Tag: 822.9402

Pharmacogenetic variability and the probability of site of action target attainment during tuberculosis meningitis treatment: A physiologically based pharmacokinetic modeling and simulations study was written by Mehta, Krina;Narayanan, Navaneeth;Heysell, Scott K.;Bisson, Gregory P.;Subbian, Selvakumar;Kurepina, Natalia;Kreiswirth, Barry N.;Vinnard, Christopher. And the article was included in Tuberculosis (Oxford, United Kingdom) in 2022.Recommanded Product: 13292-46-1 This article mentions the following:

Our objective was to investigate the role of patient pharmacogenetic variability in determining site of action target attainment during tuberculous meningitis (TBM) treatment. Rifampin and isoniazid PBPK model that included SLCO1B1 and NAT2 effects on exposures resp. were obtained from literature, modified, and validated using available cerebrospinal-fluid (CSF) concentrations Population simulations of isoniazid and rifampin concentrations in brain interstitial fluid and probability of target attainment according to genotypes and M. tuberculosis MIC levels, under standard and intensified dosing, were conducted. The rifampin and isoniazid model predicted steady-state drug concentration within brain interstitial fluid matched with the observed CSF concentrations At MIC level of 0.25 mg/L, 57% and 23% of the patients with wild type and heterozygous SLCO1B1 genotype resp. attained the target in CNS with rifampin standard dosing, improving to 98% and 91% resp. with 35 mg/kg dosing. At MIC level of 0.25 mg/L, 33% of fast acetylators attained the target in CNS with isoniazid standard dosing, improving to 90% with 7.5 mg/kg dosing. In this study, the combined effects of pharmacogenetic and M. tuberculosis MIC variability were potent determinants of target attainment in CNS. The potential for genotype-guided dosing during TBM treatment should be further explored in prospective clin. studies. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Recommanded Product: 13292-46-1).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Recommanded Product: 13292-46-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial was written by Kwak, Nakwon;Jeon, Doosoo;Park, Youngmok;Kang, Young Ae;Kim, Kyung Jong;Kim, Young Ran;Kwon, Byoung Soo;Kwon, Yong-Soo;Kim, Hyung-Jun;Lee, Jae Ho;Lee, Ji Yeon;Lee, Jung-Kyu;Mok, Jeongha;Cheon, Minkyoung;Park, Jiwon;Hahn, Seokyung;Yim, Jae-Joon. And the article was included in Trials in 2022.SDS of cas: 13292-46-1 This article mentions the following:

The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a min. duration of 6 mo, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. This study is a multicenter, open-label randomized clin. trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 wk after the achievement of neg. conversion of sputum culture. The control group will be treated for 6 mo with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 mo after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 mo after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. Trial registration: ClinicalTrials.gov NCT04485156. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1SDS of cas: 13292-46-1).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.SDS of cas: 13292-46-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Anti-infective composite cryogel scaffold treats osteomyelitis and augments bone healing in rat femoral condyle was written by Qayoom, Irfan;Srivastava, Ekta;Kumar, Ashok. And the article was included in Biomaterials Advances in 2022.COA of Formula: C43H58N4O12 This article mentions the following:

Bone and joint infections pose a serious challenge in the orthopedic medical condition which presents a major health care problem and economic burden to the patients. The current treatment strategies adopted have a very limited successful outcome in majority of the cases and need serious reconsiderations in terms of management, diagnosis and effective treatment approach. Herein, we have developed a composite cryogel scaffold from nanohydroxyapatite and collagen mimicking natural bone composition for the local delivery of antibiotic to treat osteomyelitis. The biomimetic and biodegradable antibiotic-loaded composite scaffold was found to be biocompatible with potent osteogenic capacity and anti-infective characteristics under in vitro conditions. Moreover, the anti-infective potency of the antibiotic-loaded composite cryogel was also evaluated in rat osteomyelitis model to cure the infection and promote bone healing. It was observed that anti-infective collagen-nanohydroxyapatite composite cryogel when loaded with bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) could completely eradicate the infection in rat femoral condyle and simultaneously, accelerate bone healing at the dead space created during surgical procedures. The approach developed in this study is the development of biomimetic and bioactive composite carrier of antibiotics for the treatment of bone infection. The findings of this study insinuate that this antibiotic-loaded composite cryogel scaffold could potentially be used as an anti-infective biomaterial for the treatment of bone infections which will simultaneosuly promote bone healing at the dead space created during surgical procedures. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1COA of Formula: C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).COA of Formula: C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial was written by Kerckhove, Nicolas;Tougeron, David;Lepage, Come;Pezet, Denis;Le Malicot, Karine;Pelkowski, Manon;Pereira, Bruno;Balayssac, David. And the article was included in BMC Cancer in 2022.Formula: C43H58N4O12 This article mentions the following:

The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer’s disease and dementia, is reported to have a good safety profile in humans, and preclin. data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models. The DONEPEZOX trial will be a proof-of-concept, randomised, triple-blinded, and multicentre study. It will be the first clin. trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 mo after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 wk of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 wk of treatment. The comparison vs. the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming’s one-stage design will be used for sample size estimation This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned. This study will allow, in the case of pos. results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clin. study to assess the therapeutic interest of donepezil to treat OIPN. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Formula: C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Formula: C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II-III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis was written by Berry, Catherine;du Cros, Philipp;Fielding, Katherine;Gajewski, Suzanne;Kazounis, Emil;McHugh, Timothy D.;Merle, Corinne;Motta, Ilaria;Moore, David A. J.;Nyang’wa, Bern-Thomas. And the article was included in Trials in 2022.Synthetic Route of C43H58N4O12 This article mentions the following:

Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 mo duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-wk regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irresp. of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Addnl., two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) resp. Treatment was administered under direct observation for 24 wk in investigational arms and 36 to 96 wk in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavorable outcomes at 72 wk post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Medecins sans Frontieres ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centered approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, addnl., the planned final anal. at 72 wk after the end of recruitment. Trial registration: Clinicaltrials.gov NCT02589782. Registered on 28 Oct. 2015. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Synthetic Route of C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Synthetic Route of C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Carbendazim shapes microbiome and enhances resistome in the earthworm gut was written by Song, Jiajin;Li, Tongxin;Zheng, Zhiruo;Fu, Wenjie;Long, Zhengnan;Shi, Nan;Han, Yuling;Zhang, Luqing;Yu, Yunlong;Fang, Hua. And the article was included in Microbiome in 2022.COA of Formula: C43H58N4O12 This article mentions the following:

It is worrisome that several pollutants can enhance the abundance of antibiotic resistance genes (ARGs) in the environment, including agricultural fungicides. As an important bioindicator for environmental risk assessment, earthworm is still a neglected focus that the effects of the fungicide carbendazim (CBD) residues on the gut microbiome and resistome are largely unknown. In this study, Eisenia fetida was selected to investigate the effects of CBD in the soil-earthworm systems using shotgun metagenomics and qPCR methods. CBD could significantly perturb bacterial community and enrich specific bacteria mainly belonging to the phylum Actinobacteria. More importantly, CBD could serve as a co-selective agent to elevate the abundance and diversity of ARGs, particularly for some specific types (e.g., multidrug, glycopeptide, tetracycline, and rifamycin resistance genes) in the earthworm gut. Addnl., host tracking anal. suggested that ARGs were mainly carried in some genera of the phyla Actinobacteria and Proteobacteria. Meanwhile, the level of ARGs was pos. relevant to the abundance of mobile genetic elements (MGEs) and some representative co-occurrence patterns of ARGs and MGEs (e.g., cmx-transposase and sul1-integrase) were further found on the metagenome-assembled contigs in the CBD treatments. It can be concluded that the enhancement effect of CBD on the resistome in the earthworm gut may be attributed to its stress on the gut microbiome and facilitation on the ARGs dissemination mediated by MGEs, which may provide a novel insight into the neglected ecotoxicol. risk of the widely used agrochems. on the gut resistome of earthworm dwelling in soil. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1COA of Formula: C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. COA of Formula: C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Sarcoid-like lesions obfuscating the diagnosis of disseminated Mycobacterium genavense infection in a patient with IL-12Rβ1-associated immunodeficiency was written by Denicolo, Sara;Laydevant, Sophie;Fink, Julia;Geiger, Christoph;Pizzini, Alex;Sarcletti, Mario;Zschocke, Johannes;Bellmann-Weiler, Rosa;Weiss, Guenter;Tancevski, Ivan. And the article was included in BMC Infectious Diseases in 2022.Recommanded Product: 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins This article mentions the following:

Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histol. However, similar histol. findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis. A 31-yr-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with s.c. type I interferon, which eventually led to a gradual improvement over the next months. Differentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Recommanded Product: 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Recommanded Product: 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Nasal carriage of Methicillin-Resistant Staphylococcus aureus among sympatric free-ranging domestic pigs and wild Chlorocebus pygerythrus in a rural African setting was written by Kalule, John Bosco;Nakintu, Valeria Zalwango;SSendawula, Simon Peter. And the article was included in BMC Veterinary Research in 2022.Application of 13292-46-1 This article mentions the following:

Methicillin Resistant Staphylococcus aureus (MRSA) nasal carriage in domestic pigs and vervet monkeys is a risk factor for subsequent severe infections in domestic pigs and for dissemination to the human population. This study assessed nasal carriage of MRSA in domestic pigs and sympatric vervet monkeys in a rural African village during an outbreak of a virus hemorrhagic fever suspected to be contracted from wild primates. This study was conducted during the 2012 Ebola outbreak to determine nasal carriage of MRSA in free-ranging domestic pigs and sympatric freely roaming vervet monkeys using conventional methods. Staphylococcus aureus (S. aureus) isolated from the anterior nares were tested for susceptibility to commonly used antibiotics and conventional PCR was used to confirm methicillin resistance. The MRSA strains were then genotyped using SCCmec typing. Overall, there was a high level of resistance to tetracycline [90% (63/70) in pigs and 67% (10/15) in vervet monkeys], trimethoprim/sulphamethoxazole [90% (63/70) in pigs and 67% (10/15) in vervet monkeys], and penicillin [83% (58/70) in pigs and 67% (10/15) in vervet monkeys]. Most of the MRSA strains (91.6%, 11/12) were of the SCCmec type I [1B] genotype. The nasal carriage of drug resistant S. aureus in freely roaming domestic and wild animals presents a risk for widespread environmental spread of antimicrobial resistance thus presenting a risk for treatment failure in domestic animals, wild animals, and humans. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Application of 13292-46-1).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Application of 13292-46-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics