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Tuberculosis (TB) is a chronic, air-borne infectious disease caused by Mycobacterium tuberculosis (Mtb), which prominently affects the lungs and usually manifests in other organs. TB is preventable and curable but what makes it challenging is the emergence of resistance to the available treatment options. MDR-continued TB's expansion is one of the world's most pressing and difficult problems. Mtb revives via the reciprocity between Mycobacterium and host signalling pathways. Mtb secretes a virulence component called Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB), which helps to survive against host macrophages. It indicates that targeting secreted virulence factors offers more benefits to circumvent the emergence of resistance. Many effective inhibitors of MptpA and MptpB have been discovered, providing a solid foundation for future research and development. Aside from possessing a structurally unique binding site in the Mtb enzyme, MptpB's minimal resemblance to other human phosphatases provides a broad platform for improving selectivity over host PTPs. We believe that addressing several parts of infection processes in the host and bacteria with combination therapy is the greatest way to reduce treatment burden and medication resistance. We have discussed the recent potent, selective, and efficacious MptpB inhibitors, such as natural and marine-based, isoxazole- linked carboxylic acid-based, oxamic acid-based, and lactone-based inhibitors, as potential strategies for treating TB.
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Mycobacterium tuberculosis , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Antituberculosos/química , Tuberculose/tratamento farmacológico , Transdução de Sinais , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Fosfatases/farmacologiaRESUMO
Background: Low-density lipoprotein-cholesterol (LDL-C) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) progression. Although lipid lowering therapies remain the cornerstone of secondary ACSVD prevention, there exists residual dyslipidemia. The current study aimed to evaluate the real-world experience related to the treatment patterns and LDL-C control in Indian Acute Coronary Syndrome (ACS) patients. Methods: This was a real-world, descriptive, retrospective, observational, and multicentric study conducted across India. The data was collected for 1 year following the ACS event. The change in the levels of LDL-C from the baseline to the follow-up visits and the control of LDL-C, the change in lipid profile, lipoprotein levels, treatment patterns for lipid-lowering, and tolerability of existing treatments were evaluated. Results: Overall, 575 patients were included from 11 centers across India. The mean age of the patients was 52.92 years, with male predominance (76.35%). Although there was a significant reduction in the mean levels of LDL-C from the baseline [(122.64 ± 42.01 mg/dl to 74.41 ± 26.45 mg/dl (p < 0.001)], it was observed that despite high-intensity statin therapy, only 20.87% patients managed to achieve target LDL-C of <55 mg/dL and 55.65% were unable to reach LDL-C levels of <70 mg/dl one year after the event. Six patients reported adverse events without treatment discontinuation. Conclusion: The majority of the patients received high-intensity statins and did not attain target LDL-C levels, suggesting LDL-C control after an ACS event requires management with novel therapies having better efficacy as recommended by international and national guidelines.
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Traumatic brain injury (TBI) related impact results in a permanent need for help in performing daily activities. Standard treatment consists of removing the cause, restore perfusion, support metabolic requirement and limit inflammatory and oxidative damage. Hyperbaric oxygen therapy (HBOT) is one such newer promising treatment that enhances neurological recovery to some extent. HBOT is intermittent inhalation of 100% oxygen at greater than normal atmospheric pressure and is internationally accepted for its role in well-defined indications. It is hypothesised that HBO has a role in reviving 'idling neurons', also called the ischemic penumbra defined as area of reduced cerebral blood flow, abolished synaptic activity but preserved structural integrity. We carried out a retrospective analysis of medical records of 20 patients of TBI who had been treated with HBOT in addition to standard management. These were placed in Group A (test group) and received at least 30 sessions of HBO along with standard treatment. The patients were assessed along the Disability Rating Scale (DRS), Glasgow coma scale (GCS) and Rancho Los Amigos Scale (RLAS). Another 20 patients of TBI, matched in age and severity of brain injury, who received standard treatment but not HBOT, were selected as the control group (Group B). Assessment on the DRS showed maximum improvement in patients with scores of 22-24 (vegetative state).The percentage of patients in the test group fell from 45% to 5% whereas only 20% patients in Group B had similar progress. After the treatment, a significantly higher proportion of HBOT treated subjects showed a good response in cognitive functions, as measured by RLA. In group A, 90% patients had a score of ≤ 3 and in Group B 95% had a similar score, which improved to ≥ 3 in 60% patients versus 30% patients respectively. In both groups maximum patients are in 1-6 months post-injury category and within the groups this category showed the greatest recovery, with a greater improvement in the test group as compared to control group.
