Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

INTRODUCTION: Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. OBJECTIVES: We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. METHODS: Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. RESULTS: We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. CONCLUSION: Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα.

OBJECTIVES: Increased fructose consumption causes dyslipidemia and fatty liver in postmenopausal women, both independent risk factors for cardiovascular disease. This study explored the potential mechanisms by which amla (Emblica officinalis) reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver in a fructose-fed, ovariectomized rat model of menopause. METHODS: Sham-operated and ovariectomized rats were put on a chow or high fructose diet. They were further divided into groups with or without amla. After 18 weeks of treatment, livers were harvested and subjected to Western blot and histological analyses. RESULTS: In all groups, amla increased the protein expression of liver farnesoid X receptor (FXR) and liver X receptor (LXR), key proteins involved in lipid metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here amla produced an exceptional rise in LXR and insulin-induced gene-2 (Insig-2) which prevented the maturation of sterol regulatory element-binding protein-1 and steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also increased the protein expression of ATP binding cassette transporter A1 (ABCA1), involved in high density lipoprotein (HDL) synthesis as well as low density lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides this, amla increased the protein expression of peroxisome proliferator activated receptor α (PPARα) involved in ß oxidation of fatty acids. CONCLUSIONS: Amla increased the protein expression of liver FXR, LXRα, PPARα and their downstream proteins Insig-2, ABCA1 and LDLR. This property of amla to modulate some of the key proteins involved in lipid metabolism promises its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.

Association of sympathovagal imbalance with cardiovascular risks in patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risks like obesity, insulin resistance, dyslipidemia that can lead to sympathovagal imbalance (SVI). The study was designed to assess the cardiovascular risk in PCOS and link of metabolic derangements to SVI. Thirty-five newly diagnosed PCOS patients and 32 age-matched controls were recruited. Waist-hip ratio, body mass index (BMI), basal cardiovascular parameters such as basal heart rate (BHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and rate pressure product (RPP) were recorded. Autonomic functions were assessed using short-term heart rate variability (HRV) analysis, heart rate and blood pressure response to standing (30:15 ratio), deep breathing (E:I ratio) and isometric handgrip (ΔDBPihg). Fasting plasma glucose, insulin, lipid profile and testosterone were assayed. Insulin resistance (HOMA-IR) and lipid risk factors were calculated. The cases had increased BHR, BMI, SBP, DBP, MAP and RPP. The ratio of low-frequency to high-frequency (LF-HF) of HRV, the marker of SVI was significantly increased in cases. 30:15 ratio and ΔDBPihg were increased and E:I ratio was decreased in the cases. HOMA-IR, lipid risk factors and testosterone were significantly elevated in cases. There was a significant correlation of LF-HF with BMI, BHR, RPP, insulin resistance and lipid risk factors. On regression analysis, insulin resistance and lipid risk factors had independent association with LF-HF. PCOS patients have SVI, decreased HRV and increased RPP and the potential cardiovascular risks. The insulin resistance and dyslipidemia contribute to SVI and cardiovascular risks in PCOS patients.

Pentraxin-3 and nitric oxide as indicators of disease severity in alcoholic cirrhosis.

Recent studies have indicated that pentraxin-3 can be used as a marker to assess the severity of hepatic fibrosis in non-alcoholic steatohepatitis. The present study was designed to assess pentraxin-3, nitric oxide and tumour necrosis factor-α (TNFα) in alcoholic cirrhosis and their association with disease severity. We enrolled 47 alcoholic cirrhosis cases and 32 controls. Serum pentraxin-3, nitric oxide (NO) and TNFα levels were estimated in both groups. Serum pentraxin-3, NO and TNFα were significantly increased in alcoholic cirrhosis patients compared to controls. Pentraxin-3 had a significant positive correlation with TNFα (r=0.303, P=0.039), Child-Pugh score (r=0.394, P=0.006) and MELD score (r=0.291, P=0.047) in alcoholic cirrhosis cases. Also we found positive association between NO with Child-Pugh score (r=0.391, P=0.007) and MELD score (r=0.311, P=0.033) in these cases. Linear regression analysis shows significant association of pentraxin-3 and NO (ß=0.375, r2=0.141, P=0.009). We conclude that elevated pentraxin-3 and NO levels are associated with severity of alcoholic cirrhosis.

