of the intracellular ice formation (IIF) and growth is essential to the mechanistic understanding of cellular damage through freezing. In the aid of high speed and high resolution cryo-imaging technology, the transient intracellular ice formation and growth processes of the attached human umbilical vein endothelial cells (HUVEC) were successfully captured during freezing. It was found that the intracellular ice nucleation site was on the cell membrane closer to the nucleus. The ice growth was directional and toward the nucleus, which covered the whole nucleus before growing into the cytoplasm. The crystal growth rate in the nucleus was much larger than that in the cytoplasm, and its morphology was influenced by the cooling rate. During the thawing process, small crystals fused into larger ones inside the nucleus. Moreover, the cumulative fraction of the HUVEC with IIF was mainly dependent on the cooling rate not the confluence of the cells attached. | 18,950,613 |
Toxoplasma gondii: Identification and characterization of bradyzoite-specific deoxyribose phosphate aldolase-like gene (TgDPA). | Toxoplasma gondii undergoes stage conversion from tachyzoites to bradyzoites in intermediate hosts. There have been many reports on bradyzoite-specific genes which are thought to be involved in stage conversion. Here, we described a novel T. gondii deoxyribose phosphate aldolase-like gene (TgDPA) expressing predominantly in bradyzoites. The TgDPA gene encodes 286 amino acids having a predicted molecular weight of 31kDa. Sequence analysis revealed that TgDPA had a deoxyribose phosphate aldolase (DeoC) domain with about 30% homology with its Escherichia coli counterpart. RT- and quantitative PCR analyses showed that the TgDPA gene was more expressed in bradyzoites and that its expression gradually increased during in vitro tachyzoite-to-bradyzoite stage conversion. A polyclonal antibody against recombinant TgDPA protein was raised in rabbits, and immunofluorescent analysis demonstrated that TgDPA was expressed in bradyzoites in vivo and in vitro. These findings indicate that the TgDPA gene is a new bradyzoite-specific marker and might play a role in bradyzoites. | 18,950,626 |
ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality. | PtdIns(3,5)P(2) (with PtdIns indicating phosphatidylinositol) is vital in the differentiation and development of multicellular organisms because knockout of the PtdIns(3,5)P(2)-synthesizing enzyme PIKfyve (phosphoinositide kinase for position 5 containing a FYVE finger domain) or its associated regulator ArPIKfyve is lethal. In previous work with endogenous proteins, we identified that Sac3, a phosphatase that turns over PtdIns(3,5)P(2), associates with the PIKfyve-ArPIKfyve biosynthetic complex. However, whether the three proteins suffice for the organization/maintenance of this complex [referred to as the PAS (PIKfyve-ArPIKfyve-Sac3) complex], how they interact with one another, and what the functional relevance of this ternary association would be remained unresolved. Using co-immunoprecipitation analyses in transfected mammalian cells with increased or decreased levels of the three proteins, singly or in double versus triple combinations, herein we report that the triad is sufficient to form and maintain the PAS complex. ArPIKfyve is the principal organizer interacting with both Sac3 and PIKfyve, whereas Sac3 is permissive for maximal PIKfyve-ArPIKfyve association in the PAS complex. We further identified that ArPIKfyve scaffolds the PAS complex through homomeric interactions, mediated via its conserved C-terminal domain. Introduction of the C-terminal peptide fragment of the ArPIKfyve-ArPIKfyve contact sites effectively disassembled the PAS complex and reduced the in vitro PIKfyve lipid kinase activity. Exploring insulin-regulated GLUT4 translocation in 3T3L1 adipocytes as a functional readout, a process that is positively regulated by PIKfyve activity and ArPIKfyve levels, we determined that ectopic expression of the ArPIKfyve C-terminal peptide inhibits GLUT4 surface accumulation. Our data indicate that the PAS complex is organized to provide optimal PIKfyve functionality and is maintained via ArPIKfyve homomeric and heteromeric interactions. | 18,950,639 |
Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction. | In this review we discuss the evidence that drug addiction, defined as a maladaptive compulsive habit, results from the progressive subversion by addictive drugs of striatum-dependent operant and Pavlovian learning mechanisms that are usually involved in the control over behaviour by stimuli associated with natural reinforcement. Although mainly organized through segregated parallel cortico-striato-pallido-thalamo-cortical loops involved in motor or emotional functions, the basal ganglia, and especially the striatum, are key mediators of the modulation of behavioural responses, under the control of both action-outcome and stimulus-response mechanisms, by incentive motivational processes and Pavlovian associations. Here we suggest that protracted exposure to addictive drugs recruits serial and dopamine-dependent, striato-nigro-striatal ascending spirals from the nucleus accumbens to more dorsal regions of the striatum that underlie a shift from action-outcome to stimulus-response mechanisms in the control over drug seeking. When this progressive ventral to dorsal striatum shift is combined with drug-associated Pavlovian influences from limbic structures such as the amygdala and the orbitofrontal cortex, drug seeking behaviour becomes established as an incentive habit. This instantiation of implicit sub-cortical processing of drug-associated stimuli and instrumental responding might be a key mechanism underlying the development of compulsive drug seeking and the high vulnerability to relapse which are hallmarks of drug addiction. | 18,950,658 |
Evidence for parallel explicit and implicit sequence learning systems in older adults. | Some research indicates that explicit learning of a sequence can impair procedural learning, particularly in populations with reduced cognitive capacity. However, these studies usually do not distinguish the effects of explicit processes on procedural learning from their effects on performance. The current study demonstrates that explicit learning affects performance, but not procedural sequence learning, in healthy older adults even when sequences are complex. These findings support capacity-independent theories which propose that procedural and declarative learning operate in parallel. | 18,950,663 |
Neurocomputational models of basal ganglia function in learning, memory and choice. | The basal ganglia (BG) are critical for the coordination of several motor, cognitive, and emotional functions and become dysfunctional in several pathological states ranging from Parkinson's disease to Schizophrenia. Here we review principles developed within a neurocomputational framework of BG and related circuitry which provide insights into their functional roles in behavior. We focus on two classes of models: those that incorporate aspects of biological realism and constrained by functional principles, and more abstract mathematical models focusing on the higher level computational goals of the BG. While the former are arguably more "realistic", the latter have a complementary advantage in being able to describe functional principles of how the system works in a relatively simple set of equations, but are less suited to making specific hypotheses about the roles of specific nuclei and neurophysiological processes. We review the basic architecture and assumptions of these models, their relevance to our understanding of the neurobiological and cognitive functions of the BG, and provide an update on the potential roles of biological details not explicitly incorporated in existing models. Empirical studies ranging from those in transgenic mice to dopaminergic manipulation, deep brain stimulation, and genetics in humans largely support model predictions and provide the basis for further refinement. Finally, we discuss possible future directions and possible ways to integrate different types of models. | 18,950,662 |
Regional distribution of calcium elevation during sensory transduction in spider mechanoreceptor neurons. | Spider mechanosensory VS-3 neurons receive peripheral efferent synaptic modulation, with regional variations in the types of efferent synapses and transmitter receptors. VS-3 somata possess a voltage-activated calcium current, but the levels and time courses of calcium changes in other regions are unknown. The roles of calcium in these neurons are not completely understood, but could include modulation of both mechanosensitivity and response dynamics. Here, we measured calcium concentration rises caused by single, mechanically induced action potentials in VS-3 sensory dendrites, somata and axons, using Oregon Green BAPTA-1 fluorescence. Calcium concentration rose by approximately 1 nM following each action potential. Time courses of calcium rise and fall were similar in the three regions but the rise in amplitude was about 50% higher in the sensory dendrite than in the soma. Antibody to the Ca(V)3.1(alpha(1g)) isotype of T-type calcium channel labeled all three neuronal regions. Some Ca(V)3.1 labeling colocalized with synapsin labeling, suggesting that calcium channels play some part in efferent modulation. We conclude that mechanically stimulated action potentials start near sensory dendrite tips and pass rapidly through the neurons to the axons, activating low voltage activated calcium channels in all three regions and causing calcium concentration to rise rapidly in each region. These results suggest important roles for calcium in several stages of mechanosensation. | 18,950,665 |
Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. | The purpose of this study was to develop Cremophor EL-free nanoparticles loaded with Paclitaxel (PTX), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation. The incorporation efficiency of PTX was higher with the nanoprecipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol and to Cremophor EL. When exposed to 25 microg/ml of PTX, the cell viability was lower for PTX-loaded nanoparticles than for Taxol (IC(50) 5.5 vs 15.5 microg/ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol and PTX-loaded nanoparticles induced the same percentage of apoptotic cells. PTX-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol. Therefore, PTX-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy. | 18,950,666 |
A local reaction at or near injection site: case definition and guidelines for collection, analysis, and presentation of immunization safety data. | The need for developing a case definition and guidelines for a local reaction at or near the injection site, methods for the development of the case definition and guidelines as an adverse event following immunization as well as the rationale for selected decisions about the case definition for a local reaction at or near the injection site are explained in the Preamble section. The case definition is structured in 2 levels of diagnostic certainty: level 1 includes any description of morphological or physiological change at or near the injection site that is described or identified by a healthcare provider. Level 2 is any description of morphological or physiological change at or near injection site that is described by any other person. In Guidelines section, the working group recommends to enable meaningful and standardized data collection, analysis, and presentation of information about a local reaction at or near the injection site. However, implementation of all guidelines might not be possible in all settings. The availability of information may vary depending upon resources, geographic region, and whether the source of information is a prospectively designed clinical trial, a post-marketing surveillance or epidemiologic study, or an individual report of a local reaction at injection site. | 18,950,670 |
