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Several studies have shown that diverse components of the bone marrow (BM) microenvironment play a central role in the progression, pathophysiology, and drug resistance in multiple myeloma (MM). In particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-κB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-κB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma. Considering that H929 cells were also directly susceptible to PKC and NF-κB inhibition, we showed that treatment of co-cultures with the HKPS peptide and BAY11-7082, followed by bortezomib, increased H929 cell death. Therefore, targeting simultaneously connected signalling elements of BM-MSC responsible for MM cells support with compounds that also have anti-MM activity can be an improved treatment strategy.

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The pharmacokinetics of oral ranitidine were studied in 24 Mexican male healthy volunteers. Subjects received a tablet containing 150 mg of ranitidine (Azantac, Glaxo de México, Mexico City) after an overnight fast and blood samples were drawn at several times for a period of 24 h. Ranitidine concentration in plasma was measured by high performance liquid chromatography and pharmacokinetic parameters were determined by non-compartmental analysis. Ranitidine plasma concentration increased with time, reaching a maximum of (mean +/- SEM) 484 +/- 34 ng/ml in 2.7 +/- 0.2 h. Plasma levels then decayed with a terminal half-life of 4.8 +/- 0.3 h. The area under the plasma concentration against time curve was 2440 +/- 126 ngh/ml. Oral ranitidine pharmacokinetic parameters in Mexicans appeared to be similar to those previously reported for Caucasians.

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To examine the effects of avocado on plasma lipid concentrations a two-diet trial involving 8 phenotype IV and 8 phenotype II dyslipidemia patients was carried out. A diet rich in monounsaturated fatty acids (DRCA) using the avocado as their major source (30% of the total calories were consumed as fat, 75% of the total fat from the avocado), with restriction of saturated fat and less of 300 mg of cholesterol per day was evaluated. Patients also were in a low-saturated fat diet without avocado (DRSA). The three daily meals were eaten at our clinical unit. Diets were four weeks in duration and they were assigned in a crossover design. In phenotype II both DRCA and DRSA significantly reduced total cholesterol and LDL-cholesterol levels. On phenotype IV DRCA produced a mild reduction on triglyceride levels while DRSA increased them. On HDL-cholesterol concentrations DRCA produced a significant increase in both phenotypes while DRSA did it only in phenotype IV. Avocado is an excellent source of monounsaturated fatty acids in diets designed to treat hypercholesterolemia with some advantages over low-fat diets with a greater amount of carbohydrates.

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The relationships between nifedipine plasma concentrations and its hypotensive and positive chronotropic effects were studied in healthy volunteers who received either a 10 mg capsule (CAP) or a 20 mg slow release tablet (SRT). Plasma concentrations rose more rapidly after CAP than after SRT, Cmax being 131 +/- 39 and 40 +/- 7 ng/ml and tmax being 0.5 +/- 0.07 and 1.8 +/- 0.4 h, respectively. Both formulations produced a reduction in diastolic blood pressure which exhibited a significant linear correlation (p < 0.01) with nifedipine plasma concentration. However, the slope obtained with SRT was significantly higher than that of CAP (0.24 +/- 0.05 vs 0.07 +/- 0.01, p < 0.01). That is, a similar hypotensive effect was produced at a lower concentration with SRT than with CAP. A positive chronotropic effect which exhibited a highly significant correlation with nifedipine plasma concentration (p < 0.0001) was observed with CAP. Conversely, with SRT heart rate increase was smaller and there was no significant correlation with nifedipine plasma concentration (p > 0.45). Since the measured decrease in blood pressure is the outcome of nifedipine-induced vasodilation and of homeostatic responses, results are interpreted as follows. Fast nifedipine input after CAP induced a brisk change in physiological conditions and hence triggered an important homeostatic response, visualized as heart rate increase, which partially offset the hypotensive effect. With SRT, there was a gradual change in blood pressure producing lesser activation of compensatory mechanisms and therefore the hypotensive effect of nifedipine was less antagonized than with CAP. Nifedipine SRT does not only exhibit pharmacokinetic advantages, but also a more favorable pharmacodynamic profile than CAP.

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Eighty-six Mexican young healthy volunteers received a 500-mg oral sulfamethazine dose. Urine was collected 0--6 h after medication and acetylated, and unchanged sulfamethazine were determined by the Bratton--Marshall method. The frequency distribution of acetylated/unchanged sulfamethazine, determined by probit analysis, appeared to be trimodal, allowing the discrimination of three acetylator phenotypes. The frequencies of rapid, intermediate, and slow acetylators were 28%, 42%, and 30% respectively, being consistent with the Hardy-Weinberg law.

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The bioavailability of ketorolac after administration of two oral formulations containing 10 mg of ketorolac tromethamine, Exodol and Dolac, to 12 healthy Mexican volunteers was compared. Subjects received both formulations according to a randomized crossover design and blood samples were drawn at selected times during 24 h. Ketorolac plasma concentrations were determined by HPLC and individual plasma-concentration-against-time curves were constructed. Maximal plasma concentration and AUC0-24 values were compared by analysis of variance followed by Westlake's confidence interval test. 90% confidence limits ranged from 80 to 125% for Cmax and from 85 to 118% for AUC0-24. It is concluded that the two assayed formulations are bioequivalent.

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Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.

