Effect of ischaemia on sensory potentials of normal subjects of different ages

In 73 normal subjects, from 10 to 82 years of age, maximum orthodromic sensory nerve conduction velocity was measured in the median nerve before and during a 30 minute period of vascular occlusion. During ischaemia progressive slowing in conduction velocity, decrease in amplitude, and increase in duration of the sensory action potential evoked at wrist and elbow by supramaximal stimulation of digit III were observed. However, a statistically significant difference (P<0·05 to P<0·01) between subjects was noted by grouping them by age: the older the subject, the longer the persistence of sensory response and the less marked the slowing in conduction velocity. The mechanism of the phenomenon has been discussed in relation to a similar longer resistance to ischaemia found in peripheral nerves of diabetic and uraemic patients.     

Skin Vasodilator Function and Vasomotion in Patients with Morbid Obesity: Effects of Gastric Bypass Surgery

Obesity-associated microvascular dysfunction (MVD) involves different body tissues, including skin, and concurs to increased cardiovascular risk in obese patients (Ob-P). Generalized improvement of MVD is an important goal in obesity treatment. Since skin MVD mirrors generalized systemic MVD, skin microvascular investigation in prospective studies in Ob-P may surrogate microvascular investigation in organs more important for cardiovascular risk of the studied patients. In this prospective study, we measured forearm skin post-occlusive reactive hyperaemia (PORH), as percentage flow increase from baseline, and skin vasomotion in 37 Ob-P before Roux-en-Y gastric bypass (RYGB), and in 24 of them about 1 year after RYGB, using laser Doppler flowmetry (LDF). The spectral contribution of skin LDF signal oscillations in the frequency intervals of 0.01–0.02 Hz, 0.02–0.06 Hz, and 0.06–0.2 Hz—corresponding to endothelial-, sympathetic-, and myogenic-dependent vasomotion, respectively, was measured by means of spectral Fourier analysis. The same measurements were also performed in 28 healthy, lean subjects (HLS). Before RYGB, Ob-P had a significant reduction in PORH and in the all vasomotion parameters investigated, compared with HLS. After RYGB, Ob-P who completed the follow-up, had a significant weight loss (∼40 kg on average), together with a full normalisation in PORH and in vasomotion parameters, regardless of diabetes status. Surgically induced sustained weight loss resulted in full normalisation of skin microvascolar function in Ob-P about 1 year after RYGB. This result suggests a beneficial effect of sustained weight loss on generalized MVD of the studied Ob-P.     

Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects

OBJECTIVE: Inflammation plays a pivotal role in the atherosclerotic process, and some chemokines seem to be crucial in the pathogenesis of vascular damage. High-serum homocysteine, recently recognized as an independent risk factor for vascular disease might increase cytokine and chemokine levels, thus amplifying endothelial damage; moreover, it might worse insulin resistance, thus further contributing to enhance cardiovascular risk. The effect of folic acid supplementation in improving in vivo endothelial function is still debated. In this study, we investigated the effect of folic acid supplementation on insulin sensitivity and peripheral markers of inflammation in overweight healthy subjects. DESIGN: The study was performed as an unmasked randomized placebo-controlled trial of 12 weeks duration. SUBJECTS: Sixty healthy volunteers with normal glucose tolerance and BMI between 25 and 29 kg/m2 were enrolled. MEASUREMENTS: Biochemical parameters and plasma concentrations of homocysteine and of some inflammatory molecules were measured at baseline and at the end of the study, together with an estimation of insulin sensitivity. RESULTS: Subjects receiving folic acid supplementation showed a decrement of homocysteine and an amelioration of insulin sensitivity; this treatment was also associated with a significant drop in the circulating concentration of monocyte chemoattractant protein-1, interleukin-8 and C-reactive protein, in the absence of any significant variation of BMI or fat mass. CONCLUSIONS: In healthy overweight subjects a short-term folic acid supplementation reduces the circulating level of some inflammatory mediators independently of weight change, thus suggesting a potential therapeutic role for folic acid in the protection from atherogenesis and cardiovascular diseases.     

Benzydamine: an alternative nonsteroidal anti-inflammatory drug in patients with nimesulide-induced urticaria

BACKGROUND: Cutaneous adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), in particular urticaria/angiedema syndrome, represent a frequent problem in clinical practice. To date laboratory tests for the diagnosis of these adverse reactions are not available. A patient with an adverse drug reaction to NSAIDs needs an alternative drug to assume if necessary. Nimesulide is a highly prescribed nonsteroidal anti-inflammatory drug (NSAID) world-wide. It is also described as one of the most tolerated NSAID. In this paper we present data on the tolerability of benzydamine in nimesulide-sensitive patients. PATIENTS AND METHODS: One hundred and thirty-seven patients with nimesulide-induced urticaria were submitted to a single-blind, placebo-controlled peroral challenge with increasing doses of benzydamine. RESULTS: One hundred and thirty-four out of 137 (98%) patients tolerated benzydamine without adverse effects, only three (2%) experienced immediate systemic urticaria (1 at the first dose and 2 at the second dose). CONCLUSION: Benzydamine is a well tolerated drug in patients with nimesulide-induced urticaria and it may represent a valid alternative NSAID in nimesulide-sensitive patients.     

Insulin resistance in essential hypertension

High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.