Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects.

Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the same as the levels after equimolar administration of DPH. While 2 delivered the same levels of DPH to the brain as DPH did, it was twice as potent as DPH in rats (ED50 was 7.

Concentration-response relationships of disopyramide in patients with ventricular tachycardia.

The protein binding of disopyramide is altered when concentration is increased within the therapeutic range. A wide range of free concentrations may be produced at a given total concentration. The present study assessed whether intracardiac electrophysiologic responses to disopyramide related better to free or to total concentration.

Angiographic recognition of coronary ostial stenosis in nonspecific aorto-arteritis.

A 17-year-old girl was seen with acute anterior myocardial infarction resulting in congestive heart failure. Clinical examination followed by detailed investigation revealed diffuse nonspecific aorto-arteritis, with left coronary ostial stenosis, which is a very rare association. The relevant literature is reviewed.

Role of central histaminergic mechanism in behavioural depression (swimming despair) in mice.

The role of the central histaminergic system in depression was studied by using swimming despair test in mice - a behavioural model of depression. In this test, immobility of mice reflects a state of depression. Intracerebral (ic) injection of histamine (50-200 micrograms) increased significantly the immobility.

Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril.

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved.

Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy.

We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups.

The blood pressure responses of thiazide-resistant hypertensives to a once-a-day bevantolol regimen.

The antihypertensive efficacy of a single daily dose of bevantolol (200 mg) alone or in combination with hydrochlorothiazide (25 mg) has been compared against conventional twice daily propranolol (80 mg) therapy in a group of 22 hypertensive patients whose blood pressures did not respond to thiazide monotherapy. Addition of bevantolol to the diuretic resulted in a significant (P less than 0.001) fall in sitting blood pressures (144/97 to 137/90 mmHg), supine blood pressures (147/100 to 141/92 mmHg) and heart rate (83 to 73 beats/min) 24 h after administration.

The metabolism of nifedipine during long-term therapy.

The serum concentrations and urinary excretion of nifedipine and 3 of its metabolites have been compared in two groups of hypertensive patients, one receiving prolonged (1-2 years) nifedipine monotherapy, the second receiving the same dosage of nifedipine in conjunction with a variety of other antihypertensive and cardioactive drugs. It was found that prolonged administration of nifedipine was associated with an eight-fold reduction in serum nifedipine concentration, one hour following a 10 mg dose, compared with the levels observed at the same time after an acute 10 mg dose. The serum concentration of the metabolite dehydronifedipinic acid was concomitantly increased, but no evidence for dehydronifedipinolactone, derived from hydroxylation of dehydronifedipinic acid, was found.

High performance liquid chromatography analysis of nifedipine and some of its metabolites in hypertensive patients.

Techniques are described for the analysis of nifedipine and three of its metabolites; dehydronifedipine (I), dehydronifedipinic acid (II), and dehydronifedipinolactone (III) in human serum and urine. The analytes are extracted at pH 9 or 3 with ethyl acetate and chromatographed on a C8 reverse-phase column. Recoveries from spiked control serum and urine ranged from 70 to 95% depending on the polarity of the analyte.

Increased metabolic heat production following chronic alpha-methyldopa therapy in hypertensives.

The objective of this study was to measure metabolic heat production in mild-moderate hypertensives when given chronic alpha-methyldopa for control of hypertension and to compare this with hydrochlorothiazide. Four men and one woman, age range 29-55 years, euthyroid, and not previously on alpha-methyldopa, had their drugs replaced by placebo for 4 weeks, and then alpha-methyldopa or hydrochlorothiazide was randomized single blindly to patients. The dose of each drug was increased until the ambulatory diastolic blood pressure was less than 95 mmHg (1 mmHg = 133.

Infant nutrition and supplements.

Today, American consumers believe they need more and better nutrients than their diets provide. Consequently, consumers spend approximately three billion dollars each year on vitamin and nutrition products. Vitamin and/or mineral supplements are relatively inexpensive and available without a prescription; therefore, it is understandable that they are used by a substantial portion of the population.

Ajmaline-induced torsade de pointes.

A patient with primary myocardial disease and left bundle-branch block who developed marked QT prolongation and torsade de pointes following an intravenous injection of ajmaline during an electrophysiologic study is reported. The patient could be resuscitated successfully 1 h after the onset of tachycardia.

Effect of alcohols on the permeability of blood-brain barrier.

Effect of alcohols on the permeability of blood-brain barrier was studied in anaesthetised dogs using sodium fluorescein as circulant. Entry of sodium fluorescein in the cerebrospinal fluid (CSF) was measured spectrophotofluorometrically. Methyl, ethyl, propyl and butyl alcohols were used in the study.

Hypoxemia during hemodialysis.

Decrease in arterial oxygen tension has been reported during hemodialysis.(1-3) The etiology of the hypoxemia has not been clearly demonstrated. Intravascular leukostasis,(1) pulmonary arterial microembolization,(3) and loss of CO(2) through the dialyzer are some of the explanations given for this abnormality.

Newer formazans and tetrazolium indoles as potential CNS-active agents.

Some new 2-aryl-5-(3'-indole)-3'-substituted phenyl tetrazolium bromide/iodide salts (IV) were synthesized by the oxidation of 1-aryl-3-(3'-indole)-5-substituted phenyl fromazans (III). These compounds III and IV were evaluated for their monoamine oxidase (MAO) inhibitory activity in vitro and various CNS activities in vivo. Several compounds exhibited promising CNS activities, III-b being the most active member of the present series showing marked antidepressant and MAO inhibitory activities and having low toxicity.