SCID MOUSE MODEL OF PSORIASIS: A UNIQUE TOOL FOR DRUG DEVELOPMENT OF AUTOREACTIVE T-CELL AND TH-17 CELL-MEDIATED AUTOIMMUNE DISEASES

In both skin and synovial tissues of psoriatic arthritis (PsA) patients, there are prominent lymphocytic infiltrates localized to the dermal papillae in the skin and the sublining layer stroma in the joint. T-cells, with a predominance of CD4+ lymphocytes, are the most significant lymphocytes in the tissues; in contrast, this ratio is reversed in the epidermis, synovial fluid compartment, and at the enthesis, where CD8+ T-cells are more common. This differential tropism of CD8+ T-cell suggests that the CD8+ T-cells may be driving the immune response in the joint and skin. This is supported by an association with MHC class I. The cytokine network in the psoriatic skin and synovium is dominated by monocyte and T-cell-derived cytokines: IL-1β, IL-2, IL-10, IFN-γ, and TNF-α. In PsA synovium, higher levels of IFN-γ, IL-2, and IL-10 have been detected than in psoriatic skin. An analysis of T-cell receptor beta-chain variable (TCRβV) gene repertoires revealed common expansions in both skin and synovial inflammatory sites, suggesting an important role for cognate T-cell responses in the pathogenesis of PsA and that the inciting antigen may be identical or homologous between the afflicted skin and synovium. Traditionally, T-cells have been classified as T helper 1 (Th1) or Th2 cells by production of defining cytokines, IFN-γ and IL-4, respectively. Recently, a new type of T-cell, Th17, has been linked to autoimmune inflammation. T-helper 17 (Th17) cells are a unique effector CD4+ T-cell subset characterized by the production of interleukin (IL)-17. Murine diseases that were previously considered to be pure Th1-mediated responses have been shown to contain mixed populations of Th1 and Th17 cells. Also, in humans, a critical immunoregulatory role of Th-17 cells in infectious and autoimmune diseases has been identified. It has been postulated that IL-17 may be important in psoriasis. Our initial observations demonstrate that IL-17 and its receptor system are important for PsA also. In in vivo and in vitro studies we have demonstrated that IL-17/IL-17R are enriched in skin, synovial tissue, and synovial fluid of psoriatic arthritis patients and Th17 cells are functionally significant in the pathogenesis of psoriasis and psoriatic arthritis. Here we will share our experience of the SCID mouse model of psoriasis in respect to its use in investigating psoriatic diseases and development of immune-based drugs for psoriasis, psoriatic arthritis, and other autoimmune diseases.     

Reduced expression of the inhibitory synapse scaffolding protein gephyrin in Alzheimer's disease

Excitotoxicity may contribute to neuronal and synaptic loss in Alzheimer's disease (AD). Aberrant levels of gephyrin, a post-synaptic receptor-stabilizing protein, could affect the inhibitory modulation of excitatory impulses. We assayed gephyrin protein in two brain areas susceptible to neuronal loss in AD, and in a spared area, in autopsy tissue from normal subjects (n=15) and AD patients (n=5). Quantification was by in-gel immunodetection against known concentrations of a recombinant truncated gephyrin standard. Gephyrin abundance was significantly reduced (P<0.01) in AD. Area-wise analysis showed that gephyrin levels were reduced in both spared and susceptible regions, indicating a global phenomenon. When samples were categorized on an index of pathological severity, gephyrin levels decreased with increasing severity until a moderate index was reached, and then increased, suggesting that higher gephyrin levels might compensate for excitotoxic damage in late stages of the disease. AD males showed a more pronounced reduction in gephyrin levels than AD females cf same-sex controls. A major splice variant of gephyrin was detected in all cases and in all three brain areas. This is the first study of gephyrin expression in AD.     

Fine needle aspiration cytology in tumoral calcinosis cases ＆ review of literature

Objective:To investigate them by the non-invasive technique of fine needle aspiration cytology(FNAC).Methods: In this study cases were described in which FNAC was indicative of tumoral calcinosis.Total numbers of cases studied were 18.Male to female ratio was 1∶8.11 cases(61.11%) were less than 20 years of age.3 cases had history of trauma in the past(16.67%).8 cases had lesions located in the hip region(44.44%).Results:The size of lesion varied from 2.5 to 4 cm.In none of the case diagnosis of tumoral calcinosis was considered clinically.All other investigations were normal and no significant family or medical history was present.Cytology in all cases showed only abundant acellular calcium.The patients on follow up were clinically well with no changes.Conclusion:The cases are interesting,since the cytohistological findings in the aspirate sample are strongly indicative of tumoral calcinosis.     

