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Biomedical subjects

R Salisbury

Publications and source records attributed to R Salisbury.

At least 19 recordsLinked to original sources

Neonatal sympathectomy reduces adult blood pressure and cardiovascular pathology in Y chromosome consomic rats.

The hypothesis was tested that the sympathetic nervous system (SNS) developmentally influences circulating testosterone (T), systolic blood pressure (SBP) and cardio-renal pathology in SHR/y animals. A sympathoplegic drug, guanethidine, and an antibody to nerve growth factor were administered to WKY and borderline hypertensive SHR/y male rats (n = 20/group) for the first 3 weeks of life; control groups (n = 20/group) received saline. SBP, serum T and luteinizing hormone (LH) were measured. SBP in the WKY and SHR/y sympathectomy (sympx) groups decreased 10mmHg (p < 0.001) and 50mmHg (p < 0.001), respectively, when compared to their control groups. Serum T levels in the sympx WKY group were lower (p < 0.01) than those in controls, and the rise of T typically observed in SHR/y from weeks 6-8 was delayed in the sympx SHR/y group, similar to the pattern in WKY. Serum LH levels were increased in the sympx WKY group, but not in the SHR/y group. Sympx caused a greater reduction in renal glomerular changes (p < 0.01), coronary artery collagen deposition (p < 0.01) and myocardial fibrosis (p < 0.01) in SHR/y than WKY rats. In conclusion, the SHR Y chromosome has a locus that enhances SNS activity, which can raise SBP and result in renal and cardiovascular tissue damage.

Animals↗

Castration lowers and testosterone restores blood pressure in several rat strains on high sodium diets.

The objective of this study was to determine the effect of a high sodium diet and prepubertal castration (5-6 weeks) and androgen replacement therapy on blood pressure in male normotensive, borderline hypertensive and hypertensive rats on a high sodium diet between 9-22 weeks of age. The strains used were: Wistar Kyoto-(WKY), spontaneously hypertensive rat-(SHR), and borderline hypertensive rat-(BHR). Castration significantly reduced blood pressure (20-30 mmHg) and testosterone replacement in castrated males restored blood pressure in all strains. Plasma norepinephrine (NE) increased with castration in the WKY and SHR strains but decreased in the BHR. However, there was a significant elevation in all strains between the midpoint and endpoint NE values. The high sodium diet did not prevent the blood pressure lowering effect of castration.

Animals↗

The spontaneously hypertensive rat Y chromosome produces an early testosterone rise in normotensive rats.

OBJECTIVE: To investigate the relationship between testosterone and blood pressure during the rapid development phase of blood pressure rise in four strains of rats: Wistar-Kyoto (WKY) rats; spontaneously hypertensive rats (SHR); SHR/y, a substrain with an SHR Y chromosome and WKY rat autosomes and X chromosomes; and SHR/a, a substrain with SHR autosomes and X chromosomes and the WKY rat Y chromosome. METHODS: Blood pressure was measured every 2 weeks by the tail-cuff method, and was verified in selected rats at 23 weeks by aortic telemetry. Serum testosterone was measured, by radioimmunoassay, every 2 weeks from 5 to 23 weeks of age. RESULTS: During the rapid phase of blood pressure rise, between 5 and 9 weeks of age, there was a significantly larger rise in serum testosterone in SHR and SHR/y than in WKY rats and SHR/a groups. The hypertensive Y chromosome in the SHR and SHR/y accelerated peak testosterone approximately 4 weeks earlier, and blood pressure was increased in these two groups compared with the SHR/a and WKY rat groups, respectively. A gene on the SHR Y chromosome (Tty) affecting the timing of testosterone in development is proposed. At approximately 15 weeks of age testosterone levels decreased sharply towards prepubertal levels in WKY rats and at 23 weeks in SHR/y, whereas testosterone levels were maintained in SHR and SHR/a, which suggests an autosomal component. CONCLUSION: The SHR Y chromosome may accelerate the start of puberty and a cascade of molecular and neuroendocrine events that raise blood pressure.

Aging↗

Androgen receptor and the testes influence hypertension in a hybrid rat model.

The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasma luteinizing hormone levels in normal and prenatally stressed male and female rat fetuses and their mothers.

Concentrations of luteinizing hormone (LH) were measured in plasma of fetal and neonatal rats obtained from control mothers and from mothers exposed to stress from Days 14 to 21 of gestation. The regimen of stress used is known to be associated with an abnormal ontogenetic pattern of testosterone secretion from the fetal testes. The overall ontogenetic pattern of immunoreactive LH levels in plasma was similar in male and female rats, and was unaffected by stress. In all groups, LH was low from Days 16 to 20 of gestation, and then rose progressively through birth, i.e. Day 23. However, stressing the mother significantly decreased the already low levels of LH between Days 16 and 20, as indicated by a larger percentage of samples from stressed fetuses of both sexes with LH levels below the limit of sensitivity of the assay. Sex differences in both the control and stressed group became evident only after Day 20 of gestation, with plasma concentrations of females exceeding those of males from Day 21 to 23 post-conception.

Analysis of Variance↗

Results of a multicenter outpatient burn study on the safety and efficacy of Dimac-SSD, a new delivery system for silver sulfadiazine.

