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Guzman D.C.,Instituto Nacional Of Pediatria Inp | Garcia E.H.,Laboratorio Of Farmacologia | Brizuela N.O.,Laboratorio Of Patologia Experimental | Jimenez F.T.,Laboratorio Of Farmacologia | And 7 more authors.
Archives of Pharmacal Research | Year: 2010

The effect that osteltamivir has on the metabolism of catecholamines and oxidative damage in the brains of young patients remains unclear. The purpose of this study was to measure the effects of oseltamivir, in the presence of oligoelements, on biogenic amines and select oxidative biomarkers in the brains of uninfected, young rats under normal conditions. The study was conducted using male Wistar rats intraperitoneally treated for three days with either a control dose of 0.9 % NaCl, oseltamivir (50 mg/kg), oligoelements (50 μL/rat), or oseltamivir (50 mg/kg) and oligoelements (50 μL/rat). The brain tissue extracted from the treated rats was used to determine the concentrations of adrenaline, noradrenaline, and dopamine, as well as the levels of GSH, lipid peroxidation, and ATPase activity. An increase in the concentration of adrenaline and noradrenaline and in the level of GSH in the group treated with oligoelements (p < 0.001) was observed, while the group treated with oseltamivir and oligoelements, the levels of dopamine increased (p < 0.001), and in the groups treated with oligoelements alone or combination with oseltamivir a decrease in lipid peroxidation was observed (p < 0.001). The results of this study suggest that the consumption of oseltamivir and oligoelements induce biphasic changes in the metabolism of catecholamines; thereby, inducing a protective mechanism against oxidative damage in the brains of young rats. © 2010 The Pharmaceutical Society of Korea and Springer Netherlands.


Calderon Guzman D.,Instituto Nacional Of Pediatria Inp | Bratoeff E.,National Autonomous University of Mexico | Ramirez Lopez E.,National Autonomous University of Mexico | Hernandez Garcia E.,National Autonomous University of Mexico | And 6 more authors.
Andrologia | Year: 2011

Flutamide is a steroid used to treat androgen-dependent disorders and as antiepileptic, but it induces a number of non-desirable side effects. This work was aimed at assaying the effect of flutamide and two novel synthetic steroids on the levels of GABA, glutamine and oxidative stress markers. Male Wistar rats (weight 180g) received a single diazepam dose (5mg/kg) 30min prior to sacrifice (group A). Group B, flutamide; group C, 16β-methyl-17α-benzoyloxypregnen-4-en-3,20-dione; group D, estrone-3-hemisuccinate; group E, testosterone; group F, progesterone; all administered intraperitoneally at 10mg/kg, daily for 3days. Brain and prostate were obtained to assess lipid peroxidation (TBARS), Na+, K+ ATPase activity, reduced glutathione (GSH), γ-amino butiric acid (GABA), glutamine and serotonin (5-HT) concentrations through spectrophotometry, fluorescence and HPLC. GABA levels increased and glutamine decreased in group A (P<0.05). Total ATPase activity increased in group F and TBARS decreased in group B (P<0.05). GSH decreased in A, B and C groups. 5-HT increased in group A and the prostate weight was increased in group E. The conclusion is that 16β-methyl-17α-benzoyloxypregnen-4-en-3,20-dione may be considered novel and promising to treat androgen-dependent diseases and epilepsy, since it showed an antioxidant effect and seemed to impair the GABAergic and serotonergic metabolism. © 2011 Blackwell Verlag GmbH.


Sanjuan N.A.,Laboratorio Of Patologia Experimental | Simula S.,Laboratorio Of Patologia Experimental | Casas J.,University of Buenos Aires | Woscoff A.,Hospital Naval
Medicina | Year: 2010

The family Polyomaviridae is composed of small, non-enveloped, double-stranded DNA viruses widely used to study cell transformation in vitro and tumor induction in vivo. The development of pilomatricomas in mice experimentally infected with polyomavirus led us to detect the viral major capsid protein VP-1 in human pilomatricomas. This tumor, even uncommon, is one of the most frequent benign hair follicle tumors in humans and is composed of proliferating matrix cells that undergo keratinization, and form cystic neoplasms. The detection of VP-1 was performed using the peroxidase-antiperoxidase technique in paraffinembedded slides with a specific primary serum. Adjacent slides treated with normal rabbit serum as a primary were employed as internal control. Positive and negative controls were also employed as well as slides of lesions caused by human papillomavirus to rule out any unspecific cross-reactivity. In 4 out of 10 cases polyomavirus VP-1 was clearly detected in nuclei of human pilomatricomas proliferating cells, in a patchy pattern of distribution. The controls confirmed the specificity of the immunocytochemical procedure. These results could indicate either an eventual infection of the virus in already developed tumors or alternatively, a direct involvement of polyomavirus in the pathogenesis of some pilomatricomas. The recent discovery of a new human polyomavirus associated with Merkel cell carcinomas has been a strong contribution to better understand the pathogenesis of some human uncommon skin cancers. Hopefully the results reported in this work will encourage further research on the role of polyomavirus in other human skin neoplasms.