TNFAIP3 and TNIP1 polymorphisms confer psoriasis risk in South Indian Tamils.

Psoriasis is a chronic inflammatory skin disease with genetic and environmental factors having an important role in its aetiology. Several genome-wide association studies have reported the association of the genes of the TNFα signalling, tumour necrosis factor alpha-induced protein 3 (TNFAIP3), TNFAIP3-interacting protein 1 (TNIP1) with psoriasis in Western and Chinese populations. The aim of this study is to demonstrate whether the TNFAIP3 and TNIP1 genes contribute to the risk of psoriasis in the ethnically distinct South Indian population. 360 psoriatic subjects and 360 healthy controls were recruited in this case control study. TNFAIP3 (rs610604) and TNIP1 (rs17728338) polymorphisms were typed by using TaqMan 5 allele discrimination assay. The results demonstrated that the SNPs rs610604 and rs17728338 of the TNFAIP3 and TNIP1 genes, respectively, were associated with psoriasis in our population at both allelic and genotypic levels. Thus, our results suggest that TNFAIP3 (rs610604) and TNIP1 (rs17728338) polymorphisms confer increased risk of psoriasis and may play a vital role in its pathogenesis in our ethnic South Indian Tamils.

Platelet activation in chronic urticaria and its correlation with disease severity.

Chronic urticaria (CU) is characterized by the occurrence of wheals lasting for more than 6 weeks. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook a cross-sectional study among 45 patients with CU and 45 age- and gender-matched healthy controls. The severity of the disease was assessed using the urticaria severity score. The autologous plasma skin test (APST) was done in all cases of CU. The platelet count and indices were estimated by an automated haematological laser optical analyzer. Platelet aggregation and soluble P-selectin levels were estimated in all study participants. It was observed that there was a significantly higher mean platelet volume (MPV) and platelet distribution width (PDW) in patients with CU when compared to controls. Platelet aggregation and soluble P-selectin levels were significantly higher in patients with CU, as compared to controls. Urticaria severity score correlated positively with platelet aggregability and soluble P-selectin levels. APST-positive patients had significantly higher platelet aggregation and higher soluble P-selectin levels, when compared to the APST-negative patients, indicating more platelet activation in the autoimmune group. There is significant platelet activation in patients with CU, especially in those with autoreactivity.

Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria.

BACKGROUND: Recent studies implicate the role of immune-inflammatory responses in chronic spontaneous urticaria (CSU). Although it is well known that platelets release inflammatory mediators and reactive oxygen species upon activation, their role in CSU is poorly characterized. The present study was designed to evaluate platelet oxidative stress [platelet malondialdehyde (MDA), platelet superoxide dismutase (SOD), platelet glutathione peroxidase (GPx)] and systemic inflammatory markers [plasma Interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP)] in patients with CSU and their association with disease severity. METHODS: Forty-five patients with CSU and 45 age- and gender-matched healthy controls were included in the study. Severity grading was completed according to the urticaria severity score (USS). Autologous plasma skin test (APST) was done in all patients with CSU. Platelet MDA, SOD and GPx and inflammatory markers plasma IL-6 and hs-CRP were assayed in all study participants. RESULTS: In patients with CSU, platelet SOD and GPx were significantly lowered, while platelet MDA levels were significantly elevated in comparison to healthy controls. Both IL-6 and hs-CRP were significantly elevated in patients with CSU and correlated with platelet oxidative stress parameters (p<0.05). Platelet MDA, SOD and GPx and inflammatory markers (plasma IL-6 and hs-CRP) showed a significant correlation with USS in patients with CSU. CONCLUSIONS: Our results indicate significant systemic inflammation and platelet oxidative stress in patients with CSU.

