Evaluation of Pharmacodynamic interaction between Tinospora Cordifolia Alcoholic extract and Gliclazide : An herb-drug interaction study

Many diabetic people today consume herbs or herbal formulations along with prescription and non-prescription medications which may result in the herb-drug interaction Tinospora Cordifolia, with berberine being one of the most abundant active phytoconstituent widely used as an antidiabetic While Gliclazide is indicated to treat type 2 diabetes mellitus whichacts asan insulin secretagogue .T. Cordifolia is a potent inhibitor of CYP2C9 and Gliclazide is known to be metabolized by this enzyme. Potential Pharmacodynamic herb drug interaction might be possible in case of co administration of both. The pharmacodynamic interaction between TCE and Gliclazide was evaluated on hypoglycemic activity in normal and streptozotocinnicotinamide-induced diabetic rats. The study was conducted in 2 parts viz. acute study and sub-acute study in both normal and diabetic animals. The serum triglyceride level and histopathology of pancreawas performed to assess effect on glucose metabolism and pancreas.FTIR Analysis was also carried out to evaluate the interaction between functional groups. The combination showed pharmacodynamic interaction as reduction the time of onset of action and increasing the duration of action of gliclazide when administered in combination with T. cardiofolia. In FTIR studies of combination showed no physical interaction betweenfunctional groups suggesting both drugs might be acting on the different receptors. The study concludes that the combination of Gliclazide with TCE showed an increase in the hypoglycemic effect as compared to the gliclazide alone in STZ-NIC induced diabetic rats. This might be utilized clinically as a beneficial drug interaction in patients after thorough investigations in clinical studie

Unique cellular immune signatures of multisystem inflammatory syndrome in children

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8(+) T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4(+) and CD8(+) T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242

Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities

Background: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. Methods: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. Results: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1β, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. Conclusions: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children