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PloS One 2024Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in...
Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
Topics: Humans; Paclitaxel; Mucin 5AC; A549 Cells; Drug Interactions; Mucin-5B; Mucins; Mucin-2; Rifampin; Cyclosporine; Protein Binding
PubMed: 38935605
DOI: 10.1371/journal.pone.0306058 -
Indian Journal of Public Health Oct 2023The Saharia tribe of Madhya Pradesh has a very high tuberculosis (TB) burden. However, there is no report of adverse drug reaction (ADR) available in patients receiving... (Observational Study)
Observational Study
Adverse Drug Reaction Patterns of First-line Anti-tubercular Drugs among Saharia Tuberculosis Patients: An Observational Study in Particularly Vulnerable Tribal Group of Madhya Pradesh, India.
The Saharia tribe of Madhya Pradesh has a very high tuberculosis (TB) burden. However, there is no report of adverse drug reaction (ADR) available in patients receiving anti-TB chemotherapy in the community. Reporting and monitoring of ADRs among TB patients is still rare in marginalized communities. An observational prospective study was performed from November 2019 to June 2020 to assess the patterns of ADRs in 250 Saharia TB patients, who were prescribed Category-I daily DOTS (HRZE) by the physician. Both male and female participants equally experienced ADR during the treatment, but relatively more females (92.6%) than males (88.6%) reported ADR during Phase I. Out of 250 patients, 224 patients (89.6%) experienced one or more ADRs in Phase I. The central nervous system-related (75.6%) ADR was mostly reported followed by any gastrointestinal (74.4%), cardiovascular (49.2%) and any dermatological related (44.4%) ADRs. It is paramount to timely monitor and proactively manages ADRs pertaining to anti-TB drug treatment with minimal alteration in the treatment course.
Topics: Humans; India; Male; Female; Antitubercular Agents; Adult; Prospective Studies; Middle Aged; Tuberculosis; Drug-Related Side Effects and Adverse Reactions; Adolescent; Young Adult; Directly Observed Therapy; Aged
PubMed: 38934815
DOI: 10.4103/ijph.ijph_865_22 -
Polish Archives of Internal Medicine Jun 2024
Topics: Humans; Kidney Transplantation; Male; Antitubercular Agents; Tuberculosis; Allografts; Middle Aged; Female; Adult
PubMed: 38934247
DOI: 10.20452/pamw.16785 -
Polish Archives of Internal Medicine Jun 2024
Topics: Humans; Kidney Transplantation; Tuberculosis; Allografts; Antitubercular Agents
PubMed: 38934246
DOI: 10.20452/pamw.16786 -
The Pan African Medical Journal 2024tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study...
INTRODUCTION
tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs).
METHODS
a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05).
RESULTS
two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109).
CONCLUSION
site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.
Topics: Humans; Nigeria; HIV Infections; Adult; Female; Antitubercular Agents; Male; Tuberculosis; Middle Aged; Coinfection; Treatment Outcome; Young Adult; Anti-HIV Agents; Isoniazid; Retrospective Studies; Tuberculosis, Pulmonary
PubMed: 38933432
DOI: 10.11604/pamj.2024.47.149.35719 -
Frontiers in Immunology 2024
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Antitubercular Agents; Disease Management
PubMed: 38933279
DOI: 10.3389/fimmu.2024.1433345 -
International Journal of Molecular... Jun 2024C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component... (Review)
Review
C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results.
Topics: Humans; Kidney Transplantation; Complement C3; Graft Rejection; Glomerulonephritis; Mycophenolic Acid
PubMed: 38928213
DOI: 10.3390/ijms25126508 -
Biomolecules Jun 2024Incidences of drug-resistant tuberculosis have become common and are rising at an alarming rate. Aminoacyl t-RNA synthetase has been validated as a newer target against...