Protective effect of cactus (Opuntia ficus indica) cladode extract upon nickel-induced toxicity in rats. | The purpose of this study carried out on male Wistar rats, was to evaluate the protective effects of regular ingestion of juice from the prickly pear cactus (Opuntia ficus indica) cladodes against nickel chloride toxicity. Rats were given either normal tap water or water containing 25% of cactus juice for one month. Then, rats of each group were injected daily, for 10 days, with either NiCl(2) solution (4mg (30micromol)/kg body weight) or with the same volume of saline solution (300mM NaCl). Significant increases of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase activities and of cholesterol, triglycerides and glucose levels were observed in blood of nickel-treated rats. In the liver, nickel chloride was found to induce an oxidative stress evidenced by an increase in lipid peroxidation and changes in antioxidant enzymes activities. Superoxide-dismutase (SOD) activity was found to be increased whereas glutathione peroxidase and catalase activities were decreased. These changes did not occur in animals previously given cactus juice, demonstrating a protective effect of this vegetal extract. | 18,950,672 |
Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. | The present study investigated the effects of Punica granatum aqueous extract (PgAq) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, lipid profiles (atherogenic index), lipid peroxidation (LPO) and activities of both non-enzymatic and enzymatic antioxidants. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg) to albino Wistar rats. The increase in blood glucose level, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), LPO level with decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH) content and antioxidant enzymes namely, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of PgAq at doses of 250 mg/kg and 500 mg/kg for 21 days resulted in a significant reduction in fasting blood glucose, TC, TG, LDL-C, VLDL-C and tissue LPO levels coupled with elevation of HDL-C, GSH content and antioxidant enzymes in comparison with diabetic control group. The results suggest that PG could be used, as a dietary supplement, in the treatment of chronic diseases characterized by atherogenous lipoprotein profile, aggravated antioxidant status and impaired glucose metabolism and also in their prevention. | 18,950,673 |
The stimulation of mitogenic signaling pathways by N-POMC peptides. | The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC(1-28) stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC(1-28) and N-POMC(1-49) in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC(1-49) stimulated the phosphorylation of Akt more robustly than N-POMC(1-28). We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal. | 18,950,678 |
HSP27 regulates IL-1 stimulated IKK activation through interacting with TRAF6 and affecting its ubiquitination. | Heat shock protein 27 (HSP27) is an ubiquitiously expressed protein, which has been mediated in various biological functions. Here, we present a novel mechanism utilized by HSP27 in regulating IL-1beta induced NF-small ka, CyrillicB activation. Both over-expression and RNAi experiments indicate that HSP27 physically interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) and promotes TRAF6 ubiquitination. Over-expressed HSP27 augments IL-1beta induced TRAF6 ubiquitination and Ismall ka, CyrillicB kinase (IKK) activation. On the other hand, IL-1beta stimulation reduces endogenous HSP27/TRAF6 association, but inhibiting HSP27 phosphorylation by using SB202190, an inhibitor of p38, and MAPKAPK2 RNAi increases HSP27/TRAF6 association and thereby enhances TRAF6 ubiquitination, IKK phosphorylation as well as NF-small ka, CyrillicB activation. Furthermore, co-transfection study shows that HSP27 S78/82A, two phosphorylated serine site deficient mutants, but not wild-type HSP27 (HSP27 WT) and HSP27 S15A mutant increases TRAF6 ubiquitination and thereby mediates IL-1beta triggered IKK phosphorylation. Taken together, our data indicate that HSP27 regulates IL-1beta triggered NF-small ka, CyrillicB activation via a feedback loop which includes the interaction between HSP27 phosphorylation and ability of HSP27 to bind with TRAF6. The findings of this study reveal a novel mechanism by which HSP27 controls cytokine stimulation. | 18,950,704 |
Genome-wide high throughput analysis of DNA methylation in eukaryotes. | Cytosine methylation is the quintessential epigenetic mark. Two well-established methods, bisulfite sequencing and methyl-DNA immunoprecipitation (MeDIP) lend themselves to the genome-wide analysis of DNA methylation by high throughput sequencing. Here we provide an overview and brief review of these methods. We summarize our experience with MeDIP followed by high throughput Illumina/Solexa sequencing, exemplified by the analysis of the methylated fraction of the Neurospora crassa genome ("methylome"). We provide detailed methods for DNA isolation, processing and the generation of in vitro libraries for Illumina/Solexa sequencing. We discuss potential problems in the generation of sequencing libraries. Finally, we provide an overview of software that is appropriate for the analysis of high throughput sequencing data generated by Illumina/Solexa-type sequencing by synthesis, with a special emphasis on approaches and applications that can generate more accurate depictions of sequence reads that fall in repeated regions of a chosen reference genome. | 18,950,712 |
Phosphatase and tensin homologue deleted on chromosome 10: extending its PTENtacles. | Since its discovery in 1997, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has become one of the most important molecules in tumor biology. Mutations, deletions or dysregulation of PTEN is found in many human tumors. Recent studies have extended the reach of PTEN to include diabetes and neurological diseases such as Parkinson's and autism. In this review, we summarize the traditionally characterized function of PTEN as the lipid phosphatase that dephosphorylates PI-3,4,5-P(3), and several other newly discovered functions. The inhibition of the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway may account for most of PTEN's tumor suppressing function. However, other growth inhibiting functions of PTEN may not involve this pathway. PTEN can also inhibit growth through its protein phosphatase activity and in ways not related to its enzymatic activity at all. We survey the many functions and biochemical interactions of PTEN in cytoplasm, the nucleus and throughout the cell in this paper. | 18,950,730 |
VHL loss of function and its impact on oncogenic signaling networks in clear cell renal cell carcinoma. | Loss of von Hippel-Lindau tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma, resulting in the aberrant expression of genes that control cell proliferation, metabolism, invasion and angiogenesis. The molecular mechanisms by which loss of function leads to tumorigenesis are not yet fully defined. The von Hippel-Lindau gene product is part of an ubiquitin ligase complex that targets hypoxia inducible factors for polyubiquitination and proteasomal degradation, linking hypoxia response genes to renal cell carcinoma oncogenesis. Loss von Hippel-Lindau gene function also promotes cell invasiveness in response to hepatocyte growth factor, an important regulator of kidney development and renal homeostasis. Increased cell invasiveness is mediated by another ubiquitin ligase target with relevance to the molecular pathogenesis of renal cell carcinoma: beta-catenin. This discovery and other recent insights into kidney cancer oncogenesis implicate convergent developmental and homeostatic signaling pathways in tumorigenesis, tumor invasiveness and metastasis. | 18,950,731 |
Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. | Clubfoot is one of the most common severe musculoskeletal birth defects, with a worldwide incidence of 1 in 1000 live births. In the present study, we describe a five-generation family with asymmetric right-sided predominant idiopathic clubfoot segregating as an autosomal-dominant condition with incomplete penetrance. Other lower-limb malformations, including patellar hypoplasia, oblique talus, tibial hemimelia, developmental hip dysplasia, and preaxial polydactyly, were also present in some family members. Genome-wide linkage analysis with Affymetrix GeneChip Mapping 10K mapping data from 13 members of this family revealed a multipoint LOD(max) of 3.31 on chromosome 5q31. A single missense mutation (c.388G-->A) was identified in PITX1, a bicoid-related homeodomain transcription factor critical for hindlimb development, and segregated with disease in this family. The PITX1 E130K mutation is located in the highly conserved homeodomain and reduces the ability of PITX1 to transactivate a luciferase reporter. The PITX1 E130K mutation also suppresses wild-type PITX1 activity in a dose-dependent manner, suggesting dominant-negative effects on transcription. The propensity for right-sided involvement in tibial hemimelia and clubfoot suggests that PITX1, or pathways involving PITX1, may be involved in their etiology. Implication of a gene involved in early limb development in clubfoot pathogenesis also suggests additional pathways for future investigations of idiopathic clubfoot etiology in humans. | 18,950,742 |
Association between blocking folate receptor autoantibodies and subfertility. | The association between blocking folate receptor (FR) autoantibodies and subfertility was investigated in a longitudinal study of women attempting to become pregnant. Seventeen women with subfertility (failure to conceive during 12 menstrual cycles) and 25 control women (women who conceived and went on to have normal pregnancy outcomes) were studied. Subfertility risk was 12 times higher in women with blocking FR autoantibodies compared with those without (odds ratio, 12; 95% confidence interval, 1.9-129.6). | 18,950,755 |
Is there a role for second-look capsule endoscopy in patients with obscure GI bleeding after a nondiagnostic first test? | Long-term follow-up data on patients with obscure GI bleeding subjected to capsule endoscopy (CE) are missing. Our purpose was to follow up patients with a nondiagnostic test and determine whether a second-look CE would be beneficial. We enrolled 293 subjects. CE studies were classified as diagnostic (positive findings) or nondiagnostic (findings of uncertain significance/no findings). Patients were followed up for a mean (SD) 24.8 (5.2) months. Outcome was defined as continued or complete resolution of bleeding. Patients with a nondiagnostic test were subjected to a repeat CE if they manifested a new bleeding episode or a drop in hemoglobin >or=2 g/dL. Positive findings, findings of uncertain significance, and no findings were identified in 41.6%, 16.0%, and 42.3% of our patients, respectively. Therapeutic intervention was possible in 72.1% of those with positive findings and in 30% of those with findings of uncertain significance. Complete resolution of bleeding occurred more often in patients with a diagnostic test (65.2%) compared with those with a nondiagnostic test (35.4%, P < .001). Second-look CE was performed in a subgroup of our patients (n = 76) and was diagnostic in those whose presentation changed from occult to overt or those whose hemoglobin dropped >or=4 g/dL. In patients with obscure GI bleeding, a diagnostic CE leads to therapeutic interventions and a favorable outcome. Patients with a nondiagnostic test would definitely benefit from a second-look CE if the bleeding presentation changes from occult to overt or if the hemoglobin value drops >or=4 g/dL. | 18,950,762 |
