Background: Both European and American trials showed superior effect of ulipristal acetate (UPA) to placebo. However, the latter, which included black patients with known higher vitaminD3 deficiency risk, showed lower rate of amenorrhea responders and insignificant uterine fibroid (UF) size reduction. Our objective is to investigate whether adding vitamin D3 to UPA can enhance UPA potency on UF phenotype in vitro. Methods: We screened the antiproliferative effect of different (UPA/vitaminD3) combinations on UF cell proliferation using dimethylthiazolyl diphenyltetrazolium bromide assay. Cells then were treated with UPA 100 nM in the presence or absence of vitamin D3 100 nM, and expression level of several markers related to proliferation, apoptosis, fibrosis, inflammation, and angiogenesis was measured on RNA or at protein level using quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, or multiplex enzyme-linked immunosorbent assay techniques. Results: Significant dose- and time-dependent growth inhibitory effects of UPA/vitamin D3 combinations were observed compared to untreated cells at 2 and 4 days ( P < .05). Importantly, vitamin D3/UPA combination significantly reduced cell proliferation as compared to UPA at 2, 4, 6, and 8 days ( P < .05). Combination treatment significantly decreased protein expression of proliferation markers Ki-67, PCNA, and CyclinD1 by more than 50% compared to UPA ( P < .05) along with a significant increase in apoptosis induction. Combination treatment resulted in a 2-fold decrease in protein levels of extracellular matrix markers collagen-1 and fibronectin besides pro-fibrogenic cytokine transforming growth factor β3 ( P < .05). Moreover, it significantly decreased the production of pro-inflammatory cytokines interleukins 6, 8, 1α, and 1β compared to UPA ( P < .05). Conclusion: Combination of vitamin D3 with UPA exhibits additional and orchestrated anti-UF effects, therefore might offer a more favorable clinical option.

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Background: Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. Methods: A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. Results: Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. Conclusion: Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns.

Context Uterine fibroids (UF) are the most common benign tumor of the myometrium (MM) in women of reproductive age. However, the mechanism underlying the pathogenesis of UF is largely unknown. Objective To explore the link between nuclear β-catenin and UF phenotype and β-catenin crosstalk with estrogen and histone deacetylases (HDACs). Design Protein/RNA levels of β-catenin (CTNNB1 gene), its responsive markers cyclin D1 and c-Myc, androgen receptor (AR), p27, and class-I HDACs were measured in matched UF/MM tissues or cell populations. The effects of chemical inhibition/activation and genetic knockdown of CTNNB1 on UF phenotype were measured. The anti-UF effect of 2 HDAC inhibitors was evaluated. Main Outcome Measure β-catenin nuclear translocation in response to β-catenin inhibition/activation, estrogen, and HDAC inhibitors in UF cells. Results UF tissues/cells showed significantly higher expression of nuclear β-catenin, cyclin D1, c-Myc, and HDACs 1, 2, 3, and 8 than MM. Estradiol induced β-catenin nuclear translocation and consequently its responsive genes in both MM and UF cells, while an estrogen receptor antagonist reversed this induction effect. Treatment with β-catenin or HDAC inhibitors led to dose-dependent growth inhibition, while Wnt3a treatment increased proliferation compared with control. Chemical inhibition of β-catenin decreased cyclin D1 and c-Myc expression levels, while β-catenin activation increased expression of the same markers. Genetic knockdown of CTNNB1 resulted in a marked decrease in β-catenin, cyclin D1, c-Myc, and AR expression. Treatment of UF cells with HDAC inhibitors decreased nuclear β-catenin, cyclin D1, and c-Myc expression. Moreover, HDAC inhibitors induced apoptosis of UF cells and cell cycle arrest. Conclusion β-catenin nuclear translocation contributes to UF phenotype, and β-catenin signaling is modulated by estradiol and HDAC activity.

Background: Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis. Methods: In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7–15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters. Results: Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (−79.6%; P <0.001), hs-CRP (−46.5%; P <0.001), IL-6 (−27.1%; P <0.001), and TNF-α (−51.7%; P <0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences −12.0 [95% CI −18.0 to −9.5] and −9.0 [95% CI −12.0 to −4.5]; P <0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed. Conclusions: Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04582097.

Objective: This study was undertaken to evaluate the antibody response of hepatitis B virus infection in patients on maintenance hemodialysis (MHD) by detecting different viral markers. Method: Study subjects comprised a total of 88 chronic kidney disease (CKD) patients from Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) and Bangabandhu Sheikh Mujib Medical University (BSMMU). Of them 63 patients on MHD and 25 predialysis patients served as cases and controls respectively. Clinical history was taken and serological markers for HBV (HBsAg, Anti-HBs, and Anti-HBc) were determined by using ELISA. Results: Hepatitis B virus was positive in 1.6% of maintenance hemodialysis (MHD) patients and in 16% of controls (p<0.02). Anti-HBc antibody was positive in 62% of dialysis patients and 72% of controls (p=NS) and the positivity was significantly associated in dialysis subjects with longer duration of dialysis (18 ± 22 vs. 10 ± 7, months, p<0.04), multiple units of blood transfusions (22 ± 29 vs. 10 ± 12, units, p<0.04) and more reuse of dialyzer (3 ± 1 vs. 2 ± 1, times, p<0.03) than the negative ones. Among MHD patients 84% were vaccinated against HBV with a schedule of 3 (79%) and 4 (21%) doses and protective antibody titer (>10 IU/L) was found in 57%. None of the controls were vaccinated but 66% had protective titer indicating post exposure natural immunity. Conclusions: Hepatitis B virus positivity was significantly higher among the predialysis subjects compared to dialysis group. Key words: Hepatitis B virus, Antibody response, Hemodialysis doi: 10.3329/bjms.v8i1.3185 Bangladesh Journal of Medical Science Vol.8 No. 1-2; 2009 15-21

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Renal allograft survival requires multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro‐protective medications, notably, proton pump inhibitors (PPI). This study aimed to compare the influence of pantoprazole and esomeprazole on serum cyclosporine trough levels (C0) in renal transplant recipients (RTR). A prospective, parallel, open‐label trial was conducted on 47 adult RTR receiving cyclosporine doses adjusted to attain trough concentrations of 100 to 150 μg/L, mycophenolate mofetil (MMF) 750 mg q12 hour and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt from January to September 2016. Patients were randomized into the esomeprazole group (25) or pantoprazole group (22) receiving the same dose (40 mg once daily). The study outcomes included clinical signs of rejection and renal function decline, assessed by elevations in serum creatinine, caused by cyclosporine level variations in either of the two study groups. Renal function, C0 and CBC measurements were measured at baseline and monthly for 6 months. The mean C0 values were higher in the pantoprazole group than in the esomeprazole group in the sixth month only (P = .007). Serum creatinine level was lower in the sixth month than at baseline in the esomeprazole group (P = .004). There were no signs of rejection biochemical or clinical in any of the study groups. In conclusion, PPIs should be used with caution and doses should be titrated to reach the C0 targets in RTR, which is of more importance in pantoprazole than esomeprazole to avoid C0 level elevation or decline affecting the allograft function.