Relationship between difference of preoperative and cardiopulmonary bypass mean arterial pressure, and acute kidney injury in cardiac surgical patients undergoing valve surgery.

BACKGROUND: Modifiable and non-modifiable factors contribute to development and progression of acute kidney injury (AKI) during cardiac surgery. We hypothesized that, the difference between preoperative mean arterial pressure (MAP) and the average mean arterial pressure maintained on cardiopulmonary bypass (CPB) would be strongly predictive of AKI. We also measured plasma Neutrophil gelatinase-associated lipocalin (NGAL), to establish its association with cardiac surgery associated-AKI (CSA-AKI). METHODS: One hundred and twelve high-risk patients undergoing valve, and valve plus coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB) were included in this study. Delta mean arterial pressure (MAP) was calculated as the difference between the average of pre-operative and on-bypass MAP, and blood was sampled for NGAL levels, at baseline, and 6-h after CPB. Detailed data collection was done, tabulating most of the factors which might influence development of post-operative cardiac surgery associated-AKI (CSA-AKI). To define CSA-AKI within the first 24-h post-operatively, the Kidney Disease Improving Global Outcomes (KDIGO) classification was used. RESULTS: Out of 112 patients, 44 (39.3%) developed CSA-AKI postoperatively. With an ROC analysis cut-off of delta MAP of more than 25.67 mmHg, 46.4% patients developed post-operative AKI, and the average CPB flows which were 1.8 ± 0.2 were not contributory to the development of early CSA-AKI. In our study, ELISA test for human NGAL was performed on serum samples, and the estimated cut-off value of 1661 ng/mL was found to be significantly associated with early CSA-AKI. CONCLUSIONS: Delta MAP and CPB flows are not related to early post-surgical CSA-AKI in cases with prior high-risk elements. However, baseline serum NGAL, as well as its percent change during the early post-surgical period independently predicted the development of CSA-AKI. This implies that, there may be patients with a higher pre-operative preponderance to develop this complication, which could actually be delineated by the use of serum NGAL estimations at baseline.

Neurotrophin-3 gene polymorphism in schizophrenia and its relation with diseases severity and cognitive dysfunction.

Objectives: Synaptic plasticity markers are known to alter in schizophrenia. The objective of the study was to investigate the genotype and allele frequency of neurotrophin-3 (NT-3) gene polymorphism (rs6489630, rs6332, and rs11063714) and plasma NT-3 levels in schizophrenia and their relation with cognitive status. Materials and Methods: The study was conducted on 216 Schizophrenia patients and 216 controls. Single-nucleotide polymorphism (SNP) of NT-3 and its plasma levels were assessed in both groups. Cognitive status was evaluated using Addenbrooke Cognitive examination-III scores. Results: The rs6489630 polymorphism was found to be significantly associated with the severity of schizophrenia (P = 0.004). The CT genotype (P = 0.02, OR = 1.631 [1.10-2.43]) and minor allele T (P = 0.004, OR = 1.58 [1.16-2.16]) of rs6489630 conferred an increased susceptibility to develop schizophrenia. The rs6332 variant was found to affect cognitive status significantly in schizophrenia (P = 0.040), and memory dysfunction was seen in individuals with AG (P < 0.01) and AA variant (P = 0.03) of rs6332. Conclusion: We conclude that SNPs of NT-3 enhance the risk of schizophrenia and are related to cognitive dysfunction.

Stress and psoriasis: Exploring the link through the prism of hypothalamo-pituitary-adrenal axis and inflammation.

