Pharmacokinetics of cyclosporine as a function of energy--protein deficiency in children with chronic renal failure.

The present study was conducted to determine whether malnutrition in patients with chronic renal failure requiring cyclosporine therapy for renal transplantation has some effect on the clinical pharmacokinetics of cyclosporine. Eleven pediatric patients were enrolled in this study before renal transplantation and divided into two groups (group I: six well-nourished patients with a deficit in weight/height ratio < or = 7%; group II: five malnourished patients with a deficit in weight/height > 8%). The patients received a single oral dose of cyclosporine (3.0 mg/kg). Blood samples were collected for a 26-hour period, and serum concentrations of cyclosporine were measured using fluorescence-polarization immunoassay technology. The results suggest that, when malnutrition is present, the median Cmax of cyclosporine decreases by almost threefold (from 387.5 ng/mL in group I to 136.1 ng/mL in group II). An observed 52% reduction in AUC0-infinity (from 2,856.0 ng/mL/hr in group I to 1,481.4 ng/mL/hr in group II) was caused by the increased volume of distribution (from 4.6 L/kg in group I to 11.1 L/kg in group II). The elimination half-life (t1/2) was longer in group II compared with that of group I (12.4 hr for group II; range, 7.8-13.5 hr versus 8.9 hr for group I; range, 5.2-16.0 hr). Differences in t1/2 were not statistically significant at 5% confidence intervals. The effects of energy malnutrition on the pharmacokinetics of cyclosporine could explain in part some of the interindividual variability. This study provides pharmacokinetic guidelines for the use of cyclosporine.

Patterns of muscle and fat mass repair during recovery from advanced infantile protein-energy malnutrition.

OBJECTIVE: This paper shows the pattern of body composition within the frame three-compartment model repair during recovery from advanced infantile protein-energy malnutrition. DESIGN: Body composition was assessed in 26 severely malnourished male infants aged 1-7 months at the time of their admission at Instituto Nacional de Pediatria in Mexico City and through the initial process of nutritional recovery (NR), by means of radiological, anthropometrical procedures and 24-h creatinine excretion at fortnightly intervals. Throughout of NR period all children were fed with milk formula (13-14% protein, 40% carbohydrates and the remainder fat). RESULTS: There was high frequencies of children's intakes were above the median (160 kCa1/k/d), but in last period their intakes were close to child normal requirements. Repletion of weight-for-height deficit was complete in all children. Leg-muscle roentgenographic area showed significantly increment in size only the first 15 days (P < 0.05). The leg-fat area showed size increments in all 15-day intervals (P < 0.05 or P < 0.01). The leg-bone area did not show any change during NR. Body Weight as well as arm and arm-fat-free areas and calculated total muscle and fat body mass augmented significantly during nutritional rehabilitation (P < 0.01). However, the ratio of muscle to body mass increased only during the first month of NR (P < 0.05), while absolute and relative fat mass did so during the whole observation period (P < 0.05). The remainder of body organ mass (EOM) did not suffer any change during all NR period. CONCLUSIONS: This dysrythmic repair of body compartments might offer explanation of certain features of psychomotor performance of infants recovering from severe protein-energy malnutrition.

[Genetic influence on energy requirements. III. Multifactorial inheritance modified by gender]. / Influencia genética en requerimientos de energía. III. Herencia multifactorial modulada por género.

A conversion index (CI) which measures the efficiency of utilization of dietary energy was found to be normally distributed in Wistar rats. The CI used was a ratio of the amount of food ingested to achieve an increment of one gram of body weight during the period of 32 days starting on day 21 after weaning. We have previously reported that male rats are more efficient energy converters than females. As a way to explore the hypothesis that the inheritance of the regulation of energy requirements is multifactorial, we mated F1 rats with high CI (poor energy converters) and studied the CI of their F2 offspring. The males behaved in agreement with the hypothesis as the F2 males had higher CI than the F1 males, but the behavior in females was different, i.e. the F2 were better converters than the F1. We have no explanation for this gender discrepancy.

Nutritional state of beta-carotene and retinol in institutionalized elderly individuals of México City.

A study of the nutritional status of beta-carotene and retinol of 228 institutionalized elderly individuals, in four elderly homes of México City was carried out. Subjects varied between 61 and 101 years of age (151 were females and 77 were males). High pressure liquid chromatography was used to quantitate retinol and beta-carotene. Ninety eight percent of elderly individuals showed beta-carotene levels less than acceptable (at risk); 85.2% were deficient (high risk), and 12.9% were low (medium risk), only 1.85% had acceptable values (low risk). Ninety two percent of subjects had acceptable values (low risk) of retinol, while 6.0% and 2.0% were low (medium risk) and deficient (high risk) respectively. There were not significant differences among the four elderly homes. No significant correlation with age was found for any of the two vitamins. No sex related difference (p > 0.05) was observed in serum vitamin A and beta-carotene in either group.

Utilization of dietary energy in the rat. IV. Multifactorial inheritance modulated by gender.

