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1.
J Family Med Prim Care ; 13(2): 627-634, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38605793

ABSTRACT

Background: Tribes are the most socially excluded group in the nation due to their restricted access to healthcare. There are little data on the real burden and distribution of illnesses among tribes. The present study determines the types and patterns of sickness among tribal populations in West Bengal. Methods: Five blocks from five districts in West Bengal were used for this cross-sectional study. Between the years 2018 and 2019, 52,189 patients visited these mobile medical clinics (MMCs), but only 36,128 were included in our study. Data were analyzed using the SPSS software (ver. 27.0). Results: Younger age groups (1-25 years) show higher primary registration compared to other age categories; older age groups (>60 years) show higher repeat registration. High prevalence in infectious diseases (44.5% of the total primary registration) and high repeated cases in NCDs (11.5% to 33.2%), which are nearly three times higher than primary cases (Cramer's V test = 0.29; P = .001) are observed. Among the studied MMCs, Binpur II and Matiali MMC have more than two times the risk of gastrointestinal problems, while Madarihat MMC has more than one time the risk. Garbeta II MMC shows more than three times the risk of NCDs (adjusted odds ratio = 3.97; 95% confidence interval: 3.05-5.17) than the other diseases. Conclusion: The present study shows high prevalence of infectious diseases, injury and pain, NCDs, gastrointestinal problems, and vertigo in tribal populations of West Bengal.

2.
Public Health Pract (Oxf) ; 7: 100490, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38523625

ABSTRACT

Objective: Tribal population in India (8.6% of the total population) have a greater prevalence of tuberculosis compared to the national average. The article aims to study out-of-pocket expenditure (OOPE), hardship financing, and impoverishment effects of TB hospitalisation treatment among tribal populations in India. Methods: Data of three rounds of National Sample Surveys (NSS) 60th (2004-05), 71st (2013-14) and 75th (2017-18) rounds were analyzed. Descriptive statistics, bivariate estimates and multivariate models were performed to calculate the OOPE, healthcare burden (HCB), catastrophic health expenditure (CHE), hardship financing and impoverishment effects using standard definitions at February 2023 price values. Propensity score matching (PSM) was used to examine the effect of health insurance coverage on catastrophic health expenditure, and impoverishment. Results: Over two-thirds of the TB cases are seen in the economically productive age group (14-59 years). Substantial OOPE and its impact on HCB, CHE, and poverty impact observed among 15-35 age group across all three rounds. Illiterate patients and those availing private hospitals for TB treatment had higher OOPE, HCB, hardship financing, CHE, and poverty impact. 38.5% (2014) and 33.2% (2018) are covered with any kind of public healthcare coverage, PSM analysis shows households with health insurance have lower incidence of CHE and impoverishment effects due to TB hospitalisation expenditure. Conclusions: The current study aids in comprehending the patterns in the financial burden of TB on tribal households during the previous 15 years and gives policy makers information for efficient resource allocation management for TB among Indian tribal communities.

3.
JBI Evid Synth ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38465423

ABSTRACT

OBJECTIVE: The objective of this systematic review is to provide an overview of economic evaluation studies of interventions for neglected tropical diseases in low- and/or middle-income countries. INTRODUCTION: The majority of people most susceptible to neglected tropical diseases reside in low- and middle-income countries and suffer significant economic impact due to these diseases. The World Health Organization suggests utilizing a systematic and cross-cutting approach with multiple interventions to lessen the neglected tropical disease burden. INCLUSION CRITERIA: Studies will be eligible for inclusion if they include economic evaluations of interventions for neglected tropical diseases and are conducted in low- and/or middle-income country settings. METHODS: A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as neglected tropical disease, economic evaluation, therapeutics, low- and/or middle-income countries. Two reviewers will screen titles and abstracts independently, followed by a full-text review against the inclusion criteria. Disagreements will be resolved by discussion or with a third reviewer. To assess methodological quality, the JBI checklist for economic evaluations will be used. For economic evaluations, data will be extracted using the standardized JBI data extraction form. The Dominance Ranking Matrix will be used to summarize and compare the results of different types of economic evaluations. Cost per quality adjusted life year gained and cost per disability adjusted life year averted will be measures for economic evaluation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of economic evidence, such as resource use and costs. REVIEW REGISTRATION: PROSPERO CRD42017070386.

