Input: This finding is equivalent to a transport into feces as well as blood system in the in vivo situation.


Input: Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet.

Oleuropein

noradrenaline

testosterone

corticosterone


Input: The effects of oleuropein, a phenolic compound in extra virgin olive oil, on protein metabolism were investigated by measuring testicular testosterone and plasma corticosterone levels in rats fed diets with different protein levels.

oleuropein

phenolic

testosterone

corticosterone


Input: In Experiment 1, rats were fed experimental diets with different protein levels (40, 25 and 10 g/100 g casein) with or without 0. 1 g/100 g oleuropein.

oleuropein


Input: After 28 days of feeding, the testosterone level in the testis was significantly higher and the plasma corticosterone level was significantly lower in rats fed the 40% casein diet with oleuropein than in those fed the same diet without oleuropein.

testosterone

corticosterone

oleuropein

oleuropein


Input: The urinary noradrenaline level, nitrogen balance and hepatic arginase activity were significantly higher in rats fed the 40% casein diet with oleuropein supplementation than in those fed the 40% casein diet without oleuropein supplementation.

noradrenaline

nitrogen

oleuropein

oleuropein


Input: In Experiment 2, the effects of oleuropein aglycone (a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein ingested in the gastrointestinal tracts) on the secretion of luteinizing hormone (LH) from the pituitary gland, which regulates testosterone production in the testis, were investigated in anesthetized rats.

oleuropein

phenolic

oleuropein

testosterone


Input: Plasma LH level increased dose dependently after the administration of oleuropein aglycone (P <. 001, r = 0. 691).

oleuropein


Input: These findings suggest that dietary supplementation with 0. 1 g/100 g oleuropein alters the levels of hormones associated with protein anabolism by increasing urinary noradrenaline and testicular testosterone levels and decreasing plasma corticosterone level in rats fed a high-protein diet.

oleuropein

noradrenaline

testosterone

corticosterone


Input: The influence of the choice of digestion enzyme used to prepare rat hepatocytes on xenobiotic uptake and efflux.


Input: Isolated rat hepatocytes are widely used to assess the metabolism and toxicity of xenobiotics.


Input: The choice of digestion enzyme used to prepare the cells has been shown previously to influence their metabolic capability.


Input: This study investigates the effect of the digestion enzyme (collagenase II, collagenase A/trypsin inhibitor, or collagenase plus dispase) on the uptake of xenobiotics into, and efflux from, hepatocytes.


Input: The choice of digestion enzymes used in this study does not affect uptake of either pravastatin (an organic anion probe substrate for Oatp transporter) or metformin (an organic cation probe substrate for Oct transporter).

pravastatin

metformin


Input: With regard to efflux transporters, hepatocyte differentiation was better maintained when cells were isolated using collagenase II alone.


Input: An appeal for the presentation of detailed human derived data for dose-response calculations in nutritional science.


Input: If a diet, food or food constituent is recognised to have both health benefits and health risks, the benefits have to be compared with the risks to develop coherent scientific evidence-based dietary advice.


Input: This means that both risk and benefit assessment should follow a similar paradigm and that benefits and risks are expressed in a common currency.


Input: Dose-response functions are vital for that purpose.


Input: However, the construction of these functions is often of second interest in the currently available (epidemiological) literature.


Input: In order to bring forward the potential of epidemiological studies for the construction of the dose-response functions for benefit-risk purposes, the scientific (nutrition and health) community is asked to expand on their data presentation, either by presenting more detailed data focusing on dose-response necessities, and/or by sharing primary data.


Input: Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.


Input: Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.


Input: Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used.

aminophylline

Carbopol


Input: Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin ((R)) 350, tablets Purdue Frederic, Canada (R-II).

Aminofilin

Phyllocontin


Input: Results: Calculated release rate constants and the f 2 values between R-I/F-I (84. 1) and R-II/F-III (83. 4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport.


Input: Higher Tmax, was found in the rabbits, dosed with F-II (12. 00 h), F-III (10. 50 h), and R-II (15. 00 h) formulation.


Input: The highest Cmax (9. 22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5. 58 mg/L) and R-II (4. 18 mg/L).


Input: Higher AUC values were detected for all three formulations (from 115. 90 to 204. 06 mgh/L) in relation to commercial products (105. 33 and 113. 25 mgh/L).


Input: Discussion and conclusion: The results demonstrated a good correlation of Level A (r (2) = 0. 97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.


Input: Impact of lead and mercuric ions on the interleukin-2-dependent proliferation and survival of T cells.

mercuric


Input: Mercury and lead are widespread in the environment, causing chronic exposure of a large population to low concentrations of these metals.

Mercury


Input: While several studies demonstrated that low levels of both metals affect the immune system, little is known about underlying molecular mechanisms.


Input: The objective of this study was to investigate the impact of mercuric (Hg (2 +)) and lead (Pb (2 +)) ions on T cells.

mercuric

Hg (2 +)

Pb (2 +)


Input: Up to 100 mu M Pb (NO (3)) (2) had no effect on cellular viability and proliferation.

Pb (NO (3)) (2)


Input: In contrast, HgCl (2) caused a concentration-dependent decline of viable leukocytes and especially of activated T cells.

HgCl (2)


Input: Additionally, Hg (2 +) induced reactive oxygen species (ROS) generation accompanied by the loss of mitochondrial transmembrane potential, measured by Dihydrorhodamine and Rhodamine-123, respectively.

Hg (2 +)

oxygen

Dihydrorhodamine


Input: The antioxidant N-acetylcysteine partially reversed the toxic effects of Hg (2 +), pointing to an involvement of ROS.

N-acetylcysteine

Hg (2 +)


Input: The major cytokine controlling T-cell survival and proliferation is interleukin (IL)-2.


Input: Hg (2 +) had no effect on the secretion of IL-2, but on IL-2 mediated signal transduction pathways, reducing phosphorylation of the downstream kinases ERK1/2 and AKT.

Hg (2 +)


Input: Moreover, Hg (2 +) led to an arrest of the cells in the S phase of the cell cycle.

Hg (2 +)


Input: Taken together, these data fit a model in which Hg (2 +) disrupts mitochondria, and the resulting release of ROS inhibits IL-2-dependent signal transduction, reducing proliferation and survival of T cells.

Hg (2 +)


Input: Quantitative ultrasound of cortical bone in the femoral neck predicts femur strength: results of a pilot study.


Input: A significant risk of femoral neck (FN) fracture exists for men and women with an areal bone mineral density (aBMD) higher than the osteoporotic range, as measured with dual-energy X-ray absorptiometry (DXA).


Input: Separately measuring the cortical and trabecular FN compartments and combining the results would likely be a critical aspect of enhancing the diagnostic capabilities of a new technique.


Input: Because the cortical shell determines a large part of FN strength a novel quantitative ultrasound (QUS) technique that probes the FN cortical compartment was implemented.


Input: The sensitivity of the method to variations of FN cortical properties and FN strength was tested.


Input: Nine femurs (women, mean age 83 years) were subjected to QUS to measure the through transmission time-of-flight (TOF) at the FN and mechanical tests to assess strength.


Input: Quantitative computed tomography (QCT) scans were performed to enable analysis of the dependence of TOF on bone parameters.


Input: DXA was also performed for reference.


Input: An ultrasound wave propagating circumferentially in the cortical shell was measured in all specimens.


Input: Its TOF was not influenced by the properties of the trabecular compartment.


Input: Averaged TOF for nine FN measurement positions/orientations was significantly correlated to strength (R2 = 0. 79) and FN cortical QCT variables: total BMD (R (2) = 0. 54); regional BMD in the inferoanterior (R2 = 0. 90) and superoanterior (R2 = 0. 57) quadrants; and moment of inertia (R2 = 0. 71).


Input: The results of this study demonstrate that QUS can perform a targeted measurement of the FN cortical compartment.


Input: Because the method involves mechanical guided waves, the QUS variable is related to the geometric and material properties of the cortical shell (cortical thickness, tissue elasticity, and porosity).


Input: This work opens the way to a multimodal QUS assessment of the proximal femur, combining our approach targeting the cortical shell with the existing modality sensitive to the trabecular compartment.


Input: In vivo feasibility of our approach has to be confirmed with experimental data in patients.


Input: Isolation and characterization of two new non-hemorrhagic metalloproteinases with fibrinogenolytic activity from the mapanare (Bothrops colombiensis) venom.


Input: Colombienases are acidic, low molecular weight metalloproteinases (Mr of 23, 074. 31 Da colombienase-1 and 23, 078. 80 Da colombienase-2; pI of 6. 0 and 6. 2, respectively) isolated from Bothrops colombiensis snake venom.


Input: The chromatographic profile in RP-HPLC and its partial sequence confirmed its high homogeneity.


Input: Both colombienases present fibrino (geno) lytic activity, but did not show any hemorrhagic, amidolytic, plasminogen activator or coagulant activities, and no effect on platelet aggregation induced by collagen or ADP.

ADP


Input: Both enzymes were strongly active on fibrinogen A alpha chains followed by the B beta chains, and colombienases-2, at high doses, also degraded the gamma chains.


Input: This activity was stable at temperatures ranging between 4 and 37 degrees C, with a maximum activity at 25 degrees C, and at pHs between 7 and 9.


Input: The homology demonstrated by the comparison of sequences, with zinc-dependent metalloproteinases, as well as the metal chelant effects on, confirmed that the colombienases were metalloproteinases, particularly to alpha-fibrinogenases belonging to the P-I class of SVPMs (20-30 kDa), which contain only the single-domain proteins.

zinc


Input: The biological characteristics of the colombienases confer a therapeutic potential, since they contain a high fibrino (geno) lytic activity, devoid of hemorrhagic activity.


Input: These metalloproteinases might be explored as thrombolytic agents given that they dissolve fibrin clots or prevent their formation.


Input: A step toward the reactivation of aged cholinesterases-Crystal structure of ligands binding to aged human butyrylcholinesterase.


