摘要:

Acute hypoxia in newborns of various species including humans is associated with decreased thermogenesis and a fall in body temperature. We have investigated the cardiorespiratory consequences of correcting the fall in colonic temperature (Tc) during acute hypoxia in newborn cats. Experiments were conducted on 21 unanesthetized kittens (12 ± 1 d SEM, 244 ± 8 g) instrumented with catheters in the left common carotid artery and superior vena cava for measurements of systemic arterial pressure, central venous pressure, heart rate, arterial blood gases, arterial O2saturation (Sao2) and mixed venous O2saturation. Oxygen consumption (˙Vo2) and CO2production (˙Vco2) were also measured. Alveolar ventilation (˙Va), cardiac index (CI), and systemic vascular resistance index (SVRI) were calculated. These determinations were made in 21% O2at an ambient temperature (Tamb) of 25 °C, and after 80 min of exposure to Fio2= 0.10. In one group Tamb was maintained at 25 °C (n= 8) during hypoxia and Tc fell by 2.7 ± 0.4 °C whereas in a second group Tamb was increased to 35°C for the second 40 min of hypoxia to raise Tc to the prehypoxic level(n= 13). ˙Vo2, ˙Vco2, ˙Va, Sao2, and systemic arterial pressure during hypoxia did not differ between the animals which were warmed and those which were not. However, CI and heart rate were greater (452 ± 23versus346 ± 30 mL·min-1·kg-1p < 0.05, 279 ± 8versus228 ± 12 beats·min-1p < 0.05) and SVRI lower (0.115 ± 0.022versus0.153 ± 0.014 mm Hg·mL-1·min·kg,p< 0.05) during hypoxia in the warmed animals compared with the unwarmed group. Thus, artificially raising Tc during hypoxia resulted in peripheral vasodilatation, whereas systemic arterial pressure was maintained by the increase in cardiac output. We conclude that, in the hypoxic kitten, raising Tc to normoxic values elicits a response that may reflect a condition of relative hyperthermia.Abbreviations: Cao2, arterial blood oxygen content;CI,cardiac index;C[horizontal bar over]vo2, mixed venous blood oxygen content;Fio2, fractional inspired oxygen;Sao2, arterial blood oxygen saturation;STPD,standard temperature, standard pressure, dry;S[horizontal bar over]vo2, mixed venous blood oxygen saturation;SVRI,systemic vascular resistance index;Tamb,ambient temperature;Tb,body temperature;Tc,colonic temperature;˙Va,alveolar ventilation;˙Vco2, gaseous carbon dioxide production;˙Ve,minute ventilation;˙Vo2, gaseous oxygen consumption

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The aims of this study were1) to define normal perinatal maturational changes in proton metabolite peak-area ratios in two regions of the neonatal brain, the thalamic and occipitoparietal regions, and2) to investigate abnormalities of these ratios after perinatal hypoxia-ischemia. Fifty-four infants were studied: 35 normal control infants at 31-42 wk of gestational plus postnatal age, and 19“asphyxiated” infants suspected of cerebral hypoxic-ischemic injury. Proton spectra were collected at 2.4 tesla from (2 cm)3voxels using the point-resolved spectroscopy technique with a 270-ms echo time. Lactate was detected in all infants studied. In the normal infants, lactate relative toN-acetylaspartate (NAA), choline and creatine was significantly greater in the occipitoparietal region than in the thalamus, and fell with increasing maturity in both regions, whereas NAA/choline increased. The 19 asphyxiated infants were studied on a total of 34 occasions during the 1st wk of life (median age 1.8 d), at gestational plus postnatal ages of 27-41 wk. Maximum lactate/NAA was above 95% confidence limits for the control data in one or both regions in 11 of the 19 infants. Minimum NAA/choline was below 95% confidence limits in only one asphyxiated infant, who was later found to have congenital hypothyroidism. SD scores for lactate, relative to NAA, choline, and creatine, were higher in both regions in the asphyxiated infants compared with the normal infants, particularly in the thalamus. Early results of 1-y follow-up examinations indicate that raised lactate/NAA carries a poor long-term prognosis.Abbreviations: Cho,choline-containing compounds;Cr,creatine plus phosphocreatine;GPA,gestational plus postnatal age;Lac,lactate;MRS,magnetic resonance spectroscopy;NAA,N-acetylaspartate;OP,occipitoparietal;ppm,parts per million;PRESS,point-resolved spectroscopy;1H,proton;SNR,signal-to-noise ratio;STEAM,stimulated-echo amplitude mode;T2, transverse relaxation time;TE,echo time

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

For quantitative evaluation of lipid peroxidation after perinatal hypoxia in umbilical arterial cord blood samples from 109 healthy, acidotic, and asphyctic neonates with a gestational age ranging from 26 to 41 wk, the levels of aldehydic lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynon-2-enal (HNE) were measured. Furthermore, the concentrations of oxidized and reduced glutathione (GSSH and GSH) and the purine compounds hypoxanthine and uric acid were determined. With increasing gestational age MDA and HNE levels increased. Furthermore, an increased level of GSH was also found. After perinatal hypoxia the concentrations of MDA and HNE rose distinctly (p< 0.001), reflecting sensitively the extent ofin vivolipid peroxidation. HNE is proposed to be a new parameter for quantitative evaluation of posthypoxic cellular damage in the perinatal period. HNE is a more specific parameter for estimation of lipid peroxidation processes in comparison with MDA. Additionally, HNE is cytotoxic and mutagenic at nanomolar concentrations. The increased levels of both MDA and HNE were accompanied by a strong decrease of GSH concentrations (p< 0.001), indicating the rapid consumption of GSH via a glutathione peroxidase reaction but additionally the high reactivity of HNE with sulfhydryl groups. During oxygen deficiency, increased levels of hypoxanthine (p< 0.01) and uric acid (p< 0.05) were due to the accelerated degradation of purine nucleotides. The rate of purine degradation including xanthine oxidase reactions characterizes the extent of an important radical source during oxygen deficiency, contributing to peroxidation of polyunsaturated fatty acids and the formation of secondary aldehydic lipid peroxidation products.Abbreviations: GSSG,oxidized glutathione;GSH,reduced glutathione;HNE,4-hydroxynon-2-enal;MDA,malondialdehyde

