Assessment of medication adherence among hypertensive patients: a cross-sectional study

Background: Hypertension affects around one billion individuals worldwide and is expected to increase by 29% to reach 1.56 billion by 2025. It is usually asymptomatic, chronic disorder needing lifelong treatment. The objective of this study was to study the medication adherence among hypertensive patients using hill-bone compliance to high blood pressure therapy scale (HILL-BONE CHBPTS) and to compare medication adherence in hypertensive patients with controlled and uncontrolled blood pressure.Methods: A cross-sectional, observational study was conducted for a period of one year in the Outpatient department of Medicine in a tertiary care hospital, Navi Mumbai. A total of 129 hypertensive patients who were on at least six months on antihypertensive medications were enrolled. Blood pressure was measured and details of drug therapy were noted. Medication adherence was assessed using HILL-BONE CHBPTS and respective scores were calculated.Results: HILL-BONE CHBPTS scores were on the higher side signifying poor medication adherence among hypertensive patients. HILL-BONE CHBPTS score correlated significantly in a positive direction with diastolic blood pressure, duration of treatment and the number of medications, As per JNC 8 recommendations, 58.9% (76) hypertensive patients were having blood pressure under control, whereas 41.1% (53) were having uncontrolled blood pressure. HILL-BONE CHBPTS scores were significantly higher (reflecting lower adherence) in hypertensive patients with uncontrolled blood pressure than those having optimally controlled blood pressure.Conclusions: Overall the medication adherence was poor in hypertensive patients. Adherence to therapeutic regimens is an important factor in blood pressure control among hypertensive patients and needs priority. Health education related to medication adherence needs be improved in hypertensive patients

Role of Hippocampal Lipocalin-2 in Experimental Diabetic Encephalopathy

Diabetic encephalopathy is a severe diabetes-related complication in the central nervous system (CNS) that is characterized by degenerative neurochemical and structural changes leading to impaired cognitive function. While the exact pathophysiology of diabetic encephalopathy is not well-understood, it is likely that neuroinflammation is one of the key pathogenic mechanisms that cause this complication. Lipocalin-2 (LCN2) is an acute phase protein known to promote neuroinflammation via the recruitment and activation of immune cells and glia, particularly microglia and astrocytes, thereby inducing proinflammatory mediators in a range of neurological disorders. In this study, we investigated the role of LCN2 in multiple aspects of diabetic encephalopathy in mouse models of diabetes. Here, we show that induction of diabetes increased the expression of both Lcn2 mRNA and protein in the hippocampus. Genetic deficiency of Lcn2 significantly reduced gliosis, recruitment of macrophages, and production of inflammatory cytokines in the diabetic mice. Further, diabetes-induced hippocampal toxicity and cognitive decline were both lower in Lcn2 knockout mice than in the wild-type animals. Taken together, our findings highlight the critical role of LCN2 in the pathogenesis of diabetic encephalopathy

Lipocalin-2 promotes adipose-macrophage interactions to shape peripheral and central inflammatory responses in experimental autoimmune encephalomyelitis

Objective: Accumulating evidence suggests that dysfunctional adipose tissue (AT) plays a major role in the risk of developing multiple sclerosis (MS), the most common immune-mediated and demyelinating disease of the central nervous system. However, the contribution of adipose tissue to the etiology and progression of MS is still obscure. This study aimed at deciphering the responses of AT in experimental autoimmune encephalomyelitis (EAE), the best characterized animal model of MS. Results and methods: We observed a significant AT loss in EAE mice at the onset of disease, with a significant infiltration of M1-like macrophages and fibrosis in the AT, resembling a cachectic phenotype. Through an integrative and multilayered approach, we identified lipocalin2 (LCN2) as the key molecule released by dysfunctional adipocytes through redox-dependent mechanism. Adipose-derived LCN2 shapes the pro-inflammatory macrophage phenotype, and the genetic deficiency of LCN2 specifically in AT reduced weight loss as well as inflammatory macrophage infiltration in spinal cord in EAE mice. Mature adipocytes downregulating LCN2 reduced lipolytic response to inflammatory stimuli (e.g. TNFα) through an ATGL-mediated mechanism. Conclusions: Overall data highlighted a role LCN2 in exacerbating inflammatory phenotype in EAE model, suggesting a pathogenic role of dysfunctional AT in MS

Cathelicidin-Related Antimicrobial Peptide Negatively Regulates Bacterial Endotoxin-Induced Glial Activation

Recent studies have suggested that mouse cathelicidin-related antimicrobial peptide (CRAMP) and its human homologue leucine leucine-37 (LL-37) play critical roles in innate immune responses. Here, we studied the role of mouse CRAMP in bacterial endotoxin lipopolysaccharide (LPS)-induced neuroinflammation. CRAMP peptide treatment significantly inhibited LPS-mediated inflammatory activation of glial cells in culture. In the animal model of LPS-induced neuroinflammation, CRAMP expression was highly induced in multiple cell types, such as astrocytes, microglia, and neurons. Injection of exogenous CRAMP peptide significantly inhibited inflammatory cytokine expression and the reactivity of glial cells in the mouse brain following intraperitoneal or intracerebroventricular LPS administration. Altogether, results of the study suggest that CRAMP plays an important part in containment of LPS-induced neuroinflammatory responses, and that CRAMP can be exploited for the development of targeted therapies for neuroinflammatory conditions associated with bacterial infection

The microglial innate immune protein PGLYRP1 mediates neuroinflammation and consequent behavioral changes

Summary: Peptidoglycan recognition protein 1 (PGLYRP1) is a pattern-recognition protein that mediates antibacterial actions and innate immune responses. Its expression and role in neuroinflammatory conditions remain unclear. We observed the upregulation of PGLYRP1 in inflamed human and mouse spinal cord and brain, with microglia being the primary cellular source. Experiments using a recombinant PGLYRP1 protein show that PGLYRP1 potentiates reactive gliosis, neuroinflammation, and consequent behavioral changes in multiple animal models of neuroinflammation. Furthermore, shRNA-mediated knockdown of Pglyrp1 gene expression attenuates this inflammatory response. In addition, we identify triggering receptor expressed on myeloid cell-1 (TREM1) as an interaction partner of PGLYRP1 and demonstrate that PGLYRP1 promotes neuroinflammation through the TREM1-Syk-Erk1/2-Stat3 axis in cultured glial cells. Taken together, our results reveal a role for microglial PGLYRP1 as a neuroinflammation mediator. Finally, we propose that PGLYRP1 is a potential biomarker and therapeutic target in various neuroinflammatory diseases