title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Skin area visit 1 | Click here for additional data file. | PMC10734405 | ||
Skin area visit 2 | Click here for additional data file. | PMC10734405 | ||
DET Score | Click here for additional data file. | PMC10734405 | ||
Case Report Form (annotated) | Click here for additional data file. | PMC10734405 | ||
Baseplate Change scoring | Click here for additional data file. | PMC10734405 | ||
Randomisation | SKIN | Click here for additional data file.The authors wish to extend a special thanks to the patients with PSCs and health care professionals who participated in the study and provided valuable insight into their experience of living with/managing patients with PSCs. Moreover, the authors would like to thank the members of t... | PMC10734405 | |
Additional Information and Declarations | PMC10734405 | |||
Competing Interests | HANSEN | During the investigation, Nana O. Herschend, Zenia Størling and Helle Doré Hansen were employed by Coloplast A/S, and Amy Findley, Abi Williams and Kate Sully were employed by Adelphi Values. | PMC10734405 | |
Human Ethics | The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):The study was approved by the local ethics committee in each country (UK: 20/LO/0220, Germany: 19-363 and 00012177, the Netherlands: NL71653.068.19, Italy: NP 3841, and Norway: 65025). | PMC10734405 | ||
Data Availability | The following information was supplied regarding data availability:The raw measurements and an annotated Case Report Form are available in the | PMC10734405 | ||
References | PMC10734405 | |||
Abstract | PMC9804082 | |||
Aim | schizophrenia | The aim of this study was to explore the effectiveness and safety of pentoxifylline as an adjuvant to risperidone in mitigating the negative symptoms in patients with chronic schizophrenia. | PMC9804082 | |
Methods | schizophrenia | SYNDROME | In this randomized, placebo‐controlled study, eighty outpatients with chronic schizophrenia were given risperidone for 8 weeks along with either pentoxifylline or a placebo. The positive and negative syndrome scale (PANSS) was used to assess patients at the start of the trial, as well as at 2, 4, 6, and 8 weeks. Pre‐ a... | PMC9804082 |
Results | The pentoxifylline group revealed a significant effect for time‐treatment interaction on PANSS‐negative subscale scores ( | PMC9804082 | ||
Conclusion | inflammation, schizophrenia, TNF‐α | INFLAMMATION, PATHOPHYSIOLOGY | Pentoxifylline adjunctive therapy with risperidone for 8 weeks was found to be promising in mitigating the negative symptoms in patients with chronic schizophrenia. Trial registration number: NCT04094207.Phosphodiesterases and inflammation play a role in the pathophysiology of schizophrenia negative symptoms. Treatment... | PMC9804082 |
INTRODUCTION | motivational deficits, Schizophrenia, neuropsychiatric diseases, claudication symptoms | DISORDER, DISEASE, PATHOGENESIS | Schizophrenia is a chronic psychiatric disorder that contributes significantly to the burden of mental disease worldwide.Several attempts have been made to define the distinctive mechanisms responsible for these negative symptoms to introduce new therapeutic agents that could target those mechanisms.Studies over the pa... | PMC9804082 |
METHODS | PMC9804082 | |||
Study design | This study was a prospective, parallel‐group, randomized, double‐blind, 8‐week trial. The Menoufia University Faculty of Medicine's ethical committee granted approval for this study (4/2021NEUR1), and it was carried out in accordance with the Declaration of Helsinki and its subsequent amendments. The study was register... | PMC9804082 | ||
Participants | mental disorders, depression, schizophrenia, intellectual disability | DISORDERS, SYNDROME | From September 2019 to January 2022, patients between the ages of 20 and 40 were recruited from the neuropsychiatric department of Menoufia University Hospital. Patients with a confirmed diagnosis of schizophrenia using a structured interview conducted in accordance the Diagnostic and Statistical Manual of Mental Disor... | PMC9804082 |
Sample size | With an effect size (Cohen's | PMC9804082 | ||
Randomization and blinding | Randomization was performed by impartial person using electronic random number generator. (Assignment ratio was 1:1, blocks of two). Blinding of the assignment was achieved by using serially numbered, solid, and stapled wrappers. Placebo tablets were manufactured in Zeta Pharma Company, and they were indistinguishable ... | PMC9804082 | ||
