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S Diamant

Publications and source records attributed to S Diamant.

At least 37 records · Page 2Linked to original sources

Potentiation of [3H]inositol phosphate formation by receptor activation and membrane depolarization in brain cortical slices (I).

Potentiation of [3H]inositol phosphate ([3H]IP) accumulation by receptor agonists combined with depolarizing agents was studied in rat brain cortical slices, prelabeled with [3H]inositol. Muscarinic agonists, alpha 1-adrenergic, histaminergic and serotonergic agonists remarkably enhanced (2-7-fold) the accumulation of [3H]IP in the presence of KCl (30 mM). The potentiated levels of [3H]IP were strongly dependent on K+ concentration and displayed a dose-response relationship with the agonist. Other depolarizing agents such as veratridine and ouabain induce potentiation of [3H]IP formation similarly to that observed by KCl, but to a lesser extent. The production of elevated levels of [3H]IP is Ca2+-dependent with maximal effect at 0.6 mM which is similar to the Ca2+ dependency observed for the agonist and the depolarizing agent alone. Enhanced [3H]IP levels induced by agonists in the presence of depolarizing agents affect Vmax values only, since the apparent half maximal effective concentration of carbachol (CCh)-induced-IP-formation (1.2 x 10(-4) M) and of the phenylephrine-induced IP-formation (8 x 10(-6) M), were not affected in the presence of either K+ or veratridine. In addition the efficacy of various muscarinic agonists as inducers of IP-accumulation was conserved under depolarizing conditions as compared to IP accumulation under normal conditions. In the presence of KCl (30 mM) the maximal degree of potentiation was at a range of 5-7-fold, with order efficacy of ACh greater than CCh greater than Oxo M greater than arecoline much greater than pilocarpine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Young long distance runners. Physiological and psychological characteristics.

This study presents the physiological and psychological characteristics and the running histories of 16 subjects who began long distance running at age 4-12 years. Running duration was 3-15 years (mean 8.4 +/- 3.6 yrs). Seven children completed 41 marathons, seven 30-mile races, and eight 60-mile races. The other nine competed at shorter distances. All trained at 30-105 miles/week. Two stress fractures, one back sprain and one knee injury occurred. Athletes who reported injuries from recollection may have underreported some injuries. At age 15.4 +/- 4.2 years bone age was 15.3 +/- 2.6 years and height was at 51 +/- 26.0 percentile. Athletes had larger left ventricular diastolic diameter, higher max O2 uptake, and delayed onset of anaerobic metabolism compared to controls. Psychological profile: IQ = 121 +/- 11, scholastic grade point average (GPA) (n = 13) was less than or equal to 3.0 in four, 3.6-3.9 in four, and 4.0 in five. Cattell 16 personality factor (PF): Seven scored above the 85th percentile on boldness, warmth, conformity, sensitivity, dominance, and high drive with tension. Eight scored above the 93rd percentile for self discipline and emotional stability. Human Figure Drawing showed a distorted body image in seven. Two developed anorexia nervosa, and another girl committed suicide. Thus, high physical fitness and no growth retardation were observed. These runners, however, shared distinct positive and negative personality characteristics. The relatively high incidence of severe psychological disorders possibly suggests a need for psychological screening for young children entering a strenuous training program and for close monitoring for development of psychological problems during the program.

Adolescent↗

Role of prenatal detection of cardiac tumours in the diagnosis of tuberous sclerosis--report of two cases.

Tuberous sclerosis is an autosomal dominant disease with variable expression. Little is known about the intrauterine course of the disease and the fetal age at which specific abnormalities may be detected. The role of prenatal detection of cardiac tumours in the diagnosis of two fetuses at 28 and 32 weeks' gestation based on fetal echocardiography is discussed. The prenatal and postnatal course of the disease is described.

Adult↗

Muscarinic agonists evoke neurotransmitter release: possible roles for phosphatidyl inositol bisphosphate breakdown products in neuromodulation.