Patient predictors of histopathologic response after photodynamic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. | Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma. To identify patient variables that influence the likelihood of response to PDT. A retrospective cohort study. Tertiary-referral center. A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer. PDT with porfimer sodium. (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium. Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone. Retrospective study, limited sample size without a control group for comparison. PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure. | 18,950,764 |
Morphology syntheses and properties of well-defined Prussian Blue nanocrystals by a facile solution approach. | Large-scale syntheses of Prussian Blue (PB) uniform nanocubes and nanospheres, together with an interesting PB micro-frame structure, have been achieved by direct dissociation of a single-source precursor K(3)[Fe(CN)(6)] with polyvinylprrolidone (PVP) as a capping and reducing agent. The reaction temperature has been proved to be a key factor for morphology development of PB nanocrystals, and the size of PB nanocrystals can be tuned by adjusting the feed ratio of K(3)[Fe(CN)(6)] to PVP and the concentration of K(3)[Fe(CN)(6)]. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected-area electron diffraction (SAED), and high resolution transmission electron microscopy (HRTEM) were used to characterize the resulting nanocrystals and investigate their growth mechanisms. Optical and magnetic studies showed size- and shape-dependent optical and magnetic properties in the PB nanocrystals. An excellent electro-catalytic property to hydrogen peroxide reduction was observed at the PB nanocube-modified electrode. | 18,950,787 |
Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. | To determine the clinical course and outcomes of infants with chronic lung disease (CLD) and pulmonary hypertension (PH) who received prolonged sildenafil therapy. We conducted a retrospective review of 25 patients <2 years of age with CLD in whom sildenafil was initiated for the treatment of PH while they were hospitalized from January 2004 to October 2007. Hemodynamic improvement was defined by a 20% decrease in the ratio of pulmonary to systemic systolic arterial pressure or improvement in the degree of ventricular septal flattening with serial echocardiograms. Chronic sildenafil therapy (dose range, 1.5-8.0 mg/kg/d) was initiated at a median of 171 days of age (range, 14-673 days of age) for a median duration of 241 days (range, 28-950 days). Twenty-two patients (88%) achieved hemodynamic improvement after a median treatment duration of 40 days (range, 6-600 days). Eleven of the 13 patients with interval estimates of systolic pulmonary artery pressure with echocardiogram showed clinically significant reductions in PH. Five patients (20%) died during the follow-up period. Adverse events leading to cessation or interruption of therapy occurred in 2 patients, 1 for recurrent erections, and the other had the medication held briefly because of intestinal pneumatosis. These data suggest that chronic sildenafil therapy is well-tolerated, safe, and effective for infants with PH and CLD. | 18,950,791 |
Health-related quality of life in children with neurofibromatosis type 1: contribution of demographic factors, disease-related factors, and behavior. | To investigate health-related quality of life (HR-QOL) in children with neurofibromatosis type 1 (NF1) with parental reports and children's self-reports, and to investigate the potential contribution of demographic factors, disease-specific factors, and problems in school performance or behavior. In a prospective observational study, parents of 58 children with NF1 (32 boys, 26 girls, age 12.2 +/- 2.5 years) visiting a university clinic, and their 43 children 10 years or older were assessed with the Child Health Questionnaire (CHQ). Potential determinants of domain scores were assessed in 3 explorative regression models. Parents reported a significant impact of NF1 on 9/13 CHQ scales, with moderate effect sizes on 8 (general health perceptions, physical functioning, general behavior, mental health, self esteem, family activities, role functioning emotional/behavioral, and parent emotional impact). Children report an impact on bodily pain, and an above average general behavior. Multiple CHQ scales were sensitive to demographic factors and behavioral problems, and 1 to NF1 severity. NF1 visibility and school problems did not influence HR-QOL. Parents, but not the children with NF1, report a profound impact of NF1 on physical, social, behavioral, and emotional aspects of HR-QOL. Multiple HR-QOL domains were most sensitive to behavioral problems, which points to an exciting potential opportunity to improve HR-QOL in children with NF1 by addressing these behavioral problems. | 18,950,800 |
The impact of posttraumatic stress disorder on impairment in the UK military at the time of the Iraq war. | The aims of this study were to assess: (1) the relationship between PTSD and impairment, (2) whether there is a threshold in the association of PTSD score and impairment, and (3) whether any of the PTSD criteria are more strongly associated with impairment. We studied 10,069 service personnel from a representative sample of the British Armed Forces to assess the effects of the Iraq war. Participants completed the PTSD checklist (PCL), the general health questionnaire-12 (GHQ-12), the alcohol use disorder identification test (AUDIT) and five questions to assess impairment. 78% of those with a PCL-score of 50 or more endorsed at least one impairment item in comparison to 27% of those with a score below 50. The odds ratio (OR) of impairment in the PCL group with a score of 50 or more was 16.7 (95% CI 12.9-21.6). There was an increasing risk of impairment with an increasing category of PCL-score without a noticeable threshold. For each PTSD subscale: intrusiveness, avoidance/numbing and hyper-arousal, divided into four score categories, there was an increased association with impairment, but the association of avoidance/numbing with impairment was the greatest and independent of the other two criteria (OR 7.2 (95% CI 4.8-10.9). Having a good relationship with a partner had minimal effect on the level of association between PTSD and impairment. Functional impairment is a serious problem for those with PTSD. The impairment is not confined to those with the highest PCL-score. Avoidance/numbing is the criterion which makes the greatest independent contribution to impairment. | 18,950,801 |
[Maxillary ridge expansion for dental implant placement with alveolar corticotomy]. | Maxillary ridge transversal expansion is based on osseous plasticity obtained by corticotomy. It allows progressively for an adequate transversal intercortical diameter large enough to insert one or several dental implants. We present a pre-implant maxillary ridge transversal osseous expansion technique. Surgery is carried out under local or general anesthesia. Infiltration of a local anesthetic with adrenaline reduces bleeding and facilitates dissection. One horizontal crestal and two vertical vestibular surgical incisions are made in the mucosa. The operating site is exposed by lifting a mucoperiostic flap. Two vertical osteotomies are performed 2mm away on either side of the future implant and one horizontal crestal osteotomy. A guided bone fracture following the osteotomy lines is performed with an osteotome. An alveolar bone flange with a superior hinge is thus obtained. If implant placement is immediately possible, the implant bed is made with the osteotomes and/or drill. An osseous graft is inserted in the intercortical space around the cervical implant area and in the corticotomy zones. The mucosa is sutured on a resorbable collagen membrane. The indications are maxillary crestal thickness ranging from 1.5 to 3mm. This technique allows gaining 4 to 5.5mm of thickness on a length of up to 40 mm. Implants are often placed during the same surgery. Morbidity is limited and aesthetic prosthetic results are satisfactory. | 18,950,821 |
Socioeconomic and environmental factors important for acquiring non-severe malaria in children in Yemen: a case-control study. | Little is known about the relative importance of environmental and socioeconomic factors for acquiring malaria in Yemen. A case-control study was conducted to determine the importance of these factors for acquiring malaria among children in Yemen. Cases of non-severe malaria were recruited from health centres; community controls were from the neighbourhood of the cases. Data were collected by personal interview and direct inspection during home visits. In total, 320 cases and 308 controls were recruited. In the multivariate analysis, environmental factors (living near streams and freshwater marshes), earth roofs of houses and history of travel were all significantly and positively associated with the occurrence of malaria, whilst regular spraying with insecticides at home was a protective factor. There was no association with socioeconomic factors, including crowding, education and occupation of parents, and ownership of house assets. An index created based on a number of indicators of wealth showed a significant association with malaria in the univariate analysis but was not significant in the multivariate analysis. Control activities can be targeted on identifiable environmental factors such as stream and freshwater marshes, although this needs further investigation. Extra protective measures may be needed by all those who travel in Yemen. | 18,950,826 |
[An aphasic reader]. | Nonsemantic reading is the capacity to read without understanding by impairment of the lexical-semantic pathway. We report the case of a female steno secretary with nonsemantic reading capacity associated with severe aphasia caused by a left hemisphere ischemic stroke in Broca's area. Arguments in favor of a right hemisphere contribution to the reading ability are presented. | 18,950,824 |
Epstein-Barr virus growth/latency III program alters cellular microRNA expression. | The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers. | 18,950,829 |