Incidences of drug-resistant tuberculosis have become common and are rising at an alarming rate. Aminoacyl t-RNA synthetase has been validated as a newer target against . Leucyl t-RNA synthetase (LeuRS) is ubiquitously found in all organisms and regulates transcription, protein synthesis, mitochondrial RNA cleavage, and proofreading of matured t-RNA. Leucyl t-RNA synthetase promotes growth and development and is the key enzyme needed for biofilm formation in Mycobacterium. Inhibition of this enzyme could restrict the growth and development of the mycobacterial population. A database consisting of 2734 drug-like molecules was screened against leucyl t-RNA synthetase enzymes through virtual screening. Based on the docking scores and MMGBSA energy values, the top three compounds were selected for molecular dynamics simulation. The druggable nature of the top three hits was confirmed by predicting their pharmacokinetic parameters. The top three hits-compounds (ZINC000001543916), (ZINC000001554197), and (ZINC000008214483)-were evaluated for their binding affinity toward leucyl t-RNA synthetase by an isothermal titration calorimetry study. The inhibitory activity of these compounds was tested against antimycobacterial activity, biofilm formation, and LeuRS gene expression potential. Compound (Macimorelin) was found to be the most potent molecule, with better antimycobacterial activity, enzyme binding affinity, and significant inhibition of biofilm formation, as well as inhibition of the LeuRS gene expression. Compound , the top hit compound, has the potential to be used as a lead to develop successful leucyl t-RNA synthetase inhibitors.
Topics: Mycobacterium tuberculosis; Ligands; Antitubercular Agents; Leucine-tRNA Ligase; Molecular Docking Simulation; Enzyme Inhibitors; Calorimetry; Molecular Dynamics Simulation; Tuberculosis; Computer Simulation; Protein Binding; Humans
PubMed: 38927114
DOI: 10.3390/biom14060711 -
BMJ Case Reports Jun 2024SummaryUlcerative colitis (UC), a chronic inflammatory bowel disease, can cause extraintestinal manifestations (EIMs) in approximately 40% of individuals. This case...
SummaryUlcerative colitis (UC), a chronic inflammatory bowel disease, can cause extraintestinal manifestations (EIMs) in approximately 40% of individuals. This case report discusses the diagnostic procedure of a woman in her 20s who initially had non-specific symptoms. The patient underwent a thorough evaluation, which initially pointed towards tuberculosis (TB) due to necrotic lymphadenopathy and granulomatous hepatitis. However, no microbiological evidence of TB was found, and her symptoms worsened despite antitubercular therapy. The patient developed painful nodular-ulcerative skin lesions consistent with cutaneous polyarteritis nodosa (cPAN) on biopsy. Eventually, a definitive diagnosis of UC was made, revealing the true nature of her multisystemic manifestations. Cutaneous vasculitis, including leucocytoclastic vasculitis and cPAN, is a rare EIM of UC, with only five reported cases in the literature. This case report highlights the clinical implications of EIMs and contributes to the expanding knowledge of rare EIMs such as cPAN and granulomatous hepatitis.
Topics: Humans; Polyarteritis Nodosa; Female; Colitis, Ulcerative; Hepatitis; Diagnosis, Differential; Granuloma; Adult; Antitubercular Agents
PubMed: 38926121
DOI: 10.1136/bcr-2023-257581 -
Biological & Pharmaceutical Bulletin 2024Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are...
Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are considered the key to examining the drug-drug interaction (DDI). In this study, using human HepaRG cells as an in vitro model system, we analyzed the potential DDI based on the expression levels of CYP3A4 and CYP1A2. Rifampicin and omeprazole, the potent inducers for CYP3A4 and CYP1A2, respectively, induce expression of the corresponding CYP enzymes at both the mRNA and protein levels. We noticed that, in addition to inducing CYP1A2, omeprazole induced CYP3A4 mRNA expression in HepaRG cells. However, unexpectedly, CYP3A4 protein expression levels were not increased after omeprazole treatment. Concurrent administration of rifampicin and omeprazole showed an inhibitory effect of omeprazole on the CYP3A4 protein expression induced by rifampicin, while its mRNA induction remained intact. Cycloheximide chase assay revealed increased CYP3A4 protein degradation in the cells exposed to omeprazole. The data presented here suggest the potential importance of broadening the current DDI examination beyond conventional transcriptional induction and enzyme-activity inhibition tests to include post-translational regulation analysis of CYP enzyme expression.
Topics: Omeprazole; Humans; Cytochrome P-450 CYP3A; Rifampin; RNA, Messenger; Drug Interactions; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP1A2; Cell Line
PubMed: 38925922
DOI: 10.1248/bpb.b24-00161