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Biomedical subjects

P Hamosh

Publications and source records attributed to P Hamosh.

At least 91 records · Page 5Linked to original sources
PubMed1982

Respiratory depression produced by glycine injected into the cisterna magna of cats.

Glycine (0.8-64.8 mumol) was administered into the cisterna magna of alpha-chloralose anesthetized cats to determine its effect on ventilation. Glycine caused a dose-related decrease in respiratory minute volume with the highest dose resulting in a decrease from 454 +/- 35 to 159 +/- 44 ml/min (p less than 0.05). This decrease was due primarily to a reduction in tidal volume which decreased from 31 +/- 2 to 12 +/- 2 ml (p less than 0.05). The two largest doses tested (21.6 and 64.8 mumol) also produced a decrease in respiratory rate from 14 +/- 1 to 11 +/- 1 and from 15 +/- 1 to 12 +/- 1 breaths/min (p less than 0.05), respectively. Apnea occurred in 2 of 7 animals given 64.8 mumol of glycine. No consistent dose-related changes in inspiratory and expiratory durations were observed. Intravenous administration of glycine (64.8 mumol) did not affect respiratory activity. These results indicate that glycine causes respiratory depression by an action in the central nervous system.

Animals↗
PubMed1982

Effect of smoking a cigarette on the density dependence of maximal expiratory flow.

We have shown that tobacco smoke causes an increase in airways resistance and a drop in expiratory flow at 50% of the vital capacity (FEF50). To better define the nature and site of this bronchoconstrictive effect we measured maximal expiratory flow while breathing air and a low-density gas mixture (helium-oxygen), in 12 healthy volunteers, before and after smoking a cigarette. There was a significant drop in FEF50 while breathing air (FEF50Air) (5.52 +/- 1.83--5.05 +/- 1.86 liters/s; p less than 0.001). No changes were observed in the helium-oxygen FEF50 (FEF50 He) after smoking. The increase in FEF50 after breathing the low-density gas as a percentage of FEF50Air (delta Vmax50) increased from 47.1 +/- 11.4% before smoking to 57.0 +/- 13.3% after smoking (p less than 0.05). There were no changes in forced vital capacity (FVC), flow at 75% FVC and volume of isoflow. We discuss these observations in light of the equal pressure points (EPP) analysis and wave speed theory of flow limitation. We conclude that after smoking flow becomes more density dependent because there is constriction of a flow-limiting segment downstream from the EPP, located in lobar and segmental bronchi. No acute effect of tobacco smoke on the small airways could be demonstrated.

Adolescent↗
PubMed1981

Postheparin lipolytic activity and Intralipid clearance in very low-birth-weight infants.

The effect of heparin (10 U/kg) on serum lipolytic activity, triglyceride and FFA levels, during four hours infusion of 0.5 gm/kg Intralipid was measured in 18 AGA infants, 25 to 32 weeks' gestational age. PHLA, TG, and FFA were measured at 0, 10, 30, 120, and 240 minutes of infusion of Intralipid, before and following a bolus of 10 U/kg heparin iv. Lipolytic activity, measured by hydrolysis of activated tri-3H-oleate and expressed in mumol FFA released per milliliter serum per hour, was not detected in serum before heparin administration. Ten minutes after heparin administration peak PHLA was significantly higher in infants of 27 to 32 weeks' gestation than in infants of 25 to 26 weeks' gestation. There was no significant difference in peak PHLA between infants of 27 to 28 and 29 to 32 weeks' gestation. PHLA returned to baseline (zero) two hours after heparin administration in all infants. Infants of 25 to 26 weeks' gestational age had significantly higher concentrations of serum triglycerides before and during Intralipid infusion than in infants of 27 to 32 weeks' gestational age. Although there was a transient rise in FFA 10 and 30 minutes after heparin administration, the levels of FFA and triglycerides were not different at the end of infusion with or without heparin in either group, suggesting that a single bolus of heparin has only a transient effect on Intralipid clearance.

Fatty Acids, Nonesterified↗
PubMed1981

Respiratory depression produced by activation of GABA receptors in hindbrain of cat.

