Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

The Chiraiya project: a retrospective analysis of breast cancer detection gaps addressed via mobile mammography in Jammu Province, India.

BACKGROUND: Breast cancer remains a pervasive threat to women worldwide, with increasing incidence rates necessitating effective screening strategies. Timely detection with mammography has emerged as the primary tool for mass screening. This retrospective study, which is part of the Chiraiya Project, aimed to evaluate breast lesion patients identified during opportunistic mammography screening camps in Jammu Province, India. METHODS: A total of 1505 women aged 40 years and older were screened using a mobile mammographic unit over a five-year period, excluding 2020 and 2021 due to the COVID-19 pandemic. The inclusion criterion was women in the specified age group, while the exclusion criterion was women with open breast wounds, history of breast cancer or a history of breast surgery. The screening process involved comprehensive data collection using a detailed Proforma, followed by mammographic assessments conducted within strategically stationed mobile units. Radiological interpretations utilizing the BI-RADS system were performed, accompanied by meticulous documentation of patient demographics, habits, literacy, medical history, and breastfeeding practices. Participants were recruited through collaborations with NGOs, army camps, village panchayats, and urban cooperatives. Screening camps were scheduled periodically, with each camp accommodating 90 patients or fewer. RESULTS: Among the 1505 patients, most were aged 45-50 years. The number of screenings increased yearly, peaking at 441 in 2022. The BI-RADS II was the most common finding (48.77%), indicating the presence of benign lesions, while the BI-RADS 0 (32.96%) required further evaluation. Higher-risk categories (BI-RADS III, IV, V) were less common, with BI-RADS V being the rarest. Follow-up adherence was highest in the BI-RADS III, IV, and V categories, with BI-RADS V achieving 100% follow-up. However, only 320 of 496 BI-RADS 0 patients were followed up, indicating a gap in continuity of care. The overall follow-up rate was 66.89%. Compared to urban areas, rural areas demonstrated greater screening uptake but lower follow-up rates, highlighting the need for tailored interventions to improve follow-up care access, especially in rural contexts. CONCLUSION: This study underscores the efficacy of a mobile mammographic unit in reaching marginalized populations. Adherence to screening protocols has emerged as a linchpin for early detection, improved prognosis, and holistic public health enhancement. Addressing misconceptions surrounding mammographic screenings, especially in rural settings, is crucial. These findings call for intensified efforts in advocacy and education to promote the benefits of breast cancer screening initiatives. Future interventions should prioritize improving access to follow-up care and addressing screening to enhance breast cancer management in Jammu Province.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.

Spectrum of intimate partner violence in patients with psychiatric illness-From victimization to perpetration.

PURPOSE: Persons with psychiatric illness are vulnerable to be the victims of intimate partner violence (IPV) and at risk of perpetrating IPV. OBJECTIVES: To estimate the prevalence and association of IPV in patients with psychiatric disorders, both as victims and as perpetrators. METHODOLOGY: We conducted a questionnaire based, cross-sectional study using systematic random sampling at psychiatric Outpatient Department (OPD) in a tertiary care hospital, in Haryana, India. A total of 500 participants diagnosed with psychiatric disorder were assessed using Operational WHO Criteria for IPV Victimization assessment and IPV Perpetration Assessment scale by Rhodes et al. RESULTS: The prevalence of IPV victimization was 16% during the last year and 26% during lifetime. IPV victimization was found significantly more in females (especially sexual), young and unemployed participants, during the initial 10 years of marriage and 10 years of the illness. Sexual IPV was the most common. The prevalence of IPV perpetration by the participants was 6% during last year and 10.6% in lifetime. Perpetrators were more likely to be males of higher age (40-50 years), unemployed, having lower income, belonging to joint family, and residing in rural areas. Diagnosis of a psychiatric illness, especially psychosis increased chances of perpetration. As the duration of illness increased, prevalence of IPV perpetration increased. CONCLUSION: Intimate partner violence among persons with psychiatric disorders is common and they are more vulnerable to being victims of IPV, rather than perpetrating IPV. Vulnerability and risk factors for IPV should be taken into account and optimized strategies should be devised for prevention.

Direct Extracellular NAMPT Involvement in Pulmonary Hypertension and Vascular Remodeling. Transcriptional Regulation by SOX and HIF-2α.