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting mainly the skin. Chronic stress leads to the blunted hypothalamic-pituitary-adrenal axis (HPA) that might induce pro-inflammatory conditions. Hence, we assessed the blood levels of the HPA hormones and interleukin-17 (IL-17) and the effect of stress and emotional distress to understand the link between stress and psoriasis better. METHODS: This cross-sectional study included 45 patients with psoriasis and 45 age and gender-matched apparently healthy volunteers (n = 45). IL-17, cortisol, and adrenocorticotrophic hormone (ACTH) levels were assessed in both groups. Psoriasis Area Severity Index (PASI) was used to assess disease severity. Presumptive Stressful Life Events scale [PSLE], Perceived Stress scale [PSS] and Daily Hassles and Uplifts Scale [DHUS] scoring were used to assess stress levels and emotional distress. RESULTS: Patients with psoriasis had higher levels of IL-17 and ACTH and lower levels of cortisol, as compared to controls. Stress scores (PSS, PSLE & DHUS) were significantly elevated in cases, as compared to the controls. IL-17, ACTH and stress scores showed a significant positive correlation with one another and a significant negative correlation with cortisol levels. They also showed a significant positive correlation with PASI, while cortisol levels showed a significant negative correlation. CONCLUSION: Psoriasis patients having high ACTH, IL-17 and stress scores had lower levels of cortisol, indicating a dysregulated HPA axis with the pro-inflammatory state. This might lead to exacerbation of psoriatic flares, which needs investigation in further prospective studies.

Etiology and outcomes of acute kidney disease in children: a cohort study.

BACKGROUND: There is paucity of information regarding the etiology and outcomes of Acute Kidney Disease (AKD) in children. METHODS: The objectives of this cohort study were to evaluate the etiology and outcomes of AKD; and analyze predictors of kidney survival (defined as free of CKD 2, 3a, 3b, 4 or 5). Patients aged 1 month to 18 years who developed AKD over a 4-year-period (January 2018-December 2021) were enrolled. Survivors were followed-up at the pediatric nephrology clinic, and screened for residual kidney injury. RESULTS: Among 5710 children who developed AKI, 200 who developed AKD were enrolled. The median (IQR) eGFR was 17.03 (10.98, 28) mL/min/1.73 m2. Acute glomerulonephritis, acute tubular necrosis (ATN), hemolytic uremic syndrome (HUS), sepsis-associated AKD, and snake envenomation comprised of 69 (34.5%), 39 (19.5%), 24 (12%), 23 (11.5%) and 15 (7.5%) of the patients respectively. Overall, 88 (44%) children required kidney replacement therapy (KRT). There were 37 (18.5%) deaths within the AKD period. At a follow-up of 90 days, 32 (16%) progressed to chronic kidney disease stage-G2 or greater. At a median (IQR) follow-up of 24 (6, 36.5) months (n = 154), 27 (17.5%) had subnormal eGFR, and 20 (12.9%) had persistent proteinuria and/or hypertension. Requirement of KRT predicted kidney survival (free of CKD 2, 3a, 3b, 4 or 5) in AKD (HR 6.7, 95% CI 1.2, 46.4) (p 0.04). CONCLUSIONS: Acute glomerulonephritis, ATN, HUS, sepsis-associated AKD and snake envenomation were common causes of AKD. Mortality in AKD was 18.5%, and 16% progressed to CKD-G2 or greater at 90-day follow-up.

In vitro detection of suspected drug in maculopapular drug reaction to antibiotics using secreted cytokines from drug-specific activated T cells.

BACKGROUND: Maculopapular drug eruption (MPE) in reaction to antibiotics is associated with enhanced expression of T-helper (Th)1 cytokines such as interferon gamma (IFN-gamma) or Th2 cytokines such as interleukin (IL)-5. Identifying the culprit drug usually involves rechallenge, which may not be forthcoming. Memory lymphocytes remain responsive to the culprit drug long after the reaction has resolved. On reactivation in vitro, there is increased proliferation and expression of certain markers, which provides us with an opportunity to predict the causal drug. OBJECTIVES: The study aimed to assess drug-specific cytokine production (IL-5 and IFN-gamma) in peripheral blood mononuclear cell (PBMC) culture supernatants to predict the causal antibiotic in cases of MPE. METHODS: PBMCs of 18 patients who developed MPE to 20 suspected antibiotics (2 patients had 2 suspected antibiotic allergies each), along with 11 drug-matched healthy controls, were incubated for 5 days with the respective drugs at 2 different concentrations. Secreted cytokines were measured in the supernatants, using enzyme-linked immunosorbent assay (ELISA) for IL-5 and IFN-gamma, at 6 h of incubation, then on day 2 and day 5. RESULTS: Drug-specific IL-5 and IFN-gamma production could be demonstrated in 65% and 74% of the cases, respectively. Maximal secretion of IL-5 and IFN-gamma was observed on day 5 and day 2 of incubation, respectively. The cut-off delta values, defined as the difference in cytokine concentration between drug-stimulated and unstimulated samples, were 4 pg mL-1 for IL-5 and 6 pg mL-1 for IFN-gamma. CONCLUSIONS: The measurement of drug-specific secretion of IL-5 and IFN-gamma using ELISA is a valuable method for detecting antibiotic-induced MPE.

