Neuropathic pain treatment between drug therapy and supplement effects

Neuropathic pain (NP) is a medical condition induced by diseases or lesions in the primary or inner cell systems that influence somatosensory nervous system buildings. Central NP, including backbone pain; multiple sclerosis, is recurrent. NP has an important impact on the life of patients and a strong economic impact on people and the society. some small neuropathy responds like a NSAID, aspirin and ibuprofen to an over-the-counter drug. More strong medicine (such as anti-depressants and serotonin-epinephrine reuptake inhibitors), anticonvulsants (pregabalin and gabapentin), and topical lidocaine-these are recognized as the most advanced neuropathical treatment-is also needed for other serious circumstances to increase ache leadership. Supplemental drugs, such as beta lipoic acid, acetyl-L-carnitine, benfotiamine, taurine and others, have been studied for neuropathic pain relieve under doctors to guarantee safe use and not bring any medicines that may interact with the dietary supplement. A medical procedure has been investigated for a neuro-lipoic pain relief. In specific, owing to the power of drug contrast with alternative products and owing to the effect of some drugs, it was considered that the drugs are (in spite of their side effects) more helpful and efficient to relieve neuropathic pain than the option, since neuropathic pain represents a serious illness and needs a more strong and effective therapy technology (particularly in severe cases).

A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial for Efficacy of Acetyl-L-carnitine in Patients with Dementia Associated with Cerebrovascular Disease

BACKGROUND AND PURPOSE: Acetyl-L-carnitine (ALC) is a widely used drug for various neurodegenerative diseases including dementia. The aim of the present study was to elucidate the efficacy of ALC in dementia patients with cerebrovascular disease (vascular cognitive impairment; VCI). METHODS: Fifty-six patients were randomized to treatment with 500 mg ter in die ALC, or placebo in this 28-week, double-blind, placebo-controlled trial. The primary outcome measure was the Korean version of Montreal Cognitive Assessment (MoCA-K). RESULTS: Following treatment with ALC, the cognitive function measured by the MoCA-K was significantly improved in the ALC-treated groups. However, other secondary outcomes were not statistically significant between ALC- and placebo-treated groups. In MoCA-K analysis, attention and language sub-items significantly favored the ALC-treated group. CONCLUSIONS: Compared with placebo, treatment with ALC 1,500 mg/day produced significant changes in MoCA-K in dementia patients with VCI. ALC was well tolerated in this population. Despite the study limitations, the findings suggested the potential benefits associated with the use of ALC in dementia patients with VCI.

Acetyl-L-carnitine: An Effective Antioxidant against Cryo-damage on Human Spermatozoa with Asthenospermia / 华中科技大学学报（医学）（英德文版）

A variety of natural and artificial cryoprotectant extenders have been explored to enhance sperm recovery following cryopreservation-thawing process.The current investigation is aimed at evaluating the effect of acetyl-L-carnitine on human spermatozoa and reactive species oxygen (ROS) level after freezing-thawing process.The spermatozoa were collected from 35 male patients diagnosed as having asthenospermia.The cryopreservation of human spermatozoa treated with acetyl-L-camitine at different concentrations (group B:2.5 mmol/L,group C:7.5 mmol/L,group D:15 mmol/L) was compared with control (group A:no acetyl-L-carnitine given).For the frozen-thawed spermatozoa,the viability,motility and DNA integrity were measured by comet assay,acrosome integrity by FITC-PNA staining and ROS level was determined in each group.The results showed that there were no significant differences in motility and viability between group A and group B,while the motility and viability of spermatozoa in group C and group D were significantly increased as compared with those in group A.As compared with group A,the values for DNA integrity parameters including comet rate (CR),tail DNA percentage (TD),tail length (TL) and Oliver tail moment (OTM) were significantly reduced in group C and group D.Group C and group D also displayed a higher proportion of intact acrosome than group A.No significant difference in ROS level was found between group A and group B,while with the increase in acetyl-L-camitine concentration,the ROS level in groups C and D was significantly reduced as compared with that in group A.In conclusion,acetyl-L-camitine at a concentration of 7.5 mmol/L is an effective antioxidant against cryo-damage on post-thawed human spermatozoa.

Cerebral Perfusion Changes after Acetyl-L-Carnitine Treatment in Early Alzheimer's Disease Using Single Photon Emission Computed Tomography

BACKGROUND AND PURPOSE: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined. RESULTS: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant (p>0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly (p<0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus (p<0.001), the right middle frontal gyrus (p<0.001), and the right insular cortex (p=0.001) at follow-up. CONCLUSIONS: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients.

Effects of Acetyl-l-carnitine on Autophagy, Apoptosis, and Locomotor Function after Acute Spinal Cord Injury in Rats / 中国康复理论与实践

Objective To observe the effects of acetyl-l-carnitine (ALC) on autophagy, apoptosis and motor function after acute spinal cord injury (ASCI) in rats. Methods Thirty-six adult female Sprague-Dawley rats were randomly divided into sham operation group (Sham group, n=12), simple spinal cord injury group (SCI group, n=12), ALC treatment group (ALC group, n=12). Spinal cord injury model at the level of T10 segment was established using Allen's method. They were assessed with Basso-Beattle-Bresnahan (BBB) scale three days after injury. Then the rats were sacrificed, and the expression of microtubule associated protein 1 light chain 3 (LC3)-II in spinal cord was detect-ed with Western blotting and immunofluorescent labeling, and the number of apoptotic cells were assessed with TUNEL staining. Results The expression of LC3-II and the number of apoptotic cells increased in SCI group compared with those in Sham group (P<0.01), while the BBB score decreased (P<0.001). The expression of LC3-II increased and the number of apoptotic cells decreased in ALC group compared with those in SCI group (P<0.001), while the BBB score increased (P<0.01). Conclusion ALC may promote autophagy, and inhibit apopto-sis to improve the locomotor function after ASCI.

