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.

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.

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.

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.

Matrix metalloproteinase-9 increases the risk of cognitive impairment in schizophrenia.

PURPOSE OF THE ARTICLE: Synaptic plasticity is known to play role in pathogenesis of schizophrenia. Cognitive impairment is one of the complications of schizophrenia, leading to poor quality of life. Matrix metalloprotease-9 (MMP-9) and neurotrophin-3 (NT-3) are markers of synaptic plasticity, widely investigated in neuropsychiatric disorders. The objective of the study was to investigate the levels of MMP-9 and NT-3 and their association with cognitive impairment in schizophrenia. MATERIAL AND METHODS: 124 schizophrenia patients and 124 controls were enrolled in the study. MMP-9 and NT-3 were estimated in both the groups using ELISA. Cognition was assessed using Addenbrooke cognitive examination-III (ACE-III) and disease severity was assessed using PANSS. RESULTS: MMP-9 (p = .003) and NT -3 (p < .001) were found to be elevated in schizophrenia cases compared to controls. There was significant association of MMP-9 with fluency (r = -0.195, p = .030), language (r = -0.196, p = .029) and total ACE-III scores (r = -0.197, p = .029). Also we observed that MMP-9 increases the risk of cognitive impairment in schizophrenia patients (OR = 2.509, CI= 1.215 - 5.18, p = .013). CONCLUSION: MMP-9 and NT-3 are elevated in schizophrenia. MMP-9 was associated with fluency and language component of cognition and increases the risk of cognitive impairment in schizophrenia.

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.

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.

Association Analysis of Tumor Necrosis Factor Alpha Promoter Polymorphisms and Vitiligo Susceptibility in South Indian Tamils.

Tumor necrosis factor alpha (TNF-α) has been associated with the pathogenesis of several autoimmune diseases. Also, various studies in different ethnics showed an association between TNF-α gene polymorphisms and susceptibility to vitiligo. The paucity of genetic data led us to undertake this study to evaluate the association of five TNF-α SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) with the development of vitiligo in South Indian Tamils. A total of 264 vitiligo patients and 264 healthy controls were recruited and TNF-α genotyping was performed using amplification-refractory mutation system polymerase chain reaction and TaqMan allele discrimination assay. Circulatory TNF-α levels were measured by enzyme-linked immunosorbent assay. We observed that a single polymorphic allele A in the promoter region -308 (rs1800629) conferred significant risk to develop vitiligo (p = 0.0002, OR = 1.70, 95% CI = 1.28-2.25), whereas the other polymorphisms failed to contribute to disease risk (p > 0.05). From the constructed haplotypes, TCCAG was found to be a significant risk factor for vitiligo (p < 0.05). Also, a strong linkage disequilibrium was observed between the following SNPs: (1) rs1799964 and rs1800629 (2) rs1800630 and rs1799724 (D' = 0.90). Analysis of the influence of genotype on phenotypes revealed that the A allele of rs361525 was a risk factor for vitiligo in females (p = 0.04, OR = 0.45, 95% CI = 0.21-0.95), whilst the rs1800629 allele conferred protection against early disease onset (p < 0.05). A statistically significant difference in plasma TNF-α levels was found between cases and controls (p < 0.05). The TNF-α -308A allele and TCCAG haplotype were identified as genetic risk factors for vitiligo susceptibility in South Indian Tamils.

Association of Nod-like receptor protein-1 (rs2670660) and Toll-like receptor-4 (rs4986790) with non-segmental vitiligo: A case-control study in South Indian population.

