Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice

CD4⁺ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RB^highCD4⁺ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RB^lowsubset or with unfractionated CD4⁺ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RB^lowpopulation with the CD45RB^high population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RB^high and CD45RB^lowCD4⁺T cell subsets and that disruption of this mechanism has fatalconsequences.     

Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D,Vitamin C,Melatonin, and Zinc

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.     

An independent indicator of erectile dysfunction is C-reactive protein/albumin ratio

Research has found that, instead of passive lipid-accumulated vascular damage, atherosclerosis which is the primary cause of erectile dysfunction (ED) can be seen as an active inflammatory cycle and that inflammation has a central role in the entire atherosclerotic process. As an inflammatory marker, serum C-reactive protein (CRP)/albumin ratio (CAR) may link to ED and ED severity. The CAR, demographic features and other criteria of 198 patients with ED who visited our outpatient clinic during March 2019–April 2020 were prospectively evaluated. The research also included healthy control subjects without systemic or infectious diseases. The mean difference of CAR between ED and no ED was statistically significant (0.55 ± 0.27 and 0.79 ± 0.49, p = .002 respectively). On the basis of the ROC analysis, CAR has a good ED diagnostic value with an area under the curve (AUC) of 0.63 (95% CI:0.541–0.714) and better diagnostic performance to distinguish ED severity (AUC:0.73, 95% CI:0.620–0.842). Additionally, mean CAR gradually increased with increasing severity of ED (for all p < .001). The CAR has been described as an independent ED indicator in the multivariate analysis (p = .001OR = 8.934; 95% CI:2.449–32.583). Increased CAR is associated with ED severity and increased ED risk. For CAR predicting ED and ED severity, a considerable cut-off point was identified.     

Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma

The effect of systemic glucocorticoid therapy on immune parameters was studied in patients with bronchial asthma. Patients were divided into two groups: 1) those receiving oral glucocorticoid; 2) control patients who did not receive systemic glucocorticoid treatment. The glucocorticoid dose varied between 5 and 70 mg per day. Patients had been taking oral therapy for at least 1 year. Glucocorticoid treatment was associated with an increased frequency of respiratory tract infections. Therefore, we need to define immune parameters which may predict an increased risk of infections. In this study, we analyzed several surface markers on lymphocytes and monocytes by flow cytometry. A significant reduction of the ratio of peripheral blood CD4⁺ to CD8⁺ T cells was associated with the administration of oral glucocorticoids. Furthermore, the expression of the HLA-DR molecule on monocytes was reduced in patients with systemic glucocorticoid therapy compared to control patients. Moreover, the capacity to elaborate cytokines by peripheral blood mononuclear cells upon stimulation was greatly reduced after exposure to glucocorticoids in vivo and in vitro. In addition, the humoral immune response was affected, because reduced IgG, IgM, and IgA levels were observed in patients receiving oral glucocorticoids. These results indicate that systemic glucocorticoid treatment in patients with bronchial asthma is associated with cellular and humoral immunosuppression which results in an increased risk of bacterial and viral infections.     

Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-{alpha}-mediated cell death

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharideon the sensitivity to tumor necrosis factor (TNF)--medlatedcell death was studied In an In vitro system. Since secretionof TNF- Is a part of the early host response to viral and bacterialinfection, we examined whether mimicking the Infection withviral and bacterial products could affect the response of cellsto TNF-. Incubation of WEHI 164 fibrosarcoma cells with dsRNAor lipopolysaccharide (LPS) significantly increased their sensitivityto TNF--mediated lysis and to TNF-secreting inflammatory T cell-mediatedlysis. Thus, these products could induce Increased sensitivityto TNF- In cells In an inflammatory focus, possibly contributingto selective elimination of Infected but not healthy cells bythis non-specific cytokine. Additionally, our data show thatboth dsRNA and LPS, as well as TNF- Itself, rapidly Induce nuclearfactor-xB (NF-*B), a DNA-bindlng protein Implicated In regulationof gene expression. We suggest that NF-xB could regulate genescrucial for the induction of cell death by TNF-.     

