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Biomedical subjects

P Hamosh

Publications and source records attributed to P Hamosh.

At least 73 records · Page 4Linked to original sources
PubMed1984

Central gamma-aminobutyric acid involvement in blood pressure control.

The role of gamma-aminobutyric acid (GABA) in central nervous system (CNS) control of arterial blood pressure has been studied by testing the effects of drugs that either counteract or enhance CNS GABAergic mechanisms while monitoring the arterial pressure of normotensive and hypertensive animals. Drugs that antagonize the effects of GABA (either directly by blocking GABA-mediated responses or indirectly by inhibiting GABA synthesis) cause an increase in arterial pressure. This effect occurs in the forebrain and leads to an increase in sympathetic outflow to the vasculature, including the coronary vessels. GABA and drugs that stimulate GABA receptors (either directly or indirectly by inhibiting GABA metabolism, competing with an endogenous inhibitor of GABA, or activating a GABA chloride ionophore) cause a decrease in arterial pressure. This effect is, in some cases, associated with respiratory depression, and it occurs in the hindbrain, especially at the intermediate area on the ventral surface of the medulla. Hypertensive animals appear to be more sensitive to the hypotensive action of these agents. These results suggest that CNS GABA may have an important role in controlling blood pressure.

Animals↗
PubMed1983

Gastric lipolysis in the developing rat. Ontogeny of the lipases active in the stomach.

The first step in fat digestion occurs in the stomach, where 10-30% of dietary triacylglycerols are hydrolyzed to partial (di- and mono-) acylglycerols and free fatty acids. Preduodenal fat digestion is an important compensatory mechanism in the newborn because of immature pancreatic (lipase) and hepatic (bile acid synthesis) function. Since hydrolysis of fat in the stomach can be catalyzed by enzymes of lingual (Hamosh, M. (1979) Pediatr. Res. 13, 615-622) and possibly gastric origin, we have studied the developmental pattern and quantitative contribution of these two enzymes to intragastric fat digestion by measuring lipase activity in homogenates of lingual glands and gastric mucosa of rats from birth until 60 days of age. Total lipolytic activity in rat gastric mucosa was only 2-10% of that in the lingual glands throughout the entire period studied. Lingual lipase activity increased steadily from birth until day 50, whereas the activity in the gastric mucosa reached peak levels at 17-20 days and declined sharply after weaning. Throughout the period of study--suckling, weaning, and young adulthood--lingual and gastric lipase had very similar characteristics: pH optimum in the range of 5.0-6.0 and 2.5-5.0-fold higher activity on medium-chain (tri[14C]octanoin) than long-chain (tri[3H]olein) triacylglycerols. In the lingual glands, lipase activity was higher during fasting, probably because of accumulation of enzyme (without depletion during meals), whereas in the gastric mucosa lipase levels were higher after feeding, suggesting adsorption of lingual lipase (which reaches the stomach with the ingested food) onto the gastric mucosa. From birth to weaning, there was rapid and extensive hydrolysis of triacylglycerol in the stomach (decrease from 98 mol% in rat milk to 33.6-48.9 mol% in the stomach contents half an hour after feeding). The intragastric lipolysis remained almost constant from birth until day 20, in spite of a marked increase in food consumption, probably because of the continued rise of lingual lipase levels. The direct relationship between high intragastric lipolysis and high lingual lipase activity suggests that lingual lipase is the major digestive enzyme in the newborn.

Aging↗
PubMed1983

Central respiratory stimulant effect of bombesin in the cat.

Bombesin (0.62-6.2 nmol) was administered into the cisterna magna of chloralose-anesthetized cats while monitoring tracheal airflow with a pneumotachograph. The peptide produced dose-related increases in respiratory activity which were seen primarily as increases in tidal volume. Intravenous administration of bombesin (6.2 nmol) did not cause any respiratory effects. These results indicate that bombesin acts in the brain to stimulate respiration.

