Положительное влияние ацетил-L-карнитина на болевой синдром, регенерацию нервов и вибрационное чувство у пациентов с хронической диабетической нейропатией. Анализ результатов двух рандомизированных плацебоконтролируемых исследований

Objective — we evaluated frozen databases from two 52‑week randomized placebocontrolled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine (alc): 500 and 1,000 mg / day t. i. d.Research design and methods — intention-to-treat patients amounted to 1,257 or 93 % of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.Results — data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg alc.Conclusions — these studies demonstrate that alc treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.Постановка вопроса. Рассмотрены результаты двух рандомизированных плацебоконтролируемых клинических исследований по оценке эффективности применения ацетил-L-карнитина (АЦ-L-К) при диабетической полинейропатии (ДПН) в дозе 500 и 1000 мг / сут, 3 раза в день, продолжительностью 52 нед.Дизайн исследований и методы. В исследованиях приняли участие 1257 пациентов, или 93 % всех осмотренных больных. Эффективность терапии в конечных точках оценивалась по данным морфометрии биоптата икроножного нерва, определению скорости распространения возбуждения (СРВ) по нерву, порогу вибрационного чувства, шкалам клинических симптомов и визуальной аналоговой шкале (ВАШ) при оценке наиболее беспокоящих симптомов, включая боль. Результаты оценивались как для каждого исследования отдельно, так и для всех пациентов, участвующих в обоих исследованиях.Результаты. Полученные данные показали значительное увеличение числа нервных волокон и регенерирующих волокон в кластерах биоптата икроножного нерва. СРВ и амплитуда потенциала нерва не изменялись, в то время как улучшение показателей порога вибрационного чувства отмечено в обоих исследованиях. Уменьшение выраженности боли, как наиболее беспокоящего симптома при ДПН, было отмечено при приеме АЦ-L-К в дозе 1000 мг.Заключение. Оба исследования показали, что прием АЦ-L-К приводит к уменьшению выраженности симптомов у пациентов с установленной ДПН, особенно болевого синдрома, повышает регенерационную способность нервных волокон и вибрационную чувствительность

Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients An adaptive phenomenon?

OBJECTIVE—Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women. RESEARCH DESIGN AND METHODS—Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 ± 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. RESULTS—No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 0.005). CONCLUSIONS—After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity

Use of propionyl L-carnitine for the preparation of a medicament for the treatment of glaucoma.

Uso della propionil L-carnitina per la preparazione di un medicamento per il trattamento del glaucom

Acetyl-L-carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fission.

P>In this work we report that carnitines, in particular acetyl-l-carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho0 strains, suggesting that the protective effects pass through the Yca1 caspase and mitochondrial functions. ALC can also prevent apoptosis in pro-apoptotic mutants, pointing to the importance of mitochondrial functions in regulating yeast apoptosis and aging. We also demonstrate that ALC attenuates mitochondrial fission in aged yeast cells, indicating a correlation between its protective effect and this process. Our findings suggest that ALC, used as therapeutic for stroke, myocardial infarction and neurodegenerative diseases, besides the well-known anti-oxidant effects, might exert protective effects also acting on mitochondrial morphology

Proteomic analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by Lacetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative stress.

Impaired function of the central nervous system (CNS) in aged animals is associated with increased susceptibility to the development of many neurodegenerative diseases. Age-related functional deterioration in brain is consistent with the free radical theory of aging that predicts, among other things, that free radical reactions with and damage to biomolecules, such as proteins and membrane lipid bilayers, leads to loss of neurons and subsequently diminished cognition. These oxidatively modified biomolecules are believed to contribute to the decreased antioxidant content, mitochondrial dysfunction, and impaired plasticity in aged brains. Treatment of rodents with L-acetylcarnitine (LAC; �-trimethyl-�-acetylbutyrobetaine) can improve these functional losses. Although it is well established that administration of LAC can decrease protein oxidation in aged brains, it is not clear which proteins are decreased in their level of oxidation in the brains of aged rats treated with LAC. The current study used a parallel redox proteomics approach to identify the proteins that are oxidized in aged rat cortex and hippocampus of aged rats. Moreover, those proteins that are reduced in oxidation status were identified in aged brains from rats treated in vivo with LAC. The findings are discussed in reference to brain aging and age-related cognitive impairment. Antioxid. Redox Signal. 8, 381–394