Effect of hypoxia on monoamine synthesis in brains of developing rats. II. Different length of exposure.
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Animals↗
Biomedical subjects
T Hedner
Publications and source records attributed to T Hedner.
Changes in cerebrospinal fluid homovanillic acid in children with Ondine's curse.
The cerebrospinal fluid (CSF) concentrations of three acid monoamine metabolites, two purines, and a group of amino acids were determined in two children with chronic central alveolar hypoventilation (Ondine's curse). The levels of all assayed neuroactive substances, metabolites, and amino acids, with one exception, were normal compared to an age-matched group of neurologically healthy children. The levels of the dopamine metabolite homovanillic acid in the children with Ondine's curse were approximately 2.4 times higher than expected for age range. The present findings may indicate a link between central nervous system dopamine activity and chronic central alveolar hypoventilation. Among other possible explanations, the changes seen might represent a primary alteration in dopamine activity or may reflect a change in dopamine turnover resulting from the chronic hypoventilation.
Adenosine↗
Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol.
Naringenin, quercetin and kaempferol, which may be found in glycoside form in natural compounds such as grapefruit, are potent inhibitors of cytochrome P-450 metabolism. The influence of these flavonoids on the metabolism of 17 beta-estradiol was investigated in a microsome preparation from human liver. The flavonoids were added in concentrations of 10, 50, 100, 250 and 500 mumol/l to the microsome preparation. The metabolism of 17 beta-estradiol was concentration dependently inhibited by all the flavonoids tested. Addition of the flavonoids to the microsome preparation did not influence estrone formation, while a potent inhibition of estriol formation was observed. At the highest concentrations tested of the respective flavonoid, there was approximately 75-85% inhibition of estriol formation. However, naringenin was a less potent inhibitor of 17 beta-estradiol metabolism as compared to quercetin and kaempferol. The most likely mechanism of action of the flavonoids on 17 beta-estradiol metabolism is inhibition of the cytochrome P-450 IIIA4 enzyme, which catalyzes the reversible hydroxylation of 17 beta-estradiol into estrone and further into estriol. These hydroxylation processes represent the predominant steps of the hepatic metabolic conversion of endogenous as well as exogenous 17 beta-estradiol. This interaction would be expected to inhibit the first-pass metabolism of 17 beta-estradiol, and this has recently been demonstrated after oral administration of 17 beta-estradiol to women.
Adult↗
Localization of pain in suspected acute myocardial infarction in relation to final diagnosis, age and sex, and site and type of infarction.
OBJECTIVES: To describe the localization of pain in consecutive patients admitted to the coronary care unit for possible acute myocardial infarction (AMI) and to relate it to the development of AMI, age, and gender. DESIGN: Prospective evaluation. SETTING: Sahlgrenska Hospital, covering half the area of the city of Göteborg, with half a million inhabitants. SUBJECTS: Nine hundred three consecutive patients admitted to the coronary care unit for possible AMI between 24 and 87 years old with a mean age of 64 years. OUTCOME MEASURES: Localizations of pain according to a self-constructed figure. Patient were approached between 1 and 14 days after onset of symptoms and asked to describe the localization of pain according to the figure, including nine positions on the chest, left and right arm, neck, and back. RESULTS: AMI developed in 50% of patients during the first 3 days in hospital. Patients in whom AMI developed localized their pain to an extent similar to those without AMI in seven of nine chest areas. However, patients with AMI reported pain in the upper right square of the chest more frequently (p < 0.001) and in the middle left square of the chest less frequently (p < 0.01) than did patients without AMI. Pain in both the right (p < 0.001) and left arms (p < 0.01) was more frequently reported by patients who had AMI. Among patients with AMI, women reported pain in the neck (p < 0.05) and in the back (p < 0.01) more frequently than did men. Compared with elderly patients, younger patients reported pain more frequently in the left arm (p < 0.01), right arm (p < 0.01), and neck (p < 0.05). CONCLUSIONS: Among consecutive patients with possible AMI admitted to the coronary care unit, patients who had confirmed AMI reported pain in both arms more frequently than did patients without AMI. However, both groups described their chest surface distribution of pain similarly in the majority of positions, thereby indicating that the localization of chest pain is of limited use in predicting which patients will eventually have AMI.
Adult↗
Dose-responsive antihypertensive efficacy of valsartan, a new angiotensin II-receptor blocker.
Predictable dose-related efficacy is considered to be an important attribute of any antihypertensive agent. To determine the magnitude of dose-responsive efficacy for valsartan, a highly selective angiotensin II-receptor blocker, we conducted an integrated analysis of efficacy data from nine double-masked, randomized, placebo-controlled, parallel studies of similar design and of at least 4 weeks' duration. The intent-to-treat analysis included 4067 patients with mild-to-moderate hypertension who had received valsartan (n = 2901) 10, 20, 40, 80, 160, or 320 mg once daily or placebo (n = 1166). Blood pressure was assessed at trough (24 hours after the last dose). In all nine studies, valsartan doses > or = 80 mg produced statistically significant reductions in supine or seated diastolic blood pressure (SDBP) and systolic blood pressure (SSBP) compared with placebo (P < 0.05). The integrated analysis demonstrated a clear increase in blood-pressure-lowering efficacy with increasing dose across the range 10 to 320 mg (placebo-subtracted mean changes from baseline to end point for valsartan 10, 20, 40, 80, 160, and 320 mg, respectively: SDBP, -0.8, -2.8, -2.6, -3.9, -5.1, and -6.4 mm Hg; SSBP, -1.3, -5.7, -5.3, -6.8, -8.6, and -9.0 mm Hg). The data demonstrate that valsartan provides dose-responsive antihypertensive efficacy across the therapeutic dose range, with clinically relevant blood-pressure lowering at doses > or = 80 mg once daily.