4.
JBI Evid Synth ; 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38287736

ABSTRACT

OBJECTIVE: The purpose of the systematic review is to assess the cost-effectiveness of targeted/selective newborn screening compared with universal screening for sickle cell disease across various countries and settings. INTRODUCTION: The incidence of sickle cell disease is increasing worldwide and it is a widespread and potentially fatal hematologic disorder that affects thousands of newborns worldwide. The cost of newborn screening creates a burden on households and the economy. INCLUSION CRITERIA: Studies will be eligible for inclusion in the review if they include cost-effectiveness studies of newborn screening for sickle cell disease comparing targeted/selective screening with universal screening. METHODS: A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as sickle cell disease, newborn, and economic evaluations. Two reviewers will screen the titles, abstracts, and full text independently against the inclusion criteria. Disagreements will be resolved by discussion or with a third reviewer. To assess methodological quality, the JBI checklist for economic evaluation will be used. Data will be extracted by 2 reviewers using a modified JBI data extraction form. The JBI dominance ranking matrix for economic evaluations will be used to summarize and compare the results. Cost-effectiveness will be measured on the basis of cost per test/case detected, quality-adjusted life years gained, or disability-adjusted life years averted. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment will be conducted to evaluate the certainty of economic evidence, such as use of resources and expenditures, and to incorporate the results into the decision-making process. REVIEW REGISTRATION: PROSPERO CRD42017057963.

5.
Tob Control ; 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38216315

ABSTRACT

BACKGROUND: Tobacco product litter may be a form of postconsumption marketing if the littered items are branded. We conducted an observational study in India to assess the presence of tobacco product litter and determine the proportion that included branding. METHODS: During November-December 2022, we identified tobacco product litter (cigarette/bidi butts and packaging; smokeless tobacco packaging) in nine Indian cities: Bengaluru, Bhubaneswar, Chennai, Delhi, Guwahati, Hyderabad, Lucknow, Mumbai and Patna. In each city, we conducted observations along 15 different routes, each approximately 250 m in distance, for a total of 135 observational routes. Data collectors classified each piece of tobacco litter (product/packaging) and recorded if the litter had visible branding, such as brand names and/or logos. RESULTS: The study identified 17 261 pieces of tobacco product litter; SLT packaging comprised the largest proportion of the sample (62%), followed by cigarette butts (26%), bidi butts (8%), cigarette packaging (3%) and bidi packaging (1%). Across the sample, 81% (n=13 924) of the litter was branded. A brand was visible on most packaging for cigarettes (98%), bidis (97%) and SLT (86%), and present on 82% of cigarette butts and 26% of bidi butts. CONCLUSION: This study found that the majority of tobacco product litter in India is branded, which could function as a form of postconsumption marketing. Plain and standardised packaging and banning branding features on filters would reduce tobacco litter branding.

6.
JBI Evid Synth ; 22(1): 97-105, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37779435

ABSTRACT

OBJECTIVE: The purpose of this systematic review is to assess the available economic evidence of a decentralized care model compared to a centralized model for treating multi-drug-resistant tuberculosis (MDR-TB) in low- and middle-income countries (LMICs). INTRODUCTION: Diseases that affect physiological health create a burden on human livelihoods and the economy. There is a lack of studies examining the economic evaluation of MDR-TB across different countries. A preliminary search identified no published or ongoing reviews on MDR-TB in LMICs. INCLUSION CRITERIA: Studies will be eligible if they include both patients receiving centralized care (ie, care provided by specialist centers through inpatient or outpatient services) and patients receiving decentralized care (ie, care provided by grassroots community workers in peripheral facilities or in the patients' residence) for MDR-TB in LMICs. Eligible studies will report economic evaluations of treatment for MDR-TB. METHODS: A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as MDR-TB, economic evaluation, therapeutics, LMICs . Two reviewers will independently screen the titles, abstracts, and full text against the inclusion criteria. Disagreements will be resolved through discussion or with a third reviewer. The JBI checklist for economic evaluations will be utilized to evaluate the methodological quality. Data will be extracted using a modified JBI data extraction form for economic evaluations. The Dominance Ranking Matrix, developed by JBI for economic evaluations, will be used to summarize and compare the results of different types of economic evaluations (cost-effectiveness, cost-benefit analysis, cost-utility analysis, or cost-minimization analysis). Cost per quality-adjusted life year gained and cost per disability-adjusted life year averted will be measures for economic evaluation. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the certainty of economic evidence. REVIEW REGISTRATION: PROSPERO CRD42022368696.


