Vandana Saini

MCP-1: Chemoattractant with a role beyond immunity: A review

BACKGROUND Monocyte Chemoattractant Protein (MCP)-1, a potent monocyte attractant, is a member of the CC chemokine subfamily. MCP-1 exerts its effects through binding to G-protein-coupled receptors on the surface of leukocytes targeted for activation and migration. Role of MCP-1 and its receptor CCR2 in monocyte recruitment during infection or under other inflammatory conditions is well known. METHOD A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicines digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT Recent and ongoing research indicates the role of MCP-1 in various allergic conditions, immunodeficiency diseases, bone remodelling, and permeability of blood - brain barrier, atherosclerosis, nephropathies and tumors. CONCLUSION MCP-1 plays an important role in pathogenesis of various disease states and hence MCP-1 inhibition may have beneficial effects in such conditions.

Role of leptin and adiponectin in insulin resistance.

Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-α, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat.

Cytokines in recurrent pregnancy loss

BACKGROUND Recurrent pregnancy loss (RPL) is defined as the occurrence of three or more consecutive miscarriages prior to 20 weeks gestation. Exaggerated maternal immune response to fetal antigens has been proposed to be one of the mechanisms underlying recurrent pregnancy loss. METHOD A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicines digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT In normal pregnancy, tolerance of the genetically incompatible fetus by the maternal immune system depends on the interactions of an array of cytokines secreted by maternal and fetal cells at the site of implantation. Earlier research indicated that altered immunity in RPL is dominated by the Th1/Th2 hypothesis, which proposed that the fetus escapes maternal-derived T-cell responses through skewing the Th0 differentiation toward Th2 pathway which dampens pro-inflammatory Th1-type immunity. Recent studies indicate the role of proinflammatory Th17 cells and immunoregulatory Treg cells in RPL in addition to Th1/Th2 interactions. CONCLUSION Cytokines form a complex regulatory network which maintains homeostasis between the fetal unit and the maternal immune system. If this delicate balance is adversely affected, immunoregulatory mechanisms may be insufficient to restore homeostasis and this may lead to pregnancy failure.

Role of hormones in acne vulgaris

OBJECTIVE To elucidate the role of endogenous hormones like testosterone, progesterone, estrogen, insulin-like growth factor, insulin and glucocorticoids in a common skin condition acne vulgaris. DESIGN AND METHODS We conducted a systematic review of the literature and abstracted the data for every published cut point. RESULTS We screened more than 1000 studies and found that serum testosterone, progesterone, glucocorticoids, insulin and insulin-like growth factors are increased in patients with acne vulgaris and serum estrogen levels are low in patients. CONCLUSIONS Various endogenous hormones play important role in the pathogenesis of acne vulgaris. Thus, in the clinical practice it is important to evaluate serum levels of these hormones and patients must be treated accordingly to avoid serious endocrine disorders at an early age.

Association of endothelial dysfunction with endothelin, nitric oxide and eNOS Glu298Asp gene polymorphism in coronary artery disease

The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p < 0.001) whereas, the NO level in CAD group was significantly lower (p < 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p < 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population.

Correlation of creatinine with TSH levels in overt hypothyroidism — A requirement for monitoring of renal function in hypothyroid patients?

OBJECTIVE Renal function is influenced by thyroid status. Therefore, this study was done to determine the relationship between renal function and different degrees of thyroid dysfunction. DESIGN AND METHODS Thyroid and kidney function tests were analyzed in 47 patients with overt (TSH ≥ 10.0 μIU/L) and 77 patients with subclinical hypothyroidism (TSH 6.0-9.9 μIU/L) in a cross-sectional study. These were compared with 120 age- and sex-matched euthyroid controls. RESULTS Overt hypothyroid subjects showed significantly raised serum urea, creatinine and uric acid levels as compared to controls whereas subclinical hypothyroid patients showed significant increased levels of serum urea and creatinine levels. TSH showed significant positive correlation with creatinine and uric acid values and, fT4 had a negative correlation with uric acid in overt hypothyroidism. CONCLUSION Hypothyroid state is associated with significant derangement in biochemical parameters of renal function. Hence the renal function should be regularly monitored in hypothyroid patients.

Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary artery disease patients with type 2 diabetes mellitus.

