Efficacy and safety of Duloxetine compared with placebo for diabetic neuropathy pain: meta-analysis.

Background: Duloxetine is relatively considered as a treatment for diabetic neuropathy pain due it is balanced and potent reuptake inhibitor of both serotonin and nor epinephrine where these neurotransmitters play a great in pain inhibition. Materials and Methods: We searched DLX related articles in Pubmed, Cochrane and Embase from 2005 to 2010. 158 articles were found after through search out of which 68 articles were case reports, reviews and meta-analysis, 40 studies were clinical trials but not efficient data was available, 45 studies were RCTs but not related to our topic. Only 5 RCTs included after exclusion. We then performed the meta-analysis of the studies which met our eligibility criteria we performed fixed effect model network meta-analysis to analyze the efficacy of DLX compare to placebo. We chose diabetic neuropathy duration, diabetes mellitus duration, types of diabetes and DLX with regard to MNSI scale. Results: 5 published RCTs were included in this meta-analysis no significant difference observed for DLX and DND [(SD mean difference 0.22 (95%CI -0.16 to 0.60); P=0.25)] , on diabetes mellitus duration for HbA1c and fasting blood glucose (FBG) [(SD mean difference -0.00 (95%CI-0.087 to 0.87); P=1.00)] and on types of diabetes[(COR 1.00 (95% CI 0.73 to 1.38; P=0.98)] and [(OR 1.00 (95% CI 0.72 to 1.37); P=0.98)] .DLX shown to have significant efficacious compared to placebo for MNSI (95% CI -0.37 to – 0.03); P=0.02)]. Conclusion: In the fixed effect model analyses of DLX, showed similar efficacy to placebo for efficacy parameters, except on MNSI scale but not clinically relevant.

Tityus zulianus and Tityus discrepans venoms induced massive autonomic stimulation in mice

Venezuelan scorpion envenomation is a public health problem produced by Tityus discrepans (TD) and Tityus zulianus (TZ) species. Patients-envenomend by TD developed gastrointestinal and pacreatic disorders and scorpion accidents involving TZ are associated with high mortality rate, which showed cardiopulmonary clinical disorders may be associated to the high levels of plasma catecholamines levels. This distinctive clinical output seems to be associated to a toxin repertoire diversity, which has been previously demonstrated. Trying to mimic the human-envenomation, some toxinological studies have been performed using TD and TZ venoms in several biomedels such as mice and anesthetized rams. The purpose of this study was to evaluate, in vivo using biomodels (mice), the role of autonomic nervous system (sympathetic) stimulation producing some of the clinical signs, via the catecholamines release, on the patho-physiology of the TZ and TD induced envenomation. Thus, a clinical signs here reported during a period of 1 hr, after a single intra-peritoneal injection of sub-lethal doses of TZ or TD venom, which are related with diarrhea, diaphoresis, intense salivation, dehydratation, dyspnea and spasticity in hind limbs. However, these animals did not exhibit vomiting, which is the most frequent human-envenomed TD patients. All animals inoculated with (TD or TZ) venoms develped diarrhea being more pronounced in TD group. Diaphoresis, sialorrhea and dehydratation were mainly observed in TD group. Dyspnea and the hind limb spasticity were only developed in TZ mice. These clinical manifestations (diarrhea, sialorrhea, dehydratation and intense salivation) are related to an activation of autonomic nervous system, via an intense release of their related neurotransmitters. Thus, autonomic stimulation (sympathetic) was evaluated following the catecholamine (Nor-Epinephrine) (NE) plasma levels in a function of envenomation time. We found a significant increments at 1 hr,...

El escorpionismo en Venezuela es un problema actual de salud pública producido por las especies de Tityus discrepans (TD) y Tityus zulianus (TZ). Los pacientes que presentan escorpionismo producido por TD desarrollan trastornos gastrointestinales y pancreáticos mientras que los afectados por TZ presentan una alta mortalidad y muestran una sintomatología relacionada a desordenes cardiopulmonares, los cuales parecen estar asociados a niveles elevados de las catecolaminas plasmáticas. Esta clínica diferente parece estar asociada a una composición distinta de toxinas de dichos venenos, lo cual ha sido previamente demostrado. En un intento de mimetizar o reproducir el escorpionismo en humanos se han realizado estudios toxinológicos con los venenos de TZ y TD utilizando varios biomodelos como son ratones y carneros anestesiados. El propósito de este trabajo fue evaluar, “in vivo” usando un Biomodelo (ratones), el papel de la estimulación del sistema nervioso autónomo (simpático) para producir algunos signos clínicos, vía la liberación de catecolaminas, en la fisiopatología del escorpionismo producido por TZ y TD. Así, los signos clínicos aquí descritos y observados durante 1 hr., después de la inyección de una dosis sub-letal de los venenos de TZ y TD, fueron la presencia de diarrea, diaforesis, salivación intensa, deshidratación, disnea y parálisis en las extremidades posteriores. Sin embargo, estos animales no presentaron vómitos, el cual es uno de los signos más frecuentemente observado en los pacientes con accidentes escorpiónicos por TD. Todos los animales inyectados con los venenos de TD y TZ presentaron diarrea especialmente en grupo TD. La disnea y la parálisis en los miembros posteriores fueron sólo observadas en el grupo de ratones inyectados con TZ. Las manifestaciones clínicas como son diarrea, diaforesis y la salivación intensa están asociadas a una activación del sistema nervioso autónomo...

Effect of Clonidine on the Blood Pressure, Heart Rate and Plasma Catecholamine Concentration during General Anesthesia / 대한마취과학회지

BACKGROUND: Induction of general anesthesia with tracheal intubation and skin incision are potent stimuli that can induce increased sympathetic activity, heart rate and blood pressure. We compared the hemodynamic response and catecholamine concentration during general anesthesia with intravenous clonidine pretreatment, a centrally acting -2 adrenoceptor agonist, and without pretreatment. METHODS: Forty ASA I or II patients aged from 20 to 60 years undergoing elective surgery were randomly allocated to two groups. In group I, 5 ml of 0.9% normal saline as control administered intravenously 10 minutes before induction of anesthesia, and anesthesia was induced with thiopental sodium, succinylcholine and maintained with N2O (2.5L/min)-O2 (2.5L/min)-enflurane (1.3~1.8 vol%). In group II, 4 g/kg clonidine diluted in 5ml of normal saline administered intravenously 10 minutes before induction of anesthesia, and anesthesia was induced with thiopental sodium, succinylcholine and maintained with N2O-O2-enflurane (0.5~1.0vol%) and 2 g/kg/hr clonidine was continuously infused. We measured blood pressure, heart rate and plasma catecholamine at preinduction, 1 minute after intubation (T1), 1 (T2) and 30 minutes after skin incision (T3) and compared with group I. RESULTS: There was statistical significance in systolic and diastolic pressure at T1 between two groups. There was statistical significance in heart rate, epinephrine and norepinephrine at T1, T2 and T3 between two groups. CONCLUSION: The elevation of blood pressure, heart rate and plasma catecholamine accompanying tracheal intubation and skin incision may be prevented by administration of intravenous clonidine.