Urinary tract endometriosis: clinical, diagnostic, and therapeutic aspects. | To describe our experience at La Paz University Hospital with 12 patients with urinary tract endometriosis, an uncommon pathologic finding, the most extensive series published by Spanish investigators to our knowledge. We performed a retrospective analysis of 12 cases of urinary tract endometriosis diagnosed from 1993 to 2008. The mean patient age was 37.75 years. Of the 12 patients, 5 had bladder involvement and 7 had ureteral involvement, 2 bilateral, 2 left, and 3 right. In those with bladder endometriosis, the diagnosis was made by cystoscopy and biopsy in 4 patients. Treatment consisted of laparoscopic hysterectomy and partial cystectomy in 1 patient and exploratory laparotomy, transvesical resection, and transurethral resection of the bladder in 3 patients. One of the patients who underwent transurethral resection of the bladder experienced 2 relapses. The first relapse was treated with transurethral resection of the bladder and the second with laparoscopic partial cystectomy. In the patients with ureteral endometriosis, the diagnosis was mainly established by magnetic resonance imaging. Treatment consisted of ureteroneocystostomy in 5 patients (bilateral in 1) and laparoscopic ureterolysis in 2, with later ureteral resection and end-to-end anastomosis in 1 of them. The patient who underwent bilateral ureteroneocystostomy finally required right autotransplantation because of early ureteral relapses. Urinary tract endometriosis is an uncommon pathologic finding. Surgery is the treatment of choice. We believe partial cystectomy should be considered as an initial option in selected cases, depending on the extent and location of lesions. For cases of ureteral endometriosis, the initial technique depends on the location and depth of the lesion. | 18,950,841 |
Suture or hemostatic agent during laparoscopic partial nephrectomy? A randomized study using a hypertensive porcine model. | To compare the efficacy of 3 biologic hemostatic devices with that of conventional suture during laparoscopic partial nephrectomy (LPN) in a hypertensive porcine model. Improving hemostasis, urinary tract closure, and the warm ischemia (WI) time are important in the development of LPN. A total of 40 pigs were randomized prospectively into 4 groups before bilateral LPN. Right LPN involved 30% of the renal parenchyma without a urinary tract opening, and left LPN involved 40% of the renal parenchyma with a urinary tract opening. The renal section was treated with fibrin/thrombin sealant, fibrin glue, thrombin/gelatin granules, and conventional suture in groups 1, 2, 3, and 4, respectively. At 10 days postoperatively, left retrograde pyelography was performed. The pigs were then killed and the kidneys sent for pathologic analysis. The main criteria were the estimated blood loss, perioperative WI time, leaking pressure during retrograde pyelography, and parenchyma necrotic-induced lesions. The estimated blood loss was lower in the pigs treated with either thrombin/gelatin granules or suture (P < .001). The use of thrombin/gelatin granules decreased the WI time compared with the use of suture (P < .001). However, the leaking pressure was greater in the pigs treated with suture (P < .01). The mean area of necrosis around the renal section was shorter when no suturing was performed (P < .01). The use of thrombin/gelatin granules alone controlled hemostasis as effectively as suture and significantly decreased the WI time. However, conventional suture of the urinary tract, when opened, should be considered. Additional evaluation in humans is required before any clinical recommendation can be made. | 18,950,843 |
From self-control capabilities and the need to control others to proactive and reactive aggression among adolescents. | The purpose of this study was to explore the associations between aspects of control (self-control capability and the need to control others) and forms of aggression (reactive and proactive). Data were derived from a structured questionnaire administered to 660 male and female adolescents with an average age of 14.99 years, from two urban schools in northern Israel. Findings demonstrate a negative association between the need to control others and the capability to control the self. Findings also show that proactive violence is especially associated with high need to control others, whereas reactive violence is linked more closely to low self-control capability. The effects of gender and age on control and aggression factors are also shown. Findings are discussed on both the behavioral and the motivational levels. | 18,950,851 |
Factors that adolescent males take into account in decisions about an unplanned pregnancy. | Little is known about what factors adolescent males consider important when making decisions concerning the resolution of an unplanned pregnancy with a teenage partner. Young men's influence on pregnancy outcome decisions can play an important part in the subsequent psychological adjustment of the female. The present report draws on data from a larger study with teenage males [Condon, J. T., Corkindale, C. J., Russell, A., & Quinlivan, J. A. (2006). Processes and factors underlying adolescent males' attitudes and decision-making in relation to an unplanned pregnancy. Journal of Youth and Adolescence, 35, 447-458], and extends the findings of that study. Using a 25-item scale embedded in an electronic role-play, data were obtained from 330 male Australian school students on their priorities and concerns in relation to possible outcomes of a partner's pregnancy. Common factors taken into account by almost the entire adolescent sample related to the negative effects of becoming a teenage father. The differences between participants were identified using cluster analysis, which produced three groupings. The majority group was characterised as 'well-balanced' (80.6%), and the two minority groups as 'unwilling/unready' (10.9%) and 'family-centred' (8.5%). Group membership was strongly predictive of the males' final decision regarding the hypothetical pregnancy outcome. Understanding adolescent attitudes and beliefs when faced with this decision may assist practitioners in their guidance of the young couple and help prevent negative psychological sequelae. | 18,950,852 |
Systematic review of dose-volume parameters in the prediction of esophagitis in thoracic radiotherapy. | With dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the treatment of thoracic malignancies. The advent of 3DCT planning has enabled investigators to study esophageal dose-volume histogram (DVH) parameters as predictors of RE. The purpose of this study was to assess published dosimetric parameters and toxicity data systematically in order to define reproducible predictors of RE, both for potential clinical use, and to provide recommendations for future research in the field. We performed a systematic literature review of published studies addressing RE in the treatment of lung cancer and thymoma. Our search strategy included a variety of electronic medical databases, textbooks and bibliographies. Both prospective and retrospective clinical studies were included. Information relating to the relationship among measured dosimetric parameters, patient demographics, tumor characteristics, chemotherapy and RE was extracted and analyzed. Eighteen published studies were suitable for analysis. Eleven of these assessed acute RE, while the remainder assessed both acute and chronic RE together. Heterogeneity of esophageal contouring practices, individual differences in information reporting and variability of RE outcome definitions were assessed. Well-described clinical and logistic modeling directly related V(35Gy), V(60Gy) and SA(55Gy) to clinically significant RE. Several reproducible dosimetric parameters exist in the literature, and these may be potentially relevant in the prediction of RE in the radiotherapy of thoracic malignancies. Further clarification of the predictive relationship between such standardized dosimetric parameters and observed RE outcomes is essential to develop efficient radiation treatment planning in locally advanced NSCLC in the modern concurrent chemotherapy and image-guided IMRT era. | 18,950,881 |
The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer. | The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC). The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of the Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up. During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89). Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy. | 18,950,883 |
Non-invasive organization variation assessment in the onset and termination of paroxysmal atrial fibrillation. | Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia. Recently, it has been suggested that AF is partially organized on its onset and termination, thus being more suitable for antiarrhythmia and to avoid unnecessary therapy. Although several invasive and non-invasive AF organization estimators have been proposed, the organization time course in the first and last minutes of AF has not been quantified yet. The aim of this work is to study non-invasively the organization variation within the first and last minutes of paroxysmal AF. The organization was evaluated making use of sample entropy, which can robustly estimate electrical atrial activity organization from surface ECG recordings. This work proves an organization decrease in the first minutes of AF onset and an increase within the last minute before spontaneous AF termination. These results are in agreement with the conclusions reported by other authors who made use of invasive recordings. | 18,950,894 |
Synthesis and antioxidant potential of novel synthetic benzophenone analogues. | Considering that oxidative stress is strongly implicated in the toxicity of chemotherapy, much effort is focused on the research of diverse antioxidants as protective agents. An efficient synthesis of three novel benzophenones containing 1,3-thiazol moiety (6a-c) is described. Their antioxidant power was evaluated in vitro and in three cell lines (the cancerous MCF7 and the non-cancerous hTERT-HME1 mammary cells, and the H9c2 cardiomyoblastic cells). One analogue 5-(2,5-dihydroxybenzoyl)-2(3H)-benzothiazolone (6c), displayed an important antioxidant activity, a low cytotoxicity, and could decrease reactive oxygen species production generated by tert-butyl hydroperoxide (tBHP) in all three cell lines. Interestingly, 6c was able to protect the non-cancerous cells against tBHP-induced death. Further studies are underway to determine its relevance as an adjuvant in oxidative stress inducing chemotherapy. | 18,950,902 |
Activation of tumor-infiltrating antigen presenting cells by high intensity focused ultrasound ablation of human breast cancer. | Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can trigger activation of host antitumor responses after direct tumor destruction. The goal of this study was to investigate the status and functions of tumor-infiltrating antigen presenting cells (APCs) after HIFU ablation of human breast cancer, and to explore the mechanisms regarding HIFU-enhanced antitumor response. Forty-eight women with biopsy-proven breast cancer were divided randomly into a control group (n = 25) and a HIFU group (n = 23). Patients in the control group received modified radical mastectomy, and those in the HIFU group underwent HIFU ablation of primary breast cancer, followed by modified radical mastectomy within 1-2 weeks. Using immunohistochemical analysis, tumor-infiltrating dendritic cells (DCs), macrophages, B lymphocytes and expression of HLA-DR and costimulatory molecules on DCs and macrophages were assessed in all patients. The results showed that APCs infiltrated along the margins of the ablated regions in all HIFU-treated tumors, and numbers of tumor-infiltrating DCs, macrophages and B lymphocytes increased significantly in the HIFU group. Compared with the values in the control group, the percentage of DCs and macrophages expressing HLA-DR, CD80 and CD86 was significantly greater in the HIFU group. There were statistically significant differences between numbers of S-100(+) HLA-DR(+), S-100(+) CD80(+), S-100(+) CD86(+), CD68(+) HLA-DR(+), CD68(+) CD80(+) and CD68(+) CD86(+) cells in the control and HIFU groups, respectively. It was concluded that HIFU ablation induces significant infiltration of APCs within the residual tumor debris in patients with breast cancer, and most of the tumor-infiltrating DCs and macrophages were activated after HIFU ablation. | 18,950,932 |
Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis. | Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases. To evaluate whether TKIs can be discontinued in these selected patients with mRCC. A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs. Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day. Response according to Response Evaluation Criteria in Solid Tumours (RECIST). We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design. Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe. | 18,950,936 |
Comparative evaluation of eight serological assays for diagnosing Chlamydophila abortus infection in sheep. | Chlamydophila abortus is one of the principal causes of late-term abortion (enzootic abortion of ewes or EAE) in sheep across Europe. Serological diagnosis of EAE is routinely carried out by the complement fixation test, although the interpretation of results can often be difficult because of cross reaction with Chlamydophila pecorum, which also commonly infects sheep. The purpose of this study was to evaluate and compare four ELISAs developed at Moredun Research Institute and based on whole C. abortus elementary bodies (EBs), an outer membrane preparation of the whole organism (SolPr) and two recombinant polymorphic outer membrane protein fragments (rOMP90-3 and rOMP90-4), with 3 commercial tests, the CHEKIT Chlamydophila Abortus, Pourquier ELISA Chlamydophila abortus and ImmunoComb Ovine Chlamydophila Antibody tests. The tests were evaluated using a panel of 202 sera from experimentally and naturally infected animals, as well as from EAE-free flocks. The EB, SolPr and CHEKIT ELISAs performed similarly to the CFT, all lacking in specificity by cross reacting with sera from C. pecorum infected animals. The ImmunoComb also lacked specificity with C. pecorum sera, but also badly cross reacted with sera from EAE-free flocks. The rOMP90-3, rOMP90-4 and Pourquier ELISAs were the most specific, although the Pourquier test appeared less sensitive with sera from naturally infected animals. Overall, the rOMP90-3 ELISA performed the best, with high sensitivity (96.8%) and no cross reaction with sera from C. pecorum infected animals or from EAE-free flocks (100% specificity) and so would be a suitable alternative to the CFT for the serological diagnosis of EAE. | 18,950,964 |
Massive subcutaneous emphysema and pneumomediastineum after finger subtotal amputation with barotrauma. | Advancement of pressurized air through subcutaneous tissue after barotraumas involving skin laceration has been documented in the literature. The type and anatomic location of injury, amount of pressure, and time elapsed all play a role in determining the destination of the air advancing through tissues. To report a case demonstrating the vascular system as the anatomic pathway for subcutaneous pressurized air resulting from an industrial accident. We present the case of a 28-year-old laborer wounded by an air valve blast. An enormous accumulation of air was released through a subtotal fingertip amputation. The clinical appearance of massive subcutaneous emphysema around the upper extremity, neck, and chest suggested chest trauma to the clinicians, despite the absence of signs of respiratory distress. X-ray studies revealed pneumomediastinum. After confirmation that the respiratory system was undamaged, microsurgical repair of the injured finger was performed. Resolution of subcutaneous emphysema and pneumomediastinum was complete at the end of follow-up. Compressed air injuries constitute a well-known form of industrial accident. Although most result in localized subcutaneous emphysema, the risk of pneumomediastinum should not be overlooked due to the anatomic structure of the vascular system. The clinician should consider the pressure of compressed air, and must be alert for potential complications. | 18,950,976 |
Ex vivo gene delivery of ephrin-B2 induces development of functional collateral vessels in a rabbit model of hind limb ischemia. | In this study, we delivered ephrin-B2 to the ischemic hind limb of rabbits using an ex vivo method of gene transfer and evaluated whether the in vivo application of ephrin-B2 contributed to the development of functional collateral vessels. Ephrin-B2 is a transmembrane ligand of several Eph receptors and bidirectional signaling between ephrin-B2 and Eph-B4 is considered to be essential in angiogenesis and the development of arteries and veins. The left femoral artery of male Japanese White rabbits was excised to induce limb ischemia, and a primary culture of autofibroblasts was obtained from a skin section. Nineteen days later, the gene expressing ephrin-B2 (ephrin group) or beta-galactosidase gene (control group) was adenovirally transfected to the cultured auto-fibroblasts (5 x 10(6) cells); then 48 hours later, the gene-transduced cells were injected through the left internal iliac artery of the same rabbit. At 28 days after injection, the development of collateral vessels and their function were assessed (control group, n = 12; ephrin group, n = 10). The gene expressing ephrin-B2 was successfully transferred to the rabbit autofibroblasts, and ephrin-B2, expressed on the cell membrane, possessed binding ability with its receptor, Eph-B4. Calf blood pressure ratio (control group: 0.523 +/- 0.047 vs ephrin group: 0.658 +/- 0.049, P < .0001), angiographic score (0.344 +/- 0.091 vs 0.525 +/- 0.109, P = .0006), in vivo blood flow of the left internal iliac artery (rest: 11.963 +/- 2.806 vs 17.202 +/- 3.622 mL/min, P = .0014; maximum: 27.652 +/- 10.377 vs 43.400 +/- 7.108 mL/min, P = .0007), collateral conductance (32.740 +/- 7.408 vs 54.489 +/- 18.809 mL/min/100 mm Hg, P = .0097), and capillary density of the left thigh muscle (118.517 +/- 18.669 vs 167.400 +/- 31.271, P = .0002) showed significant improvement in the ephrin-B2 group compared with controls. These findings suggest that auto-fibroblasts expressing ephrin-B2 potentially promote arteriogenesis as well as angiogenesis in the adult vasculature, resulting in the development of functional collateral vessels to an ischemic lesion. | 18,950,979 |
Objective evaluation of fine motor manipulation-a new clinical tool. | A new performance-based tool has been developed to accurately and precisely evaluate finger/hand function during manipulation of any object, independent of geometric and surface properties. The objectives of this study were to show test-retest reliability and evaluate criterion validity. Twenty healthy, right-handed participants were recruited. Three objects ranging in weight and size, requiring two or three fingers, were instrumented with a motion sensor that tracked 3D linear/angular motion. A computerized visual-guided tracking task was used to quantify motor performance during object manipulation. Two testing periods, one week apart were performed to evaluate test-retest reliability. Criterion validity was assessed by comparing performance with this tool to performance on commonly used clinical dexterity tests. Global performance, temporal accuracy, and amplitude consistency during manipulation of the objects compared with the reference waveform were highly reliable on the two testing occasions. Low-moderate correlations between the clinical dexterity tests and the task protocol indicate that different aspects of hand function were measured. The task protocol directly measures the ability of the hand to coordinate movement in response to a visual tracking target. Providing effective and objective ways to evaluate manual dexterity and hand function is a critical part of evidence-based practice. | 18,950,989 |
The use of ziprasidone in clinical practice: analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey. | This study related clinical effects to daily doses and serum concentrations of ziprasidone by retrospective analysis of data from a therapeutic drug monitoring (TDM) survey established for patients treated with the new antipsychotic drug. In the total sample of 463 patients ziprasidone doses ranged between 20 and 320 mg/d and correlated significantly (r(2)=0.093, P<0.01) with serum concentrations. The latter were highly variable within and between individual patients (between patients median 67 ng/ml, 25-75th percentile 40-103 ng/ml). Pharmacokinetic interactions with comedication played a minor role. According to the clinical global impressions (CGI) scale most of the 348 patients who were under antipsychotic monotherapy with ziprasidone were either much or very much improved (43.3 and 17.3%, respectively). The previously proposed therapeutic range of 50-130 ng/ml ziprasidone in serum or plasma, which can in effect be used interchangeable, was confirmed. In patients who were at least much improved and defined as "responders" mean serum concentrations of ziprasidone were 80 ng/ml and 78 ng/ml in patients who did not reach this improvement score. In patients with serum levels above or below 50 ng/ml, the number of responders was 66 or 63%, respectively. The difference between the two groups was not significant (P=0.375), and improvement or side effects did not correlate significantly (P>0.05) with doses or serum levels. It is concluded that TDM of ziprasidone may be useful for treatment optimization because of highly variable serum concentrations resulting under therapeutically recommended doses of the drug. | 18,950,992 |
Static progressive splinting for restoration of rotational motion of the forearm. | This study examined the use of a bidirectional, patient-directed orthosis that used the principles of static progressive stress to improve forearm rotation. Thirty-eight patients who had limited pronation and supination motions after injuries and who failed other physical therapy techniques underwent a 30- to 60-minute stretching protocol with the orthosis one to three times per day. The mean arc of rotation increased by 42 degrees (range, 0-122) after a mean treatment duration of 12 weeks (range, 3-57). The mean patient satisfaction score was 8.1 points on a scale of 0-10 points. All of the patients completed the treatment and no short-term complications were reported. The gains in motion were comparable to the published results of other orthoses as well as surgical procedures such as external fixators and closed manipulation, but fewer complications occurred with the static progressive stress technique. This orthosis is a useful treatment for patients who have limitations of forearm rotation. | 18,950,990 |
Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study. | The effect of minor orthopaedic day surgery (MiODS) on patient's mood. A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery. | 18,950,993 |
Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. | Formula supplemented with docosahexaenoic acid (DHA) improves retinal function of preterm infants but the optimal dose is unknown. In a randomized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants. Infants born <33 weeks gestation were fed high-DHA milk (1% total fat as DHA) or standard-DHA milk (0.2-0.3% DHA) until reaching their estimated due date (EDD). Milk arachidonic acid (AA) concentration was approximately 0.5% for both groups. At EDD, erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with standard-DHA (mean+/-SD, high-DHA 6.8+/-1.2, standard-DHA 5.2+/-0.7, p<0.0005) but AA was lower (high-DHA 14.9+/-1.3, standard-DHA 16.0+/-1.2, p<0.0005). Feeding preterm infants human milk and formula with 1% DHA raises but does not saturate erythrocyte phospholipids with DHA. Milk exceeding 1% DHA may be required to increase DHA status to levels seen in term infants. | 18,951,004 |
