Institute Investigaciones Clinicas Dr Americo Negrette


Institute Investigaciones Clinicas Dr Americo Negrette

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Valero N.,Institute Investigaciones Clinicas Dr Americo Negrette | Mosquera J.,Institute Investigaciones Clinicas Dr Americo Negrette | Levy A.,University of Zulia | Anez G.,Institute Investigaciones Clinicas Dr Americo Negrette | And 3 more authors.
Viral Immunology | Year: 2014

Immunosuppressive status against infections in monocytes from neonates and elderly subjects has been reported. The interaction between dengue virus and monocytes/macrophages plays an important role during dengue disease. The aim of this study was to determine the cytokine response of monocytes from individuals with different ages after infection with dengue virus. Monocyte/macrophage cultures from neonatal, adult, and elderly subjects (n=10 each group) were incubated with all four dengue virus types (DENV-1 to -4). After 1 and 3 days of culture, cytokine concentrations (TNF-α, IL-6, and IL-1β) were determined in culture supernatants by enzyme-linked immunosorbant assay. Increased production of all studied cytokines was induced by the different viral types in monocyte/macrophage cultures regardless of their source. However, lower cytokine concentrations were found in neonatal and elderly monocytes. The relative monocyte/macrophage immunosuppressive status observed in neonates and the elderly could be relevant during dengue infection in those age groups and important in innate and adaptive immunity responses against this virus. Copyright © 2014 Mary Ann Liebert, Inc.

Moron-Medina A.,Institute Investigacion | Viera N.,Institute Investigacion | de Morales T.R.,Institute Investigacion | Alcocer S.,Institute Investigaciones Clinicas Dr Americo Negrette | Bohorquez D.,University of Zulia
Investigacion Clinica (Venezuela) | Year: 2014

Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1β, IL-6 y TNF-α in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32μM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis. © 2014, Investigacion Clinica (Venezuela). All rights reserved.

Bermudez J.E.,Institute Investigaciones Clinicas Dr Americo Negrette | Levy A.C.,Catedra de Embriologia | Gonzalez K.,Institute Investigaciones Clinicas Dr Americo Negrette | Espina L.M.,Institute Investigaciones Clinicas Dr Americo Negrette | And 3 more authors.
Kasmera | Year: 2011

Introduction: Various viruses affect the central nervous system (CNS) causing encephalitis, mainly in pediatric patients. Objective: To determine the involvement of viral agents for central nervous system (CNS) infections in children in the State of Zulia, Venezuela during the year 2007. Patients and Methods: 109 samples of cerebrospinal fluid (CSF) and serum were collected from patients between 1 day and 14 years of age, who presented clinical symptoms suggestive of CNS involvement and whose conventional CSF bacteriological study proved negative. The CSF Albumin /serum relationship was determined in order to rule out contamination, resulting in 24 optimal pairs for determining the IgM and IgG antibodies specific for herpes simplex virus (HSV), Epstein Barr (EBV), Dengue fever, rubella, measles and Venezuelan Equine Encephalitis (VEE) using the ELISA technique. Results: Of the 24 cases examined, 15 (62.5%) were positive. The causative agents for encephalitis were 11 cases of Dengue (45.8%) (p<0.05), 3 VHS (12.5%) and 1 case of EBV (4.2%). There were no cases of rubella, measles or VEE. Pleocytosis with lymphocyte predominance was the most common finding in cases with confirmed viral encephalitis (VE), without significant differences related to the infecting viral agent. Conclusions: Results show that a significant proportion of encephalitis in children is due to viral agents, highlighting an increase in dengue cases with CNS affection in the region.

Ryder E.,Institute Investigaciones Clinicas Dr Americo Negrette | Mijac V.,University of Zulia | Fernandez E.,Institute Investigaciones Clinicas Dr Americo Negrette | Palazzi N.,University of Zulia | And 5 more authors.
Investigacion Clinica (Venezuela) | Year: 2014

Clinical observation indicates that many obese individuals do not display important metabolic alterations. Consequently, the objective of this study was to establish whether simple obesity, non concurrent with other important risk factors, was associated with metabolic alterations; or if the phenomenon known as “obesity paradox” was present. A clinical history, measurements of anthropometric and metabolic parameters and estimation of hepatic steatosis and visceral fat, were determined in 30, apparently healthy, individuals from Maracaibo, Venezuela, between 20 and 59 years of age and a body mass index (BMI) above 25 kg/m2, and compared to a lean control group of 11 individuals with BMI less than 25 kg/m2. The study demonstrated that only one third of overweight/obese individuals (OW/OB), with high body mass index (BMI) and waist circumference (WC), presented elevated values of insulin, HOMA-IR and triglycerides. Nevertheless, the presence of hepatic steatosis was elevated in the OW/OB group (91%) vs. 9% in the control group. The visceral fat in the lean control group was associated with both, WC and glycemia; however, it was not related to the BMI or insulin, HOMA-IR and HDLc. The visceral fat in the OW/OB group, although elevated in relation to the lean group, revealed a loss of these associations. In the OW/OB it was the BMI that was associated with insulin and HOMA-IR. The results emphasize the importance of investigating for the presence of hepatic steatosis, rather than visceral fat, in individuals with OW/OB, to identify subjects with high cardiometabolic risk. © 2014, Investigacion Clinica (Venezuela). All rights reserved.

