Zinc as An Emerging Therapy in the Management of Migraine: A Systematic Review.

Migraine, a common neurological condition, is characterized by a chronic and recurring headache that affects numerous people globally. Several drugs are available for the treatment and prophylaxis of migraine with their shortfalls. Zinc could play a role in migraine management because of its anti-inflammatory and antioxidant properties. This study was planned to systematically review the scientific databases to gather evidence regarding the role of zinc in the management of migraine. The protocol was registered with the PROSPERO (CRD42023398478). Three databases PubMed, The Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched with the keywords "migraine", "migraine disorders" and "zinc". A literature search led to the retrieval of 35 studies; of these five studies (2 clinical trials and 3 observational studies) were comprised in a systematic review. Clinical trials' risk of bias assessment is low. The review suggested a positive role of zinc in managing migraine however, the evidence requires further strengthening. The available clinical literature on the effectiveness of zinc in migraines is limited; hence, more robust and large clinical trials are required to support the role of zinc in migraines.

Are we providing complete drug information to its users? Status of information adequacy of package insert in India.

Background: Package inserts (PIs) serve detailed information on drug products to the users and primary care physicians, so information should be accurate, reliable, and as per the regulatory guidelines. The study aims to analyze the information adequacy of the PIs available in the Indian market as per Drug and Cosmetic Rule 1945 and US Food and Drug Administration criteria. Materials and Methods: A cross-sectional study was conducted on PIs collected from accessible pharmacy stores. Information provided was recorded as per criteria, and total information adequacy score (IAS) and information deficiency (IDS) score were calculated. The association of factors like single-drug/FDCs, a company of origin Indian/multinational, and route of administration (ROA) with IDS was statistically analyzed. Results: Of 120 PIs, 60%, 86.66%, and 73% were single-drug, prescription-drug, and drugs by Indian manufacturers, respectively. Most PIs provided generic names, ROA, and indications for use. 85%, 12%, 29.16%, and 3.33% provided information on PIs on the ability to drive, drug-food interactions, drug-drug interactions, and addiction potential, respectively. Lacking area was information on use in pediatrics-geriatrics (30%), excipients (28.3%), preclinical (15.83%), post-surveillance data (18.33%), and approval date (2.5%). There was a statistically significant difference between pharmaceutical score (3.22 vs 4.12), therapeutic score (11.5 vs 13.18), and total IAS (14.78 ± 3.39 vs 17.31 ± 2.33) of Indian and multinational companies. IDS was statistically significantly different in both pharmaceutical and therapeutic categories for single-drug vs FDCs (P = 0.00001), OTC vs prescription drugs (P < 0.05), and Indian vs multinational companies' PIs (P = 0.00001). Conclusion: Numerous facets of information are lacking in PIs, and they do not impart whole information, especially of Indian origin, as per objective IDS.

Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.

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.

Potential of Cytochrome P450, a Family of Xenobiotic Metabolizing Enzymes, in Cancer Therapy.

Significance: Targeted cancer therapy with minimal off-target consequences has shown promise for some cancer types. Although cytochrome P450 (CYP) consists of 18 families, CYP1-4 families play key role in metabolizing xenobiotics and cancer drugs. This eventually affects the process of carcinogenesis, treatment outcomes, and cancer drug resistance. Differential overexpression of CYPs in transformed cells, together with phenotypic alterations in tumors, presents a potential for therapeutic intervention. Recent Advances: Recent advances in molecular tools and information technology have helped utilize CYPs as cancer targets. The precise expression in various tumors, X-ray crystal structures, improved understanding of the structure-activity relationship, and new approaches in the development of prodrugs have supported the ongoing efforts to develop CYP-based drugs with a better therapeutic index. Critical Issues: Narrow therapeutic index, off-target effects, drug resistance, and tumor heterogeneity limit the benefits of CYP-based conventional cancer therapies. In this review, we address the CYP1-4 families as druggable targets in cancer. An emphasis is given to the CYP expression, function, and the possible mechanisms that drive expression and activity in normal and transformed tissues. The strategies that inhibit or activate CYPs for therapeutic benefits are also discussed. Future Directions: Efforts are needed to develop more selective tools that will help comprehend molecular and metabolic alterations in tumor tissues with biological end-points in relation to CYPs. This will eventually translate to developing more specific CYP inhibitors/inducers. Antioxid. Redox Signal. 38, 853-876.

