Use of intravesical injections of platelet-rich plasma for the treatment of bladder pain syndrome: A comprehensive literature review

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. Methods: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: “platelet-rich plasma”, “interstitial cystitis”, “PRP”, “bladder pain syndrome”, and “painful bladder syndrome”. Results: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. Conclusions: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA

Effects of different diet alternatives to replace the use of pharmacological levels of zinc on growth performance and fecal dry matter of weanling pigs

A total of 300 weanling pigs (Line 400 × 200, DNA, Columbus, NE, initially 4.83 kg) were used in a 46-d trial to evaluate the effects of different nutritional strategies to replace pharmacological levels of Zn, provided by zinc oxide (ZnO), in nursery diets on growth performance and fecal dry matter (DM). Six treatments with 10 replicate pens per treatment and 5 pigs per pen were used. Diets consisted of: (1) positive control (ZnO providing 3,000 mg/kg added Zn from d 0 to 7 and 2,000 mg/kg added Zn from d 8 to 25 and 21% crude protein, CP); (2) negative control (NC; no added ZnO); (3) NC plus 1.2% Na diformate; (4) NC with 4% coarse ground wheat bran; (5) NC but formulated to 18% CP; and (6) the combination of NC with 18% CP, 1.2% Na diformate, and 4% coarse ground wheat bran. The diets formulated to 18% CP contained 1.2% standardized ileal digestible (SID) Lys from d 0 to 25, whereas the 21% CP diets contained 1.4% SID Lys from d 0 to 7 and 1.35% SID Lys from d 7 to 25. From d 25 to 46, all pigs were fed a common diet. From d 0 to 7, no differences in any variables were observed between treatments. From d 7 to 25, pigs fed the diet with added ZnO had greater (P < 0.01) average daily gain (ADG) and average daily feed intake (ADFI) than all other treatments. Pigs fed the diet formulated to 18% CP had decreased (P < 0.01) ADG when compared with pigs fed the other diets. From d 25 to 46, no previous treatment effects on ADG or gain to feed ratio (G:F) were observed. Overall (d 0 to 46), pigs fed the diet with added ZnO from d 0 to 25 had greater (P < 0.01) ADG, ADFI, and final body weight than pigs fed added Na Diformate, or 4% coarse ground wheat bran, or with the 18% CP diet, or with pigs fed the combination of the additives intermediate. There was no evidence for differences in overall G:F. Pigs fed the NC diet had the lowest fecal DM and highest fecal scores (P < 0.05), indicating the greatest incidence of loose stools. Pigs fed added ZnO had greater fecal DM than pigs fed the NC, 4% added wheat bran, or 18% CP diets, or with pigs fed the combination of additives intermediate (P < 0.01). These results suggest that adding pharmacological levels of Zn from ZnO improves nursery pig performance and increases DM content of feces when compared with pigs fed diets with either Na diformate, 4% course wheat bran, or 18% CP alone. However, a combination of all three alternatives appeared to be additive and partially restored growth performance similar to adding pharmacological levels of Zn

Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors

The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials

A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Erectile and sexual dysfunction in male and female patients with celiac disease: A cross-sectional observational study

Introduction: Sexual function is often impaired in patients with chronic illnesses. Several patients with chronic gastrointestinal and liver disorders have been shown to suffer from sexual dysfunction, and celiac disease is a highly prevalent gastroenterological disorder. Aim: The aim of this study was to investigate the sexual function incidence and the risk factors for sexual dysfunction in both male and female celiac disease patients. Methods: Two hundred and eighty-four patients (170 females, 114 males) participated in this cross-sectional observational study in an anonymous manner. Female sexual function was assessed through the Female Sexual Function Index questionnaire. Male sexual function was assessed through the International Index of Erectile Function-5 questionnaire. Clinical-demographic variables were recorded. We investigated differences in the patient-reported outcomes among the different subgroups and whether there were clinical-demographic predictors of sexual dysfunction in our setting. Main outcome measures: Prevalence and assessment of sexual dysfunction in celiac disease patients. Results: In the female group, 85 subjects (50%) had a total score compatible with sexual dysfunction: 43 (61.42%) showed low desire, 79 (46.47%) showed arousal disorder, 66 (38.82%) lubrication disorder, and 84 (49.41%) inability of obtaining an orgasm. Also, a large proportion of our female patients, 161 (94.70%), showed sexual discomfort during intercourse. In the male group, 79 patients (62.2%) showed scores compatible with normal erectile function, eight (7.01%) had mild erectile dysfunction, 24 (21.05%) mild to moderate erectile dysfunction, and three (2.63%) presented severe erectile dysfunction. Altered body mass index was significantly associated with sexual dysfunction both in male and female patients. Early age at diagnosis was a significant predictor of sexual dysfunction in male celiac disease patients. Conclusions: A significant proportion of celiac disease patients present sexual dysfunction. Early age at diagnosis and high body mass index seem to predict sexual dysfunction in this clinical setting. Assessment of sexual function should be part of the initial evaluation of celiac disease patients in order to establish a prompt diagnosis and early treatment

A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer

Background: Lipid alterations may serve as potential tumour biomarkers. The ratio of triglycerides to HDL cholesterol (TG/HDL ratio) is associated with various cancers. Pseudocholinesterase (PChE) activity, involved in TG hydrolysis, plays an important role in the metabolism of lipoprotein. There is scarce data assessing the reliability of both the TG/HDL ratio and PChE levels in correctly classifying patients suffering from bladder cancer. Methods: Three hundred and ninety-six patients undergoing cystoscopy or transurethral resection of the bladder (TURB), broken into two major groups, i.e., patients with histologically confirmed, non-metastatic bladder cancer (n = 208) and without bladder cancer (no bladder cancer, n = 188), formed the study population. The last group was split into two subgroups consisting of a cohort of patients never suffering from bladder cancer but with other bladder diseases (no CaBD, n = 100) and another cohort formed by patients characterised by eradicated bladder cancer after TURB with no recurrence during a three-month follow-up (previous bladder cancer, n = 88). Pieces of information by both metabolic derangement (the presence of type 2 diabetes mellitus), hypertension and lipid profile were retrieved from patient records upon entry to the study. Sensitivity, specificity, areas under the ROC (AUROC) of the TG/HDL ratio, and PChE levels were used in diagnostic decision making. Results: The TG/HDL ratio as well as PChE concentrations of bladder cancer patients were significantly different when compared to those with previous bladder cancer and the no CaBD patients (p = 0.023 and 0.0004, respectively). There was an independent role of both the TG/HDL ratio and PChE levels in predicting the presence of bladder cancer (OR: 1.22 and 0.99, respectively), but the reliability of the TG/HDL ratio (AUROC: 0.587) was superior to that of PChE levels (AUROC: 0.374). The AUROC of a new parameter resulting from the combination of the TG/HDL ratio with PChE levels showed a further increment in the discriminant power of the bladder cancer presence (0.6298), interestingly with a negative predictive value (89%) according to the Bayesian approach. The cut-off of the TG/HDL ratio, the main marker of the present study that better distinguishes bladder cancer from no bladder cancer patients, was 2.147. Discussion and Conclusions: The reliability of the TG/HDL ratio is based on the fact that this parameter likely mirrors the insulin resistance (IR) underlying bladder cancer patients. Furthermore, PChE levels evidence both IR and the associated non-alcoholic fatty liver disease. The TG/HDL ratio and PChE levels as well as their combined use could help physicians to assess/confirm the presence of this very common cancer, where early detection is important to ensure the best therapeutical approach