Input: Organophosphorus nerve agents irreversibly inhibit cholinesterases.

Organophosphorus


Input: Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes.

serine

oximes


Input: But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i. e., a conjugated enzyme that is no longer reactivable by oximes.

oximes


Input: One strategy to regain reactivability is to alkylate the phosphylic adduct.


Input: Specific alkylating molecules were synthesized and the crystal structures of the complexes they form with soman-aged human butyrylcholinesterase were solved.

soman


Input: Although the compounds bind in the active site gorge of the aged enzyme, the orientation of the alkylating function appears to be unsuitable for efficient alkylation of the phosphylic adduct.


Input: However, these crystal structures provide key information to design efficient alkylators of aged-butyrylcholinesterase and specific reactivators of butyrylcholinesterase.


Input: Analysis of cytotoxic T lymphocyte antigen-4 (CTLA-4) promoter-318C/T and + 49A/G gene polymorphisms in Turkish patients with familial Mediterranean fever.


Input: Either the role of the adaptive immune system or the interaction between innate and adaptive immune systems in familial Mediterranean fever (FMF) is not clear so far.


Input: So, we planned to search for the interaction between the innate and adaptive immune systems in the pathogenesis of FMF by investigating polymorphism for CTLA-4 gene, which plays a role in controlling antigen presentation to T cells.


Input: We also aimed to investigate whether there is an association between-318C/T and + 49A/G polymorphisms in the CTLA-4 gene and the main clinical features of the disease.


Input: 75 FMF patients and 179 controls were studied.


Input: Polymorphism was detected by the PCR-RFLP technique.


Input: The CT genotype and T allele frequencies of the-318C/T polymorphism and the haplotype frequency for the-318T/+ 49A in the CTLA-4 gene were higher in the FMF (21. 3, 21. 3, and 10. 7%) when compared with the controls (10. 6, 10. 6, and 5. 3%; P = 0. 029, 0. 044, and 0. 029).


Input: However, these differences did not reach a statistically significant level after the Bonferroni correction.


Input: A significant linkage disequilibrium was found between the-318C/T and + 49A/G polymorphisms in the CTLA-4 gene (D' = 0. 997, r (2) = 0. 027, P = 0. 0002).


Input: Genotype and carrier frequencies of the CTLA-4 gene + 49A/G polymorphism were not significantly different between FMF patients and healthy controls.


Input: No association was found between the studied polymorphisms and the main clinical features of the disease.


Input: Our findings suggest that although not statistically significant, higher frequencies of CTLA-4 gene-318CT genotype, T allele, and-318T/+ 49A haplotype in FMF patients may be related to the non-autoimmune pathogenesis of FMF.


Input: Anticholinesterase insecticide retrospective.


Input: The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades.

organophosphorus

methylcarbamate


Input: About 90 of these compounds are still in use-the largest number for any insecticide chemotype or mode of action.


Input: In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death.

acetylcholine


Input: The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction.


Input: Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations.

amino acid


Input: Species selectivity is determined in part by inhibitor and target site specificity.


Input: Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity.


Input: Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others.

glutathione S


Input: Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains.


Input: The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10years ago for several reasons: there have been no major new compounds for 30years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed.


Input: Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system.


Input: The OPs and MCs are down but not out.


Input: Disposition and metabolism of [(1) 4 C] PTZ601 in healthy volunteers.

[(1) 4 C] PTZ601


Input: 1. Six healthy male subjects were given a single dose of 500 mg of [14C] PTZ601 (mean radioactivity 79. 2 mu Ci) by intravenous (IV) infusion over 1 h, and observed for 5 days post-dose during which pharmacokinetic (PK) samples were collected.

[14C] PTZ601


Input: Plasma PTZ601 concentrations and metabolite identification were determined using LC-MS/MS; PK parameters were estimated by non-compartmental analysis.


Input: Excretion and mass balance were determined with liquid scintillation analysis and metabolites profiling was characterized by HPLC online radiochemical detection.


Input: 2. The disposition of PTZ601 was best described by a fast absorption, followed by a biphasic elimination phase.


Input: Peak PTZ601 plasma concentrations were reached within 0. 5-1 h.


Input: The mean elimination half-life was 1. 6 h and clearance was 13 L/h.


Input: 3. Recovery of the radioactivity dose was complete (mean 92%).


Input: The main route of excretion (parent and metabolites) was the renal route, as urine accounted for 69-77%, while feces only 13-22%, of the total radioactivity.


Input: 4. The majority of the drug was excreted in urine as multiple open ring metabolites: M17. 3 (oxidative ring-opened product) and M22. 2 (di-cysteine conjugate of 17. 3); unchanged PTZ601 in urine contributed to 15% of radioactivity.

di-cysteine


Input: The major metabolites detected in plasma were M17. 3, M12. 8 (acetylated M17. 3), M22. 2, and M41. 4 (methylated M17. 3).


Input: 5. PTZ601 was well tolerated.


Input: Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes.


Input: OBJECTIVE To examine the cost-effectiveness of a hepatitis B vaccination program for unvaccinated adults with diagnosed diabetes in the U. S.


Input: RESEARCH DESIGN AND METHODS We used a cost-effectiveness simulation model to estimate the cost-effectiveness of vaccinating adults 20-59 years of age with diagnosed diabetes not previously vaccinated for or infected by hepatitis B virus (HBV).


Input: The model estimated acute and chronic HBV infections, complications, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.


Input: Data sources included surveillance data, epidemiological studies, and vaccine prices.


Input: RESULTS With a 10% uptake rate, the intervention will vaccinate 528, 047 people and prevent 4, 271 acute and 256 chronic hepatitis B infections.


Input: Net health care costs will increase by $91. 4 million, and 1, 218 QALYs will be gained, producing a cost-effectiveness ratio of $75, 094 per QALY gained.


Input: Results are most sensitive to age, the discount rate, the hepatitis B incidence ratio for people with diabetes, and hepatitis B infection rates.


Input: Cost-effectiveness ratios rise with age at vaccination; an alternative intervention that vaccinates adults with diabetes 60 years of age or older had a cost-effectiveness ratio of $2. 7 million per QALY.


Input: CONCLUSIONS Hepatitis B vaccination for adults with diabetes 20-59 years of age is modestly cost-effective.


Input: Vaccinating older adults with diabetes is not cost-effective.


Input: The study did not consider hepatitis outbreak investigation costs, and limited information exists on hepatitis progression among older adults with diabetes.


Input: Partly based on these results, the Advisory Committee on Immunization Practices recently recommended hepatitis B vaccination for people 20-59 years of age with diagnosed diabetes.


Input: Postpartum corticosterone administration reduces dendritic complexity and increases the density of mushroom spines of hippocampal CA3 arbours in dams.

corticosterone


Input: Postpartum depression (PPD) affects approximately 15% of mothers after giving birth.


Input: A complete understanding of depression during the postpartum period has yet to be established, although disruptions in the hypothalamic-pituitary-adrenal axis and stress during the postpartum may be involved.


Input: To model these components in rats, we administered high corticosterone (CORT) postpartum, which increases immobility in the forced swim test (FST), and reduces maternal care, body weight and hippocampal cell proliferation in dams.

corticosterone

CORT


Input: The hippocampus is altered in response to chronic stress, exposure to high glucocorticoids and in major depression in humans.


Input: In the present study, we examined whether high CORT reduced dendritic complexity and spines in the CA3 region of the hippocampus.

CORT


Input: Additionally, housing complexity was manipulated so that dams and litters were housed either with tubes (complex) or without tubes (impoverished) to investigate the consequences of new animal care regulations.


Input: Dams received 40 mg/kg/day of CORT or oil starting on day 2 postpartum for 23 days.

CORT


Input: Maternal behaviours were assessed on postpartum days 2-8 and dams were tested using the FST on days 21 and 22.


Input: Dams were killed on day 24 and brains were processed for Golgi impregnation.


Input: Pyramidal cells in the CA3 subfield were traced using a camera lucida and analysed for branch points and dendritic complexity, as well as spine density and type on both basal and apical arbours.


Input: As previously established, high CORT postpartum reduced maternal care and increased immobility in the FST, which is a measure of depressive-like behaviour.

CORT


Input: High CORT postpartum reduced the complexity of basal arbours and increased mushroom spines on both apical and basal dendrites.

CORT


Input: Housing complexity had no effect on spines of CA3 pyramidal cells but modest effects on cell morphology.


Input: These data show that chronic high CORT in postpartum females alters hippocampal morphology and may provide insight regarding the neurobiological consequences of high stress or CORT during the postpartum period, as well as be relevant for postpartum stress or depression.

CORT

CORT


Input: Drug metabolizing enzymes in the perinatal and neonatal period: differences in the expression and activity.


Input: Physiological changes occurring perinatally and in the first month of life can affect the answer to a pharmacological treatment and the individual response to a drug in terms of efficacy and toxicity is highly variable in the neonatal population.


Input: Among potential causes for such variability, differences in drug metabolism may have a great impact.


Input: This article aims to review qualitative and quantitative differences in drug metabolizing enzymes in neonates, since both phase I and phase II metabolic pathways are immature at birth and subject to maturational changes in the first period of extrauterine life.


Input: Moreover, clinical implications will be discussed.


Input: Effects of anti-cocaine vaccine and viral gene transfer of cocaine hydrolase in mice on cocaine toxicity including motor strength and liver damage.

cocaine

cocaine

cocaine


Input: In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination.

cocaine

cocaine

cocaine

cocaine


Input: Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice.

cocaine


Input: Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120mg/kg, i. p.).

cocaine


Input: We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1mg/kg; antibody, 8mg/kg), they provided complete protection of liver tissue and motor function.


Input: When the enzyme levels were ~ 400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone.


Input: The prolyl-isomerase Pin1 activates the mitochondrial death program of p53.

prolyl


Input: In response to intense stress, the tumor protein p53 (p53) tumor suppressor rapidly mounts a direct mitochondrial death program that precedes transcription-mediated apoptosis.


