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Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.
Subject(s)
COVID-19 , Heart Failure , Myocarditis , Zika Virus Infection , Zika Virus , Humans , SARS-CoV-2 , Post-Acute COVID-19 Syndrome , Myocarditis/etiologyABSTRACT
Widespread overuse of antibiotics has led to the emergence of numerous antibiotic-resistant bacteria; among these are antibiotic-subsisting strains capable of surviving in environments with antibiotics as the sole carbon source. This unparalleled expansion of antibiotic resistance reveals the potent and diversified resistance abilities of certain bacterial strains. Moreover, these strains often possess hypermutator phenotypes and virulence transmissibility competent for genomic and proteomic propagation and pathogenicity. Pragmatic and prospicient approaches will be necessary to develop efficient therapeutic methods against such bacteria and to understand the extent of their genomic adaptability. This review aims to reveal the niches of these antibiotic-catabolizing microbes and assesses the underlying factors linking natural microbial antibiotic production, multidrug resistance, and antibiotic-subsistence.
Subject(s)
Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Drug Resistance, Microbial , Bacteria/drug effects , Bacteria/genetics , Bacteria/metabolism , Computational Biology/methods , Fungi/drug effects , Fungi/genetics , Fungi/metabolism , Gene Transfer, Horizontal , Genes, MDR , Humans , Mutation , Web BrowserABSTRACT
BACKGROUND: The purpose of this study was to assess the impact of metabolic and bariatric surgery (MBS) on Quality of Life (QoL) in Indian patients with obesity over 10 years. METHODS: A retrospective chart review was conducted at 11 centres for individuals with MBS between February 2013 and May 2022. Patient medical records provided the source of de-identified data. RESULTS: Data from 2132 individuals with a mean age of 43.28 ± 11.96 years was analysed. There were 37.43% men and 62.57% females in the study population. The study population had a mean preoperative body mass index (BMI) of 45.71 ± 10.38 kg/m2. The Bariatric Analysis and Reporting Outcome System (BAROS) scoring method showed a higher overall QoL score throughout all follow-up periods, with 'very good' outcomes at one, three and 7 years and 'good' outcomes at 5 and 10 years. Improvements in QoL were associated with a substantial improvement (p < .01) in BMI at every follow-up time point. CONCLUSIONS: Following MBS, individuals with obesity exhibited a substantial and long-term improvement in their overall QoL for up to 10 years. This study presents Indian data on QoL, which is considered one of the most important decision-making factors for or against an intervention.
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BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent literature, the diabetic ketoacidosis mortality rate, depending on age, is 2-5%. Insulin discontinuation and infection remain the two most common triggers for diabetic ketoacidosis. About 50% of cases of ketoacidosis result from bacterial infections like urinary tract infections and pneumonia. It is also important to diagnose the presence of infection in diabetic ketoacidosis patients to prevent the excessive use of antibiotics, which may lead to antibiotic resistance. Although performing bacterial culture is confirmatory for the presence or absence of bacterial infection, the time required to obtain the result is long. At the same time, emergency treatment needs to be started as early as possible. METHODS: This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA". RESULTS: This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.
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Bronchial asthma is a widely prevalent illness that substantially impacts an individual's health standard worldwide and has a significant financial impact on society. Global guidelines for managing asthma do not recommend the routine use of antimicrobial agents because most episodes of the condition are linked to viral respiratory tract infections (RTI), and bacterial infection appears to have an insignificant impact. However, antibiotics are recommended when there is a high-grade fever, a consolidation on the chest radiograph, and purulent sputum that contains polymorphs rather than eosinophils. Managing acute bronchial asthma with sepsis, specifically the choice of whether or not to initiate antimicrobial treatment, remains difficult since there are currently no practical clinical or radiological markers that allow for a simple distinction between viral and bacterial infections. Researchers found that serum procalcitonin (PCT) values can efficiently and safely minimize antibiotic usage in individuals with severe acute asthma. Again, the clinical manifestations of acute asthma and bacterial RTI are similar, as are frequently used test values, like C-reactive protein (CRP) and white blood cell (WBC) count, making it harder for doctors to differentiate between viral and bacterial infections in asthma patients. The role and scope of each biomarker have not been precisely defined yet, although they have all been established to aid healthcare professionals in their diagnostics and treatment strategies.
