Ацетил-L-карнитин при дистимических расстройствах в пожилом возрасте: двойное слепое, мультицентровое, контролируемое рандомизированное исследование в сравнении с флуоксетином

Introduction. L-Acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with dysthymic disorder in comparison with a traditional antidepressant such as fluoxetine.Methods. Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of dysthymic disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments.Results. Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse–Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression.Discussion. The results obtained with LAC and fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity.Введение. Показано, что ацетил-L-карнитин (АЦ-L-К), ацетиловый эфир карнитина, в норме присутствующий в центральной нервной системе и участвующий в метаболических процессах нервной ткани, обладает активностью в различных экспериментальных моделях животных, напоминающих депрессию у человека. Цель исследования – подтвердить антидепрессивное действие АЦ-L-К у пожилых пациентов с дистимическими расстройствами по сравнению с традиционным антидепрессантом флуоксетином.Материалы и методы. В мультицентровое двойное слепое плацебоконтролируемое рандомизированное исследование продолжительностью 7 нед были включены 80 пациентов с диагнозом дистимического расстройства по DSM-IV. Пациенты были разделены на 2 группы: в группе А получали АЦ-L-К и плацебо; в группе Б получали флуоксетин по 20 мг 2 раза в день и плацебо. Клиническая оценка эффекта проводилась 6 раз по нескольким психометрическим шкалам.Результаты. В группе А отмечено статистически достоверное улучшение по следующим шкалам: HAM-D, HAM-A, BDI и тесту Тулуза–Пьерона. Сопоставление групп А и Б выявило практически одинаковую клиническую динамику.Обсуждение. Получены одинаковые результаты по эффективности приема АЦ-L-К и флуоксетина. В связи с пожилым возрастом пациентов предполагается, что положительное влияние АЦ-L-К на настроение может быть связано с улучшением когнитивных симптомов. Различие во времени наступления клинического эффекта (через 1 нед после начала приема АЦ-L-К и через 2 нед от начала приема флуоксетина) предполагает наличие разных механизмов действия, возможно связанных с быстрой активацией метаболических процессов в нервной ткани

Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

Compound useful for preventing cognitive deficit disorders in a new born from HIV-seropositive pregnant female who is in treatment with azidothymidine - N. EP2586438

The present invention relates to acetyl L-carnitine for use in preventing cognitive deficit disorders in a new born from HIV-seropositive pregnant female who is in treatment with azidothymidin

Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia

Objective: To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s): Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration &gt; 20 × 10 6 / mL, sperm forward motility &lt; 50 %, and normal sperm morphology &gt; 30 %; 59 patients completed the study.Intervention(s): Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s): Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s): Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s): The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71.©2005 by American Society for Reproductive Medicine.).</p

L-carnitine: a partner between immune response and lipid metabolism ?

The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions

Effect of propionyl-L-carnitine, L-arginine and nicotinic acid on the efficacy of vardenafil in the treatment of erectile dysfunction in diabetes

Objective: The association of diabetes-related vascular damage and the role of metabolic factors in erectile dysfunction are well known in the literature. The compounds propionyl-L-carnitine (PLC), L-arginine (L-Arg) and nicotinic acid have numerous metabolic actions which have been reported to improve endothelial function. This study investigated the administration of the combination of these three compounds alone and in association with an inhibitor of 5-phosphodiesterase (5PDE), vardenafil, on endothelial function in diabetic patients with erectile dysfunction. Methods: A total of 40 patients aged between 50 and 60 years with insulin-dependent diabetes (IDDM) for 3-4 years were selected from 509 patients presenting with erectile dysfunction. The patients were randomly subdivided into four groups of ten to be treated for 12 weeks. Group A was administered one sachet each day of test formulation containing PLC, L-Arg and nicotinic acid (Ezerex); group B with one 20 mg capsule of vardenafil (Levitra) twice a week; group C was treated with one sachet each day of the test formulation plus vardenafil 20 mg twice a week. Group D was administered placebo capsules twice weekly. Endothelial function was evaluated by examining flow-mediated dilation (FMD) and erectile function was estimated with the International Index of Erectile Function (IIEF5) questionnaire in all subjects. Results: At the end of treatment group A showed an increment of 2 points in the IIEF5; group B showed an increment of 4 points; group C, the group which was administered all the treatments, showed an increment of 5 points, and group D, treated with placebo, showed no increment in the IIEF5. Conclusion: Although there was a small number of subjects in this study the data suggest that the test formulation may improve the endothelial situation in diabetes. The test formulation together with vardenafil was better than the 5PDE inhibitor alone, but further studies are needed to confirm these findings

L acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine

Introduction: L-acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with Dysthymic Disorder in comparison with a traditional antidepressant such as Fluoxetine. Methods: Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of Dysthymic Disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received Fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments. Results: Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression. Discussion: The results obtained with LAC and Fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with Fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity. (C) 2012 Elsevier B.V. and ECNP. All rights reserved