Subject(s)
Cost-Effectiveness Analysis , Tuberculosis, Multidrug-Resistant , Humans , Cost-Benefit Analysis , Developing Countries , Systematic Reviews as Topic , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
7.
JMIR Res Protoc ; 12: e50985, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38079215

ABSTRACT

BACKGROUND: Globally, among all the vector-borne diseases, mosquito-borne diseases are responsible for a substantial number of cases and deaths and amount to an economic cost of US $12 billion per year. However, there is a dearth of systematic research conducted on the economic burden of mosquito-borne diseases. To address the lack of comprehensive information on this topic, a systematic review will be conducted to synthesize evidence for informing targeted policies and strategies addressing this growing burden and for better financial protection of households. OBJECTIVE: The systematic review aims to review the economic burden of mosquito-borne diseases in low- and middle-income countries (LMICs). The review estimates the total cost, which is the compilation of both the direct costs and indirect costs. Additionally, it reports cost estimates per disease, country, and patient. The review outcome will also discuss the impact of the economic burden in terms of out-of-pocket expenditure, catastrophic health expenditure, impoverishment, and gross domestic product impact due to mosquito-borne diseases in LMICs. METHODS: Systematic searches will be conducted in PubMed (MEDLINE), Ovid Embase, Scopus, the cumulative index of nursing and allied health literacy, and Cochrane CENTRAL. Additionally, websites of the World Bank, World Health Organization, and Asian Development Bank as well as grey literature (eg, Malaria No More and the Ministry of Health websites) will be searched to gather comprehensive information on the topic and identify studies published in the English language. The titles and abstracts will be independently screened by 2 reviewers, followed by a full-text review against the inclusion criteria. Disagreements will be resolved through discussion with a third author. The methodological reporting quality of the studies will be evaluated using the Larg and Moss checklist, Cochrane risk-of-bias tool for randomized trials, and the Consensus on Health Economic Criteria. Data will be extracted using a standardized data extraction form. RESULTS: The protocol was registered in PROSPERO (CRD42023427111) prior to the initiation of the search strategy. The review is currently ongoing and will synthesize information from the identified studies through a process involving structured screening, data extraction, and critical appraisal in the form of tables and a narrative summary of studies reporting the economic burden incurred due to mosquito-borne diseases in LMICs. CONCLUSIONS: This review seeks to report the economic burden of mosquito-borne diseases. It will act as evidence for policymakers to prioritize their decisions regarding containing the prevalence of mosquito-borne diseases and the means to lowering the incidence of diseases spread by mosquitoes. TRIAL REGISTRATION: PROSPERO CRD42023427111; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=427111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50985.

8.
Heliyon ; 9(3): e14419, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36942214

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has devastated mankind. To date, no approved treatment is available to completely combat this disease. Although many studies reported the potential of silver nanoparticles' (AgNPs) action mechanism and effect against SARS-CoV-2, this is the first clinical trial that aimed to prove this effect. This open-label, randomized, parallel-group, investigator-initiated study (IIS) was conducted in India from 2021 to 2022 and included 40 patients diagnosed with moderately-severe to severe COVID-19 pneumonia. This study proved a significantly higher survival rates (p < 0.05) and significantly lower number of days until supplemental oxygenation was required (p < 0.0001) for patients receiving intravenous AgNPs in form of AgSept® in addition to the standard COVID-19 treatment. This study highlights the importance of intravenous AgNPs administration in the treatment of virus-induced pneumonia.