Animals↗
PubMed1983

Respiratory depression produced by centrally administered taurine in the cat.

The effects of taurine (0.8-64.8 mumol) were studied on respiratory activity following intracisternal (cisterna magna) and intracerebroventricular (lateral ventricle) injections in cats anesthetized with alpha-chloralose. Respiratory activity was measured by using a Fleisch pneumotachograph and monitoring tracheal airflow. The flow signal was integrated to obtain tidal volume (VT) and respiratory rate (f) was obtained by counting the number of VT excursions over one minute. Inspiratory (TI), expiratory (TE) and total (TTOT) cycle durations were also determined during this time period. In addition, end-tidal CO2 was continuously monitored. Associated changes in arterial pressure (femoral artery cannula) and heart rate were also determined. After injections into the cisterna magna, taurine caused dose-related decreases in minute ventilation (VE). The maximal decrease in VE was from 495 +/- 59 to 64 +/- 14 ml/min (p less than 0.05), and was due to both decreases in VT (from 27 +/- 3 to 5 +/- 1 ml; p less than 0.05) and f (from 18 +/- 1 to 12 +/- 2 breaths/min; p less than 0.05). TE and TTOT were increased from 2.4 +/- 0.4 to 4.5 +/- 0.6 sec (p less than 0.05) and from 3.7 +/- 0.4 to 6.4 +/- 0.8 sec (p less than 0.05), respectively. Mean inspiratory flow (VT/TI), a measure of inspiratory drive, was decreased from 21 +/- 4 to 4 +/- 2 ml/sec (p less than 0.05). Apnea occurred in 5 of 6 animals after the 64.8 mumol dose. This respiratory depression occurred without any significant change in arterial pressure. After lateral ventricle injections, taurine also caused dose-related, but not as pronounced, decreases in respiratory activity. In addition, taurine caused significant decreases (p less than 0.05) in arterial pressure in doses that decreased VE. Taurine administered intravenously had no significant cardiorespiratory depressant effects. These data indicate that centrally administered taurine produces respiratory depression and, depending on the route of CNS administration, also produces hypotension.

Animals↗
PubMed1983

Comparison of the lipid composition of breast milk from mothers of term and preterm infants.

Milk was collected from mothers of 18 very premature (26 to 30 wk gestation age), 28 premature (31 to 36 wk), and six term (37 + wk) infants on day 2 to 3 (colostrum), and at 1, 3, 6, and 12 wk postpartum. Fat content for 154 milk samples was 2.80 g/dl gravimetrically and 2.66 g/dl by quantitative thin-layer chromatography. Fat content increased during lactation, whereas phospholipids and cholesterol declined. Concentrations of medium-chain fatty acids increased from colostrum to mature milk and were highest in preterm milk. Compensatory decreases were observed in very premature and premature oleic acid. Long-chain polyunsaturated fatty acids were highest in colostrum and reduced in mature milk. Long-chain polyunsaturated fatty acids were also higher in very premature and premature milk than in term milk. These elevated levels of readily absorbed medium-chain fatty acids and long-chain polyunsaturated fatty acids in preterm milk may be of special benefit for the needs of premature infants.

Adolescent↗
PubMed1983

Respiratory distress syndrome in the newborn: relationship to serum prolactin, thyroxine, and sex.

