摘要:

ABSTRACT.Insulin is a potent mitogen for many cell typesin vitro. During tissue culture, supraphysiological concentrations of insulin are necessary to promote cell replication in connective or musculoskeletal tissues. Insulin promotes the growth of these cells by binding, with low affinity, to the type I insulin-like growth factor (IGF) receptor, not through the high affinity insulin receptor. In other cell types, such as hepatocytes, embryonal carcinoma cells, or mammary tumor cells, the type I IGF receptor is virtually absent, and insulin stimulates the growth of these cells at physiological concentrations by binding to the high affinity insulin receptor. Both receptor systems activate phosphorylation reactions within the cell which extend to ribosomal proteins. Insulin acts synergistically with other factors, such as platelet-derived growth factor and epidermal growth factor, to stimulate the progression of cells through the cycle of proliferation. Abnormal insulin secretion or action, before or after birth, often is associated with disordered growth suggesting that insulin may function as a growth factorin vitro. Poor growth follows impaired insulin secretion in diabetes mellitus. This is associated with reduced circulating levels of IGF's which may be partly responsible for the growth failure. Insulin has a direct action on release of IGF's from the liverin vitro. but during experimental diabetes there is a reduced number of hepatic somatotropic receptors which could limit the ability of growth hormone to regulate IGF release. Diabetic children, treated conventionally, have normal circulating IGF levels, but both growth rate and serum IGF concentration may increase dramatically when diabetic control is optimized. Hyperinsulinaemia in the human fetus of a diabetic mother may result in somatic overgrowth as well as adiposity, whereas experimental fetal (animal) hyperinsulinaemia does not result in skeletal overgrowth, and promotes IGF release only at extreme levels. Conversely hypoinsulinemia, with or without nutritional deprivation, is associated with fetal growth retardation accompanied by low circulating IGF levels. It can be concluded that insulin functions as a growth factor in both normal and abnormal development. Insulin promotes the growth of selected tissues by a direct action; in others, such as the musculoskeletal system, the action is indirect via the regulation of IGF release.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTInotropic support with digoxin is commonly used in patients with left ventricular volume overload due to ventricular septal defect (VSD). However, the hemodynamic consequences of inotropic agents with VSD have not been experimentally explored. We studied two inotropic agents, digoxin and amrinone, in chronically instrumented lambs with left ventricular volume overload due to a surgically created VSD. Intravenous digoxin (40 µg/kg) produced serum levels of 3.5 ± 0.9 ng/ml (mean ± SD) in seven lambs 60 min after administration, reduced the heart rate by 16% (172 to 149 beats/min,p< 0.05), increased the stroke volume 16% (29.8 to 34.5 ml/beat,p< 0.05) but did not significantly alter the systemic flow index (&OV0422;s), the pulmonary flow index (&OV0422;p), or the volume of left to right shunt (&OV0422;L-R, 6.74 to 6.77 liter/min/m2). The mean left atrial pressure ( -14.0) was unchanged (17.6versus17.1 mm Hg) following digoxin. Chronic digoxin use in four lambs for 4 days (25 ± 8 µg/kg/8 h) produced trough serum levels of 1.2 ± 0.2 ng/ml. There was no additional hemodynamic effect compared to acute digoxin, the &OV0422;P/&OV0422;Sratio was unchanged (3.10versus3.08) and evidence of left ventricular volume overload (– 14.0versus13.4) was unchanged. Amrinone lowered the systemic resistance index in a dose dependent fashion. The peak reduction of 20% (25.3 to 20.3 U/m2,p< 0.01) occurred at 20 min after an intravenous (3 mg/kg) bolus in seven Iambs. The &OV0422;sincreased from 2.58 to 3.10 liter/min/m2(p< 0.01). The &OV0422;pwas unchanged, thus the &OV0422;p/&OV0422;sratio was lowered by 16% (p< 0.05). Amrinone caused a 17% reduction in (17.9 to 14.9,p< 0.05) and increased the heart rate by 7%. The data indicate that the peripheral vascular effects of amrinone offer a hemodynamic advantage compared to acute digoxin.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.This study assessed the liver vitamin A concentrations at birth in a group of very low birth weight neonates (n= 25) (<1500 g birth weight, <32 wk gestation), dying within 24 h of birth, prior to possiblechanges in vitamin A status induced by postnatal intervention. Serum concentrations of vitamin A and retinol-binding protein were also measured in 16 of these neonates. The mean (± SD) liver vitamin A concentration was 30.0 ± 12.9 Mg/g (range 2.0-49.0 µg/g)- The mean (± SD) serum vitamin A concentration was 13.0 ± 4.7 µg/dl (range 6.7-22.8 µg/dl). The mean (± SD) serum retinol-binding protein concentration was 2.2 ± 0.8 mg/dl (range 1.5–4.8 mg/ dl). Liver vitamin A, serum vitamin A, and serum retinolbinding protein concentrations did not correlate significantly with gestational age or birth weight. Linear regression analysis did not show a significant correlation between liver vitamin A, and serum vitamin A or retinol-binding protein concentrations. This study provides reference values for vitamin A concentrations at birth in very low birth weight neonates, which may be helpful in future studies designed to evaluate postnatal changes in the vitamin A status of these high-risk neonates.