Use of a new mixture for embolization of intracranial vascular malformations

Summary The internal carotid artery system in swine has a special anatomic configuration similar to a brain arterial-arterial malformation. The internal carotid artery breaks up into a multitude of fine channels (rete mirabile) situated at the base of the skull on the side of the hypophysis. This anatomic arterial model was used to analyze acute and chronic angiographic and histological changes after occlusion of the rete mirabile with I) avitene, II) avitene, and 50% ethanol, III) avitene, 30% ethanol and Polyvinyl alcohol, IV) avitene 50% ethanol and Polyvinyl alcohol, V) IBCA and VI) silk. Histopathological changes observed in the rete mirabile six weeks following occlusion demonstrated that a mixture of avitene, 30% ethanol and Polyvinyl alcohol and IBCA produced the best anatomic results. Embolization with avitene, PVA and ethanol induced a more bland histological reaction than the one observed with IBCA. Preliminary clinical experience with this mixture is reassuring in those cases in which the AVM was surgically resected. The partially thrombosed AVM was easily depressed and compressed by the neurosurgeon allowing for satisfactory hemostasis in and around the nidus of the AVM.This paper was presented in part at the International Symposium on Cerebral Stroke, Sendai, Japan, 1987     

A Clinicopathologic Series of 22 Cases of Tonsillar Granulomas

Objectives Tonsils are uncommonly affected by granulomatous inflammation, often with an obscure cause. This study attempts to elucidate the nature of tonsillar granulomatous inflammation. Design Retrospective clinicopathologic review. Methods Twenty‐two cases of tonsillar granulomas diagnosed between 1940 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. H&E slides and a series of histochemical stains were reviewed, and patient follow‐up was obtained. Results There were 11 males and 11 females, aged 7 to 64 years (mean, 29.9 y). Most of the cases presented bilaterally (n = 19) with sore throat, dysphagia, and/or nasal obstruction. The clinical differential included chronic tonsillitis, tuberculosis, nonspecific infection, sarcoidosis, and a neoplasm. Histologically, the granulomas were focal and scattered, or diffuse, identified in the interfollicular zones (n = 16) and/or the germinal centers (n = 13), and occasionally associated with necrosis (n = 6). Based on histochemical and clinical follow‐up information, the etiology of the granulomas included sarcoidosis (n = 8), tuberculosis (n = 3), Hodgkin's lymphoma (n = 2), toxoplasmosis (n = 1), squamous cell carcinoma (n = 1), and no specific known cause (n = 7). Twelve patients were either alive at last follow‐up or had died with no evidence of disease (mean, 12.4 y), and 9 were either alive at last follow‐up or had died with disease (mean, 24.9 y). One patient was alive with unknown disease status (lost to follow‐up after 13.3 y). Conclusions Although a cause for tonsillar granulomas is frequently identified, a number may not develop an identifiable etiology, with the granulomas probably representing an exaggerated immune response to chronic tonsillitis. However, a careful work‐up must be conducted to exclude specific causes and avoid clinical mismanagement.     

The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo

1. In order to accumulate at sites of inflammation, leukocytes initially roll on endothelial cells of post-capillary venules before becoming firmly attached. This process of rolling is mediated by selectins which bind to carbohydrate counter-ligands present on the surface of both leukocytes and endothelial cells. The polysaccharide fucoidin has been previously shown to inhibit leukocyte rolling in the mesenteric circulation and to reduce neutrophil accumulation in the skin and meninges in experimental inflammation.
2. In the present study we have assessed the effects of fucoidin on eosinophil function in vitro and eosinophil accumulation at sites of inflammation in guinea-pig skin.
3. At concentrations of up to 1200 μg ml⁻¹, fucoidin inhibited phorbol myristate acetate (PMA)-induced eosinophil homotypic aggregation by up to 60% but had no inhibitory effect on PMA-induced eosinophil adhesion to serum-coated plates.
4. Fucoidin effectively reduced the binding of the anti-L-selectin mAb MEL-14 to guinea-pig eosinophils. Binding of a P-selectin-IgG chimera to eosinophils was also partially inhibited by fucoidin, but binding of an anti-CD18 or an anti-VLA-4 mAb were unaffected.
5. When given systemically to guinea-pigs, fucoidin suppressed ¹¹¹In-labelled eosinophil recruitment to sites of allergic inflammation. ¹¹¹In-labelled eosinophil accumulation induced by platelet-activating factor (PAF) and zymosan-activated plasma (as a source of C5a des Arg) was also inhibited.
6. These results demonstrate a role for fucoidin-sensitive selectins in mediating eosinophil recruitment in vivo.