Association of hyperglycaemia and hyperlipidaemia with cognitive dysfunction in schizophrenia spectrum disorder.

The objective of the study was to investigate the association of blood glucose and lipid profile parameters with cognitive impairment in schizophrenia. A total of 200 schizophrenia patients and 169 controls were enrolled in the study. Blood glucose and lipid profile were estimated in all the subjects. Cognition was assessed using Addenbrooke cognitive examination-III (ACE-III). Fasting glucose (p ≤ .001) and triacylglycerol (p = .018) were increased and HDL-Cholesterol (p ≤ .001), was reduced in schizophrenia. Glucose (r = -0.158, p = .026), total cholesterol (r = -0.249, p = .0001) and triacylglycerol (r = -0.168, p = .018) was negatively correlated with total ACE III score. Triacylglycerol (p = .041) was elevated in cases with mild cognitive impairment. Plasma glucose, total cholesterol and triacylglycerol were associated with various cognitive domains suggesting that hyperglycaemia and hyperlipidaemia might increase the risk of cognitive impairment in schizophrenia.

Early Markers of Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVES: To detect early atherosclerosis changes using flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (CIMT), inflammatory markers (hs-CRP, IL-6), and endothelial markers (sICAM and sVCAM). METHODS: The authors recruited 4 to 18-y-old children with type 1 diabetes mellitus (T1DM) and age- and sex-matched normal children, excluding those with familial hypercholesterolemia, syndromic disorders, and cardiovascular disease. CIMT and FMD were measured in both the groups. Biomarkers hs-CRP, IL-6, sICAM, and sVCAM, were analyzed in the T1DM group. RESULTS: Forty T1DM children and 40 controls with 27 (67.5%) girls were enrolled in each group. The mean age was 9.68 y. The T1DM group had 4 (10%) obese and 4 (10%) overweight children. Among cases, 9 (22.5%) had diabetes for > 5 y, 24 (60%) required daily insulin between 0.8 and 1.2 IU/kg/d and 26 (65%) had HbA1c > 10 g/dL. The CIMT values were significantly higher in cases (0.69 mm) than in controls (0.59 mm); 29 (72.5%) cases had abnormal combined CIMT values. FMD was lesser in cases than in controls but not significant. The median values of hs-CRP, IL-6, sICAM, sVCAM were 0.81 mg/L, 6.27 pg/mL, 46.33 ng/mL and 668.81 ng/mL, respectively. A significant correlation of IL-6 with CIMT (r = 0.543, p = < 0.001) and sICAM with FMD (r = -0.397, p = 0.011) was observed. VCAM was low in the obese and overweight children. CONCLUSION: Children with type 1 diabetes had higher CIMT than normal children, whereas FMD did not differ. The association between elevated inflammatory markers with high CIMT and low FMD indicates that inflammation plays an essential role in endothelial dysfunction.

Prevalence and Patterns of Latex Glove Allergy among Healthcare Workers in a Tertiary Care Center In South India - A Cross-Sectional Study.