9.
BMJ Open ; 13(1): e065729, 2023 01 23.
Article in English | MEDLINE | ID: mdl-36690398

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has posed unprecedented challenges to health systems and populations, particularly in India. Comprehensive, population-level studies of the burden of disease could inform planning, preparedness and policy, but are lacking in India. In West Bengal, India, we conducted a detailed analysis of the burden caused by COVID-19 from its onset to 7 January 2022. SETTING: Open-access, population-level and administrative data sets for West Bengal were used. PRIMARY AND SECONDARY OUTCOME MEASURES: Disability-adjusted life years (DALYs), years of potential productive life lost (YPPLL), cost of productivity lost (CPL: premature mortality and absenteeism), years of potential life lost (YPLL), premature years of potential life lost, working years of potential life lost (WYPLL) and value of statistical life (VSL) were estimated across scenarios (21 for DALY and 3 each for YPLL and VSL) to evaluate the effects of different factors. RESULTS: COVID-19 had a higher impact on the elderly population with 90.2% of deaths arising from people aged above 45. In males and females, respectively, DALYs were 190 568.1 and 117 310.0 years, YPPLL of the productive population was 28 714.7 and 16 355.4 years, CPL due to premature mortality was INR3 198 259 615.6 and INR583 397 335.1 and CPL due to morbidity was INR2 505 568 048.4 and INR763 720 886.1. For males and females, YPLL ranged from 189 103.2 to 272 787.5 years and 117 925.5 to 169 712.0 years for lower to higher age limits, and WYPLL was 54 333.9 and 30 942.2 years. VSL (INR million) for the lower, midpoint and upper life expectancies was 883 330.8; 882 936.4; and 880 631.3, respectively. Vaccination was associated with reduced mortality. CONCLUSIONS: The losses incurred due to COVID-19 in terms of the computed estimates in West Bengal revealed a disproportionately higher impact on the elderly and males. Analysis of various age-gender subgroups enhances localised and targeted policymaking to minimise the losses for future pandemics.


Subject(s)
COVID-19 , Male , Female , Humans , Aged , COVID-19/epidemiology , Disability-Adjusted Life Years , Pandemics , Life Expectancy , India/epidemiology , Quality-Adjusted Life Years , Cost of Illness
11.
Asian Pac J Cancer Prev ; 22(S2): 65-70, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34780140

ABSTRACT

BACKGROUND: Tobacco use among young and adolescents is the biggest threat to public health globally. In Bangladesh, every one in 14 youth (13-15 years) uses tobacco in some form. While this problem is growing in the country, we estimate the underage initiation of tobacco use and present evidence that policy measures like increasing the age of purchase and use from the current 18 years to 21 years in the country backed with current tobacco control efforts and adopting vendor licensing will significantly reduce future tobacco burden. METHOD: We analysed the two rounds of nationally representative Global Adult Tobacco Survey (GATS) data: GATS-1 (2009-10) and GATS-2 (2016-17) and segregated the data for two categories of tobacco consumption (smokers and smokeless tobacco users) based on the age of initiation (<18, 18-21 and >21 years). Consumption patterns were also analyaed by using the GATS-2 data. Projections from sub-national level analysis for youth initiating tobacco use before 21 years and change in the prevalence of overall underage tobacco users were calculated based on weighted value. RESULT: According to GATS-2, around 89% of current tobacco users initiated tobacco use into daily use before the age of 18 years in Bangladesh. Whereas, striking differences were observed (statistically significant) for the average age of initiation of smoking among smokers aged 20-34 increased from 17.4 in 2009 to 19.3 years; and 20.1 to 22 years for SLT.  Moreover, more than 24% of them initiated into regular smoking before the age of 15 years. CONCLUSION: There is an increasing trends of tobacco initiation among the underage youth of Bangladesh. By increasing the age of access, sale, purchase, and use of tobacco from current 18 years to 21 years will significantly reduce youth initiation and taper down the overall adult tobacco use prevalence over the long run in Bangladesh.