The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neoplasia

Several studies have investigated the accuracy of naked eye visual inspection with acetic acid (VIA) in the early detection of cervical neoplasia. It is not clear whether low-level (2-4x) magnification (VIAM) can improve the sensitivity and specificity of VIA. The accuracy of both VIA and VIAM, provided by independent health workers, were evaluated in three cross-sectional studies involving 18,675 women aged 25-65 years in Kolkata and Mumbai in India. All screened women were investigated with colposcopy and biopsies were obtained based on colposcopy findings. The final disease status was based on the reference standard of histology (if biopsies had been taken) or colposcopy. Data from the studies were pooled to calculate the test characteristics for the detection of high-grade squamous intraepithelial lesions (HSIL). 14.1% and 14.2% were positive on testing with VIA and VIAM respectively. Two hundred twenty-nine were diagnosed with HSIL and 68 with invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values for VIA in detecting high-grade squamous intraepithelial lesions (HSIL) were 60.3% (95% CI: 53.6-66.7), 86.8% (95% CI: 86.3-87.3), 5.9% (95% CI: 5.0-7.0), and 99.4% (95% CI: 99.2-99.5), respectively. The values were 64.2% (95% CI: 57.6-70.4), 86.8% (95% CI: 86.2-87.3), 6.3% (95% CI: 5.3-7.3) and 99.4% (95% CI: 99.3-99.6), respectively, for VIAM. Low-level magnification did not improve the test performance of naked eye visualization of acetic acid impregnated uterine cervix.     

Prevalence of incidental and total human immunodeficiency virus,hepatitis B and hepatitis C seropositivity among patients posted for cataract surgery at a tertiary care center in India

Purpose:To study the prevalence of human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) viral seropositive among the patients posted for cataract surgery at a tertiary care center in north India.Methods:It was a cross-sectional study done for 30 months duration. All the patients posted for cataract surgery underwent comprehensive ophthalmic evaluation followed by routine hematological workup, including viral markers for HIV, Hepatitis B surface antigen (HBsAg), and anti-HCV. Data were analyzed by the Statistical Package for Social Science (SPSS Version 20).Results:A total of 7,316 individuals underwent cataract surgery from Jan 2016 to August 2018, 4,073/7,316 (55.7%) were males. The prevalence for HIV was 58/7,316 (0.8%), HBsAg was 151/7,316 (2.1%), and HCV was 11/7,316 (0.1%); 28/58 (48.3%) HIV positives were unaware of their seropositivity till testing, as were 37/151 (24.5%) of HBsAg positives, and 4/11 (36.4%) HCV positives. There was a significant relationship between the mean age in the patients with HIV (P = 0.002) and anti-HCV (P = 0.045). A majority of the seropositive patients were found to be illiterate (45.6%), followed by educated up to high school level (29.1%), and graduate (25.0%).Conclusion:Viral seropositivity was significant among the patients posted for cataract surgery. The eye care providers could refer these patients for counseling and further management for the patient’s and their caretaker’s benefit.     

Epigenetics and Peripheral Artery Disease

The term epigenetics is usually used to describe inheritable changes in gene function which do not involve changes in the DNA sequence. These typically include non-coding RNAs, DNA methylation and histone modifications. Smoking and older age are recognised risk factors for peripheral artery diseases, such as occlusive lower limb artery disease and abdominal aortic aneurysm, and have been implicated in promoting epigenetic changes. This brief review describes studies that have associated epigenetic factors with peripheral artery diseases and investigations which have examined the effect of epigenetic modifications on the outcome of peripheral artery diseases in mouse models. Investigations have largely focused on microRNAs and have identified a number of circulating microRNAs associated with human peripheral artery diseases. Upregulating or antagonising a number of microRNAs has also been reported to limit aortic aneurysm development and hind limb ischemia in mouse models. The importance of DNA methylation and histone modifications in peripheral artery disease has been relatively little studied. Whether circulating microRNAs can be used to assist identification of patients with peripheral artery diseases and be modified in order to improve the outcome of peripheral artery disease will require further investigation.