Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia

Cyclooxygenase-2 is involved in the inflammatory component of the ischemic cascade, playing an important role in the delayed progression of the brain damage. The present study evaluated the pharmacological effects of the selective cyclooxygenase-2 inhibitor nimesulide on delayed neuronal death of hippocampal CA1 neurons following transient global cerebral ischemia in gerbils. Administration of therapeutically relevant doses of nimesulide (3, 6 and 12 mg/kg; i.p.) 30 min before ischemia and at 6, 12, 24, 48 and 72 h after ischemia significantly (P<0.01) reduced hippocampal neuronal damage. Treatment with a single dose of nimesulide given 30 min before ischemia also resulted in a significant increase in the number of healthy neurons in the hippocampal CA1 sector 7 days after ischemia. Of interest is the finding that nimesulide rescued CA1 pyramidal neurons from ischemic death even when treatment was delayed until 24 h after ischemia (34+/-9% protection). Neuroprotective effect of nimesulide is still evident 30 days after the ischemic episode, providing the first experimental evidence that cyclooxygenase-2 inhibitors confer a long-lasting neuroprotection. Oral administration of nimesulide was also able to significantly reduce brain damage, suggesting that protective effects are independent of the route of administration. The present study confirms the ability of cyclooxygenase-2 inhibitors to reduce brain damage induced by cerebral ischemia and indicates that nimesulide can provide protection when administered for up to 24 h post-ischemia

Ozone treatment reduces blood oxidative stress and pancreas damage in a streptozotocin-induced diabetes model in rats

A pesar de que la ozonoterapia se ha utilizado con éxito en la terapia con efectos beneficiosos, se han realizado pocos estudios bioquímicos o farmacodinámicos dirigidos al estudio de su mecanismo de acción. Hemos demostrado previamente que la administración controlada del ozono promueve el precondicionamiento oxidativo o adaptación al estrés, fenómeno que previene del daño causado por las Especies Reactivas del Oxígeno (ERO) mediante la preservación de los sistemas antioxidantes endógenos. Teniendo en consideración que la estreptozotocina (STZ) es un ageneradosr de ERO que promueve el daño pancreático, estudiamos el efecto del ozono sobre marcadores sanguíneos del estés oxidativo y su relación con el daño tisular originado por STZ. Se trabajó con 5 grupos experimentales: (1) control no diabético, tratado solo con solución amortiguadora citrato, (2) Control positivo, al que se le inoculó el agente inductor de daño STZ, (3) grupo tratado con ozono, que recibió 10 tratamientos (1,1 mg/kg) antes de inducir el daño con STZ, (4) grupo tratado con oxígeno Oxygen (26 mg/kg) con la misma frecuencia de tratamientos que el grupo (3) y (5) control ozono, que recibió un tratamiento similar a grupo 3 pero no se indujo daño con STZ. El grupo tratado con ozono + STZ produjo una mejoría del control glicémico en comparación con el grupo tratado con STZ (16,1 ± 1,45 vs 27,12 ± 2,12 mmol/L). El ozono controló el estrés oxidativo en plasma al reducir las concentraciones de malondialdehido, hidroperóxidos totales y el potencial de peroxidación. Adicionalmente, el sistema de antioxidantes endógenos se incrementó (superóxido dismutasa, catalasa, glutatión peroxidasa y glutatión reducido). En correspondencia con estos resultados se observó una disminución en el porcentaje de daño de los islotes pancreáticos en el grupo tratado con ozono. Las propiedades antioxidantes del ozono preservaron la función de las células β-pancreáticas y redujeron la hiperglicemia. Este conjunto de resultados sugiere que el ozono como terapia complementaria representa una alternativa potencial en el tratamiento de la diabetes y sus complicacionesIn spite of the fact that ozone has been used as a therapeutical agent and beneficial effects have been observed, so far only a few biochemical and pharmacodynamic mechanisms have been studied. We have demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by Reactive Oxygen Species (ROS) through preservation of antioxidant endogenous systems. Taking into account that STZ produces ROS generation, which promotes pancreas damage with loss of its function, we studied ozone effects on blood oxidative stress and its relationship with pancreas injury mediated by STZ. Five groups of rats were classified as follows: (1) Non-diabetic control group treated only with citrate buffer solution; (2) positive control group using as a diabetes inductor; (3) Ozone group, receiving 10 treatments (1.1 mg/kg) one per day after STZinduced diabetes; (4) Oxygen (26 mg/kg) one per day, as in group 3 but using oxygen only; (5) control ozone, as group 3, but without STZ. Ozone + STZ treatment improved glycemic control with regard to STZ group (16.1 ± 1.45 vs 27.12 ± 2.12 mmol/L). Blood oxidative stress was controlled by ozone as it was showed in the reduction of malondialdehyde, total hydroperoxides and peroxidation potential. In addition, antioxidant endogenous systems were increased (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione). In line with these results, there was a decrease in the percentage of damaged pancreatic islets by ozone treatment. Ozone antioxidant properties preserved β-cells functions and reduced hyperglycemia. Taken together, these results suggest that this complementary medical approach may represent a potential alternative in the treatment of diabetes and its complicationsColegio de Farmacéuticos de la Provincia de Buenos Aire