Background: Latex glove allergy and its impact on healthcare workers (HCWs) have been studied in many countries, but the data is scarce from developing countries. Objectives: We wanted to estimate the prevalence and patterns of latex glove allergy among HCWs and to study the factors associated with it. Materials and Methods: We conducted a cross-sectional study among 1088 HCWs of a tertiary care center in South India with the screening questionnaire adopted from "Allergy and Asthma network." Skin prick test, patch test, and serum total immunoglobulin E (IgE) were performed only in consenting symptomatic HCWs. Results: The prevalence of latex glove allergy in our study subjects was 9.1% (99/1088). This includes latex protein allergy and contact dermatitis to rubber glove allergens. The most common manifestation of latex glove allergy was irritant contact dermatitis observed in 68 HCWs (68.6%). Other presentations were allergic rhinitis (40.4%), allergic contact dermatitis (17.1%), contact urticaria (11.1%), allergic conjunctivitis (6.06%), and asthma (3.03%). The risk factors associated with latex glove allergy in our study were atopy (OR = 20.51), working in both ward and operation theater (OR = 26.6), auxiliary staff (OR = 4.75), and more than ten years of hospital work experience (OR = 3.85). Conclusion: Our study reported a high prevalence of latex glove allergy. With irritant contact dermatitis being the most common manifestation in our study, HCWs at risk shall be educated on the appropriate use of gloves and hand moisturizer to prevent occupational irritant contact dermatitis (ICD). We recommend further research to address the gaps in our knowledge around latex allergy in a healthcare setting.

Relationship Between Neural Cell Adhesion Molecule-1 and Cognitive Functioning in Schizophrenia Spectrum Disorder.

Abnormal synaptic plasticity leads to cognitive impairment in schizophrenia. Markers of synaptic plasticity are known to be altered in schizophrenia, but there are limited data available about neural cell adhesion molecule-1 (NCAM-1) levels and its association with cognitive functions in schizophrenia. The objective of the study was to analyze NCAM-1 levels and its association with various cognitive domains in schizophrenia. One hundred and seventy-six schizophrenia cases and 176 controls were recruited for the study. Serum NCAM-1 levels were analysed in both the groups. Cognitive examination was performed using Addenbrooke cognitive examination-III (ACE-III) and disease severity was assessed using Positive and negative symptoms scale (PANSS). Serum NCAM-1 levels were elevated in schizophrenia cases (p = 0.006) compared to controls. NCAM-1 was positively associated with attention (r = 0.196, p = 0.009), language (r = 0.192, p = 0.011), visuospatial abilities (r = 0.207, p = 0.006) and total ACE-III score (r = 0.189, p = 0.012). We conclude that elevated levels of NCAM-1 are associated with better cognitive functioning in schizophrenia.

Predictive markers in chronic kidney disease.

Chronic kidney disease (CKD) is defined by gradual deterioration of the renal parenchyma and decline of functioning nephrons. CKD is now recognized as a distinct risk factor for cardiovascular disease (CVD). This risk rises in tandem with the decline in kidney function and peaks at the end-stage. It is important to identify individuals with CKD who are at a higher risk of advancing to end-stage renal disease (ESRD) and the beginning of CVD. This will enhance the clinical benefits and so that evidence-based therapy may be started at the initial stages for those individuals. A promising biomarker must represent tissue damage, and be easy to detect using non-invasive methods. Current CKD progression indicators have difficulties in reaching this aim. Hence this review presents an update on markers studied in the last decade, which help in the prediction of CKD progression such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid-binding protein, cystatin-C, asymmetric dimethylarginine, symmetric dimethylarginine, endotrophin, methylglyoxal, sclerostin, uric acid, and miRNA-196a. Additional research is needed to determine the predictive usefulness of these indicators in clinical samples for disease development. Their utility as surrogate markers need to be explored further for the early identification of CKD progression.

Utility of Urinary Biomarkers Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as a Marker for Diagnosing the Presence of Renal Scar in Children with Vesicoureteral Reflux (VUR): A Cross-Sectional Study.

Aim: To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR). Materials and Methods: This cross-sectional study was conducted in 94 children aged 0-16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t-test, Mann-Whitney U-test, and analysis of variance Kruskal-Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars. Results: The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant (P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity. Conclusion: uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role.

Assessment of Causality in Hospitalized Children With Aminoglycoside-Related Nephrotoxicity.