Subject(s)
Age Factors , Smokers/statistics & numerical data , Tobacco Products/legislation & jurisprudence , Tobacco Use/epidemiology , Adolescent , Adult , Bangladesh/epidemiology , Consumer Behavior , Female , Humans , Male , Prevalence , Smokers/legislation & jurisprudence , Tobacco Use/legislation & jurisprudence , Young Adult
13.
Curr Opin Psychiatry ; 32(5): 416-421, 2019 09.
Article in English | MEDLINE | ID: mdl-31135489

ABSTRACT

PURPOSE OF REVIEW: To examine developments in the understanding of certain aspects of depression in diabetes mellitus patients with a special focus on diabetes distress, screening of depression and its management in persons with type 2 diabetes mellitus. RECENT FINDINGS: Recent studies reviewed indicate an increasing trend of both major and minor depression in patients with diabetes. Depression is also reported to be persistent and chronic in diabetes patients. There is a bidirectional link between depression and diabetes. Diabetes-related distress independently increases the diabetes-related complications. Collaborative care is both applicable and helpful in managing depression in diabetes. SUMMARY: Although a significant number of patients with diabetes suffer from depression or diabetes-related distress, majority of them remain undiagnosed and untreated. This treatment gap suggests the need for routine screening for depression and distress in patients with diabetes. Studies have confirmed that treatment focussing on diabetes may alleviate depressive symptoms. Diabetes-specific psychological interventions may prove useful in improving diabetes self-management in depressed diabetes patients. Effect of specific psychopharmacological and psychological interventions in treating depression in diabetes patients should be examined in future studies.


Subject(s)
Depression , Diabetes Mellitus, Type 2/psychology , Depression/physiopathology , Depression/therapy , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/therapy , Humans , Patient Care Management/methods
14.
Asian J Psychiatr ; 32: 8-13, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29197711

ABSTRACT

BACKGROUND: Sleep disorders are frequently associated with psychiatric disorders and can be both cause and effect of the same. AIM: To study the prevalence of sleep disorders and the severity of insomnia in psychiatric outpatients. METHODS: 500 patients were randomly selected using purposive sampling from patients attending a tertiary level mental health care facility were evaluated for the presence of any sleep disorder along with their sleep quality. In patients having insomnia, severity of the same was determined. RESULTS: 83.4% of the population had some type of sleep disorder. Symptoms of insomnia were reported by 78.2% of the population and 29.2% had moderate to severe insomnia. 78.4% of the population had poor sleep quality. Significant difference was noted among the different psychiatric groups when insomnia severity index (ISI) was compared. In multinomial logistic regression, chance of severe insomnia is more if the diagnosis is depression, but less if mania or ocd, compared to psychosis. CONCLUSION: This study was the first in India to assess the prevalence of sleep disorders in psychiatric outpatients. Our study underscores the importance of careful evaluation of sleep problems for proper management of the patients.


Subject(s)
Mental Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/physiopathology , Sleep Wake Disorders/epidemiology , Adolescent , Adult , Comorbidity , Cross-Sectional Studies , Female , Humans , India/epidemiology , Male , Mental Health Services , Middle Aged , Outpatients , Prevalence , Severity of Illness Index , Tertiary Healthcare , Young Adult
16.
Asian J Psychiatr ; 12: 148-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25453533

ABSTRACT

Clinical lycanthropy is a rare form of reverse intermetamorphosis; intermatamorphosis being one of the delusional misidentification syndromes, in which patients believe that they are undergoing transformation or have transformed into a non-human animal. Psychiatric diseases commonly associated with it are schizophrenia, affective disorders, substance use, personality disorders and general medical conditions. Here we report the unique case of an ophidianthropy along with other psychopathologies in a patient of schizophrenia. The different neurochemicals associated with lycanthropy are also discussed.