Dimac with silver sulfadiazine (Dimac-SSD), a new silver sulfadiazine delivery system, was evaluated prospectively in a multicenter study for the treatment of outpatient burn injuries. The goal of this study was to evaluate the effect of Dimac-SSD on the microbiology of the burn wounds and to quantitate its clinical safety and efficacy. A total of 197 patients were evaluated. Eight (4%) of these patients did not complete the study. Six patients withdrew because of local discomfort caused by the Dimac-SSD and two patients were terminated because of technical problems. The mean +/- SD duration of treatment with Dimac-SSD was 12 +/- 8.5 days, during which time the mean number of dressing changes was 2.9 per patient. During treatment with Dimac-SSD, the burn wound bacterial flora remained stable and overgrowth with Pseudomonas species or Gram-negative bacilli did not occur. Only four (2%) patients developed clinical infections; thus the Dimac-SSD appeared to have good antimicrobial effectiveness. This dressing was not associated with any organ system or metabolic side-effects and patient discomfort during application and removal was minimal. Thus this new delivery system for silver sulfadiazine was associated with excellent wound healing, a low incidence of wound infections, reduced frequency for dressing changes, and excellent patient compliance.

Acrylates↗

Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis.

Clinical assessment, plasma and synovial fluid kinetics were studied in 29 rheumatoid patients receiving 100 mg flurbiprofen twice daily. Clinical assessment and pharmacokinetic measurements varied widely within the group of patients. The average values for plasma clearance, volume of distribution and elimination halflife of flurbiprofen were 0.65 +/- 0.24 ml min-1 kg-1, 0.160 +/- 0.093 l kg-1 and 3.1 +/- 1.7 h, respectively. Synovial fluid drug concentrations peaked later and were lower than corresponding plasma concentrations: 5.2 h and 4.4 mg l-1 as against 1.49 h and 12.5 mg l-1, respectively. At 48 h after an oral dose of flurbiprofen, all the drug had been cleared from the synovial fluid. Synovial fluid drug concentrations were not related to synovial fluid albumin concentration or pH. There was a weak relationship between synovial fluid drug concentration and the thermographic measurements of disease activity. The fractions of flurbiprofen not bound to protein in synovial fluid and plasma were not significantly different. A simple model is proposed to account for the plasma and synovial fluid pharmacokinetics.

Adolescent↗

Assessment of inflammation in the rheumatoid knee joint: correlation between clinical, radioisotopic, and thermographic methods.

Standard clinical methods of assessing joint inflammation are being supplemented increasingly by radioisotopic and thermographic studies. However, the correlation between these different methods has not been firmly established. In the quantification of synovitis by infrared thermography we have shown that the heat distribution index (HDI) based on thermal pattern is more reliable and is less affected by diurnal variations in joint temperature than the commonly used thermographic index, which is based on average skin temperature values. In 20 patients with rheumatoid arthritis whose knees were being treated with intra-articular steroid we obtained 184 serial paired observations over a period of 24 weeks for clinical assessment, HDI, and 99mTc pertechnetate uptake. We found significant correlations (p less than 0.001) between the three methods of assessment (except for pain and HDI (p = 0.116)).

Adult↗

Prostaglandin E1 vasospastic disease and thermography.

This is the first study to show a quantitative thermographic difference between patients with Raynaud's syndrome and normal controls after cold stress testing. An improved thermographic response to cold stress testing after treatment of Raynaud's syndrome with PGE1 has also been shown for the first time. Discriminant analysis of the change in temperature of a finger after cold stress, and the mean thermal gradient along the finger during rewarming, clearly separated patients from controls. After treatment with PGE1 the patients' discriminant values moved into the normal range. Symptomatic improvement after PGE1 correlated well with thermographic improvement, and both persisted for up to 12 weeks.

Adult↗

Pathways of hydrogen utilization from NADPH generated by glucose-6-phosphate dehydrogenase in circumventricular organs and the hypothalamo-neurohypophysial system: a cytochemical study.

Cytochemistry was used to examine the distribution of two pathways of utilization of hydrogen (Type I and Type II H) generated by glucose-6-phosphate dehydrogenase (G6PD) in circumventricular organs (CVOs) and the hypothalamo-neurohypophysial system in cryostat sections of rat brain. Type I H is defined as that portion of the total reducing equivalents (Total H) that is passed, in the intact cells, along the cytochrome chain (NADPH-diaphorase system). In the liver, energy from Type I H is used for cytochrome P-450-dependent oxidation of steroids, as well as xenobiotics. We proposed that mixed function oxidation, and therefore Type I H, would be preferentially localized in brain regions lacking a blood-brain barrier, such as CVOs and magnocellular cells with terminals in such brain regions. Type I H was identified in tissue sections using neotetrazolium. This reagent, when reduced, precipitates as formazan granules that can be quantified. The large difference in redox potential between NADPH and neotetrazolium ensures that only hydrogen (Type I H) passed in the intact cell along the cytochrome chain, can reduce the tetrazole. Total NADPH generation (Total H) from glucose-6-phosphate, was identified using medium containing phenazine methosulphate, a hydrogen acceptor that transfers all reducing equivalents from NADPH to the tetrazole. Type II H, the difference between Total and Type I H, is presumed to be used for NADPH-dependent biosynthetic functions such as lipid synthesis, or reduction of glutathione. In CVOs formazan granules indicative of Type I H were selectively concentrated and localized within cells throughout the SFO, organum vasculosum of the lamina terminalis, pineal gland and in the apical cytoplasm of columnar ependymocytes in the subcommissural organ. Formazan granules attributable to Type I H were also prominent throughout the hypothalamo-neurohypophysial system. Reaction product was present in the cytoplasm of some magnocellular neurons in both the supraoptic and paraventricular nuclei, in the median eminence, including the zona interna, and in and between cells in the neurohypophysis. The distribution of NADPH-diaphorase in sections incubated with NADPH instead of glucose-6-phosphate was similar to that of Type I H. These findings are consistent with the hypothesis that mixed function oxidation involving NADPH and the cytochrome chain occur in these brain regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