Insights into the efficient removal and mechanism of NiFeAl-LDH with abundant hydroxyl to activate peroxymonosulfate for sulfamethoxazole wastewater.

Layered double hydroxide (LDH) material with abundant OH was successfully prepared by co-precipitation method, and a water purification system of Ni2Fe0.25Al0.75-LDH activated peroxymonosulfate (PMS) was constructed to rapidly degrade sulfamethoxazole (SMX) pollutants. The optimal conditions for the degradation of SMX in the system were as follows: 0.30 g/L Ni2Fe0.25Al0.75-LDH, 0.30 mM PMS, pH = 7 and 90 % SMX was removed in 10 min and almost completely in 40 min, which was consistent with the predicted results of response surface methodology (RSM) analysis. The abundant OH in Ni2Fe0.25Al0.75-LDH could form M(O)OSO3 complexes with PMS, accelerating the generation of reactive oxygen species (ROS) and promoting the removal of SMX. Quenching experiments and electron paramagnetic resonance (EPR) spectra showed that SO4-, OH, O2- and 1O2 also existed in the system. The surface-bound SO4- and O2- contributed greatly to the removal of SMX and the electron transfer between metals was also conducive to the production of active substances. The possible degradation pathways and intermediates of SMX were proposed. The toxicity assessment software tool (T.E.S.T) and total organic carbon (TOC) results indicated that the Ni2Fe0.25Al0.75-LDH/PMS system could reduce the overall environmental risk of SMX to some extent. This study provided a new strategy for the practical application of heterogeneous catalysts in sewage treatment.

Degradation of sulfamethoxazole in a falling film dielectric barrier discharge system: Performance, mechanism and toxicity evaluation.

The ubiquitous presence of sulfonamides (SAs) in wastewater poses serious risks to human health and ecosystem safety. This study evaluated the performance of a falling film dielectric barrier discharge (DBD) system on the removal of five SAs, namely sulfamethoxazole (SMX), sulfisoxazole (SIZ), sulfathiazole (STZ), sulfadiazine (SDZ) and sulfamerazine (SMR). Removal efficiencies >99 % were observed for all target SAs within 30 min of treatment, with pseudo-first order rate constants varying between 0.17 and 0.27 min-1. Superior removal efficiencies were achieved under acidic conditions compared to neutral and alkaline conditions. Using SMX as a model compound, mechanistic investigations revealed that the synergy of reactive oxygen species (ROS) and reactive nitrogen species (RNS) led to its efficient degradation, with peroxynitrites (ONOO-/ONOOH) and hydroxyl radical (OH) playing pivotal roles. SMX degradation pathways encompassing nitration/nitrosation, hydroxylation, deamination, CS and SN bond cleavage were proposed. The toxicity evaluation results demonstrated that the solution toxicity diminished following the plasma treatment under specific conditions. In particular, the solution treated with air or oxygen discharge enhanced the growth of wheat seedlings, suggesting the potential for reusing plasma-treated wastewater in agriculture. This study enhances our understanding of the underlying mechanisms involved in the plasma degradation of SAs and reveals the significant potential of plasma technology as a sustainable approach for treating wastewater.

Successful Treatment of Recurrent Extensively Drug-Resistant Elizabethkingia anophelis Bacteremia Secondary to Ventricular Assist Device-Associated Infection.

Elizabethkingia anophelis is an emerging pathogen increasingly implicated in health care-associated infections. Here, we report a case of recurrent ventricular assist device-associated infection caused by multidrug-resistant Elizabethkingia anophelis and describe the clinical course, treatment challenges, and ultimate case resolution. Our results demonstrate that standard clinical methodologies for determining trimethoprim-sulfamethoxazole minimum inhibitory concentration, including VITEK2 and gradient diffusion tests, may be unsuitable for Elizabethkingia anophelis as they result in false-negative susceptibility results. The discrepancy between antimicrobial susceptibility testing reported here highlights the importance of investigating and validating the applicability of standard clinical antimicrobial susceptibility testing and interpretation when treating emerging pathogens such as Elizabethkingia anophelis.

Removal of sulfamethoxazole in an algal-bacterial membrane aerated biofilm reactor: Microbial responses and antibiotic resistance genes.