Intervention | Pentoxifylline 400 mg SR tablets twice day, or a placebo, were given to participants for 8 weeks. Pentoxifylline dose selection was based on our previous study | PMC9804082 | ||
Outcomes | schizophrenia | The PANSS validated 30‐item rating scale, which comprises positive (seven items), negative (seven items), psychopathological symptoms in general (16 items), and PANSS total scores, was used to assess the drug efficacy and severity of symptoms in patients with schizophrenia. | PMC9804082 | |
Safety | ADVERSE EFFECTS | Patients were advised to notify the study team if they experienced any unusual symptoms during the trial. At each appointment, adverse effects (AEs) were meticulously recorded using a checklist. Physical examinations were also performed, and the participants' vital signs and body weight were listed during the screening... | PMC9804082 | |
Measurements | Fasting morning blood samples | Fasting morning blood samples (10 a.m.) were collected at the same time for all patients in vacutainers. The samples were then centrifuged at 4500 | PMC9804082 | |
Statistical analysis | ® | Data analysis was done using IBM® SPSS® Statistics version 22 software (USA). Shapiro–Wilk and Kolmogorov–Smirnov tests were used to examine the normal distribution of continuous variables. Student's | PMC9804082 | |
RESULTS | Depression, Extrapyramidal Symptoms | SYNDROME, POSITIVE | According to the inclusion and exclusion criteria, 116 patients were assessed for their eligibility. Eighty outpatients were randomized to receive either pentoxifylline or placebo (Flow chart of the study participantsParticipants' demographics and baseline characteristics
Abbreviations: BMI, body mass index; CRP, C‐Rea... | PMC9804082 |
Outcomes | PMC9804082 | |||
SD | SYNDROME, SYNDROME, POSITIVE | No significant differences were found between the two groups' baseline PANSS‐negative subscale scores (The two therapies' effects on the Positive and Negative Syndrome Scale (PANSS). Data presented as means ± SD: (A) Negative, (B) Positive, (C) General psychopathology, and (D) Total scores. NS, non‐significantBaseline‐... | PMC9804082 | |
When comparing the two groups, the baseline PANSS‐positive subscale scores were not substantially different ( | PMC9804082 | |||
When the two groups' baseline PANSS general psychopathology subscale scores were compared, there was no significant difference ( | PMC9804082 | |||
When the two groups' baseline PANSS total scores were compared, there was no significant difference ( | PMC9804082 | |||
Hamilton depression rating scale | The baseline HDRS total score in the pentoxifylline group was 7.35 ± 0.95, whereas in the placebo group it was 7.55 ± 0.85, with no statistically significant difference between the two groups ( | PMC9804082 | ||
Extrapyramidal symptoms rating scale | The baseline ESRS total score in pentoxifylline group was 1.78 ± 0.42 and 1.73 ± 0.45 in the placebo group, with no statistically significant difference between the two groups ( | PMC9804082 | ||
Effect on | There was no statistically significant difference in baseline cAMP, TNF‐α, and IL‐6 serum levels between the pentoxifylline and placebo groups. (Changes in cAMP and inflammatory markers
Baseline and 8‐week comparisons between groups.Within group comparison.Furthermore, cAMP serum level in the pentoxifylline group was s... | PMC9804082 | ||
Clinical side effects | diarrhea, heartburn, abdominal pain, extrapyramidal symptoms, dizziness, sexual dysfunction, insomnia, headache | The frequency of side effects was not substantially different between the two groups. In pentoxifylline group, five patients suffered from headache, three from dizziness, five from insomnia, six from abdominal pain, five from heartburn, seven from diarrhea, six from decrease appetite, two from increase appetite, and fi... | PMC9804082 | |
DISCUSSION | deficit syndrome, schizophrenia, cognitive dysfunction | DISEASES, CORTEX | As far as we know, our study is the first randomized, double‐blind, placebo‐controlled trial that assessing the efficacy and safety of pentoxifylline as PDE inhibitor in alleviating the negative symptoms in chronic schizophrenia. Patients received pentoxifylline showed significant enhancement in PANSS negative, general... | PMC9804082 |
