The effect of Spirulina platensis versus soybean on insulin resistance in HIV-infected patients: a randomized pilot study.

UNLABELLED: HIV-infected patients develop abnormalities of glucose metabolism due to the virus and antiretroviral drugs. Spirulina and soybean are nutritional supplements that are cheap, accessible in our community and affect glucose metabolism. We carried out a randomized study to assess the effect of Spirulina platensis versus soybean as a food supplement on HIV/HAART-associated insulin resistance (IR) in 33 insulin-resistant HIV-infected patients. The study lasted for two months at the National Obesity Centre of Cameroon. Insulin resistance was measured using the short insulin tolerance test. Physical activity and diet did not change over the study duration. On-treatment analysis was used to analyze data. The Mann-Whitney U test, the Students T test and the Chi square test were used as appropriate. Curve gradients were analyzed using ANCOVA. Seventeen subjects were randomized to spirulina and 16 to soybean. Each received 19 g of supplement daily. The follow up rate was 65% vs. 100% for spirulina and soybean groups, respectively, and both groups were comparable at baseline. After eight weeks, insulin sensitivity (IS) increased by 224.7% vs. 60% in the spirulina and soybean groups respectively (p < 0.001). One hundred per cent vs. 69% of subjects on spirulina versus soybean, respectively, improved their IS (p = 0.049) with a 1.45 (1.05-2.02) chance of improving insulin sensitivity on spirulina. This pilot study suggests that insulin sensitivity in HIV patients improves more when spirulina rather than soybean is used as a nutritional supplement. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01141777.

Molecular determinants of mexiletine structure for potent and use-dependent block of skeletal muscle sodium channels.

On the basis of the information about drug receptor on voltage-gated sodium channels, mexiletine (Mex) analogs with substitutions at either the asymmetric carbon atom or the aromatic ring were synthesized as pure enantiomers. The compounds were tested in vitro for their ability to produce voltage- and use-dependent block of sodium currents (I(Na)) of frog muscle fibers by the vaseline-gap voltage-clamp method. In all experimental conditions, the drug potency was highly correlated with the lipophilicity of the group on the asymmetric center, the derivative with a benzyl moiety (Me6) having IC(50) values more than 10 times lower than those of Mex, followed by the phenyl (Me4) and the isopropyl (Me5) derivative. All of the compounds showed a further reduction of IC(50) values at depolarized membrane potentials and at high frequency of stimulation (10 Hz). Mex and Me5, but not Me4, produced a stereoselective tonic block of I(Na), the R-(-) isomers being 2-fold more potent than the S-(+) ones. The removal of both methyl groups from the aromatic ring of Mex (Me3) caused a 7-fold reduction of the potency, whereas similar substitutions on the phenyl derivative Me4 (Me7 and Me8) produced opposite effects. In fact, the IC(50) of R-(-) Me7 for use-dependent block of I(Na) was 30 times lower than that of R-(-) Mex. Me8 and Me7 were stereoselective during both tonic and use-dependent blockade. All of the compounds left-shifted the steady-state inactivation curves in relation to their potency and to the duration of the inactivating prepulse. Finally, the presence of apolar groups on the asymmetric center of mexiletine is pivotal to reinforce hydrophobic interactions with the proposed aromatic residues at the receptor, and lead to potent and therapeutically interesting inactivated channel blockers.

Verapamil acute administration: a new dynamic test in hyperprolactinemic states.

We studied the effect of acute administration of the calcium-channel blocker verapamil (VER) in 27 patients with tumoral hyperprolactinemia ([THPRL] prolactinomas and pseudoprolactinomas). We also studied the effect of VER in seven patients with idiopathic hyperprolactinemia (IHPRL) and a small group of patients with normal prolactin (PRL) levels and minimal incidental anomalies shown by magnetic resonance imaging (MRI). The study was performed on 2 separate days: on the first day, all subjects received VER, and on the second they received placebo. Acute administration of VER evoked a remarkable increase in serum PRL in IHPRL (as in normal healthy subjects used as controls), but no response was shown in THPRL, with no overlap between the two conditions. Acute administration of VER stimulated PRL secretion in patients with minimal incidental lesions shown by MRI; however, this increase was smaller in patients whose PRL level consistently reached the upper-normal limit. Although the meaning of such minimal anomalies shown by MRI is unknown, this could suggest that the test is precociously altered. To further elucidate the action of VER on lactotropes, we investigated the effect of VER given intravenously (IV) and compared different oral formulations in healthy subjects. Our data show that the VER test is effective in distinguishing between THPRL and IHPRL, but unfortunately, like other tests, it is not able to individualize patients in whom THPRL is the result of diminished dopaminergic tone (pseudoprolactinoma). From a pathophysiological point of view, calcium influx would appear less important in PRL regulation in chronic disorders of PRL secretion. VER given IV did not stimulate PRL release in normal subjects. This suggests that IV administration could produce a peak with an inadequate duration or that oral formulations may act also by metabolites formed on first-pass metabolism in the liver.

[Autoimmune hypophysitis. Review of the literature and a case report]. / L'ipofisite autoimmune. Rassegna della letteratura e descrizione di un caso.

Lymphoid hypophysitis is a rare disease (fewer than 30 cases) which is associated with lymphocytic infiltration of the pituitary gland with complete or partial hypopituitarism, pituitary mass, and occurrence exclusively in women, often during pregnancy or in the postpartum period. The majority of the women had autoimmune endocrine and not endocrine disorders and in some cases antipituitary antibodies were present. For these reasons an autoimmune cause has been suggested. We report a patient in menopause with chronic thyroiditis and anti nuclear, anti smooth muscle and anti mitochondrial autoantibodies who developed a panhypopituitarism with an empty sella. This case is the third observation of a possible autoimmune atrophy of the pituitary.