Diuretic treatment and serum lipoproteins: Effects of tienilic acid and indapamide

Summary Treatment with the commonly used diuretic, chlorthalidone, has previously been found to increase the serum low-density-lipoprotein cholesterol (LDL-C) fraction. Therefore, the effects of two new agents, tienilic acid (a combined diuretic-uricosuric) and indapamide on serum lipid and lipoprotein levels were assessed. Six weeks of treatment with tienilic acid, 250 mg/day, markedly decreased serum uric acid and significantly increased LDL-C and triglycerides in 16 men. In contrast, indapamide 2.5 mg/day, had no apparent influence on serum lipids or lipoproteins in 18 men.Supported in part by the Swiss National Science Foundation     

Relationship of resting blood pressure and heart rate to experienced anger and expressed anger

Forty-five nonmedicated subjects rated on analog scales the anger they experienced at home and at work (Experienced Anger). They also rated the extent to which others were aware of their anger (Expressed Anger) and the extent to which anger had been expressed in their families or origin (Family Expressed Anger). They were then physiologically monitored during a 2-min relaxation period that followed habituation to the laboratory setting. For the group as a whole, Expressed Anger was inversely related to systolic (SBP) and diastolic (DBP) blood pressure while Family Expressed Anger was inversely related to SBP only. When the sample was divided into normotensive and hypertensive subgroups, the normotensives showed significant associations between Experienced Anger and SBP, Expressed Anger and DBP, and Family Expressed Anger and SBP. The hypertensive subgroup showed no significant associations. Both males and females showed a significant association between Expressed Anger and DBP, but only females showed this relationship with SBP. It is concluded that coping with anger by conscious inhibition of its expression is associated with increases in both systolic and diastolic blood pressure.     

Persistent hyperexcitability in isolated hippocampal CA1 of kainate-lesioned rats.

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 microM bicuculline for > or = 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABAA-receptor-mediated inhibition and that the loss of inhibition is only partial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system

Recently, in-vitro maturation (IVM) of immature human oocytes recovered from non-stimulated follicles has been applied in the treatment of infertility. However, in previous reports, very few embryos cultured in conventional medium have reached the expanded blastocyst stage following in-vitro maturation and fertilization (IVM/IVF). The objective of this study was to investigate whether the developmental competence of human embryos following IVM/IVF could be enhanced by the use of a human ampullary cell co-culture system. Immature human oocytes were aspirated from small follicles at Caesarean section and then cultured in medium containing human menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes were randomly cultured either in conventional culture medium alone or in the co-culture system. Of 48 embryos cultured in conventional medium alone, all arrested at the 2-16- cell stage on day 3 after insemination. Of 46 embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at the 2-16-cell stage. Six embryos (13%) developed to the morula stage. Fourteen embryos (30.4%) developed to expanded blastocysts and two blastocysts were hatching on day 7 after insemination. We conclude that co-culture significantly enhances the development of blastocysts in embryos resulting from IVM/IVF.      

Role of nitric oxide in the biology, physiology and pathophysiology of reproduction

Following its benchmark discovery, nitric oxide (NO) is nowknown to play important functional roles in a variety of physiologicalsystems. Within the vasculature, NO induces vasodilation, inhibitsplatelet aggregation, prevents neutrophil/platelet adhesionto endothelial cells, inhibits smooth muscle cell proliferationand migration, regulates programmed cell death (apoptosis) andmaintains endothelial cell barrier function. NO generated byneurons acts as a neurotransmitter, whereas NO generated bymacrophages in response to invading microbes acts as an antimicrobialagent. Because neurons, blood vessels and cells of the immunesystem are integral parts of the reproductive organs, and inview of the important functional role that NO plays in thosesystems, it is likely that NO is an important regulator of thebiology and physiology of the reproductive system. Indeed, inthe past 10 years, NO has established itself as a polyvalentmolecule which plays a decisive role in regulating multiplefunctions within the female as well as the male reproductivesystem. This review provides an overview of the role of NO invarious reproductive organs under physiological and pathologicalconditions.     

Sleep need in adolescents: a longitudinal approach

A sample of 190 male and female "high school" students completed a sleep questionnaire for the first time when they were 10 to 14 years old. The survey was repeated five times at 2 year intervals. Ninety-three subjects answered the questionnaire each time. Subjective sleep need was assessed by the indicated wish for more sleep. The wish for more sleep was very pronounced, varying between 54.3% and 74.5% across the years. Individual consistency, however, was low since only 14.5% of the adolescents indicated the wish for more sleep in each survey, emphasizing the state dependency of this variable. Within each total sample, subjects with the wish for more sleep (MSL) and with sufficient sleep (SSL) were compared. Subjective sleep need was consistently validated by a syndrome of morning-tiredness. In the last two surveys, there was reduced time in bed (TIB) on weekdays in MSL subjects and longer TIB during vacation in surveys 2 through 5. Furthermore, MSL subjects more often showed irregular sleep habits. The previous sleep history of the MSL subjects in the last survey indicated that concomitants of the wish for more sleep were already experienced earlier in adolescence. The desired sleep duration of these subjects was 1.7 h longer than their current sleep on weekdays, an amount they had not obtained on weekdays since early adolescence. It is concluded that a substantial proportion of the adolescents seem to have had difficulties adapting to the general sleep time reduction occurring in adolescence.     

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra- cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.      

A short-term quantitative XC assay for murine leukemia virus.

A syncytial-plaque (SXC) assay for murine leukemia virus is described which utilizes a single cycle of infection, thus allowing quantitation of virus-producing mouse cells in 3 to 4 days. Depending upon the Fv-1 genotype of infected mouse cells, the assay will reflect single or multiple “hitness” after infection by N- or B-tropic MuLV. The test is equally sensitive to the uv-XC plaque assay for tissue culture adapted MuLV, but is less sensitive to in vivo derived MuLV from an AKR/J mouse. Newly isolated AKR MuLV requires a longer latent period than the in vitro adapted Moloney strain of MuLV.     

Craniofacial serial dimensions related to age, sex, and cleft-type from six months of age to two years.

The first two postnatal years are a time of rapid craniofacial growth. We selected 30 cleft lip/palate children, each seen at 6, 12, 18, 24 months, at which time lateral X-ray headfilms were taken. There were five boys, five girls, in each of three cleft-types: cleft palate only (CP), unilateral cleft lip/palate (UCLP), and bilateral cleft lip/palate (BCLP). Three dimensions were selected: 1) anterior cranial base (S-N); 2) upper face height (N-Pt.A); 3) maxillary depth (Pt.A-Ptm). All were in the midsagittal plane. This is a repeated measures study on the factor patient age, so that for each combination of sex and cleft-type the same subject was measured at the four levels of patient age. The multiple comparison technique utilized was the Newman-Keuls Procedure. There is no significant joint effect in the 6-24 months period. The factors seem to operate singly. There is no main effect due to the factor sex. Dimensions N-Pt.A. and Pt.A-Ptm show a significant main effect due to the factor cleft-type. There is a highly significant main effect due to the patient age factor.