Respiratory responses to activation of gamma-aminobutyric acid (GABA) receptors in the hindbrain were measured in chloralose-anesthetized cats using a Fleisch pneumotachograph. GABA receptors were activated by intracisternal injections of muscimol and GABA. Muscimol (0.05--6.65 micrograms) administered to seven animals caused a depression of respiratory activity with apnea occurring in each animal. Before apnea occurred, a decrease in tidal volume was observed (from 25.7 +/- 0.9 to 14.7 +/- 1.1 ml). Respiratory rate and inspiratory and expiratory durations were unchanged. GABA (0.05--12.15 mg) administered to five animals produced the same effect as muscimol on respiratory activity. Apnea produced by both agents was reversed by intracisternal administration of the GABA-receptor antagonist drug, bicuculline. Administration of bicuculline to four naive animals increased tidal volume (from 31.3 +/- 1.7 to 36.5 +/- 0.7 ml) but had no effect on either respiratory rate or inspiratory duration. These results indicate that activation of GABA receptors causes respiratory depression and suggest that GABA may be an important neurotransmitter in CNS neural pathways involved in regulating respiratory activity.

Animals↗
PubMed1981

Airways response to inhaled tobacco smoke: time course, dose dependence and effect of volume history.

We have measured puff by puff the effect of smoking three brands of cigarettes with different composition on airways resistance (Raw) thoracic gas volume (TGV) and the maximal expiratory flow volume (MEFV) curve. Raw increased significantly with all three brands of cigarettes after one puff. The maximum effect was reached after three puffs. Instantaneous flow at 50% of vital capacity (FEF50) decreased significantly with cigarettes high in nicotine content, but not so after smoking a low nicotine (0.31 mg) cigarette. Instantaneous flow at 75% of vital capacity out (FEF75) increased significantly 30 min after the low nicotine cigarette was smoked. A deep inspiration prior to Raw determination reduced by approximately one third the bronchoconstrictor effect of cigarette smoke. All effects were reversible within 30 min, except the delayed effect of the low nicotine cigarette on the FEF75. We conclude that the probable site of action of tobacco smoke is in the large and central airways. The bronchoconstrictor effect rapidly reaches a plateau. A delayed bronchodilation of the small airways observed after smoking the low nicotine cigarette might represent a response usually masked by other long-acting components in smoke. We suggest that the airway response to tobacco smoke is complex and probably a result of several components present in smoke which still have to be identified.

Adult↗
PubMed1981

Effect of dexamethasone on lipoprotein lipase activity of fetal rat lung.

Dexamethasone was administered by continuous subcutaneous infusions (16 microgram/kg/h) to pregnant rats from day 16 of gestation. Administration of the hormone markedly affected maternal and fetal weight gain, fetal lung:body weight ratio and lipoprotein lipase activity of the lung. Cumulative maternal weight gain from days 15-21 of gestation was 80 +/- 4.0 g in control and 30 +/- 10 g in dexamethasone-treated rats. Fetal weight at 22 days of gestation and 1 day after birth was 5.5 +/- 0.39 and 8.6 +/- 0.30 in control and 4.65 +/- 0.26 and 5.9 +/- 0.34 in dexamethasone-treated rats. The ratio of lung weight to body weight was lower throughout the last 5 days of gestation in dexamethasone-treated than in control rats. Dexamethasone administration led to a 2- to 3-fold increase in lipoprotein lipase activity levels in fetal rat lung at 19 and 20 days' gestation and prevented the decline in enzyme activity shortly before birth. Stimulation of fetal lung lipoprotein lipase activity suggests that increased uptake of triglyceride-fatty acids by the lung could be a contributory factor to corticosteroid-enhanced surfactant synthesis.

Animal Nutritional Physiological Phenomena↗
PubMed1981

Fat digestion in the newborn. Characterization of lipase in gastric aspirates of premature and term infants.