Immunotherapy and Targeted Therapy in the Management of Oral Cancers.

Oral cancers (OCs), being one of the frequent malignancies in the head and neck region, need prompt diagnosis and treatment. Apart from basic therapeutic modalities, immunotherapy has now been utilized as a novel approach to combat the disease. With the comprehension of the strategies adopted by cancer cells to evade the immune elimination by the body's immune system, targeted immunotherapies have now become the core area of research. The immune expression of epidermal growth factor receptor (EGFR), programmed cell death protein ligand-1 (PDL-1), etc., are enhanced in OC and have been associated with evasion of the immune system. Targeted immunotherapies now include monoclonal antibodies targeting EGFR like cetuximab and panitumumab, programmed cell death-1 (PD-1) inhibitors like pembrolizumab, cemiplimab, and nivolumab, and PD-L1 inhibitors like atezolizumab, avelumab, and durvalumab. Targeted immunotherapies like chimeric antigen receptor T-cell treatment and small molecule inhibitors are in several clinical trials tried as monotherapy and adjuvant immunotherapy and have shown promising results. Other immunothera-peutic approaches such as cytokines like interferons or interleukins, vaccines, and gene therapy have also been an area of research for the management of OC. However, the cautious selection of appropriate patients with specific immune characteristics as a candidate for immunotherapeutic agents is a crucial component of targeted immunotherapy. This article elaborates on the immune contexture of oral cancer cells, the mechanism of immune evasion by cancer cells, targets for immunotherapies, existent immunotherapeutic agents, and prospects in the field of immunotherapy.

Insulin delivery methods: Past, present and future.

Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral hyperinsulinemia. Therefore, the need exists for delivering insulin in a minimally invasive or noninvasive and in most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver insulin, but it has been withdrawn from the market. Technologies are being explored to make the noninvasive delivery of insulin possible. Some of the routes of insulin administration that are under investigation are oral, buccal, nasal, peritoneal and transdermal. This review article focuses on the past, present and future of various insulin delivery techniques. This article has focused on different possible routes of insulin administration with its advantages and limitation and possible scope for the new drug development.

Evaluation of the appropriateness of prescribing in geriatric patients using Beers criteria and Phadke's criteria and comparison thereof.

OBJECTIVES: To evaluate appropriateness of prescribing medicines in geriatric patients using both Beers criteria and Phadke's criteria and compare them for validation of Phadke's criteria as a tool to evaluate rationality of prescribing in elderly. MATERIALS AND METHODS: A cross-sectional prospective observational study was conducted and the baseline data were collected from different inpatient and outpatient departments in Shree Krishna Hospital (SKH), Karamsad. A total of 400 patients of geriatric age group (≥65 years) from various inpatient and outpatient departments of SKH were included in the study. Relevant information from patients included in the study was recorded in a structured proforma from their case files. Data were evaluated for appropriateness of prescribing by using both Beers criteria and Phadke's criteria and comparison between the two criteria was also carried out. RESULTS: Out of total 400 patients, 291 (72.75%) patients were prescribed appropriately according to Beers criteria. Based on Phadke's criteria, 158 (39.5%) prescriptions were rational, 129 (32.3%) were semirational and 113 (28.3%) were irrational. Mean rationality score on a 30-point semiscientific scale was found to be 18.47 ± 9.66 (mean ± SD). The comparison of outcome by both the criteria showed no significant difference in appropriateness of prescribing (P>0.05). CONCLUSIONS: Inappropriate prescribing is common in elderly patients. Beers criteria is a well-established method for evaluating appropriateness of prescribing. This study has shown that Phadke's method of evaluating rationality of prescriptions compares equally well and hence can be a valuable objective tool for assessing appropriateness of prescribing in geriatric patients.