Nadolol, a new beta-adrenergic blocking agent, was administered orally in gradually increasing single daily doses to 13 hospitalized patients with essential hypertension. Maximal doses ranged from 200 to 480 mg/day. Blood pressure was reduced in nine patients and heart rate was decreased in 11 patients. The decrease in blood pressure was either partial or temporary in five of the nine patients who responded. Concomitant administration of the diuretic chlorthalidone decreased blood pressure in a previously unresponsive patient. Nadolol effectively inhibited isoproterenol-induced tachycardia and decreased cardiac output by 18 per cent. Plasma renin activity and plasma aldosterone concentration were not changed significantly by the treatment. Body weight was not altered significantly. Blood pressure response was independent of the pretreatment renin levels or the change in renin induced by nadolol; it was also independent of the changes in cardiac output and heart rate but was more pronounced in patients with milder baseline hypertension. The decline in serum concentration of nadolol was consistent with the drug's reported half-life of 12.2 hours. The results indicate that single daily doses of nadolol alone can reduce blood pressure significantly with minimal cardiodepressant effects and no important side effects. The effectiveness of nadolol may be enhanced by the addition of a diuretic.

Adrenergic beta-Antagonists↗

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Additional psychiatric illness by Diagnostic Interview Schedule in male alcoholics.

Seventy-four male veterans entering an alcohol abuse treatment program were screened for additional psychiatric diagnoses using the Diagnostic Interview Schedule (DIS). Fifty-four of these also completed a questionnaire on personal and family drinking history. Over half (54.1%) had another diagnosis. The most common syndromes other than substance abuse were antisocial personality disorder, phobic disorder, and depression. In each of these cases, the presence of the additional disorder accelerated the course of the alcohol problem significantly. The difference in course between syndromes was dwarfed by the time of presentation by the difference between "pure" alcoholism and alcoholism with another diagnosis. The primary versus secondary distinction appeared to account for only a part of this effect.

Adult↗

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Effect of aging on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in the rat corpus striatum.

Cyclic AMP levels and activities of adenylate cyclase and phosphodiesterase in the striatum were measured in 4, 12, 24 and 30 month-old rats. No age-related changes were observed either in cyclic AMP levels or basal adenylate cyclase activity. However, there was an age-related decline in dopamine sensitivity of adenylate cyclase without affecting NaF-induced stimulation. There was also an age-dependent decrease in phosphodiesterase activity at low substrate concentrations (3 X 10(-7) and 3 X 10(-6) M) but not at high substrate concentrations (3 X 10(-5) and 3 X 10(-4) M). These results suggest that the functions of dopaminergic neurons may have been altered by aging.

Adenylyl Cyclases↗

PubMedDate not supplied

beta-adrenergic receptor sensitivity in cultured vascular smooth muscle cells: effect of age and of dietary restriction.

The effect of age and of dietary restriction on vascular beta-receptor sensitivity was investigated using cultured smooth muscle cells from rat aortas. The growth rate was slower in cells obtained from 36-month-old rats than in cells obtained from 24-month-old rats and the cells from older animals achieved lower densities. The dietary restriction did not affect growth of cells from 24-month-old rats but increased cell numbers in 36-month-old rats. The elevation of the cyclic AMP level in response to epinephrine was decreased with age. Cells from dietary restricted animals responded more to epinephrine than cells from animals of the same age fed ad libitum.

Aging↗

PubMedDate not supplied

Involvement of free radicals in dementia of the Alzheimer type: a hypothesis.

We propose that increased formation of oxygen-derived free radicals, such as the superoxide and hydroxyl species, may be responsible for progressive neural degeneration in dementia of the Alzheimer type (DAT). Several processes increase free radical formation and some of them (e.g., brain trauma, aging) are risk factors for DAT. There is some evidence for increased free radical formation in Down's syndrome which is associated with development of DAT pathology. Free radicals alone may induce cell death by damaging lipids or proteins while reactions between free radicals and neurotransmitters may lead to formation of endogenous neurotoxin(s). Recently, we have demonstrated that partial oxidation of serotonin by exposure to hydroxyl radicals results in formation of a novel neurotoxin, tryptamine-4,5-dione. Elucidation of the role of free radicals in DAT could open new avenues to prevention and treatment of this disease.

Aging↗

PubMedDate not supplied

Circadian locomotor activity and core-body temperature rhythms in Alzheimer's disease.

Sleep-wake cycle disturbances suggest that circadian rhythms may be disrupted in patients with Alzheimer's disease (AD). In this study, we examined the circadian rhythms of core-body temperature and locomotor activity in 28 patients with probable AD and 10 healthy controls. AD patients had higher percent nocturnal activity than controls, corresponding to the clinical picture of fragmented sleep. The amplitude of the activity cycle in the AD patients was lower than that of controls and the acrophase of this cycle in AD patients was 4.5 h later. There was no difference in the amplitude of the core-body temperature circadian rhythm, but AD patients had delayed temperature acrophases. A subgroup of AD patients with large mean time differences between the acrophases of their activity and temperature cycles had lower temperature amplitudes and greater activity during the night. These findings suggest that a subgroup of AD patients with impaired endogenous pacemaker function may have a diminished capacity to synchronize the rhythm of core-body temperature with the circadian cycle of rest-activity. This circadian rhythm dysfunction may partly explain the fragmented nocturnal sleep exhibited by these patients.

Aged↗

PubMedDate not supplied

Cyclic nucleotides and ethanol tolerance and dependence.

Acute ethanol administration decreases cyclic AMP levels in brains of some animal strains. The ethanol-induced decrease of cyclic GMP levels cannot be blocked by intraventricular infusion of calcium but it can be prevented by pretreatment with pyrazole. Although cyclic AMP levels in the cerebral cortex change reciprocally after acute ethanol administration and during withdrawal, the increase observed during withdrawal is probably secondary to some withdrawal processes. Ethanol decreases cerebellar GABA levels only in rats which are stressed prior to sacrifice. Chronic intraventricular infusion of calcium increased the intensity of an acoustic startle response during ethanol withdrawal while EGTA infusion delayed the development of tolerance to the hypothermic effect of ethanol. The ratio of cyclic GMP to GABA levels is postulated to be important for expression of the withdrawal syndrome.

Animals↗

PubMedDate not supplied

Assessment of behavioral symptom management in demented individuals.

This article is intended to stimulate interdisciplinary research by social, behavioral, and biomedical researchers to solve some of the problems for persons with Alzheimer disease who suffer from behavioral symptoms. We identify the need for using conceptually based measures that have adequate reliability and validity to operationalize indicators of psychological well-being, suggest instruments to assess mood, engagement, agitation, resistiveness and comfort, and pose research questions to explore responses to active involvement (individual or group), passive involvement, lack of activity, aversive activity (related to activities of daily living), and limitation of activity (restraints) in persons with dementia. Answers to the research questions posed in this article will lead to expanded knowledge and can redefine how we give care to those in need.

Aged↗