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACTThe role of electrolyte, carbohydrate, and base composition, as well as osmolality, of oral hydration solutions (OHS), was investigated using a nonabsorbable marker and tritiated water in an in vivo intestinal perfusion system in rats. The OHS tested were the World Health Organization recommended formula, containing 90 mEq/ liter sodium and 111 mM glucose, which was taken as the reference solution; five variants of this solution with different sodium and glucose concentrations; and two solutions without sodium,i.e.isotonic glucose and deionized water. Also tested were one solution with acetate in lieu of bicarbonate, and two commercial preparations where citrate substituted for bicarbonate. The best water absorption rates were obtained with World Health Organization-type OHS characterized by a combination of low osmolality and moderate sodium and glucose content. Hypotonic OHS (190, 220, and 155 mosmol/kg) in which the sodium: glucose ratios were 60:30, 60:60, and 30:55, respectively, produced mean jejunal water transport rates of 3.46, 3.20, and 2.91 µl/min/cm, respectively, whereas the standard World Health Organization OHS (330 mosmol/kg) resulted in a rate of 1.36 µl/min/cm (p<0.001). Similar good water absorption was achieved when Ac was the base (270 mosmol/kg and 60:111 sodium:glucose ratio) and with one of the commercial solutions (245 mosmol/kg and 50:111 sodium:glucose ratio). The reference World Health Organization OHS allowed for sodium absorption, as did the OHS with sodium:glucose ratios of 90:45,60:30,60:60, and acetate-containing 60:111. Sodium at a concentration of 30 mEq/liter or less resulted in the efflux of this electrolyte. High glucose concentration and lower osmolality exacerbated this effect. The results obtained in this investigation may assist in better evaluating OHS and in selecting modified formulae geared to specific hydration needs and possible replacement of water and sodium losses.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.Cortisone, thyroxine, epidermal growth factor, or insulin were administered to 8-day-old rats for 4 days. In comparison to saline-injected controls, cortisone treatment: 1) lowered the sialic acid and raised the fucose content of the intestinal microvillus membranes, 2) increased [3H]fucose incorporation into these membranes, and 3) decreased the membrane binding of125I-wheat germ agglutinin, while increasing the binding of125I-ulex europeus agglutinin I and125I-peanut agglutinin. Thyroxine treatment had similar effects on fucose content and125Iulex europeus agglutinin I binding, but did not alter [3H] fucose incorporation or sialic acid content. At the doses used, epidermal growth factor and insulin had no significant effects. The effect of cortisone treatment on sialic acid and fucose was commensurate with a 5- to 6-day acceleration of postnatal intestinal maturation. The changes in lectin binding, however, suggested qualitative differences between developmental and cortisone-induced membrane glycosylation. In addition, this study demonstrates significant quantitative and qualitative differences in the response of intestinal glycosylation to pharmacologic doses of the four hormones.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.The sustained increase in ventilation (&OV0312;1) that occurs during acute hypoxemia in adults is not characteristic of the neonate as &OV0312;1falls to or below baseline values soon after onset of the hypoxic stimulus. Associated with this decline in &OV0312;1is a decrease in tidal volume, lung compliance, inspiratory duration, and an increase in functional residual capacity and respiratory frequency. We hypothesized that hypoxemia induced small airway constriction and pulmonary time constant inequalities resulting in a frequency dependent fall in lung compliance and tidal volume and retention of lung volume. In seven newborn subhuman primates, responses to acute hypoxemia were measured prior to and after administration of atropine methyl bromide to prevent vagally mediated narrowing of peripheral airways. The increase in frequency and fall in inspiratory duration characteristic of the ventilatory decline during hypoxemia was eliminated by the drug but functional residual capacity and lung compliance were unaffected. Also, the initial rise in &OV0312;1was blunted or blocked in all subjects. Bilateral vagotomy caused &OV0312;1to fall significantly requiring oxygen supplementation but responses to hypoxemia were still biphasic in nature. These findings suggest that cholinergically mediated mechanisms in the airways do not alter effective lung distensibility related to respiratory rate. Acetylcholine may be important at the peripheral chemosensor since cholinergic blockade eliminated the initial ventilatory increase. Finally, although vagotomy radically affected respiratory pattern during eupnea and hypoxia, the ventilatory response to hypoxemia remained biphasic ruling out this pathway as a primary modulator in the newborn response.