Carbachol (CCh), a muscarinic agonist that elicits the formation of inositol trisphosphate (IP3) and diacylglycerol (DG), induces a calcium-dependent [3H]norepinephrine ([3H]NE) release [IC50 = (2.7 +/- 0.5) X 10(-4) M] in rat brain slices. Similarly, other muscarinic agonists evoke [3H]NE release which is specifically inhibited by muscarinic antagonists such as 3-quinuclidinyl benzilate, atropine, and N-methyl-4-piperidyl benzilate. The atropine-sensitive evoked release is effectively inhibited by neomycin (IC50 = 50 microM), a phospholipase C inhibitor that interferes with IP3-dependent cellular processes. In addition, polymyxin B, a rather selective inhibitor of protein kinase C (PK-C), abolishes the agonist-mediated release with a half-maximal effective concentration of 0.53 microM (750 ng/ml). These results have a significant implication for the mechanism by which agonists generating IP3 and DG act as inducers of neurotransmitter release in the CNS. However, since both neomycin and polymyxin B act also as N-calcium-channel blockers, other possible mechanisms are discussed. The CCh-induced release suggests that in the CNS an agonist-receptor interaction leads to a calcium-dependent neurotransmitter release, most likely via promoting the IP3/DG as second messengers followed by activation of PK-C.

Animals↗

Histamine or adenosine blockade alters intestinal blood flow autoregulation in swine.

The possible role of histamine or adenosine in intestinal blood flow autoregulation in 1-mo-old swine was examined by obtaining pressure-flow relationships before and during intestinal histamine H1- or adenosine-receptor blockade in two groups of fasting animals under anesthesia with pentobarbital sodium (30 mg/kg). Changes in abdominal and thoracic aortic pressures and in superior mesenteric and left renal arterial flows were recorded during controlled aortic compression above the celiac artery. After control intestinal and renal pressure-flow relationships were obtained, a test dose of agonist (0.1 microgram histamine or 0.2 microgram adenosine/kg body wt) was given into the superior mesenteric artery. Then an intra-arterial infusion of blocking agent was started (0.1 mg.kg-1.min-1 chlorpheniramine or 10 mumol/min theophylline). Degree of blockade was assessed with doses of agonist given before and after a second set of intestinal and renal pressure-flow relationships was obtained. Complete blockade of intestinal vascular histamine H1-receptors with chlorpheniramine abolished, and incomplete blockade of adenosine-receptors with theophylline attenuated, intestinal blood flow autoregulation. Renal blood flow autoregulation remained at its control level. These results indicate that both histamine and adenosine are among the physiological vasodilators contributing to intestinal blood flow autoregulation when arterial pressure is decreased in young swine.

Adenosine↗

Vasoactive compound effects on autoregulating versus nonautoregulating intestinal and renal circulations in young swine.

Vascular resistance changes to single intra-arterial injections of norepinephrine, histamine and adenosine were examined in 12 kidney and 10 jejunum preparations perfused in situ in fasting swine anesthetized with pentobarbital. Threshold doses were higher and other response magnitudes were smaller in the nonautoregulating renal circulation of 1-week-olds and jejunal circulation of 2-week-olds than in autoregulating circulations of 1-month-olds. These results suggest a correlation between maturation of autoregulatory capability and of vasodilator histamine and adenosine receptors.

Adenosine↗

A low molecular weight brain substance interacts, similarly to clonidine, with alpha 2-adrenoceptors of human platelets.

In the present study, we explored the effects of a clonidine-displacing substance (CDS) which was isolated and partially purified from bovine brain. The low molecular weight brain substance competes with clonidine and rauwolscine in rat brain membranes, and mimics clonidine's inhibitory action in rat vas deferens. We find that CDS competes with [3H]rauwolscine-labeled alpha 2-adrenoceptors in human platelets. Further characterization of CDS in human platelets reveals that, like clonidine, it inhibits the epinephrine-induced aggregation, potentiates the ADP- and the collagen-induced aggregation however, by itself, CDS is unable to induce aggregation. Unlike clonidine, CDS does not affect the prostacyclin (PGI2)-stimulated cAMP accumulation in intact platelets. The presence of CDS in human plasma, as we have recently shown, implies a possible role of CDS in the regulation of platelet action.

Animals↗

Neomycin inhibits K+- and veratridine-stimulated noradrenaline release in rat brain slices and rat brain synaptosomes.

