Effects of 5-hydroxytryptamine uptake blockers on the concentration in brain of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male rats, pro-oestrous rats and ovariectomized rats treated with oestrogen and progesterone

The aim of this study was to determine the effect of 5-hydroxytryptamine (5-HT) uptake blockade on 5-HT turnover by measuring the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain with the aid of high performance liquid chromatography and electrochemical detection. The indoleamines were measured in the anterior hypothalamus (AH), posterior hypothalamus (PH) and raphe nuclei 30 min after the i.v. injection of either alaproclate (30 mg/kg) or zimelidine (20 mg/kg). The effect of alaproclate was studied in male rats, pro-oestrous female rats, rats ovariectomized and injected s.c. with 20 micrograms oestradiol benzoate (OB) on dioestrus and at 12.00 h of the next day (presumptive pro-oestrus) with 2 mg progesterone (model 1) and rats ovariectomized 3-4 weeks before an s.c. injection of 20 micrograms OB followed 72 h later by an s.c. injection of 2 mg progesterone (model 2). Alaproclate caused a significant decrease in the 5-HIAA/5-HT ratio in the AH and PH of the brain of male rats, in the PH and raphe nuclei in pro-oestrous rats and model 1, and in the raphe nuclei alone in model 2. Zimelidine had no effect on the 5-HIAA/5-HT ratio in any area in model 2. In male rats the injection of parachlorophenylalanine produced a marked reduction in the brain concentrations of 5-HT and 5-HIAA, but the 5-HIAA/5-HT ratio was unchanged by a subsequent injection of alaproclate. None of the pharmacological agents affected significantly the brain concentrations of noradrenaline, dopamine or dihydroxyphenylacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroid levels and steroid metabolism in relation to early gonadal development in the tilapia Oreochromis niloticus (Teleostei: cyprinoidei)

Sex steroid levels and steroid metabolism were investigated in relation to early gonadal development in a mixed sex population of the tilapia Oreochromis niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts. Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and metabolites were identified by thin-layer chromatography coupled with radioisotope image analysis. Histology revealed the presence of gonadal structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other individuals exhibiting undifferentiated gonads containing germinal cells, presumably eventual testes. Androgen levels were initially high in eggs then decreased severalfold prior to the emergence of gonads. A transient increase in the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or undetectable except for a transient increase (43 dpf) after ovaries were present. Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally increased throughout development. Metabolites were generally similar, consisting of T predominantly as well as 5beta-reduced androgen derivatives and 11-oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids were not formed. Two types of steroid metabolic profiles occurred at 50 dpf. These results demonstrate that changes in the steroidogenic profile occur during early transitions of gonadal development. Notably, (1) steroid biosynthetic capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs after ovarian development has begun, and (3) bimodality of levels of T and differential steroid metabolism later in development may reflect the onset of sexual divergence.     

Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality?

Background: The death rate from cardiovascular disease in Tasmania has been among the highest in Australian States for a number of years. The North-West (NW) and Northern regions of Tasmania account for most of the increased mortality.
Aims: To determine the prevalence of cardiovascular risk factors in the North and NW regions of Tasmania and to ascertain whether any differences are consistent with the regional patterns of mortality for ischaemic heart disease (IHD) within the State.
Methods: The design of the study was almost identical to the previous National Heart Foundation (NHF) Risk Factor Prevalence Survey conducted in 1989. The subjects, aged 20–69 years, were randomly selected from the Electoral Roll with 1146 subjects participating in the North and 1219 in the NW. Subjects answered a detailed questionnaire and then underwent a brief physical examination with venipuncture for blood lipids. Hobart data from the NHF Risk Factor Prevalence Survey in 1989 were used as an estimate of risk factor prevalence in the Southern region.
Results: In both males and females, mean systolic blood pressure was significantly higher in the NW than the South which was in turn higher than the North. Mean serum cholesterol levels in males were higher in the NW than the North. Smoking behaviour was similar in males and females in all regions. Males and females in the NW and North were more inactive than those in the South. Similar proportions in all regions were on either 'no specific' or 'fat modified' diets. Body mass index in males and females was higher in the NW and North but waist to hip ratios failed to show a consistent trend.
Conclusions: While the NW has an unfavourable risk factor profile compared with the South, the North does not. The risk factor data are broadly consistent with, but unlikely to be sufficient to explain fully, the regional differences in mortality from IHD. (Aust NZ J Med 1995; 25: 290–296.)     

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus

OBJECTIVES: The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM. PATIENTS: Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state. METHODS: The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant-like emulsion was determined from the appearance of 13CO2 in the breath using isotope-ratio mass spectrometry and multicompartmental modelling. apoB-48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC-III was measured by immunoturbidimetric assay. RESULTS: Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB-48 concentration (16.40 +/- 1.18 mg/l vs. 13.0 +/- 0.9 mg/l; mean +/- standard error mean; P = 0.021), higher plasma apoC-III concentration (204.24 +/- 15.18 mg/l vs. 170.74 +/- 10.75 mg/l; P = 0.042) and lower FCR of the chylomicron remnant-like emulsion (0.06 +/- 0.05 pools/h vs. 0.12 +/- 0.02 pools/h; P < 0.001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB-48 levels (r = -0.641, P = 0.007) but not with apoC-III levels. CONCLUSIONS: In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.     

Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe

OBJECTIVE: The aetiopathogenesis of the primary systemic vasculitides (PSV) is unknown but includes both environmental and genetic factors. The development of classification criteria/definitions for PSV allows comparison of the epidemiology between different regions. METHODS: The same methods and the American College of Rheumatology (1990) criteria or Chapel Hill definitions were used to compare the epidemiology of Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and polyarteritis nodosa in Norwich (east England population 413 500) and Lugo (northwest Spain population 204 100). Patients with PSV were identified between 1 January 1988 and 31 December 1998. RESULTS: Overall, the incidence of PSV in adults was almost equal in Norwich (18.9/million) and Spain (18.3/million). The incidence of Wegener's granulomatosis in Norwich (10.6/million) was greater than in Spain (4.9/million). There was a marked age-specific increase in incidence in Norwich with a peak age 65-74 years (52.9/million), but a virtually equal age distribution between ages 45 and 74 in Lugo (34.1/million). There was no significant increase with time in either population, or evidence of cyclical changes in incidence. CONCLUSION: These data support the suggestion that environmental factors may be important in the pathogenesis of PSV.     

Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.     

Pragmatic language interpretation after closed head injury: Relationship to executive functioning

Introduction: Closed head injury is associated with impairment in a range of executive skills, and with everyday difficulties in social interactions. Comprehension of pragmatic language plays an important role in social interactions. The present study was designed to examine performance on a task involving pragmatic judgement in people who had suffered closed head injury (CHI), and the relationship between this and any impairments in executive skills. Methods: Participants with CHI were compared to a matched healthy control group on a pragmatic inference task consisting of a series of brief vignettes. Participants made judgements about alternative responses in relation to social appropriateness/skill, and carried out several nonsocial executive tasks thought to play a role in pragmatic judgement. Results: The CHI group was poorer than the control group on the pragmatic measure, showing less discrimination than the control group between direct, literal interpretations and correct, indirect interpretations. They also performed more poorly on the nonsocial executive measures. Regression analysis showed an association between pragmatic performance and one of the executive tasks, a measure of inhibition. Conclusions: More work is needed to explore further the nature of any relationship between pragmatic judgement and executive skills.