Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension.

OBJECTIVE--To see whether low dose thiazide diuretics given to patients with essential hypertension might avoid the adverse metabolic consequences seen with conventional doses. DESIGN--Double blind randomised crossover study of two 12 week treatment periods with either low dose (1.25 mg) or conventional dose (5.0 mg) bendrofluazide given after a six week placebo run in period. SETTING--Outpatient clinics serving the greater Belfast area. SUBJECTS--16 white non-diabetic patients (9 male) under 65 with essential hypertension recruited from general practices within the greater Belfast area. MAIN OUTCOME MEASURES--Systolic and diastolic blood pressure and peripheral and hepatic insulin action. RESULTS--One man failed to complete the study. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had substantially less effect on serum potassium concentration than the 5.0 mg dose. There were no intertreatment differences in fasting glucose, insulin, cholesterol, and triglyceride concentrations. Bendrofluazide 5.0 mg significantly increased postabsorptive endogenous glucose production compared with baseline (mean 10.9 (SD 1.2) v 10.0 (0.8) mumol/kg/min), whereas bendrofluazide 1.25 mg did not. Postabsorptive endogenous glucose production was significantly higher with bendrofluazide 5.0 mg compared with 1.25 mg (10.9 (1.2) v 9.9 (0.8) mumol/kg/min) but was suppressed to a similar extent after insulin (bendrofluazide 5.0 mg 2.8 (1.5) mumol/kg/min v bendrofluazide 1.25 mg 2.2 (1.5) mumol/kg/min). Exogenous glucose infusion rates required to maintain euglycaemia were not significantly different between doses and were similar to baseline. CONCLUSIONS--Bendrofluazide 1.25 mg is as effective as conventional doses but has less adverse metabolic effect. In contrast with conventional doses, low dose bendrofluazide has no effect on hepatic insulin action. There is no difference between low and conventional doses of bendrofluazide in their effect on peripheral insulin sensitivity.     

THE DISTRIBUTION OF NEUROPHYSINS AND POSTERIOR PITUITARY HORMONES IN THE PORCINE NEUROHYPOPHYSEAL SYSTEM

Specific, homologous porcine neurophysin I and II radioimmunoassays were established together with specific oxytocin and vasopressin radioimmunoassays. The levels of each of these proteins and peptides were measured in acid extracts of individual paraventricular nuclei, supraoptic nuclei, neurohypophyseal stalks and posterior pituitary lobes of 12 pigs in order to quantitate the neurophysin-hormone relationships in the porcine neurohypophyseal system. Neurophysin III was found to be immunologically identical to neurophysin I. Neurophysin measurements by radioimmunoassay were quantitatively validated by scanning densitometry of polyacrylamide gels stained with 0.5% amido schwarz. In the hypothalamic nuclei vasopressin was in 3–4 M excess of oxytocin but in the neurohypophyseal stalk and posterior pituitary lobe the hormones were equimolar suggesting that the rate of formation of vasopressin differs from that of oxytocin. Neurophysin I immunoreactivity was present in a 3:1 molar ratio with neurophysin II throughout the porcine neurohypophyseal system. In posterior pituitary lobes total neurophysins were equimolar to total hormone concentrations. The specific activity (pmol/mg extracted protein) of oxytocin increased 1800 times, vasopressin 560 times and neurophysins about 360 times from the paraventricular nucleus to the posterior pituitary lobe. In the hypothalamic nuclei relationships between immunoreactive neurophysin I and vasopressin, and between neurophysin II and oxytocin were highly significant. In the posterior pituitary lobe each immunoreactive neurophysin level correlated with both hormone levels. Quantification of densitometric scans of stained polyacrylamide gels from neurophypophyseal extracts and immunoreactivity patterns of neurophysins in eluates of sliced, duplicate gels indicated that neurophysin III decreased distally within the neurohypophyseal tract while neurophysin I increased. The results demonstrated that vasopressin was associated with porcine neurophysin I. However, oxytocin may be associated with both immunoreactive neurophysin I and neurophysin II in the porcine neurohypophyseal system if a 1:1 molar ratio of neurophysin to hormone is to be maintained. Neurophysin III contributed to the stoichiometry of this relationship.     

An NMR study of the exchange rates for protons involved in the secondary and tertiary structure of yeast tRNA Phe.

Solvent exchange rates of all the protons of yeast tRNAphe resonating in the lowfield NMR region (-11 to-15 ppm from DSS) have been measured by saturation-recovery long-pulse Fourier transform NMR. All these protons in yeast tRNAphe are in the fast exchange limit with H2O relative to their intrinsic longitudinal relaxation processes. Most rates show very little temperature dependence; however, tertiary base pair protons are preferentially destabilized in the absence of Mg++ at higher temperatures. The measured exchange rates are between 2 and 125 sec-1 for a temperature range from 10 degrees C to 45 degrees C and MgCl2 concentrations between 0 and 15 mM.     

