Probiotic supplements prevented oxonic acid-induced hyperuricemia and renal damage.

Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals.

Metabolic profiling of a chronic kidney disease cohort reveals metabolic phenotype more likely to benefit from a probiotic.

SCOPE: Persistent reduction in Glomerular Filtration Rate (GFR) is a hallmark of Chronic Kidney Disease (CKD) and is associated with an elevation of Blood Urea Nitrogen (BUN). This metabolomics pilot study sought to identify metabolites that differentiated patients with CKD whose BUN decreased on a probiotic and possible mechanisms. METHODS AND RESULTS: Metabolomics was used to analyze baseline plasma samples previously diagnosed with CKD Stage III-IV. Patients had participated in a dose escalation study of the probiotic Renadyl™. A total of 24 samples were categorized depending on whether BUN increased or decreased from baseline after 4 months of probiotic use. Multivariate analysis was used to analyze the data and determine the metabolites that best differentiated the phenotypic groups. The sixteen patients who had a decrease in BUN were not significantly different based on demographic and clinical measures from those whose BUN increased or did not change with the exception of age. Eleven of the fourteen metabolites that differentiated the groups were known to be modulated by gut microflora, which may eventually provide a mechanistic link between probiotic and outcomes. CONCLUSIONS: Metabolomics revealed metabolites at baseline that may predict individuals with CKD that would most benefit from a probiotics.

Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients.

BACKGROUND: Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. METHODS: Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. RESULTS: 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count (-0.51 × 10(9)/L, P = 0.057) and reductions in levels of C-reactive protein (-8.61 mg/L, P = 0.071) and total indoxyl glucuronide (-0.11 mg%, P = 0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL. CONCLUSIONS: Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power-further studies are warranted.

Methanol poisoning: predictors of visual outcomes.

OBJECTIVE: To determine whether laboratory markers of methanol ingestion and subsequent toxicity can serve as predictors of visual outcomes in patients. METHODS: Retrospective medical record review of 122 patients in a cluster outbreak of methanol poisoning. Data collected included history, complete ocular and systemic examination details, time to presentation, amount of alcohol ingested, and results of laboratory investigations, such as hemogram, glucose levels, hematocrit level, arterial pH, methanol levels, potassium and bicarbonate levels, and anion and osmolar gap determination, as well as hepatic and renal function tests. Therapy administered consisted of ethyl alcohol, sodium bicarbonate, and nutritional supplements, with hemodialysis in severe cases. Visual acuity (VA), pupillary reaction, and optic disc findings were assessed at presentation and 3 months after discharge. Patients were classified according to their visual disturbance: transient (group 1) or permanent (group 2). Appropriate statistical analysis was performed. Outcome measures included determining the association between biochemical markers of methanol poisoning and final VA. RESULTS: A total of 122 patients (1 female and 121 male) were admitted for treatment; of these, 10 died. Only 1 patient showed a 2-line drop in VA. pH was the strongest predictor of final VA and improvement in VA among all markers. The odds that a patient with an initial pH greater than 7.2 would have only transient visual disturbances were high (odds ratio, 31; 95% CI, 6-149). CONCLUSIONS: The degree of acidosis at presentation appears to determine final VA; early presentation and treatment did not seem to significantly alter the visual outcome, especially in severe poisoning.

Probiotics, prebiotics, and synbiotics: gut and beyond.

The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical) studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management.

Magnitude and determinants of ocular morbidities among persons with diabetes in a project in Ahmedabad, India.

BACKGROUND: Visual disabilities due to diabetes are on the rise, especially in urban areas of developing countries. Proper health planning will need evidence-based information. STUDY DESIGN AND METHODS: We estimated the prevalence and identified the determinants of eye complications among persons with diabetes screened in Ahmedabad, India, during 2007-2008. This was a review of the data from a health institution-based project. Physicians collected information on diabetes, and ophthalmologists examined the patients for visual acuity, diabetic retinopathy (DR), glaucoma, and cataracts. World Health Organization-recommended grading of DR was used. Frequencies, prevalence, and 95% confidence interval (CI) values were calculated. RESULTS: Of 40,919 persons who we examined for diabetes, 9,246 (66.6%) persons knew that they had diabetes, whereas 4,641 (33.4%) persons were detected with diabetes for the first time. The prevalence of DR, early cataract, and glaucoma among those who knew that they had diabetes was 14.6% (95% CI 13.9-15.3), 44.4% (95% CI 43.4-45.4), and 5.4% (95% CI 4.9-5.9), respectively. The prevalence of DR among persons with diabetes (new and old) was 10.1% (95% CI 9.6-10.6). Although poor vision was positively associated with DR (chi2 = 706), 40% of those with DR had vision better than 20/60. Male sex (odds ratio [OR] = 1.31), longer duration of diabetes (chi2 = 1,808), hypertension (OR = 1.13), good sugar control (OR = 0.09), and nephropathy (OR = 2.16) were the factors associated with DR. Regression analysis suggested that longer duration of diabetes and poor control of diabetes were the predictors of DR. CONCLUSIONS: The prevalence of DR was low. Long duration of diabetes, poor control of blood sugar, presence of nephropathy, and hypertension were associated with DR. Good vision could mislead about the severity of DR.

Evaluation of sparfloxacin eye drop in the management of conjunctival and corneal infection.

Sparfloxacin 03% eye drop was evaluated in consecutive culture proven cases of conjunctivitis and corneal infection. Sparfloxacin 03% eye drop was found to provide 100% cure rate clInIcally as well as bacteriologically. This can be due to better ocular penetration and higher therapeutic index of sparfloxacin 03% eye drops. Sparfloxacin seems to be a better antibiotic for topical application for themanagement of external ocular Infections like conjunctivitis, keratitis and corneal ulcers.