CONCLUSION | inflammation, schizophrenia | INFLAMMATION, PATHOPHYSIOLOGY | Pentoxifylline adjuvant to risperidone enhanced the negative symptoms in chronic schizophrenia patients without remarkable side effects. These effects could be attributed to inhibition of PDEs and inflammatory cytokines. Our findings could indirectly support the role of PDEs and inflammation in the schizophrenia‐negati... | PMC9804082 |
CONFLICT OF INTEREST | The authors state they have no competing or financial interests. | PMC9804082 | ||
ACKNOWLEDGMENTS | Zeta Pharma is acknowledged by the authors for producing the placebo. | PMC9804082 | ||
DATA AVAILABILITY STATEMENT | On reasonable request, the corresponding author will provide the data that underpin the study's conclusions. | PMC9804082 | ||
REFERENCES | PMC9804082 | |||
Aims/hypothesis | hyperglycaemia, glucometabolic | HYPERGLYCAEMIA, TYPE 2 DIABETES | Hyperbaric oxygen (HBO) therapy may improve hyperglycaemia in humans with type 2 diabetes, but underlying mechanisms are unclear. Our objective was to examine the glucometabolic effects of HBO on whole-body glucose disposal in humans with type 2 diabetes. | PMC9729133 |
Methods | Diabetes | TYPE 2 DIABETES, DIABETES | In a randomised placebo-controlled crossover trial located at the German Diabetes Center, 12 male individuals with type 2 diabetes (age 18–75 years, BMI <35 kg/m | PMC9729133 |
Results | INSULIN SENSITIVITY | HBO decreased fasting blood glucose by 19% and increased whole-body, hepatic and WAT insulin sensitivity about one-third ( | PMC9729133 | |
Conclusions/interpretation | TYPE 2 DIABETES, INSULIN SENSITIVITY | HBO-mediated improvement of insulin sensitivity likely results from decreased endoplasmic reticulum stress and increased mitochondrial capacity, possibly leading to low-dose reactive oxygen species-mediated mitohormesis in humans with type 2 diabetes. | PMC9729133 | |
Funding | German Federal Ministry of Health, German Federal Ministry of Education and Research, North-Rhine Westfalia Ministry of Culture and Science, European-Regional-Development-Fund, German-Research-Foundation (DFG), Schmutzler Stiftung | PMC9729133 | ||
Graphical abstract | PMC9729133 | |||
Supplementary Information | The online version of this article (10.1007/s00125-022-05797-0) contains peer-reviewed but unedited supplementary material.. | PMC9729133 | ||
Keywords | PMC9729133 | |||
Introduction | type 2 diabetes | OXIDATIVE STRESS, TYPE 2 DIABETES | Various studies have suggested a causal relationship between oxidative stress and insulin resistance [Hyperbaric oxygen (HBO) treatment provides for 100% oxygen (OThis study compared the acute effects of one single session of 100% OStudy design. Participants with type 2 diabetes ( | PMC9729133 |
Methods | PMC9729133 | |||
Volunteers | TYPE 2 DIABETES | Fifteen male volunteers with type 2 diabetes were enrolled in this randomised, placebo-controlled, crossover clinical trial ( | PMC9729133 | |
Randomisation | Diabetes | DIABETES | The random allocation sequence (1:1) was generated by an experienced statistician at the German Diabetes Center (DDZ) (PB) using SAS software, version 9.3 (SAS Institute, Cary, NC, USA). Participants were randomly assigned to their treatment sequence by a person at the DDZ who was not involved in the conduct of the stu... | PMC9729133 |
Experimental protocol | The visits took place at an interval of 3 weeks. Each visit covered a period of 31 h, divided into four time periods (Fig. | PMC9729133 | ||
Indirect calorimetry | Indirect calorimetry was performed in the canopy mode with Vmax Encore 29n (CareFusion, Höchberg, Germany) during the last 30 min of the basal, pre-clamp and clamp periods [ | PMC9729133 | ||
Skeletal muscle and WAT biopsy | Skeletal muscle and WAT biopsy samples were taken from the vastus lateralis muscle and subcutaneous adipose tissue of the lower abdomen, respectively, as described before [ | PMC9729133 | ||
MRI and MRS | BEST | All MRI/MRS measurements were conducted on a 3.0-T MR scanner (Achieva X-series; Philips Healthcare, Best, the Netherlands). Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) contents were quantified by | PMC9729133 | |
High-resolution respirometry | Ex vivo analysis of mitochondrial respiration was performed in permeabilised muscle fibres and WAT using high-resolution respirometry (Oxygraph-2k; Oroboros, Innsbruck, Austria), as previously described [ | PMC9729133 | ||
