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Biomedical subjects

J Stessman

Publications and source records attributed to J Stessman.

At least 19 recordsLinked to original sources
PubMed1989

Effect of age on the pharmacokinetics of dipyrone.

The pharmacokinetics of the dipyrone metabolite, 4-methylaminoantipyrine (MAA) was evaluated, following the administration of a single oral dose of dipyrone 1.0 g to 12 young (21-30 years) and 9 elderly (73-90 years) healthy volunteers. Maximal concentration, time to peak and absorption rate of MAA were similar for both groups. The elimination half-life was 2.6 (0.2) h for the young and 4.5 (0.5) h for the elderly subjects. Total clearance of MAA, corrected for lean body mass (LBM), was lower in the elderly than in the young 2.65 vs 3.97 ml.min-1.kg-1 LBM. There was no differences between the groups in the apparent volume of distribution. A good correlation was found between the total body clearance of MAA and the creatinine clearance, which was also reduced in the elderly (r = 0.61).

Adult↗
PubMed1987

Isoelectric focusing of human platelet phospholipase C: evidence for multimolecular forms.

Polyacrylamide gel isoelectric focusing was employed to characterize phospholipase C activity in the supernatant fraction after disruption of human platelets. Three bands of enzyme activity were detected on focused gels: a major band of activity (B) and two additional bands (A,C) were consistently identified. The isoelectric points of the three bands were in the range of pH 7.5-8.0. Phospholipase C activity was assayed using both phosphatidylinositol and phosphatidylinositol-4-monophosphate. The prominent B band was active against both substrates and no evidence for substrate preference towards phosphoinositides was obtained. These data suggest that isozyme forms of cystolic phospholipase C are present in human platelet supernatant and suggest the possibility of functional and structural differentiation of the various forms of the enzyme.

Animals↗
PubMed1986

Calcium channel blockers in the management of hypertension in the elderly.

Calcium channel blockers seem to be particularly suitable for elderly hypertensive patients since these agents do not cause salt and fluid retention, postural hypotension, sedation, depression, or biochemical abnormalities. Moreover, their use is compatible with several common diseases of old age, such as diabetes, obstructive lung disease, and peripheral vascular disease. We recently conducted a study in 21 patients (average age, 79 +/- 2 years) who completed an eight-week trial with 20-mg nifedipine tablets taken twice daily. Mean blood pressure decreased from 191 +/- 2/96 +/- 2 mm Hg to 151 +/- 4/80 +/- 3 mm Hg. In 15 patients (71 percent), blood pressure decreased to less than or equal to 160/90 mm Hg; in four additional patients (19 percent), diastolic blood pressure decreased by 15 to 25 percent. Thus, there was a sustained lowering of blood pressure in 90 percent of the participants receiving nifedipine monotherapy. A review of recent studies in elderly hypertensive patients revealed similarly favorable results with calcium channel blockers given alone or in combination with other agents. The accumulating data suggest that these compounds may offer a useful new approach to the treatment of hypertension in old age. However, in these studies, the number of patients and the duration of follow-up need to be extended to confirm the favorable impression obtained thus far.

Aged↗
PubMed1986

Age related decline in aluminum-activated human platelet adenylate cyclase: post-receptor changes in cyclic AMP second messenger signal amplification in normal aging and dementia of the Alzheimer type.

Low, micromolar concentrations of aluminum (in the presence of NaF) were shown to strongly activate human platelet adenylate cyclase and provided a useful probe for evaluating cyclic AMP second messenger function distal to the receptor: The effect of normal aging and disease state on second messenger activity in man was studied by measurements of the aluminum-activated enzyme. A significant decline in aluminum-stimulated platelet adenylate cyclase activity in older, healthy subjects was observed. An age-associated decline in NaF-stimulated cyclic AMP synthesis was also demonstrated for normal, non-demented subjects. These findings suggest an age-associated lesion at the level of the guanine nucleotide regulatory protein/catalytic subunit of the adenylate cyclase complex. However, for patients with Alzheimer's disease no such decline in platelet adenylate cyclase activity was detected, and increased sensitivity to both aluminum and NaF was demonstrated.

Adenylyl Cyclases↗
PubMed1986

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements.

Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.

Adult↗
PubMed1986

The cyclic AMP second messenger system in man: the effects of heredity, hormones, drugs, aluminum, age and disease on signal amplification.

The intracellular effects of a number of hormonal signals are mediated by the cyclic AMP second messenger system in man and the ubiquitous distribution of hormone-stimulated adenylate cyclase suggests the importance of this enzyme complex in normal aging and pathophysiological states. Various vectors including heredity, endogenous catecholamines, steroid hormones, and drugs affect the activity of hormone-stimulated adenylate cyclase in man. The effect of heredity was studied using lymphocytes obtained from monozygotic twin pairs and age and sex-matched sib pairs. Only for forskolin-stimulated activity is a significant proportion of individual variance attributable to heredity, suggesting the relative stability of the catalytic subunit. Beta-adrenergic and prostaglandin E-1 activity are "state" characteristics and their activities are controlled by environmental parameters. A significant reduction in isoproterenol-stimulated cyclic AMP accumulation between the menses and luteal phase of the menstrual cycle is observed in lymphocytes obtained from 11 female subjects. The lowest level of beta-adrenergic receptor activity is associated with the highest levels of progesterone and estradiol hormone levels in blood. Lithium at therapeutic concentrations markedly inhibits adenylate cyclase activity in platelet membranes. Moreover, marked individual differences are observed in sensitivity to lithium as determined by Dixon plot derived Ki values for 9 normal, healthy subjects. Human adenylate cyclase obtained from platelets and lymphocytes is activated by micromolar amounts of aluminum in the presence of NaF. Irreversible activation of adenylate cyclase by aluminum is suggested as a possible mechanism of this metal's neurotoxicity. The biochemical basis for the age-associated decline in beta-adrenergic responsiveness in man is discussed. Several investigations suggest a deficit at two levels in the adenylate cyclase complex: an impaired coupling of the receptor/N protein subunits and an additional lesion distal to the receptor at the level of N/C coupling. Perfusion studies with salbutamol suggest that the decline in beta-adrenergic sensitivity is general and not restricted to lymphocytes. Possible abnormalities in cyclic AMP signal amplification and recognition in various disease states is discussed. Increased prostaglandin E-1-stimulated cyclic AMP accumulation is observed in lymphocytes obtained from patients with Alzheimer's disease compared to age-matched controls and correlated with severity of the disease state.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1986

Laetrile intoxication and hepatic necrosis: a possible association.

A 65-year-old woman with cirrhosis and hepatoma lapsed into deep coma, hypotension, and acidosis after ingestion of 3 gm of Laetrile, a cyanogenetic glucoside. After initial treatment, the patient regained consciousness, but massive hepatic damage led to her death. We suggested a possible relationship between Laetrile poisoning and massive hepatic necrosis.

Aged↗
PubMed1985

Beta-adrenergic-stimulated adenylate cyclase activity in normal and EBV-transformed lymphocytes.

Beta-adrenergic-associated cyclic AMP accumulation was studied in intact lymphocytes before and after transformation with Epstein-Barr virus into immortal cell lines. Although a marked reduction in isoproterenol-stimulated cyclic AMP synthesis was observed in transformed cells, forskolin-stimulated cyclic AMP accumulation was preserved. A parallel loss of 125-iodocyanopindolol binding sites suggests that the reduction in beta-adrenergic-stimulated AMP synthesis is due to receptor down-regulation.

Adenylyl Cyclases↗
PubMed1985

Nifedipine in the treatment of hypertension in the elderly.

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.

Age Factors↗
PubMed1985

The effect of age on beta-adrenergic function in man: a review.