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Background@#High blood glucose levels in diabetes lead to vascular inflammation which accelerates atherosclerosis. Herein, Morin was orally administered in male Wistar rats, at the dose of 40 mg/kg for 28 days, and on the 27th and 28th day, ISO was administered to designate groups at the dose of 85 mg/kg s.c., to induce myocardial infarction. @*Results@#Free radical generation, including ROS, in diabetes following ISO administration, leads to the activation of both intrinsic and extrinsic pathways of apoptosis. Morin significantly (p ≤ 0.05) reduced oxidative stress (GSH, MDA, SOD), cardiac injury markers (CK-MB, LDH), inflammation (TNF, IL-6), and apoptosis (Bax, BCl 2 , Caspase-3). In addition, it also reduced insulin and blood glucose levels. Akt/eNOS, Nrf2/HO-1, MAPK signaling pathways, and Insulin signal transduction pathways were positively modulated by morin pre-treatment. @*Conclusions@#Morin attenuated oxidative stress and inflammation and also modified the activity of various molecular pathways to mitigate cardiomyocyte damage during ISO-induced MI in diabetic rats.
ABSTRACT
The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (P<0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelinA and endothelinB receptors may have potential as a mode of therapy for myocardial infarction.
Subject(s)
Cardiotonic Agents/pharmacology , Endothelin A Receptor Antagonists , Endothelin B Receptor Antagonists , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/prevention & control , Sulfonamides/pharmacology , Animals , Blood Pressure/physiology , Bosentan , Creatine Kinase/metabolism , Diastole/physiology , Heart Rate/physiology , Male , Malondialdehyde/metabolism , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Myocardium/cytology , Myocardium/pathology , Rats , Rats, Wistar , Survival Analysis , Systole/physiology , Time FactorsABSTRACT
Using, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 167 patients of acute lymphoblastic leukemia (ALL) from India at different stages of the disease (presentation 125, remission 33, first relapse nine), MRP1 and GSTpi expression were significantly higher at relapse than presentation (P=0.03 and P=0.01, respectively) and remission (P=0.007 and P=0.003, respectively). MRP1, GSTpi and GSTmu were expressed simultaneously in several samples with significant association of expression levels (P=0.0001). Association with clinicopathological features included higher MDR1 expression with age >15 years (P=0.04) and higher MRP1, GSTpi, GSTmu expression with WBC counts >100x10(9)/l. In 71 patients (age <25 years), inability to achieve CR was associated with a significantly higher MDR1 mRNA expression (P=0.03) indicating a prognostic significance. However, relapse or shorter Event Free Survival was independent of mRNA expression levels of the four genes. In view of the increased mRNA expression of MRP1/GST at the time of relapse and an association with risk factors such as a high WBC count, further studies directed towards investigating the functional aspects of GSH/GST/MRP1 mediated drug transport are warranted.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP-Binding Cassette Transporters/genetics , Glutathione Transferase/genetics , Isoenzymes/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA, Messenger/biosynthesis , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , ATP-Binding Cassette Transporters/biosynthesis , Adolescent , Adult , Age Factors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Disease-Free Survival , Drug Resistance, Multiple , Female , Gene Expression , Glutathione S-Transferase pi , Glutathione Transferase/biosynthesis , Humans , Infant , Isoenzymes/biosynthesis , Male , Multidrug Resistance-Associated Proteins , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Treatment OutcomeABSTRACT
In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x10(9)/l vs. 103.7x10(9)/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x10(9)/l vs. 63. 4x10(9)/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.
Subject(s)
Gene Rearrangement, B-Lymphocyte , Gene Rearrangement, T-Lymphocyte , Leukemia-Lymphoma, Adult T-Cell/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Child , Child, Preschool , Genotype , Humans , Immunoglobulins/genetics , Immunophenotyping , India , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , ResearchABSTRACT
The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.
