Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles.

Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve. The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP). For this purpose, a 3(2)factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization. The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug. The optimal nanoparticle formulation using 0.25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized. The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1:1), polyD,L-lactide-co-glycolide (PLGA) 50:50 as polymer and an initial mass of 6.6 mg of methylprednisolone. Nanoparticles size and ζ potential of optimized formulation were respectively around 230 nm and -14 mV. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles. Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h. This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of

Digit preferences observed in the measurement of blood pressure: repercussions on the success criteria in current treatment of hypertension.

In a multicenter, open, noncomparative trial to assess the efficacy of an angiotensin-converting enzyme inhibitor, quinapril (Accupril; Parke-Davis), after 12 weeks of treatment in 667 adult patients 19-83 years of age with stage 1-3 hypertension, conducted by 85 physicians in primary health care, with systolic blood pressure (SBP) < 140 mm Hg and diastolic blood pressure (DBP) < 90 mm Hg as criteria for normalization, the efficacy of the drug was 75.1%. When an analysis was made of the frequency tables of BP recorded by the physicians in the case-report forms, a clear numerical preference was found in which the DBP was expressed in multiples of 5 in 81.3% of the cases and the SBP was expressed in multiples of 10 in 19% of the records, so that when a cutoff point <140/90 mm Hg is chosen in daily practice, 130/85 mm Hg is actually being selected. It suffices to change the criteria to accept as normal values less than or equal to instead of less than 140/90 mm Hg to increase the efficacy of the drug from 75.1% to 90.7% in our trial. Therefore, it is proposed to use multiples of 5 for DBP and multiples of 10 for SBP as cutoff points and the diffusion of clear recommendations on BP measurement.

Usefulness of low-dose, once-daily quinapril as monotherapy for patients with hypertension.

A drug surveillance study was performed to determine the tolerance and safety of quinapril in the treatment of patients with stage 1 or 2 hypertension. The trial was noncomparative, open-label, uncontrolled, and nonrandomized. Patients with secondary hypertension, heart failure, other heart diseases, and other serious conditions were excluded. After a washout period of 2 weeks, 752 patients (316 men and 436 women) with diastolic blood pressure (DBP) between 90 and 115 mm Hg and systolic blood pressure (SBP) between 140 and 200 mm Hg were entered into the treatment phase. The mean age of patients (+/- SD) was 53.1 +/- 11.4 years. Patients initially received 10 mg/d quinapril for 4 weeks. For nonresponders, the dosage was titrated up to a maximum of 40 mg. Active treatment continued for 12 weeks. Initial blood pressures (mean +/- SD) were DBP, 102 +/- 6.1 mm Hg, and SBP, 163 +/- 14.4 mm Hg. Final blood pressures were DBP, 83 +/- 6.5 mm Hg, and SBP, 135 +/- 11.6 mm Hg. The response rate for the therapeutic goal (DBP < 90 mm Hg and SBP < 140 mm Hg, or a reduction in SBP > or = 20 mm Hg) was 67.1%; 41 patients did not complete the study. The most common adverse events were cough, headache, and dizziness; only 10 patients (1.3%) failed to complete the study because of adverse events. Quinapril, as used in current private clinical practice, is well tolerated and effective for the treatment of patients with stage 1 or 2 hypertension.

Meta-analysis of three trials with quinapril in the treatment of mild-to-moderate hypertension in the Mexican population.

A meta-analysis was performed to examine the therapeutic effect of quinapril in the treatment of patients with mild-to-moderate hypertension. Data from three clinical trials conducted in Mexico and including a total of 426 patients were examined using a retrospective approach and statistical methods. The meta-analysis proved that quinapril induces positive diastolic and systolic responses at all the doses studied, particularly at the 10-mg dose. At this dose, 94.1% of patients reduced their diastolic blood pressure (DBP) by 10 mm Hg or attained a DBP of < or = 90 mm Hg. Overall, quinapril reduced DBP by between 14.8 and 24.8 mm Hg proportionally to the baseline DBP. Systolic blood pressure decreased 16 to 35.7 mm Hg from baseline levels. We conclude that the meta-analysis allowed a clearer and more dependable handling of the results regarding effectiveness and optimum dose of quinapril.

Quinapril in the treatment of hypertension in primary care centers.

A multicenter, open, prospective study was carried out to establish the efficacy and safety of quinapril 10.0, 20.0, or 40.0 mg, or 20 mg plus 12.5 mg hydrochlorothiazide (HCTZ) given once daily in 256 patients with mild-to-moderate essential hypertension treated in primary care units in Mexico. The study consisted of a 4-week placebo washout period, followed by 12 weeks of active treatment. Quinapril doses were titrated upward at 4-week intervals to three dosage levels. Patients who did not respond to 20-mg doses were randomly assigned to receive 40 mg quinapril daily or 20 mg quinapril plus 12.5 mg HCTZ daily until the end of the study. Quinapril was useful as monotherapy in 78% of the 256 patients (92.9% of patients who completed the study were evaluable): 73.3% of patients required only 10 mg, and their average blood pressure was similar to that of patients who required doses of greater than 10 mg. Only 12.2% of responsive patients required either 40 mg of quinapril or 20 mg of quinapril plus HCTZ 12.5 mg. Quinapril was equally effective and safe in elderly patients (> 60 years old) and in obese and nonobese patients. A low incidence of adverse effects in our patients confirms quinapril's safety, and no adverse changes were observed in laboratory tests.

" Primera experiencia Venezolana en la construcción de edificios utilizando la albañilería armada como sistema constructivo"

Este trabajo se presenta la primera experiencia realizada en Venezuela en la construcción de edificios de mampostería armada. Se describen los diferentes bloques, los ensayos de laboratorio realizados, el diseño arquitectónico, modulación, la relación Arquitectura-Estructura, las condiciones básicas de diseño sismo - resistente y el proceso constructivo (AU)