OBJECTIVE: To evaluate the incidence of aminoglycoside-related nephrotoxicity and ascertain drug causality and its risk factors. METHODS: This prospective study was conducted from January, 2019 to January, 2021, and recruited 110 consecutively admitted children aged 1 month to 12 years, receiving aminoglycosides for ≥4 days. Drug causality was assessed using Liverpool adverse drug reaction causality assessment tool. RESULTS: 42 (38.2%) children developed acute kidney injury (AKI), with 71 (64.5%) having composite nephrotoxicity (AKI and/or tubular-dysfunction). Only 17 (15.5%) had AKI definitively attributable to aminoglycosides. Hypotension [OR 0.016 (95% CI 0.01-0.71), P=0.03], PRISM-III score 20-29% [OR 55.48 (95% CI 3.66-840.53), P=0.004] and post-surgery patients [OR 3.2 (95% CI 1.01-10.1), P=0.047] were independent predictors of AKI. Conclusions: Only a small proportion of children receiving aminoglycosides had AKI definitively attributable to the drug.

Perceptions about controlled human infection model (CHIM) studies among members of ethics committees of Indian medical institutions: A qualitative exploration.

Introduction: Controlled Human Infection Model (CHIM) studies provide a unique platform for studying the pathophysiology of infectious diseases and accelerated testing of vaccines and drugs in controlled settings. However, ethical issues shroud them as the disease-causing pathogen is intentionally inoculated into healthy consenting volunteers, and effective treatment may or may not be available. We explored the perceptions of the members of institutional ethics committees (IECs) in India about CHIM studies. Methods: This qualitative exploratory study, conducted across seven sites in India, included 11 focused group discussions (FGD) and 31 in-depth interviews (IDI). A flexible approach was used with the aid of a topic guide. The data were thematically analyzed using grounded theory and an inductive approach. Emerging themes and sub-themes were analyzed, and major emergent themes were elucidated. Results: Seventy-two IEC members participated in the study including 21 basic medical scientists, 29 clinicians, 9 lay people, 6 legal experts and 7 social scientists. Three major themes emerged from this analysis-apprehensions about conduct of CHIM studies in India, a perceived need for CHIM studies in India and risk mitigation measures needed to protect research participants and minimize the associated risks. Conclusion: Development of a specific regulatory and ethical framework, training of research staff and ethics committee members, and ensuring specialized research infrastructure along with adequate community sensitization were considered essential before initiation of CHIM studies in India.

Therapeutic outcome of diphencyprone and its correlation with serum cytokine profile in alopecia areata.

INTRODUCTION: Diphencyprone (DPCP) is considered as the first line of management in severe and extensive alopecia areata. The present study aims to evaluate the effectiveness of DPCP in alopecia areata and identify various prognostic factors and biomarkers associated with clinical response. MATERIALS AND METHODS: The study included participants with patchy and extensive alopecia areata (>30% scalp hair loss) treated with DPCP. Participants with Macdonald Hull and Norris grade 3 and 4 at the end of 6 months were considered as responders. We performed cytokine analysis prior and post-therapy. The protocol was registered with CTRI (REF/2017/09/015424). RESULTS: The response rate was 54.5%. Longer disease duration, nail involvement, and high severity of alopecia tool (SALT) scores were associated with non-response. There was no significant difference in the cytokine levels among responders and non-responders before therapy. Among the responders, we found a significant decrease in IFN-γ, IL-17A, IL-9, TGF-ß, and IL-13 except for IL-4, which significantly increased whereas, among the non-responders, only IL-17A and IL-13 levels have reduced considerably. DISCUSSION: Diphencyprone reduced the level of Th1, Th17, and Th9 cytokines and increased the level of Th2 cytokines (IL-4) in the present study, which induced remission and promoted hair regrowth.