Subject(s)
Cardiotonic Agents/therapeutic use , Curcuma/chemistry , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Analysis of Variance , Animals , Antioxidants/metabolism , Blood Pressure , Disease Models, Animal , Heart Rate , Histological Techniques , Lipid Peroxidation/physiology , Male , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/physiopathology , Rats , Rats, Wistar , Time Factors , Ventricular Function, Left/physiologyABSTRACT
INTRODUCTION: The present study evaluated the effects of benazepril, an angiotensin-converting enzyme inhibitor on haemodynamic, biochemical, and immunohistochemical (Bax and Bcl-2 protein) indices in ischaemia and reperfusion (IR) injury. MATERIALS AND METHODS: Male Wistar albino rats were divided into three groups and were orally administered saline once daily (IR-sham and IR-control) or benazepril (30 mg/kg/day; IR-benazepril) for 14 days. On the 15(th) day, in the IR-control and IR-benazepril groups, rats were subjected to left anterior descending coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical estimation and immunohistochemistry. RESULTS: In the IR-control group, significant ventricular dysfunctions (p<0.05 vs. IR-sham group) were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in lactate dehydrogenase activity and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, were observed. Benazepril pretreatment significantly improved mean arterial pressure (p<0.01), reduced left ventricular end-diastolic pressure (p<0.05), and improved both inotropic and lusitropic function of the heart (+LVdP/dt and - LVdP/dt) (p<0.05; p<0.01) as compared to IR-control. Furthermore, benazepril treatment significantly decreased the level of thiobarbituric acid reactive substances and restored the activity of lactate dehydrogenase towards normal value (p<0.05 vs. IR-control). CONCLUSION: This study demonstrates that benazepril upregulated Bcl-2 protein and decreased Bax protein expression, thus exhibiting anti-apoptotic effects. These beneficial effects of benazepril will have an important implication in the therapeutic use of benazepril in ischaemic heart disease.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzazepines/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Animals , Gene Expression/drug effects , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Myocardial Infarction/enzymology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Rats , Rats, Wistar , bcl-2-Associated X Protein/biosynthesisABSTRACT
<p><b>OBJECTIVE</b>To our knowledge, prescription of homeopathic medicines by homeopathic undergraduate students has not been studied before though it may possess serious implications. We aimed to determine the practice and attitudes of prescription by homeopathic undergraduate students.</p><p><b>METHODS</b>A cross-sectional study was carried out involving all the students from four government homeopathic schools of West Bengal, India. Ethical requirements were ensured and data were collected using self-administered questionnaires. Chi-square tests and logistic univariate regression analyses were performed to identify associations and differences.</p><p><b>RESULTS</b>A total of 328 forms were completed. Of these, 264 (80.5%) homeopathic undergraduate students admitted of prescribing medicines independently and most (40.5%) said that they did this 2-3 times a year. The most common reasons for this were 'urgency of the problem' (35.2%), 'previous experience with same kind of illness' (31.8%), and 'the problem too trivial to go to a doctor' (25.8%). About 63.4% of the students thought that it was alright to independently diagnose an illness while 51.2% thought that it was alright for them to prescribe medicines to others. Common conditions encountered were fever, indigestion, and injury. Students who prescribed medicines were more likely to belong to Calcutta Homeopathic Medical College and Hospital (odds ratio = 5.8; 95% confidence interval 2.247-14.972). Prescription by students gradually increased with academic years of homeopathic schools. Many students thought it was alright for students to diagnose and treat illnesses.</p><p><b>CONCLUSION</b>Prescription of medicines by homeopathic undergraduate students is quite rampant and corrective measures are warranted.</p>
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Adult , Female , Humans , Male , Young Adult , Cross-Sectional Studies , Drug Prescriptions , Reference Standards , Homeopathy , Education , Workforce , Reference Standards , India , Students , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>Improper prescribing habits and inappropriate drug use lead to serious health and economic consequences. This study was undertaken to evaluate drug utilization services and prescription patterns of homeopathic doctors in a government homeopathic teaching hospital in India.</p><p><b>METHODS</b>No standardized homeopathic drug use indicators are available. The researchers used indicators for health care setting (drug availability)-modified prescribing indicators and patient care indicators, based on World Health Organization's core drug use indicators. A cross-sectional, prospective, institutional, observational study of 2-month duration with record analysis was conducted on 600 patients visiting seven different outpatient departments (OPDs) for the first time at Mahesh Bhattacharyya Homeopathic Medical College and Hospital, Howrah, West Bengal, India, using the developed indicators.</p><p><b>RESULTS</b>Overall availability of prescribed drugs was quite satisfactory (92.28%). Centesimal potencies accounted for the majority of prescriptions (74.76%). There was a poor record of diagnosis (39.17%) except in the OPDs of Gynecology and Obstetrics (68.48%, P < 0.01) and Dermatology (64.58%, P < 0.01). Records of investigational findings and ongoing therapies, if any, were also poor except OPDs of Gynecology and Obstetrics, and Pediatrics. Structure of prescriptions was maintained satisfactorily in all the OPDs. Though tendency of using 'individualized homeopathy' predominated, there also existed the use of 'polypharmacy'. Mean consultation time was 5.9 min. Labeling was extremely poor and is an area needing improvement. The prescriptions were highly legible.</p><p><b>CONCLUSION</b>This was a preliminary study, conducted for the first time in homeopathy using newly developed indicators that yield meaningful results. Further studies are necessary in order to evaluate the different factors involved and to plan future interventions to improve the quality of care in healthcare settings.</p>