Current Issue : April - June Volume : 2012 Issue Number : 2 Articles : 7 Articles
Background: The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of\nsingle-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm\nand Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common\nSTH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a\ncommunity-based randomized controlled trial in the Peopleââ?¬â?¢s Republic of China.\nMethodology/Principal findings: The hookworm CR and fecal ERR were assessed in 314 individuals aged $5 years who\nsubmitted two stool samples before and 3ââ?¬â??4 weeks after administration of single-dose oral albendazole (400 mg) or\nmebendazole (500 mg) or triple-dose albendazole (36400 mg over 3 consecutive days) or mebendazole (36500 mg over 3\nconsecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured\nsignificantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69%\n(95% confidence interval [CI]: 55ââ?¬â??81%) and 29% (95% CI: 20ââ?¬â??45%); triple dose: respective CRs 92% (95% CI: 81ââ?¬â??98%) and\n54% (95% CI: 46ââ?¬â??71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Tripledose\nregimens outperformed single doses against T. trichiura; three doses of mebendazole ââ?¬â?? the most efficacious treatment\ntested ââ?¬â?? cured 71% (95% CI: 57ââ?¬â??82%). Both single and triple doses of either drug were highly efficacious against A.\nlumbricoides (CR: 93ââ?¬â??97%; ERR: all .99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose\napplications cured only half of them.\nConclusions/Significance: Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To\nachieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted....
The present investigation is aimed to develop a new formulation containing chemically cross-linked guar gum microspheres loaded with aspirin for targeting colorectal cancer. The emulsification polymerization method involving the dispersion of aqueous phase of guar gum in castor oil was used to prepare microspheres. Characteristics of microspheres were greatly affected by varying guar gum concentration, glutaraldehyde concentration with 5% v/v span 80, at 800-1000 rpm stirring rate, for a period of 4 h stirring time at 50ºC. Particle size and surface morphology of the microspheres were determined using SEM and phase contrast microscopy. The in vitro release was investigated in simulated gastro intestinal medium of different pH and phosphate buffer saline with and without rat ceacal contents, which was found to be affected by changing the concentration of guar gum and glutaraldehyde. The drug release in phosphate buffer solution (pH 7.0) and simulated gastric fluids followed a similar pattern and had a similar release rate, while a significant increase in drug release (83.23%) was observed in the medium containing 3 % rat ceacal content. In this way, aspirin loaded guar gum microspheres have shown promising results in the management of colorectal cancer....
Aims: Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death.\nBlockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what\nextent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose\nenalapril treatment on these alterations.\nMethods: Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight\nweeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of\nfurosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological\ntechniques and TaqMan PCR.\nResults: After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly\nhigher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac\ninterstitial tissue (2.5760.43% in SNX vs 1.5060.43% in sham, p,0.05) and a significantly lower capillary length density\n(45326355 mm/mm3 in SNX vs 50236624 mm/mm3 in sham, p,0.05) were found. Treatment of SNX with enalapril from\nweek 8ââ?¬â??12 significantly improved myocardial fibrosis (1.6360.25%, p,0.05), but not capillary reduction (39086486 mm/\nmm3) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect.\nSignificantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of\nelastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause\ncomplete regression of these alterations.\nConclusions: The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular\nchanges in SNX....
Introduction: The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to\r\nimprove vaccine efficacy.\r\nMethods: A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR\r\nCanadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard\r\ndoses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to\r\nthe 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (FluviralTM) was used. Serum\r\nhemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess\r\nimmunogenicity.\r\nResults: 297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/mL) and HIV RNA (76% of\r\npatients with viral load ,50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of\r\ninfluenza vaccine across time points and the three influenza strains assessed was poor (Range HAI $40 = 31ââ?¬â??58%). Double\r\ndose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane\r\nand B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen\r\ndose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious\r\nadverse events were thought to be immunization-related.\r\nConclusion: Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is\r\npoor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population....
Background: Artemisinin-based combination therapy is currently recommended worldwide for the treatment of\r\nuncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on\r\nthe initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation\r\ntablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of\r\nboth industrialized and low income countries.\r\nMethods: Pharmaceutical development was performed by a research laboratory at the University Bordeaux\r\nSegalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further\r\ntransferred to a company specialized in pharmaceutical development, and then provided to another company for\r\nclinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal)\r\nwithin a larger Public Private partnership (the FACT project), set up by WHO/TDR, M�©decins Sans Fronti�¨res and the\r\nDrugs for Neglected Disease initiative (DNDi).\r\nResults: The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles\r\nwhile preventing artesunate degradation under tropical conditions. Several options were attempted and failed to\r\nprovide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH\r\nregulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in\r\ncontrolled conditions. However, long-term stability could be achieved, in experimental batches under GMP\r\nconditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu\r\nblisters. Conduction of the workplan was monitored by DNDi.\r\nConclusions: Collaborations between research and industrial groups greatly accelerated the process of\r\ndevelopment of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the\r\ndevelopment process, and no intellectual property right was claimed. This approach resulted in a rapid technology\r\ntransfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO prequalification\r\nof the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under\r\nthe names of Coarsucam�® and Artesunate amodiaquine Winthrop�®, Sanofi-Aventis. The issue related to the\r\ndifficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of\r\napplied research is discussed....
A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15?mg/mL) is currently being investigated for postsurgical analgesia via peripheral nerve block (PNB). Single-dose toxicology studies of EXPAREL (9, 18, and 30?mg/kg), bupivacaine solution (Bsol, 9?mg/kg), and saline injected around the brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints included clinical pathology, pharmacokinetics, and histopathology evaluation on Day 3 and Day 15 (2/sex/group/period). EXPAREL resulted in a nearly 4-fold lower Cmax versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30?mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24 dogs) in the brachial plexus sites. The results indicate that EXPAREL was well tolerated in these models and did not produce nerve damage after PNB in rabbits and dogs....
The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term ââ?¬Å?aspirin resistanceââ?¬Â was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations....
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