Antibiotics are frequently detected in wastewater, but often are poorly removed in conventional wastewater treatment processes. Combining microalgal and nitrifying bacterial processes may provide synergistic removal of antibiotics and ammonium. In this research, we studied the removal of the antibiotic sulfamethoxazole (SMX) in two different reactors: a conventional nitrifying bacterial membrane aerated biofilm reactor (bMABR) and algal-bacterial membrane aerated biofilm reactor (abMABR) systems. We investigated the synergistic removal of antibiotics and ammonium, antioxidant activity, microbial communities, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and their potential hosts. Our findings show that the abMABR maintained a high sulfamethoxazole (SMX) removal efficiency, with a minimum of 44.6 % and a maximum of 75.8 %, despite SMX inhibition, it maintained a consistent 25.0 % ammonium removal efficiency compared to the bMABR. Through a production of extracellular polymeric substances (EPS) with increased proteins/polysaccharides (PN/PS), the abMABR possibly allowed the microalgae-bacteria consortium to protect the bacteria from SMX inactivation. The activity of antioxidant enzymes caused by SMX was reduced by 62.1-98.5 % in the abMABR compared to the bMABR. Metagenomic analysis revealed that the relative abundance of Methylophilus, Pseudoxanthomonas, and Acidovorax in the abMABR exhibited a significant positive correlation with SMX exposure and reduced nitrate concentrations and SMX removal. Sulfonamide ARGs (sul1 and sul2) appeared to be primarily responsible for defense against SMX stress, and Hyphomicrobium and Nitrosomonas were the key carriers of ARGs. This study demonstrated that the abMABR system has great potential for removing SMX and reducing the environmental risks of ARGs.

Myasthenia gravis complicated with pulmonary infection by Nocardia cyriacigeorgica: a case report and literature review.

Myasthenia gravis (MG) is an autoimmune disease. Patients with MG due to compromised autoimmune regulation, progressive muscle weakness, and prolonged use of immunosuppressants and glucocorticoid, often present with concomitant infections. However, cases of MG complicated by Nocardia infection are rare. In this case, we report MG complicated with pulmonary infection by Nocardia cyriacigeorgica. A 71-year-old male farmer who was admitted for management of MG. After 7 weeks of treatment of MG, the patient reported improvement. However, clinical presentation, inflammatory markers, and imaging findings supported a diagnosis of pulmonary infection. To further elucidate the etiology, Nocardia was identified in sputum smear microscopy and sputum culture, with 16S rRNA gene sequencing confirming N. cyriacigeorgica. The patient was prescribed trimethoprim-sulfamethoxazole. After 1 month of treatment, clinical symptoms of MG and pulmonary nocardiosis showed significant improvement. Additionally, we searched PubMed for case reports of Nocardia cyriacigeorgica pulmonary infection from 2010 to 2024 and conducted a statistical analysis of the case information. This report aims to highlights the increased risk of pulmonary Nocardia infection in MG patients after the use of steroids and immunosuppressants, thereby enhancing clinical awareness.

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study.

OBJECTIVES: Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. METHODS: This retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0-20.0 mg/kg/d) and low-dose (7.5-15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. RESULTS: Among 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, -1.4 %; 95 % CI, -4.5-1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3-6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, -4.0 %; 95 % CI, -7.4 to -0.6 %; P = 0.020). CONCLUSION: Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. METHODS: We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. RESULTS: Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). CONCLUSIONS: This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

Neuropsychiatric Adverse Effects of Trimethoprim-Sulfamethoxazole: A Rare Case of Acute Psychosis in an Immunocompetent Patient.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination of two antibiotics used to treat various bacterial infections, generally well-tolerated but can rarely cause neuropsychological adverse effects, including psychosis. This case report describes a 69-year-old immunocompetent female who developed acute visual and auditory hallucinations three days after starting TMP-SMX for a urinary tract infection (UTI). The patient had a history of depression, successfully treated with mirtazapine a decade ago, and no other psychiatric or medical conditions. Laboratory tests and imaging were unremarkable. Symptoms resolved completely within two days of discontinuing TMP-SMX, suggesting a causal relationship. This case highlights the need for vigilance regarding the neuropsychiatric side effects of TMP-SMX, even in immunocompetent individuals, and underscores the importance of considering medication-induced psychosis in differential diagnoses. Further research is warranted to elucidate the mechanisms underlying this adverse drug reaction.

Sulfamethoxazole degradation pathways in wastewater treatment: Bayesian network-based approach for a meta-analysis of scientific papers.