Analyses of lipid peroxidation, antioxidative capacity and oxidative stress | In skeletal muscle | Concentrations of thiobarbituric acid reactive substances (TBARS) were assessed fluorometrically in serum and biopsy samples from subcutaneous fat and skeletal muscle according to the manufacturer’s instructions (BioTek, Bad Friedrichshall, Germany) [In skeletal muscle and WAT samples, total glutathione and oxidised gl... | PMC9729133 | |
GC-MS | Determination of atom per cent enrichment of blood [ | PMC9729133 | ||
Western blotting | Expression levels of proteins of interest were assessed by western blot analysis, as described before [ | PMC9729133 | ||
Measurement of circulating metabolites and hormones | Plasma concentrations of insulin, glycerol, NEFA, alanine aminotransferase, aspartate aminotransferase, triacylglycerol and chylomicrons, as well as whole-blood measurements of glucose and HbA | PMC9729133 | ||
Calculations | During pre-clamp and clamp periods, whole-body glucose disposal rate ( | PMC9729133 | ||
Statistics | The power calculation was based on a previous study on HBO-induced glucose lowering, using two simultaneous two-sided paired | PMC9729133 | ||
Results | PMC9729133 | |||
HBO raises tissue oxygen pressure | During HBO treatment, tissue oxygen pressure as measured by tcpO | PMC9729133 | ||
HBO rapidly improves hyperglycaemia | fasting blood glucose | TYPE 2 DIABETES | After HBO treatment, blood glucose decreased by 19% from baseline compared with CON (iAUC Time course of circulating metabolites and hormones in humans with type 2 diabetes before and after HBO or CON treatment. Concentrations (means ± SEM) of fasting blood glucose ( | PMC9729133 |
HBO leads to improvement of hepatic, skeletal muscle and WAT insulin sensitivity | TYPE 2 DIABETES | During the pre-clamp period, REE (Whole-body and tissue-specific glucose and lipid metabolism after HBO or CON treatment in humans with type 2 diabetes. ( | PMC9729133 | |
HBO acutely stimulates energy metabolism but also increases oxidative stress and antioxidative defence | TYPE 2 DIABETES | Changes were analysed by comparing the difference (Δ) between pre-clamp and basal periods for each intervention. Non-invasive Variables of tissue-specific energy metabolism and antioxidative capacity after HBO or CON treatment in humans with type 2 diabetes. Difference (Δ) between pre-clamp and basal periods for hepati... | PMC9729133 | |
HBO acutely improves myocellular insulin signalling while reducing endoplasmic reticulum stress | TYPE 2 DIABETES | First, changes were analysed by comparing the difference (Δ) between pre-clamp and basal periods. During the pre-clamp period, expression of biomarkers of endoplasmic reticulum (ER) stress was measured in skeletal muscle. Expression levels of eIF2α were comparable between the interventions (ΔeIF2α, Myocellular ER stres... | PMC9729133 | |
HBO does not immediately affect biomarkers of systemic low-grade inflammation | Serum IL-6, IL-1ra, TNF-α, FGF-21, MPO, SOD3, and total and high-molecular-weight adiponectin were not different between interventions (iAUCs | PMC9729133 | ||
Discussion | generalised, skeletal muscle, inflammation, beta cell loss, diabetes endotypes, hyperglycaemia, normoglycaemia, mitochondrial damage | INFLAMMATION, DISEASE, IMPAIRED GLUCOSE TOLERANCE, INSULIN RESISTANCE, HYPERGLYCAEMIA, TYPE 2 DIABETES, PATHOGENESIS, INSULIN SENSITIVITY | This study demonstrates that a single HBO treatment with 100% OThe observation of a clinically meaningful reduction in fasting hyperglycaemia in humans with type 2 diabetes extends previous data [The novelty resides in the investigation of the initial tissue-specific cellular mechanisms underlying the beneficial metabo... | PMC9729133 |
Supplementary information |
(PDF 531 kb) | PMC9729133 | ||
Acknowledgements | A. Shokouhmehr, Diabetes | DIABETES | We would like to thank F. Ziehve, M. Eßer, D. Höhn, D. F. Markgraf, U. Partke, A. Shokouhmehr, J. Leonhard and A. Sparla, all co-workers at the German Diabetes Center (DDZ), for their excellent support. | PMC9729133 |
Authors’ relationships and activities | MR | MR received personal fees from Allergan, Eli Lilly, Fishawack Group, Gilead Sciences, Novo Nordisk, Pfizer, Prosciento and Target RWE and investigator-initiated research support from Boehringer-Ingelheim, Nutricia/Danone and Sanofi-Aventis. CH received research support from Sanofi-Aventis and is a member of the Editori... | PMC9729133 | |