Preparation of gold nanoparticles/functionalized multiwalled carbon nanotube nanocomposites and its glucose biosensing application. | Gold nanoparticles stabilized by amino-terminated ionic liquid (Au-IL) have been in situ noncovalently deposited on poly(sodium 4-styrene-sulfonate) (PSS)-functionalized multiwalled carbon nanotubes (MWCNTs) to form a MWCNTs/PSS/Au-IL nanocomposite. PSS can interact with MWCNTs through hydrophobic interaction. Amino-terminated ionic liquid was applied to reduce aqueous HAuCl(4), and the resulting gold nanoparticles were attached to the PSS-functionalized MWCNTs simultaneously. Most gold nanoparticles dispersed well on the functionalized MWCNTs. Transmission electron microscopy, Raman and X-ray photoelectron spectroscopy were used to confirm the composition and structure of the nanocomposites. The resulting MWCNTs/PSS/Au-IL composite exhibits good electrocatalysis toward oxygen and hydrogen peroxide reduction. And good biocompatibility with glucose oxidase was also demonstrated due to its good biocatalysis toward glucose substrate, which offered a friendly environment for the immobilization of biomolecules. Such bionanocomposite provides us potential applications in fabrication of biosensors. The resulting biosensor exhibits good response to glucose with a low detection limit 25 microM. It also has excellent reproducibility, satisfied operational stability and good storage stability. | 18,951,009 |
Modification of carbon nanotubes with redox hydrogel: improvement of amperometric sensing sensitivity for redox enzymes. | This study demonstrated that redox hydrogel-modified carbon nanotube (CNT) electrodes can be developed as an amperometric sensor that are sensitive, specific and fast and do not require auxiliary enzymes. A redox polymer, poly(vinylimidazole) complexed with Os(4,4'-dimethylbpy)(2)Cl (PVI-dmeOs) was electrodeposited on Ta-supported multi-walled CNTs. The resulted PVI-dmeOs thin film did not change the surface morphology of the CNTs, but turned the CNT surface from hydrophobic to hydrophilic, as studied by scanning electron microscopy (SEM) and static water contact angle measurements. Cyclic voltammetry measurements in a Fe(CN)(6)(3-) solution and electrochemical impedance measurements in an equimolar Fe(CN)(6)(3-/4-) solution demonstrated that the PVI-dmeOs hydrogel thin film was electronic conductive with a resistance of about 15Omega. The PVI-dmeOs/CNT electrodes sensed rapidly, sensitively and specifically to model redox enzymes (glucose oxidase (GOD) and lactate oxidase (LOD)) in amperometric experiments in electrolyte solutions containing the substrates of the measured redox enzymes. Both the CNT substrate and the thin PVI-dmeOs film enhanced the sensing sensitivities. Exploration of the mechanisms suggests that the PVI-dmeOs film may enhance the sensing sensitivities by wiring the enzyme molecules through the redox centers tethered on the mobile redox polymer backbones to the CNT electrodes. | 18,951,014 |
Development of a mutant of Trichoderma citrinoviride for enhanced production of cellulases. | Considering importance of a microbial strain capable of increased cellulases production and insensitive to catabolite repression for industrial use, we have developed a mutant strain of Trichoderma citrinoviride by multiple exposures to EMS and ethidium bromide. The mutant produced 0.63, 3.12, 8.22 and 1.94 IU ml(-1) FPase, endoglucanase, beta-glucosidase and cellobiase, respectively. These levels were, respectively, 2.14, 2.10, 4.09 and 1.73 fold higher than those in parent strain. Glucose (upto 20 mM) did not repress enzyme production by the mutant under submerged fermentation conditions. In vitro activity assay with partially purified cellulase showed lack of inhibition by glucose. Interestingly, the partially purified endoglucanase and beta-glucosidase were activated by 2.0 fold and 2.6 fold, respectively, by 20 mM and 30 mM ethanol in the assay mixture. Genetic distinction of the mutant was revealed by the presence of two unique amplicans in comparative DNA fingerprinting performed using 20 random primers. | 18,951,016 |
Ca(2+) signaling occurs via second messenger release from intraorganelle synthesis sites. | Cyclic ADP-ribose is an important Ca(2+)-mobilizing cytosolic messenger synthesized from beta-NAD(+) by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response to stimuli. We have cloned and characterized three ARCs in the sea urchin egg and found that endogenous ARCbeta and ARCgamma are intracellular and located within the lumen of acidic, exocytotic vesicles, where they are optimally active. Intraorganelle ARCs are shielded from cytosolic substrate and targets by the organelle membrane, but this barrier is circumvented by nucleotide transport. We show that a beta-NAD(+) transporter provides ARC substrate that is converted luminally to cADPR, which, in turn, is shuttled out to the cytosol via a separate cADPR transporter. Moreover, nucleotide transport is integral to ARC activity physiologically because three transport inhibitors all inhibited the fertilization-induced Ca(2+) wave that is dependent upon cADPR. This represents a novel signaling mechanism whereby an extracellular stimulus increases the concentration of a second messenger by promoting messenger transport from intraorganelle synthesis sites to the cytosol. | 18,951,023 |
Antigens for cancer immunotherapy. | Progress in tumor immunology has not been translated to effective immunotherapies for cancer. Most of the current effort in basic and clinical research concentrates on generating effective immune responses against model or well characterized antigens, yet vaccines targeting defined antigens have been less clinically successful than those based on whole tumor cells or their extracts. This review considers characteristics of proteins that determine how effectively they might serve as targets of immune control, and how different sources of antigens have fared in clinical trials. | 18,951,039 |
Molecular modelling of co-receptor CD8 alpha alpha and its complex with MHC class I and T-cell receptor in sea bream (Sparus aurata). | T-cells are the main actors of cell-mediated immune defence; they recognize and respond to peptide antigens associated with MHC class I and class II molecules. In this paper, we investigated by molecular modelling methods in the teleost sea bream (Sparus aurata) the interaction among the molecules of the tertiary complex CD8/MHC-I/TCR, which determines the T-cell-mediated immunological response to foreign molecules. First, we predicted the three-dimensional structure of CD8 alpha alpha dimer and MHC-I, and, successively, we simulated the CD8 alpha alpha/MHC-I complex. Finally, the 3D structure of the CD8/MHC-I/TCR complex was simulated in order to investigate the possible changes that can influence TCR signalling events. | 18,951,040 |
Vertebral augmentation with a flexible curved needle: preliminary results in 17 consecutive patients. | This report details a trial demonstrating the viability of a blunt-tipped curved needle for use as a cement injection device for vertebral body augmentation. Between January and September 2007, 17 consecutive patients (eight men and nine women; average age, 76 years; age range, 52-97 years) underwent vertebral body augmentation with a blunt-tipped curved nitinol injection needle via a single pedicle to treat pain due to acute vertebral body compression fractures. All patients were successfully treated without complication. The results of the trial demonstrate that a curved blunt-tipped nitinol needle is a viable alternative to a rigid injection cannula when performing vertebral body augmentation with cement. | 18,951,044 |
Precise alignment of peptidyl tRNA by the decoding center is essential for EF-G-dependent translocation. | Translocation is an essential step in the elongation cycle of the protein synthesis that allows for the continual incorporation of new amino acids to the growing polypeptide. Movement of mRNA and tRNAs within the ribosome is catalyzed by EF-G binding and GTP hydrolysis. The 30S subunit decoding center is crucial for the selection of the cognate tRNA. However, it is not clear whether the decoding center participates in translocation. We disrupted the interactions in the decoding center by mutating the universally conserved 16S rRNA bases G530, A1492, and A1493, and the effects of these mutations on translocation were studied. Our results show that point mutation of any of these 16S rRNA bases inhibits EF-G-dependent translocation. Furthermore, the mutant ribosomes showed increased puromycin reactivity in the pretranslocation complexes, indicating that the dynamic equilibrium of the peptidyl tRNA between the classical and hybrid-state configurations is influenced by contacts in the decoding center. | 18,951,096 |
Vasopressin decreases sepsis-induced pulmonary inflammation through the V2R. | The early use of vasopressors in sepsis has been associated with a decrease in immune activation independent of hemodynamic effects, although the mechanism behind this remains unclear. We hypothesize that low dose vasopressin will reduce the pulmonary inflammation associated with sepsis. Our aims were to (1) determine whether vasopressin reduces lipopolysaccharide (LPS)-induced pulmonary inflammation and (2) determine which vasopressin receptor is responsible for pulmonary immune modulation. Mice were treated with intraperitoneal LPS to induce both systemic and pulmonary inflammation. Vasopressin or saline was infused via peritoneal pump and interleukin 6 (IL-6) in lung and serum was measured at 6h. NF-kappaB activation as was determined in the lung through immunoblotting total and phospho-IkappaB. Hemodynamic data was also obtained at the 6h mark. In a separate series of experiments mice received both LPS and vasopressin infusion following pretreatment with vasopressin receptor antagonists to V1R, V2R and OTR. Low dose LPS dramatically raises both serum IL-6 and pulmonary levels of IL-6 and phospho-IkappaB despite no significant changes in mean arterial pressure at 6h. Compared to saline, vasopressin infusion significantly decreases both the pulmonary IL-6 levels and phospho-IkappaB in LPS treated mice without raising arterial pressure. Pretreatment with V2R antagonist results in complete attenuation of vasopressin's immunosuppressive effects, with restoration of pulmonary IL-6 and phospho-IkappaB levels to those seen with LPS alone. Vasopressin exerts a local anti-inflammatory effect on the lung through the V2R in a model of sepsis. | 18,951,114 |