Given the widespread presence of micropollutants in urban water systems, it is imperative to gain a comprehensive understanding of their degradation pathways. This paper focuses on sulfamethoxazole (SMX) as a model molecule due to its extensive study, aiming to elucidate its degradation pathways in biological (BIO) and oxidative (AOP) processes. Numerous reaction pathways are outlined in scientific papers. However, a significant deficiency in current methodologies has led to the development of a novel meta-analytical approach, seeking consensus among researchers by synthesizing data from studies characterized by their heterogeneity and contradictions. As an innovative alternative, probabilistic graphical models such as Bayesian networks (BNs) could illuminate the relationships and dependencies between various transformation products, providing a holistic view of the degradation process. Based on the analysis of an extensive bibliography gathering more than 45 articles for more than 140 molecules and 177 reaction pathways, this study proposes a meta-analysis methodology based on Bayesian networks.

Efficacy and safety of a low-dose sulfamethoxazole/trimethoprim regimen in preventing pneumocystis pneumonia: A retrospective study using a large-scale electronic medical record database.

INTRODUCTION: Sulfamethoxazole/trimethoprim (ST) is a first-line drug for preventing pneumocystis pneumonia (PCP). Several small-scale studies have suggested the usefulness of the low-dose regimen of ST (200/40 mg/day) over the standard-dose one (400/80 mg/day). Thus, this study aimed to investigate the efficacy and safety of low-dose and standard-dose regimens of ST in preventing PCP in patients with non human immunodeficiency virus infection using a large-scale electronic medical record database. METHODS: This retrospective study included patients who received ST prophylaxis for PCP registered in the RWD database between June 2007 and February 2023. Patients received either standard-dose (400/80 mg/day) or low-dose (200/40 mg/day) regimen groups. The incidence of cases initiated PCP therapeutic dose (ci-PCPTD) (ST ≥ 3600/720 mg/day) and adverse events (AEs) was evaluated, and risk factors for ci-PCPTD were investigated. RESULTS: A total of 11,384 patients received the standard-dose, whereas 7973 received the low-dose regimen groups. No significant difference in the cumulative incidence of ci-PCPTD was observed between the standard-dose (0.67%) and low-dose regimen group (0.47%). Lung disease was a significant risk factor for ci-PCPTD. The cumulative incidence of ci-PCPTD in patients with acute exacerbation of interstitial pneumonia was 1.3% in both groups, and no significant difference was observed between the two groups. The low-dose regimen group had a lower incidence of all AEs than the standard-dose regimen group. CONCLUSION: These results based on a large-scale electronic medical record database provide important evidence supporting the clinical significance of low-dose regimen of ST.

Efficient sulfamethoxazole biotransformation and detoxification by newly isolated strain Hydrogenophaga sp. SNF1 via a ring ortho-hydroxylation pathway.

Sulfonamides are frequently detected with high concentrations in various environments and was regarded as a serious environmental risk by fostering the dissemination of antibiotic resistance genes. This study for the first time reported a strain SNF1 affiliated with Hydrogenophaga can efficiently degrade sulfamethoxazole (SMX). Strain SNF1 prefers growing under extra carbon sources and neutral condition, and could degrade 500 mg/L SMX completely within 16 h. Under the conditions optimized by response surface method (3.11 g/L NaAc, 0.77 g/L (NH4)2SO4, pH = 7.53, and T = 34.38 â„ƒ), a high removal rate constant 0.5104 /h for 50 mg/L SMX was achieved. Coupling the intermediate products identification with comparative genomic analysis, a novel SMX degradation pathway was proposed. Unlike Actinomycetota degraders, SMX was deaminized and ring ortho-hydroxylated in strain SNF1 using a Rieske dioxygenase in combination with glutamine synthetase system. Rieske dioxygenase gene expression was up-regulated by 1.09 to 6.02-fold in response to 100 mg/L SMX. When SMX is fully degraded, its antimicrobial activity drops by over 90 %, and its anticipated toxicity to aquatic organisms were overall reduced. These findings provided new insights into SMX-degrading microorganisms and mechanisms and highlighted the potential of Hydrogenophaga. sp. SNF1 for biological elimination of SMX from wastewater.

Iron metal-organic framework nanofiber membrane for the integration of electro-Fenton and effective continuous treatment of pharmaceuticals in water.