Input: By eliminating severely damaged cells, this pathway contributes to tumor suppression as well as to cancer cell killing induced by both genotoxic drugs and non-genotoxic p53-reactivating molecules.


Input: Here we have explored the role had in this pathway by the prolyl-isomerase Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1), a crucial transducer of p53' s phosphorylation into conformational changes unleashing its pro-apoptotic activity.

prolyl


Input: We show that Pin1 promotes stress-induced localization of p53 to mitochondria both in vitro and in vivo.


Input: In particular, we demonstrate that upon stress-induced phosphorylation of p53 on Ser46 by homeodomain interacting protein kinase 2, Pin1 stimulates its mitochondrial trafficking signal, that is, monoubiquitination.


Input: This pathway is induced also by the p53-activating molecule RITA, and we demonstrate the strong requirement of Pin1 for the induction of mitochondrial apoptosis by this compound.


Input: These findings have significant implications for treatment of p53-expressing tumors and for prospective use of p53-activating compounds in clinics.


Input: Applicability of a keratinocyte gene signature to predict skin sensitizing potential.


Input: There is a need to replace animal tests for the identification of skin sensitizers and currently many alternative assays are being developed that have very promising results.


Input: In this study a gene signature capable of very accurate identification of sensitizers was established in the HaCaT human keratinocyte cell line.


Input: This signature was evaluated in a separate study using six chemicals that are either local lymph node (LLNA) false-positive or false-negative chemicals in addition to nine sensitizers and four non-sensitizers.


Input: Similar studies do not apply these more difficult to classify chemicals, which show the true potential for human predictions of an assay.


Input: Although the gene signature has improved prediction accuracy compared to the LLNA, the misclassified compounds were comparable between the two assays.


Input: Gene profiling also showed a sensitizer specific response of the Nrf2-keap1 and Toll-like receptor signaling pathways.


Input: After exposure to non-sensitizing chemicals that induce either of the pathways the signature misclassified all Nrf2-inducers, while the Toll-like receptor ligands were correctly classified.


Input: In conclusion, we confirm that keratinocyte based prediction assays may provide essential information on the properties of compounds.


Input: Furthermore, chemical selection is critical for assessment of the performance of in vitro alternative assays.


Input: Configuration space partitioning and matrix buildup scaling for the vibrational configuration interaction method.


Input: The accurate computation of anharmonic vibrational states for medium to large molecules is a requirement for the detailed understanding of nonlinear multidimensional infrared spectra and the dynamical information encoded in them.


Input: The vibrational configuration interaction (VCI) method constitutes a particularly promising tool in this respect.


Input: It is generally hampered though by its unfavorable scaling with respect to system size.


Input: We analyze the scaling behavior of several well-known as well as some new approximate VCI schemes in detail, which are complementary to the class of configuration selection schemes developed recently.


Input: We find that the combination of a configuration space partitioning, possibly based on configuration selection, with energetic thresholding and resonance screening provides an efficient scheme for the reduction of computational effort involved in VCI calculations while at the same time maintaining sufficient accuracy for the vibrational energies.


Input: Carbon nanotube functionalization with carboxylic derivatives: a DFT study.

Carbon

carboxylic


Input: Chemical functionalization of a single-walled carbon nanotube (CNT) with different carboxylic derivatives including-COOX (X = H, CH3, CH2NH2, CH3Ph, CH2NO2, and CH2CN) has been theoretically investigated in terms of geometric, energetic, and electronic properties.

carbon

carboxylic

COOX

H


Input: Reaction energies have been calculated to be in the range of-0. 23 to-7. 07 eV.


Input: The results reveal that the reaction energy is increased by increasing the electron withdrawing character of the functional groups so that the relative magnitude order is-CH2NO2 >-CH2CN >-H >-CH2Ph >-CH3 >-CH2NH2.

H


Input: The chemical functionalization leads to an increase in HOMO/LUMO energy gap of CNT by about 0. 32 to 0. 35 eV (except for-H).

HOMO


Input: LUMO, HOMO, and Fermi level of the CNT are shifted to lower energies especially in the case of-CH2NO2 and-CH2CN functional groups.


Input: Therefore, it leads to an increment in work function of the tube, impeding the field electron emission.


Input: Ultrasound promoted one-pot synthesis of 2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile scaffolds in aqueous media: a complementary' green chemistry' tool to organic synthesis.

2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile


Input: A green and simple approach to assembling of 2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile scaffolds via three-component reaction of kojic acid, malononitrile, and aromatic aldehydes in aqueous media under ultrasound irradiation is described.

2-amino-4, 8-dihydropyrano [3, 2-b] pyran-3-carbonitrile

kojic acid

malononitrile

aromatic aldehydes


Input: The combinatorial synthesis was achieved for this methodology with applying ultrasound irradiation while making use of water as green solvent.


Input: In comparison to conventional methods, experimental simplicity, good functional group tolerance, excellent yields, short routine, and selectivity without the need for a transition metal or base catalyst are prominent features of this green procedure.

transition metal


Input: Cell transplantation approaches to retinal ganglion cell neuroprotection in glaucoma.

retinal


Input: Glaucoma is a complex neurodegenerative disease that involves interactions among multiple signaling pathways, ultimately leading to progressive retinal ganglion cell (RGC) death.

retinal


Input: The development of neuroprotective approaches to glaucoma therapy could preserve vision by modulating these pathologic pathways or by acting directly on RGCs to attenuate cell death and maintain function.


Input: Intraocular cell transplantation is being evaluated as one approach to achieve sustained RGC neuroprotection.


Input: Unlike traditional pharmacological approaches, transplanted cells might be capable of simultaneously targeting multiple pro-survival pathways via local delivery of secreted factors and/or via modulation of the intraocular microenvironment.


Input: Elucidating the mechanisms by which different cell types attenuate RGC death in models of glaucoma may uncover additional novel mechanisms of neuroprotection.


Input: In this review, we will discuss the rationale for transplantation-based approaches to neuroprotection for glaucoma and explore the various mechanisms of action proposed to account for RGC neuroprotection achieved by two distinct cell classes that have been studied most extensively for this purpose: glial cells and mesenchymal stem cells.


Input: Adenosine and autism: a spectrum of opportunities.

Adenosine


Input: In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism.

adenosine


Input: In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities.

adenosine


Input: Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine' s influence might be a new therapeutic target for autism with multiple beneficial effects.

adenosine

adenosine


Input: This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.


Input: Rett syndrome treatment in mouse models: searching for effective targets and strategies.


Input: Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting girls with a prevalence of 1 in every 10, 000 births; it represents the second most common cause of intellectual disability in females.


Input: Mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2) have been identified as clear etiological factors in more than 90% of classical RTT cases.

methyl

CpG


Input: Whereas the mechanisms leading to the severe, progressive and specific neurological dysfunctions when this gene is mutated still remain to be elucidated, a series of different mouse models have been generated, bearing different Mecp2 mutation.


Input: Neurobehavioural analysis in these mouse lines have been carried out and phenotyping analysis can be now utilised to preclinically evaluate the effects of potential RTT treatments.


Input: This review summarizes the different results achieved in this research field taking into account different key targets identified to ameliorate RTT phenotype in mouse models, including those not directly downstream of MeCP2 and those limited to the early phases of postnatal development.


Input: This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.


Input: Rhythm and blues: animal models of epilepsy and depression comorbidity.


Input: Clinical evidence shows a strong, bidirectional comorbidity between depression and epilepsy that is associated with decreased quality of life and responsivity to pharmacotherapies.


Input: At present, the neurobiological underpinnings of this comorbidity remain hazy.


Input: To complicate matters, anticonvulsant drugs can cause mood disturbances, while antidepressant drugs can lower seizure threshold, making it difficult to treat patients suffering from both depression and epilepsy.


Input: Animal models have been created to untangle the mechanisms behind the relationship between these disorders and to serve as screening tools for new therapies targeted to treat both simultaneously.


Input: These animal models are based on chemical interventions (e. g. pentylenetetrazol, kainic acid, pilocarpine), electrical stimulations (e. g. kindling, electroshock), and genetic/selective breeding paradigms (e. g. genetically epilepsy-prone rats (GEPRs), genetic absence epilepsy rat from Strasbourg (GAERS), WAG/Rij rats, swim lo-active rats (SwLo)).

pentylenetetrazol

kainic acid

pilocarpine


Input: Studies on these animal models point to some potential mechanisms that could explain epilepsy and depression comorbidity, such as various components of the dopaminergic, noradrenergic, serotonergic, and GABAergic systems, as well as key brain regions, like the amygdala and hippocampus.


Input: These models have also been used to screen possible therapies.


Input: The purpose of the present review is to highlight the importance of animal models in research on comorbid epilepsy and depression and to explore the contributions of these models to our understanding of the mechanisms and potential treatments for these disorders.


Input: Erectile dysfunction as a cardiovascular risk factor in patients with diabetes.


Input: Erectile dysfunction (ED) is a highly prevalent disorder among patients with diabetes mellitus (DM).


Input: In most cases, ED is considered a vascular disease and its development is significantly related to the exposure to CVD risk factors.


Input: In this context, ED and coronary artery disease (CAD) have been proposed as different manifestations of the same systemic disease; in nondiabetic patients, ED has progressively emerged as an important sentinel marker of the subsequent onset of CVD events.


Input: The aim of this review was to evaluate the association between ED and CAD in diabetic patients and to evaluate the role of ED as an independent CVD risk factor in these patients.


Input: Three large prospective studies confirmed that ED is a powerful predictor of CAD and cardiac mortality in patients with DM.


Input: Overall, diabetic patients with ED had roughly 1. 4-fold higher risk of CAD as compared with those without ED.


Input: Interestingly, in diabetic patients, CAD is often silent and CAD screening according to the current guidelines can miss up to 40% patients with occult myocardial perfusion abnormalities.


Input: Indeed, patients with ED have higher risk of silent myocardial ischemia compared to those without ED, and when ED is added to the risk factors, it can even improve the sensitivity of screening for asymptomatic CAD.