The possible involvement of phosphoinositides' turnover in the process of neurotransmitter release in the central nervous system (CNS) was studied using rat brain slices and synaptosomes. A depolarizing concentration of potassium chloride (25 mM) induces an 8.6 +/- 0.4% increase of [3H]noradrenaline [( 3H]NA) fractional release in cerebral cortical slices above spontaneous release, and 15 mM KCl induces a 3-fold increase of [3H]NA release in rat brain synaptosomes. Neomycin, an aminoglycoside which binds phosphoinositides, inhibits the potassium-induced release in cortical slices with an IC50 = 0.5 +/- 0.07 mM and with IC50 = 0.2 +/- 0.03 mM in synaptosomes. Veratridine, a veratrum alkaloid which increases membrane permeability to sodium ions and causes depolarization of neuronal cells, induces a net 13.4 +/- 0.3% increase of [3H]NA fractional release above spontaneous release in cortical slices. In analogy to K+ stimulation, neomycin inhibits the veratridine-stimulated release in cortical slices with an IC50 = 0.65 +/- 0.1 mM. It appears that the recycling of phosphoinositides, which is necessary for Ca2+ mobilization, participates in the Ca2+-dependent induced neurotransmitter release in the central nervous system.

Animals↗

Chest pain, dyspnea on exertion, and exercise induced asthma in children and adolescents.

UNLABELLED: The contribution of maximal exercise tests to the evaluation of 180 patients with chest pain associated with exercise (n = 147) or dyspnea on exertion (DOE, n = 33) was examined. The ages ranged from 5 to 22 (mean 13.2) years, and 68 patients were females. All patients had a normal cardiovascular examination, electrocardiogram, chest x-ray, and 2D-echocardiogram. Maximal exercise tests were performed on a treadmill or bicycle ergometer, and flow volume loops were performed before and after exercise (n = 65). Exercise tests did not reveal any cardiovascular abnormalities, but 14 patients with chest pain (9.5%) and seven patients with DOE (21.2%) developed exercise-induced asthma. Postexercise decrease in peak expiratory flow rate was 26.2 +/- 3.7 percent in patients with chest pain and 39.4 +/- 8.9 percent in those with DOE. Only five patients had a personal history and four others had a family history of asthma. Seven patients had a personal or family history of allergies. IMPLICATIONS: exercise-induced asthma should be considered in pediatric patients with symptoms of chest pain or dyspnea on exertion; when exercise tests are performed, flow volume loops should be included before and after exercise; maximal exercise tests are unlikely to unmask any cardiovascular abnormalities in such patients.

Adolescent↗

The brain's own clonidine: purification and characterization of endogenous clonidine displacing substance from brain.

An endogenous clonidine-like substance was isolated from bovine brain and characterized by its chemical and pharmacological properties. The clonidine displacing substance (CDS) is a noncatecholamine, nonpeptide compound. It is devoid of NH2-group, is thermostable, and has a molecular weight of 587.8 +/- 2 daltons. CDS binds selectively to alpha 2-adrenergic receptors in rat brain membranes as measured by displacement of specifically bound [3H]clonidine, an alpha 2-adrenergic agonist, and [3H]rauwolscine, an alpha 2-antagonist, with no affinity for alpha 1-adrenergic receptors. In physiological studies CDS mimics clonidine's action as an inhibitor of the electrically induced twitch response and as a partial agonist of the epinephrine-induced platelet aggregation. At the central nervous system CDS antagonizes clonidine action, increases mean arterial pressure when injected into the nucleus reticularis lateralis of rats, and reduces the hypotensive effect upon intracisternal injection. CDS, which interacts at alpha 2-adrenergic receptors and increases mean arterial pressure upon intracerebral injection, may represent a neuroregulator that plays an important role in cardiovascular events.

Animals↗

Raised levels of an endogenous nonadrenergic substance in the serum of pregnancy-induced hypertension patients.

A clonidine-displacing substance (CDS) was isolated from bovine brain and shown to mimic clonidine in peripheral tissues. CDS acts--contrary to clonidine--by increasing the mean arterial pressure in the CNS. Methanolic extract from sera of patients with pregnancy-induced hypertension (PIH) showed a significant increase in CDS levels as compared with sera of either normal or chronic hypertensive pregnancy. Although small amounts of CDS were found in the placenta, no positive correlation between placental levels of CDS and serum CDS levels was observed. The pharmacological properties of CDS and its higher levels in sera of PIH patients suggest that CDS is a sympathetic agent involved in the pathophysiology of PIH.

Adult↗

An endogenous brain substance, CDS (clonidine-displacing-substance), inhibits the twitch response of rat vas deferens.