Role of ventromedial hypothalamus on energy homeostasis in albino rats: effect of gender.

Various brain areas like the ventromedial hypothalamus (VMH) are known to influence food intake and body weight. Though obesity is more common in females, the reports on gender difference in the neural regulation of energy homeostasis are not adequate. Therefore, the present study was conducted to assess the gender difference in the effect of VMH lesion on food intake (FI), body weight (BW), serum lipid profile, thyroid profile, glucose and insulin levels and glucose-insulin ratio (GIR) in Wistar albino rats. Twenty-four Wistar albino rats were divided equally into control and experimental groups with 6 male and 6 female rats in each. In the experimental group, bilateral electrolytic lesion of VMH was performed by stereotaxy and post-lesion parameters were recorded. In the control group, VMH sham lesion was made. Male-female difference in each parameter was determined. Following VMH lesion, FI was increased (females, P < 0.01) and BW (males, P < 0.05) and GIR decreased in males (P < 0.001), which was significantly correlated with BW. T3 was more significantly correlated with FI and BW in females (P < 0.000 and P < 0.001). Following VMH lesion, male rats exhibited significant weight gain in the absence of proportionate hyperphagia indicating that weight-gain was mainly metabolic in nature. Also, the male rats developed more susceptibility to insulin resistance. The female rats developed resistance to weight-gain inspite of hyperphagia, which could be due to the higher T3 level.

Effect of lesion of nucleus septal medialis on energy homeostasis in Wistar rats.

Mesolimbic areas such as nucleus accumbens, amygdala and septal nuclei are known to influence food intake and body weight. However, the reports on gender difference in the neural regulation of obesity and energy homeostasis are incomplete. Therefore, the present study was conducted to assess the effect of lesions of nucleus septal medialis (NSM) and the gender difference of lesion on food intake (FI), body weight (BW), serum lipid profile, thyroid profile, glucose and insulin levels and glucose-insulin ratio (GIR) in Wistar albino rats. Twenty-four rats were divided equally into control and experimental groups having 6 male and 6 female rats in each group. In the experimental group, bilateral electrolytic lesion of NSM was performed by stereotaxy and post-lesion parameters were recorded. In the control group, sham-lesions of NSM were produced. Following lesion, blood glucose and serum insulin levels were decreased and GIR was increased significantly in female rats, but not in male rats. It was concluded that NSM is involved in energy homeostasis, especially in female rats.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis. OBJECTIVES: We determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils. METHODS: 300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5' allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA. RESULTS: VEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity. CONCLUSIONS: Our results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.

Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort.

BACKGROUND: Psoriasis is a T-cell mediated chronic systemic inflammatory skin disease. Emerging evidences suggest the interleukin (IL)-12B and IL-23R genes encoding the common p40 subunit of IL-12 and IL-23 are the key cytokines in T-helper (Th)1 and Th17 differentiation and function. Certain allelic variants of these genes significantly influence the risk of psoriasis. Hence we undertook to study the association of IL-12B and IL-23R gene polymorphisms with disease susceptibility in South Indian Tamil patients with psoriasis. METHODS: 360 psoriatics and 360 healthy controls were included in this case control study. IL-12B gene (rs3212227) and IL-23R gene (rs2201841, rs10889677 and rs11805303) polymorphisms were typed by using TaqMan 5'allele discrimination assay and cytokine levels were assayed by ELISA. RESULTS: We observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis. We did not find any significant association between IL-23R (rs10889677 and rs11805303) gene polymorphisms and psoriasis risk in South Indian Tamil population. We did not observe any significant difference in haplotypes between the psoriasis cases and controls. We observed a significant increase in the mean IL-23 levels in psoriatics and the higher levels of IL-23 were found in the minor variant genotype CC when compared with that of heterozygous CT and major variant TT genotypes of rs2201841. Individual genotypes of rs10889677 and rs11805303 and IL-12 (rs3212227) were not significantly associated with their plasma levels. CONCLUSION: Our results suggest that IL-12B (rs3212227) and IL-23R (rs2201841) polymorphisms confer increased risk of psoriasis in our ethnic South Indian Tamils.