Ozone treatment reduces blood oxidative stress and pancreas damage in a streptozotocin-induced diabetes model in rats

A pesar de que la ozonoterapia se ha utilizado con éxito en la terapia con efectos beneficiosos, se han realizado pocos estudios bioquímicos o farmacodinámicos dirigidos al estudio de su mecanismo de acción. Hemos demostrado previamente que la administración controlada del ozono promueve el precondicionamiento oxidativo o adaptación al estrés, fenómeno que previene del daño causado por las Especies Reactivas del Oxígeno (ERO) mediante la preservación de los sistemas antioxidantes endógenos. Teniendo en consideración que la estreptozotocina (STZ) es un ageneradosr de ERO que promueve el daño pancreático, estudiamos el efecto del ozono sobre marcadores sanguíneos del estés oxidativo y su relación con el daño tisular originado por STZ. Se trabajó con 5 grupos experimentales: (1) control no diabético, tratado solo con solución amortiguadora citrato, (2) Control positivo, al que se le inoculó el agente inductor de daño STZ, (3) grupo tratado con ozono, que recibió 10 tratamientos (1,1 mg/kg) antes de inducir el daño con STZ, (4) grupo tratado con oxígeno Oxygen (26 mg/kg) con la misma frecuencia de tratamientos que el grupo (3) y (5) control ozono, que recibió un tratamiento similar a grupo 3 pero no se indujo daño con STZ. El grupo tratado con ozono + STZ produjo una mejoría del control glicémico en comparación con el grupo tratado con STZ (16,1 ± 1,45 vs 27,12 ± 2,12 mmol/L). El ozono controló el estrés oxidativo en plasma al reducir las concentraciones de malondialdehido, hidroperóxidos totales y el potencial de peroxidación. Adicionalmente, el sistema de antioxidantes endógenos se incrementó (superóxido dismutasa, catalasa, glutatión peroxidasa y glutatión reducido). En correspondencia con estos resultados se observó una disminución en el porcentaje de daño de los islotes pancreáticos en el grupo tratado con ozono. Las propiedades antioxidantes del ozono preservaron la función de las células β-pancreáticas y redujeron la hiperglicemia. Este conjunto de resultados sugiere que el ozono como terapia complementaria representa una alternativa potencial en el tratamiento de la diabetes y sus complicacionesIn spite of the fact that ozone has been used as a therapeutical agent and beneficial effects have been observed, so far only a few biochemical and pharmacodynamic mechanisms have been studied. We have demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by Reactive Oxygen Species (ROS) through preservation of antioxidant endogenous systems. Taking into account that STZ produces ROS generation, which promotes pancreas damage with loss of its function, we studied ozone effects on blood oxidative stress and its relationship with pancreas injury mediated by STZ. Five groups of rats were classified as follows: (1) Non-diabetic control group treated only with citrate buffer solution; (2) positive control group using as a diabetes inductor; (3) Ozone group, receiving 10 treatments (1.1 mg/kg) one per day after STZinduced diabetes; (4) Oxygen (26 mg/kg) one per day, as in group 3 but using oxygen only; (5) control ozone, as group 3, but without STZ. Ozone + STZ treatment improved glycemic control with regard to STZ group (16.1 ± 1.45 vs 27.12 ± 2.12 mmol/L). Blood oxidative stress was controlled by ozone as it was showed in the reduction of malondialdehyde, total hydroperoxides and peroxidation potential. In addition, antioxidant endogenous systems were increased (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione). In line with these results, there was a decrease in the percentage of damaged pancreatic islets by ozone treatment. Ozone antioxidant properties preserved β-cells functions and reduced hyperglycemia. Taken together, these results suggest that this complementary medical approach may represent a potential alternative in the treatment of diabetes and its complicationsColegio de Farmacéuticos de la Provincia de Buenos Aire

Contribution to characterization of oxidative stress in diabetic patients with macroangiopatic complications