Input: Therefore, ED should be considered an independent CVD risk factor, and it could improve the identification of diabetic patients suitable for screening, leading to an early detection of CAD, and thus potentially enhancing the therapeutic effectiveness.


Input: Resistance training decreases serum inflammatory markers in diabetic rats.


Input: Inflammation plays an important role in the genesis and progression of diabetes.


Input: The purpose of this study was to investigate the effect of resistance training on serum levels of some inflammatory markers associated with diabetes mellitus.


Input: Twenty-four male Wistar rats (290 +/- 19 g) were randomly divided into three groups: non-diabetic control (non-DC), diabetic control (DC), and diabetic trained (DT).


Input: Animals in DT group were subjected to a resistance training program with the use of a ladder (3 days/week, for 4 weeks).


Input: Body weight, serum high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, fasting glucose, and insulin were measured.

glucose


Input: Four weeks of resistance training decreased serum levels of TNF-alpha, hs-CRP, and IL-6 in diabetic rats when compared with DC animals.


Input: We conclude that resistance training with appropriate intensity, duration, and recovery between exercise bouts has marked anti-inflammatory effects on diabetic rats.


Input: This may be an efficient strategy to protect against some diabetic complications.


Input: Generation of monoclonal antibodies against the Gal beta 1-4Gal epitope: a key tool in studies of species-specific glycans expressed in fish, amphibians and birds.


Input: Whereas the Gal beta 1-4Gal epitope is rarely found in mammalian glycans, it has been found in glycans of various species of non-mammalian vertebrates, such as fish, amphibians and birds.


Input: Although glycans containing Gal beta 1-4Gal in these vertebrates were detected by precise structural analysis of the glycans using mass spectrometry and/or NMR spectrometry, there are no convenient methods to detect Gal beta 1-4Gal from various samples.


Input: To analyze systematically the distribution of Gal beta 1-4Gal in nature, we generated mouse monoclonal antibodies (mAbs) specific for Gal beta 1-4Gal using extracts of medaka eggs as an immunogen.


Input: Four mAbs (two immunoglobulin (Ig) Ms and two IgG1s) were obtained by enzyme-linked immunosorbent assay-based screening.


Input: The specificities of these mAbs were evaluated by frontal affinity chromatography using 142 kinds of 2-aminopyridine (PA)-derivatized oligosaccharides.


Input: While all mAbs interacted with (Gal beta 1-4Gal)-containing oligosaccharides at their non-reducing termini with dissociation constants (K (d)) ranging from 1. 0 x 10-5 to 2. 8 x 10-4 M, no apparent interaction was observed with any other glycans.


Input: The number of branches containing Gal beta 1-4Gal on N-glycans did not significantly affect K (d) of mAbs of IgG1 subclasses, but those of IgM mAbs were decreased by ~ 1 order of magnitude, in increments of the number of branches present.

N


Input: Using the mAbs, we established that Gal beta 1-4Gal is also expressed on glycoproteins in various tissues from the African clawed frog.


Input: Immunohistochemical staining of medaka sections revealed that Gal beta 1-4Gal epitopes were expressed in the endothelium, epithelium and epidermis, which directly contact the external environment or invading organisms.


Input: Thus, these mAbs are useful for systematically investigating the species-specific expression of glycans, which may act as a barrier against infection.


Input: Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation.

Diethyldithiocarbamate

copper


Input: Dithiocarbamates are nitrogen-and sulfur-containing compounds commonly used in pharmacology, medicine and agriculture.

Dithiocarbamates

nitrogen

sulfur


Input: The molecular effects of dithiocarbamates on neuronal cell systems are not fully understood, especially in terms of their ability to accumulate copper ions inside the cell.

dithiocarbamates

copper


Input: In this work, the molecular effects of N, N-diethyldithiocarbamate (DEDTC) were studied in human SH-SY5Y neuroblastoma cells to determine the role of copper in the DEDTC toxicity and the pathway trigged in cell by the complex Cu-DEDTC.

N, N-diethyldithiocarbamate

DEDTC

copper

DEDTC

Cu-DEDTC


Input: From concentration-dependent studies, we found that 5 mu M of this compound induced a drastic decrease in viable cells with a concomitant accumulation in intracellular copper resulted from complexation with DEDTC, measured by atomic absorption spectroscopy.

copper

DEDTC


Input: The mechanism of DEDTC-induced apoptosis in neuronal model cells is thought to occur through the death receptor signaling triggered by DEDTC-copper complex in low concentration that is associated with the activation of caspase 8.

DEDTC

DEDTC-copper


Input: Our results indicated that the mechanism of cell death involves cytochrome c release forming the apoptosome together with Apaf-1 and caspase 9, converting the caspase 9 into its active form, allowing it to activate caspase 3 as observed by immunofluorescence.


Input: This pathway is induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions present in the culture medium and transports them into the cell, suggesting that the DEDTC by itself was not able to cause cell death and the major effect is from its copper-complex in neuroblastoma cells.

DEDTC

copper

DEDTC

copper


Input: The present study suggests a role for the influence of copper by low concentrations of DEDTC in the extracellular media, the absorption and accumulation of copper in the cell and apoptotic events, induced by the cytotoxic effects that occur when DEDTC forms a complex with the copper ions.

copper

DEDTC

copper

DEDTC

copper


Input: Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.


Input: As part of the ACuteTox project aimed at the development of non-animal testing strategies for predicting human acute oral toxicity, aggregating brain cell cultures (AGGR) were examined for their capability to detect organ-specific toxicity.


Input: Previous multicenter evaluations of in vitro cytotoxicity showed that some 20% of the tested chemicals exhibited significantly lower in vitro toxicity as expected from in vivo toxicity data.


Input: This was supposed to be due to toxicity at supracellular (organ or system) levels.


Input: To examine the capability of AGGR to alert for potential organ-specific toxicants, concentration-response studies were carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression levels of four selected genes.


Input: The lowest observed effect concentration (LOEC) determined for each chemical was compared with the IC20 reported for the 3T3/NRU cytotoxicity assay.


Input: A LOEC lower than IC20 by at least a factor of 5 was taken to alert for organ-specific toxicity.


Input: The results showed that the frequency of alerts increased with the level of toxicity observed in AGGR.


Input: Among the chemicals identified as alert were many compounds known for their organ-specific toxicity.


Input: These findings suggest that AGGR are suitable for the detection of organ-specific toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay, improve the predictive capacity of in vitro toxicity testing.


Input: Silver nanoparticle-induced cytotoxicity in rat brain endothelial cell culture.

Silver


Input: Silver nanoparticles (AgNPs) are among the most widely commercialised engineered nanomaterials, because of their antimicrobial properties.

Silver


Input: They are already commonly used in medical devices, household products and industry.


Input: Concerns have been raised about potential adverse health effects due to increasing dispersion of AgNPs in the environment.


Input: The present study examined the cytotoxic effects of spherical, citrate-coated AgNPs (10, 50 and 100 nm) in rat brain endothelial (RBE4) cells and investigated whether the observed effects can be explained by the intrinsic toxicity of the particles or the silver ions released from the particles.

citrate

silver


Input: The results indicated that exposure of RBE4 cells to AgNPs lead to significant reduction in dye uptake as measured with the Neutral red (NR) assay.

Neutral red


Input: The effect was found to be related to particle size, surface area, dose and exposure time.


Input: In contrast, silver ions increased NR uptake (ca. 10%) in RBE4 cells after 1h, while a reduction in NR uptake was observed after 24h exposure at high concentrations (20-30 mu M).

silver


Input: Colony formation, as an indicator of proliferation ability, was completely inhibited by AgNPs at concentrations higher than 1 mu g/ml.


Input: Silver ions had less effect on the colony formation of RBE4 cells than AgNPs.

Silver


Input: The effects of sonographic and demographic features and needle size on obtaining adequate cytological material in sonography-guided fine-needle aspiration biopsy of thyroid nodules.


Input: The aim of this study is to investigate the effects of the sonographic characteristics of the nodule, demographic features of patient, and nodule size and needle size used for sampling, on obtaining adequate cytological material (CM) in thyroid fine-needle aspiration biopsy (FNAB).


Input: We performed 270 FNAB between September 2010 and June 2012.


Input: Size, echogenicity, and localization of all nodules were evaluated by ultrasonography (US) before the biopsy.


Input: Nodules were grouped as < 1, 1-3, and > 3 cm according to their size and as hypoechoic, isoechoic, hyperechoic, or heterogeneous according to their US characteristics.


Input: 20-, 22-, and 24-G needles were used for the biopsies.


Input: Different sonographic characteristics of the nodules did not affect the needle selection.


Input: All specimens were classified as adequate or inadequate CM by a cytopathologist.


Input: A total of 270 nodules were biopsied, 184 (68. 1%) specimens were considered as adequate CM and 86 (31. 9%) specimens were considered as inadequate CM.


Input: Patient age and the presence of heterogeneous echogenicity were found to have prognostic significance in univariate analysis (p < 0. 05).


Input: In a multivariate logistic regression model with forward stepwise method, advanced age (p = 0. 001, OR = 1. 042, 95CI 1. 018-1. 068) and heterogeneous echogenicity (p = 0. 017, OR = 1. 955, 95CI 1. 129-3. 385) remained associated with an increased risk of inadequate CM obtainment after adjustment for other potential confounders (nodule size > 3 cm and needle size 20-G usage) and variables found to be statistically significant in univariate analysis.


Input: Non-diagnostic FNAB remains a significant problem in the evaluation of thyroid nodules and can be as high as 30%.


Input: Inadequate CM rates for elderly patients and heterogeneous nodules were significantly higher than that for other factors.


Input: The nodule size and needle size used for sampling did not affect the adequacy of FNAB.


Input: Delayed temporal increase of hepatic Hsp70 in ApoE knockout mice after prenatal arsenic exposure.

arsenic


Input: Prenatal arsenic exposure accelerates atherosclerosis in ApoE (-/-) mice by unknown mechanism.

arsenic


Input: Arsenic is a hepatotoxicant, and liver disease increases atherosclerosis risk.