In this study, an iron metal-organic framework (Fe-MOF) was synthesized and immobilized by electrospinning technique with the objective of obtaining a membrane composed of nanofibers of this material (Fe-MOF nanofiber membrane). The characterization performed by XRD, TEM, SEM, EDS mapping and FTIR confirmed the correct synthesis of Fe-MOF as well as its correct retention in the elaborated membranes. The usefulness and effectiveness of the Fe-MOF nanofiber membrane as a catalyst for the electro-Fenton process was evaluated by performing sulfamethoxazole degradation tests. Different parameters such as the effect of intensity (25 and 100 mA), the effect of the drug initial concentration (10-50 mg/L) and the reusability of membranes were studied. Then, the degradation of a drug mixture formed by sulfamethoxazole and antipyrine was evaluated, reaching a degradation of 92.10 % and 87.43 % respectively for each drug in 4 h at 25 mA. In addition, the identification of reactive oxygen species was ascertained by scavenger assays. The study of degradation products was also carried out and their toxicity was predicted by ECOSAR program, concluding that the environmental toxicity would disappear with mineralization. Finally, given the good results obtained in batch tests, the behavior of the process was studied in a system that works continuously, achieving a stable degradation of 83.10 % in the case of treatment with a mixture of drugs. This confirmed the stability of the Fe-MOF nanofiber membrane, as well as, its catalytic activity, making it suitable for long-term treatments.

Pyrolytic conversion of cattle manure into value-added products and application of biochar for adsorption of sulfamethoxazole.

This study investigated the thermochemical conversion of cattle manure (CM) to propose a sustainable platform for its valorization, and explored the applicability of CM-derived biochar (CMB) as an environmental medium for the adsorptive removal of sulfamethoxazole (SMZ). CM pyrolysis was conducted under two atmospheric conditions (N2 and CO2), and the pyrogenic products were quantified and characterized. Real-time syngas monitoring revealed that CO2 enhanced CO generation from the CM, leading to the formation of a highly porous carbon structure in the produced biochar (CMBCO2). The adsorptive removal of SMZ by CMBCO2 was highly dependent on the pH conditions. The adsorption kinetics of SMZ onto CMBCO2 reached equilibrium within 540 min, following a pseudo-second-order model. The SMZ adsorption isotherms fit the Langmuir-Freundlich model, highlighting the importance of chemisorption in the adsorption process. X-ray photoelectron spectroscopy revealed that SMZ was adsorbed by non-electrostatic mechanisms, including hydrogen bonding, Lewis acid-base interactions, surface complexation, and π-π electron-donor acceptor interactions. This study presents an exemplary strategy for converting livestock waste into valuable resources, enabling the harvesting of energy resources and the production of treatment media for environmental remediation.

Decorated Electrode Surfaces with Nanostructures and Metal-Organic Frameworks as Transducers for Sensing.

In this study, several materials are presented as modifiers of the screen-printed carbon electrodes with the aim of developing new sensing platforms for the voltammetric analysis of drugs. Specifically, Clotiapine and Sulfamethoxazole were selected as models for antipsychotics and antibiotics, respectively. Different nanostructures were studied as modifiers, including both transition metals and carbon-based materials. Moreover, biochar and two metal-organic frameworks (MOFs) were tested as well. The NH2-MIL-125(Ti) MOF showed an 80% improvement in the analytical signal of Sulfamethoxazole, but it partially overlapped with an additional signal associated with the loss of the MOF ligand. For this reason, several immobilization strategies were tested, but none of them met the requirements for the development of a sensor for this analyte. Conversely, carbon nanotubes and the NH2-MIL-101(Fe) MOF were successfully applied for the analysis of Clotiapine in the medicine Etumine®, with RSD below 2% and relative errors that did not exceed 9% in any case, which demonstrates the precision and accuracy achieved with the tested modifications. Despite these promising results, it was not possible to lower the limits of detection and quantification, so in this sense further investigation must be performed to increase the sensitivity of the developed sensors.

The role of trimethoprim/sulfamethoxazole in preventing opportunistic infections in systemic lupus erythematosus patients receiving low-level immunosuppressive treatment: an open-label, randomized, controlled trial.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. METHODS: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. RESULTS: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. CONCLUSIONS: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids.

OBJECTIVES: To compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. METHODS: We retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. RESULTS: A total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. CONCLUSIONS: Lower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

Microalgae Enhances the Adaptability of Epiphytic Bacteria to Sulfamethoxazole Stress and Proliferation of Antibiotic Resistance Genes Mediated by Integron.

The transmission of ARGs in the microalgae-associated epiphytic bacteria remains unclear under antibiotic exposure, apart from altering the microbial community structure. In this study, Chlorella vulgaris cocultured with bacteria screened from surface water was examined to explore the spread of ARGs in the presence of sulfamethoxazole (SMX). The extracellular polymers released by Chlorella vulgaris could reduce antibiotic-induced collateral damage to bacteria, thus increasing the diversity of the microalgae-associated epiphytic bacteria. The abundances of sul1 and intI1 in the phycosphere at 1 mg/L SMX dose increased by 290 and 28 times, respectively. Metagenomic sequencing further confirmed that SMX bioaccumulation stimulated the horizontal transfer of sul1 mediated by intI1 in the microalgae-associated epiphytic bacteria, while reactive oxygen species (ROS)-mediated oxidative stress induced the SOS response and thus enhanced the transformation of sul1 in the J group. This is the first study to verify that microalgae protect bacteria from antibiotic damage and hinder the spread of ARGs mediated by SOS response, while the transfer of ARGs mediated by integron is promoted due to the bioaccumulation of SMX in the phycosphere. The results contribute to present comprehensive understanding of the risk of ARG proliferation by the presence of emerging contaminants residues in river.

