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1.
J Pharm Bioallied Sci ; 15(Suppl 1): S702-S705, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37654385

RESUMO

Background: Obstructive sleep apnea (OSA) is a sleep disorder characterized by periodic and repetitive partial or complete collapse of the upper airway during sleep, resulting in reduced ventilation (hypopnea) or absent ventilation (apnea). Materials and Methods: The present study was conducted on 100 adult OSA patients attending hospitals of Jodhpur and the dental clinic in Vyas Dental College and Hospital in Jodhpur city. The sample consisted of 65.0% males and 35.0% females, belonging to 18 years ≥60 years of age with a mean age of 47.61 ± 8.53. Results: In our study, we have used AHI for the assessment of OSA, the major significant association (P = 0.001) was seen between AHI and periodontitis. The finding suggest that the prevalence of periodontitis is greater among patient with OSA with almost 39 patients with AHI value between 11to15 having loss of attachment between 4 mm ≥8 mm. Conclusion: Obstructive sleep apnea is acting as a significant risk factor for major Dental diseases. The study concludes that there was a significant association found between oral health status and OSA patients.

2.
Heart ; 108(7): 517-522, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34226195

RESUMO

OBJECTIVE: The pharmacological management of atrial fibrillation (AF) comprises anticoagulation, for stroke prophylaxis, and rate or rhythm control drugs to alleviate symptoms and prevent heart failure. The aim of this study was to investigate trends in the proportion of patients with AF prescribed pharmacological therapies in the UK between 2008 and 2018. METHODS: Eleven sequential cross-sectional analyses were performed yearly from 2008 to 2018. Data were derived from an anonymised UK primary care database. Outcomes were the proportion of patients with AF prescribed anticoagulants, rhythm and rate control drugs in the whole cohort, those at high risk of stroke and those with coexisting heart failure. RESULTS: Between 2008 and 2018, the proportion of patients prescribed anticoagulants increased from 45.3% (95% CI 45.0% to 45.7%) to 71.1% (95% CI 70.7% to 71.5%) driven by increased prescription of non-vitamin K antagonist anticoagulants. The proportion of patients prescribed rate control drugs remained constant between 2008 and 2018 (69.3% (95% CI 68.9% to 69.6%) to 71.6% (95% CI 71.2% to 71.9%)). The proportion of patients prescribed rhythm control therapy by general practitioners (GPs) decreased from 9.5% (95% CI 9.3% to 9.7%) to 5.4% (95% CI 5.2% to 5.6%). CONCLUSIONS: There has been an increase in the proportion of patients with AF appropriately prescribed anticoagulants following National Institute for Health and Care Excellence and European Society of Cardiology guidelines, which correlates with improvements in mortality and stroke outcomes. Beta-blockers appear increasingly favoured over digoxin for rate control. There has been a steady decline in GP prescribing rates for rhythm control drugs, possibly related to concerns over efficacy and safety and increased availability of AF ablation.


Assuntos
Fibrilação Atrial , Medicina Geral , Insuficiência Cardíaca , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Reino Unido/epidemiologia
3.
Saudi J Biol Sci ; 28(8): 4793-4799, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34354468

RESUMO

The Pinus wallichiana, Daphne oleiodes and Bidens chinensis have a long history of being used traditionally for treatment of various types of disorders. Most of the uses have been without any scientific evidence and toxicological assessment. We evaluated the mutagenic and cytotoxic capabilities of various parts of P. wallichiana, D. oleoides and B. chinensis. Ames Salmonella mutagenicity assay determined the mutagenicity activity against TA 98 and TA 100 bacterial strains of Salmonella typhimurium without metabolic activator S9 system. The number of mutant colonies in negative control was considered as limit to determine the mutagenicity effects of every extract. Brine shrimps lethality bioassay was used to determine the cytotoxic capabilities of the selected plants. The P. wallichiana, D. oleiodes and B. chinensis did not showed any mutagenic activity both for frameshift mutation (TA98) and base-pair substitution (TA100) without S9 mixture. The crude methanolic extract of P. wallichiana stem showed moderate cytotoxicity (53.33%) at 1000 µg/ml with LD50 value 599.634. The D. oleoides fruit showed a toxicity of 60% at 1000 µg/ml with LD50 value 367.730. The B. chinensis (whole plant) showed lethality of 63.3% at 1000 µg/ml, with LD50 204.833. The absence of any mutagenic activity of crude extract of the tested plants in both bacteria strains, TA 98 and TA 100 without the S9 mix confirms the safety of these plants to the consumers.

