Susmita Sinha

Response to Letter in regards to Metformin’s Enigma: Bridging Gaps in Research on Potential Benefits & Associated Risks - A Critical Plea for Comprehensive Investigation [Letter]

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.

Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils. Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs; 3 and 6 PUFAs) are essential for human health because they serve as metabolic precursors of eicosanoids, a class of signaling molecules that are essential for controlling a body’s inflammation. Since humans are unable to produce any of the omega-3 or omega-6 PUFAs, they both constitute imperative nutritional ingredients. Long-standing concerns about long-chain omega-3 fatty acids’ impact on diabetes management have been supported by experimental investigations that found significant increases in fasting glucose following omega-3 fatty acid supplementation and foods rich in PUFA and omega-3 fatty acid. Cellular explanations to explain the connection between inflammation and IR include mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and oxidative stress. Modifications in the lipid composition of mitochondrial membranes and/or receptor-mediated signaling may be part of the mechanism behind the activation of mitochondrial fusion by fish oil/omega-3 PUFA. The exact molecular processes by which omega-3 PUFAs control mitochondrial activity to defend against IR are still unknown.

Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.

Thalassemias are a group of congenital hemoglobin (Hb) disorders distinguished by dwindling or total curtailment of production of one or more globin chains of hemoglobin tetramers, ensuing in unrestrained destruction of red blood cells (RBC) that causes severe anemia. The severity of the disease often remains immensely variable. Children with thalassemia suffer from the disease's consequences and treatment complications. The disease also causes a negative impact on family members, who suffer mentally, socially, financially, and even physically. In this review, we highlight the challenges experienced by the family and caregivers; for instance, repeated blood transfusion as the dominant origin of tissue casualty, morbidity, and fatal clinical outcomes. Treatment modalities regarding thalassemias were not successful until the inception of bone marrow transplantation and gene therapy.

Graft tolerance is a pathophysiological condition heavily reliant on the dynamic interaction of the innate and adaptive immune systems. Genetic polymorphism determines immune responses to tissue/organ transplantation, and intricate humoral and cell-mediated mechanisms control these responses. In transplantation, the clinician's goal is to achieve a delicate equilibrium between the allogeneic immune response, undesired effects of the immunosuppressive drugs, and the existing morbidities that are potentially life-threatening. Transplant immunopathology involves sensitization, effector, and apoptosis phases which recruit and engages immunological cells like natural killer cells, lymphocytes, neutrophils, and monocytes. Similarly, these cells are involved in the transfer of normal or genetically engineered T cells. Advances in tissue transplantation would involve a profound knowledge of the molecular mechanisms that underpin the respective immunopathology involved and the design of precision medicines that are safe and effective.

Introduction: Septicemia is globally considered the most important cause of neonatal morbidity and fatality. Serum C-Reactive Protein (CRP) is an acute phase reactant, which is brought out in response to the inflammatory reaction. It is prophesied to drop down speedily after the coherent weeding out of microbial incitation due to the short half-life of CRP. CRP levels reflect the individual's association between microbial infection and defensive mechanisms. Methods: This hospital-based cross-sectional study included 150 admitted patients with suspected sepsis in the Department of Pediatrics, Rajendra Institute Medical Sciences (RIMS), Ranchi, India, over a study period of one year (2020 to 2021). CRP was estimated on the day of admission and repeated after 72 hours, on the fifth day, and on the seventh day for serial values of CRP, and the findings were compared by making three groups. Further, the research participants were designated to three different groups according to the CRP estimation levels. Results: Out of the 150 assumed neonatal septicemia patients, antibiotics were paused in 42 neonates (28%) within 72 hours. In group 2, 8% of neonates’ antibiotics were stopped in five days, and a total of 102 neonates (68%) could be discharged on the seventh day of antibiotic therapy as their CRPs became negative on the third day and seventh day consecutively, along with negative blood culture reports. In group 3, antibiotics of 48 neonates (32%) were continued beyond seven days. Conclusion: CRP has a skyscraping specificity and negative predictive values (NPV); thus, by estimating serial CRPs, the antibiotic therapy duration can be determined, which further helps determine the period of hospitalization.