Evaluation of cytokine gene expression in psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory disease affecting the skin with an unclear etiological significance. AIM: In this study, we determined the mRNA expression and circulating levels of T helper (Th)/T regulatory (Treg) cytokines in psoriasis and analyzed their association with disease severity and treatment response. MATERIAL AND METHODS: 189 psoriasis patients and 189 controls were recruited. Circulating Th/Treg cytokines (IL-12, IFN-γ, IL-17, IL-23, TGF-ß and IL-4) were measured at baseline and at follow-up after 12 weeks of methotrexate treatment by ELISA and their relative mRNA expression at baseline was estimated by quantitative PCR. RESULTS: We observed increased levels of Th1/Th17 cytokines (IFN-γ, IL-17, IL-12 and IL-23) and a decrease in levels of Th2/Treg cytokines (IL-4 and TGF-ß) in psoriasis patients at baseline, as compared to controls. Further, we observed that there was a significant decrease in Th1/Th17 cytokines, whilst Th2/Treg cytokine levels were significantly increased on follow-up after treatment with systemic metho trexate, as compared to pre-treatment levels. Our results were further confirmed by the significantly higher mRNA expression of Th1/Th17 cytokine genes and significantly lower mRNA expression of Th2/Treg cytokine genes in patients with psoriasis, as compared to controls. A significant positive correlation of Th1/Th17 cytokines was observed with disease severity in cases, whilst Th2/Treg cytokines correlated negatively with disease severity. CONCLUSIONS: Our results show that increased Th1/Th17 cytokines and decreased Th2/Treg cytokines, both at the circulatory and gene expression level, play an important role in the immunopathogenesis and severity of psoriasis.

Vitamin D deficiency in chronic kidney disease: Myth or reality?

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a public health problem, which has a prevalence of 17.2% in India. As kidney function decreases, there is a gradual deterioration in the regulation of bone mineral homeostasis. Vitamin D is recognized as the central player in the maintenance of bone health in CKD. Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines suggest that vitamin D supplementation should be given to all CKD patients with serum 25-hydroxy vitaminD (25(OH)D) level < 30 ng/mL. Hence we undertook this study to evaluate the vitamin D status in South Indian patients with CKD. METHODS: Fifty-nine non-dialysis CKD patients of stage 3 and 4 were recruited and screened for 25(OH)D deficiency. Circulating levels of 25(OH)D were measured using chemiluminescence immunoassay. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Serum calcium, phosphorous, creatinine and alkaline phosphatase levels were measured spectrophotometrically by an autoanalyzer. RESULTS: Contrary to published literature, 75% of South Indian CKD patients had normal 25(OH)D (≥30 ng/mL), 15% of them had insufficient (20-29 ng/mL) and 10% had 25(OH)D deficiency (<20 ng/mL). Alkaline phosphatase levels were found to be increased in only 20% of cases. Calcium1 levels were normal in all CKD cases and hyperphosphatemia was observed in 5% of CKD patients. CONCLUSION: We found that most of our CKD patients (75%) had normal vitamin D levels. This paradoxical finding could be explained by the fact that most of them gave a history of intake of vitamin D and calcium supplements, as advised by their doctors before coming to our institute. Hence we conclude that before prescribing vitamin D or calcium supplements to CKD patients, their 25(OH)D status should be ascertained to prevent hypervitaminosis D and its complications.

Is vitiligo associated with systemic aquaporin-3 deficiency?

INTRODUCTION: Recent studies on pathomechanisms of vitiligo have focused on the abnormality of keratinocytes that affect the melanocytes. Aquaporin-3 (AQP3) was implicated as a mechanism for keratinocyte apoptosis owing to the relationship between the PI3K/AKT pathway and the E-cadherin-catenin complex. AIM: Based on this evidence, we undertook a cross-sectional study to assess the skin and blood AQP-3 levels in patients with non-segmental vitiligo in comparison to controls and to correlate these levels with malondialdehyde (MDA) levels and total antioxidant status (TAS) in the skin and blood of patients with non-segmental vitiligo and also with their disease activity. MATERIAL AND METHODS: Thirty-six patients with non-segmental vitiligo and 36 controls were included in this study. AQP3, TAS and MDA levels were assayed both in skin as well as in circulation. RESULTS: We observed that skin and plasma aquaporin and TAS were lowered and MDA levels were increased in patients with non-segmental vitiligo as compared to controls. There was a significant negative correlation of skin and plasma aquaporin levels with disease activity. We also observed the local and systemic AQP3 deficiency to correlate with the local and systemic oxidative stress in vitiligo. CONCLUSIONS: Our results demonstrate a systemic and local AQP3 deficiency in vitiligo correlating with the disease severity and oxidative stress which might have therapeutic implications.

Ocular surface disorder among adult patients with type II diabetes mellitus and its correlation with tear film markers: A pilot study.