Isolation of metabolic plasmid DNA from Pseudomonas putida

Metabolic plasmids conferring on $\text{Pseudomonas putida}$ the aromatic growth phenotypes naphthalene, Nah⁺, salicylate, Sal⁺, or toluate, Tol⁺, have been isolated as covalently closed circular DNA in 100 μg amounts. Plasmid DNA was banded in CsCl-ethidium bromide density gradients and sedimentation rates measured in sucrose gradients and by analytical centrifuge. The plasmid sizes found, in millions, were /NAH 42, /SAL 43, /TOL 55, 42. Transformation of metabolic plasmid free $\text{P. putida}$ with the isolated DNA confirmed the respective aromatic pathway gene contents.     

Evolutionary temperature adaptation and the calcium regulation of fish actomyosin ATPases

Summary Actomyosins have been isolated from the white skeletal muscles of fish inhabiting thermal environments with characteristically low seasonal temperature variations for example, Antarctica, arctic rivers and the equatorial oceans.Calcium regulation of actomyosin ATPase was correlated with environmental temperature. Increased assay temperature resulted in a progressive loss of calcium sensitivity. This occurred at lower temperatures in the more cold adapted species.In general cold adapted ATPases have lower activation enthalpies (H ) and higher activities at low temperatures than their tropical counterparts. In contrast to environmental temperature acclimation (Johnston, 1979) calcium regulatory proteins of stenothermal species were not directly involved in the temperature adaptation of actomyosins. Similar relationships were obtained between environmental temperature and thermodynamic activation parameters for both natural and desensitized actomyosins from which tropomyosin and troponins had been removed. Instead, evidence is presented that the mechanism of temperature adaptation over evolutionary time periods involves selective modifications in the structure of both the heavy and light chains of myosin.     

Hereditary and environmental determinants of growth in height in a longitudinal sample of children and youth of Guatemalan and European ancestry

The effects of hereditary and environmental factors upon the growth in stature of children living in Guatemala City has been studied. Heights at yearly examinations were fitted, by individual, to a double logistic curve in samples of Guatemalan and European children attending a private school in Guatemala City. These two samples differed genetically yet shared the same environment. Their growth was compared, by a multivariate analysis of the parameterized curves, to that of children from the Berkeley Growth Study, genetically similar to the European sample, yet living in different environments. The European children in Guatemala grew, before adolescence, more similar to Guatemalan and differed significantly from the Berkeley sample children. However, the amount of growth during the adolescent years experienced by the European children was similar to that of the Berkeley sample and differed from their Guatemalan counterparts.     

Synaptophysin: structure of the human gene and assignment to the X chromosome in man and mouse.

Synaptophysin is an integral membrane protein of small synaptic vesicles in brain and endocrine cells. We have determined the structure and organization of the human synaptophysin gene and have established the chromosome localizations in man and mouse. Analysis of a cosmid clone containing the human synaptophysin gene (SYP) revealed seven exons distributed over approximately 20 kb, when compared with the previously published cDNA sequence. The exon-intron boundaries have been identified and do not correlate with functional domains. One intron interrupts the 3' untranslated region. Chromosomal localization of the human and murine genes for synaptophysin established the human SYP locus on the X chromosome in subbands Xp11.22-p11.23 and the mouse synaptophysin gene locus (Syp) on the X chromosome in region A-D. In addition, an Eco0109 RFLP has been identified and used in genetic mapping of the human SYP locus and supports the order TIMP-SYP-DXS14 within a span of approximately 4-7 centimorgans.     

Muscle fibre differentiation and vascularisation in the juvenile European eel (Anguilla anguilla L.)

Summary The development of the pituitary gland and its blood vessels is described in rat embryos (gestational day 12 through day 21) injected with India-ink via the umbilical vessels. The vascularization of all components of the pituitary gland develops from the surface network covering the prosencephalic vesicle. However, vascular connections exist between the prospective median eminence and the anterior pituitary gland in the earliest stages examined (day 12) but are not augmented by vessels from the stomatodeal roof until day 13. Primary portal veins appear initially on day 13, the vascularization of the pars distalis is visible on day 15. The Mantelplexus covering the floor of the diencephalon is discernible on day 16. Large-caliber portal veins appear immediately before birth, but otherwise there is no significant change in the vascular pattern during the last five days of gestation. The pars intermedia and the median eminence-pituitary stalk region remain avascular throughout embryonic life.