We previously demonstrated involvement of NAMPT (nicotinamide phosphoribosyltransferase) in pulmonary arterial hypertension (PAH) and now examine NAMPT regulation and extracellular NAMPT's (eNAMPT's) role in PAH vascular remodeling. NAMPT transcription and protein expression in human lung endothelial cells were assessed in response to PAH-relevant stimuli (PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor], TGF-ß1 [transforming growth factor-ß1], and hypoxia). Endothelial-to-mesenchymal transition was detected by SNAI1 (snail family transcriptional repressor 1) and PECAM1 (platelet endothelial cell adhesion molecule 1) immunofluorescence. An eNAMPT-neutralizing polyclonal antibody was tested in a PAH model of monocrotaline challenge in rats. Plasma eNAMPT concentrations, significantly increased in patients with idiopathic pulmonary arterial hypertension, were highly correlated with indices of PAH severity. eNAMPT increased endothelial-to-mesenchymal transition, and each PAH stimulus significantly increased endothelial cell NAMPT promoter activity involving transcription factors STAT5 (signal transducer and activator of transcription 5), SOX18 (SRY-box transcription factor 18), and SOX17 (SRY-box transcription factor 17), a PAH candidate gene newly defined by genome-wide association study. The hypoxia-induced transcription factor HIF-2α (hypoxia-inducible factor-2α) also potently regulated NAMPT promoter activity, and HIF-2α binding sites were identified between -628 bp and -328 bp. The PHD2 (prolyl hydroxylase domain-containing protein 2) inhibitor FG-4592 significantly increased NAMPT promoter activity and protein expression in an HIF-2α-dependent manner. Finally, the eNAMPT-neutralizing polyclonal antibody significantly reduced monocrotaline-induced vascular remodeling, PAH hemodynamic alterations, and NF-κB activation. eNAMPT is a novel and attractive therapeutic target essential to PAH vascular remodeling.

Evaluating Static Bone Cysts (SBCs) Through Long-Term Volumetric Analysis Using CBCT: A Study with 6-Month Follow-Up.

Background: Salivary gland bone defects are static lesions which are rare entities, generally asymptomatic and found in routine imaging exams. However, in atypical cases or when misdiagnosed, surgical intervention is carried out. Purpose: a) The study is intended to investigate the frequency of SBC's and to describe the radiological characteristics of its subtypes; b) To evaluate the efficacy of volumetric analysis tool in CBCT and; c) To describe the confirmative role of CBCT in the diagnosis of SBC's without the need for surgical intervention. Material and Methods: The study was conducted on 11 subjects with SBC detected on 3304 panoramic radiographs. CBCT images for each patient were captured at baseline and at an interval of 6 months. Radiographic sub-types of SBC based on the relationship to mandibular canal and bucco-lingual expansion were studied. Files in DICOM format were transferred into OnDemand 3D program (Cybermed Co, Seoul, Korea) and volumes in mm3 of the cavities were measured by 2 observers at both intervals. Inter and intra reliability of volumetric measurements between observers was compared using correlation coefficient and student t test. Results: There were 8 males and 3 females who had SBC in this study (age range: 22-70 years). According to the relationship of SBC with mandibular canal, most SBCs were Type 1 (63.5 %) followed by Type 2 & 3 (18.5 %) each. The total volume of SBC in patients ranged from 146 mm3 to 650 mm3 (mean: 332.5 mm3). There was no significant difference between observers for volume measurements at baseline and at 6 months interval (p>0.05). Conclusions: Based on the results of this study, CBCT should be considered as a definitive diagnostic modality for volumetric analysis of SBCs. Over diagnosis, unnecessary surgical exploration and agony to patients can be avoided using this tool. Key words:Stafne bone cavity, CBCT, Volumetric analysis, salivary gland, panoramic radiography.