Prolactin and thyroxine levels were measured by radioimmunoassay in cord blood of 61 premature infants of 26-36 weeks gestation. 30 of the infants subsequently developed respiratory distress syndrome (RDS). The infants who developed RDS had a mean cord prolactin level of 174.5 +/- 24.5 ng/ml and a mean cord thyroxine level of 5.9 +/- 0.4 micrograms/dl. In the 31 healthy infants, the mean cord prolactin and thyroxine levels were significantly higher (226.3 +/- 25.8 ng/ml and 7.1 +/- 0.4 micrograms/dl, respectively). The correlation coefficient between prolactin and thyroxine was r = 0.56 in infants with RDS (p less than 0.0008). Both prolactin and thyroxine correlated with gestational age in the RDS group (r = 0.71 and 0.47, respectively). Discriminant analysis shows that the correlation between prolactin and thyroxine is independent of gestational age (r2 = 0.32, p less than 0.05). There was no correlation between the levels of prolactin and thyroxine in infants without RDS. In the healthy group, the cord prolactin levels were significantly higher (p less than 0.01) in female (335.8 +/- 47.7 ng/ml) than in male infants (209 +/- 17.2 ng/ml). Premature infants who develop RDS have significantly lower thyroxine and prolactin levels in cord blood than infants who remain healthy.

Female↗
PubMed1983

Central nervous system site of action for the respiratory depressant effect of diacetylmorphine (heroin) in the cat.

The purpose of our study was to identify central nervous system sites involved in the respiratory depressant effect of drugs that stimulate opioid receptors. Diacetylmorphine (heroin) was administered into several cerebroventricular regions of chloralose-anesthetized cats, while monitoring pulmonary ventilation with a Fleisch pneumotachograph. Administration of heroin (17, 50, 150, and 450 micrograms) into the forebrain ventricles, which was restricted to these ventricles, resulted in no significant respiratory effects. In contrast, administration of heroin into either the fourth ventricle or the cisterna magna resulted in a significant (P less than 0.05) decrease in respiratory minute volume (VE). In the fourth ventricle this was because of a decrease in frequency (f) and in the cisterna magna, to a decrease in tidal volume (VT). Intravenous administration of heroin in the same dose-range produced a decrease in VE, which was primarily due to a decrease in f. Bilateral application of heroin (70 micrograms/side) to each of three ventral medullary surface sites (Mitchell's, Schlaefke's, and Loeschcke's areas) known to influence respiration elicited a decrease in VE only at Mitchell's area. This decrease was due to decreases in f and VT. The role of this site in the action of intravenously administered heroin was tested by topical application of naloxone to this area in animals with respiratory depression evoked by intravenous heroin. Bilateral application of naloxone (15 micrograms/side) to Mitchell's area restored breathing to normal. These results lead us to suggest that the site of heroin-induced respiratory depression is a specific area (Mitchell's area) on the ventral surface of the medulla.

Administration, Topical↗
PubMed1983

Activation of central nervous system cholecystokinin receptors stimulates respiration in the cat.

Cholecystokinin-octapeptide (CCK-OP) was injected into the lateral brain ventricle of chloralose-anesthetized cats while monitoring pulmonary ventilation, mean blood pressure (BP) and heart rate (HR). Initial values for respiratory minute volume, BP and HR were 436 +/- 32 ml/min, 126 +/- 8 mm Hg and 204 +/- 9 beats/min, respectively. CCK-OP in doses of 8.8 x 10(-13) to 8.8 x 10(-10) M (i.e., 1 to 1000 ng) increased respiratory minute volume by +56 +/- 18 ml/min to +370 +/- 73 ml/min, respectively. This response was due to an increase in tidal volume (P less than .05) with no effect on respiratory rate. Most of these doses increased BP and HR (P less than .05). These responses were mimicked when CCK-OP was administered into and restricted to the lateral and 3rd ventricles, whereas no significant responses occurred with administration into the 4th ventricle. The highest dose of CCK-OP, when given i.v., produced no significant effects. Central nervous system injections (lateral ventricle) of CCK-OP in deafferented animals also produced respiratory and cardiovascular stimulation, but higher doses were required. Central nervous system injections of comparable doses of desulfated CCK-OP or pentagastrin had no effect on respiratory minute volume, BP or HR. Proglumide (0.8 and 8.0 mg), a specific CCK receptor antagonist, prevented both respiratory and cardiovascular effects induced by CCK-OP. These doses of proglumide exerted no antagonism of CO2-induced respiratory stimulation. These data suggest that a specific receptor reacting with CCK-OP may be important for the control of respiration.