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Oral pharmacokinetics of rifampin were studied in eight Mexican young healthy male volunteers after administration of a 600 mg oral dose. After an overnight fast, subjects received medication and blood samples were drawn at selected times over a 24-h period. Rifampin plasma levels were determined by HPLC. Pharmacokinetic parameters (mean +/- SEM) were: Cmax 13.514 +/- 1.775 micrograms/ml, tmax 1.88 +/- 0.30 h, AUC 73.61 +/- 9.48 micrograms.h/ml and half-life 2.98 +/- 0.29 h. Results were compared with those obtained for other populations under similar conditions in order to explore the possibility of interethnic variability, since it has been reported that rifampin pharmacokinetics in Indonesian subjects differ from those found in Europeans. Pharmacokinetic data found in Mexicans were comparable with those observed in British, Indian, Japanese and Italian individuals. As the pharmacokinetics of rifampin seem to be similar in different populations, it is concluded that ethnic origin does not appear to play an important role. Therefore, dosing regimens designed for Caucasians can be extrapolated for other populations.

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Post-harvest problems are important constraints to the expansion of production of food in many Latin American countries. Besides problems of bulkiness, perishability and seasonal production patterns, the necessity of reducing transportation costs, increasing rural employment, and finding new markets for processed products, requires the development of processing technologies. Possible processed products include a vast range of alternatives. Given limited time and resources, it is not always feasible to carry out detailed studies. Hence a practical, low-cost methodology is needed to evaluate the available options. This paper presents a series of methods to evaluate different processing possibilities. It describes in detail each method including a rapid initial assessment, market and consumer research, farm-oriented research, costs and returns analysis and finally, some marketing and promotion strategies.

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Two oral pharmaceutical formulations (URO-TS D and Bactrim F) containing 800 mg of sulfamethoxazole (SMZ) and 160 mg of trimethoprim (TMP) were given to 10 Mexican healthy volunteers, following a randomized cross-over design. Blood and urine samples were obtained, concentrations of TMP, SMZ, and its metabolite N4-acetyl SMZ were measured by HPLC and pharmacokinetic analyses were performed. The observed Cmax, tmax, half-life, AUC, and cumulative urinary excretion values for the three compounds studied were within the ranges that have been previously reported for European and North American subjects. Therefore, it appears that pharmacokinetics of SMZ and TMP in Mexicans are similar to those observed in Caucasian populations. When the two studied formulations were compared, no statistically significant differences were detected in any pharmacokinetic parameter. Therefore, it is concluded that both brands tested are bioequivalent. Moreover, these two formulations manufactured in Mexico yield SMZ and TMP plasma and urine levels similar to those obtained with equivalent formulations of European or North American origin.

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Four groups from a urban population of Morelia were inquired, to determine frequency of high blood pressure and provide basic information of arterial hypertension in relation with other variables; 2638 persons were checked. Age ranged from 10 to 90 years, (771 men, 1867 women). Age, sex, weight and height were also measured. Evaluations were performed in the morning with mercury sphygmomanometer registering first and fifth korotkoff's sounds in orthostatic position with a second selective evaluation in sitting position. Availability of medical services and knowledge about presence of arterial hypertension were also evaluated. Blood pressure and prevalence of hypertension had similar behavior with regard to age: pressure recordings were higher in men before 40 years. After this age were higher in women. In general, 14% had high blood pressure, in the second evaluation this value dropped to 7%. For 11% of the studied population, high blood pressure had been previously recorded 7 out of 10 cases of hypertension did not have any control. Three of them had not information about this illness. We found a positive correlation between weight and blood pressure (p less than 0.001) specially among women.

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Nifedipine kinetics after ingestion of 20 mg slow release tablets were studied in 12 young, healthy, Mexican subjects. Plasma levels were determined by a nifedipine-specific HPLC assay. Levels rose after drug administration reaching a maximum concentration of 48.7 +/- 7.3 ng/ml in 2.1 +/- 0.7 h (mean +/- SEM). Concentrations then decayed with a terminal half-life of 16.9 +/- 3.1 hours. AUC was 526 +/- 62 ng h/ml. Five individuals were fast and seven were slow nifedipine metabolizers, according to the AUC criterion proposed by Kleinbloesem and coworkers. Individual AUC/Dose values from this and from other two studies on oral nifedipine kinetics in Mexicans were cumulated and the frequency histogram and probit analyses were performed (N = 30). A bimodal distribution was clearly observed. Fast and slow metabolizers were distinguished as those subjects with AUC/Dose values either lower or higher than 22.5 ng h/ml mg. Unlike European populations, it appears that slow metabolization is more frequent in Mexicans. Data strongly support the hypothesis of the existence of a polymorphism concerning nifedipine disposition kinetics due to genetic basis.

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Pharmacokinetics of oral Nifedipine was studied in 12 Mexican young healthy volunteers, six men and six women, who received a 10 mg capsule. Plasma levels were determined by a nifedipine specific HPLC assay. Experimental data were fitted and pharmacokinetic parameters were calculated using an open two compartment model. No statistically significant difference was detected between men and women, thus both sexes were considered as a single population. Nifedipine plasma levels rose rapidly (ka = 8.46 +/- 1.96 h-1) reaching a maximum concentration of 145 +/- 23 ng/ml in 0.61 +/- 0.07 h. Plasma levels then decayed with a distribution phase (alpha = 1.98 +/- 0.40 h-1, t1/2 alpha = 0.46 +/- 0.06 h) and a terminal elimination phase (beta = 0.17 +/- 0.03 h-1, t1/2 beta = 4.98 +/- 0.55 h). AUC was 384 +/- 41 ng h/ml. Values of AUC and t1/2 beta were higher than those reported by other authors. Differences in the AUC could be due to ethnic origin, environmental factors or nutritional habits. Ten subjects presented plasma concentration-time curves in which the distribution phase was clearly distinguishable, having a ka/alpha relationship higher than 1.5. For the other two subjects, the distribution phase was not apparent and ka/alpha was lower than 1.5. The results show that an adequate characterization of the distribution phase is required if one pretends to use pharmacokinetic data for dosage regimen design.

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