PURPOSE: The purpose is to study the ocular surface changes among patients with diabetes mellitus (DM) and to correlate them with tear film markers such as insulin-like growth factor (IGF)-1, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α levels. MATERIALS AND METHODS: The study was carried out on diabetic patients (>5 years' duration) and healthy age- and gender-matched controls with 21 individuals in each group. Schirmer's test for basal and reflex tear secretion, tear film breakup time (TBUT) for tear stability, ocular staining score (OSS) for dryness severity, ocular surface disease index (OSDI) for symptomatic assessment of dryness and conjunctival impression cytology (IC) for epithelial cell integrity, keratinization, squamous metaplasia, and goblet cell density was studied. Thirty microliters of tears were collected to test IGF-1, IL-1ß, and TNF-α levels. RESULTS: Patients with DM showed significantly low Schirmer's, TBUT, and OSS values than controls. OSDI score showed moderate-severe dryness in patients with DM and only mild symptoms among controls. An abnormal IC score was seen among cases and controls. The level of TNF-α was significantly increased in patients with DM and positively correlated with Schirmer and TBUT values (P < 0.05). CONCLUSION: Dry eye is more prevalent in patients with DM compared to controls as evidenced by poor OSDI score, Schirmer, TBUT, and OSS. TNF-α in the tears of patients with DM is a useful marker that showed a good correlation with Schirmer, TBUT, and dry eye symptoms. IC could not conclusively differentiate the dry eye status in patients with DM from controls.

Assessment of Patients with Periorbital Melanosis for Hyperinsulinemia and Insulin Resistance.

BACKGROUND: Periorbital melanosis (PM) is one of the most common dermatological condition seen in routine practice. Several cutaneous markers such as acanthosis nigricans have been associated with insulin resistance (IR). However, the association of PM with IR needs to be substantiated. OBJECTIVE: The objective of the study is to evaluate the association of circulating adipokines and IR with PM. MATERIALS AND METHODS: In this cross-sectional study, we recruited 100 patients with PM and 100 age- and gender-matched healthy controls. The serum levels of leptin, adiponectin, fasting glucose, fasting insulin, insulin-like growth factor-1 (IGF-1), homeostatic model assessment of insulin resistance (HOMA-IR), and leptin: adiponectin ratio (L/A ratio) were assayed. RESULTS: The serum levels of leptin, fasting glucose, fasting insulin, HOMA-IR, L/A ratio were significantly higher in patients with PM as compared to controls. The serum levels of adiponectin were significantly lower in cases as compared to controls. On multivariate regression analysis, leptin, adiponectin, and HOMA-IR were found to be significant, even after adjusting for BMI, blood pressure and LDL and HDL cholesterol. CONCLUSION: Our findings suggest that patients with PM have hyperinsulinemia, IR, and elevated L/A ratio. PM as a marker of IR in adults may help in identifying patients early and thus aid in the early prevention and management of the disease.

Utility of Urinary Nephrin in Patients With and Without Diabetic Nephropathy and Its Correlation With Albuminuria.

Introduction Nephrin is a podocyte-specific protein that may serve as a urinary biomarker in patients with diabetic nephropathy. The objectives of the study were to determine urinary nephrin levels in patients with and without type 2 diabetic nephropathy and to assess the correlation between urinary nephrin and albuminuria. Methods This was a cross-sectional comparative study that was carried out at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry over 18 months. Diabetic study subjects were divided into three groups-normoalbuminuria, microalbuminuria, and macroalbuminuria. Urinary albumin was detected by the dipstick method in a spot urine sample for all study subjects. In subjects with trace or no albuminuria, nephelometry was used to quantify urinary albumin levels. Urinary nephrin was estimated by the ELISA technique for all study subjects. Results Subjects in the microalbuminuria group had higher urinary nephrin levels than those in the normoalbuminuria and macroalbuminuria groups. There was a weak positive correlation between urinary albumin and nephrin levels among the study subjects (p < 0.001). Conclusion Urinary nephrin levels are increased in patients with diabetic nephropathy. There was a weak positive correlation between urinary albumin and nephrin levels among these patients.