Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

Is Citicoline Effective in Preventing and Slowing Down Dementia?-A Systematic Review and a Meta-Analysis.

BACKGROUND: Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance. METHODS: We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models. RESULTS: We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor. DISCUSSION: Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.

Postinfarction ventricular septal defect closure.

After a median full sternotomy, cardiopulmonary bypass is installed in the usual manner. Apical ventriculotomy is performed through the infarcted myocardium. Polypropylene pledgeted mattress sutures are passed from the right to the left ventricular side through the ventricular septal defect, with the pledgets remaining on the right ventricle. Great care must be taken to place the suture on healthy myocardium and away from the edge of the ventricular septal defect; otherwise the chances of a recurrent postoperative ventricular septal defect would increase. The sutures are subsequently positioned through a heterologous patch, previously prepared to be appropriate for the ventricular septal defect closure. A collar of 3 to 4 cm is left on the external side of the patch. A 4-0 polypropylene running suture is placed through this collar and the left ventricle to further reinforce the ventricular septal defect closure. The left ventricular incision is closed with polypropylene 3-0 continuous sutures. For each ventricular edge, the running suture is passed through 2 polytetrafluoroethylene felts: one on the endoventricular side and the other on the epicardial side. Finally, the suture line is reinforced with a continuous 2-0 polypropylene suture, which is passed through the polytetrafluoroethylene felts, the ventricular wall, and the heterologous patch used to close the ventricular septal defect.