Subject(s)
Antipsychotic Agents/therapeutic use , Delusions/complications , Haloperidol/therapeutic use , Schizophrenia/complications , Delusions/drug therapy , Delusions/psychology , Humans , Male , Schizophrenia/drug therapy , Treatment Outcome , Young Adult
17.
Chem Commun (Camb) ; 50(99): 15784-7, 2014 Dec 25.
Article in English | MEDLINE | ID: mdl-25369787

ABSTRACT

An efficient cross-coupling of alkynes with alkynyl and alkenyl halides catalysed by a Ni-Cu system without any ligand has been achieved. The reaction is suggested to proceed by Ni(0) catalysis assisted by Cu(I). A series of functionalised diaryl, aryl-alkyl, aryl-heteroaryl, diheteroaryl 1,3-di-ynes and en-ynes are obtained in high yields.


Subject(s)
Copper/chemistry , Diynes/chemistry , Nickel/chemistry , Carbon/chemistry , Catalysis , Isomerism , Quantum Theory
18.
Chemistry ; 19(46): 15759-68, 2013 Nov 11.
Article in English | MEDLINE | ID: mdl-24123356

ABSTRACT

A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalysed by Cu(II) /Al2 O3 has been achieved. This protocol has been employed for the synthesis of a library of arenes bearing a cyclic amide and an amine moiety at two ends, including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry (ICP-MS) studies of the catalyst at different stages of the reaction. The Cu(II) /Al2 O3 catalyst was recovered and recycled for subsequent reactions.


Subject(s)
Amides/chemistry , Amines/chemistry , Copper/chemistry , Hydrocarbons, Halogenated/chemistry , Solvents/chemistry , Catalysis , Crystallography, X-Ray , Electron Spin Resonance Spectroscopy , Molecular Structure , Photoelectron Spectroscopy
19.
J Org Chem ; 78(21): 11110-4, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24116379

ABSTRACT

A convenient, efficient, and general procedure for the synthesis of diaryl chalcogenides including sulfides, selenides and tellurides has been developed by the reaction of diazonium tetrafluoroborates and diaryl dichalcogenides on the surface of alumina under ball-milling without any solvent or metal. A wide range of functionalized diaryl chalcogenides are obtained in high purity by this procedure.

20.
J Biol Chem ; 288(27): 19685-97, 2013 Jul 05.
Article in English | MEDLINE | ID: mdl-23696643

ABSTRACT

Overproduction of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) has been etiologically linked to several inflammatory, immunological, and neurodegenerative diseases. As dimerization of NOS is required for its activity, several dimerization inhibitors, including pyrimidine imidazoles, are being evaluated for therapeutic inhibition of iNOS. However, the precise mechanism of their action is still unclear. Here, we examined the mechanism of iNOS inhibition by a pyrimidine imidazole core compound and its derivative (PID), having low cellular toxicity and high affinity for iNOS, using rapid stopped-flow kinetic, gel filtration, and spectrophotometric analysis. PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). We utilized the iNOS oxygenase domain (iNOSoxy) and two monomeric mutants whose dimerization could be induced (K82AiNOSoxy) or not induced (D92AiNOSoxy) with H4B to elucidate the kinetics of PID binding to the iNOS monomer and dimer. We observed that the apparent PID affinity for the monomer was 11 times higher than the dimer. PID binding rate was also sensitive to H4B and Arg site occupancy. PID could also interact with nascent iNOS monomers in iNOS-synthesizing RAW cells, to prevent their post-translational dimerization, and it also caused irreversible monomerization of active iNOS dimers thereby accomplishing complete physiological inhibition of iNOS. Thus, our study establishes PID as a versatile iNOS inhibitor and therefore a potential in vivo tool for examining the causal role of iNOS in diseases associated with its overexpression as well as therapeutic control of such diseases.


Subject(s)
Enzyme Inhibitors/chemistry , Imidazoles/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pyrimidines/chemistry , Amino Acid Substitution , Animals , Arginine/chemistry , Arginine/pharmacology , Biopterins/analogs & derivatives , Biopterins/chemistry , Biopterins/pharmacology , Cell Line , Enzyme Inhibitors/pharmacology , Heme/chemistry , Heme/metabolism , Imidazoles/pharmacokinetics , Mice , Mutation, Missense , Nitric Oxide Synthase Type II/chemistry , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Protein Multimerization/drug effects , Protein Multimerization/genetics , Pyrimidines/pharmacology
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