Arsenic


Input: Prenatal arsenic exposure may predispose to liver disease by priming for susceptibility to other environmental insults.

arsenic


Input: Earlier microarray analyses showed prenatal arsenic exposure increased Hsc70 (HspA8) and Hsp70 (HspA1a) mRNAs in livers of 10-week-old mice.

arsenic


Input: We determined effects of prenatal arsenic exposure on hepatic Hsp70 and Hsc70 expression by Western blot and on DNA methylation by methyl acceptance assay during prenatal and postnatal development.

arsenic

methylation


Input: Pregnant ApoE (-/-) mice were given drinking water containing 85 mg/l NaAsO (2) (49 ppm arsenic) from gestation day (GD) 8 to 18.

NaAsO (2)

arsenic


Input: Hsp70 and Hsc70 expression and DNA methylation were determined in GD18 fetuses and 3-, 10-, and 24-week-old mice.


Input: Hsc70 expression was unchanged at all ages.


Input: Hsp70 induction was observed at 3 and 10 weeks, but was unchanged in GD18 fetuses and 24-week livers of mice.


Input: Global DNA methylation increased with age; arsenic had no effects.

arsenic


Input: Bisulfite sequencing of DNA from livers of 10-week-old mice showed Hsp70 promoter region methylation was unchanged, but methylation was increased within the transcribed region.

Bisulfite


Input: Hsf1 and Nrf2 nuclear translocation were investigated as potential mechanisms of Hsp70 induction and found unaltered.


Input: Putative binding sites were identified in HSP70 for in utero arsenic exposure-suppressed microRNAs suggesting a possible mechanism.

arsenic


Input: Thus, prenatal arsenic exposure causes delayed temporal hepatic Hsp70 induction, suggesting a transient state of stress in livers which can predispose the mice to developing liver disease.

arsenic


Input: Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-alpha pharmacology.


Input: Inhibitor-of-apoptosis (IAP) proteins suppress apoptosis and are overexpressed in a variety of cancers.


Input: Small-molecule IAP antagonists are currently being tested in clinical trials as novel cancer therapeutics.


Input: GDC-0152 is a small-molecule drug that triggers tumor cell apoptosis by selectively antagonizing IAPs.


Input: GDC-0152 induces NF-kappa B transcriptional activity leading to expression of several chemokines and cytokines, of which tumor necrosis factor alpha (TNF-alpha) is the most important for single-agent tumor activity.


Input: TNF-alpha is a pleiotropic cytokine that drives a variety of cellular responses, comprising inflammation, proliferation, and cell survival or death depending on the cellular context.


Input: As malignant and normal cells produce TNF-alpha upon IAP antagonism, increased TNF-alpha could drive both efficacy and toxicity.


Input: The toxicity profile of GDC-0152 in dogs and rats was characterized after iv dose administration once every 2 weeks for four doses.


Input: Findings in both species consisted of a dose-related, acute, systemic inflammatory response, and hepatic injury.


Input: Laboratory findings included elevated plasma cytokines, an inflammatory leukogram, and increased liver transaminases with histopathological findings of inflammatory infiltrates and apoptosis/necrosis in multiple tissues; a toxicology profile consistent with TNF-alpha-mediated toxicity.


Input: Dogs exhibited more severe findings than rats, and humans did not exhibit these findings, at comparable exposures across species.


Input: Furthermore, elevations in blood neutrophil count, serum monocyte chemoattractant protein-1, and other markers of inflammation corresponded to GDC-0152 exposure and toxicity and thus may have utility as safety biomarkers.


Input: Don' t judge a neuron only by its cover: neuronal function in in vitro developmental neurotoxicity testing.


Input: Classical cases of developmental neurotoxicity (DNT) in humans and advances in risk assessment methods did not prevent the emergence of new chemicals with (suspected) DNT potential.


Input: Exposure to these chemicals may be related to the increased worldwide incidence of learning and neurodevelopmental disorders in children.


Input: DNT is often investigated in a traditional manner (in vivo using large numbers of experimental animals), whereas development of in vitro methods for DNT reduces animal use and increases insight into cellular and molecular mechanisms of DNT.


Input: Several essential neurodevelopmental processes, including proliferation, migration, differentiation, formation of axons and dendrites, synaptogenesis, and apoptosis, are already being evaluated in vitro using biochemical and morphological endpoints.


Input: Yet, investigation of chemical-induced effects on the development of functional neuronal networks, including network formation, inter-and intracellular signaling and neuronal network function, is underrepresented in DNT testing.


Input: This view therefore focuses on in vitro models and innovative experimental approaches for functional DNT testing, ranging from optical and electrophysiological measurements of intra-and intercellular signaling in neural stem/progenitor cells to measurements of network activity in neuronal networks using multielectrode arrays.


Input: The development of functional DNT assays will strongly support the decision-making process for measures to prevent potential chemical-induced adverse effects on neurodevelopment and cognition in humans.


Input: We therefore argue that for risk assessment, biochemical and morphological approaches should be complemented with investigations of neuronal (network) functionality.


Input: Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.

nitric oxide

acrolein

cyclophosphamide


Input: Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent.

cyclophosphamide


Input: Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis.

Acrolein

cyclophosphamide


Input: Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats.

acrolein


Input: Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h.

Acrolein


Input: Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h.

Acrolein


Input: Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment.

nitric oxide

NO

acrolein


Input: Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder.

acrolein

nitrite

nitrate


Input: The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels.

acrolein

nitrite

nitrate


Input: IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels.

acrolein


Input: The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody.

acrolein

acrolein


Input: Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment.

acrolein


Input: Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis.

acrolein


Input: These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.

cyclophosphamide


Input: A novel reproductive peptide, phoenixin.

phoenixin


Input: Normal anterior pituitary function is essential for fertility.


Input: Release from the gland of the reproductive hormones luteinising hormone and follicle-stimulating hormone is regulated primarily by hypothalamically-derived gonadotrophin-releasing hormone (GnRH), although other releasing factors (RF) have been postulated to exist.

gonadotrophin-releasing hormone

GnRH


Input: Using a bioinformatic approach, we have identified a novel peptide, phoenixin, that regulates pituitary gonadotrophin secretion by modulating the expression of the GnRH receptor, an action with physiologically relevant consequences.

phoenixin

GnRH


Input: Compromise of phoenixin in vivo using small interfering RNA resulted in the delayed appearance of oestrus and a reduction in GnRH receptor expression in the pituitary.

phoenixin

GnRH


Input: Phoenixin may represent a new class of hypothalamically-derived pituitary priming factors that sensitise the pituitary to the action of other RFs, rather than directly stimulating the fusion of secretary vesicles to pituitary membranes.

Phoenixin


Input: Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.


Input: Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth.


Input: Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain.


Input: In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome.


Input: These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans.


Input: Robust and aligned carbon nanotube/titania core/shell films for flexible TCO-free photoelectrodes.

carbon

titania


Input: Carbon nanotube (CNT)/semiconducting oxide hybrids are an ideal architecture for light-harvesting devices, in which the CNTs are expected to not only act as a scaffold but also provide fast transport paths for photogenerated charges in the oxide.

Carbon

oxide

oxide


Input: However, the current potential of CNTs for charge transport is largely suppressed due to the nanotubes not being interconnected but isolated by the low conductive oxide coatings.

oxide


Input: Herein, a flexible and conductive CNT/TiO (2) core/shell heterostructure film is reported, with aligned and interconnected CNTs wrapped in a continuous TiO (2) coating.

TiO (2)

TiO (2)


Input: Without using additional transparent conducting oxide (TCO) substrates, this unique feature of the film boosts the incident photon-to-electron conversion efficiency to 32%, outperforming TiO (2) nanoparticle electrodes fabricated on TCO substrates.

oxide

TiO (2)


Input: Moreover, the film shows high structural stability and can generate a stable photocurrent even after being bent hundreds of times.


Input: The core cysteines, (C909) of islet antigen-2 and (C945) of islet antigen-2 beta, are crucial to autoantibody binding in type 1 diabetes.

cysteines


Input: Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA-2) autoantibodies (IA-2A), possibly through disulfide bond formation.

Cysteines

disulfide


Input: We therefore investigated which cysteines are critical to IA-2A binding in patients with newly diagnosed type 1 diabetes.

cysteines


Input: All 10 cysteines in the intracellular domain of IA-2 were modified to serine by site-directed mutagenesis, and the effects of these changes on autoantibody binding in comparison with wild-type control were investigated by radiobinding assay.

cysteines

serine


Input: Mutation of the protein tyrosine phosphatase (PTP) core cysteine (C909) in IA-2 caused large reductions in autoantibody binding.

tyrosine

cysteine


Input: In contrast, little or no reduction in binding was seen following substitution of the other cysteines.

cysteines


Input: Modification of the core cysteine (C945) in IA-2 beta also greatly reduced autoantibody binding.

cysteine


Input: Lysine substitution of glutamate-836 in IA-2 or glutamate-872 in IA-2 beta resulted in modest reductions in binding and identified a second epitope region.

Lysine

glutamate

glutamate


Input: Binding to IA-2 PTP and IA-2 beta PTP was almost abolished by mutation of both the core cysteine and these glutamates.

cysteine

glutamates


Input: The core cysteine is key to the major PTP conformational epitope, but disulfide bonding contributes little to IA-2A epitope integrity.

cysteine


Input: In most patients, at disease onset, > 90% of antibodies binding to the PTP domain of IA-2 recognize just two epitope regions.


Input: Role of oestrogen receptors on the modulation of NADPH-diaphorase-positive cell number in supraoptic and paraventricular nuclei of ovariectomised female rats.

oestrogen

NADPH


Input: Modulation of the nitric oxide producing system (demonstrated via the NADPH-diaphorase histochemical reaction) by oestradiol has been established in several structures of the rat brain.

nitric oxide

NADPH

oestradiol


Input: The present study aimed to explore the possible regulation of NADPH-diaphorase activity by oestradiol in neurones of the supraoptic (SON) and paraventricular (PVN) nuclei and the role of oestrogen receptors (ER alpha and ER beta) in this regulation.