The HLA-C*06 allele as a possible genetic predisposing factor to psoriasis in South Indian Tamils.

Psoriasis is a multi-factorial heritable prototypical immune-mediated inflammatory disease, characterized by hyperproliferation of keratinocytes in the affected skin. There are no studies till date, to the best of our knowledge, about the association of HLA-C*06, the risk variant in the PSORS 1 susceptibility locus that confers the greatest risk for early onset of psoriasis, with the disease in South Indian Tamil patients with psoriasis. The present study was performed to determine the association of HLA-C*06 with psoriasis in the South Indian Tamil ethnic population. Three hundred and fifty-five cases of psoriasis and 360 healthy controls were included in this case-control study. Severity grading according to psoriasis area severity index (PASI) scoring was done in patients with psoriasis. PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-C*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-C*06. We observed that those with the HLA-C*06-positive allele had a 3.5 times higher odds of having psoriasis compared to those without, [p < 0.0001, OR 3.5, 95 % CI (2.59-4.79)]. Among cases of psoriasis, it was noted that there was a significant association of HLA-C*06 positivity with female psoriatics [p = 0.006; OR 2.49 (1.28-4.87)] and early age of onset of psoriasis [p = 0.002; OR 2.04 (1.29-3.20)]. Our results suggest that the HLA-C*06 allele is positively associated with susceptibility to psoriasis, female gender and early onset of psoriasis in South Indian Tamils.

Effects of vitamin D and calcium supplementation on side effects profile in patients of breast cancer treated with letrozole.

BACKGROUND: Vitamin D deficiency (<10ng/mL) and insufficiency (10-30ng/mL) may contribute to musculoskeletal symptoms observed in patients taking letrozole. This study was undertaken to assess the vitamin D status in breast cancer patients who received letrozole for >2months and to see the effects of vitamin D3 and calcium supplementation on them. METHODS: Eighty-two breast cancer patients were included. Baseline serum 25-hydroxy vitamin D concentrations were assayed and standard questionnaire was completed. They were given vitamin D3 and calcium supplementation (2000IU/1000 mg and 4000IU/1000mg) based on their baseline serum 25-hydroxy vitamin D concentration for 12weeks. RESULTS: Baseline serum 25-hydroxy vitamin D concentrations showed that 13.4% of patients were deficient and 73.2% of patients were insufficient in 25-hydroxy vitamin D. There was an increase in the concentrations of calcium, phosphorus and decrease in the concentrations of parathyroid hormone, alkaline phosphatase as the concentration of serum 25-hydroxy vitamin D increases. Patients who received letrozole for a longer duration had a low concentration of serum 25 (OH) vitamin D. Vitamin D3 and calcium supplementation increased the concentrations of calcium, phosphorous and decreased the concentrations of parathyroid hormone and alkaline phosphatase. Patients who had low serum 25-hydroxy vitamin D concentrations had more musculoskeletal symptoms which was improved following supplementation (9.14 vs 8.10 p=0.000). CONCLUSION: Vitamin D3 supplementation significantly improved serum 25-hydroxy vitamin D concentrations and decreased letrozole-induced arthralgia.

Markers of Oxidative Stress in Pregnant Women with Sleep Disturbances.