The effect of CDS, an endogenous brain substance that specifically displaces bound [3H]clonidine and [3H]rauwolscine in rat brain membranes and human platelets, has been tested in isolated, field-stimulated rat vas deferens. CDS, obtained after an extensive purification procedure as a single peak from an HPLC sizing column, inhibited the electrically stimulated rat vas deferens similarly to the inhibitory action of clonidine, an alpha 2-agonist. The effective dose of CDS as an inhibitor of the vas deferens is equivalent to its effective dose in displacing specifically bound [3H]-clonidine in rat brain membranes. Furthermore, the CDS inhibition of the twitch response is reversed by two alpha 2-adrenergic antagonists, yohimbine and phentolamine. From these results, it is suggested that CDS extracted from brain, with affinity for clonidine sites, may be involved in the nonadrenergic fast response of the sympathetic transmission of the vas deferens.

Animals↗

CT assessment of calcinosis in a patient with dermatomyositis.

A case of juvenile dermatomyositis developing intermuscular fascial plane calcification in the thighs early in the course of the disease is described. The use of CT was helpful in localizing the calcium deposits between the muscular layers before surgical removal of the calcification. These procedures may have prevented fistulization and development of contracture of the joints.

Adolescent↗

Determination of right ventricular pressure in the presence of a ventricular septal defect using continuous wave Doppler ultrasound.

Continuous wave Doppler ultrasound was employed in 38 patients with ventricular septal defects, many with associated lesions, to measure the velocity (V) of the shunted blood. Using the modified Bernoulli equation (delta P = 4V2) the pressure difference (delta P) between the ventricles was determined. In 22 patients both right ventricular and either left ventricular or ascending aortic pressure were measured at the time shunt velocity was determined. In another 16 patients these measurements were not obtained simultaneously but in most they were done within 24 hours of each other. In the entire group, measured pressure differences between the ventricles (or aorta and right ventricle) ranged from 0 to 97 mm Hg (mean 52 +/- 24). On the basis of velocity measurements the pressure difference ranged from 7 to 112 mm Hg (mean 51 +/- 24). A close correlation was found between the two methods (r = 0.95, SEE = 7.8 mm Hg). This accuracy was not altered by associated lesions. These findings indicate that by the use of continuous wave Doppler interrogation right ventricular pressure can be accurately measured in the presence of a ventricular septal defect.

Adolescent↗

The relationship between motor activity and transmural potential difference in the guinea pig intestine in vitro: is there a neural link?

The aim of the experiments was to examine, in vitro, the role of the enteric nervous system in the relationship between motor activity and transmural potential difference (PD) in the guinea pig jejunum and colon using the nerve blocking agents tetrodotoxin (TTX) and aconitine. Histological data showed that perfusion of the intestinal segments with gassed Hepes solution was essential for the maintenance of transmural PD. Disruption of the mucosa was associated with a loss of spontaneous fluctuations in transmural PD without any loss of spontaneous motor activity. Under spontaneous conditions, a neural pathway exists linking jejunal and colonic motility with transmural PD. However, in some cases a mechanical link was also apparent, as an attenuated TTX and aconitine-resistant component.

Aconitine↗

Beta-adrenergic activity and conformation of the antihypertensive specific alpha 2-agonist drug, guanabenz.

In recent research a new series of specific drugs, one of which is guanabenz (GBZ, 2,6(dichlorobenzyliden)-aminoguanidine) has been introduced into the clinical treatment of centrally mediated hypertension. Guanabenz (GBZ) is considered to be among the most specific alpha 2-adrenergic agonists, acting similarly to clonidine by decreasing the sympathetic outflow from the brain to the peripheral circulatory system. In the present report we show that GBZ displays a significant affinity for beta-adrenoceptors. In displacement studies of the iodinated beta-antagonist [125I]cyanopindolol (CYP) from turkey erythrocyte membranes, the dissociation constant of GBZ was 3.8 microM. Inhibition of the (-) epinephrine induced adenylate cyclase activity by GBZ is competitive, with an apparent dissociation constant of 30 microM. A similar value was obtained by studies of GBZ's effect on the (-) epinephrine-induced [3H]cAMP accumulation in intact turkey erythrocytes. In view of its unexpected affinity for beta-adrenoceptors, we examined the three-dimensional structure of crystalline GBZ. In these studies substantial differences between clonidine and GBZ were observed, despite their strong structural resemblance. These dissimilarities (angle of rotation phi = 39.7 degrees as compared to 76 degrees in clonidine, and the rotational restriction of clonidine as compared to the greater mobility in rotation of GBZ) could explain the difference of specificity between these two compounds.

Adenylyl Cyclases↗