SOX9 gene shows association with adolescent idiopathic scoliosis predisposition in Northwest Indians.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common structural deformity of the spine affecting adolescent individuals globally. The disorder is polygenic and is accompanied by the association of various genetic loci. Genetic studies in Chinese and Japanese populations have shown the association of genetic variants of SOX9 with AIS curve severity. However, no genetic study evaluating the association of SRY-Box Transcription Factor 9 (SOX9) variants with AIS predisposition has been conducted in any Indian population. Thus, we aimed to investigate the association of the genetic variants of the SOX9 along with 0.88 Mb upstream region with AIS susceptibility in the population of Northwest India. METHODS: In total, 113 AIS cases and 500 non-AIS controls were recruited from the population of Northwest India in the study and screened for 155 genetic variants across the SOX9 gene and 0.88 Mb upstream region of the gene using Global Screening Array-24 v3.0 chip (Illumina). The statistical significance of the Bonferroni threshold was set at 0.000322. RESULT: The results showed the association of 11 newly identified variants; rs9302936, rs7210997, rs77736349, rs12940821, rs9302937, rs77447012, rs8071904, rs74898711, rs9900249, rs2430514, and rs1042667 with the AIS susceptibility in the studied population. Only one variant, rs2430514, was inversely associated with AIS in the population, while the ten variants were associated with the AIS risk. Moreover, 47 variants clustered in the gene desert region of the SOX9 gene were associated at a p-value ≤ 0.05. CONCLUSION: The present study is the first to demonstrate the association of SOX9 enhancer locus variants with AIS in any South Asian Indian population. The results are interesting as rs1042667, a 3' untranslated region (UTR) variant in the exon 3 and upstream variants of the SOX9 gene, were associated with AIS susceptibility in the Northwest Indian population. This provides evidence that the variants in the enhancer region of SOX9 might regulate its gene expression, thus leading to AIS pathology and might act as an important gene for AIS susceptibility.

Dens Evaginatus and Dens Invaginatus in Dilacerated Maxillary Lateral Incisor Diagnosed Using Cone Beam Computed Tomography - A Case Report and Review of Literature.

INTRODUCTION: Dens invaginatus (DI) and Dens evaginatus (DE), the developmental anomalies affecting the morphology of the tooth structure are extremely rare to occur. DI occurs because of invagination of a crown into dental papillae. DE is a tubercular emergence from occlusal surfaces of posterior teeth and lingual surfaces of anterior teeth. The two anomalies on separate teeth are frequently mentioned, but their co-occurrence in a single tooth is a rare entity. PATIENT CONCERNS: A 20-year-old male patient presented with the rare combination of DE and DI on a dilacerated maxillary right lateral incisor diagnosed using cone beam CT. Treatment: The patient was managed conservatively and is undergoing fixed orthodontic treatment for malocclusion. Despite its uniqueness, very few localized cases have been documented. TAKEAWAY LESSONS: These anomalies act as an etiological factor for several dental problems for neighboring & opposing tooth. Early diagnosis of such anomalies should be done so that prophylactic management can be initiated.

The first study of epidemiology of adolescent idiopathic scoliosis shows lower prevalence in females of Jammu and Kashmir, India.

AIS is a heterogeneous 3D spinal deformity with Cobb angle ≥10°. It affects children in the age group of 10-16 years globally with 2-3% prevalence and significant female predominance. The exact etiology of AIS is not known however, it is supposed to be associated with factors such as anthropometric, metabolic, neuromuscular abnormalities and genetics. OBJECTIVES: To determine the prevalence of AIS and association of anthropometric factors with AIS in the studied population group. METHODOLOGY: Scoliosis screening of 9,500 individuals was carried out at different educational institutions of Jammu region in Jammu and Kashmir, India using a scoliosis-meter. The subjects were later examined radiologically. RESULTS: In population of the region, AIS was most prevalent among all types of scoliosis with overall prevalence of 0.61%. The prevalence was observed to be lower in females (0.31%) than males (0.88%). Based on angle of trunk rotation (ATR), lumbar curves were more prevalent than thoracic curves. Average Cobb angle in males and females were 24.9° and 22.6°, respectively. BMI showed significant association with AIS in the age group of 12-16 years (P value =0.028). Furthermore, height was significantly associated with AIS in the overall screened population (P-value =0.029). CONCLUSIONS: The AIS patients in the Jammu region of India have unique clinical features. In contrast to the global prevalence data, the prevalence of AIS in females in the region was less in comparison to males. Based on epidemiological literature and our findings, we hypothesized that genetic factors might be a major contributor in the AIS pathogenesis along with other confounding factors such as height, BMI, ethnicity, etc.