OBJECTIVE: The quality and duration of sleep is impaired during pregnancy. Our study aimed to determine whether maternal sleep deprivation occurring during the second and third trimester of pregnancy could alter fetal well-being with respect to birth weight and APGAR score by altering the inflammatory status and oxidative stress in the mothers. . METHODS: Sleep adequacy was assessed using the Pittsburgh Sleep Quality Index (PSQI). We investigated the inflammatory status and oxidative stress at term in the blood of pregnant subjects with and without sleep deprivation by measuring the levels of protein-bound sialic acid (PBSA), high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA) and protein carbonyl (PCO). Homocysteine (Hcy) and its vitamin determinants were also measured. Fetal outcome with respect to birth weight and APGAR score were compared between study subjects. . RESULTS: A significant increase was observed in the levels of hsCRP, PBSA, Hcy, MDA, and PCO, in the sleep-deprived group when compared to the control group. Fetal outcome at birth showed a significant difference between the cases with high sleep deprivation and those with low sleep deprivation. . CONCLUSION: Sleep deprivation in pregnancy leads to an increase in the inflammatory parameters, oxidative stress, and Hcy levels. Fetal outcome at birth was affected more in mothers with high sleep deprivation than those with low sleep deprivation. Follow-up in these babies are needed to reveal any differences in their growth and development.

Screening for diabetes among presumptive tuberculosis patients at a tertiary care centre in Pondicherry, India.

SETTING: Designated microscopy centre (DMC) attached to a tertiary care centre in Pondicherry, India. OBJECTIVES: To determine 1) the proportion of diabetes mellitus (DM), 2) the additional yield of newly diagnosed DM cases, and 3) the number needed to screen (NNS) to find a new case of DM among presumed TB patients. DESIGN: An institution-based cross-sectional study was carried out among 650 presumed TB patients attending the DMC. Capillary blood glucose was measured using fasting blood sugar and/or oral glucose tolerance test, and evaluated according to the World Health Organization criteria. RESULTS: Of 570 presumed TB patients evaluated for DM, 121 (21.2%) were found to be diabetic. Of these, 69 were previously known to have DM, while 52 were newly diagnosed. The additional yield of diabetes was 43%. The NNS to detect a new case of DM was 11; among those aged >40 years, the NNS was 9.3, and among smear-positive TB patients it was 4.6. CONCLUSION: One fifth of the presumed TB patients had diabetes, and nearly half of these patients were newly diagnosed. Opportunity screening of presumed TB patients for DM in routine care will help in early detection of diabetes and pre-diabetes.

Serotonin and interleukin-6: Association with pruritus severity, sleep quality and depression severity in Prurigo Nodularis.

Prurigo Nodularis (PN) is a chronic skin condition of unknown etiology. It is said to be associated with psychological factors. However, studies to identify the same are few. Hence, we undertook to assess the association between quality of sleep, depression, pruritus severity in cases of PN and to assess association of serum serotonin, interleukin (IL)-6 with sleep, depression and pruritus severity. This cross-sectional study involves 39 patients with PN and 39 age and gender matched healthy controls. Subjective quality of sleep, depressive symptom severity and pruritus severity were collected through clinician based interview. Serum serotonin and serum IL-6 were estimated by ELISA. Spearman correlation was used to assess the strength of association between biochemical parameters and clinical parameters. Cases had significantly higher percentage of depression, a higher score of depression severity, higher serum IL-6 level and lower serum serotonin levels. Serum serotonin and serum IL-6 showed significant correlation with the severity of pruritus (r=-0.66, p<0.01 and r=0.60, p<0.01). However, both these parameters showed a significantly negative correlation between them (r=-0.92, p<0.01). Though cause and effect cannot be established in this type of study, there is a disturbance of the inflammatory-neuroendocrine axis (interleukins-serotonin). PN is characterized by higher IL-6 and lower serotonin and greater depression severity than healthy controls. Findings of this study may have an influence on the treatment of PN.

Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters.