In Wistar rats the conversion indexes (CIs) are normally distributed. A conversion index is the amount of food consumed necessary to increase the body weight by 1 g in a 32-day period, which begins at weaning (day 21) and ends on the 52nd day of life of the rat. Some experiments have been designed trying to demonstrate that inheritance of energy dietary utilization in Wistar rats may be multifactorial modulated by gender. In the study presented here parental males (F1) with CIs below the male median were paired with females of the same F1 who also had CIs below the female median. It was postulated, if the hypothesis is correct, that the offspring (F2) obtained from these pairings would have conversion indexes below the median of the CIs of the parental rats(F1). The results indicate precisely that both males and females behave as expected. Thus it appears that inheritance of efficiency of dietary energy utilization in the Wistar rat is a multifactorial trait.

Purkinje cell density in cerebella of alcoholized and non-alcoholized male rat offspring.

The effect of alcohol intake by male rats was evaluated on Purkinje cell morphology and number in their offspring. Forty five male Wistar rats, 45 days old, were used and divided into three groups of 15 rats each: control group (CG), fed with conventional Purina rodent feed (CPRF) and water ad libitum; experimental group (EG), fed with CPRF ad libitum and a mixture of water/ethanol, which represented 36% of kilocalories in food; and an equienergetic intake control group (ECG), which was given CPRF (in grams) and sugar in their drinking water, in order to substitute the energetic value provided by alcohol. Five subgroups (n = 3) were created to be used for different treatment periods: 60, 90, 120, 150 and 180 days; all groups started treatment when they were 70 days old. At the end of each treatment period, male rats were mated with nulliparous females not having undergone treatment. Offspring were obtained and studied at 14 and 21 days of age. The Purkinje cells of the cerebella of 14- and 21-day-old offspring belonging to the CG and ECG showed no morphological changes. On the other hand, in 14-day-old offspring belonging to the experimental group of parents alcoholized during 90, 120, and 180 days, a large number of hyperchromatic Purkinje cells were seen, forming zones of cells undergoing a degenerative process. No significant differences in cellular density were determined between the CG and the ECG. When comparing the CG vs. EG and the ECG vs. EG, significant differences were found in the 14-day-old offspring as well as in the 21-day-old ones with a p < 0.05 of rats belonging to parents alcoholized for 90, 120, and 180 days. The results may indicate that there are changes in the germinal plasma of males due to alcohol consumption; therefore, reflecting this effect on a decrease of Purkinje cells and probably on other cell populations.

A new dosing regimen for metronidazole in malnourished children.

The use of metronidazole for the treatment of intestinal parasitosis has increased markedly, particularly in developing countries, where the association of malnutrition and parasitosis is very common. Since biotransformation of metronidazole is significantly affected by severe malnutrition, and undesirable effects of the drug seem to be related to its plasma concentration, it was decided to carry out a study to establish a dosing-regimen of metronidazole in severely malnourished children. A single dose of 30 mg/kg body weight, and computer simulation of a steady-state was studied in 10 malnourished and in 10 patients undergoing nutritional rehabilitation. Due to ethical considerations (refusal of parents to allow a second dose of metronidazole) acute malnourished children and rehabilitated patients are 2 distinct groups. The results indicate that a predicted drug cumulation would occur in malnourished children with the ordinary dosage regimen (30 mg/kg/day). Based on the clearance data, daily maintenance doses for pediatric patients with severe malnutrition should be 12.0 mg/kg/day, corresponding to a 60% reduction of the common dose calculated to achieve and maintain a plasma concentration of 6.0 micrograms/ml of metronidazole. The study illustrates the need for pharmacokinetic data to establish the individual dose of a drug particularly under conditions that alter biotransformation processes.

[Genetic influence on energy requirements. I. Development of an experimental model]. / Influencia genética sobre los requerimientos de energia. I. Desarrollo de un modelo experimental.

In attempting to explore the mechanisms of interaction of genetic and environmental factors that affect the quantitative requirements of energy by man, the convenience of an animal model was considered and searched for. The idea was to start with male and female Wistar rats and through inbreeding segregate the highly effective users of energy from the poor users. The efficiency of dietary energy utilization was measured by the index of conversion (IC) defined as the dietary intake necessary to increase 1 g of body weight in a 32-day period, from day 21st to day 52nd of extrauterine life. The median value of the IC for all animals included in each experiment was the cut-off point to classify each individual as a good or a poor energy user. The first generation had three males and five females with a median IC = 2.90 and a range from 2.54 to 3.25. The proportion of males below the median was 3/3 while the proportion of females was 2/5. The difference in proportions was striking and led immediately to the consideration of a sex-link hypothesis, and to test it the, IC of 91 Wistar rats randomly selected at birth was obtained. The median value of the series was 2.99 with a range from 2.24 to 3.95. The proportion of male rats with values below the median was 33/38 while the corresponding proportion for females rats was 13/53. In other words, while nine of every ten male animals were good users of energy, only two out of ten females fell into this category.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of metronidazole in severely malnourished and nutritionally rehabilitated children.

