Interleukin-9 serves as a key link between systemic inflammation and angiogenesis in psoriasis.

BACKGROUND: Psoriasis is a T helper cell-mediated chronic immune-mediated inflammatory disease affecting mainly the skin, although systemic pathological effects are also observed. Cytokine-mediated interaction between T lymphocytes and keratinocytes lead to excessive proliferation of keratinocytes, which in turn leads to formation of a proinflammatory milieu and finally to psoriatic plaque formation. AIM: To measure interleukin (IL)-9, IL-17 and vascular endothelial growth factor (VEGF) levels in patients with psoriasis compared with controls, and to evaluate the effect of methotrexate (MTX) monotherapy on the aforesaid cytokine levels in psoriasis. METHODS: This cohort study included 54 patients with psoriasis and 54 age- and sex-matched healthy controls (HCs). IL-9, IL-17 and VEGF levels were measured by using commercially available ELISA kits. Patients with psoriasis who were on MTX monotherapy were followed up for a period of 3 months. RESULTS: Patients with psoriasis had increased levels of IL-9, IL-17 and VEGF at baseline, compared with the HC group. After 3 months of MTX monotherapy, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI) and levels of cytokines (IL-9, IL-17 and VEGF) were significantly decreased compared with baseline. PASI and DLQI at baseline also showed a positive correlation with IL-9, IL-17 and VEGF. CONCLUSION: Our results suggest the existence of a proinflammatory milieu in psoriasis, with increased levels of IL-9, IL-17 and the proangiogenic growth factor VEGF, showing an increasing trend with increasing disease severity and impaired quality of life (QoL). MTX treatment helps to reduce levels of IL-9, IL-17 and VEGF, thereby limiting disease progression and improving QoL in psoriasis.

Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD. METHODS: In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist. RESULTS: CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD. CONCLUSION: In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

Effect of methotrexate monotherapy on T-cell subsets in the peripheral circulation in psoriasis.

BACKGROUND: Psoriasis is a T-helper (Th)1/Th17-mediated chronic inflammatory disease. There is an increased population of Th cells in skin lesions and peripheral circulation of patients with psoriasis. Systemic methotrexate (MTX) is an effective treatment for moderate to severe psoriasis; however, its effect on different T-cell subsets is not yet clear. AIM: To study the effect of MTX monotherapy on the psoriatic T-cell profile in the peripheral circulation of patients with psoriasis. METHODS: This was a follow-up study involving 50 patients with moderate to severe psoriasis treated with systemic MTX for 12 weeks. Blood samples (5 mL) were collected from participants, from which PBMCs were isolated, and T-cell phenotyping was performed by flow cytometry. RESULTS: Following 12 weeks of MTX treatment, there was an increase in the percentages of Th2/Treg cells, and a relative decrease in the percentages of Th1/Th17 cells, along with a significant reduction in the median Psoriasis Area and Severity Index (PASI). CONCLUSION: MTX helps in the restoration of the immune balance by decreasing the numbers of Th1 and Th17 cells and increasing the numbers of Th2 and Treg cells, thus resulting in a significant reduction in disease severity. MTX converts a proinflammatory T-cell phenotype to a protective anti-inflammatory phenotype, thus significantly suppressing the inflammation in psoriasis.

Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. RESULTS: CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. CONCLUSION: The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone.

Immunophenotyping of T cells in the peripheral circulation in psoriasis.

BACKGROUND: Psoriasis is a T-helper (Th)-1/Th17-mediated chronic inflammatory disease. Cytokine mediated interaction between T lymphocytes and keratinocytes lead to keratinocyte hyper-proliferation, which leads to further inflammation in the psoriatic plaques. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in psoriasis. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is understudied. Our aim was to study the immune-phenotype of the different T-helper/T-reg cell subsets in patients with psoriasis, with respect to healthy controls. MATERIALS AND METHODS: A total of 189 cases of psoriasis and 189 age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease severity was determined by psoriasis area severity index (PASI) scoring. Peripheral blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. RESULTS: In psoriasis, we observed an imbalance in T-cell immunophenotype, characterised by an increase in Th1/Th17 cells and a relative decrease in Th2/T-reg cells, as compared to the healthy controls. We also found that the percentage of Th1/Th17 cells showed a linear trend, increasing with increasing disease severity (PASI). CONCLUSION: Our results suggest an immune-dysregulation in psoriasis associated with a predominance of Th1/Th17 phenotype, especially with increasing severity of the disease.

Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

BACKGROUND: Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. METHODS: We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. RESULTS: We observed a significantly decreased serum bilirubin levels (p < 0.001) in patients with lower eGFR values, compared to those with higher eGFR levels. There was a significant positive correlation between the eGFR levels and the total bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p < 0.001). CONCLUSIONS: Our results suggest that there is significant hypobilirubinemia in CKD, especially with increasing severity and co-existing diabetes mellitus. This finding has importance in the clinical setting, as assay of simple routine biochemical parameters such as serum bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry.

Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching-learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (<50%: group 1, n = 23), medium (50-75%: group 2, n = 74), and high (>75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016.

Comprehensive lipid tetrad index, atherogenic index and lipid peroxidation: Surrogate markers for increased cardiovascular risk in psoriasis.

BACKGROUND AND OBJECTIVES: Recently, the concept of "psoriatic march" has come to the fore, in which chronic cutaneous inflammation in psoriasis leads to systemic inflammation which, in conjunction with increased oxidative stress, triggers a cascade of events resulting in increased cardiovascular risk in patients with severe psoriasis. We, therefore, decided to study the levels of some biochemical cardiovascular risk markers: lipid peroxidation (malondialdehyde), lipoprotein (a), lipid indices and atherogenic index, in patients with psoriasis and their association with disease severity. METHODS: Forty five patients with psoriasis and 45 age and gender-matched healthy controls were included in this cross-sectional study. Disease severity was assessed by the Psoriasis Area Severity Index (PASI). Serum malondialdehyde, lipoprotein (a) and fasting lipid profile were estimated in all study subjects. Lipoprotein ratios were computed using standard formulae. Atherogenic index was calculated as ratio of lipoprotein (a)/high-density lipoprotein. RESULTS: In psoriasis, we observed significantly higher levels of malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lipoprotein (a), lipid ratios, atherogenic index and comprehensive lipid tetrad index, compared to controls. These levels were directly proportional to disease severity. Serum levels of malondialdehyde correlated positively with serum lipoprotein (a), comprehensive lipid tetrad index and atherogenic index. LIMITATIONS: Different morphological types of psoriasis were not included and follow-up post-therapy was not done. A larger sample size would have validated the results further. CONCLUSION: Our results indicate that psoriasis, especially the severe variants, are associated with increased oxidative stress and dyslipidemia, which correlate positively with atherogenic index and hence, an increased cardiovascular risk.