NADPH

oestradiol

oestrogen


Input: Adult ovariectomised rats were divided into six groups and injected either with vehicle or a single dose of oestradiol, a selective ER alpha agonist-PPT [4, 4', 4''-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol], a selective ER beta agonist-DPN [2, 3-bis (4-hydroxyphenyl)-propionitrile], a selective ER alpha antagonist-MPP [1, 3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride] or a selective ER beta antagonist-PHTPP (4-[2-phenyl-5, 7-bis (trifluoromethyl) pyrazolo [1, 5-a] pyrimidin-3-yl] phenol).

oestradiol

PPT

4, 4', 4''-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol

DPN

2, 3-bis (4-hydroxyphenyl)-propionitrile

MPP

1, 3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol

1H-pyrazole dihydrochloride

PHTPP

4-[2-phenyl-5, 7-bis (trifluoromethyl) pyrazolo [1, 5-a] pyrimidin-3-yl] phenol


Input: The number of NADPH-diaphorase positive elements in the SON and the PVN was modulated by both ERs but, depending on the nucleus, ER alpha and ER beta ligands induced different effects.

NADPH


Input: These results suggest that the regulation of nitrergic system by ERs may play a role in the control of oestrogen-dependent physiological mechanisms regulated by the SON and the PVN.

oestrogen


Input: Influence of stimulant-induced hyperactivity on social approach in the BTBR mouse model of autism.


Input: Translational research is needed to discover pharmacological targets and treatments for the diagnostic behavioral domains of autism spectrum disorders.


Input: Animal models with phenotypic relevance to diagnostic criteria offer clear experimental strategies to test the efficacy and safety of novel treatments.


Input: Antagonists of mGluR5 receptors are in clinical trials for Fragile X syndrome and under investigation for the treatment of autism spectrum disorders.


Input: However, in preclinical studies of mGluR5 compounds tested in our laboratory and others, increased locomotion following mGluR5 modulation has been observed.


Input: Understanding the influence of general activity on sociability and repetitive behaviors will increase the accuracy of interpretations of positive outcomes measured from pharmacological treatment that produces locomotor activating or sedating effects.


Input: In the present studies, dose-response curves for d-amphetamine (AMPH)-induced hyperlocomotion were similar in standard B6 mice and in the BTBR mouse model of autism.

d-amphetamine

AMPH


Input: AMPH produced significant, robust reductions in the high level of repetitive self-grooming that characterizes BTBR, and also reduced the low baseline grooming in B6, indicating that AMPH-induced hyperlocomotion competes with time spent engaged in self-grooming.

AMPH

AMPH


Input: We then tested AMPH in B6 and BTBR on the 3-chambered social approach task.

AMPH


Input: One component of sociability, the time spent in the chamber with the novel mouse, in B6 mice was reduced, while the sniffing time component of sociability in BTBR mice was enhanced.


Input: This finding replicated across multiple cohorts treated with AMPH and saline vehicle.

AMPH


Input: In-depth analysis revealed that AMPH increased the number and decreased the duration of sniffing bouts in BTBR, suggesting BTBR treated with AMPH mostly engaged in brief sniffs rather than true social interactions with the novel mouse during the social approach task.

AMPH

AMPH


Input: Our data suggest that compounds with stimulant properties may have some direct benefits on reducing repetitive behaviors in autism spectrum disorders, particularly in the subset of autistic individuals with hyperactivity.


Input: This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.


Input: Estrogen receptor-alpha is required for the osteogenic response to mechanical loading in a ligand-independent manner involving its activation function 1 but not 2.

Estrogen


Input: Estrogen receptor-alpha (ER alpha) is crucial for the adaptive response of bone to loading but the role of endogenous estradiol (E2) for this response is unclear.

Estrogen

estradiol


Input: To determine in vivo the ligand dependency and relative roles of different ER alpha domains for the osteogenic response to mechanical loading, gene-targeted mouse models with (1) a complete ER alpha inactivation (ER alpha (-/-)), (2) specific inactivation of activation function 1 (AF-1) in ER alpha (ER alpha AF-1 (0)), or (3) specific inactivation of ER alpha AF-2 (ER alpha AF-2 (0)) were subjected to axial loading of tibia, in the presence or absence (ovariectomy [ovx]) of endogenous E2.


Input: Loading increased the cortical bone area in the tibia mainly as a result of an increased periosteal bone formation rate (BFR) and this osteogenic response was similar in gonadal intact and ovx mice, demonstrating that E2 (ligand) is not required for this response.


Input: Female ER alpha (-/-) mice displayed a severely reduced osteogenic response to loading with changes in cortical area (-78% +/- 15%, p < 0. 01) and periosteal BFR (-81% +/- 9%, p < 0. 01) being significantly lower than in wild-type (WT) mice.


Input: ER alpha AF-1 (0) mice also displayed a reduced response to mechanical loading compared with WT mice (cortical area-40% +/- 11%, p < 0. 05 and periosteal BFR-41% +/- 8%, p < 0. 01), whereas the periosteal osteogenic response to loading was unaffected in ER alpha AF-2 (0) mice.


Input: Mechanical loading of transgenic estrogen response element (ERE)-luciferase reporter mice did not increase luciferase expression in cortical bone, suggesting that the loading response does not involve classical genomic ERE-mediated pathways.

estrogen


Input: In conclusion, ER alpha is required for the osteogenic response to mechanical loading in a ligand-independent manner involving AF-1 but not AF-2.


Input: Green tomato extract attenuates high-fat-diet-induced obesity through activation of the AMPK pathway in C57BL/6 mice.


Input: Obesity is a risk factor for numerous metabolic disorders.


Input: Recently, natural compounds that may be beneficial for improving obesity have received increasing attention.


Input: In this study, we investigated whether red and green tomato extracts attenuate high-fat-diet-induced obesity in C57BL/6 mice.


Input: The mice were maintained on a normal diet (ND) or high-fat diet (HFD) for 4 weeks and then fed ND, HFD, HFD plus 2% red tomato extract (RTE) or HFD plus 2% green tomato extract (GTE) for 13 weeks.


Input: The weekly food intakes among the groups were not significantly different.


Input: Body weight of mice fed HFD plus GTE was significantly decreased to the level of mice fed ND, but the body weight was only slightly reduced in mice fed HFD plus RTE.


Input: Epididymal adipose tissue and liver weights were significantly decreased in mice fed HFD plus GTE compared to those in HFD.


Input: Serum total cholesterol and low-density lipoprotein cholesterol levels in mice fed GTE were modestly reduced, and liver total cholesterol level was strongly decreased in HFD plus GTE-fed mice compared to that in HFD-fed mice.

cholesterol

cholesterol

cholesterol


Input: Adenosine-monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase phosphorylation in liver from HFD plus GTE-fed mice was significantly elevated, and HMG-CoA reductase expression was also significantly decreased.

Adenosine-monophosphate

acetyl-CoA

HMG-CoA


Input: GTE strongly decreased the expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha and perilipin in the adipose tissue of mice fed HFD plus GTE.


Input: Our results indicate that the antiobesity effects of GTE may be associated with activation of the AMPK pathway.


Input: Opportunities for functional selectivity in GPCR antibodies.


Input: Monoclonal antibodies (mAbs) have been used for decades as tools to probe the biology and pharmacology of receptors in cells and tissues.


Input: They are also increasingly being developed for clinical purposes against a broad range of targets, albeit to a lesser extent for G-protein-coupled receptors (GPCRs) relative to other therapeutic targets.


Input: Recent pharmacological, structural and biophysical data have provided a great deal of new insight into the molecular details, complexity and regulation of GPCR function.


Input: Whereas GPCRs used to be viewed as having either " on " or " off " conformational states, it is now recognized that their structures may be finely tuned by ligands and other interacting proteins, leading to the selective activation of specific signaling pathways.


Input: This information coupled with new technologies for the selection of mAbs targeting GPCRs will be increasingly deployed for the development of highly selective mAbs that recognize conformational determinants leading to novel therapeutics.


Input: Nephrogenic systemic fibrosis-like effects of magnetic resonance imaging contrast agents in rats with adenine-induced renal failure.

adenine


Input: Nephrogenic systemic fibrosis (NSF) is a scleroderma-like disease associated with prior administration of certain gadolinium chelates (GCs).

gadolinium


Input: NSF occurs in patients with severe renal failure.


Input: The purpose of this study was to set up a rat model of GC-associated NSF to elucidate the mechanism of this devastating disease.


Input: Firstly, after characterization of the model, male Wistar rats received a 0. 75% adenine-enriched diet for 8, 14, or 16 days to obtain various degrees of renal failure.

adenine


Input: Rats received five consecutive daily iv injections of saline or gadodiamide (2. 5 mmol/kg/day).

gadodiamide


Input: Secondly, the safety profile and in vivo propensity to dissociate of all categories of marketed GCs (gadoterate, gadobutrol, gadobenate, gadopentetate, and gadodiamide) were compared in rats receiving adenine-enriched diet for 16 days.

gadoterate

gadobutrol

gadobenate

gadopentetate

gadodiamide

adenine


Input: Serial skin biopsies were performed for blinded histopathological study.


Input: Total Gd concentration in tissues was measured by Inductively Coupled Plasma Mass Spectrometry.

Gd


Input: Relaxometry was used to evaluate the presence of dissociated Gd in skin and bone.

Gd


Input: Gadodiamide-induced high mortality and skin lesions (dermal fibrosis, calcification, and inflammation) were related to adenine diet duration.

Gadodiamide

adenine


Input: No skin lesions were observed with other molecules.