Animals↗
PubMed1983

Pentobarbital causes cardiorespiratory depression by interacting with a GABAergic system at the ventral surface of the medulla.

A tonically active gamma-aminobutyric acid (GABA) system at Schlaefke's area (intermediate area) on the ventral surface of the medulla exerts control over cardiorespiratory function. This is the same site where Feldberg and Guertzenstein elicited pentobarbital-induced hypotension. To determine whether pentobarbital-induced cardiorespiratory depression is mediated by a GABAergic mechanism at this site, we applied this agent locally to the intermediate area in eight chloralose-anesthetized cats while monitoring respiratory activity, blood pressure and heart rate. Pentobarbital (0.5-1.5 mg) reduced minute ventilation from 383 +/- 19 to 227 +/- 31 ml/min (P less than .05) by reducing tidal volume from 29.8 +/- 2.4 to 16.1 +/- 1.6 ml (P less than .05), without changing respiratory rate. Mean blood pressure and heart rate were reduced from 150 +/- 16 mm Hg and 182 +/- 8 beats/min to 73 +/- 16 mm Hg and 136 +/- 12 beats/min (P less than .05), respectively. Respiratory depression culminated in apnea in each animal tested. Bicuculline applied to the intermediate area in doses that selectively counteract GABA-induced apnea (5.0-17.5 micrograms) reestablished breathing, mean arterial pressure and heart rate to values equal to or greater than control levels. This dose range of bicuculline had no effect on heroin-induced respiratory depression. Cardiorespiratory depression observed with i.v. administration of pentobarbital in four cats was also reversed by bicuculline (10-20 micrograms) applied to the intermediate area. These results indicate that pentobarbital acts at the intermediate area to activate a GABAergic system resulting in cardiorespiratory depression.

Animals↗
PubMed1982

Triacylglycerol hyrolysis in the isolated, perfused rat lung.

We have studied the mechanism of hydrolysis of labeled long-chain triacylglycerols in the isolated, ventilated, perfused rat lung. Hydrolysis of emulsified tri[3H]oleate or doubly labeled [3H]glyceryl, tri[14C]oleate was measured by quantitation of [3H]oleate or of [14C]oleate and [3H]glycerol released into the perfusate. Hydrolysis was directly proportional to the initial triacylglycerol concentration of the perfusate in the range of 0.30 to 2.2 mM. The release of free fatty acids was linear after an initial lag period, the length of which was inversely proportional to the triacylglycerol concentration. Studies with doubly labeled [3H]glyceryl, tri[14C]oleate showed that, during triacylglycerol hydrolysis, the molar ratio of free fatty acid to glycerol released is close to 1, suggesting that about one-third of the fatty acids hydrolyzed is released into the pulmonary circulation. The earlier appearance of free fatty acid than glycerol in the venous effluent indicates that the first step in triacylglycerol hydrolysis occurs at the endothelial surface. In order to investigate the role of lipoprotein lipase in this process, we administered heparin, which leads to immediate release of lipoprotein lipase from the endothelium to the circulation in vivo, 10 min and 4 h before isolation and perfusion of the lungs. Heparin administration 10 min prior to perfusion led to marked release of lipoprotein lipase from the lungs and completely abolished the subsequent hydrolysis of circulating triacylglycerols. Perfusions carried out 4 h after heparin administration show that in the lung, endothelial lipoprotein lipase levels did not return to normal within 4 h after heparin administration. The data show that circulating triacylglycerols are hydrolyzed by endothelial lipoprotein lipase during passage through the lung.

Animals↗
PubMed1982

Medullary ventral surface GABA receptors affect respiratory and cardiovascular function.