4.
J Dent Child (Chic) ; 88(2): 101-107, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34321141

RESUMO

Purpose: To describe the geographic distribution of pediatric dentists (PDs) in Florida and the sociodemographic characteristics of communities in which they are located compared with communities without a PD.
Methods: The ratio of PDs to children for each county in Florida and the distribution of PDs in Florida counties at the census tract (CT) level were calculated. Each CT was categorized as having or not having PDs to examine the geographic distribution of PDs, and the sociodemographic differences between CTs with and without a PD were tested by using t-tests. PDs' participation in Medicaid and acceptance of new patients were also investigated.
Results: Of the 67 counties in Florida, 31 had no PD. There were 4,181,677 children younger than 18 years served by 388 PDs, for a statewide ratio of 9.2 PDs per 100,000 population (range 0 to 34.9). Median household income, family income, and education were higher in CTs with PDs, and poverty level, unemployment rate, and percentage of African American population were higher in CTs with fewer PDs. Although 49 percent of PDs accepted Medicaid, only 32 percent accepted new patients.
Conclusion: There are regional and sociodemographic disparities in the distribution of PDs in Florida.


Assuntos
Odontólogos , Medicaid , Criança , Escolaridade , Florida/epidemiologia , Humanos , Pobreza , Estados Unidos
5.
Pak J Pharm Sci ; 34(6): 2205-2211, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35034882

RESUMO

Plant components have been extensively evaluated for their pharmacological activities. This study provides scientific rationale towards the therapeutic effect of Eucalyptus camaldulensis aqueous bark extract against induced atherosclerosis and hyperlipidemia in pigeons. Phytochemical components of Eucalyptus bark extract possess a great antioxidant activity that potentially reduced the risk of heart diseases. A total of 42 Pigeons of both sexes were distributed into negative control (fed normal grain diet), hyperlipidemic control (fed HFD 1% animal fat oil and 0.1% cholesterol for 3 months), test groups of variable doses (0.05, 0.1, 0.2 to 0.4 gms/kg BW for 21 days) and the group received atorvastatin daily after induction used. At the end of the experiment biochemical and histological evaluation has been performed. After HFD induction the serum levels of liver enzyme AST, glucose, urea, cholesterol, LDL, VLDL, and TG were significantly increased with the reduction in HDL levels. The atherogenic index was also found significantly raised. Microscopic examination of the liver and aorta showed the appearance of lipid-filled foam cells all over the liver parenchyma and intima after the HFD induction. Thus it was concluded that Eucalyptus aqueous bark extract can be effective against atherosclerosis and hyperlipidemia.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Eucalyptus , Hiperlipidemias/prevenção & controle , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Ração Animal , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Biomarcadores/sangue , Columbidae , Dieta Hiperlipídica , Modelos Animais de Doenças , Eucalyptus/química , Feminino , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/isolamento & purificação , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Casca de Planta , Extratos Vegetais/isolamento & purificação , Placa Aterosclerótica
7.
J Family Med Prim Care ; 9(3): 1700-1706, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32509675

RESUMO

INTRODUCTION: Use of internet has increased exponentially worldwide with prevalence of internet addiction ranging from 1.6% to 18 % or even higher. Depression and insomnia has been linked with internet addiction and overuse in several studies. AIMS AND OBJECTIVES: Present study has looked in to pattern and prevalence of internet addiction in university students. This study has also explored the association of internet addiction with depression and insomnia. MATERIAL AND METHODS: In this cross sectional study 954 subjects were enrolled who had been using internet for past 6 months. Information regarding pattern of use and socio demographic characteristics were recorded. Internet addiction Test (IAT), PHQ-9,and insomnia Severity Index (ISI) were applied to measure internet addiction, depression and insomnia respectively. RESULTS: Among 954 subjects, 518 (60.59%) were male and 376 (39.41%) were female with mean age of 23.81 (SD ± 3.72). 15.51% study subjects were internet addicts and 49.19% were over users. Several parameters including graduation level, time spent per day on line, place of internet use, smoking and alcohol had significant association with internet addiction. Internet addiction was predominantly associated with depression and insomnia. CONCLUSION: Internet addiction is a rising concern among youth. Several parameters including gender, time spent on line, alcohol, smoking predicts higher risk of internet addiction. Depression and insomnia are more common in internet addicts and overusers.

