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Biomedical subjects

P Argibay

Publications and source records attributed to P Argibay.

At least 19 recordsLinked to original sources

Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression).

Although a putative role has been attributed to inflammation in the pathogenesis of depressive disorders, the relationship of prostaglandins, known mediators of inflammation, and depression has not been elucidated. Clomipramine is an antidepressive drug with a pro-depressive paradoxical effect in adult rats when administrated neonatally. Using this effect as a model of depression, we investigated the differential expression of the cyclooxygenase (COX-2) gene in rat brains. Rats injected neonatally with clomipramine showed depressive-like symptoms in adulthood, as well as decreased levels of the brain-derived neurotrophic factor (BDNF) and a quantitative differential expression of the COX-2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As evidenced, the relationship between a key enzyme in the prostaglandin synthesis and biological and behavioral depression-like changes opens an interesting line of investigation regarding the molecular bases of depression and its potential treatment through immunomodulatory drugs.

Animals↗

Culture of porcine hepatocytes: the dogma of exogenous matrix revisited.

The use of exogenous matrices has been described as an essential component in securing the viability and functionality of hepatocytes in vitro whether cultured for extracorporeal devices or cell transplantation. Here we report on the in vitro culture of porcine hepatocytes in polystyrene tissue-culture flasks without exogenous matrices showing adequate attachment and viability. Cell proliferation was evidenced by uptake of 5-bromo-2'-deoxyuridine, with peaks at Days 2 (19.7 +/- 8.5%), 15 (20.8 +/- 3.3%), and 35 (21.4 +/- 0.3%). Detoxification capacity was assessed by determination of monoethylglycinexylidide, a product of lidocaine metabolism (highest value 156.5 +/- 10.1 ng/ml at Day 4), and by diazepam clearance (maximum clearance 66.2% at Day 6). Diazepam metabolite levels were highest at Day 4 both for temazepam and oxazepam (6.5 +/- 0.1 and 0.10 +/- 0.01, respectively). These results suggest that the need for an exogenous matrix to achieve sustained proliferative activity and differentiated hepatocyte function should not necessarily be considered a sine qua non condition.

Animals↗

[Characteristics of murine primordial germ cells and their relation with hemopoiesis].

Primordial germ cells (PGC) are a population of cells characterised by a positive reaction to alkaline phosphatase, usually present in the mouse embryo at 7.5 days post coitus (dpc). These cells migrate through various tissues before they become incorporated into the gonadal ridges. Hematopoiesis is a complex developmental system in which the hemopoietic stem cells (HSC) were experimentally shown to have been derived from a single multipotent stem cell. PGC, as well as HSC are regulated by a range of growth factors that control both proliferative and differentiative processes. Leukemia inhibitory factor (LIF) is a cytokine that regulates the differentiation and the totipotentional phenotype of PGC. Recently, other growth factors, such as stem cell factor (SCF), macrophage growth factor (MGF), and forskolin (FRKL) have been proposed as the possible in vivo and in vitro regulators for PGCs and HSCs. Induction of hematopoiesis in an embryonic germ cell derived from PGCs indicates that germ cells acquire the potentiality to differentiate toward hematopoietic cells. The coincidental presence of both PGCs and HSCs at the sites where early hemopoiesis is established, together with similar growth factor requirements support the hypothesis that PGCs may also be considered hemopoiesis initiating cells.

Animals↗

[Isoforms modulation of CD44 adhesion molecule in a murine model of ischemia and intestinal reperfusion].

Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mRNA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IR specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to lymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.

Adjuvants, Immunologic↗

Trans-sialidase from Trypanosoma cruzi induces apoptosis in cells from the immune system in vivo.

Trypanosoma cruzi, the etiologic agent of Chagas' disease, expresses trans-sialidase, an enzyme able to direct transfer of sialyl residues among macromolecules. The enzyme is shed and can be detected in blood during the acute phase of the disease. Several alterations of the immune response and apoptosis of cellular components of the immune system are observed early in the infection. The possible involvement of bloodstream trans-sialidase on these events was analyzed here. The enzyme induced apoptosis in cells of the immune system in the spleen, thymus, and peripheral ganglia. Both natural and recombinant trans-sialidases induced apoptosis to a similar extent. No effect was detected when enzymatically inactive recombinant molecules were used. In dose-response assays, apoptosis was observed even when an amount of trans-sialidase was administered that was enzymatically undetectable in blood. These findings strongly suggest a role for sialic acid mobilization in T. cruzi-induced apoptosis of immune system cells.

Animals↗

[Kidney and pancreas transplantation: initial experience at a single transplant center in Argentina].

After more than 10,000 cases reported all over the world until 1998, simultaneous kidney and pancreas transplantation has become a safe clinical practice, and it may probably represent the best treatment available for diabetic patients in end-stage renal disease. Here we present our results after 12 cadaveric pancreas transplants (8 whole organ, and 4 islet transplants), performed on insulin-dependent diabetic patients. Eleven of these patients received a kidney simultaneously, and one of them required a kidney retransplantation. All vascularised pancreatic grafts were positioned intraperitoneally, anastomosed to the iliac vessels, and bladder drained. One year patient, whole pancreas, and kidney survival rates were 86%, 86% and 71%, respectively. All of these patients remain insulin and dialysis-free, the longest for 37 months. Islets for transplantation were obtained from single cadaveric donors. Fresh, unpurified cells were transplanted intraperitoneally by laparoscopy (equivalent islet yields: 3 x 10(5), 4 x 10(5), 1 x 10(6) and 5 x 10(5)). None of the islet recipients resulted insulin-independent but they all reduced daily requirements in about 40%, with better metabolic control (mean HbA1c pretransplant 9.4 +/- 1.8, vs 7.9 +/- 1.6 posttransplant). One kidney graft was lost due to venous thrombosis. Simultaneous kidney and pancreas transplantation offers the diabetic patient in end-stage renal disease a chance of independence both from dialysis and exogenous insulin. Whole pancreas transplantation has better functional outcome than islet transplantation. Nevertheless, for those diabetic patients who do not meet the criteria to receive a vascularised graft, pancreatic cells may still improve carbohydrate metabolism with minor surgical risk.

Adult↗

[Small intestine transplantation. Experimental microsurgical model in rats].

Small bowel transplantation may eventually become the definitive solution for those patients who suffer from irreversible intestinal failure and that currently depend on parenteral nutrition for survival. Microsurgical transplantation models in rats are widely used for the application of a great variety of immunological and physiological tests. Herein we report our experience after 30 intestinal harvestings and 12 intestinal transplantations in rats. The following criteria were established to assess the surgical procedures: operative time (harvesting and back table, cold ischemic time and warm ischemic time), vascular and intestinal complications and gut histology before and after transplantation. Average time for the donor surgery (harvesting and back table) was 97.19 min. Average warm ischemic time (includes vascular anastomoses) was 115 min. Histological assessment after 3, 4 and 5 hours of cold ischemia (lactated Ringer's solution with 2.4% mannitol at 4 degrees C) showed only mild ischemic changes. Two thrombotic complications were observed: one at the site of the portalcava anastomosis and one at the aortic suture. Hypovolemic shock was the most common cause of death (9/12) and there was no survival beyond 48 hours. Post-transplantation gut histology showed moderate ischemic injury. We conclude that the harvesting technique, as well as the preservation method used are adequate to obtain grafts in a fast and reliable fashion. However, the number of rats transplanted in this experience do not permit statistical analysis of morbidity and mortality at the present time.

Animals↗