PROBLEM: Pathophysiological mechanisms contributing to abnormal cardiovascular (CV) parameters in obesity have not been fully elucidated. Role of sympathovagal imbalance (SVI) in the prediction of abnormalities in CV functions in obesity has not been studied. METHODS: Anthropometric indices, CV parameters, autonomic function tests (AFTs) such as spectral heart rate variability (HRV) analysis, heart rate and blood pressure response to standing, deep breathing, and isometric-handgrip, and biochemical parameters like insulin resistance (HOMA-IR), lipid risk factors and inflammatory marker [high-sensitive C-reactive protein (hsCRP)] were assessed in control group (non-obese, n=43) and obese group (n=45). Association of anthropometric indices and abnormal CV parameters with low-frequency to high-frequency ratio (LF-HF) of HRV was performed by Pearson's correlation. Independent contribution of anthropometric indices and abnormal CV parameters to LF-HF was assessed by using a multiple regression analysis. LF-HF prediction of rate-pressure product (RPP), the indicator of CV dysfunction was assessed by logistic regression. RESULTS: LF-HF, the marker of SVI was more in obese group compared to control group. AFTs of sympathetic activity were increased and of parasympathetic activity were reduced in obese group. Anthropometric indices, HOMA-IR, lipid risk factors and hsCRP were correlated with LF-HF. These metabolic biomarkers had independent contribution to SVI. Among, anthropometric indices, waist-to-height ratio (WHtR) had maximum association with LF-HF. LF-HF had significant prediction of RPP in obese group. CONCLUSION: SVI in obesity is due to both increased sympathetic and decreased vagal activity. Abnormal CV parameters in obesity are linked to SVI, which is contributed by insulin resistance, dyslipidaemia and low-grade inflammation. LF-HF predicts abnormal CV parameters in obesity.

High serum testosterone levels during postpartum period are associated with postpartum depression.

In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD.

Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis?

BACKGROUND: Psoriasis is an immune mediated inflammatory skin disease associated with systemic inflammation resulting in increased risk for associated cardiovascular co-morbidities. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook to study the platelet activation markers in psoriasis, as compared to controls and to identify its association with disease severity in psoriasis. METHODS: Sixty-two patients with psoriasis and 62 age and gender matched healthy controls were enrolled in this cross-sectional study. The severity of the disease was assessed using the psoriasis area severity index (PASI) scoring. The platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] were estimated by an automated haematological laser optical analyzer. Plasma soluble P-selectin and platelet derived microparticle (PDMP) concentrations, serum high sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentrations were estimated in all study participants. Platelet aggregation was assessed using adenosine diphosphate (ADP) as aggregating agent. RESULTS: We observed that there was significantly higher platelet indices (MPV and PDW) in patients with psoriasis, when compared to controls. Plasma soluble P-selectin concentrations, PDMP and platelet aggregation were significantly elevated in patients with psoriasis, as compared to controls. We also found significantly higher concentrations of hs-CRP and IL-6 in patients with psoriasis, as compared to controls. Platelet activation and systemic inflammation markers correlated positively with PASI, except PDW. We also observed significant positive correlation between platelet activation and systemic inflammation in psoriasis. CONCLUSION: Significant platelet activation and systemic inflammation were observed in patients with psoriasis, especially when associated with severe disease. The increased platelet activation might be the missing link between the persistent inflammation and the development of atherosclerotic plaque leading onto cardiovascular co-morbidities seen associated with psoriasis.

Effect of cyproheptadine on glucose tolerance, serum insulin and structure of pancreatic islets in rats.

The effect of cyproheptadine (CPH) on glucose tolerance, serum immunoreactive insulin (IRI) and structure of pancreatic islets in albino rats has been studied. Hyperglycemia with glucose intolerance was observed after 10 days of administration of CPH (40 mg/kg, ip). There was insignificant change of fasting IRI after the treatment. Histological studies indicated degranulation and vacuolation of beta cells with enlargement of capillaries. Improvement in blood glucose, glucose tolerance and structure of islets with proliferation of small pancreatic ducts and cell cords were observed 10 days after the withdrawal of CPH.