8.
J Am Dent Assoc ; 151(1): 51-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31902400

RESUMO

OBJECTIVES: The authors aimed to compare the incidence of oropharyngeal cancer (OPC) from 2011 through 2015 and the rate of human papilloma virus (HPV) vaccination from 2015 through 2017 in the United States overall and in Florida. METHODS: Using SEER*Stat software (Surveillance Research Program, National Cancer Institute), the authors calculated age-specific OPC incidence rates for various age groups and age-adjusted rates by sex and race to analyze Surveillance, Epidemiology, and End Results program and National Program of Cancer Registries data. The authors used Joinpoint software (Surveillance Research Program, National Cancer Institute) to model time trends of OPC incidence. They estimated the rate of HPV vaccination among teenagers in Florida and explored the main reasons parents gave for not getting their children vaccinated by means of analyzing data from the National Immunization Survey-Teen. The authors used the χ2 test to determine the association between sociodemographic factors and HPV vaccination and to compare the rate of HPV vaccination in the United States overall with that in Florida. RESULTS: The incidence of OPC was higher and the rate of HPV vaccination was lower in Florida than in the United States overall. The OPC incidence rate was highest in those who were aged 50 through 70 years, non-Hispanic white, and male. The rate of being up-to-date on HPV vaccination in Florida was higher among female teenagers than male teenagers but did not differ significantly by other sociodemographic characteristics. The top reason for not getting an HPV vaccination in Florida was that it had not been recommended. CONCLUSIONS: The authors found relatively higher and increasing incidence rate of OPC in Florida and lower rate of HPV vaccination among adolescents in Florida than in the nation overall. PRACTICAL IMPLICATIONS: The trends illustrated may stimulate policy changes to increase HPV vaccination for children and enhance the understanding of its benefits.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Idoso , Criança , Feminino , Florida , Humanos , Imunização , Incidência , Masculino , Estados Unidos , Vacinação
9.
Thromb Haemost ; 119(7): 1171-1181, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129911

RESUMO

BACKGROUND: Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery. OBJECTIVES: This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI). MATERIALS AND METHODS: In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341). RESULTS: P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups. CONCLUSION: Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Plaquetas/fisiologia , Vasos Sanguíneos/patologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Ticagrelor/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Idoso , Plaquetas/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Masculino , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Intervenção Coronária Percutânea , Ativação Plaquetária , Testes de Função Plaquetária , Receptores Purinérgicos P2Y12/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos
10.
Int J Pharm Pract ; 27(5): 424-435, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30028562

RESUMO

OBJECTIVES: Heart failure is an escalating 'pandemic' with malignant outcomes. Clinical pharmacist heart failure services have been developing for the past two decades. However, little clarity is available on the additional advanced knowledge, skills and experience needed for pharmacists to practice safely and competently. We aimed to provide an expert consensus on the minimum competencies necessary for clinical pharmacists to deliver appropriate care to patients with heart failure. METHODS: There were four methodological parts; (1) establishing a project group from experts in the field; (2) review of the literature, including existing pharmacy competency frameworks in other specialities and previous heart failure curricula from other professions; (3) consensus building, including developing, reviewing and adapting the contents of the framework; and (4) write-up and dissemination to widen the impact of the project. KEY FINDINGS: The final framework defines minimum competencies relevant to heart failure for four different potential levels of specialism: all pharmacists regardless of role (Stage 1); all patient-facing clinical pharmacists (Stage 2); clinical pharmacists with specific planned roles in the care of heart failure patients (Stage 3); and regionally/nationally/internationally recognised expert pharmacists with a direct specialism in heart failure (Stage 4). CONCLUSIONS: The framework delivers the vital first step needed to help standardise care, give pharmacists a blueprint for career progression and continuing professional development and bring clarity to the role of the pharmacist. Future collaboration between professional bodies and training providers is needed to develop structured programmes to align with the framework and facilitate training and resultant accreditation.


Assuntos
Competência Clínica/normas , Insuficiência Cardíaca/tratamento farmacológico , Farmacêuticos/normas , Serviço de Farmácia Hospitalar/normas , Consenso , Currículo/normas , Educação Continuada em Farmácia/normas , Humanos , Papel Profissional
11.
Artigo em Inglês | MEDLINE | ID: mdl-27678388

RESUMO

INTRODUCTION: We aimed to evaluate the efficacy of lycopene on renal tissue antioxidant enzymes and angiotensin converting enzyme (ACE) gene expression and serum activity in diet-induced hyperlipidaemia. METHODS: Thirty-two female Wistar albino rats (200-250 g weight), 5-6 months of age, were randomly selected and divided into four groups. Group I received normal diet; group II received 24 g high fat diet/100 g of daily diet; group III received 24 g high fat diet/100 g daily diet and 200 ml of lycopene extract (twice a week) for 8 weeks; and group IV received 200 ml oral lycopene extract twice a week for 8 weeks. RESULTS: A marked increase was observed in plasma urea and creatinine levels, serum C-reactive protein, kidney weight, tissue renal malonyldialdehyde level, ACE gene expression and serum level, while a decrease catalase level among hyperlipidaemic rats was observed. Histologically, interstitial inflammation and proliferation was seen. Lycopene supplementation significantly decreased plasma urea and creatinine, serum ACE, renal tissue malonyldialdehyde level and C-reactive protein level, while it increased tissue antioxidant enzymes level and total protein. Tissue inflammation and proliferation was improved. CONCLUSIONS: This finding suggests that supplementation of lycopene is effective for renal antioxidant enzymes, ACE gene expression and ACE serum level in hyperlipidaemic rats.