El propósito del presente trabajo fue el estudio del comportamiento de un grupo de indicadores redox en pacientes diabéticos con complicaciones macroangiopáticas y su comparación con los valores de sujetos sanos. Se tomaron muestras de sangre de 101 pacientes y 60 voluntarios sanos y los indicadores del balance redox fueron analizados mediante técnicas espectrofotométricas. Todos los biomarcadores del estado antioxidantes/por-oxidantes y las concentraciones de óxido nítrico (NO) fueron significativamente diferentes (p < 0,05) en los pacientes diabéticos cuando se compararon con los sujetos sanos. Se produjo un incremento en los indicadores de daño a biomoléculas (p.ej. el valor del malondialdehido fue de (8,91 ± 0,64 comparado con 1,80 ± 0,07 µM en los controles), una reducción significativa (p < 0,05) de los valores de antioxidantes solubles (glutatión 2,83 ± 0,30 vs. 3,32 ± 0,62 µM en los controles) y una reducción de las concentraciones de NO en los pacientes diabéticos (51,28 ± 8,58 vs. 67,82 ± 22,44 µM en los controles). La enzimas antioxidantes se activaron en estos pacientes y se observó una disrupción en el equilibrio entre el balance catalasa/superóxido dismutasa (2.16 ± 0.10) con relación al valor alcanzado por los controles (0.11 ± 0.20). Adicionalmente, el indicador global de susceptibilidad a la peroxidación lipídica se incrementó en un 82% en los pacientes diabéticos con respecto al grupo de referencia. Los indicadores evaluados pudieran extrapolarse a los ensayos clínicos de rutina indicados a este tipo de pacientes para contribuir a una visión integral del balance oxidantes / antioxidantes y a la evaluación de la eficacia de diferentes terapias.The aim of this study was to investigate the status of an extensive array of redox indices in diabetic patients with macroangiopatic complications compared to healthy subjects. Blood samples from 101 diabetic patients with macroangiopatic complications and 60 healthy subjects were tested by spectrophotometric techniques in order to measure oxidative stress indices. All measured biomarkers of antioxidant-prooxidant balance and nitric oxide (NO) were significantly (p<0.05) modified in diabetic patients compared to normal subjects. An increase of biomolecule damage markers was noted (e.g. malondiadehyde 8.91 ± 0.64 compared to 1.80 ± 0.07 µM in normal subjects). A significantly (p<0.05) reduction of the soluble antioxidant gluthathion (2.83 ± 0.30 vs. 3.32 ± 0.62 mM in control group) and NO levels (51.28 ± 8.58 vs. 67.82 ± 22.44 µM in control group) were also observed in diabetic patients. Antioxidant enzymes were activated in these patients with a disruption of the catalase/superoxide dismutase balance (2.16 ± 0.10) compared to normal subjects (0.11 ± 0.20). In addition, the global indicator susceptibility to lipid peroxidation was increased by 82% in diabetics compared to the control group. The evaluated indicators could be extrapolated to routine clinical analysis and contribute to an integral overview of the oxidant / antioxidant balance in diabetic patients and could also be used as indices of treatment efficacy.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Contribution to characterization of oxidative stress in diabetic patients with macroangiopatic complications

El propósito del presente trabajo fue el estudio del comportamiento de un grupo de indicadores redox en pacientes diabéticos con complicaciones macroangiopáticas y su comparación con los valores de sujetos sanos. Se tomaron muestras de sangre de 101 pacientes y 60 voluntarios sanos y los indicadores del balance redox fueron analizados mediante técnicas espectrofotométricas. Todos los biomarcadores del estado antioxidantes/por-oxidantes y las concentraciones de óxido nítrico (NO) fueron significativamente diferentes (p < 0,05) en los pacientes diabéticos cuando se compararon con los sujetos sanos. Se produjo un incremento en los indicadores de daño a biomoléculas (p.ej. el valor del malondialdehido fue de (8,91 ± 0,64 comparado con 1,80 ± 0,07 µM en los controles), una reducción significativa (p < 0,05) de los valores de antioxidantes solubles (glutatión 2,83 ± 0,30 vs. 3,32 ± 0,62 µM en los controles) y una reducción de las concentraciones de NO en los pacientes diabéticos (51,28 ± 8,58 vs. 67,82 ± 22,44 µM en los controles). La enzimas antioxidantes se activaron en estos pacientes y se observó una disrupción en el equilibrio entre el balance catalasa/superóxido dismutasa (2.16 ± 0.10) con relación al valor alcanzado por los controles (0.11 ± 0.20). Adicionalmente, el indicador global de susceptibilidad a la peroxidación lipídica se incrementó en un 82% en los pacientes diabéticos con respecto al grupo de referencia. Los indicadores evaluados pudieran extrapolarse a los ensayos clínicos de rutina indicados a este tipo de pacientes para contribuir a una visión integral del balance oxidantes / antioxidantes y a la evaluación de la eficacia de diferentes terapias.The aim of this study was to investigate the status of an extensive array of redox indices in diabetic patients with macroangiopatic complications compared to healthy subjects. Blood samples from 101 diabetic patients with macroangiopatic complications and 60 healthy subjects were tested by spectrophotometric techniques in order to measure oxidative stress indices. All measured biomarkers of antioxidant-prooxidant balance and nitric oxide (NO) were significantly (p<0.05) modified in diabetic patients compared to normal subjects. An increase of biomolecule damage markers was noted (e.g. malondiadehyde 8.91 ± 0.64 compared to 1.80 ± 0.07 µM in normal subjects). A significantly (p<0.05) reduction of the soluble antioxidant gluthathion (2.83 ± 0.30 vs. 3.32 ± 0.62 mM in control group) and NO levels (51.28 ± 8.58 vs. 67.82 ± 22.44 µM in control group) were also observed in diabetic patients. Antioxidant enzymes were activated in these patients with a disruption of the catalase/superoxide dismutase balance (2.16 ± 0.10) compared to normal subjects (0.11 ± 0.20). In addition, the global indicator susceptibility to lipid peroxidation was increased by 82% in diabetics compared to the control group. The evaluated indicators could be extrapolated to routine clinical analysis and contribute to an integral overview of the oxidant / antioxidant balance in diabetic patients and could also be used as indices of treatment efficacy.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Alcohol withdrawal syndrome: diagnostic and therapeutic methods

