A Slow- Compared with a Fast-Release Form of Oral Arginine Increases Its Utilization for Nitric Oxide Synthesis in Overweight Adults with Cardiometabolic Risk Factors in a Randomized Controlled Study.

BACKGROUND: Oral l-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors. OBJECTIVE: The study was designed to determine the utilization for NO synthesis of oral l-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine. METHODS: In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using [(15)N-(15)N-(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference). RESULTS: Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 ± 52.3 and 142 ± 50.8 µmol ⋅ h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group-by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form. CONCLUSION: In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740.

l-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors.

BACKGROUND: Vascular endothelial dysfunction, the hallmark of early atherosclerosis, is induced transiently by a high-fat meal. High doses of free l-arginine supplements reduce fasting endothelial dysfunction. OBJECTIVE: We sought to determine the effects of a low dose of a sustained-release (SR) l-arginine supplement on postprandial endothelial function in healthy overweight adults with cardiometabolic risk factors and to investigate whether this effect may vary by baseline arginine status. METHODS: In a randomized, double-blind, 2-period crossover, placebo-controlled trial (4-wk treatment, 4-wk washout), we compared the effects of 1.5 g SR-l-arginine 3 times/d (4.5 g/d) with placebo in 33 healthy overweight adults [body mass index (BMI, in kg/m(2)): 25 to >30] with the hypertriglyceridemic waist (HTW) phenotype [plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)]. The main outcome variable tested was postprandial endothelial function after a high-fat meal (900 kcal), as evaluated by use of flow-mediated dilation (FMD) and Framingham reactive hyperemia index (fRHI), after each treatment. By use of subgroup analysis, we determined whether the effect was related to the baseline plasma arginine concentration. RESULTS: In the total population, the effects of SR-arginine supplementation on postprandial endothelial function were mixed and largely varied with baseline fasting arginine concentration (P-interaction < 0.05). In the lower half of the population (below the median of 78.2 µmol arginine/L plasma), but not the upper half, SR-arginine supplementation attenuated the postprandial decrease in both FMD (29% decrease with SR-arginine compared with 50% decrease with placebo) and fRHI (5% increase with SR-arginine compared with 49% decrease with placebo), resulting in significantly higher mean ± SEM values with SR-arginine (FMD: 4.0% ± 0.40%; fRHI: 0.41 ± 0.069) than placebo (FMD: 2.9% ± 0.31%; fRHI: 0.21 ± 0.060) at the end of the postprandial period (P < 0.05). CONCLUSIONS: Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine concentration is relatively low. The benefits of arginine supplementation may be linked to a lower ability to mobilize endogenous arginine for nitric oxide synthesis during a postprandial challenge. This trial was registered at clinicaltrials.gov as NCT02354794.

A New, Simple and Versatile Strategy for the Synthesis of Short Segments of Zigzag-Type Carbon Nanotubes.

Short segments of zigzag single-walled carbon nanotubes (SWCNTs) were obtained from a calixarene scaffold by using a completely new, simple and expedited strategy that allowed fine-tuning of their diameters. This new approach also allows for functionalised short segments of zigzag SWCNTs to be obtained; a prerequisite towards their lengthening. These new SWCNT short segments/calixarene composites show interesting behaviour in solution. DFT analysis of these new compounds also suggests interesting photophysical behaviour. Along with the synthesis of various SWCNTs segments, this approach also constitutes a powerful tool for the construction of new, radially oriented π systems.

Fluoxetine, desipramine, and the dual antidepressant milnacipran reduce alcohol self-administration and/or relapse in dependent rats.

A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.

[Evaluation of knowledge of fibromyalgia in Tunisia]. / Evaluation De La Connaissance De La Fibromyalgie En Tunisie.

BACKGROUND: Fibromyalgia is a chronic, non inflammatory, pain syndrome, characterized by widespread musculoskeletal pain and excessive fatigue. Although it is considered like being the second pathology met in ambulatory rheumatology practice, it is again, poorly understood by medical and scientific community. AIM: value the level of knowledge, attitudes and practices of Tunisian physicians, general practitioners concerning fibromyalgia. METHODS: It was about a cross-sectional survey using questionnaire, achieved by a representative sample of Tunisian physicians, general practitioners. These last, answered a questionnaire previously used in France, in Portugal and in Russia, valuing their knowledge on fibromyalgia, their attitudes and practice in the face of patients suffering from fibromyalgia. RESULTS: Fibromyalgia was recognized as a clinical entity by 26.7% of our physicians. Each general practitioner followed an average of 5.7 patients. The diagnosis of fibromyalgia was made based on widespread pain that persists more than 3 months, sensitive to NSAIDs, for 48% of general practitioners, or on tenderness that occurs in precise, localized areas of the body (trigger points) according to 54% among them. Main symptoms of Fibromyalgia were known with various degrees: pains (87.9%), excessive fatigue (85.7%), muscular weakness (78%), sleeping troubles (65.9%) and psychological disturbance (68.1%). Knowledge of physicians about attitudes and practices in front of cases of fibromyalgia were limited. CONCLUSION: Knowledge of this disease is still mysterious and not well know. General practitioner are aware of fibromyalgia which not included in the program during that training in the medical school. In consequence, our institution, our medical schools in Tunisia should teach this disease to our student and during post graduate courses.

Fibromyalgia syndrome in the general population of France: a prevalence study.

OBJECTIVE: To estimate the prevalence of fibromyalgia (FM) syndrome in the French general population. METHODS: A validated French version of the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ) was administered via telephone to a representative community sample of 1014 subjects aged over 15 years, selected by the quota method. A positive screen was defined as: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and 2-fatigue criteria (LFESSQ-6). To estimate the positive predictive value of LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of rheumatology outpatients (n=178), who were then examined by a trained rheumatologist to confirm or exclude the diagnosis of FM according to the 1990 American College of Rheumatology criteria. The prevalence of FM in the general population was estimated by applying the predictive positive value to eligible community subjects (i.e., positive screens). RESULTS: In the community sample, 9.8% and 5.0% screened positive for LFESSQ-4 and LFESSQ-6, respectively. Among rheumatology outpatients, 47.1% screened positive for LFESSQ-4 and 34.8% for LFESSQ-6 whereas 10.6% were confirmed FM cases. Based on positive screens for LFESSQ-4, the prevalence of FM was estimated at 2.2% (95% CI 1.3-3.1) in the French general population. The corresponding figure was 1.4 % (95% CI 0.7-2.1) if positive screens for LFESSQ-6 were considered. CONCLUSION: Our findings suggest that FM is also a major cause of widespread pain in France since a point prevalence of 1.4% would translate in approximately 680,000 patients.