Input: Unlike macrocyclic GCs, gadodiamide, gadopentetate, and gadobenate gradually increased the r (1) relaxivity value, consistent with in vivo dissociation and release of soluble Gd (or, in the case of gadobenate, the consequence of protein binding).

gadodiamide

gadopentetate

gadobenate

Gd

gadobenate


Input: Gadodiamide-induced cutaneous and systemic toxicity depended on baseline renal function.

Gadodiamide


Input: We demonstrate in vivo dissociation of linear GCs, gadodiamide, and gadopentetate, whereas macrocyclic agents remained stable over the study period.

gadodiamide

gadopentetate


Input: Effects of ozone and particulate matter on cardiac mechanics: role of the atrial natriuretic peptide gene.

ozone


Input: A positive association between air pollution exposure and increased human risk of chronic heart disease progression is well established.


Input: In the current study, we test two hypotheses: (1) the cardiac compensatory changes in response to air pollution are dependent on its composition and (2) specific cardiac adaptations are regulated by atrial natriuretic peptide (ANP).


Input: We address these hypotheses by initially examining the exposure effects of ozone (O (3)) and/or particulate matter (PM) on cardiac function in C57Bl/6J (B6) mice.

ozone

O (3)


Input: Subsequently, the results are compared with cardiac functional changes to the same exposures in Nppa (the precursor gene for ANP) knockout (KO) mice.


Input: Separate groups of mice underwent 3 consecutive days of the same exposure sequence for 3h each consisting of the following: (1) 6h of filtered air (FAFA), (2) O (3) then FA (O (3) FA), (3) FA then carbon black (FACB), or (4) O (3) then CB.

O (3)

O (3)

carbon black

O (3)


Input: Cardiac function was assessed using a conductance catheter to generate cardiac pressure-volume loops 8-10h following each exposure sequence.


Input: As compared with FAFA, each sequence led to a substantial drop (as much as 33%) in stroke volume and cardiac output.


Input: However, these losses of cardiac function occurred by different compensatory mechanisms dependent on the pollutant composition.


Input: For example, O (3) FA exposure led to reductions in both end-systolic and end-diastolic left ventricular (LV) volumes, whereas FACB exposure led an increase in end-diastolic LV volume.

O (3)


Input: These same cardiac compensatory changes were largely abolished in Nppa KO mice following O (3) FA or FACB exposure.

O (3)


Input: These results suggest that cardiac functional changes in response to air pollution exposure are strongly dependent on the pollutant constituents, especially related to O (3) and/or PM.

O (3)


Input: Furthermore, ANP regulation appears to be crucial to these cardiac compensatory mechanisms induced by air pollution.


Input: Solving the lost in translation problem: improving the effectiveness of translational research.


Input: Translational research frequently fails to replicate in the clinic what has been demonstrated in the laboratory.


Input: This has been true for neuroprotection in the central nervous system, neuroprotection in glaucoma, as well as many other areas of medicine.


Input: Two fundamental reasons for this' Lost in Translation' problem are the' Butterfly Effect' (chaotic behavior of many animal models) and the' Two Cultures' problem (differences between the methodologies for preclinical and clinical research).


Input: We propose several strategies to deal with these issues, including the use of ensembles of animal models, adding intraocular pressure lowering to preclinical neuroprotection studies, changing the way in which preclinical research is done, and increasing interactions between the preclinical and clinical teams.


Input: Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning.


Input: Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption through the skin and are resistant to conventional pharmacological antidotal treatments.

organophosphorous


Input: The residence time of a stoichiometric bioscavenger, human butyrylcholinesterase (huBuChE), in the plasma more closely matches that of VX than do the residence times of conventional therapy drugs (oxime, anti-muscarinic, anticonvulsant).

oxime


Input: Intramuscular (i. m.) huBuChE afforded almost complete protection when administered prior to the onset of observable cholinergic signs of VX poisoning, but once signs of poisoning became evident the efficacy of i. m.


Input: huBuChE decreased.


Input: A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i. m.) protected 100% (8/8) of guinea-pigs from a lethal dose of VX (0. 74mg/kg) to 48h, even when administered on signs of poisoning.

oxime


Input: Survival was presumed to be due to immediate alleviation of the cholinergic crisis by the conventional pharmacological treatment drugs, in conjunction with bioscavenger that prevented further absorbed agent reaching the AChE targets.


Input: Evidence to support this proposed mechanism of action was obtained from PKPD experiments in which multiple blood samples and microdialysate samples were collected from individual conscious ambulatory animals.


Input: Plasma concentrations of intramuscularly-administered atropine, diazepam and HI-6 reached a peak within 15min and were eliminated rapidly within 4h.

atropine

diazepam


Input: Plasma concentrations of huBuChE administered by the i. m. route took approximately 24h to reach a peak, but were well-maintained over the subsequent 7days.


Input: Thus, the pharmacological therapy rapidly treated the initial signs of poisoning, whilst the bioscavenger provided prolonged protection by neutralising further nerve agent entering the bloodstream and preventing it from reaching the target organs.


Input: Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials.


Input: To overcome the limitations of in vitro exposure of submerged lung cells to nanoparticles (NPs), we validated an integrated low flow system capable of generating and depositing airborne NPs directly onto cells at an air-liquid interface (ALI).


Input: The in vitro exposure system was shown to provide uniform and controlled dosing of particles with 70. 3% efficiency to epithelial cells grown on transwells.


Input: This system delivered a continuous airborne exposure of NPs to lung cells without loss of cell viability in repeated 4h exposure periods.


Input: We sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare toxicity results to our prior in vivo inhalation studies.

copper

Cu


Input: The evaluation of cellular dosimetry indicated that a large amount of Cu was taken up, dissolved and released into the basolateral medium (62% of total mass).

Cu


Input: Exposure to Cu NPs decreased cell viability to 73% (p < 0. 01) and significantly (p < 0. 05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice.

Cu

lactate

oxygen


Input: Our results show that this exposure system is useful for screening of NP toxicity in a manner that represents cellular responses of the pulmonary epithelium in vivo.


Input: The involvement of Reelin in neurodevelopmental disorders.


Input: Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function).


Input: A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer' s disease and lissencephaly share a common feature of abnormal Reelin expression in the brain.


Input: Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders.


Input: The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities.


Input: Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits.


Input: This article is part of the Special Issue entitled' Neurodevelopmental Disorders'.


Input: Ultrasound-assisted coating of silk yarn with sphere-like Mn3O4 nanoparticles.


Input: The growth of sphere-like trimanganese tetraoxide (Mn (3) O (4)) nanoparticles on silk fiber was achieved by sequential dipping in an alternating bath of potassium hydroxide and manganese (II) nitrate under ultrasound irradiation.

trimanganese tetraoxide

Mn (3) O (4)

potassium hydroxide

manganese (II) nitrate


Input: Some parameters such as the effect of pH, numerous sequential dipping and ultrasonic irradiation on growth of the nanoparticles have been studied.


Input: The samples were characterized with powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and wavelength dispersive X-ray (WDX).


Input: The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines.


Input: Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated.

sodium iodide


Input: In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels.


Input: In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced.

radio-iodine


Input: Accordingly, in transfection experiments performed in TPC1 cells, treatment with PJ34 increased NIS promoter activity without affecting PARP-1 binding to the promoter sequence.


Input: We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark.


Input: Our data demonstrate that in various thyroid cancer cell lines PARP inhibition increases NIS gene expression through a particular modulation of transcriptional regulatory mechanisms.


Input: Therefore, we suggest that PARP inhibitors may deserve future investigations as tools for medical treatment of thyroid cancer.


Input: NMDA receptor signaling mediates the expression of protein inhibitor of activated STAT1 (PIAS1) in rat hippocampus.

NMDA


Input: Protein inhibitor of activated STAT1 (PIAS1) was shown to play an important role in inflammation and innate immune response, but how PIAS1 is regulated is not known.


Input: We have recently demonstrated that PIAS1 enhances spatial learning and memory performance in rats.


Input: In this study, we examined the signaling pathway and neural mechanism that regulate PIAS1 expression in the brain by using pharmacological and molecular approaches.


Input: Our results revealed that pias1 gene expression is rapidly induced upon NMDA receptor activation in rat hippocampus, but this effect is blocked by transfection of sub-threshold concentrations of ERK1 siRNA/ERK2 siRNA or CREB siRNA.

NMDA


Input: Pias1 gene expression is similarly induced by overexpression of the ERK1/ERK2 plasmids in rat hippocampus, and this effect is also blocked by sub-threshold concentration of CREB siRNA transfection.


Input: On the other hand, transfection of ERK1 siRNA/ERK2 siRNA or CREB siRNA at a higher concentration is sufficient to down-regulate PIAS1 expression.


Input: Inhibition of PI-3 kinase signaling and CaMKII signaling, which both result in CREB inactivation, similarly decreases PIAS1 expression.


Input: But NMDA and MK-801 do not affect the expression of IL-6 and TNF alpha.

NMDA


Input: NMDA also did not affect the expression of PIAS2, PIAS3 and PIAS4.

NMDA


Input: Further, pias1 mRNA has a similar degradation rate to that of the zif268 gene.


Input: These results together suggest that pias1 may function as an immediate early gene in an activity-dependent manner and PIAS1 expression is regulated by the NMDA-MAPK/ERK-CREB signaling pathway implicated in neuronal plasticity.

NMDA


Input: Antidepressant-like properties of three new alpha 2-adrenoceptor antagonists.


Input: Evidence suggests that depression is associated with an increase in the high-affinity conformation of the alpha 2-adrenoceptors in human brain.


Input: Such enhanced alpha 2-adrenoceptor activity could explain the deficit in central noradrenergic transmission described in the aetiology of depression.


Input: Thus, administration of alpha 2-adrenoceptor antagonists augments noradrenaline levels and provides an effective therapeutic approach for the treatment of depressive disorders.

noradrenaline


Input: In previous studies, we have characterized three new synthesized guanidine and 2-aminoimidazoline aromatic derivatives (8b, 17b and 20b) as alpha 2-adrenoceptor antagonists that are able to increase extracellular concentration of noradrenaline in rat brain.

guanidine

noradrenaline


Input: The purpose of the present study was to evaluate the in vivo antidepressant-like properties of these three new alpha 2-adrenoceptor antagonists.