Medina-Leendertz S.,Hospital Universitario Of Maracaiboestado Zulia | Paz M.,University of Zulia | Mora M.,Hospital Universitario Of Maracaiboestado Zulia | Bonilla E.,Hospital Universitario Of Maracaiboestado Zulia | And 5 more authors.
Investigacion Clinica (Venezuela) | Year: 2014

We investigated the effect of melatonin (MEL) in the activities of cytosolic superoxide dismutase (SOD) and catalase as well as in the levels of H2O2 and mitochondrial malondialdehyde (MDA) in paraquat-intoxicated Drosophila melanogaster. Paraquat (40 mM) was administrated for 36 h. Three groups of flies intoxicated with paraquat were used: PQ (exposed during 36h to paraquat), PQ-MEL (exposed during 36h to paraquat and then treated with MEL [0.43 mM] for 12 days) and PQ-Control (maintained in standard corn meal for 12 days). Two additional groups without pre-intoxication with PQ were added: Control (maintained in standard corn meal) and MEL (treated with MEL for 12 days). Immediately after PQ intoxication the concentration of MDA (17.240 ± 0.554 nmoles MDA/mg protein) and H2O2 (3.313 ± 0.086 nmol hydrogen peroxide/mg protein) and the activities of SOD and catalase (419.667 ± 0.731 and 0.216 ± 0.009 Units/mg of protein, respectively) in the PQ group were significantly increased with respect to Control. After 12 days of intoxication with PQ, the PQ-Control flies showed increases in H2O2 (4.336 ± 0.108) and MDA levels (8.620 ± 0.156), and in the activities of SOD and catalase (692.570 ± 0.433 and 0.327 ± 0.003, respectively) as compared to PQ-MEL (p<0.001). Treatment with MEL extended the life span of the groups PQ-MEL and MEL when compared to their corresponding controls. Motor activity decreased significantly in PQ-Control and PQ-MEL flies, suggesting that the damage caused by PQ affected the nervous system of flies. Our findings showed that oxidative damage caused by paraquat was observed even after 12 days and that melatonin mitigates this damage. © 2014, Instituto de Investigaciones Clinicas. All rights reserved.

Chacin-Bonilla L.,Institute Investigaciones Clinicas Dr Americo Negrette | Chacin-Bonilla L.,University of Zulia
Investigacion Clinica (Venezuela) | Year: 2012

Although many drugs destroy Entamoeba histolytica within the colonic lumen, the number of tissue amebicides used to treat invasive amebiasis is still relatively limited. Metronidazole (MTZ), which is the drug of choice for invasive amebiasis, and other nitroimidazoles have greatly simplified the chemotherapy of this disease. However, eradication of E. histolytica infection after completion of MTZ therapy requires additional treatment with luminal amebicides, such as paramomycin. After decades of the introduction of MTZ and other nitroimidazoles in the therapy of amebiasis, there have been few innovations in treating amebic infections. Meanwhile, amebiasis remains among the leading causes of morbidity and mortality in the contemporary world. The toxic effects of MTZ and recent failures in the treatment of several intestinal protozoan parasites, has led to a search for other amebicidal drugs. A recent advance is the demonstration of the effect of nitazoxanide, which has broad spectrum of antiparasitic activity, against E. histolytica. This compound could be the key in the therapy of amebiasis by its action against both luminal and invasive parasite forms. However, the design of an effective vaccine against the infection is still being desirable. Work is underway to develop a vaccine and recent experimental studies are promising. The aim of this review is to examine and discuss the most important aspects of current antiamebic pharmacotherapy and the prospects for development of new drugs and a vaccine.

Romero-Vasquez F.,Venezuelan Institute for Scientific Research | Chavez M.,University of Zulia | Perez M.,Venezuelan Institute for Scientific Research | Arcaya J.L.,Institute Investigaciones Clinicas Dr Americo Negrette | And 5 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Renal inflammation and oxidative stress are constantly present in experimental hypertension. Since the spontaneously hypertensive rat (SHR) has reduced levels of hepatocyte growth factor (HGF), which suppresses the activation of the proinflammatory nuclear transcription factor kappa B (NF-κB), we speculated that HGF deficiency could play a key role in the pathogenesis of hypertension in the SHR. To test this hypothesis we increased HGF in the SHR by HGF gene delivery. We found that kidneys of 15-week-old SHR had an important reduction in HGF mRNA and protein expression. Adult SHRs were randomly assigned to receive weekly hydrodynamic injection (1mg/kg) of a naked plasmid containing human HGF (hHGF) gene associated with a cytomegalovirus promoter (pCMV-HGF) or empty vector (pcDNA3.1) during 6weeks. WKY rats treated with pcDNA3.1 and pCMV-HGF served as controls. The kidneys in the hypertensive SHR untreated and treated with the empty vector had increased NF-κB activation, elevated mRNA and protein expression of RANTES, MCP-1 and IL-6 and increased oxidative stress. Activity of Na+-ATPase was increased while activity of Na+, K+-ATPase was normal. hHGF gene therapy normalized renal NF-κB activity, proinflammatory cytokines, antioxidant status (GSH, SOD and CAT), Na+-ATPase activity, reduced renal injury and ameliorated hypertension. Our results suggest that reduction in HGF production plays a major role in the pathogenesis of hypertension in the SHR and increasing HGF is a potential therapeutic target in the treatment of hypertension. © 2012 Elsevier B.V.

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