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1.
Cell Chem Biol ; 27(2): 172-185.e11, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31711854

RESUMO

The triazine antitubercular JSF-2019 was of interest due to its in vitro efficacy and the nitro group shared with the clinically relevant delamanid and pretomanid. JSF-2019 undergoes activation requiring F420H2 and one or more nitroreductases in addition to Ddn. An intrabacterial drug metabolism (IBDM) platform was leveraged to demonstrate the system kinetics, evidencing formation of NO⋅ and a des-nitro metabolite. Structure-activity relationship studies focused on improving the solubility and mouse pharmacokinetic profile of JSF-2019 and culminated in JSF-2513, relying on the key introduction of a morpholine. Mechanistic studies with JSF-2019, JSF-2513, and other triazines stressed the significance of achieving potent in vitro efficacy via release of intrabacterial NO⋅ along with inhibition of InhA and, more generally, the FAS-II pathway. This study highlights the importance of probing IBDM and its potential to clarify mechanism of action, which in this case is a combination of NO⋅ release and InhA inhibition.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Triazinas/química , Animais , Antituberculosos/farmacocinética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/metabolismo , Feminino , Meia-Vida , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/metabolismo , Óxido Nítrico/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/metabolismo , Triazinas/farmacocinética , Triazinas/farmacologia
2.
BMJ Support Palliat Care ; 7(2): 218-220, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27470606

RESUMO

Delirium in patients with cancer is associated with poor outcomes, but reversible causes need to be ruled out. We report the case of a 59-year-old woman who was presented with behavioural and cognitive changes over 2 weeks. She was non-verbal and combative, requiring involuntary admission and declaration of incompetence to make healthcare treatment decisions. Infectious and metabolic investigations and initial brain imaging were unremarkable. She was diagnosed with limited-stage small cell lung cancer and a paraneoplastic neuropsychiatric syndrome. Owing to the patient's delirium, chemotherapy delivery required pharmacological and physical restraints. After 2 cycles of chemotherapy, she could participate in the decision process and was discharged home. She completed radical chemo-radiotherapy and has remained free of disease progression for 18 months. Paraneoplastic neuropsychiatric syndromes, although rare, are potentially treatable and need to be excluded as a cause of delirium.


Assuntos
Carcinoma de Células Pequenas/complicações , Delírio/diagnóstico , Neoplasias Pulmonares/complicações , Polineuropatia Paraneoplásica/diagnóstico , Delírio/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/etiologia
3.
J Contemp Dent Pract ; 15(2): 190-4, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25095842

RESUMO

AIM: The aim of the study was to correlate the pH and fluoride ion uptake with surface hardness of composite resin based restorative materials after topical fluoride application. METHODOLOGY: Forty disks of each of test materials Composite (Filtek Z350XT, 3M ESPE, St Paul, MN, USA), Resin modified glass ionomer (Vitremer) and Compomer (Dyract AP) were made and ten disks of each material were placed in different test solutions - 1.23% APF gel, Sodium fluoride mouth rinse, 0.9% neutral fluoride and distilled water (Control group). After 36 hours of immersion, specimens were subjected to microhardness testing machine for evaluation of surface hardness. RESULTS: The greater hardness deterioration for all materials resulted with 1.23% APF gel when compared to the control group. Composite (Filtek Z350XT, 3M ESPE, St Paul, MN, USA) showed 17.13 VHN (control group 59.11 VHN). Vitremer showed 9.71 VHN (control group 37.71 VHN). Compomer showed 19.22 VHN (control group 36.78 VHN). CONCLUSION: 1.23% ApF gel significantly decreased hardness of composite, Vitremer and Compomer. Hardness deterioration associated with sodium fluoride mouth rinse and 0.9% neutral fluoride was less compared to 1.23% ApF gel.


