Flunarizine in Migraine Prophylaxis: An Indian Trial

Flunarizine, a calcium channel blocker is considered useful in migraine prophylaxis. We report the first Indian trial with this drug. Fifteen patients with migraine were studied in a 6 months double-blind, placebo-controlled crossover trial. Flunarizine was superior to placebo in reducing the severity and duration of the individual attacks though there was no statistically significant effect on frequency of migraine attacks. The side effects most frequently caused by flunarizine were weight gain and daytime sleepiness.     

Carrier-directed anti-hapten responses by b-cell subsets

The capacity of the trinitrophenyl (TNP) haptenic group, coupled to a series of chemically dissimilar carriers, to cross-stimulate putative T- dependent and T-independent murine B-cell subpepulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. It was found that TNP-Ficoll and TNP-dextran, two T- independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-bacterial lipopolysaccharide (LPS), a T-independent polyclonal mitogen, or TNP-horse erythrocytes (HRBC), a T-dependent antigen. On the other hand, TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T- cell signal in T-dependent B-cell responses, whereas nonmitogenic T- independent antigens cannot. However, the cumulative evidence from this and other laboratories strongly indicates that LPS and T-dependent antigens activate B cells by different mechanisms. Of particular interest, LPS is incapable of activating B cells responsive to weakly- or nonmitogenic T-independent antigens. Based on clonal burst size, T-dependent antigens are capable of inducing greater antigen-specific B-cell proliferation than T-independent antigens. However, TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B-cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen. The findings reinforce the evidence favoring existence of multiple B- cell subpopulations with distinctive activation pathways. They also strengthen the proposition that a given B-cell subset can be activated by more than one mechanism.     

Insulin hypoglycaemia test guided by a glucose controlled insulin infusion system

Insulin hypoglycaemia test (IHT) for assessment of hypothalamic-pituitary-adrenocortical (HPA) function in patients with pituitary tumours is usually performed by bolus injection of insulin, a procedure which includes the risk of overdosage and/or the need of repeated administration. This study describes that a glucose controlled insulin infusion system (GCIIS) permits to perform the IHT with standardized hypoglycaemia. Ten healthy volunteers and 10 patients with pituitary tumours were studied using the GCIIS (Biostator) on static control (Mode 1:1, BI 35, QI 10, RI 20, FI 300). Insulin administration was discontinued and the GCIIS used only for monitoring of blood glucose (BG), when BG had fallen below 40 mg/dl and initial clinical symptoms for hypoglycaemia were observed. In controls, the GCIIS guided IHT achieved a sufficient degree of hypoglycaemia (BG 27.6 +/- 2.0 mg/dl; mean +/- SEM) and physiological responses for GH (peak 49.4 +/- 6.7 ng/ml), Prl (peak 1766 +/- 614 microU/ml), ACTH (peak 76.0 +/- 8.7 pg/ml) and cortisol (peak 252 +/- 15 ng/ml). The total amount of insulin given was 0.115 +/- 0.012 U/kg. In the patients with pituitary tumours however, the required insulin dose varied markedly from 0.090 (pituitary insufficiency) to 0.340 U/kg (Cushing's syndrome). Minimum BG obtained was 32.5 +/- 1.9 mg/dl. Partial impairment of hypothalamic-pituitary function and, in particular, patients requiring exogenous cortisol supplementation during stress, could be identified. In conclusion, special advantages of the GCIIS-guided IHT are: Optimal insulin dosage with standardized hypoglycaemia due to automatic adjustment to the individual insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Profiling of levoamphetamine and related substances in dexamphetamine sulfate by capillary electrophoresis

A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity of dexamphetamine as well as the analysis of 1R,2S-(−)-norephedrine and 1S,2S-(+)-norpseudoephedrine as potential impurities has been developed and validated. Heptakis-(2,3-di-O-acetyl-6-O-sulfo)-β-cyclodextrin was chosen as chiral selector upon a screening of neutral and charged cyclodextrin derivatives. Separation of the analytes was achieved in a fused-silica capillary at 20 °C using an applied voltage of 25 kV. The optimized background electrolyte consisted of a 0.1 M sodium phosphate buffer, pH 2.5, containing 10 mg/ml of the cyclodextrin. The assay was linear in the range of 0.06–5.0% of the impurities based on a concentration of 2.0 mg/ml dexamphetamine sulfate in the sample solution. Analysis of commercial dexamphetamine sulfate samples revealed the presence of 3–4% of levoamphetamine while norephedrine or norpseudoephedrine could not be detected, indicating that the compound was prepared by fractionated crystallization of racemic amphetamine. Comparison with polarimetric measurements indicated that dexamphetamine with an enantiomeric excess as low as 80% still passes the pharmacopeial test of specific rotation while an amount of 0.06% of levoamphetamine can be detected by capillary electrophoresis.     

Pathogenesis of Herpes simplex virus infections in guinea pigs.

The pathogenesis of herpes simplex virus types 1 and 2 has been studied in guinea pigs after inoculation by various routes (subcutaneous and intradermal infection in footpads and vaginal infection). Clinical observations as well as virus isolation studies are reported. Herpes simplex virus type 2 infection by all three routes of inoculation led to acute primary and recurrent lesions. Virus persisted in the nervous system, particularly in sensory ganglia, and locally at the site of inoculation. Herpes simplex virus type 1 infection induced no or very mild primary symptoms. Recurrent lesions were only observed after intradermal inoculation. Invasion of the nervous system and consequent establishment of latent ganglionic infection was less efficient than after herpes simplex virus type 2 infection. Peripheral persistence was, however, equally common.