Bipolar affective disorder includes Bipolar Disease (BD) and Bipolar Spectrum Disorder (BSD). The prevalence of BSD, BD-I, BD-II, and subthreshold BD globally is estimated to be about 3.1%, 1.5%,0.03%, and 1.6%, respectively. BD is a multidimensional disease that exhibits a range of moods of mania, hypomania, and depression. The disease is chronic, complex, and fatal, with a high possibility of reappearance, infirmity, social incompetence, and felo-de-se. Managing emotional disruption, negative neuropsychology, physiology, and immunology is a challenge. This review focuses on therapeutic benefits, adverse drug reactions, and pharmacological intervention for BD and BSD, in particular lithium. Long-term management of BD with a single medication is ineffective and therefore, not recommended. It is advised to use multiple agents for treatment instead. Medications include mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Along with medication provision, psychotherapy is of great significance for BD patients. The review was conducted on recent available scientific literature through the electronic database like Embase, ScienceDirect, Google Scholar, and PubMed using keywords like ‘Bipolar Disease,’ ‘Bipolar Disease Therapeutics,’ ‘Bipolar Disease and Psychotherapy’ to highlight the possible effective means of management of this disease of mood instability.

Insulin resistance (IR) is stated as diminished insulin action regardless of hyperinsulinemia. The usual target organs for insulin activities are the liver, skeletal muscle, and adipose tissue. Hence, the vasculature and kidneys are nonconventional target organs as the impacts of insulin on these are comparatively separate from other conventional target organs. Vasodilation is achieved by raising endothelial nitric oxide (NO) generation by initiating the phosphoinositide 3-kinase (PI3K) pathway. In insulin-nonresponsive conditions, this process is defective, and there is increased production of endothelin-1 through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which predominates the NO effects, causing vasoconstriction. Renal tubular cells and podocytes have insulin receptors, and their purposeful importance has been studied, which discloses critical acts of insulin signaling in podocyte survivability and tubular action. Diabetic nephropathy (DN) is a prevalent problem in individuals with hypertension, poor glycemic management, hereditary susceptibility, or glomerular hyperfiltration. DN could be a significant contributing factor to end-stage renal disease (ESRD) that results from chronic kidney disease (CKD). IR and diabetes mellitus (DM) are the constituents of syndrome X and are accompanied by CKD progression. IR performs a key part in syndrome X leading to CKD. However, it is indistinct whether IR individually participates in enhancing the threat to CKD advancement rather than CKD complexity. CKD is an extensive public health problem affecting millions of individuals worldwide. The tremendous spread of kidney disease intensifies people’s health impacts related to communicable and noncommunicable diseases. Chronic disease regulator policies do not include CKD at global, local, and/or general levels. Improved knowledge of the character of CKD-associated problems might aid in reforming diagnosis, prevention, and management.

Regular intake of ready-to-eat meals is related to obesity and several noninfectious illnesses, such as cardiovascular diseases, hypertension, diabetes mellitus (DM), and tumors. Processed foods contain high calories and are often enhanced with excess refined sugar, saturated and trans fat, Na⁺ and phosphate-containing taste enhancers, and preservatives. Studies showed that monosodium glutamate (MSG) induces raised echelons of oxidative stress, and excessive hepatic lipogenesis is concomitant to obesity and type 2 diabetes mellitus (T2DM). Likewise, more than standard salt intake adversely affects the cardiovascular system, renal system, and central nervous system (CNS), especially the brain. Globally, excessive utilization of phosphate-containing preservatives and additives contributes unswervingly to excessive phosphate intake through food. In addition, communities and even health experts, including medical doctors, are not well-informed about the adverse effects of phosphate preservatives on human health. Dietary phosphate excess often leads to phosphate toxicity, ultimately potentiating kidney disease development. The mechanisms involved in phosphate-related adverse effects are not explainable. Study reports suggested that high blood level of phosphate causes vascular ossification through the deposition of Ca²⁺ and substantially alters fibroblast growth factor-23 (FGF23) and calcitriol.