Antiretroviral (ARV) therapy in HIV patients can cause hyperlipidaemia, glucose intolerance and insulin resistance, which increase the risk of cardiovascular disease (CVD). An audit carried out in Manchester found that CVD risk factors were common among HIV patients receiving ARVs; however, the management of risk factors was not satisfactory. Adopting a formal system to identify and manage CVD risk factors as well as appropriate referral for specialist management of complications of ARV therapy would improve patient care.
In this study, we examined the relative immune response of T-lymphocytes and its intracellular cholesterol homeostasis, in a mouse model system, after treatment with immunogen, mitogen, and carcinogen. We studied the T-lymphocyte percentage, their LDL-receptor expression, along with the levels of serum interleukins (IL-2, IFNγ, IL-4, and IL-10) and intracellular cholesterol concentration (cytoplasmic and nuclear). The mitogen was found to be a better stimulator of T-cell marker expressions than the immunogen; though the immunogen was more effective on immunogenic response as was marked from interleukin levels. The chemical carcinogen benzo-α-pyrene at low concentration acted potentially like a mitogen but a reduced immune response was apparent at a carcinogenic dose.The findings in our study focus on the effect of carcinogenic dose of benzo-α-pyrene (BaP) on T-cell immunity. Benzo-α-pyrene causes immunosuppression through restriction of the T-cell population by targeting intracellular cholesterol. K E Y W O R D S benzo-alpha-pyrene, cholesterol, cytokines, LDL receptor, pokeweed mitogen, T cells, tetanus toxoid J Biochem Mol Toxicol. 2019;33:e22290.wileyonlinelibrary.com/journal/jbt Differential response of T cells to an immunogen, a mitogen and a chemical carcinogen in a mouse model system.
: Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making steroid endocrines, acting as precursors of metabolic regulators and many more with its emerging prophecy in cell nucleus to drive new cell formation. Besides the crucial legacy in cellular functionality, cholesterol is ostracized as a member of LDL particle which has been proved responsible to clog blood vessels. LDL particles get deposited in the blood vessels because of its poor clearance owing to the non-functioning LDL receptor on vessel wall and surrounding tissues. Blocking of blood vessel promotes heart attack and stroke. On the other hand cholesterol has been targeted as pro-cancerous molecule. At this phase again cholesterol is biphasic. Although cholesterol is essential to construct nuclear membrane and its lipid-rafts; in cancer tumour cells cholesterol is not under control of intracellular feedback regulation and gets accumulated within cell nucleus by crossing nuclear membrane and promotes cell proliferation. In precancerous stage the immune cells also die because of lack of requisite concentration of intracellular and intranuclear cholesterol pool. Existence of cholesterol within the cell nucleus has been found in nuclear membrane, epichromosomal location and nucleoplasm. The existence of cholesterol in the microdomain of nuclear raft has been reported to be linked with gene transcription, cell proliferation and apoptosis. Hydrolysis of cholesterol esters in chromosomal domain is linked with new cell generation. Apparently Cholesterol is now a prelate in cell nucleus too ------ A serendipity in cellular haven.
Tuberculosis (TB) is the most prevalent health disorder in developing nations and is linked with decreased immunity. Vitamin D is one of the most important vitamins required to boost immune response as it is required to maintain innate immune response via its actions on TLRs and macrophages. Risk of Tuberculosis has been associated with decrease level of vitamin D in serum in various studies. Despite of these studies some discrepancies have been shown in different studies conducted in different regions which further potentiates the role of various factors like diet, ethnicity, and seasonal variations influencing the prevalence of T.B in vitamin D deficient and non-deficient population. This study has been conducted to evaluate and establish the link of serum vitamin D in TB and non TB population residing in Mathura region of U.P. Total studied population was 80. 40 participants were taken in patient group with newly diagnosed Tuberculosis both pulmonary and extrapulmonary and 40 were enrolled in healthy control group. Serum sample was collected twice first before the start of treatment in patient group and then after the three months of effective treatment initiation.Among the two groups i.e., control and patient serum level of vitamin D in patient group was found to be significantly low as compared to the control group (22.66±15.17 vs73.03±25.6 ng/mL: P<0.001)Moreover it was seen in this study that serum vitamin D level was low in extrapulmonary tuberculosis as compared to pulmonary T.B, but this is statistically insignificant (P=0.397). Likewise when serum level of vitamin D was compared before start of treatment in patient group and after treatment no significant difference was seen. (P = 0.807). Linear regression analysis ruled out any significant link in serum levels of vitamin D when matching was done including age, gender, site of tuberculosis and after treatment onset criteria P≥0.68.Healthy population has higher serum levels of vitamin D as compared to patients with tuberculosis.
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