Study of odor compounds in gaseous effluents generated during production of poultry feather and viscera meal using headspace solid phase microextraction. | This work reports the screening and characterization of odor compounds in gaseous effluents generated during the production of poultry feather and viscera meal, the by-products of the poultry meat industry. Chemical analysis was carried out by solid phase microextraction in the headspace (HS-SPME) mode. Exhaust air of thermal processing of poultry feather and viscera were sampled online from a bench-scale digester, condensed, and collected in sampling flasks. Both volatile and semivolatile organic compounds present in the condensed gases were extracted under agitation at constant temperature. The extracts were analyzed with a gas chromatograph coupled to a mass spectrometric detector (GC/MSD). The identification of compounds was carried out by comparing the mass spectra obtained with those from the Wiley library and quantification was accomplished through authentic analytical standards. For the determination of the best extraction conditions and analysis, extraction fibers of different coatings and polarities were tested: divinylbenzene/carboxen/polydimethyilsiloxane (DVB/CAR/PDMS), carbowax/divinylbenzene (CW/DVB), and polydimethylsiloxane (PDMS) and chromatography columns of different polarities: DB-WAX (polar) and DB-5 (nonpolar). The best extraction conditions and analysis of the compounds of interest were obtained by the use of the SPME fiber with DVB/CAR/PDMS coating and analysis by GC/MSD with polar capillary column. Several carboxylic acids were identified, as well as mercaptans, amines, and aldehydes of great environmental importance. | 18,951,138 |
The intranuclear environment. | Many of the chapters in this volume are concerned with processes or structures inside the nucleus, and it is relevant to consider the properties of their environment, or rather of the multiple different and specific environments that must exist in local regions of the highly heterogeneous intranuclear space. Relatively little is known about the fundamental physical properties of these environments, and theoretical treatments of phenomena in such concentrated mixtures of charged macromolecules are complex and as yet poorly developed. Some of the phenomena that occur at the molecular level are unexpected and counterintuitive for biologists, although well known to colloid and polymer scientists; for example, the existence of short-range attractive forces between macromolecules or structures with like charges. As a background for the chapters that follow, we consider here some of the particular features of intranuclear environments, how they may influence processes and structures in the nucleus, and their implications for working with nuclei. | 18,951,157 |
Methods for studying the nuclei and chromosomes of dinoflagellates. | Dinoflagellates are unicellular eukaryotic organisms whose nuclear structure, chromosome architecture, chromatin organization, DNA composition, and mitosis show original features. It has been necessary to adapt techniques and to create innovative methods for growing cells, isolating nuclei, and studies of their chromosomes by transmission electron microscope (TEM). Among these are innovative squash and whole-mount preparations for light and TEM observations of chromosome architecture and the spatial organization of nucleofilaments. Particular attention was given to adapt high-pressure freezing (fast-freeze fixation) techniques for the best preservation of delicate antigenic sites, and good immunodetection. The study of DNA replication with or without incorporation of bromodeoxyuridine (BrdU) was also refined to use confocal laser scanning microscopy. In this chapter, we describe methods that we have invented and/or improved from existing techniques in order to better understand this fragile chromosome architecture and the mechanisms intervening during mitosis and the cell cycle. These methods allowed us to detect specific DNA-binding proteins and the distribution of B-and Z-DNA in chromosomes during the cell cycle and mitosis, and to focus on the indissoluble link between chromosome structure and function. | 18,951,163 |
Analysis of telomeres and telomerase. | The terminal chromatin structures at the ends of eukaryotic chromosomes, the telomeres, are a focus of intensive research due to their importance for the maintenance of chromosome integrity. Their shortening due to incomplete replication functions as a molecular clock counting the number of cell divisions, and ultimately results in cell-cycle arrest and cellular senescence. Telomere shortening can be compensated by the nucleoprotein enzyme complex called telomerase, which is able to extend shortened telomeres. In humans, only embryonic and germ cells show telomerase activity that is sufficient for telomere length stability and cellular immortality. Unfortunately, telomerase is activated in cancer cells, which, thus, achieve unlimited growth and a malignant phenotype. Even if there were no any other links of telomere biology to other essential processes in the cell nucleus such as DNA repair, chromosome positioning, and nuclear architecture in mitosis and meiosis, the close connection of telomere biology to aging and cancer makes telomeres and techniques for their analysis important enough from the point of view of us, mortal and disease-prone people. In this chapter, we describe the most common types of analyses used in telomere biology: screening for typical and variant telomeric sequences, determination of telomere lengths, and measurement of telomerase activity. | 18,951,173 |
Combined immunofluorescence, RNA fluorescent in situ hybridization, and DNA fluorescent in situ hybridization to study chromatin changes, transcriptional activity, nuclear organization, and X-chromosome inactivation. | Epigenetic mechanisms lead to the stable regulation of gene expression without alteration of DNA and trigger initiation and/or maintenance of cell-type-specific transcriptional profiles. Indeed, modulation of chromatin structure and the global 3D organization of the genome and nuclear architecture participate in the precise control of transcription. Thus, dissection of these epigenetic mechanisms is essential for our understanding of gene regulation. In this chapter, we describe challenging combinations of immunofluorescence, and RNA and DNA fluorescent in situ hybridization and their application to our studies of a remarkable example of epigenetic control of gene expression in female mammals, the process of X chromosome inactivation. | 18,951,174 |
Using molecular beacons to study dispersal of mRNPs from the gene locus. | Before leaving the site of transcription, newborn messenger RNAs (mRNAs) become associated with a number of different proteins. How these large messenger ribonucleoprotein (mRNP) complexes then move through the dense nucleoplasm to reach the nuclear periphery has been a fascinating question for the last few years. We have studied the mechanism of this process by tracking individual mRNPs in real time. We were able to track mRNPs at single-molecule resolution because we utilized mRNAs that were engineered to have a sequence motif repeated 96 times in their untranslated region. These mRNAs were visualized with the help of molecular beacons that were specific for the repeated sequence; the binding of 96 molecular beacons to each mRNA molecule rendered them so intensely fluorescent that they were visible as fine fluorescent spots that could be tracked by high-speed video microscopy. In this chapter, we describe the details of the construction of genes containing the tandem repeats, the integration of such genes into the genome of a cell line, the design and testing of molecular beacons, time-lapse imaging of mRNPs, and computer-aided generation and analysis of the tracks of the individual mRNPs. These methods will be useful for studies of other dynamic processes such as mRNA export, splicing, and decay. | 18,951,181 |
Recognition imaging of chromatin and chromatin-remodeling complexes in the atomic force microscope. | Atomic force microscopy (AFM) can directly visualize single molecules in solution, which makes it an extremely powerful technique for carrying out studies of biological complexes and the processes in which they are involved. A recent development, called Recognition Imaging, allows the identification of a specific type of protein in solution AFM images, a capability that greatly enhances the power of the AFM approach for studies of complex biological materials. In this technique, an antibody against the protein of interest is attached to an AFM tip. Scanning a sample with this tip generates a typical topographic image simultaneously and in exact spatial registration with a "recognition image." The latter identifies the locations of antibody-antigen binding events and thus the locations of the protein of interest in the image field. The recognition image can be electronically superimposed on the topographic image, providing a very accurate map of specific protein locations in the topographic image. This technique has been mainly used in in vitro studies of biological complexes and reconstituted chromatin, but has great potential for studying chromatin and protein complexes isolated from nuclei. | 18,951,183 |
Using cells encapsulated in agarose microbeads to analyse nuclear structure and functions. | It is now generally agreed that the nuclei of higher eukaryotes, and particularly of mammalian cells, are highly structured and that different aspects of this structure contribute to the regulation of function (1, 2). Despite the general consensus, the key mechanisms that link nuclear structure and function have proved elusive. A major reason for this is a lack of techniques that allow nuclei to be manipulated in a way that preserves the complex architectural features that are present in vivo. Historically, significant progress in understanding the makeup of nuclei from mammalian cells has been made using cells that are permeabilised in a physiological buffer after being encapsulated in agarose microbeads. By using such beads, cells are protected from shear forces that otherwise can degrade crucial elements of the architecture that it is essential to preserve. | 18,951,184 |
Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia. | Neutrophil gelatinase-associated lipocalin (NGAL) concentrations, a product of neutrophils, were investigated in normal and preeclamptic pregnancies. Prospectively collected data and late second trimester (24-26 weeks) serum samples from 48 women who subsequently developed preeclampsia (PE) and 96 control women with uncomplicated pregnancies were compared. Serum NGAL values, as determined by quantitative sandwich enzyme immunoassay, were significantly increased in the preeclamptic compared to the control women: 76.9 ng/ml (interquartile range 39.7-96.5) versus 16.0 ng/ml (interquartile range 11.2-24.4) (p<0.001), and were positively correlated to blood pressure and proteinuria, showing a high sensitivity (75%) and specificity (94.5%). The results suggest that serum NGAL might be involved in the pathophysiology of PE and could be a marker for this syndrome. | 18,951,213 |
Subgroups of preterm delivery in the Norwegian Mother and Child Cohort Study. | The preterm deliveries in the Norwegian Mother and Child Cohort (MoBa) study were divided into subgroups: spontaneous preterm delivery, iatrogenic preterm delivery, multiple pregnancies, congenital malformations and intrauterine fetal deaths (IUFD). Records were linked with the Medical Birth Registry of Norway in order to permit identification of the different subgroups. The first 53,711 included pregnancies in the MoBa study were analyzed. Spontaneous preterm delivery accounted for 42% and iatrogenic preterm delivery for 28% of all preterm deliveries. Other important contributors to preterm delivery were multiple pregnancies (16%), congenital malformations (8.6%) and IUFD (5.2%). In conclusion, the subgroup composition of the preterm population in the MoBa study is similar to previously published data regarding both different and similar populations and is well suited for future studies of this complex obstetric entity. | 18,951,220 |