Unusual Richter's Hernia: Impacted foreign body leading to incarceration and perforation - A rare clinical entity.

INTRODUCTION & IMPORTANCE: Richter's hernia is a clinically deceiving entity as is particularly associated with high morbidity and mortality which can be can be abated by timely diagnosis and surgery. Direct inguinal hernias having a wide neck have lesser chances of incarceration and strangulation when compared to indirect inguinal hernias. The knowledge about this type of hernia is especially important in the context of laparoscopy as majority of the laparoscopic port site hernias are characteristically Richter's type in configuration. The objective of this report is to highlight the unusual presentation of the case and sine quo non of prompt diagnosis and timely surgery remains the cornerstone of management. CASE PRESENTATION: We report a case of Richter's hernia incarcerated due to an impacted foreign body (match stick) through a direct inguinal hernia. Patient presented with a painful, non-expansile, tender swelling in left groin. Patient was diagnosed with a complicated inguinal hernia and underwent exploration with resection of involved bowel segment and primary repair of hernia. CLINICAL DISCUSSION: Richter's hernia is a rare abdominal wall hernia specifically known for its unusual and delayed presentation leading to high rates of morbidity and mortality. Direct inguinal hernias are less prone to complications like obstruction, strangulation and incarceration owing to presence of a wide neck. Clinical suspicion, prompt radiological diagnosis and timely surgery can lead to an uneventful recovery. CONCLUSION: Surgery is the only treatment, but timely surgery remains the golden opportunity. Critical in repair is the evaluation of intestinal viability.

Xanthogranulomatous Pyelonephritis in a male child with renal vein thrombus extending into the inferior vena cava: a Case Report.

BACKGROUND: We present a case of Xanthogranulomatous pyelonephritis (XGPN) in a male child with renal vein thrombus extending into the inferior vena cava. This is a rare presentation. XGPN is a rare type of renal infection characterised by granulomatous inflammation with giant cells and foamy histiocytes. The peak incidence is in the sixth to seventh decade with a female predominance. XGPN is rare in children. CASE PRESENTATION: An 11 year old male child presented with a history of high grade fever and chills, right flank pain and progressive pyuria for two months. He had a history of vesical calculus for which he was operated four years back. In our case, a subcapsular right nephrectomy was performed. The surgical specimens were formalin fixed and paraffin embedded. The sections were stained with routine Hematoxylin & Eosin stain. Grossly; the kidney was enlarged with adherent capsule and thickening of the perinephric tissue. The pelvicalyceal system was dilated and was filled with a cast of pus. Histological evaluation revealed diffuse necrosis of the renal parenchyma and perinephric fat. Neutrophils, plasma cells, sheets of foamy macrophages and occasional multinucleate giant cells were seen. The renal vein was partially occluded by an inflammatory thrombus with fibrin, platelets and mixed inflammatory cells. The thrombus was focally adherent to the vein wall with organization. CONCLUSIONS: The clinical presentation and the macroscopic aspect, together with the histological pattern, the cytological characteristics addressed the diagnosis towards XGPN with a vena caval thrombus. Our case illustrates that the diagnosis of XGPN should be considered even in paediatric age group when renal vein and vena caval thrombi are present.

Protective effect of resveratrol and vitamin E against ethanol-induced oxidative damage in mice: biochemical and immunological basis.