Non-segmental vitiligo (NSV) is an autoimmune skin disease. Genetics plays a predominant part in disease pathogenesis. Nucleotide-binding and oligomerization domain (NOD)-like receptors and pyrin-containing protein (NLRP) and Toll-like receptors (TLR) are pattern recognition receptors in mediating innate immunity. They participate in presenting pathogens and mediating the immune responses. NLRP and TLRs are involved in mediating immune response in various dermatological diseases. Understanding the influence of genetic polymorphisms of NLRP and TLRs associated with immune homeostasis might help us to understand the complex etiopathogenesis of NSV. Thus, we aimed to study the association of NLRP-1 (rs2670660) and TLR-4 (rs4986790) and the synergistic effects on disease spectrum, disease activity of NSV in South Indian population. This research was designed as a case-control genetic study with 264 patients and 264 controls. Genotyping of NLRP-1 (rs2670660) and TLR-4 (rs4986790) was performed by Taqman 5' allele discrimination assay and ARMS-PCR. Plasma levels of proteins were measured by enzyme-linked immunosorbent assay (ELISA). A statistically significant difference was observed with the frequency of homozygous GG genotype of NLRP-1 (rs2670660) (17.8% in cases vs. 5.3% in controls) (p < 0.0001; OR-3.73; 95% CI-1.94-7.14). Allele G was significantly frequent in 38% of the cases than in controls with 30% (p = 0.004; OR-1.46; 95% CI-1.13-1.89). Plasma NLRP-1 level was significantly higher in patients compared to controls (p < 0.05). Amongst cases, the plasma NLRP-1 levels did not show any difference with respect to their genotypes (p > 0.05). In TLR-4 (rs4986790), no significant difference in the frequency of genotypes and allele between cases and controls (p = 0.80) was observed; nevertheless, plasma TLR-4 was analogous between cases and controls (p > 0.05). Influence of genotype on plasma TLR-4 showed no significant difference in TLR-4 levels between GG and ancestral genotype AA, whilst heterozygous AG genotype showed a significant increase of TLR-4 compared to AA and GG (p = 0.02) amongst NSV cases. The obtained results suggest that NLRP-1 (rs2670660), and not TLR-4 ((rs4986790), is associated with increased risk of NSV in South Indian population.

Immunophenotype of circulatory T-helper cells in patients with non-segmental vitiligo.

INTRODUCTION: Non-segmental vitiligo (NSV) is an immune-mediated skin depigmentation disease. Cytokine-mediated interaction between T lymphocytes and melanocytes leads to death of melanocytes, causing a defect in melanin synthesis and thereby depigmentation. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in NSV. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is rarely studied. AIM: To study the immunophenotype of the different T-helper/Treg cell subsets in patients with NSV, in comparison to healthy controls. MATERIAL AND METHODS: A total of 80 patients with NSV and eighty age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease activity was determined by vitiligo index of disease activity (VIDA) scoring. Peripheral blood mononuclear cells were separated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. RESULTS: In patients with NSV, we observed an imbalance in T-cell immunophenotype, characterized by an increase in Th1 (p < 0.0001) and Th17 cells (p = 0.01). There is no difference in relative percentage of Th2/Treg cells, as compared to the healthy controls (p > 0.05). CONCLUSIONS: There is a significant immune-dysregulation with a preponderance of circulatory Th1/Th17 phenotype in NSV patients.

Gene expression of insulin receptor, insulin-like growth factor increases and insulin-like growth factor-binding protein-3 reduces with increase in prostate size in benign prostatic hyperplasia.

INTRODUCTION: Although the role of insulin in the development of benign prostatic hyperplasia (BPH) is well established, there are no studies regarding alteration in the gene expression of components of insulin-signaling pathway and their association with prostate size in BPH. Hence, the study was designed to analyze the gene and protein expression of insulin receptor and its related components in patients with BPH. MATERIALS AND METHODS: Twenty-seven BPH patients aged between 55 and 75 years were recruited in the study and prostatic tissues were obtained after transurethral resection of the prostate. Gene expression levels of Insulin receptor (IR), insulin receptor substrate (IRS), insulin-like growth factor (IGF) and insulin-like growth factor-binding protein-3 (IGFBP-3) were assessed by q-PCR. RESULTS: Insulin receptor (IR-A and B) and insulin-like growth factors (IGF-1 and IGF-2) gene expression were significantly increased and IGFBP-3 gene expression was reduced in BPH patients with larger prostate size. Also, serum insulin was significantly increased and IGFBP-3 was significantly reduced in patients with larger prostate size. CONCLUSION: Increased expression of IR-A, B and IGF-1, 2 genes and reduced IGFBP-3 gene expression was associated with larger prostate size in BPH.