Assessment of early acute lung injury in rats exposed to aerosols of consumer products: attempt to disentangle the "Magic Nano" conundrum. | In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the "Magic Nano Glass & Ceramic" spray and "Magic Nano Bath" spray. In contrast, the previously marketed "Magic Nano" pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in humans caused by "Magic Nano Sprays" triggered a comparative assessment of the acute inhalation toxicity of "Magic Nano Glass & Ceramic" spray, "Magic Nano Bath" spray, and "Magic Nano" pump spray in rats. The first two test specimens were examined as spray-can aerosols using an intermittent generation principle, whereas the undiluted liquid content of the pump spray was continuously aerosolized. Groups of Wistar rats were nose-only exposed for 4 h. However, due to mortality occurring already during exposure following exposure to Glass & Ceramic spray, the exposure duration was reduced to approximately 2 h in some groups. In addition to endpoints called for by contemporary testing guidelines, respiratory tract injury was also probed by respiratory function measurements during exposure supplemented by analyses in bronchoalveolar lavage (BAL) fluid on the first postexposure day, including lung histopathology in rats exposed to Glass & Ceramic spray. The Glass & Ceramic spray caused mortality at 2269 mg/m(3) and above, the pump spray was in the beginning lethal range at 81222 mg/m(3), while the bath spray was tolerated without mortality up to the maximum tested nominal concentrations of 28100 mg/m(3). The time-adjusted 4-h LC(50) of Glass & Ceramic spray was 5098 mg/m(3). The analysis of respiratory patterns revealed changes indicative of both upper and lower respiratory tract sensory irritation. In addition to clinical signs suggestive of marked lung irritation, especially in the rats exposed to the Glass & Ceramic spray, histopathology revealed lung inflammation, hemorrhages, edema, and focal septal thickening. Lung weights and BAL endpoints (lactate dehydrogenase [LDH], protein, gamma-glutamyltransaminase, and neutrophilic granulocytes) were markedly increased. In summary, this comparative study demonstrates that the conventional OECD 403 protocol is suitable to comparatively assess the potential and potency of these types of consumer products in their end-use configuration. Measurements in BAL were most suitable for the identification of acute lung injury. By contrast, lung function measurements during exposure did not demonstrate any conclusive association with lung injury. It does not appear that the particle size per se is a key determinant in the toxicity of "Magic Nano Glass & Ceramic" spray (approximately 100% mortality occurred at a MMAD of approximately 7 microm; GSD approximately 3). This might suggest that more volatile substances or substances contained in the test articles that co-evaporate with solvents or water may be causative for the findings observed. Hence, the findings of this study support the notion that the assessment of the acute inhalation toxicity of complex end-use products is methodologically challenging and cannot be readily anticipated based on compositional or physical (particle size) data. Accordingly, in the absence of predictive and validated in vitro assays, in vivo inhalation testing of potentially toxic commercialized spray products appears to be indispensable for consumer safety. In order to prevent indiscriminant testing of such products in bioassays, the development of standardized in vitro alternatives should be considered with high priority. | 18,951,230 |
Harmful effects of cadmium on olfactory system in mice. | The inhalation of certain metals can result in olfactory epithelial injury, an altered sense of smell, and direct delivery of the metal from the olfactory epithelium to the olfactory bulbs and other parts of the central nervous system. The purpose of this study was to examine whether mice given an intranasal instillation of cadmium would develop altered olfactory function and to assess whether cadmium may be transported directly from the olfactory epithelium to the central nervous system. To evaluate cadmium's ability to induce anosmia and on the basis of olfactory epithelium sensitivity to metals, the aim of this study was first to study cadmium effects on the olfactory function and secondly to check whether cadmium may be transported from the nasal area to the central nervous system. After an intranasal instillation of a solution containing CdCl2 at 136 mM, we observed in treated mice: (1) a partial destruction of the olfactory epithelium, which is reduced to three or four basal cell layers followed by a progressive regeneration; (2) a loss of odor discrimination with a subsequent recovery; and (3) a cadmium uptake by olfactory bulbs demonstrated using atomic absorption spectrophotometry, but not by other parts of the central nervous system. Cadmium was delivered to the olfactory bulbs, most likely along the olfactory nerve, thereby bypassing the intact blood-brain barrier. We consider that cadmium can penetrate olfactory epithelium and hence be transported to olfactory bulbs. The olfactory route could therefore be a likely way to reach the brain and should be taken into account for occupational risk assessments for this metal. | 18,951,233 |
Asthma and swimming: a meta-analysis. | In this meta-analysis, studies on swimming and asthma were divided into four groups: Group I compared frequency of asthma among elite swimmers to that of other athletes; Group II examined the association between asthma and swimming during childhood; Group III evaluated effects of swimming programs on asthma severity and pulmonary function; and Group IV compared immediate respiratory effects of swimming to those of other types of exercise. The summary results were expressed as meta-odds ratios (ORs) for binary endpoints such as presence of asthma, and meta-differences for continuous endpoints such as changes in post-exercise pulmonary function tests (PFTs). All summary measures of effect were calculated using random effects models accompanied by a corresponding 95% confidence interval (CI) and a test for heterogeneity. In the analysis comparing frequency of asthma among elite swimmers to that among other athletes (Group I), meta-ORs ranged from 2.3 to 2.6 with all 95% CIs excluding 1.0. The corresponding meta-ORs reflecting the association between asthma and swimming pool use during childhood (Group II) were in the 0.63-0.82 range and were not statistically significant. In comparison to swimming, running and/or cycling was associated with a statistically significant four-to six-fold increase in exercise induced bronchospasm. Although asthma is more commonly found among elite swimmers than among other high-level athletes, it is premature to draw conclusions about the causal link between swimming and asthma because most studies available to date used cross-sectional design, because the association is not confirmed among non-competitive swimmers, and because asthmatics may be more likely to select swimming as the activity of choice because of their condition. | 18,951,254 |
Exhaled nitric oxide measurements in hospitalized children with asthma. | The reproducibility of exhaled nitric oxide (FE(NO)) measurements performed in pediatric hospitalized asthmatics has not been previously evaluated. To evaluate the reproducibility of FE(NO) measurements in the hospital; to look for differences between those who were and were not able to perform FE(NO) measurements; and to assess any factors correlated with FE(NO) measurements. 89 hospitalized pediatric asthmatics performed FE(NO), FEV1, and peak expiratory flow rate (PEFR) maneuvers in triplicate at the time of discharge. Reproducibility was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Demographic and measured variables were compared between those who were and were not able to perform FE(NO) measurements. Correlation of FE(NO) with other variables was investigated. FE(NO) measurements showed clinically acceptable ICC and CV values (0.973 and 5.59%, respectively). These values were superior to the values obtained for FEV1 and PEFR. Subjects who successfully performed the FE(NO) measurements were older, had higher PEFR readings, and had a lower asthma dyspnea score. No correlation was found between FE(NO) and traditional asthma factors, though multiple factors did trend towards significance. FE(NO) measurements can be obtained in hospitalized pediatric patients with good reproducibility. While the majority of children will be able to provide such readings, those who are younger and with a more severe exacerbation may be unsuccessful in doing so. Further research is needed to determine how best to incorporate FE(NO) values into the hospital setting. | 18,951,258 |
The effect of chitosan molecular weight on the characteristics of spray-dried methotrexate-loaded chitosan microspheres for nasal administration. | In this article, the effect of the chitosan molecular weight (MW) on the characteristics of methotrexate (MTX)-encapsulated non-cross-linked chitosan microspheres was studied. Microspheres composed of low-molecular-weight (LMW, 40,000 Da), medium-molecular-weight (MMW, 480,000 Da) and high-molecular-weight (HMW, 850,000 Da) chitosan with the same degree of deacetylation (96%) were obtained by a simple spray-drying method. The MW of chitosan had a noticeable influence on the size distribution, encapsulation efficiency, micromeritic properties (angle of repose and bulk density), controlled release behavior, and mucoadhesive properties. The entrapment efficiencies were in the range of 90-99%. Spray-dried microspheres had a D(50) value of 3.3-4.9 microm, which was suitable for nasal insufflations. The microspheres with LMW chitosan have the best flowability and highest bulk density but were found to be poor in terms of adhesion and in controlling the release behavior of MTX. The MMW chitosan microspheres exhibited the strongest adhesion to the mucosal surface, and the angle of repose values were between 34 and 47 degrees. They could control the release rate by modifying the drug/polymer ratios. Microspheres with HMW chitosan exhibited a lower adhesion than MMW chitosan and a lower release rate of MTX. The physical state of MTX in the chitosan matrix was studied by differential scanning calorimetry, which indicated the presence of a solid dispersion of the amorphous drug in the chitosan matrix. Nasal ciliotoxity showed only minor cilia irritation due to the microspheres, and consequently, they are suitable for nasal drug delivery. | 18,951,272 |
The role of sphingosine-1-phosphate and ceramide-1-phosphate in calcium homeostasis. | During the last several years, sphingolipids have been identified as a source of important signaling molecules. Particularly, the understanding of the distinct biological roles of ceramide, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P) and lyso-sphingomyelin in the regulation of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking has rapidly expanded. Additional studies have elucidated the biological roles of sphingolipids in maintaining a homeostatic environment in cells, as well as in regulating numerous cellular responses to environmental stimuli. This review focuses on the role of S1P and C1P in maintaining Ca2+ homeostasis. By studying changes in the metabolism of S1P and C1P in pathological conditions, it is hoped that altered sphingolipid-metabolizing enzymes and their metabolites can be used as therapeutic targets. | 18,951,299 |
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