Input: For that aim, compounds were tested on the tail suspension test (TST) and forced swim test (FST), two classically widely-used behavioural paradigms for the evaluation of antidepressant-like activity.


Input: Compound 8b significantly reduced the immobility time at 10, 20 and 40 mg/kg doses in both TST and FST.


Input: Compound 17b reduced the immobility time at 40 mg/kg in both TST and FST.


Input: Compound 20b showed a significant decrease in the immobility time at 20 mg/kg in the TST.


Input: As drugs of reference, fluoxetine induced a significant antidepressant-like effect in both TST and FST, while mirtazapine induced a significant antidepressant-like effect only in the FST.

fluoxetine

mirtazapine


Input: Additionally, none of the tested compounds increased locomotor activity or displayed anxiolytic-like properties.


Input: These results suggest that these new synthesized alpha 2-adrenoceptor antagonists may be useful as potential antidepressant drugs.


Input: Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes.


Input: High-fat feeding or CNS leptin overexpression in chow-fed rats results in a region-specific cellular leptin resistance in medial basal hypothalamic regions and the ventral tegmental area (VTA).


Input: The present investigation examined the effects of targeted chronic leptin overexpression in the VTA as compared with the medial basal hypothalamus on long-term body weight homeostasis.


Input: The study also examined if this targeted intervention conserves regional leptin sensitivity or results in localized leptin resistance.


Input: Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3).


Input: Tyrosine hydroxylase was measured in hypothalamus and VTA along with brown adipose tissue uncoupling protein 1.

Tyrosine


Input: Leptin overexpression in VTA tempered HF-induced obesity, but to a slightly lesser extent than that with leptin overexpression in the hypothalamus.


Input: Moreover, the overexpression of leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of the medial basal hypothalamus, whereas verexpression in the hypothalamus did not activate STAT3 signaling in the VTA.


Input: This unidirectional trans-stimulation did not appear to involve migration of either the vector or the gene product.


Input: Long-term leptin overexpression in either the medial basal hypothalamus or VTA caused desensitization of leptin signaling in the treated region and cross-desensitization of leptin signaling in the untreated region.


Input: These results demonstrate a role of leptin receptors in the VTA in long-term body weight regulation, but the trans-activation of the hypothalamus following VTA leptin stimulation suggests that an integrative response involving both brain regions may account for the observed physiological outcomes.


Input: Persistent and high-level expression of human liver prolidase in vivo in mice using adenovirus.


Input: Human liver prolidase, a metal-dependent dipeptidase, is being tested as a potential catalytic bioscavenger against organophosphorus (OP) chemical warfare nerve agents.

organophosphorus


Input: The purpose of this study was to determine whether persistent and high-levels of biologically active and intact recombinant human (rHu) prolidase could be introduced in vivo in mice using adenovirus (Ad).


Input: Here, we report that a single intravenous injection of Ad containing the prolidase gene with a 6 x histidine-tag (Ad-prolidase) introduced high-levels of rHu prolidase in the circulation of mice which peaked on days 5-7 at 159 +/- 129U/mL.

histidine


Input: This level of prolidase is ~ 120 times greater than that of the enzyme level in mice injected with Ad-null virus.


Input: To determine if all of Ad-prolidase-produced rHu prolidase was exported into the circulation, enzyme activity was measured in a variety of tissues.


Input: Liver contained the highest levels of rHu prolidase on day 7 (5647 +/- 454U/g) compared to blood or any other tissue.


Input: Recombinant Hu prolidase hydrolyzed DFP, a simulant of OP nerve agents, in vitro.


Input: In vivo, prolidase overexpression extended the survival of 4 out of 6 mice by 4-8h against exposure to two 1 x LD50 doses of DFP.


Input: In contrast, overexpression of mouse butyrylcholinesterase (BChE), a proven stoichiometric bioscavenger of OP compounds, protected 5 out of 6 mice from DFP lethality and surviving mice showed no symptoms of DFP toxicity.


Input: In conclusion, the results suggest that gene delivery using Ad is capable of introducing persistent and high levels of human liver prolidase in vivo.


Input: The gene-delivered prolidase hydrolyzed DFP in vitro but provided only modest protection in vivo in mice, delaying the death of the animals by only 4-8h.


Input: Experiences of microsurgical reconstruction for variant hepatic artery in living donor liver transplantation.


Input: There is an emergent need for improving the microsurgical technique of variant arterial anastomosis to reduce the often seen surgery-related complications.


Input: We describe in this article our experience in improving this technique, in 73 living donor liver grafts (64 right lobes, 9 left lobes) in patients with end-stage liver disease during living donor liver transplantation.


Input: The hepatic arteries were evaluated preoperatively with computed tomography and magnetic resonance angiography.


Input: In this series, 13 grafts (17. 80%) with variant hepatic artery were conducted arterioplasty on a back-table under a loupe or a high-power microscope, which included one recipient in situ interposition vessel graft of recipient proper hepatic artery for artery reconstruction.


Input: The back-table reconstruction time was 16 +/- 5. 6 min.


Input: No arterial thrombosis was found in these cases during the 6-month postoperative follow-up.


Input: On the basis of our experience, we suggest that back-table microsurgical plasty for graft with arterial variation should be applied to minimize operative difficulties and to avoid arterial complications in living donor liver transplantation.


Input: Information for clinicians: commercially available molecular diagnosis testing in the evaluation of thyroid nodule fine-needle aspiration specimens.


Input: TSH receptor mRNA reverse transcription-polymerase chain reaction, the Veracyte and Asuragen commercial methods, and the noncommercial use of BRAF, RAS, RET/PTC, and PAX8/PPAR gamma testing have promising roles in the diagnosis and treatment of patients with nodular thyroid disease and thyroid cancer.


Input: However, at this time, experience with these molecular methods remains limited, and no test has perfect sensitivity and specificity.


Input: Peer-reviewed data evaluating the diagnostic performance of these tests are increasingly available.


Input: The American Thyroid Association (ATA) feels that until an expert consensus review of existing data (now underway by the ATA Guidelines Task Force) can be completed, no evidence-based recommendation for or against the use of these methods can be made.


Input: Clinicians are therefore advised to consider the use of these genetic diagnosis methods with appropriate caution, and to remain cognizant of the limitations of the data supporting their use.


Input: Patients who are interested in the use of these tests in their own care should discuss them thoroughly with their care providers.


Input: Until evidence-based recommendations are available, determining whether or not the limited data available support the use of these methods should be considered on a case-by-case basis.


Input: Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts--in vitro.

Di 2-ethyl hexyl phthalate


Input: Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous environmental contaminant, is an established endocrine disruptor (ED).

Di-2-ethyl hexyl phthalate

DEHP


Input: Increasing evidences indicate that some EDs interfere with osteoblast differentiation and function.


Input: In the present study, we investigated the effects of DEHP on the expression of cell cycle proteins, differentiation markers, Runx2 and its co-activator TAZ in osteoblasts derived from neonatal rat calvaria.

DEHP


Input: A significant decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of DEHP (100 mu M) after 24h treatment.

DEHP


Input: DEHP treatment caused a significant decrease in ALP mRNA.

DEHP


Input: While DEHP treatment significantly decreased the TAZ at mRNA and protein levels, it decreased only the Runx2protein levels.

DEHP


Input: Histochemical localization of ALP, collagen and mineralized nodules studied from cells treated with DEHP (10 and 100 mu M) for 21 days revealed a drastic decrease in collagen, ALP and mineralization.

DEHP


Input: In conclusion, DEHP affected differentiation of neonatal rat calvarial osteoblasts and mineralization of matrix secreted by these cells.

DEHP


Input: Ultraviolet B activated 1, 25 (OH) (2) D affects the level of fibroblast growth factor-23 in human.

1, 25 (OH) (2) D


Input: Fibroblast growth factor 23 (FGF-23) is known as a phosphaturic factor regulating phosphate homeostasis.

phosphate


Input: Several studies suggest that dietary phosphate, serum phosphate and 1, 25-dihydroxyvitamin D [1, 25 (OH) (2) D] are candidate regulators of FGF-23.

phosphate

phosphate

1, 25-dihydroxyvitamin D

1, 25 (OH) (2) D


Input: While the human studies, which modulated the dietary or serum phosphate showed in rather controversial results, manipulation of the active vitamin D definitely affected FGF-23 in animals.

phosphate

vitamin D


Input: This study was conducted to elucidate the relationship between active vitamin D directly stimulated by ultraviolet B (UVB) exposure and FGF-23 level in human.

vitamin D


Input: Ten healthy young adults were recruited to get the UVB exposure thrice a week at sub-minimal erythemal dose with gradual increment by 10% only for 4 weeks.


Input: Serum calcium, phosphate, mineral-related hormones and bone turnover markers were analyzed before and after the UVB exposure every 4 week for 12 whole weeks.

calcium

phosphate


Input: Twenty five-hydroxyvitamin D [25 (OH) D] increased by 115% (19. 8 ng/mL to 40. 5 ng/mL, p < 0. 001) after 4 weeks of UVB exposure.

Twenty five-hydroxyvitamin D

25 (OH) D


Input: While 1, 25 (OH) (2) D increased by 75% (49. 9 pg/mL to 64. 4 pg/mL, p < 0. 001) then both level decreased after 4 weeks of withdrawal.

1, 25 (OH) (2) D


Input: C-telopeptide peaked at 2nd week then decreased, while osteocalcin increased gradually.


Input: FGF-23 started to increase from the 4th week of UVB exposure then significantly at the 4th week after withdrawal of UVB (27. 8 pg/mL to 41. 4 pg/mL, p < 0. 05).


Input: UVB exposure effectively increased 1, 25 (OH) (2) D with delayed stimulatory effect on FGF-23.

1, 25 (OH) (2) D