Association of PTPN22 gene polymorphism with non-segmental vitiligo in South Indian Tamils.

INTRODUCTION: Non-segmental vitiligo (NSV) is a depigmentation skin disease with loss of melanocytes in the skin. AIM: To evaluate whether the protein tyrosine phosphatase non-receptor type (PTPN22) single nucleotide polymorphism at +1858C/T had any association with non-segmental vitiligo in South Indian Tamils. MATERIAL AND METHODS: Genomic DNA was extracted using the phenol-chloroform method, and PTPN22 +1858C/T polymorphism was assayed by Taqman 5'allele discrimination assay. Protein levels were quantified by ELISA. RESULTS: We found that the allelic frequency of variants of PTPN22 (rs2476601) were significantly different between controls and cases showing a vitiligo risk in the South Indian Tamil population. PTPN22 levels were higher in the heterozygous CT genotype in NSV, when compared with that of the major variant CC genotype of rs2476601. CONCLUSIONS: This study suggests that the heterozygous CT genotype, of the PTPN22 SNP rs2476601, has a strong risk association with non-segmental vitiligo in South Indian Tamils.

Correlation of antimuscarinic acetylcholine receptor antibody titers and antidesmoglein antibody titers with the severity of disease in patients with pemphigus.

BACKGROUND: Acetylcholine receptor (AchR) antibody levels significantly correlate with disease severity at initial pemphigus diagnosis and during follow-up. However, it is not clear if they are just an epiphenomenon or a potential trigger of the known pathogenic process in pemphigus vulgaris. OBJECTIVE: We sought to assess the changes in anti-muscarinic (M3) AchR and anti-desmoglein (Dsg) antibody titers with therapy. METHODS: This was a hospital-based cohort study involving 45 patients with active pemphigus. Disease was graded clinically using Pemphigus Disease Area Index. Antibody titers were estimated using enzyme-linked immunosorbent assay at baseline, 3 months, and 15 months. RESULTS: All patients with pemphigus had significantly higher anti-M3 AchR titers when compared with a control group. Only 95.5% of patients had anti-Dsg1 antibodies and 84.4% of patients had anti-Dsg3 antibodies. A statistically significant reduction in all 3 antibody titers from baseline to follow-up with treatment was observed. There was a good correlation between all 3 antibody titer and Pemphigus Disease Area Index score at baseline and after therapy and between anti-M3 AchR and anti-Dsg1 antibody titers. LIMITATIONS: Sample size was small and follow-up period was short. CONCLUSIONS: Anti-M3 AchR antibodies are strongly associated with pemphigus. They significantly correlate with disease activity and their titers decline with therapy along with anti-Dsg antibodies.

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.