Contribution statement | MR | MR initiated the study, led the clinical experiments, and wrote, reviewed and edited the manuscript. TS led the clinical experiments, obtained and analysed the data, and wrote, edited and reviewed the manuscript. SK, HK, GB, SD, RG, SGM, PB, LM, CH and MW made significant contributions to data collection or analysis an... | PMC9729133 | |
Funding | Diabetes | DIABETES | Open Access funding enabled and organized by Projekt DEAL. This study was supported by grants to the German Diabetes Center, which is funded by the German Federal Ministry of Health and Ministry of Culture and Science of the State North Rhine-Westphalia, and to the German Center for Diabetes Research by the German Fede... | PMC9729133 |
Data availability | All data generated or analysed during this study are included in the published article (and its | PMC9729133 | ||
References | PMC9729133 | |||
Key Points | PMC10445201 | |||
Question | digestive tract cancer, cancer, death | CANCER | Can vitamin D supplementation reduce the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53 immunoreactive, defined by positivity for anti-p53 antibodies in serum and p53 protein in more than 99% of cancer cells? | PMC10445201 |
Findings | digestive tract cancer | In this post hoc analysis of a randomized clinical trial including 392 patients with digestive tract cancer, 5-year relapse-free survival was significantly higher in the vitamin D group (80.9%) than the placebo group (30.6%) among patients in the p53-immunoreactive subgroup but not in the non–p53-immunoreactive subgrou... | PMC10445201 | |
Meaning | death | These findings suggest that vitamin D supplementation may reduce the risk of relapse or death in this subgroup of patients. | PMC10445201 | |
Importance | cancer | CANCER | Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial. | PMC10445201 |
Objective | digestive tract cancer, death | To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive. | PMC10445201 | |
Design, Setting, and Participants | digestive tract cancers | This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare t... | PMC10445201 | |
Interventions | Vitamin D3 (2000 IU/d) supplementation or placebo. | PMC10445201 | ||
Main Outcomes and Measures | cancer, death | CANCER | The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for | PMC10445201 |
Results | esophageal cancer, colorectal cancer, small bowel cancer, digestive tract cancer, gastric cancer | SMALL BOWEL CANCER, COLORECTAL CANCER, OESOPHAGEAL CANCER, GASTRIC CANCER | Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was dete... | PMC10445201 |
Conclusions and Relevance | digestive tract cancer, death | This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive. | PMC10445201 | |
Trial Registration | Identifier: | PMC10445201 | ||
Introduction | cancer deaths | Worldwide, an estimated 10.0 million cancer deaths occurred in 2020,Vitamin D was previously demonstrated to upregulate innate and adaptive immunity. | PMC10445201 | |
Methods | The trial protocol ( | PMC10445201 | ||
Trial Design | This was a post hoc analysis of parent trial participants from the AMATERASU RCT | PMC10445201 | ||
Participants | digestive tract cancers | Of 417 patients with digestive tract cancers who were randomly assigned to receive vitamin D supplements (251 patients [60.2%]) or placebo (166 patients [39.8%]) and who were followed up for a median (IQR; maximum) period of 3.5 (2.5-5.3; 7.6) years, 392 participants (94.0%) had available serum samples and were eligibl... | PMC10445201 | |
Outcome | death | The outcome was prespecified as relapse or all-cause death. Elapsed time was defined as the time from starting the supplement to the date the outcome occurred or the patient was censored. | PMC10445201 | |
Detection of p53 Protein in Pathological Specimens | cancer | CANCER, PATHOLOGY | Immunohistochemical staining data of p53 in cancer tissue in pathology specimens was obtained from our previous study. | PMC10445201 |
Serum Anti-p53 Antibody Level Measurement | Patient serum p53-Ab levels at approximately 2 weeks after operation and just before starting trial vitamin D supplementation (ie, at randomization), were measured by SRL, Inc (Shinjuku, Tokyo, Japan) using chemiluminescent enzyme immune assay (CLEIA). The lowest measurable serum p53-Ab level is 0.4 U/mL. The study pop... | PMC10445201 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.