Content of L-carnitine and its acylates in plasma of patients with diabetes and diabetes complications / 中国药理学通报

Aim To investigate the changes of content of L-carnitine (LC ), acetyl-L-carnitine (ALC ) and propionyl-L-carnitine (PLC )in patients with diabetes and its complications.Methods By replicating meth-od of pre-column derivatization HPLC,the contents of plasma LC,ALC,PLC were detercted in normal sub-jects and in patients of diabetes mellitus,diabetic reti-nopathy, diabetic nephropathy, diabetic peripheral neuropathy,diabetic hypertension,diabetic coronary heart disease.Results The concentration of LC in normal subjects and in patients of diabetes mellitus, diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy,diabetic hypertension,diabetic coronary heart disease were (41.01 ±8.05 )μmol · L-1 ,(36.72 ±8.23 )μmol · L-1 ,(33.3 1 ±6.26 )μmol·L-1 ,(33.81 ±5.61 )μmol·L-1 ,(33.57 ± 6.67 )μmol · L-1 , (33.67 ±5.36 )μmol · L-1 , (32.87 ±6.05 )μmol · L-1 respectively.The plasma LC concentration in diabetic group was significantly lower than that of normal control group (P<0.05 ). Moreover,the LC concentration in other groups of dia-betic complications was lower than that in diabetic group, and LC concentration showed no significant difference in various groups of diabetic complications. There was no significant difference in the plasma con-centrations of ALC and PLC of diabetes group and the diabetic complication groups too.Conclusion In Chi-nese normal subjects,patients with diabetes and dia-betic complications,the plasma concentrations of LC in diabetic patients are lower than normal,and plasma concentration of LC in diabetic complications are lower than that in patients with diabetes mellitus.

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

The urine excretion of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-Lcarnitine (PLC) and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD), total antioxidative capacity (T-AOC), malondialdehyde (MDA) and nitrogen monoxidum (NO) activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277) or T-AOC (r = 0.9547), and a negative correlation was found between urine LC excretions and NO (r = -0.8575) or MDA (r = 0.7085). In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.

A excreção urinária de L-carnitina (LC), acetil-L-carnitina (ALC) e propionil-L-carnitine (PLC) e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g) foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentrações urinárias de LC, PLC e ALC foram detectados por HPLC. Atividades superóxido dismutase (SOD), a capacidade antioxidante total (T-AOC), malondialdeído (MDA) e óxido nítrico (NO) foram medidas por métodos espectrofotométricos. O 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excreção de LC foi 53,13±31.36 µmol, 166,93±76.87 µmol, 219,92±76.30 µmol, 100,48±23.89 µmol, 72,07±25.77 µmol, respectivamente. A excreηão de ALC foi 29,70±14.43 µmol, 80,59±32.70 µmol, 109,85±49.21 µmol, 58,65±18.55 µmol, e 80,43±35.44 µmol, respectivamente. A concentraηão de urina de PLC foi 6,63±4.50 µmol, 15,33±12.59 µmol, 15,46±6.26 µmol, 13,41±11.66 µmol e 9,67±7.92 µmol, respectivamente. A taxa de excreηão acumulada de LC foi de 6,1% 24 horas após sua administração. Houve também um aumento nas concentrações de urina de SOD e T-COA e diminuição de NO e de MDA. Correlação positiva foi encontrada entre as concentrações de urina de LC e SOD (r = 0,8277) ou T-AOC (r = 0,9547) e correlação negativa entre a excreção de LC e NO (r = -0,8575) ou MDA (r = 0,7085). Em conclusão, a administração oral única de LC leva ao aumento gradual na excreção urinária de L-carnitina, que foi associada com o aumento das enzimas antioxidantes na urina e as capacidades antioxidantes totais. Estes dados podem ser úteis no futuro para o planejamento de esquemas terapêuticos de LC ou os seus análogos, no futuro.

The Effects on Sperm Parameters and Membrane after Treatment with Progesteroneand/or Acetyl-L-Carnitine; Cryopreservation-Thawing / 대한불임학회지

OBJETIVE: To assess the effects of progesterone and acetyl-L-carnitine used after treated with IsolateR gradient before semen cryopreservation-thawing on sperm parameters and membrane integrity. MATERIALS AND METHODS: From April 2001 to July 2001, ten normal male partner of couples who were visited in vitro fertilization (IVF) clinics. the semens were treated with IsolateR gradient before cryopreservation, spermatozoa was incubated with progesterone (1, 5 and 10 micrometer), acetyl-L-carnitine (2.5, 5 and 10 micrometer), or both (progesterone, 1 micrometer; and acetyl-L-carnitine, 5 micrometer) for 30 min. RESULTS: There were no differences in sperm parameters and vital stain among isolate only treated group, progesterone (1, 5 and 10 micrometer), acetyl-L-carnitine (2.5, 5 and 10 micrometer) and both (progesterone, 1 micrometer; and acetyl-L-carnitine, 5 micrometer). But, in high concentration of acetyl-L-carnitine (10 micrometer) treated group, sperm parameters and vital stain were decreased. The statistical method was used ANOVA (Kruskal-Wallis test) and p value was <0.01. CONCLUSIONS: Neither progesterone nor acetyl-L-carnitine show to be protective effect on the cryodamage assessed by sperm parameters and vital stain (eosin-Y stain) in normal sperm. High concentration of acetyl-L-carnitine (10 micrometer), however, was harmful effect on cryoprevention.