The metabolism of ethanol gives rise to the generation of excess amounts of reactive oxygen species and is also associated with immune dysfunction. We examined the efficacy of resveratrol and vitamin E on the immunomodulatory activity and vascular function in mice with liver abnormalities induced by chronic ethanol consumption by measuring the protein, liver-specific transaminase enzymes, antioxidant enzymes and non-enzymes such as reduced glutathione (GSH) content, thiobarbituric acid reactive substance (TBARS) level, nitrite level, and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and cytokines such as interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)-alpha, gamma interferon (IFN-gamma), vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-beta1 in mice blood. Ethanol (1.6 g/kg body wt/day) exposure for 12 wks significantly increased TBARS and nitrite levels and GST activity, and significantly decreased GSH content and the activities of SOD, CAT, GR and GPx in whole blood hemolyzate of 8-10 wks-old male BALB/c mice (weighing 20-30 g). Ethanol exposure also elevated the activities of transaminase enzymes (AST and ALT), IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1, while decreasing the albumin concentration and IL-4 activity in the serum. Both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) treatment significantly reduced AST, ALT, GST, IL-10, TNF-alpha, IFN-gamma, VEGF-A and TGF-beta1 activities and levels of TBARS and nitrite, and elevated albumin content, GSH level and activities of SOD, CAT, GR and GPx, compared to ethanol-treated group. Thus, results from the study demonstrated that both resveratrol (5 mg kg(-1) day(-1)) and vitamin E (80 mg kg(-1) day(-1)) can effectively ameliorate ethanol (1.6 g kg(-1) day(-1))-induced oxidative challenges, immunomodulatory activity and angiogenesis processes.

A novel and cost-effective ex vivo orthotopic model for the study of human breast cancer in mouse mammary gland organ culture.

Mouse mammary organ culture (MMOC) is used to evaluate the efficacy of chemopreventive agents against the development of carcinogen-induced preneoplastic lesions and is highly correlative to in vivo carcinogenesis models. Here, we developed a new ex vivo MMOC model, by introducing human breast cancer cells into the mouse mammary gland. This novel model, termed human breast cancer in MMOC (BCa-MMOC), mimics in vivo orthotopic breast cancer mouse models. To develop this model, estradiol- and progesterone-sensitized female mice were injected with letrozole-sensitive and -resistant T47D breast cancer cells in the mammary glands and then euthanized. The glands were cultured in vitro with hormone-supplemented media. On day 25, the glands were fixed and processed by histopathology and immunohistochemistry to evaluate for the presence of T47D cells, growth pattern, cancer markers and estradiol responsiveness. Histopathological analyses demonstrated an identical pattern of growth between the breast cancer cells injected ex vivo and in vivo Interestingly, clusters of cancer cells in the mammary gland stroma appeared similar to those observed in human breast tumors. The injected T47D cells survived and proliferated for 15 days maintaining expression of estrogen receptor alpha (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), and aromatase. The aromatase-overexpressing T47D grown in the BCa-MMOC sufficiently metabolized estrogen, resulting in enhanced cell proliferation, induction of estrogen target genes (i.e. ER and PR-B), and showed typical changes to estrogenic milieu. In summary, here we show a novel, inexpensive ex vivo model, to potentially study the effects of therapeutic agents on cancer cells grown in an orthotopic micromilieu.This article has an associated First Person interview with the first author of the paper.

Time-dependent effects of ethanol on blood oxidative stress parameters and cytokines.

Alcohol consumption is implicated in the genesis of a spectrum of liver abnormalities, which are associated with a number of factors. In the present study, time-dependent effects of ethanol on cytokines (TNF-alpha, IL-2, IL-4, IL-10, IFN-gamma, VEGF-A and TGF-beta1) in serum, and blood oxidative stress parameters such as reduced glutathione content, TBARS level and activities of GPx, GR, GST, catalase and SOD in 8-10 weeks-old male BALB/c mice have been investigated. Ethanol administered @ 1.6 g/kg body wt/day significantly increased the activities of liver marker enzymes AST, ALT and ALP. Serum nitrite levels and haemolysate TBARS level also increased, while total antioxidant status in serum and GSH content in whole blood hemolysate decreased from 4th week onwards of exposure. In spite of the increased serum nitrite level and GST activity in the haemolysate, albumin level in serum, GPx and GR activities in haemolysate decreased after 12 weeks of exposure. Chronic ethanol treatment did not show any effect on IL-2, but IL-4 level was reduced and other cytokines such as IL-10, TNF-alpha, IFN-gamma, TGF-beta1 and VEGF-A levels were increased significantly after 12 weeks. The study indicates a relationship between free radical generation and immune response, and suggests that ethanol-induced liver damage is associated with oxidative stress and immunological alterations in a time-dependent manner.

Effect of lecithin with vitamin-B complex and tocopheryl acetate on long-term effect of ethanol induced immunomodulatory activities.

