Amoxicillin (AMX) is a common antibiotic used in both human and veterinary medicine in order to both cure and avoid bacterial infections. Traces of AMX have been found in ground and surface water, urban effluents, water, and wastewater treatment facilities due to its widespread use. The level of hazard and disposal of this class of micropollutants is the reason for concern.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
July 2023
Viral respiratory diseases (VRDs) cause lung inflammation and inflammatory cytokine production. We study whether dapsone is responsible for its observed preventive treatment effects of the sustained viral RNA interferon response. Around 2008 and 2012, Korea's Dementia Management Act stipulated drastic changes in the administration of dementia medication by medical staff.
View Article and Find Full Text PDFSome physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether dapsone is helping or not, we undertook a retrospective chart review of 29 consecutive ICU COVID-19 patients receiving dapsone and 30 not receiving dapsone. As we previously reported, of those given dapsone, 9/29 (30%) died, while of those not given dapsone, 18/30 (60%) died.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation.
View Article and Find Full Text PDFBrain inflammation generally accelerates neurodegeneration. Alzheimer's disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD.
View Article and Find Full Text PDFSince the start of the SARS-CoV-2 pandemic, refractory and relentless hypoxia as a consequence of exuberant lung inflammation and parenchymal damage remains the main cause of death. We have earlier reported results of the addition of dapsone in this population to the standard of care. We now report a further chart review of discharge outcomes among patients hospitalized for COVID-19.
View Article and Find Full Text PDFBackground & Aims: Oral therapies targeting the integrin α4β7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4β7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC).
Methods: In vitro studies measured binding properties of PTG-100.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seems to be difficult to overcome. A pandemic of such a scale has not been seen since the 1918 influenza pandemic. Although the predominant clinical presentation is respiratory disease, neurological manifestations and sequelae are increasingly being recognized.
View Article and Find Full Text PDFThe accurate classification of ambulation modes and estimation of walking parameters is a challenging problem that is key to many applications. Knowledge of the user's state can enable rehabilitative devices to adapt to changing conditions, while in a clinical setting it can provide physicians with more detailed patient activity information. This study describes the development and optimization process of a combined locomotion mode classifier and environmental parameter estimator using machine learning and wearable sensors.
View Article and Find Full Text PDFAm J Respir Crit Care Med
October 2020
Ahead of Print article withdrawn by publisher.
View Article and Find Full Text PDFUnlabelled: Children with chronic hepatitis C virus infection have limited treatment options. We evaluated the all-oral combination of sofosbuvir and ribavirin in adolescents aged 12-17 with hepatitis C virus genotype 2 or 3 (ClinicalTrials.gov NCT02175758).
View Article and Find Full Text PDFUnlabelled: No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a phase 2, multicenter, open-label study to evaluate the efficacy and safety of ledipasvir-sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients aged 12-17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks.
View Article and Find Full Text PDFUntil 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open-label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment-naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight-based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks.
View Article and Find Full Text PDFBackground: Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed.
Aim: The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease.
Background: Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis.
Aim: To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis.
Methods: We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo.
Unlabelled: Retreatment of patients who have not achieved sustained virological response (SVR) after treatment with investigational direct-acting antiviral agents (DAAs) has not been extensively studied. We conducted an open-label trial to assess the efficacy and safety of sofosbuvir (SOF) plus pegylated interferon (Peg-IFN) and ribavirin (RBV) in patients with genotype 1 hepatitis C virus (HCV) who participated in previous studies of one or more Gilead investigational DAAs in combination with RBV with or without Peg-IFN. We enrolled 80 patients at 40 sites.
View Article and Find Full Text PDFBackground: Protease inhibitors for the treatment of HCV can cause mild and reversible elevations of unconjugated bilirubin. We sought to characterize genetic determinants of bilirubin elevations using a genome-wide approach among patients with genotype 1 HCV who received combination therapy that included GS-9256, a novel potent inhibitor of HCV NS3 serine protease, as part of a Phase IIb trial.
Methods: Of the 200 patients sampled, 176 had confirmed European ancestry and were included in the analysis.
Unlabelled: This phase II trial assessed the efficacy and safety of a combination regimen of the nonstructural protein (NS)5A inhibitor ledipasvir (LDV), NS3 protease inhibitor vedroprevir (VDV), non-nucleoside NS5B inhibitor tegobuvir (TGV), and ribavirin (RBV) in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype 1 without cirrhosis. Patients were randomized 1:2 to LDV 30 mg once daily (QD; Arm 1; n = 46) or LDV 90 mg QD (Arm 2; n = 94); patients in both arms also received VDV 200 mg QD, TGV 30 mg twice-daily, and RBV 1,000-1,200 mg/day. Patients in Arm 2 with vRVR, defined as HCV RNA below the lower limit of quantification (LLOQ) from treatment weeks 2 to 10, were randomized 1:1 to stop treatment at 12 weeks or continue for 24 weeks.
View Article and Find Full Text PDFIdiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells.
View Article and Find Full Text PDFThe mechanisms by which some HIV-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. Viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. However, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression.
View Article and Find Full Text PDFJ Pediatr Gastroenterol Nutr
June 2012