Alcohol withdrawal syndrome (AWS) is a medical emergency, rare in the general population, but very common among alcoholic individuals, which can lead to severe complications when unrecognized or late treated. It represents a clinical condition which can evolve in few hours or days following an abrupt cessation or reduction of alcohol intake and is characterized by hyperactivity of the autonomic nervous system resulting in the development of typical symptoms. According to DSM-5 criteria, the alcohol withdrawal syndrome is defined as such: If patients present at least two of typical signs and symptoms. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised version (CIWA-Ar), is the tool for assessing the severity of AWS. The support to patient with AWS includes pharmacological intervention as well as general support, restoration of biochemical imbalances and specific therapy. Regarding the pharmacological treatment, benzodiazepines represent the gold standard, in particular long-acting benzodiazepines, administered with a gradual reduction up to cessation

Pharmacological treatment for dual diagnosis. A literature update and a proposal of intervention

Background. It has long been appreciated that alcohol use disorder (AUD) is associated with increased risk of psychiatric disorder. As well, people with history of mental disorder are more likely to develop lifetime AUD. Nevertheless, the treatment of dual diagnosis (DD) in alcohol addiction still remains a challenge. The efficacy of pharmacological treatment for these patients has been widely investigated with controversial results. Patients with untreated psychiatric disorder are at higher risk to return to drinking and tend to do so more quickly. The aim of this review was to collect clinical data for developing guidelines for the pharmacological treatment of psychiatric diseases in a population with AUD. Materials and methods. A literature review was conducted using the following databases: PubMed-NCBI, Cochrane database, Embase Web of Science, and Scopus, including studies published between 1980 and 2015. Search terms were: "guideline", "treatment", "comorbidity", "substance abuse", "alcohol", "dual-diagnosis", "antidepressant", "antipsychotic", "mood-stabilizer". Out of 1521 titles, 84 studies were included for their relevance on pharmacological treatment of psychiatric disorders in people with AUD. Results. Different drugs were collected in major pharmacological classes (antidepressant, mood-stabilizer, antipsychotic), in order to identify their proved efficacy for treating specific psychiatric disorder in the AUD population. Data were selected and verified for publications from randomized clinical trials, open-label trials and case reports. Conclusions. DD in alcohol dependence is a complex clinical entity, and its high prevalence is supported by epidemiological data. Pharmacological management of psychiatric disorders in patients with AUD remains partially anecdotal. Based on reviewed articles, we propose a classification of psychiatric medications for treatment of mental disorders comorbid with AUD, listed with evidence-based recommendations. More research is needed to obtain and collect clinical data, in order to organize and share evidence-based guidelines

Pharmacological treatment of alcohol use disorder. Scientific evidence

Pharmacological treatment of alcohol use disorder represents an essential core of the therapeutic project in a multidisciplinary approach. While non-drug treatment is evolving, from a medical perspective few pharmacotherapies are available; in particular acamprosate, naltrexone and more recently nalmefene among anticraving drugs, disulfiram as an antidipsotropic medication. New studies are focusing on off-label drugs. Moreover, scientific evidence has to support any therapeutic indication which should be tailored on patient needs and comorbidity by considering the individual bio-psycho-social profile. Follow-up is essential in order to assess patient compliance to treatment and monitoring outcomes