We previously demonstrated that GABA and muscimol administered either into the cisterna magna or the fourth ventricle to chloralose-anesthetized cats cause respiratory depression, hypotension, and bradycardia. Injection of these substances into the lateral and third ventricles had no effect. In order to localize the site of action, muscimol and GABA were applied by Perspex rings to the ventral surface of the medulla. Application of muscimol (0.25-2.66 micrograms) to Schlaefke's area in 6 cats reduced minute ventilation from 443 +/- 38 to 291 +/- 52 ml/min by reducing tidal volume from 31.8 +/- 2.3 to 17.6 +/- 1.4 ml, without changing respiratory rate and duration of inspiration. Hypotension and bradycardia were also observed. Application of GABA (0.14-4.86 mg) produced similar effects on respiratory activity and arterial blood pressure. No significant effects occurred when high doses of these agents were applied to Loeschcke's and Mitchell's areas. Application of bicuculline (5-25 micrograms) to Schlaefke's area had the opposite effect of muscimol and GABA on respiratory activity and blood pressure, and reversed the respiratory and cardiovascular depressant effects of both agents. We conclude that GABA receptors are present at Schlaefke's area, and that activation of these receptors results in respiratory depression, hypotension, and bradycardia. Our results suggest that GABA may be an important inhibitory neurotransmitter in the modulation of respiratory and cardiovascular control.

Animals↗
PubMed1982

Hydrolysis of triacylglycerol emulsions by lingual lipase. A microscopic study.

The effect of lingual lipase on four different triacylglycerol emulsions was observed by light microscopy at pH 5-6. The extent of hydrolysis on the microscope slide was determined with the aid of radioactive emulsions or by analyzing the products by gas-liquid chromatography. Artificial emulsions that had been stabilized with amphiphilic lipids gradually coalesced during the unstirred lipase reactions. Gum arabic-stabilized emulsions and human milk fat droplets did not stick to each other or coalesce during lingual lipase hydrolysis. No visible liquid-crystalline product phases, as are seen with pancreatic lipase (Patton, J.S. and Carey, M.C. (1979) Science 204, 145-148), were observed with lingual lipase. The products of lingual lipase activity, protonated fatty acid and diacylglycerol, appear to remain dissolved in the oil phase of the triacylglycerol particle.

Animals↗
PubMed1982

Respiratory and cardiovascular effects of intraventricular cholecystokinin.

Cholecystokinin (1-300 ng) was administered into the lateral brain ventricle of chloralose-anesthetized cats while monitoring tracheal airflow, arterial blood pressure, and heart rate. Dose-related increases in respiratory activity occurred in each animal tested, and were due to an increase in tidal volume. When 300-1000 ng of cholecystokinin was administered intravenously, no respiratory stimulant effect was observed. These results indicate that cholecystokinin acts in the brain to stimulate respiration.

Animals↗
PubMed1982

Congenital esophageal atresia: lipase activity is present in the esophageal pouch and stomach.

Lipolytic activity was studied in aspirates from the esophageal pouch and from the stomach of eight infants with congenital esophageal atresia. Lipolytic activity, tested with doubly labeled ([3H]glyceryl, [14C]fatty acid) long-chain triglyceride was present in esophageal and gastric aspirates. The activity in esophageal aspirates was in the range of 2.7-130 nmol/min/ml aspirate and that in gastric aspirates was in the range of 2.9-40.4 nmol/min/ml aspirate. The reaction products of lipolytic activity in esophageal and gastric aspirates were a mixture of mono- and diglycerides, glycerol, and free fatty acids. The lipolytic activity at the two sites--esophagus and stomach--varied with respect to pH optimum (5.0-7.6 and 6.0-6.5, respectively) and reaction products (glycerol 41.6 +/- 20% and 7.3 +/- 4.6%, respectively). These findings confirm the earlier observations that digestion of dietary fat is initiated in the stomach and suggest that the lipolytic activity present in gastric contents originates concomitantly from the oral-esophageal area as well as from the stomach. These studies do not exclude the possibility that the lipolytic activity in the stomach of infants with esophageal atresia could originate in regurgitated intestinal contents.

Esophageal Atresia↗