Development of a gradient method for sulfamethoxazole, trimethoprim, isoniazid, and pyridoxine hydrochloride in rabbit plasma through QbD-driven investigation.

The current study developed a method for quantifying four drugs-Sulfamethoxazole, Trimethoprim, Isoniazid, and Pyridoxine-in rabbit plasma. The method uses gradient liquid chromatography based on analytical quality by design. To achieve separation, a Eclip Plus C18 (250 mm × 5 mm, 4.6 µm) column with L1 packing was used, and analytes were detected at 254 nm at ambient temperature. The optimized mobile phase consisted of 50 mM potassium dihydrogen phosphate buffer (pH 6.5) and Methanol. The concentration of Methanol was 3% (0-5 min), 15% (5-15 min), 55% (15-27 min), and 3% Methanol until the end of the 30-min runtime, and the flow rate was set at 0.95 mL/min. Control Noise Experimentation was used to screen studies, revealing that flow rate, pH, and Methanol concentration significantly affected the analytical attributes. The study identified critical attributes (resolution and asymmetric factor) and developed a quality target method profile. A central composition design was used to optimize the essential parameters. The method developed for the drugs showed peaks at retention times of 6.990 min for Isoniazid, 7.880 min for Pyridoxine, 15.530 min for Sulfamethoxazole, and 26.890 min for Trimethoprim, respectively. The method was validated with linearity in the range of 10-640 ng ml-1, with R2 of 0.9993, 0.9987, 0.9993, and 0.9992 for Sulfamethoxazole, Trimethoprim, Isoniazid, and Pyridoxine, respectively.

Novel sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives as potential apoptotic and antiproliferative agents by inhibition of BCL2; design, synthesis, biological evaluation, and docking studies.

In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, IH NMR,13C NMR, Mass spectrometry, CHN data, and evaluated for their efficiency as BCL2 inhibitors that could lead to potential antiproliferative activity. The ten newly synthesized compounds were screened for their therapeutic activity using MDA-MB-231 breast cancer cell lines. All the test compounds exhibited moderate to high cytotoxic activity in MTT assay. Among them, compounds 3e and 6b exhibited promising antitumor activity, as evidenced by their IC50 values of 16.98 and 17.33 µM respectively. In addition, both compounds 3e and 6b displayed potential antioxidant and apoptosis induction properties. The qRT-PCR analysis showed down regulation of BCL2 expression and up regulation of Casp3 expression in 3e and 6b treated MDA-MB-231 cells. Further, the interaction between critical amino acids of the active domains of BCL2 and 3e and 6b was evaluated by MD simulation, and the results reflected the potent inhibitory activities of 3e and 6b. In summary, the novel compounds 3e and 6b demonstrate their potent anti-cancer properties by inducing apoptosis and selectively targeting BCL2 and caspases-3. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04111-6.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and Myocarditis: A Case Report and Literature Review on Fatal Complications of Reactivated Viral Infections.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a complex and potentially fatal hypersensitivity condition. We present a unique case report and literature review focusing on DRESS syndrome-associated myocarditis resulting from reactivated viral infections in a 21-year-old female. 3 weeks after 5-day oral co-trimoxazole consumption due to acne, she developed symptoms consistent with DRESS syndrome, including a generalized maculopapular rash. Despite prednisolone treatment, the patient developed fatal fulminant myocarditis linked to HHV-6 and CMV reactivation. The patient's death highlights the importance of early recognition and careful management of DRESS syndrome, especially considering the potential viral reactivation that can lead to severe complications. Postmortem investigations revealed that viral reactivation caused myocarditis. Careful consideration must be given to corticosteroid usage in DRESS treatment, as inappropriate prescribing may promote viral reactivation and subsequent complications. While high-dose corticosteroids initiated within the first week effectively suppress HHV-6 reactivation. Conversely, low-dose or late-start high-dose corticosteroids prove ineffective in preventing HHV-6 viremia. Late- onset or low- dose corticosteroids may lead to fatal complications following the primary viral reactivation.