Safety and effi cacy of hepatitis A vaccine in children with chronic liver disease

INTRODUCTION Hepatitis A virus (HAV) infection is common. In general, hepatitis A is a self-limited illness with a recovery time measured in months[1]. Young children are often asymptomatic, whereas adults are more likely to be symptomatic and may present…     

Abnormalities in nitric oxide and its derivatives in lung cancer

RATIONALE: A cellular prooxidant state promotes cells to neoplastic growth, in part because of modification of proteins and their functions. Reactive nitrogen species formed from nitric oxide (NO) or its metabolites, can lead to protein tyrosine nitration, which is elevated in lung cancer. OBJECTIVE: To determine the alteration in these NO derivatives and the role they may play in contributing to lung carcinogenesis. METHODS: We analyzed levels of NO, nitrite (NO2-), nitrate (NO3-), and the location of the protein nitration and identified the proteins that are modified. MEASUREMENTS AND MAIN RESULTS: Although exhaled NO and NO2- were increased, endothelial NO synthase or inducible NO synthase expression was similar in the tumor and tumor-free regions. However, immunohistochemistry showed that nitrotyrosine was increased in the tumor relative to non-tumor-bearing sections. We used proteomics to identify the modified proteins (two-dimensional polyacrylamide gel electrophoresis; mass spectrometry). Both the degree of nitration and the protein nitration profile were altered. We identified more than 25 nitrated proteins, including metabolic enzymes, structural proteins, and proteins involved in prevention of oxidative damage. Alterations of the biology of NO metabolites and nitration of proteins may contribute to the mutagenic processes and promote carcinogenesis. CONCLUSIONS: This study provides evidence in favor of a role for reactive nitrogen and oxygen species in lung cancer.     

Gastrointestinal perforation secondary to COVID-19: Case reports and literature review

Introduction:Corona virus disease-2019 (COVID-19) presents primarily with respiratory symptoms. However, extra respiratory manifestations are being frequently recognized including gastrointestinal involvement. The most common gastrointestinal symptoms are nausea, vomiting, diarrhoea and abdominal pain. Gastrointestinal perforation in association with COVID-19 is rarely reported in the literature.Patient concerns and diagnosis:In this series, we are reporting 3 cases with different presentations of gastrointestinal perforation in the setting of COVID-19. Two patients were admitted with critical COVID-19 pneumonia, both required intensive care, intubation and mechanical ventilation. The first one was an elderly gentleman who had difficult weaning from mechanical ventilation and required tracheostomy. During his stay in intensive care unit, he developed Candidemia without clear source. After transfer to the ward, he developed lower gastrointestinal bleeding and found by imaging to have sealed perforated cecal mass with radiological signs of peritonitis. The second one was an obese young gentleman who was found incidentally to have air under diaphragm. Computed tomography showed severe pneumoperitoneum with cecal and gastric wall perforation. The third case was an elderly gentleman who presented with severe COVID-19 pneumonia along with symptoms and signs of acute abdomen who was confirmed by imaging to have sigmoid diverticulitis with perforation and abscess collection.Interventions:The first 2 cases were treated conservatively. The third one was treated surgically.Outcome:Our cases had a variable hospital course but fortunately all were discharged in a good clinical condition.Conclusion:Our aim from this series is to highlight this fatal complication to clinicians in order to enrich our understanding of this pandemic and as a result improve patients’ outcome.     

Irreversible Loss of Vision in a Child due to Occipital Infarction after Gastroenteritis

A 2½-year-old girl developed a bilateral occipital infarct following severe gastroenteritis with bilateral vision of light perception. Evaluations for sickle cell anemia, hemolytic anemia and coagulopathies were negative. Cortical blindness is an uncommon but dramatic complication of gastroenteritis, hence the need of prompt hydration and other supportive measures to avoid irreversible visual loss or mental sequela.Key Words: Occipital infarct, Gastroenteritis, Visual recovery     

Ethyl glucuronide and ethyl sulfate: a review of their roles in forensic toxicology analysis of alcohol postmortem

Forensic Toxicology - This review presents the current methods used for determining ethyl glucuronide (EtG) and ethyl sulfate (EtS) concentrations in postmortem specimens, including sample...     

Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T cell responses to Cryptococcus neoformans

The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in patients with impaired CD4(+) T cell function, particularly those with AIDS. To identify cryptococcal antigens that could serve as vaccine candidates by stimulating T cell responses, C. neoformans-reactive CD4(+) T cell hybridomas were generated by immunization of C57BL/6 mice and fusion of splenocytes with thymoma cells. The antigen that stimulated one of the hybridomas, designated P1D6, to produce IL-2 was purified to homogeneity by sequential anion exchange chromatography, hydrophobic interaction chromatography, and SDS/PAGE. Based on its apparent molecular mass of 98 kDa and mannosylation, the antigen of interest was named MP98. MP98 was N terminal-sequenced, and the gene encoding the protein was cloned and sequenced. Recombinant MP98, expressed in Saccharomyces cerevisiae, stimulated P1D6 to produce IL-2. Analysis of the derived 458-aa sequence of MP98 reveals an N-terminal cleavable signal sequence, a polysaccharide deacetylase domain found in fungal chitin deacetylases, and a serine/threonine-rich C-terminal region. Overall, there were 103 serine/threonine residues serving as potential O-linked glycosylation sites as well as 12 possible N-linked glycosylation sites. Thus, a C. neoformans mannoprotein has been characterized that stimulates T cell responses and has molecular properties of a chitin deacetylase.     

Severe hypoleptinaemia associated with insulin resistance in patients with common variable immunodeficiency

Objective Common variable immunodeficiency (CVI) is a primary immunodeficiency syndrome characterized by impaired production of antibodies and recurrent infections. Delay in diagnosis leads to metabolic wastage and low body weight. Leptin, a hormone produced by white adipose tissue, modulates insulin action by signal transduction cross‐talk and by direct action on pancreatic beta‐cells. We hypothesized that patients with CVI might present a defective regulation of leptin production and insulin resistance. Patients Thirteen CVI patients (39 ± 11 years) under gammaglobulin replacement were evaluated in parallel with 13 gender‐, age‐, body weight‐ and body mass index (BMI)‐matched healthy voluntaries, and with data from two large population series, the Bruneck and the Hoorn Studies. Measurements Serum leptin and insulin levels, homeostasis model assessment – insulin resistance (HOMA‐IR), body composition, haematological, biochemical and immunoglobulin measurements were obtained. Data were analysed by a one‐way analysis of variance (anova ) and by Pearson's rank analysis. The institutional ethics committee approved the study, and informed consent was obtained from patients and controls. Results No differences were found between CVI and the control group when comparing gender distribution, age, body weight, BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels were lower (P < 0·05) in CVI patients than in controls and lower than fasting leptin levels detected in a large population study. CVI patients’ serum leptin levels did not correlate with BMI (r = 0·074, P = 0·8) and their high HOMA‐IR indicated insulin resistance. Conclusions CVI patients are relatively hypoleptinaemic and insulin resistant, and their serum leptin levels are not correlated to their BMI.