Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.

Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

Tratamiento del tinnitus en hipoacusias neurosensoriales de curvas descendentes por modulación de los neurotransmisores con el uso de acamprosato: experiencia clínica / Tinnitus treatment by neurotransmitter modulation in high frequency sensorineural hearing loss using Acamprosate: a clinical experience

Introducción: El tinnitus neurosensorial está correlacionado con numerosas patologías del oído interno y de su vía central y que pueden originarse en cualquier nivel de ésta; sin embargo todas estas noxas pueden manifestarse igual en corteza auditiva, como una sensación auditiva sin mediar un estímulo acústico externo, de tal manera que este mensajero común deben ser los neurotransmisores. Se han descrito dos en la vía auditiva aferente: el glutamato que es excitatorio y el GABA que es inhibitorio. Numerosos estudios revelan que el tinnitus neurosensorial se produciría por un desbalance de estos dos neurotransmisores con predominio excitatorio. El acamprosato es un fármaco usado en el alcoholismo que actuaría modulando el equilibrio GABA-glutamato. Existe un sólo estudio publicado con el uso del acamprosato en el tinnitus con una mejoría o disminución de su intensidad en 80 por ciento o más de los casos. Objetivos: Conocer la real utilidad del fármaco pues en este estudio, arriba mencionado, la evaluación fue sólo subjetiva y sin seguimiento. Material y Método: Fueron estudiados 20 pacientes tratados por un mes efectuándose tinnitumetría, evaluación psicoemocional (THI) y seguimiento. Resultados: De los 20 pacientes, en dos desapareció el tinnitus, en seis bajaron los niveles de la tinnitumetría en 5 dBo más con mejoría del THI en 50 por ciento o más y en doce pacientes la mejoría fue menor o ninguna. Conclusiones: Sería posible modular los neurotransmisores de la vía auditiva aferente con éxito, en aquellos pacientes con tinnitus severo. Es un estudio original con un respaldo fisiopatológico que abre nuevas perspectivas terapéuticas.

Uso do acamprosato no tratamento do zumbido: um estudo duplo-cego / Tinnitus treatment with acamprosate: double-blind study

O tratamento do zumbido é, ainda nos dias de hoje, um grande desafio para os otorrinolaringologistas. Várias lacunas persistem em sua fisiopatologia, tendo como resultado vários tipos de tratamento, com resultados muito irregulares. O acamprosato é uma droga utilizada no tratamento do alcoolismo, devido à sua ação reguladora da transmissão glutamatérgica e GABA-érgica, nunca tendo sido empregado no tratamento do zumbido. OBJETIVO: Avaliar a segurança e eficácia do uso do acamprosato, no tratamento do zumbido de causa neurossensorial. FORMA DE ESTUDO: ensaio clinico randomizado. MATERIAL E MÉTODO: 50 pacientes com zumbido de causa neurossensorial foram divididos em 2 grupos, 25 recebendo acamprosato e 25 placebo por 3 meses, em um estudo prospectivo duplo-cego, sendo analisados os efeitos terapêuticos e efeitos colaterais, de acordo com escala (nota) de 1 a 10, atribuída pelo próprio paciente. RESULTADOS: Foi observado algum grau de melhora sintomatológica em 86,9 por cento dos pacientes, sendo que em 47,8 por cento dos casos observamos melhora superior a 50 por cento, dados estatisticamente significativos em relação ao placebo. A incidência de efeitos colaterais encontrada foi baixa (12 por cento) e de intensidade leve, com boa tolerabilidade geral. CONCLUSÃO: O acamprosato, medicação utilizada no tratamento do alcoolismo, é eficaz e seguro para o tratamento do zumbido de causa neurossensorial, com percentual de melhora superior à maioria das medicações utilizadas para o tratamento do zumbido, constituindo uma excelente alternativa terapêutica.

Tratamento farmacológico da dependência do álcool / The pharmacologic treatment of the alcohol dependence

As intervencões farmacológicas podem ter um papel crucial na reducão do craving, consumo de álcool e manutencão da abstinência. Este artigo revisa a farmacoterapia para a dependência de álcool com ênfase na naltrexona, dissulfiram e acamprosato. O antagonista opióide naltrexona diminui taxas de recaída, reduz dias de consumo e prolonga períodos de abstinência. Acamprosato restaura a atividade normal dos sistemas glutamato e GABA. Dissulfiram tem demonstrado ser mais efetivo para pacientes que acreditam em sua eficácia e permanecam aderentes ao tratamento. Ondansetron tem-se mostrado promissor na dependência de álcool de início precoce, mas necessita estudos mais extensivos. Topiramato (até 300 mg/dia) foi mais eficaz do que placebo no tratamento da dependência de álcool.

Efficacy of acamprosate in the treatment of alcohol-dependent outpatients

OBJECTIVE: To evaluate the efficacy and security of acamprosate in the treatment of 75 men, aged 18 to 59 years, with diagnosis of alcohol dependence according to the ICD-10. METHODS: Double-blind, placebo-controlled study, 24-week long. After a one-week detoxification period, patients were randomly divided in two groups: the first group received acamprosate (six tablets of 333 mg/d for 12 weeks) and the second group received placebo (six tablets for 12 weeks). After the first 12 weeks, patients continued the follow-up for further 12 weeks without medication. RESULTS: Patients who were receiving acamprosate showed significantly higher continuous abstinence time within the 24 weeks of treatment compared with patients who were assigned to placebo treatment (p=.017). Twenty-five percent of patients who were receiving acamprosate and 20 percent of the placebo-treated patients dropped out. Few side-effects were reported in both groups. CONCLUSION: Acamprosate proved to be safe and effective in treating alcohol-dependent patients and to maintain the abstinence during 24 weeks