We have measured lipolytic activity in gastric aspirates obtained at birth in a group of 142 infants. The infants ranged in gestational age from 26 to 41 wk. Lipolytic activity, measured by the hydrolysis of long chain triglyceride ([tri-(3)H]oleate), and expressed as nanomoles FFA per milliliter gastric aspirate per minute was 333+/-66 in 55 small premature infants (gestational age 26-34 wk and body wt 750-2,000 g) and 558+/-45 in a group of 87 larger infants (gestational age 35-41 wk and body wt 2,020-4,000 g). No activity was detected in seven infants with an unusually low pH in the gastric aspirate, 2.88+/-0.44 (compared with a mean pH level of 5.59+/-0.22 in the other 135 infants). Attempts to characterize this lipase showed that it has a molecular weight of 44-48,000, pH optimum of 3.0-5.0, that FFA acceptors (albumin) stimulate activity, whereas bile salts, taurocholate and glycocholate, cause marked inhibition at concentration >3 mM. Our survey shows that enzyme activity is present as early as 26 wk of gestation, increases with gestational age, and has the same characteristics throughout gestation. The data show that the lipase in gastric aspirates differs from pancreatic lipase, but closely resembles human and rat lingual lipase. Because the lipase has a low pH optimum and does not require bile salts, it can act in the stomach where it initiates the hydrolysis of dietary fat. We suggest that intragastric lipolysis is probably of major importance in the newborn and especially in the premature infant where it compensates not only for low pancreatic lipase, but in addition, helps to overcome the temporary bile salt deficiency through the formation of amphiphilic reaction products.

Dietary Fats↗
PubMed1981

Pathways of palmitate metabolism in the isolated rat lung.

Plasma fatty acids represent major precursors of lung lipids. In this study, the pathways of palmitate metabolism were measured in an isolated perfused rat lung. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate containing 3% serum albumin and 0.25 mM [U-14C] and [9, 10(-3)H] palmitate. Fatty acid utilization was estimated by recovery of radiolabel in products of metabolism. Fourteen percent of a total 14C-fatty-acid utilization of 4.5 mumol fatty acid/100 min/g dry wt. was recovered as 14CO2. Degradation of fatty acid to acetyl CoA was indicated by a 3H2O production that was twice fatty acid oxidation to CO2. The majority of palmitate was recovered in lung phosphatidylcholines with a 14C to 3H ratio of 1.4 accounting for differences between 14C and 3H2O productions. Addition of glucose to the perfusate decreased fatty acid oxidation to CO2 by 32% but had no effect on 14C recovery in phospholipids. Perfusion with the uncoupler of oxidative phosphorylation 2,4-dinitrophenol stimulated fatty acid oxidation twofold but decreased 14C incorporation into lipids. These data together with estimates of fatty acid synthesis based on 3H2O incorporation into lipids, suggested that exogenous fatty acids and glucose both represent sources of carbon for de novo fatty acid synthesis and energy production.

Animals↗
PubMed1981

Fat digestion in very low-birth-weight infants: effect of addition of human milk to low-birth-weight formula.

The possible compensatory role of human milk lipase in the digestion of dietary fat was examined in a group of very low-birth-weight infants. Fat excretion was studied in 15 preterm infants of gestational age 26 to 33 weeks and birth weight 660 to 1,695 gm. The amount and composition of fecal fat were determined in stools collected for 72 hours. Eight infants were fed Similac 24 LBW exclusively and seven infants were fed a mixture of fresh human milk (40%) and formula (60%). Fat excretion was lower in infants fed a mixture of human milk and formula than in infants fed formula only (4.7% -+/- 0.50% vs 11.9% +/- 1.4% of intake, respectively). Excretion of calcium soaps, when expressed as percent of total fat, was higher in the group fed the human milk-containing diet (18.9% +/- 13.5%), than in the group fed formula only (6.8 +/- 2.5%); however, the absolute amounts excreted were similar in both groups (65 +/- 46 and 45 +/- 17 mg/kg/day, respectively). The lower fat excretion in infants fed a mixture of fresh human milk and formula could be related to the lipase present in human milk. These data suggest that human milk lipase probably contributes to the digestion and absorption of dietary fat in the "tiny premature" infant.

Dietary Fats↗
PubMed1980

The immediate effect on lung function of smoking filtered and nonfiltered cigarettes.

We measured and compared the effect of smoking a filtered and a nonfiltered cigarette on instantaneous maximal expiratory flow rates (Vmax50 and Vmax25) and airway resistance (Raw). We found a significant increase in Raw after both cigarettes, and a small decrease in Vmax50 after smoking the nonfiltered cigarette. The change in Vmax50 after smoking the filtered cigarette was not significant. We suggest, on the basis of these data, that filtered cigarette smoke reduces some of the constituents that cause bronchoconstriction in the large and central airways.