12.
Thromb Res ; 143: 141-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27259210

RESUMO

BACKGROUND: The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention. OBJECTIVES: To complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty. METHODS: We searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy. RESULTS: Twelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies. CONCLUSION: Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.


Assuntos
Adenosina/análogos & derivados , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/farmacocinética , Adenosina/farmacologia , Adenosina/uso terapêutico , Administração Oral , Clopidogrel , Humanos , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/farmacocinética , Cloridrato de Prasugrel/farmacologia , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/farmacocinética , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico
13.
BMJ Case Rep ; 20152015 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-25576507

RESUMO

An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was recently started on quetiapine in addition to regular methylphenidate, which he had been taking for a number of years. He presented with chest pain and inferolateral ST elevation, and underwent urgent coronary angiography, which showed normal coronary arteries. The initial troponin level was raised and an inpatient echocardiogram showed mild left ventricular systolic dysfunction with no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and methylphenidate were discontinued and the patient was discharged home after 1 week. He was followed up within 8 weeks with complete recovery and no symptoms.


Assuntos
Antipsicóticos/efeitos adversos , Dor no Peito/induzido quimicamente , Dibenzotiazepinas/efeitos adversos , Infarto do Miocárdio/diagnóstico , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Diagnóstico Diferencial , Inibidores da Captação de Dopamina/uso terapêutico , Humanos , Masculino , Metilfenidato/uso terapêutico , Fumarato de Quetiapina , Resultado do Tratamento
14.
Pak J Pharm Sci ; 19(1): 62-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16632456

RESUMO

The role of obesity in diabetes mellitus, hyperlipidemia, colon cancer, sudden death and other cardiovascular diseases has confirmed in many recent research studies. In present study, it is hypothesized that obesity can serve as an independent risk factor for the decreased activities of cytoprotective antioxidants in humans and for the associated systemic oxidative stress. 150 age matched, female subjects with no history of smoking or biochemical evidence of diabetes mellitus, hypertension, hyperlipidemia, renal or liver disease or cancer were included in the study and were divided into different grades of obesity according to their body mass index (BMI). Hemoglobin and erythrocyte glutathione (GSH) concentrations were measured for each subject. The study suggests that increase BMI was found to be associated with a significant decrease in erythrocyte glutathione concentration. From these observations it is concluded that obesity even in the absence of smoking, diabetes mellitus, hyperlipidemia, renal or liver diseases can decrease the activities of body's protective antioxidants, and can enhance the systemic oxidative stress and should therefore receive the same attention as obesity with complications.


Assuntos
Glutationa/sangue , Obesidade/metabolismo , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Índice de Massa Corporal , Eritrócitos/metabolismo , Feminino , Hemoglobinas , Humanos , Obesidade/complicações , Fatores de Risco
15.
Environ Toxicol Pharmacol ; 17(3): 143-8, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21782725

RESUMO

A series of antioxidants was used to explore the cytotoxicity of one particularly toxic antimycobacterial 2-pyridylcarboxamidrazone anti-tuberculosis agent against human mononuclear leucocytes (MNL), in comparison with isoniazid (INH) to aid future compound design. INH caused a significant reduction of nearly 40% in cell recovery compared with control (P < 0.0001), although the co-incubation with either glutathione (GSH, 1mM) or (NAC, 1mM) showed abolition of INH toxicity. In contrast, the addition of GSH or NAC 1h after INH failed to protect the cells from INH toxicity (P < 0.0001). The 2-pyridyl-carboxamidrazone 'Compound 1' caused a 50% reduction in cell recovery compared with control (P < 0.001), although this was abolished by the presence of either GSH or NAC. A 1h post incubation with either NAC or GSH after Compound 1 addition failed to protect the cells from toxicity (P < 0.001). Co-administration of lipoic acid (LA) abolished Compound 1-mediated toxicity, although again, this effect did not occur after LA addition 1h post incubation with Compound 1 (P < 0.001). However, co-administration of dihydrolipoic acid (DHLA) prevented Compound 1-mediated cell death when incubated with the compound and also after 1h of Compound 1 alone. Pre-treatment with GSH, then removal of the antioxidant resulted in abolition of Compound 1 toxicity (vehicle control, 63.6 ± 16.7 versus Compound 1 alone 26.1 ± 13.6% versus GSH pre-treatment, 65.7 ± 7.3%). In a cell-free incubation, NMR analysis revealed that GSH does not react with Compound 1, indicating that this agent is not likely to directly deplete membrane thiols. Compound 1's MNL toxicity is more likely to be linked with changes in cell membrane conformation, which may induce consequent thiol depletion that is reversible by exogenous thiols.

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