Adult↗
Systemic and renal hemodynamic effects of single oral doses of felodipine in patients with refractory hypertension receiving chronic therapy with beta-blockers and diuretics.
In 12 patients with primary hypertension (World Health Organization stage 2) inadequately controlled by chronic standard triple therapy, hydralazine was replaced by felodipine, a new vasodilating dihydropyridine derivative, and the acute effects of the drug on central and renal hemodynamics were monitored. Following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was given. Fifteen minutes after intake of felodipine, a significant hypotensive response was observed, and the maximal response (23% reduction of mean arterial pressure) occurred after 30 min. There was a linear relationship between the changes in mean arterial pressure and log plasma concentration of felodipine. Cardiac output (dye dilution) increased during maximal blood pressure reduction, from 5.3 +/- 1.0 to 6.6 +/- 2.4 L/min (p less than 0.01), partly because of increased heart rate from 57 +/- 4 to 65 +/- 9.1 beats/min (p less than 0.01) and partly because of increased stroke volume from 93 +/- 14 to 104 +/- 33 ml (p less than 0.05). Renal plasma flow (para-aminohippuric acid clearance) increased significantly (p less than 0.05) from 343 +/- 138 to 391 +/- 154 ml/min, while glomerular filtration rate ([51Cr]EDTA clearance) did not change. Arteriovenous noradrenaline difference increased 36% during felodipine therapy, when corrected for blood flow increase. We conclude that felodipine is a calcium inhibitor with potent vasodilating properties.
Administration, Oral↗
Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists.
Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.
Animals↗
Importance of dietary salt in the hemodynamic adjustment to weight reduction in obese hypertensive men.
Twenty-three moderately obese middle-aged men with previously untreated hypertension (World Health Organization classification 1-2) were evaluated to assess the effects on blood pressure (BP) of a diet restricted in energy (fats and carbohydrates) but unrestricted in sodium (Group 1) compared to a diet restricted in energy and sodium (Group 2). The patients were randomly allocated to either of the two groups and were comparable in age, sex, weight, and BP. The same energy- and sodium- restricted diet was given to both groups, but the intake of Group 1 (n = 13) was supplemented with dietary sodium. The average urinary output for Group 1 was 192 +/- 39 mmol/24 hr at baseline and 200 +/- 56 mmol/24 hr during the diet. For Group 2 (n = 10), which remained on the initial diet, urinary sodium excretion changed from 188 +/- 53 mmol/24 hr at baseline to 97 +/- 32 mmol/24 hr (p less than 0.001). Intraarterial BP, cardiac output (CO), plasma volume, circulating norepinephrine (NE), and urinary NE were measured at baseline and at the end of the dieting periods. Before the dietary sodium supplement while on the initial diet, the patients in Group 2 showed a reduction in body weight from 97.3 +/- 10.5 kg to 88.6 +/- 9.9 kg (p less than 0.001). Heart rate (HR) and urinary NE output were significantly reduced in comparison with baseline, but intraarterial BP was unchanged. No change in cardiopulmonary blood volume, CO, or stroke volume (SV) was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Reactivity to norepinephrine and effect of sodium on blood pressure during weight loss.
Eighteen moderately obese middle-aged men with untreated mild hypertension were randomized to two groups and placed on a low energy diet regimen for 9 to 11 weeks. In Group I (n = 10) the amount of sodium chloride in the diet maintained the urinary sodium excretion at the predieting level. Mean body mass was reduced by 9.1 +/- 0.7 (SEM) kg. Mean intra-arterial pressure showed no significant change. There were significant decreases in heart rate (p less than 0.05) and urinary norepinephrine excretion (p less than 0.05) but not in plasma concentration of norepinephrine. In Group II (n = 8) energy as well as sodium intake was restricted, with a 95 +/- 22 mmol/24 hour reduction of urinary sodium excretion. Body mass decreased by 9.3 +/- 1.1 kg, and mean arterial pressure decreased by -18.9 to -4.3 mm Hg (95% confidence interval). There were also significant reductions in heart rate (p less than 0.001) and plasma norepinephrine concentrations (p less than 0.01) but not in urinary norepinephrine excretion. The pressor response (mean arterial pressure) to norepinephrine infusion at different dose rates was significantly elevated (p less than 0.05) in Group I during dieting in comparison with baseline. The blood pressure response to norepinephrine during dieting in patients in Group II was not changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