Ciro Esposito

Bio: Ciro Esposito is an academic researcher from University of Pavia. The author has contributed to research in topics: Medicine & Renal function. The author has an hindex of 41, co-authored 188 publications receiving 6547 citations. Previous affiliations of Ciro Esposito include Columbia University & University of Miami.

Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties.

Abstract: Advanced glycosylation end products (AGE) of proteins accumulate in the vasculature with diabetes and aging, and are thought to be associated with vascular complications. This led us to examine the interaction of AGE-BSA as a prototype of this class of nonenzymatically glycosylated proteins subjected to further processing, with endothelium. Incubation of 125I-AGE-BSA with cultured bovine endothelium resulted in time-dependent, saturable binding that was half-maximal at a concentration of approximately 100 nM. Although unlabeled normal BSA was not a competitor, unlabeled AGE-BSA was an effective competitor of 125I-AGE-BSA-endothelial cell interaction. In addition, AGE modification of two alternative proteins, hemoglobin and ribonuclease, rendered them inhibitors of 125I-AGE-BSA binding to endothelium, although the native, unmodified forms of these proteins were not. At 37 degrees C, binding of 125I-AGE-BSA or gold-labeled AGE-BSA was followed by internalization and subsequent segregation either to a lysosomal compartment or to the endothelial-derived matrix after transcytosis. Exposure of endothelium to AGE-BSA led to perturbation of two important endothelial cell homeostatic properties, coagulant and barrier function. AGE-BSA downregulated the anticoagulant endothelial cofactor thrombomodulin, and induced synthesis and cell surface expression of the procoagulant cofactor tissue factor over the same range of concentrations that resulted in occupancy of cell surface AGE-BSA binding sites. In addition, AGE-BSA increased endothelial permeability, resulting in accelerated passage of an inert macromolecular tracer, [3H]inulin, across the monolayer. These results indicate that AGE derivatives of proteins, potentially important constituents of pathologic vascular tissue, bind to specific sites on the endothelial cell surface and modulate central endothelial cell functions. The interaction of AGE-modified proteins with endothelium may play an important role in the early stages of increased vascular permeability, as well as vessel wall-related abnormalities of the coagulation system, characteristic of diabetes and aging.

Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.

Abstract: Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.

One-trocar appendectomy in pediatric surgery

Abstract: Laparoscopic appendectomy is a safe alternative to open appendectomy to treat appendicitis. The author reports his experience in performing laparoscopic appendectomy with the use of only one trocar in pediatric patients. Between 1 January 1994 and 30 October 1995 at the Department of General and Pediatric Surgery, Division of Pediatric Surgery of the ``Federico II'' University of Naples, we performed 51 laparoscopic appendectomies. Patient age varied from 4 to 16 years with a mean age of 7 years. In the last 25 patients of our series we performed the one-trocar appendectomy, positioning only one trocar infraumbilically with the use of a 10-mm operative telescope. The appendix is identified, dissected when necessary, grasped laparoscopically with a 450-mm operative atraumatic instrument introduced through the operative channel of the laparoscope, and then exteriorized through the umbilical cannula. The appendectomy was performed using traditional method outside the abdominal cavity. We had no intra- or perioperative mortality or morbidity. The mean overall hospitalization time was 2 days (1–4 days). At a maximal follow-up of 20 months the children have no clinical problems nor any visible scar related to the laparoscopic appendectomy. In conclusion, the author considers the one-trocar appendectomy an appropriate alternative procedure to other techniques of laparoscopic appendectomy.

The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Abstract: Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

Biochemistry and molecular cell biology of diabetic complications

Abstract: Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage, and diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke and limb amputation. Four main molecular mechanisms have been implicated in glucose-mediated vascular damage. All seem to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain. This integrating paradigm provides a new conceptual framework for future research and drug discovery.

Ischemia and reperfusion—from mechanism to translation

Abstract: Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion-associated tissue inflammation and organ dysfunction.

Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes

Abstract: In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA). Recent evidence suggests that common stress-activated signaling pathways such as nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases underlie the development of these late diabetic complications. In addition, in type 2 diabetes, there is evidence that the activation of these same stress pathways by glucose and possibly FFA leads to both insulin resistance and impaired insulin secretion. Thus, we propose a unifying hypothesis whereby hyperglycemia and FFA-induced activation of the nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways, along with the activation of the advanced glycosylation end-products/receptor for advanced glycosylation end-products, protein kinase C, and sorbitol stress pathways, plays a key role in causing late complications in type 1 and type 2 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes. Studies with antioxidants such as vitamin E, alpha-lipoic acid, and N-acetylcysteine suggest that new strategies may become available to treat these conditions.