AIMS Endothelial dysfunction is thought to be a significant risk factor for cardiovascular disease. This study determined the role of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism and intergenotypic variation of plasma nitric oxide (NO) levels in coronary artery disease (CAD) patients with type 2 diabetes mellitus (DM). METHODS This case-control study included 28 documented CAD patients with type 2 DM and 32 non-diabetic patients with CAD. Fifty healthy volunteers without any major cardiovascular risk factors served as controls. NO was estimated by modified Griess method. The eNOS gene polymorphism was studied by amplifying DNA by PCR and digesting with BanII restriction enzyme. Restriction fragment length polymorphism was studied by using a gel documentation system. RESULTS The genotype frequencies for Glu298Asp (GT) genotype were 10.71% in diabetic CAD patients, 28.1% in non-diabetic CAD patients and 12% in controls. The T allele frequency was higher in the non-diabetic CAD group (14%) as compared with the diabetic CAD (5.4%) and control group (6%). NO level was significantly lower in non-diabetic CAD patients (10.25 mmol/L) but not in diabetic CAD patients (13.89 mmol/L) as compared to controls (16.78 mmol/L). CONCLUSION Glu298Asp polymorphism is not the mediator of increased incidence of CAD in diabetic patients.

Influence of thyroid hormones on biochemical parameters of liver function: a case-control study in North Indian population

Normal level of thyroid hormones is important for normal hepatic function and thyroid dysfunction may modulate metabolic function of liver. The purpose of this study is to determine whether liver function is associated with subclinical and overt hypothyroidism. Thyroid and liver function tests were evaluated in 47 patients with overt (TSH ≥10.0 mIU/L) and 77 patients with subclinical hypothyroidism (TSH 6.0-9.9mIU/L) and compared with 120 age-matched euthyroid controls. Subjects with overt hypothyroidism had significantly raised serum ALT, AST, ALP and total protein levels as compared to controls whereas subclinical hypothyroid patients had significantly increased levels of serum ALT, ALP and total protein. Further, TSH showed significant positive correlation with AST and ALP values whereas fT3 and fT4 had a negative correlation with AST in overt hypothyroidism. Thus, overt hypothyroid state is associated with significant derangement in biochemical parameters of liver function. Hence, liver function should be regularly monitored in hypothyroid patients. Keywords : Hypothyroidism; Liver function tests; Free T3 and T4; TSH; AST Internet Journal of Medical Update 2013 January;8(1):4-8

Atherogenic Index of Plasma and Oxidised LDL in Overt Hypothyroidism in North Indian Female Population

Introduction: Hypothyroidism is a clinical condition characterized by reduced oxidative metabolism and it is characterised by markedly increased plasma levels of lipid and lipoprotein. There is insufficient data on lipid levels from India in patients with hypothyroid; only a few studies have been performed in north India. We used oxidised LDL and atherogenic index to better understand the risk for atherosclerosis and coronary heart disease in hypothyroidism. So this study has been done in hypothyroidism which represents an important risk factor for atherosclerosis. Aims and objectives: This study was done to study the association of blood lipids, oxidised LDL and atherogenic index of plasma between hypothyroid patients and control. Material and methods: In the present study 30 hypothyroid patients and 30 healthy controls with no evident disease were included after taking an informed consent. The study was done in the hormone laboratory of a tertiary care hospital of north India. Fasting venous blood samples were obtained and Serum Lipids were measured by standard automated enzymatic techniques. Oxidised LDL was assayed with ELISA technique. Serum TSH, free T4 (ft4) and free T3 (ft3) were assayed using chemiluminescence. Statistical analysis was carried out using SPSS for windows 14.0 software (SPSS Inc.,Chicago, IL, USA). Result and observation: Hypothyroid patients had statistically significant higher levels of TSH and low levels of ft3 and ft4. There was a statistically significant decrease in the levels of HDL. The change in the levels of the atherogenic index of plasma (log LogTG/HDL) was also significant statistically (p value 0.000). There was an increase in the levels of oxidised LDL in hypothyroid patients as compared to controls but this was not statistically significant. Conclusion: The atherogenic index of plasma is better correlated with hypothyroidism and hence it can be used for risk assesment of atherosclerosis in hypothyroid patients. To establish oxidised LDL as a marker further studies are needed.