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Lesões Encefálicas/terapia , Oxigenoterapia Hiperbárica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Cognição , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/terapia , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Fondaparinux is the first approved anticoagulant drug among factor Xa inhibitors, with proven effectiveness and safety in preventing deep vein thrombosis. However, limited data are available supporting the benefit-risk profile of fondaparinux vs enoxaparin in a real-world group of Indian patients with deep vein thrombosis. OBJECTIVE: To compare the effectiveness and tolerability of fondaparinux vs enoxaparin in patients with symptomatic deep vein thrombosis in a long-term real-world setting. METHODS: Data from the electronic medical records of adult patients diagnosed with deep vein thrombosis prescribed fondaparinux (n = 503) or enoxaparin (n = 508) as monotherapy were analyzed. Effectiveness was analyzed in terms of recurrence, duration, and type of deep vein thrombosis event, and tolerability as bleeding events at initial hospitalization and follow-up visits up to 3 months duration. Appropriate statistical methods were used to determine the significance (p < 0.05) between the two groups. RESULTS: The deep vein thrombosis recurrence in the fondaparinux group was non-inferior (2.78%) when compared with enoxaparin (3.76%), with a mean duration of 47 and 48 days, respectively. The number of events and mean duration of events (in days) were not significant (p > 0.05). Major bleeding events were higher in the enoxaparin group at 3.17% than the fondaparinux group at 2.19%, and the difference was not statistically significant (p > 0.05). CONCLUSIONS: The weight-based, once-daily subcutaneous fondaparinux dose showed non-inferior effectiveness and a comparable tolerability profile when compared with the twice-daily enoxaparin dose for the management of symptomatic deep vein thrombosis.
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INTRODUCTION: Calcium channel blockers have pedal edema as one of the confining factors of treatment. A real-world study may help evident reality of the situation in regular Indian clinical practice. The aim of the study is to assess effectiveness and incidence of pedal edema in essential hypertensive patients treated with amlodipine or cilnidipine monotherapy. METHODS: Retrospective EMR data of adult essential hypertensive patients, prescribed amlodipine (n = 800) or cilnidipine (n = 800) as monotherapy, were analyzed. Incidence of pedal edema from baseline visit was analyzed in terms of dose and duration of treatment. The changes in systolic (SBP) and diastolic blood pressure (DBP) from baseline and proportion of patients achieving target BP goals were assessed. RESULTS: In amlodipine and cilnidipine groups, mean changes in SBP and DBP from baseline to end of the study period were 28.4 and 15.1 mmHg and 24.3 and 13.5 mmHg, respectively (p value <0.05). More than 50% of patients in both groups achieved BP goal at the end of the study (p value 0.266). In amlodipine group, total 23.9% reported pedal edema, while in cilnidipine, 27.6% (p value 0.0863). At the end of the study, 3.5% and 8.2% of patients remain with pedal edema, respectively, in both groups (pvalue <0.005). CONCLUSION: Amlodipine demonstrated greater BP reduction at a lower average dose, better efficacy, and tolerability in terms of pedal edema count as a lesser number of patients reported edema at the end of the study and a higher percentage of patients continued the prescribed baseline dosage regimen as compared to cilnidipine. Thus, the study established amlodipine as an effective and well-tolerated antihypertensive for Indians.
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INTRODUCTION: The renoprotective effects of dihydropyridine calcium channel blockers (CCBs) have been established as non-inferior to other classes of antihypertensive drugs. Studying their effect on renal outcome parameters, specifically for amlodipine as monotherapy, in real-world settings can further help in expanding its usage among Indian patients. This study was performed to assess the effects of amlodipine and other dihydropyridine CCBs (cilnidipine, benidipine and azelnidipine) on renal parameters and effectiveness in blood pressure reduction in Indian patients. METHODS: The retrospective data of adult patients (> 18 years) with essential hypertensive who were prescribed amlodipine (n = 92), cilnidipine (n = 91), benidipine (n = 70) or azelnidipine (n = 71) as monotherapy were analyzed. The renal outcomes, serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), microalbumin, urine albumin-to-creatinine ratio (UACR), sodium and potassium levels, and mean changes in BP were analyzed from baseline to 12 months. Appropriate statistical methods were used to determine the significance (p value < 0.05). RESULTS: From baseline to the end of the study, mean serum creatinine changed from 0.98 ± 0.17 to 1.07 ± 0.28 mg/dL with amlodipine, 0.97 ± 0.18 to 1.13 ± 0.50 mg/dL with cilnidipine, 0.98 ± 0.30 to 0.97 ± 0.27 mg/dL wi th benidipine, and 0.99 ± 0.23 to 0.98 ± 0.25 mg/dL with azelnidipine (p = 0.01). The mean microalbumin and UACR were reduced from baseline to the end of the study (p = 0.06 and p > 0.05). No significant changes were observed in BUN, sodium or potassium levels. Overall, for all CCBs, the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were reduced from baseline to the end of the study (p = 0.002). At the end of the study, the average dose of amlodipine was 7.25 mg, and the average reduction in SBP and DBP per mg dose was 1.54 and 0.57 mmHg. The corresponding numbers for the other CCBs were as follows: cilnidipine, 14.28 mg, 0.26 and 0.01; benidipine, 5.71 mg, 0.41 and 0.11; azelnidipine, 15.88 mg, 0.13 and 0.06. CONCLUSION: Amlodipine and other CCBs demonstrated good efficacy and similar effects on renal parameters from baseline to end of study. Amlodipine also showed higher potency by demonstrating greater BP reduction at a lower dose. Thus, amlodipine can remain a preferred choice among CCBs, even with the advent of the newer CCBs.