Association among stress, hypocortisolism, systemic inflammation, and disease severity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an immune-mediated disease characterized by wheals for at least 6 weeks. The role of stress and the correlation of stress, hypocortisolism, and inflammatory markers are not well understood. OBJECTIVES: To estimate C-reactive protein (CRP), interleukin (IL)-18, and cortisol levels in patients with CU and to explore their association with disease severity and stress. METHODS: Forty-five patients with CU and 45 age- and sex-matched healthy controls were recruited for this cross-sectional study. Disease severity was assessed by the urticaria activity score (UAS) and stress by Presumptive Stressful Life Events (PSLE) and Daily Hassles and Uplifts Scale-Revised (DHUS-R) scoring. IL-18 and high-sensitivity CRP (hs-CRP) were estimated using enzyme-linked immunosorbent assay kits and cortisol levels by chemiluminescence. RESULTS: We observed significant systemic inflammation (increased hs-CRP and IL-18 levels) and stress scores, whereas there was a lowering of basal cortisol levels in patients with CU compared with controls. This finding was more pronounced with increasing disease severity and autoimmune disease, except for stress scores, which did not vary between patients with positive and negative autologous plasma skin test results. We further observed that patients with CU with hypocortisolism had higher levels of hs-CRP and IL-18 and higher PSLE and DHUS-R scores compared with those without hypocortisolism. The hs-CRP level, IL-18 level, PSLE score, DHUS-R score, and duration of the symptoms are significantly positively correlated with UAS, whereas the cortisol level is significantly negatively correlated with UAS. Cortisol has a significant negative correlation with PSLE score, DHUS-R score, and the duration of the disease. CONCLUSION: CU is associated with systemic inflammation and stress, along with a significant lower basal cortisol, especially with severe disease and autoimmune urticaria. Thus, chronic stress may precipitate the vicious cycle in the pathogenesis of CU.

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.

Carbohydrate Deficient Transferrin and Interleukin-6 as Predictors of Fibrosis in Alcohol Cirrhosis.

The severity of alcoholic cirrhosis depends on the presence of liver inflammation and fibrogenesis. Previous studies have hypothesized that carbohydrate deficient transferrin can be used as marker of liver impairment in alcoholic liver disease patients. The present study was designed to assess whether carbohydrate deficient transferrin is associated with procollagen III peptide and predict fibrosis in alcohol cirrhosis patients. We enrolled 48 patients with alcoholic cirrhosis and 38 healthy controls. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 levels were estimated in both groups. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 were significantly increased in alcoholic cirrhosis patients compared to controls. Stepwise regression analysis showed that carbohydrate deficient transferrin (adjusted R(2) = 0.313, ß = 0.362, p = 0.003) and interleukin-6 (adjusted R(2) = 0.194, ß = 0.459, p = 0.001) were positively associated with procollagen III peptide when age, duration and amount of alcohol consumption were considered as covariates. We conclude that elevated carbohydrate deficient transferrin and interleukin-6 act as predictors of fibrosis in alcoholic cirrhosis.

Hypomagnesemia and atherogenic dyslipidemia in chronic kidney disease: surrogate markers for increased cardiovascular risk.

BACKGROUND: Recent reports suggest that 40-70 % chronic kidney disease (CKD) patients receiving dialysis have significant coronary artery disease. Magnesium depletion is being considered as the missing link between the cardiovascular risk factors and atherosclerosis in CKD. The present work aimed to study the association between magnesium status and lipid alterations in pre-dialysis CKD patients attending the Nephrology Clinic in a tertiary care hospital in South India. METHODS: 90 cases of CKD and 90 age and gender matched healthy controls were included in the study. Framingham risk scoring was done and presence of metabolic syndrome was assessed. Lipid profile, serum and urine magnesium, blood glucose, calcium, phosphorus, urea and creatinine levels were assayed in all study subjects. RESULTS: In this study we observed a significantly lower serum magnesium levels and dyslipidemic alterations, a significantly raised total cholesterol and low-density lipoprotein and non-HDL in patients with CKD. We also observed a significant correlation between the lowered serum magnesium concentrations and atherogenic dyslipidemia, suggesting a link to increased cardiovascular risk in CKD patients. CKD patients had higher risk of cardiovascular disease (according to their Framingham risk score), which also showed significant correlation with the hypomagnesaemia. CONCLUSIONS: Our results suggest a strong association of hypomagnesemia and atherogenic dyslipidemia in patients with CKD. This gains particular importance in the high cardiovascular risk-borne CKD patients, as supplementing magnesium would go a long way in reducing the risk of cardiovascular morbidity and mortality in CKD.