Assuntos
Cariostáticos/química , Resinas Compostas/química , Materiais Dentários/química , Fluoretos Tópicos/química , Fluoreto de Fosfato Acidulado/química , Compômeros/química , Análise do Estresse Dentário/instrumentação , Fluoretos/química , Cimentos de Ionômeros de Vidro/química , Dureza , Humanos , Concentração de Íons de Hidrogênio , Imersão , Teste de Materiais , Cimentos de Resina/química , Fluoreto de Sódio/química , Propriedades de Superfície , Fatores de Tempo , Água/química
4.
J Int Oral Health ; 6(2): 9-15, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24876696

RESUMO

BACKGROUND: This paper investigates the relationship betweendifferent types of impactions with postoperativeinflammatory tissue reaction. MATERIALS & METHODS: Consecutive patients with only mandibular third molar impactions were included in our study. They were classified by winter's classification. The disimpactions were performed under local anaesthesia. Time for surgery was noted for each surgical procedure. Postoperative inflammatory complication in terms of pain, swelling and trismus were noted. RESULTS: 150 male patients in the age groupof 18-40 years were studied. Inflammatory tissue reactions were increasing with more operative time. Distoangular and Horizontal impactions were associated with more pain on first 3 days of surgery along with more swelling and trismus. Vertically impacted teeth were associated with least complications. CONCLUSION: Post operative morbidity was increasing along with moreoperating time and increase in the depth of mandibular third molar impaction. How to cite the article: Mansuri S, Mujeeb A, Hussain SA, Hussain MA. Mandibular third molar impactions in male adults: Relationship of Operative time and Types of impaction on inflammatory complications. J Int Oral Health 2014;6(2):9-15.

5.
Oral Health Dent Manag ; 13(1): 20-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24603911

RESUMO

BACKGROUND: Mobile Dental Van (MDV) removes the barrier of accessibility and improves the care of underserved populations. Dental institutions across India, providing postgraduate training in dental public health organize and conduct MDV programs as part of their curriculum. AIM: To describe the structure, conduct and utilization of MDV programs in consideration to duration of use by the academic institutions for oral health care delivery in rural areas. METHODS: Hundred postgraduates in Public Health Dentistry representing 27 dental institutions of India completed a 40 item questionnaire on MDV program and utilization. Descriptive statistics and Fisher's exact test were used for statistical analysis. RESULTS: The mobile dental van programs were more curative with limited orientation towards preventive services. The institutionally sponsored programs with experience of more than 10 years had better organized setup and adequate emergency management system together with electricity, water and storage facilities. Chair side assistants were employed in 90 percent of newer programs compared to only 50 percent of older programs. Dental hygienists were helping the dentists in only 60 percent of programs. CONCLUSIONS: The utilization of MDV in treating rural underserved is indispensable, but revenue and high productivity is difficult to achieve as lower socioeconomic patients are predominantly served. MDV programs operational in postgraduate institutions have to improvise on correcting the shortcomings regarding the facilities and manpower to improve the utilization of the programs.

7.
Antimicrob Agents Chemother ; 46(2): 443-50, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11796356

RESUMO

The World Health Organization has identified India as a major hot-spot region for Mycobacterium tuberculosis infection. We have characterized the sequences of the loci associated with multidrug resistance in 126 clinical isolates of M. tuberculosis from India to identify the respective mutations. The loci selected were rpoB (rifampin), katG and the ribosomal binding site of inhA (isoniazid), gyrA and gyrB (ofloxacin), and rpsL and rrs (streptomycin). We found known as well as novel mutations at these loci. Few of the mutations at the rpoB locus could be correlated with the drug resistance levels exhibited by the M. tuberculosis isolates and occurred with frequencies different from those reported earlier. Missense mutations at codons 526 to 531 seemed to be crucial in conferring a high degree of resistance to rifampin. We identified a common Arg463Leu substitution in the katG locus and certain novel insertions and deletions. Mutations were also mapped in the ribosomal binding site of the inhA gene. A Ser95Thr substitution in the gyrA locus was the most common mutation observed in ofloxacin-resistant isolates. A few isolates showed other mutations in this locus. Seven streptomycin-resistant isolates had a silent mutation at the lysine residue at position 121. While certain mutations are widely present, pointing to the magnitude of the polymorphisms at these loci, others are not common, suggesting diversity in the multidrug-resistant M. tuberculosis strains prevalent in this region. Our results additionally have implications for the development of methods for multidrug resistance detection and are also relevant in the shaping of future clinical treatment regimens and drug design strategies.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Genes Bacterianos , Mycobacterium tuberculosis/genética , Proteínas de Plantas/genética , Sequência de Bases , DNA Girase/genética , DNA Bacteriano/análise , RNA Polimerases Dirigidas por DNA , Desenho de Fármacos , Humanos , Índia , Dados de Sequência Molecular , Mutação
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