Pollockmcfadden1974

In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation. Conclusion Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating pain syndrome of unknown etiology that predominantly affects females. Clinically, BPS/IC presents in a wide spectrum where all patients report severe bladder pain together with one or more urinary tract symptoms. On bladder examination, some have normal-appearing bladders on cystoscopy, whereas others may have severely inflamed bladder walls with easily bleeding areas (glomerulations) and ulcerations (Hunner's lesion). Thus, the reported prevalence of BPS/IC is also highly variable, between 0.06% and 30%. Nevertheless, it is rightly defined as a rare disease (ORPHA37202). The aetiopathogenesis of BPS/IC remains largely unknown. Current treatment is mainly symptomatic and palliative, which certainly adds to the suffering of patients. BPS/IC is known to have a genetic component. However, the genes responsible are not defined yet. In addition to traditional genetic approaches, novel research methodologies involving bioinformatics are evaluated to elucidate the genetic basis of BPS/IC. This article aims to review the current evidence on the genetic basis of BPS/IC to determine the most promising targets for possible novel treatments.Information on immune checkpoint inhibitor-induced vasculitides is limited, and predictors for this condition have not been identified. Therefore, we have examined the frequency of immune checkpoint inhibitor-induced vasculitides by analyzing the data recorded in the Japanese Adverse Drug Event Report database. Data from April 2004 to March 2020 were extracted, and vasculitides as an immune-related adverse event was defined according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Adverse event signals were recognized as significant when the reporting odds ratio estimates and lower limits of the corresponding 95% confidence intervals exceeded 1. The use of nivolumab showed a significant signal for vasculitides. Furthermore, significant signals of polymyalgia rheumatica were found when the patients were treated with nivolumab, pembrolizumab, and ipilimumab. In addition, the frequencies of nivolumab- and pembrolizumab-induced polymyalgia rheumatica were higher in patients aged ≥70 years and female patients, respectively. Polymyalgia rheumatica was reported in 38 patients treated with nivolumab; 31 (82%) of these were either in recovery or in remission. Further, polymyalgia rheumatica was reported in 17 patients treated with pembrolizumab; 13 (76%) of these were in recovery or remission, while three (18%) were not. Polymyalgia rheumatica was reported in 12 patients treated with ipilimumab; seven (58%) of these were in recovery or remission. Our study highlights that careful monitoring for the symptom of PMR (e.g., bilateral pain in shoulder and pelvic girdles) is required when the patients are aged >70 years and have been treated with nivolumab and when the patients are women and have been treated with pembrolizumab.Background Sequential low molecular weight heparin (LMWH) plus warfarin, LMWH plus edoxaban, and LMWH plus dabigatran regimens have already shown efficacy and safety in the treatment of acute pulmonary embolism (PE). The efficacy and safety of sequential LMWH plus rivaroxaban regimen in the treatment of acute PE have been understudied. Methods A retrospective study was performed to explore the efficacy and safety of sequential therapy regimens of subcutaneous LMWH (nadroparin 86 IU/kg every 12 h for a week) followed by oral rivaroxaban (20 mg once daily for 3 months) for the management of patients with established acute PE without hemodynamic instability, compared with those of nadroparin plus dabigatran and nadroparin plus warfarin. Results The number of patients with total resolution of PE were 238 (80.1%), 220 (78.0%), and 166 (62.6%), in the nadroparin + rivaroxaban, nadroparin + dabigatra, and nadroparin + warfarin groups, respectively. (p = 0.001) The prevalence of DVT at the 3-month follow-up visit was 18 (6.1%), 14 (5.0%), and 11 (4.2%), in the aforementioned three groups, respectively. (p = 0.559) The NT-proBNP level (pg/ml) at the 3-month follow-up visit was 122.5 (97.4-158.9), 131.7 (102.2-166.3), and 357.8 (275.4-433.2) in the three groups, respectively. BAPTAAM (p = 0.001) The D-dimer level (ng/ml) at the 3-month follow-up visit was 387.3 (310.9-465.2), 432.5 (382.4-489.6), and 854.0 (721.5-993.7) in the three groups, respectively (p less then 0.001). The number of patients with major bleeding events was 3(0.9%), 6(1.8%), and 18 (5.5%) in the three groups, respectively (p less then 0.001). Conclusion The regimen of sequential subcutaneous nadroparin at body-weight adjusted dose for a week followed by oral rivaroxaban at a dose of 20 mg once daily for 3 months is effective and safe in the initial treatment of patients with acute pulmonary embolism.Background Evidence-based recommendations for outpatient management of COVID-19 were published by the Italian Medicines Agency (AIFA) to limit the use of off-label treatments. The aim of this study is to measure the use of outpatient drug treatments in a COVID-19-positive population, taking into account the Italian regulatory agency's advices. Methods A descriptive observational study was conducted. All patients testing positive for COVID-19 residing in Lazio region, Italy, with diagnosis date between March 2020 and May 2021 were selected, and outpatient medicine prescription patterns were identified. Results Independent of AIFA recommendations, the use of drug therapy in the management of outpatient COVID-19 cases was frequent (about one-third of the cases). The most used drug therapy was antibiotics, specifically azithromycin, despite the negative recommendation of AIFA, while the use of corticosteroids increased after the positive recommendation of regulatory agency for the use in subjects with severe COVID-19 disease. The use of hydroxychloroquine was limited to the early pandemic period where evidence on its potential benefit was controversial. Antithrombotics were widely used in outpatient settings, even if their use was recommended for hospitalized patients. Conclusion In this study, we show a frequent use of drug therapy in the management of outpatient cases of COVID-19, mainly attributable to antibiotics use. Our research highlights the discrepancy between recommendations for care and clinical practice and the need for strategies to bridge gaps in evidence-informed decision-making.Multiple methodologies have been developed to identify and predict adverse events (AEs); however, many of these methods do not consider how patient population characteristics, such as diseases, age, and gender, affect AEs seen. In this study, we evaluated the utility of collecting and analyzing AE data related to hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information (USPIs, also called drug product labels or package inserts), the FDA Adverse Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, followed by AE classification and modeling using the Ontology of Adverse Events (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, although HCQ was reported to be associated with fewer types of cardiovascular, nervous system, and musculoskeletal AEs. According to EMBASE literature mining, CQ and HCQ were associated with QT prolongation (primarily when treating COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy (primarily when treating lupus). The FAERS data was analyzed by proportional ratio reporting, Chi-square test, and minimal case number filtering, followed by OAE classification. HCQ was associated with 63 significant AEs (including 21 cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 cardiovascular AEs) for lupus patients, supporting the hypothesis that the disease being treated affects the type and number of certain CQ/HCQ AEs that are manifested. Using an HCQ AE patient example reported in the literature, we also ontologically modeled how an AE occurs and what factors (e.g., age, biological sex, and medical history) are involved in the AE formation. The methodology developed in this study can be used for other drugs and indications to better identify patient populations that are particularly vulnerable to AEs.Background Diabetic cardiomyopathy (DCM) is a major long-term complication of diabetes mellitus, accounting for over 20% of annual mortality rate of diabetic patients globally. Although several existing anti-diabetic drugs have improved glycemic status in diabetic patients, prevalence of DCM is still high. This study investigates cardiac effect of alpha-lipoic acid (ALA) supplementation of anti-diabetic therapy in experimental DCM. Methods Following 12 h of overnight fasting, 44 male Sprague Dawley rats were randomly assigned to two groups of healthy control (n = 7) and diabetic (n = 37) groups, and fasting blood glucose was measured. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal (i.p.) administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). After confirmation of T2DM on day 3, diabetic rats received monotherapies with ALA (60 mg/kg; n = 7), gliclazide (15 mg/kg; n = 7), ramipril (10 mg/kg; n = 7) or combination of the three drugs (n = 7) for 6 weeks while utathione and superoxide dismutase activity and high-density lipoprotein-cholesterol compared to diabetic control (p less then 0.001). Mechanistically, induction of T2DM upregulated cardiac expression of TGF-β1, phosphorylated Smad2 and Smad3 proteins, which were downregulated following triple combination therapy (p less then 0.001). Conclusion Triple combination therapy of ALA, gliclazide and ramipril prevented DCM development by inhibiting TGF-β1/Smad pathway. Our findings can be extrapolated to the human heart, which would provide effective additional pharmacological therapy against DCM in T2DM patients.Background To explore the effect of combining traditional Chinese medicine (TCM) and Western medicine in hemodialysis patients with coronavirus disease 2019 (COVID-19). Methods This study was conducted from 27 January 2020 to 17 March 2020 in Wuhan Third Hospital Guanggu Branch, Wuhan, China. Fifty-three patients were included and divided into a control group (CG), which received Western medicine and a combined treatment group, which received TCM and Western medicine (TG). Clinical and laboratory data, TCM symptom scores, and chest computed tomography results were extracted and compared between the two groups. Results The TG included 21 (67.7%) men and 10 (32.3%) women with a mean age of 61.02 (standard deviation [SD] 15.07, range 26-89) years. The mean dialysis duration in the TG was 49 (SD 31) months. Of all patients in the TG, 27 (87.1%) had fatigue, 18 (58.1%) had dry cough, 16 (51.6%) had anorexia, 11 (35.5%) had dyspnea, and 11 (35.5%) had fever. The CG included 14 (63.6%) men and 8 (36.4%) women with a mean age of 61.