Kondo W.,Pontifical Catholic University of Parana | dal Lago E.A.,Estudante de Medicina da PUC PR | de Noronha L.,Laboratorio Of Patologia Experimental | Olandoski M.,PUC PR | do Amaral V.F.,PUC PR
Revista do Colegio Brasileiro de Cirurgioes | Year: 2011

Objective: To evaluate the effect of anti-TNF-α in the treatment of endometrial implants in the peritoneum of rats. Methods: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/ kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) α (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. Results: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3% vs. 0%, p = 0.005) and group I10 (+33.3% vs. +18.3%, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF-α in groups L, I5 and I10 was lower than in group C (505.6 mm 2 vs. 660.5 mm 2 vs. 317.2 mm 2 vs. 2519.3 mm 2, respectively; p <0.001). Conclusion: The anti-TNF-α therapy reduced the expression of TNF-α in endometriotic implants, but did not reduce the surface area of the lesion.


Guzman D.C.,Instituto Nacional Of Pediatria Inp | Olguin H.J.,National Autonomous University of Mexico | Brizuela N.O.,Laboratorio Of Patologia Experimental | Garcia E.H.,National Autonomous University of Mexico | And 4 more authors.
Andrologia | Year: 2011

The aim of this study was to evaluate the effect of sildenafil and prostaglandin E1 (PGE1) (drugs used in erectile dysfunction) on production of free radicals in prostate and brain of rat. A single dose of sildenafil (10mgkg-1) and PGE1 (20μgkg-1) was given to Sprague-Dawley rats (300g weight) intraperitoneally. The levels of testosterone were measured in blood. Their brains and prostate glands were separated to measure lipid peroxidation, Na+ and K+ ATPase activity, reduced glutathione (GSH) and serotonin levels, by means of validated methods. The levels of testosterone increased slightly in animals treated with sildenafil and PGE1. The activity of total ATPase was increased in the prostate of animals treated with sildenafil+PGE1 but decreased in those that received sildenafil alone. PGE1 caused significant diminution of GSH levels in both organs. Sildenafil increased the levels of serotonine in brain, whereas in prostate they decreased instead. Our results suggest that sildenafil induced changes in GSH levels as well as in the serotonergic metabolism, alone or with PGE1 in prostate and brain, respectively. Thus, the combination therapy may be ideal to sustain the biochemical balance due to biphasic stimulation on brain and prostate. © 2011 Blackwell Verlag GmbH.


Barragan Mejia G.,Instituto Nacional Of Pediatria Inp | Calderon Guzman D.,Instituto Nacional Of Pediatria Inp | Juarez Olguin H.,Laboratorio Of Farmacologia | Juarez Olguin H.,National Autonomous University of Mexico | And 9 more authors.
Naunyn-Schmiedeberg's Archives of Pharmacology | Year: 2011

Malnutrition contributes to the development of oxidative damage in the central nervous system. The selective administration of nutrients tends to show positive results in individuals who have suffered from malnutrition. To determine the effect of the administration of cocoa powder on the peroxidation of lipids and glutathione level during the nutritional recovery in brain, rats of 21 days old were subjected to a protocol that resembles malnutrition (MN) by feeding them with 60% of the daily food consumption of the control group (WN) and later to nutritional recovery with regular rodent feed (RFR) or added with cocoa (10 g of cocoa powder/kg of regular rodent feed) (CCR). Animals fed with regular rodent food showed significant reduction in brain glutathione: RFR (84.18±6.38 ng/mg protein) vs. CCR (210.61±50.10 ng/mg protein) and WN (186.55±33.18 ng/mg protein), but with similar level to that of MN (92.12±15.60 ng/mg protein). On the contrary, lipid peroxidation in RFR-fed animals increased RFR (1.32±0.2 μM malondialdehyde/g of tissue), CCR (0.86±0.07 μM malondialdehyde/g of tissue), WN (0.89±0.09 μM malondialdehyde/g of tissue), but their thiobarbituric acid reactive substances concentration is similar to that of MN group (1.50±0.2 μM malondialdehyde/g of tissue). Consumption of cocoa powder as a source of antioxidants favors the restoration of the concentration of glutathione and reduces the damage caused by oxidative stress during nutritional recovery in rat brain. © 2011 Springer-Verlag.


Calderon G.D.,Instituto Nacional Of Pediatria Inp | Esquivel G.J.,Instituto Nacional Of Pediatria Inp | Garcia E.H.,Laboratorio Of Farmacologia | Osnaya N.B.,Laboratorio Of Patologia Experimental | And 2 more authors.
Acta Biologica Hungarica | Year: 2010

Our aim was to evaluate the effects of marijuana (Mar) and diazepam (Dz) on lipid peroxidation (TBARS), Na + , K + ATP ase activity, levels of glutathione (GSH) and 5-hydroxytryptophan (5-HTP). Male Wistar rats were given a single dose per group: extract of Mar (100 μL/kg), Dz (5 mg/kg), Mar plus Dz, and NaCl for control. Sixty mins after treatment, animals were sacrificed, and their brains extracted and homogenised to measure GSH, TBARS and 5-HTP levels. Na + , K + ATP ase and total ATP ase activities. GSH and TBARS did not show differences respect to controls. Na + , K + ATP ase activity was similar as well. However, groups treated with Mar, total ATPase activity decreased significantly (p < 0.05). Levels of 5-HTP decreased significantly (p = 0.0001) in rats treated either with Mar and or Dz. Mar and Dz induced biochemical effects on the serotonergic metabolism, which can alter the development and function in rat brain, because it has also been involved in scavenging free radicals present there. © 2010 Akadémiai Kiadó, Budapest.

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