Sublineages of Mycobacterium tuberculosis Beijing genotype strains and unfavorable outcomes of anti-tuberculosis treatment.

The influence of Mycobacterium tuberculosis (MTB) lineages/sublineages on unfavorable tuberculosis (TB) treatment outcomes is poorly understood. We investigated the effects of Beijing genotype sublineages and other factors contributing to treatment outcome. Patients newly diagnosed with sputum smear-positive and culture-positive TB in Hanoi, Vietnam, participated in the study. After receiving anti-TB treatment, they were intensively followed up for the next 16 months. MTB isolates collected before treatment were subjected to drug susceptibility testing, and further analyzed to determine MTB (sub) lineages and their clonal similarities. Of 430 patients, 17 had treatment failure and 30 had TB recurrence. Rifampicin resistance was associated with treatment failure {adjusted odds ratio = 6.64 [95% confidence interval (CI), 1.48-29.73]}. The modern Beijing genotype was significantly associated with recurrent TB within 16 months [adjusted hazard ratio = 3.29 (95% CI, 1.17-9.27)], particularly after adjustment for the relevant antibiotic resistance. Human immunodeficiency virus coinfection and severity on chest radiographs were not significantly associated with unfavorable outcomes. Our findings provide further understanding of the influence of MTB strains on unfavorable treatment outcomes. Multiple risk factors should be considered for the optimal management of TB.

Effects of capsazepine, a transient receptor potential vanilloid type 1 antagonist, on morphine-induced antinociception, tolerance, and dependence in mice.

BACKGROUND: Repeated morphine treatment has been shown to induce transient receptor potential vanilloid type 1 (TRPV1) expression in the spinal cord, dorsal root ganglion (DRG), and sciatic nerve of a rat model. Increased TRPV1 expression may therefore play a role in morphine tolerance. In this study, we evaluated the hypothesis that blockage of TRPV1 may be useful as an adjunctive pain management therapy. We investigated whether blockage of TRPV1 by capsazepine, a TRPV1 antagonist, affected antinociception, development of tolerance, and physical dependence on morphine in mice. METHODS: Institute of Cancer Research mice were pretreated with capsazepine and post-treated with morphine acutely and repeatedly. Antinociception and its tolerance were assessed using the hot-plate test. Morphine dependence was examined through the manifestation of withdrawal symptoms induced by naloxone in morphine-dependent mice. RESULTS: Acute capsazepine treatment (5 mg kg⁻¹, i.p.) potentiated the antinociceptive effects of morphine, as measured by the hot-plate test. Repeated co-treatment of capsazepine (2.5 mg kg⁻¹ i.p.) with morphine attenuated the development of tolerance to the antinociceptive effect of morphine. The development of morphine dependence was also reduced by capsazepine (1.25 or 2.5 mg kg⁻¹ i.p.). CONCLUSIONS: Our results suggest that TRPV1 antagonists can be used adjunctively to morphine treatment because they strengthen morphine antinociception and prevent the development of tolerance, and also physical dependence, on morphine.

Lipid composition and structure of commercial parenteral emulsions.

In order to study the influence of the phospholipid/triacylglycerol (PL/TG) ratio of parenteral emulsions on the distribution and the physico-chemical properties of their fat particles, commercial 10, 20 or 30% fat formulas were fractionated by centrifugation into an upper lipid cake (resuspended in aqueous glycerol) and a subnatant or mesophase, from which a PL-rich subfraction (d = 1.010-1.030 g/l) was purified by density gradient ultracentrifugation. Chemical and 31P-NMR analyses of these fractions indicated that at least two types of fat particles coexist in parenteral emulsions: (i) TG-rich particles (mean diameter: 330, 400, 470 nm in the 10, 20, 30% emulsion) which contain practically all the TG and esterified phytosterols of native emulsions, but only a fraction of their PL, unesterified cholesterol and phytosterols, and other minor lipids; (ii) PL-bilayer particles or liposomes (mean diameter: 80-100 nm) which are constituted with the remaining PL and relatively very small amounts of TG and other lipids. The higher the oil content of the emulsion, the lower the amount of these PL-rich particles, which represent the major particle population of the mesophase. Indeed, minute amounts of TG-rich particles (probably the smallest ones) are also present in the mesophase, even in the PL-rich subfraction which contains the bulk of liposomal PL. Since the PL-rich particles of the infused emulsion generate lipoprotein X-like particles, only the large TG-rich particles can be considered as true chylomicron counterparts.

Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus).

Herbal remedies are widely used in Vietnam alongside modern drugs. We assessed the diuretic effect of four traditional Vietnamese herbal remedies from Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus, all claimed to produce an increase of diuresis. No influence was recorded for the 12- and 24-h urine output or on the sodium excretion for any of the drugs when tested under standardized conditions in a placebo controlled double-blind crossover model. The present study indicates the need for critical review of the present recommendations regarding therapy with plant materials in countries relying on empiric traditions.

Renal and biliary elimination of vecuronium (ORG NC 45) and pancuronium in rats.

The urinary excretion of ORG NC 45 (Vecuronium) and of pancuronium was studied in unanesthetized rats and the biliary excretion was studied in anesthetized rats. Urine and bile were analyzed for unchanged drug by a new and specific mass spectrometric assay. Pancuronium was eliminated primarily in the urine (85% +/- 6% of the dose in 12 hours), but little ORG NC 45 appeared in the urine (3.5% +/- 1.1% in 12 hours). Biliary excretion accounted for 46% +/- 4% of the ORG NC 45 dose in 7 hours, but only 7.5% +/- 5.3% of an injected dose of pancuronium appeared in the bile. Thus, it appears that ORG NC 45 (a monoquaternary ammonium compound) has a higher biliary clearance than pancuronium (a bisquaternary ammonium compound). The different biodisposition of these two compounds may be due to the greater lipophilicity and concomitant enhanced permeability into the hepatocyte of ORG NC 45. We conclude that in the rat elimination of pancuronium is primarily via the kidney whereas elimination of ORG NC 45 is dependent on nonrenal mechanisms.