Adolescent↗
PubMed1980

Serum prolactin and respiratory distress syndrome in the newborn.

Prolactin levels were measured in cord blood by radioimmunoassay in 57 premature infants between 26 and 36 weeks of gestation. The level of prolactin was in the range of 20 to 600 ng/ml. Twenty-three of the infants subsequently developed respiratory distress syndrome (RDS). The mean cord prolactin in the infants with RDS was 140 +/- 30.7 ng/ml, whereas in the healthy infants it was 276.4 +/- 26.4 ng/ml. Cord prolactin levels less than 140 ng/ml were associated with a high incidence of RDS: of 25 infants with prolactin levels of less than 140 ng/ml, 19(76%) had RDS. Of the 34 healthy infants, 28(82%) had prolactin levels above 140 ng/ml. The highest levels (500 ng/ml) or prolactin in the group of infants with RDS were in two infants of diabetic mothers. The data suggest that prolactin might have a role in lung maturation in the human fetus.

Female↗
PubMed1979

Effect of nicotine on the development of fetal and suckling rats.

Nicotine, administered at a dose of 100 micrograms/kg/day from day 14 of gestation, did not affect maternal food intake, weight gain, length of gestation, litter size or fetal development; however, a daily dose of 1 mg/kg led to smaller litter size and higher incidence of stillbirth. Continued maternal administration of nicotine (100 micrograms/kg/day) until 12 days post partum did not affect newborn growth (body weight and length and size of heart and lung) during the first week after birth; during the second week, however, the nicotine-treated group lagged behind the controls. The stomachs of pups of nicotine-treated rats contained less food than those of controls; this difference increased with age, becoming more than 40% at 12 days. We suggest that lower milk production of nicotine-treated rats interferes with the normal development of the offspring during periods of rapid growth.

Animals↗
PubMed1978

Fat digestion in the stomach of premature infants. I. Characteristics of lipase activity.

Lipolytic activity was studied in gastric aspirates of 13 premature infants of birth weight 1,050 to 1,786 gm. All infants received a diet of infant formula fed by gastric tube. Gastric aspirates were collected after irrigating the stomach with 2 to 5 ml sterile saline before regular feeding. Lipolytic activity, tested with doubly labeled 3H glyceryl-14 C tripalmitin substrate, was 55.6 +/- 11.7 n mol/min/ml (range 4.2 to 140). The lipolytic activity had a pH optimum of 5.4 and produced partial glycerides (mono and diglycerides), glycerol, and free fatty acids. Lipolysis was inhibited by bile salts. Our findings show that in premature infants, as in adults, digestion of dietary fat starts in the stomach. Since bile salt concentrations are low in premature infants, the amphiphilic reaction products formed (monoglyceride and FFA) could play a significant role in the stabilization of lipid emulsions.

Digestion↗
PubMed1978

Metabolic activity of developing rabbit lung.

The uptake and metabolism of [3H]leucine, [U-14C]glucose, and [3H]palmitate were studied in rabbits aged --3, 1, 7, 28, and 90 days up to 1--1.5 years. Although lung composition did not change markedly, there were great differences in lung metabolism between the perinatal period (late fetal and newborn) and later stages of development. Leucine incorporation into lung protein was highest (3.1--3.4 nmol/mg protein/hr) in late fetal and newborn rabbits and decreased rapidly thereafter. Palmitic acid incorporation decreased during the first week after birth from 150 nmol/100 mg/hr to 85 nmol/100 mg/hr at 7 days of age; it increased thereafter to 170 nmol/100 mg/hr at 4 weeks of age and remained at that level throughout the entire period studied. Glucose uptake and lactate production were higher in fetal lungs than in all other age groups. Lipid biosynthesis from glucose was 2--4 times higher in fetal lungs than at all other ages; furthermore, more than 60% of glucose carbon atoms channeled into lipid was incorporated into fatty acids, whereas at all other ages glucose was chiefly a precursor of lipid glycerol.

Animals↗