A comparison of the pharmacokinetics of oral metronidazole, after a single dose of 30 mg/kg body weight, was done in two groups of subjects: group I consisted of 10 severely malnourished children, aged 4 to 43 months; group II consisted of 10 children, aged 3 to 25 months, who were studied after nutritional rehabilitation. The biologic half-life of elimination was significantly longer (p less than 0.01) in severely malnourished children (median, 10.21 hours; range, 4.89 to 22.93 hours) than in rehabilitated children (median, 5.09 hours; range, 2.61 to 8.75 hours). Metabolic clearance of metronidazole was significantly lower in group I (p less than 0.01; median, 0.077 L/kg/hr; range, 0.033 to 0.192 L/kg/hr) than in nutritionally rehabilitated children (median, 0.166 L/kg/hr; range, 0.105 to 0.300 L/kg/hr). Volume of distribution was not different between groups I and II, although both showed higher values than the values reported for children who were not malnourished. These findings suggest that the dose of metronidazole should be reduced in malnourished children, and the therapeutic regimen should be individualized for each patient.

Effects of chronic toluene inhalation on avoidance conditioned behavior in rats.

Thirty-two Wistar albino rats were distributed at random in a factorial design 2 x 2, with two age groups (20 and 90 days old), and two treatments (chronically exposed to toluene vapors 30,000-40,000 ppm in air/15 minutes per day for 30 days, and controls with only air). Twenty-four hours after the last exposure, the rats were tested for conditioned behavior in a "T" maze of avoidance electric shock. Latency of initial response to escape (LIRE) and latency of escape (LE) were measured in seconds. Adult rats both exposed to chronic toluene inhalation and non-exposed showed higher values of LIRE and LE with respect young rats. Animals exposed to chronic toluene inhalation also presented higher values of latency in both LIRE and LE when compared to non-exposed to toluene (controls) of the same age. The differences were evaluated by Friedman's test. The findings are suggestive of brain dysfunction associated with chronic toluene inhalation, and may represent a delay to respond to a displeasure stimulus probably due to defect of internal mechanisms of facilitation-inhibition of neural impulses, mediated by neurotransmitters.

[Effects of stimulation available at home and of mother-child interaction on the presence and duration of diarrhea in young infants]. / Influencia de la estimulación disponible en el hogar y de la interacción madre-niño sobre la presencia y duración de la diarrea en el lactante menor.

The relationship between two key factors involved in infant care and the frequency and duration of diarrhea, was search for in a cohort of rural infants followed-up from birth onwards. The specific questions asked were if the profile of mother-infant interaction, and the total score on home stimulation available to the infant were associated with the presence or absence of diarrhea, and with its total duration, expressed as the percentage of days with diarrhea over the number of days of age, in each semester of the first year of life of the infants. Frequency an duration of diarrhea, mother-infant interaction, and scores on home stimulation available to the infant showed no difference between baby-boys and baby-girls. The behavior of mothers of infants with diarrhea was not significantly different than the behavior exhibited by mothers of infants without diarrhea; even in the scales related to "quantity of physical contact with the infant", "type of physical contact with the infant", "response to infant's needs", and "sensitivity toward the infant". Similarly, neither the quality nor quantity of home stimulation showed association with the presence of diarrhea. Finally, none of the two microenvironmental attributes influenced the duration of diarrhea in either semester of the life of the infant. Although diarrhea is one of the most frequent antecedents of severe clinical malnutrition and in the latter both mother-infant interaction and home stimulation play a prominent role in the evolution from second degree to third clinical degree malnutrition, it seems important than those factors have a minimal influence in relation to diarrhea during the first year of life.

[Stimulation at home and psychological profile of mothers of children with or without weight loss during the first 15 days of life]. / Estimulación en el hogar y perfil psicológico de madres de niños con y sin pérdida de peso en los primeros quince dias de vida.

OBJECTIVES: To determine the possible difference of the microenvironment of a group of children who lost weight in their first 15 days of life. DESIGN: Longitudinal ecological study of growth and development of a total cohort of all children born during a calendar year. SETTING: Rural village of Central Mexico. PARTICIPANTS: A group of sixteen children, who fifteen days after birth and without apparent reason, showed a decrease in weight as compared with weight at birth, they were compared with a control group from the same population and matched, case by case, according to gestation age, height at the time of birth, and body weight. MEASUREMENT AND MAIN RESULTS: To assess the influence of microenvironmental factors two indicators were used. Recording and scoring of maternal behavior was done by adaptation to local conditions by Cravioto et al, of the Maternal Behavior Profile developed by Nancy Bayley. The instrument used for estimating home stimulation was the inventory developed by Caldwell design to sample certain aspects of the quantity and/quality of social, emotional, and cognitive stimulation available to a young child within his home. No significant differences were found in relation to Maternal Behavior Profile and Home Stimulation in the two groups studied (statistical differences, P greater than 0.05). CONCLUSION: Data from present study contribute to the claim that systematic stimulation in the home and an adequate interrelation mother-child are among the main elements necessary for the proper development of the child.