Ultrastructural studies on the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits

Immunoelectron microscopy with peroxidase-conjugated Fab fragments of anti-IgG was used for studying the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits. Small amounts of IgG were found in the cell coat, in caveolae and vesicles, and also in intercellular clefts of endothelial cells from normocholesterolemic rabbits. Injured endothelial cells exhibited prominent accumulations of IgG in the cytoplasmic matrix, possibly due to leakage through plasma membrane defects. In atherosclerotic lesions from hypercholesterolemic rabbits, there was a striking increase in the amount of IgG-reactive material in the cell coat and vesicles of intact endothelial cells. Also in these animals, injured endothelial cells were characterized by a cytoplasmic IgG accumulation. There were prominent IgG depositions in the subendothelial zone of the lesions. IgG was adhering to collagen fibers, and also coating the surfaces of subendothelial foam cells. The pathophysiological significance of an interaction between such intimal IgG and phagocytes is discussed.     

CT appearance of Varicella Zoster lesions in liver and spleen in an immunocompetent patient.

An adult patient presented with vesicular rash and abdominal pain of 5 days duration. His initial laboratory results showed elevated liver enzymes. A contrast enhanced CT scan demonstrated multiple small hypodense nodules in liver and spleen. His serum was reactive for Varicella Zoster IgM. Patient was treated with intravenous Acyclovir for 5 days and followed up with oral tablets for 2 weeks. At 3 weeks, CT scan showed resolution of hypodense nodules and his serum liver enzymes returned to normal at 6 weeks. Patient is on follow up and asymptomatic for 2 years. The CT appearances of nodules and their resolution following specific antiviral therapy are useful in diagnosis and in follow up of disseminated Varicella Zoster.     

Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice

Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF^?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease.     

Serological HLA class I alleles in Senegalese blood donors detected HBs Ag positive

We analysed the HLA class I alleles in 96 blood donors HBs Ag positive compared with 93 healthy control individuals (HBs negative). The most frequent HLA-A, -B, -C alleles found were, A23 (33.6%); A2 (25%); A30 (25%); B8 (31.5%); B7 (16.3%); B58 (11.9%); B35 (11.9%); B49 (11.9%); B53 (10.8%); Cw7 (39.1%); Cw3 (36.9%); Cw4 (36.9%). Significant differences (P<0.001) were found between the blood donors and the controls for the following HLA alleles, A1; A23; B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (P<0.01; odds ratios (OR)=6.25) between positive and negative HBe antigens blood donors for HLA-A1 allele.     

Einfach und praktisch: rechtliche Grundlagen und Verhalten an Einsatzorten mit Verstorbenen

Notfall + Rettungsmedizin -     

The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis.

Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-alpha and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-alpha-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-alpha-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV-related diseases with IFN.     

Repurposing povidone-iodine to reduce the risk of SARS-CoV-2 infection and transmission: a narrative review

BackgroundAccumulating data suggest antiviral effects of povidone-iodine against the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This narrative review aims to examine the antiviral mechanisms of povidone-iodine, efficacy of povidone-iodine against the SARS-CoV-2 virus, and safety of povidone-iodine to human epithelial cells and thyroid function.MethodsWe searched the electronic databases PubMed, Embase, Cochrane Library, ClinicalTrials.gov and World Health Organization’s International Clinical Trials Registry Platform for articles containing the keywords “povidone-iodine”, “SARS-CoV-2” and “COVID-19” from database inception till 3 June 2021.ResultsDespite in vitro data supporting the anti-SARS-CoV-2 effects of povidone-iodine, findings from clinical studies revealed differences in treatment response depending on study settings (healthy vs. hospitalized individuals), treatment target (nasal vs. oral vs. pharynx), method of administration (oral rinse vs. gargle vs. throat spray) and choice of samples used to measure study endpoints (nasopharyngeal vs. saliva). One large-scale clinical trial demonstrated reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak. Povidone-iodine is also used to disinfect the oro-pharyngeal space prior to dental or otolaryngology procedures. Although existing data suggest minimal impact of povidone-iodine on thyroid function, high-quality safety data are presently lacking.ConclusionsPovidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.

Key messages

• Accumulating data suggest antiviral effects of povidone-iodine against the SARS-CoV-2 virus.
• Findings from clinical studies reveal differences in treatment response depending on study settings, treatment target, method of administration and choice of samples used to measure study endpoints. One large-scale clinical trial observed reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak.
• Povidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.