Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man

Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.     

Chronic eyelid closure and its effect upon the human cone and rod electroretinogram

The human rod and cone systems have different spectral and adaptive sensitivities. Ganzfeld electroretinogram responses show that chronic eyelid closure, such as extensive symblepharon, can lead to dark-adaptation of the rods but simultaneously permit light-adaptation of the cones of the same eye. This effect is due to the red-filtering properties of the closed eyelid and the differential sensitivity of the two photoreceptor systems to the long wavelengths.     

Breast-feeding and mental and motor development at 51/2 years.

OBJECTIVE: Breast-feeding is associated with better child development outcomes, but uncertainty remains primarily due to the close relationship between breast-feeding and socioeconomic status. This study assesses the issue in a low socioeconomic status sample where breast-feeding was close to universal. METHODS: Seven hundred eighty-four Chilean children were followed longitudinally from infancy. All but four were initially breastfed, 40% nursed beyond 12 months, and infant growth was normal. Child development was assessed at 5(1/2) years by a cognitive, language, and motor test battery. The duration of breast-feeding as the sole milk source was analyzed as a continuous variable, adjusting for a comprehensive set of background factors. RESULTS: The relationship between breast-feeding and most 5(1/2)-year developmental outcomes was nonlinear, with poorer outcome for periods of breast-feeding as the sole milk source for <2 months or >8 months--statistically significant for language, motor, and one comprehensive cognitive test, with a suggestive trend for IQ. CONCLUSIONS: The observed nonlinear relationships showed that breast-feeding as the sole milk source for <2 months or >8 months, compared with 2-8 months, was associated with poorer development in this sample. The latter finding requires replication in other samples where long breast-feeding is common and socioeconomic status is relatively homogeneous.     

Plasma homocysteine concentration and its relationship with the development of preeclampsia. Effect of prenatal administration of folic acid

The increase of plasmatic homocysteine (Hc) in pregnant women, who later develop preeclampsia/eclampsia, the cause of this increment and its pathogenic role in toxemia of pregnancy, are still controversial. The objectives of the present research were to determine the plasmatic He concentrations during the first and second trimesters of pregnancy and the effect of folic acid administration on these values, and in the prevention of preeclampsia. Ninety six pregnant women of low economic background were studied on the first prenatal consultation: 27 women in the first trimester of pregnancy and 59 in the second. After 8 hours of fasting, venous blood was extracted and each patient was provided with 1 mg folic acid tablets and instructed to ingest one tablet daily, and to come back to the laboratory after three months. Plasma homocysteine and serum folic acid were determined for each patient before and after the folic acid treatment, by using the IMX system (Abbott Lab) and radioimmunoassay, respectively. Basal homocysteine concentrations were 4.0 +/- 2.1 micromol/L and 4.8 +/- 2.1 micromol/L in the first and second trimesters respectively, with no significant modifications after three months of folic acid. Although the degree of desertion from the study was high, it was possible to determine the evolution of 65 pregnancies. Ten of them developed preeclampsia (15.4%). No significant differences were found in Hc concentrations, or the frequency of hyperhomocysteinemia in the different stages of pregnancy, between women with normal gestation and those who developed preeclampsia. The small sample size of these groups, preclude any valid conclusion, however the results do not suggest that Hc concentration or folic acid administration influence the development of toxemia of pregnancy.     

Microsatellite analysis in Turner syndrome: parental origin of X chromosomes and possible mechanism of formation of abnormal chromosomes.

Turner syndrome is a chromosomal disorder in which all or part of one X chromosome is missing. The meiotic or mitotic origin of most cases remains unknown due to the difficulty in detecting hidden mosaicism and to the lack of meiotic segregation studies. We analyzed 15 Turner patients, 10 with a 45,X whereas the rest had a second cell line with abnormal X-chromosomes: a pseudodicentric, an isochromosome, one large and one small ring, and the last with a long arm deletion. Our aims were: to detect X cryptic mosaicism in patients with a 45,X constitution; to determine the parental origin of the abnormality; to infer the zygotic origin of the karyotype and to suggest the timing and mechanism of the error(s) leading to the formation of abnormal X chromosomes from maternal origin. Molecular investigation did not revealed heterozygosity for any microsatellite, excluding X mosaicism in the 45,X cases. Parental origin of the single X chromosome was maternal in 90% of these patients. Three of the structurally abnormal Xs were maternally derived whereas the other two were paternal. These results allowed us to corroborate breakpoints in these abnormal X chromosomes and suggest that the pseudodicentric chromosome originated from post-zygotic sister chromatid exchange, whereas the Xq deleted chromosome probably arose after a recombination event during maternal meiosis.     

A potential role for beta- and gamma-crystallins in the vascular remodeling of the eye.

We demonstrate that expression of beta- and gamma-crystallins is associated with intraocular vessels during normal vascular development of the eye and also in the Nuc1 rat, a mutant in which the hyaloid vascular system fails to regress normally. Real-Time RT PCR, Western blot and metabolic labeling studies indicate an increased expression of beta- and gamma-crystallins in Nuc1 retina. The increased expression of crystallins was localized to the astrocytes surrounding the intraocular vessels. A similar pattern of crystallin expression was also observed in the retinal vessels during normal development. Cultured human astrocytes exposed to 3-nitropropionic acid, an established model of neuronal hypoxia, increased VEGF expression, as expected, but also increased expression of crystallins. Our data suggest that crystallins may function together with VEGF during vascular remodeling. Interestingly, in human PFV (persistent fetal vasculature) disease, where the hyaloid vasculature abnormally persists after birth, we show that astrocytes express both VEGF and crystallins.     

Clade analysis and surface antigen polymorphism of hepatitis B virus American genotypes

Eight genotypes (A-H) of hepatitis B virus (HBV) have been described, HBV genotypes F and H being autochthonous to America. HBV genotype F has been classified in four clusters. The objective of this study was to gain insight into the molecular epidemiology of HBV American genotypes, as well as to analyze the genotype-related polymorphism in some functional domains of the surface proteins. The sequences of the S region of 106 isolates genotype F and H were analyzed, out of which 47 isolates genotype F circulated in different Venezuelan populations. Most of the Venezuelan isolates genotype F were grouped in cluster III (n = 39) and 7 in cluster II. One isolate obtained from a blood donor could not be classified in any clade and harbored amino acid substitutions characteristic of a vaccine escape mutant (G145R) and a stop codon in the surface antigen. Amino acid analysis of the PreS and S gene products showed unique genetic characteristics in genotype F and H sequences in some important domains involved in the early steps of infection. Out of 30 available sequences, two complete genome sequences of HBV genotype F from Venezuela were obtained. Phylogenetic analysis of these complete genomes confirmed the presence of four clusters inside genotype F, differing in more than 4% nucleotide divergence. Our extended analysis showed that genotype F clades Ia, III, and IV exhibit a restricted geographic distribution (Central America, the North and the South of South America, respectively) while clades Ib and II are found in all the Americas except in the Northern South America and North America respectively.