Injection of OnabotulinumtoxinA (BTX-A) into the bladder is a widely used treatment option for patients with overactive bladder who have failed medical therapy. Urinary tract infection is the most common side effect of this procedure and therefore antibiotics are given around the time of injection in order to prevent these events. While antibiotics are commonly given at the time of injection, the duration of these antibiotic regimens are variable. The investigators propose a study to investigate different antibiotic protocols and their affect on the rate of urinary tract infection after injection.

开始日期2018-07-01

申办/合作机构

Vanderbilt University Medical Center

[+1]

NCT00510159 / Completed临床2/3期

Randomized Double Blind Clinical Trial in Mali, Comparing the Effectiveness of Artesunate + Sulfamethoxypyrazine/Pyrimethamine Versus Praziquantel in the Treatment of S. Haematobium in Children

The purpose of this study is to evaluate the efficacy of praziquantel versus As+SMP (Co-Arinate FDC ®) in the treatment of Schistosoma haematobium in 6-15 year old Malian children. The nul-hypothesis in this study is that the combination of As+SMP is more effective than praziquantel in the treatment of S. haematobium infected children.

开始日期2007-08-01

申办/合作机构

Dafra Pharma NV

100 项与 DHFR x DHPS 相关的临床结果

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100 项与 DHFR x DHPS 相关的转化医学

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0 项与 DHFR x DHPS 相关的专利（医药）

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项与 DHFR x DHPS 相关的文献（医药）

2024-07-01·Acta Tropica

Characterization of drug resistance genes in Indian Plasmodium falciparum and Plasmodium vivax field isolates

Article

作者: Singh, Vineeta ; Yadav, Karmveer ; Jakhan, Jahnvi ; Tamang, Suman ; Narang, Geetika

One of the major challenges for malaria control and elimination is the spread and emergence of antimalarial drug resistance. Mutations in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) field isolates for five drug resistance genes viz. crt, mdr1, dhps, dhfr and kelch known to confer resistance to choloroquine (CQ), sulfadoxine-pyrimethamine (SP) and artemisinin (ART) and its derivatives were analyzed. A total of 342 symptomatic isolates of P. falciparum (Pf) and P. vivax (Pv) from 1993 to 2014 were retrieved from malaria parasite repository at National Institute of Malaria Research (NIMR). Sample DNA was extracted from dried blood spots and various targeted single nucleotide polymorphisms (SNPs) associated with antimalarial drug resistance were analysed for these isolates. 72S (67.7%) and 76T (83.8%) mutations along with SVMNT haplotype (67.7%) predominated the study population for Pfcrt. The most prevalent SNPs were 108N (73.2%) and 437G (24.8%) and the most prevalent haplotypes were ACNRNI (51.9%) and SAKAA (74.5%) in Pfdhfr and Pfdhps respectively. Only two mutations in Pfmdr1, 86Y (26.31%) and 184F (56.26%), were seen frequently in our study population. No mutations associated with Pfk13 were observed. For Pv, all the studied isolates showed two Pvdhps mutations, 383G and 553G, and two Pfdhfr mutations, 58R and 117N. Similarly, three mutations, viz. 958M, 908L and 1076L were found in Pvmdr1. No variations were observed in Pvcrt-o and Pvk12 genes. Overall, our study demonstrates an increase in mutations associated with SP resistance in both Pf and Pv, however, no single nucleotide polymorphisms (SNPs) associated with ART resistance have been observed for either species. Various SNPs associated with CQ resistance were seen in Pf; whereas only Pvmdr1 associated resistant SNPs were observed in Pv. Therefore, molecular characterization of drug resistance genes is essential for timely monitoring and prevention of malaria by identifying the circulating drug resistant parasites in the country.

2024-06-12·Journal of Biomolecular Structure and Dynamics

Systems-wide analysis of A. fumigatus using kinetic modeling of metabolic pathways to identify putative drug targets

Article

作者: Gupta, Lovely ; Chikara, Aryan ; Kulshrestha, Sudeepti ; Gupta, Payal ; Kakrania, Mahi ; Vijayaraghavan, Pooja ; Sengupta, Abhishek ; Gupta, Vinayak ; Narad, Priyanka ; Saxena, Ritika

Aspergillosis is a major causative factor for morbidity in those with impaired immune systems, often caused by Aspergillus fumigatus. The diagnosis and treatment are difficult due to the diversity of individuals and risk factors and still pose a challenge for medical professionals. To understand the pathogenicity of any organism, it is critical to identify the significant metabolic pathways that are involved. Our work focused on developing kinetic models of critical pathways crucial for the survival of A. fumigatus using COPASI. While focusing on the folate biosynthesis, ergosterol biosynthesis and glycolytic pathway; sensitivity, time-course and steady-state analysis were performed to find the proteins/enzymes that are essential in the pathway and can be considered as potential drug targets. For further analysis of the interaction of drug targets identified, a protein-protein interaction (PPI) network was built, and hub nodes were identified using the Cytohubba package from Cytoscape. Based on the findings, dihydropteroate-synthase, dihydrofolate-reductase, 4-amino-4-deoxychorismate synthase, HMG-CoA-reductase, PG-isomerase and hexokinase could act as potential drug targets. Further, molecular docking and MM-GBSA analysis were performed with ligands chosen from DrugBank, and PubChem, and validated by experimental evidence and existing literature based on results from kinetic modeling and PPI network analysis. Based on docking scores and MM-GBSA results, molecular simulations were carried out for 1AJ2-dapsone, 1DIS-sulfamethazine, 1T02-lovastatin and 70YL-3-bromopyruvic acid complexes, which validated our findings. Our study provides a deeper insight into the mechanisms of A. fumigatus's metabolism to reveal dapsone, sulfamethazine, lovastatin and 3-bromopyruvic acid as potential drugs for the treatment of Aspergillosis.

2024-05-01·Journal of Infection

Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers

Article

作者: Bambo, Gizela ; Drakeley, Chris ; Brokhattingen, Nanna ; Tetteh, Kevin K A ; Mbeve, Henriques ; Ndimande, Nelo ; Quintó, Llorenç ; Matambisso, Glória ; Maculuve, Sónia ; Cuna, Boaventura ; Chitnis, Chetan ; Mayor, Alfredo ; Melembe, Cardoso ; Macete, Eusébio ; Gamain, Benoit ; Cístero, Pau ; Chauhan, Virander ; Escoda, Anna

OBJECTIVEThe effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique.METHODSP. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes.RESULTS84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSA_DBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013).CONCLUSIONA sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.