The alcoholic liver disease usually causes overall immunological alterations which might be attributed to hepatic disease, to ethanol action, and/or to malnourishment. In the present study, efficacy of lecithin with vitamin-B complex to treat ethanol induced immunomodulatory activity was compared with the effect of lecithin alone and tocopheryl acetate (vitamin E). Ethanol (1.6 g/kg body wt/day for 12 weeks) exposure increased thiobarbituric acid reactive substance (TBARS) level, while decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in whole blood hemolysate of 8-10 week-old male BALB/c mice (weighing 20-30 g). The activities of transaminase (AST and ALT) enzymes, interleukin (IL)-10 and gamma interferon (IFN-gamma) elevated, while IL-2 and IL-4 reduced in mice serum due to ethanol exposure. These suggested that oxidative stress and immunomodulatory activities were interdependent and associated with ethanol induced liver damage. Lecithin treatment significantly reduced AST (32.44%), ALT (32.09%), IL-10 (25.63%) activities and TBARS content (12.76%) compared to ethanol treated group. However, lecithin with vitamin-B complex treatment, significantly reduced AST (62.83%); ALT (61.96%); IL-10 (35.88%); IFN-gamma (22.55%) activities and TBARS content (31.58%), while significantly elevated GSH content (36.49%) and SOD activity (61.21%). Tocopheryl acetate treatment significantly reduced AST (62.83%); ALT (61.54%); IL-10 (36.35%): IFN-gamma (23.28%) activities and TBARS content (35.84%). while significantly elevated GSH content (28.76%) and SOD activity (62.42%) compared to ethanol treated group. These findings persuasively argued that lecithin with vitamin-B complex was a new promising therapeutic approach in controlling ethanol induced immunomodulatory activities involving liver damage processes. Prevention of oxidative stress with correction of nutritional deficiency caused alteration in the ethanol-induced immunomodulatory activities and associated liver diseases.

Composite pheochromocytoma masquerading as solid-pseudopapillary neoplasm of pancreas.

Pheochromocytoma and ganglioneuroma form rare composite tumours of the adrenal medulla comprising less than 3% of all sympathoadrenal tumours. We present a case of intraoperatively detected adrenal medullary tumour of composite pheochromocytoma and ganglioneuroma diagnosed on histopathology, in a normotensive patient. A 50-year-old male with a past history of chronic obstructive pulmonary disease presented with abdominal pain and significant weight loss since one month. Ultrasound and contrast-enhanced computed tomography abdomen revealed a large lobulated lesion in the distal body and tail of pancreas suggestive of solid and papillary neoplasm of body and tail of pancreas. Intra-operatively, a 15 cm × 10 cm solid lesion with cystic areas was seen arising from the left lower pole of the adrenal gland pushing the pancreas which appeared unremarkable. In our case, exploratory laparotomy with tumour excision was done. Extensive sectioning and microscopic examination of this adrenal tumour confirmed a diagnosis of composite Pheochromocytoma with Ganglioneuroma on histopathology. Immunophenotyping with S-100 further supported the diagnosis. The goal of this report is to increase the awareness of this rare disease and to further identify its variable presentation.

Evaluation of CD4+/CD8+ T-cell expression and IFN-γ, perforin secretion for B-T constructs of F1 and V antigens of Yersinia pestis.

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Understanding the immune response generated by epitopes recognized by CD4+ and CD8+ T cells is important for the development of safe and effective vaccines designed to promote protective cellular immunity. Apart from humoral response, CD4+ T cells have shown to have a major role in combating the pneumonic form of the disease. In the present study, the secretion of IFN-γ and IL-4 by splenocytes, stimulated by different constructs of B and T cell epitopes of F1 and V antigens, was measured by ELISpot assay. We also measured perforin and IFN-γ expression as a function of cell mediated immunity by flow cytometry. Three B-T constructs of F1 and seven B-T constructs of V antigens produced a high number of IFN-γ secreting cells as compared to native antigen and a low number of IL-4 secreting cells. B-T conjugates of F1 and V antigens showed significantly high (p<0.001) percentage of CD4+ IFN-γ(+) cells as compared to CD8+ IFN-γ(+) cells. Thus, the study highlights the importance of Th1 cytokine and existence of high proportion of CD4+ T cells probably contributing protection in the host. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.