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.The toxicity of bilirubin was investigated in 2 neural cell lines NBR10A and N115 using a quantitative dye assay 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium biomide (MTT) as a measure of cell viability and [3H]thymidine incorporation as a measure of DNA synthesis. Short exposures (up to 2 h) to bilirubin, even up to a bilirubin-albumin molar ratio of 1.5, yielded no evidence of toxicity using these assays. At longer exposure times (24 h) a decrease in cell viability and [3H]thymidine incorporation was detected at a molar ratio of 0.8 when the bilirubin concentration was 0.1 mM or higher, whereas lower bilirubin levels at this molar ratio showed no deleterous effect. The effect of bilirubin is more pronounced at a molar ratio of 1.5 with longer incubation periods. The MTT assay showed the N115 cells appeared to be more resistant to bilirubin cytotoxicity than NBR10A cells, a finding which was not obtained from [3H]thymidine incorporation studies. This discrepancy can be explained by the fact that we are measuring two different variables; the MTT assay estimates the number of viable cells at the end of the experiment by measuring mitochondrial function whereas the [3H]thymidine assay measures the rate of DNA synthesis during the last 2 h of the experiment. The concentration effect of bilirubin is evident from the [3H]- thymidine studies in that at a molar ratio of 1.5 and bilirubin concentration of 0.075 mM or higher, there is both cell kill (decrease in DNA) and inhibition of [3H]- thymidine incorporation (decrease in specific activity). When the bilirubin concentration is reduced to 0.03 mM, there is little or no cell death (no change DNA) but inhibition still exists (42% decrease in specific activity). Thus, cell viability and function of these two neural lines is dependent not only on the bilirubin albumin molar ratio, but also on the absolute concentration of bilirubin and albumin as well as the time of exposure.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.The present study has been carried out to define whether endogenous dopamine contributes to the regulation of renal sodium handling and the function of the renin-angiotensin-aldosterone system in low birth weight premature infants. Twelve premature infants with mean birth weight of 1420 g and mean gestational age of 29.2 wk were given metoclopramide (MTC) in a dose of 0.1 mg/ kg/day to treat delayed gastric emptying, regurgitation, and abdominal distension at the age of 17-23 days. Infants were kept on either a low (2-3 mEq/kg/day) or high (4-7 mEq/kg/day) sodium diet to modulate activity of RAAS. Prior to and after a 3-day period of MTC administration, blood samples were taken, and in six male infants 24-h urine collections were made to determine plasma and urine electrolytes, plasma renin activity, plasma aldosterone concentration, and urinary aldosterone excretion. We demonstrated that plasma sodium and potassium concentrations and plasma renin activity were not altered by MTC. On the other hand, in response to MTC, there was a significant increase in urinary sodium excretion (1.8 ±0.3 versus 2.3 ±0.3 mEq/kg/day) and a decrease in potassium excretion (1.2 ±0.2versus0.8 ±0.1 mEq/kg/day); plasma aldosterone concentration and urinary aldosterone excretion decreased significantly from initial values of 2101 ±274 pg/ml and 2.91 ±0.52 µg/day to 1500 ±207 pg/ml (p< 0.01) and 2.21 ±0.43 µg/day (p< 0.01), respectively, after MTC. These alterations were independent of the pretreatment hormone levels. We conclude that in low birth weight premature infants endogenous dopamine has no influence on plasma renin activity and enhances rather than inhibits aldosterone production and renal tubular sodium reabsorption.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.Human milk was fractionated to obtain a partially purified growth factor preparation. The growth factor in this fraction, designated as human milk growth factor III, exhibits chromatographic and biological characteristics similar to epidermal growth factor-urogastrone. Pretreatment of mice with human milk growth factor III significantly reduces the incidence, number, total length, and severity score of cysteamine-induced duodenal ulcers.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

ABSTRACT.The intestinal contents of 17 neonates with necrotizing enterocolitis were analyzed for pH, carbohydrate, protein, and bacteria. The intraluminal pH was <5.0 (16/17). Sufficient carbohydrate and bacteria capable of fermenting the carbohydrate to organic acids were found. The intraluminal protein content was >5 g/dl. The variables of acid and protein were then examined in a rabbit intestinal loop model. The hemorrhagic response in individual loops was measured using Cr51tagged red blood cells such that the microliters of blood per centimeter intestine could be determined. Loops with organic acid and protein had significantly (p< 0.01) more intramural blood than control loops. Organic acid (possibly generated by bacterial mixed acid fermentation of carbohydrate) in the presence of protein promotes intramural hemorrhage similar to that seen in neonates with necrotizing enterocolitis.

ISSN:0031-3998    

出版商:OVID    

年代:1985

数据来源: OVID