The structure and function of the beta-adrenergic adenylate cyclase complex in the elderly is reviewed. The function of the beta-adrenergic receptor in man is modulated by levels of circulating catecholamines, noncatecholamine hormones, drugs, disease, and age. Although a number of clinical observations demonstrate an age-related decrease in catecholamine responsiveness, the molecular basis of this phenomenon is unknown. Simple reduction in beta-receptor number does not appear to explain age-associated loss of catecholamine responsiveness. Recent investigations from our laboratory employed salbutamol-induced rise in plasma cyclic AMP (cAMP) levels to study the molecular basis for this phenomenon. In young individuals there was a threefold increase in plasma cAMP levels after salbutamol infusion. In older subjects only a 50% rise in plasma cAMP levels was observed. These results suggest that the basis for reduced catecholamine responsiveness in the elderly is due to a defect in the peripheral beta-receptor-linked adenylate cyclase complex. The finding of reduced beta-adrenergic-stimulated adenylate cyclase activity in the aged prompted us to determine the specificity of this decline by measuring the activity in older and younger individuals of another hormone-sensitive adenylate cyclase. However, no effect of subject age was observed on glucagon-sensitive adenylate cyclase activity, suggesting that the blunted response of the beta-receptor adenylate cyclase complex in the elderly represents a specific loss of function and is not due to a general age-associated decline in hormone-stimulated cyclase function. Specific molecular defects which could account for decline in beta-adrenergic responsiveness in the elderly are discussed.

Adenylyl Cyclases↗
PubMed1985

Erythrocyte Na+-K+ cotransport in elderly hypertensive subjects.

Na+-K+ cotransport was measured in 21 hospitalized geriatric patients, all recovering from hip surgery. Twelve of these had hypertension, and the other 9 were the control group. Although both groups were comparable for age, blood pressure was significantly different. Mean cotransport values in red blood cells showed no significant difference between the two groups. While Na+-K+ cotransport activity may be hereditary, the authors do not feel the test may be used as a genetic marker for hypertension.

Aged↗
PubMed1984

Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer's disease.

The effect of prior incubation with a single concentration of isoproterenol (10(-4) M) for 2 hours at 37 degrees C on isoproterenol-stimulated cyclic AMP accumulation in intact lymphocytes from young, old and subjects with Alzheimer's disease was studied. In lymphocytes from all three subjects groups prior incubation of cells with isoproterenol resulted in a significant reduction of cyclic AMP accumulation upon subsequent stimulation with isoproterenol.

Adenylyl Cyclases↗
PubMed1984

Alzheimer's disease: isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation in lymphocytes.

Reduced lymphocyte beta-adrenergic receptor activity was observed in patients with Alzheimer's disease and in aged controls; a parallel decline in lymphocytic prostaglandin E1 receptor activity was seen in the aged controls. In the Alzheimer patients, however, such lymphocytic prostaglandin E1 receptor activity was significantly raised and correlated with a rating scale for severity of dementia.

Adult↗
PubMed1984

Deterioration of beta-receptor-adenylate cyclase function in elderly, hospitalized patients.

Salbutamol infusion was used to study the molecular basis for reduced catecholamine responsiveness in a group of elderly hospitalized individuals. Salbutamol-induced plasma cyclic 3', 5'-adenosine monophosphate (cyclic AMP) rise in a group of 10 elderly (mean age 77 years) patients, 8 of whom were hospitalized 6 to 8 weeks after femoral fracture, and 10 younger (mean age 27 years) individuals was compared. Parallel clinical response was monitored by changes in pulse rate and blood pressure. In the younger group there was a three-fold increase in plasma cyclic AMP levels after salbutamol infusion. In the older adults only a one-and-one-half-fold rise in plasma cyclic AMP levels was observed. There was an increase in pulse rate and systolic blood pressure and a decrease in diastolic blood pressure in the younger group compared with the older participants. These results suggest that the basis for reduced catecholamine responsiveness in elderly hospitalized individuals is due to a defect in the peripheral beta-receptor-linked adenylate cyclase complex.

Adult↗