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 ± 0.06 compared with 0.22 ± 0.04μmol·g-1·min-1in controls (mean ± SD,p< 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 ± 0.05 to 0.48 ± 0.06(p< 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact.Abbreviations: CBF,cerebral blood flow;CMRglc, cerebral metabolic rate for glucose;MRI,magnetic resonance imaging;PET,positron emission tomography;PKU,phenylketonuria;ROI,region of interest

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Congenital ornithine transcarbamylase (OTC) deficiency results in neuropathologic damage to the cerebral cortex, basal ganglia, and thalamus. However, the precise nature of the cell loss, as well as the pathophysiologic mechanisms responsible for it, have not been fully elucidated. In the present study, densities of the M1and M2subclasses of muscarinic cholinergic binding sites were assessed using quantitative receptor autoradiography in the brains of sparse-fur (spf) mice with congenital OTC deficiency and in age-matched CD-1 controls. Densities of binding sites for the muscarinic M1subtype ligand[3H]pirenzepine were reduced by 24-54% (p< 0.01) in frontal cortex, caudate/putamen, and hippocampal CA1and CA2areas. Since muscarinic M1sites are localized presynaptically, their selective loss, together with a previous report of reduced activities of the presynaptic cholinergic enzyme choline acetyltransferase, confirms that loss of cholinergic neurons is an important feature of congenital OTC deficiency. Densities of binding sites for the predominantly postsynaptic muscarinic M2subtype ligand3H-AFDX 384 were increased by up to 60%(p< 0.01) in cerebral cortex, hippocampus, globus pallidus, as well as in thalamic and hypothalamic structures of OTC-deficient mice. Increased M2sites in the cerebral cortex, hippocampus, and thalamus are most likely the result of up-regulation of these sites after the loss of the presynaptic neuron. These findings support the presence of a central muscarinic cholinergic lesion in congenital OTC deficiency.Abbreviations: OTC,ornithine transcarbamylase;ChAT,choline acetyltransferase;PZ,pirenzepine;spf,sparse-fur

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The high prevalence of obesity at an early stage of Duchenne muscular dystrophy (DMD) could result not solely from reduced physical activity, but may also involve low resting energy expenditure (REE), abnormal nutrient utilization, or overfeeding. We hypothesized that the dramatic muscle mass loss in DMD should reduce the REE. REE was measured by indirect calorimetry in 13 9-13-y-old DMD boys (5 obese, 8 nonobese) and 9 male age-matched controls. Muscle mass was estimated from 3-d creatinine excretion in urine. Daily energy intake was estimated from 7-d diet records. In the nonobese DMD group (NODMD) the muscle mass was reduced by 71%, and the REE was 13% lower than in controls(47.5versus54.6 kcal·h-1,p< 0.05). Postabsorptive respiratory quotients appeared higher in both DMD groups than in the controls; however, the difference was significant only for the NODMD group (0.88versus0.83,p< 0.05). Respiratory quotients were not different between the two DMD groups. Diet records were not contributive in revealing a different dietary behavior between groups. Our results suggest that:1) muscle mass loss in DMD is associated with a low REE,2) low postabsorptive fat utilization might occur at an early stage of the disease, and3) obesity is not associated with an increase in fat utilization in DMD. This study warrants further research to test low REE and low fat utilization as risk factors in developing obesity in DMD.Abbreviations: DMD,Duchenne muscular dystrophy;REE,resting energy expenditure;ODMD,obese DMD;NODMD,nonobese DMD;Vo2, oxygen consumption;Vco2, carbon dioxide production;RQ,respiratory quotient;FFM,fat-free mass

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We hypothesized that, in children with homozygous sickle cell anemia(HbSS), the shortened life-span of erythrocytes places an increased demand on protein stores, accelerates whole body protein turnover, and consequently, energy expenditure, as well as the rate of utilization of glutamine, a major fuel for reticulocytes. Eight (11.2 ± 0.4 y old) children with HbSS who were free of infection or vaso-occlusive disease, and seven (11.3 ± 0.4 y old) healthy black children were therefore studied in the postabsorptive state. Each received a continuous 4-h infusion of L-[1-13C]leucine to determine the rate of leucine oxidation, leucine rate of appearance, and nonoxidative leucine disposal, indicators of whole body protein breakdown and synthesis, respectively. Infusion of L-[2-15N]glutamine was used to assess rates of glutamine utilization. Resting energy expenditure and cardiac output were measured using indirect calorimetry and echocardiography, respectively. Compared with control subjects, HbSS children had a 58 and 65% higher leucine rate of appearance and nonoxidative leucine disposal, respectively (bothp< 0.001), 47% higher rates of whole body glutamine utilization (p< 0.01), 19% higher resting energy expenditure (p< 0.05), and 66% higher cardiac output(p< 0.01). In conclusion, children with HbSS show evidence of hypermetabolism with regard to protein, energy, and glutamine utilization. Both increased Hb synthesis and increased cardiac workload may contribute to excess protein and energy utilization. Whatever the mechanism of hypermetabolism, the data suggest that children with HbSS may have greater protein and energy requirements than the general population.Abbreviations: HbSS,homozygous sickle cell anemia;REE,resting energy expenditure;Ra,rate of appearance;KIC,α-ketoisocaproate;Vco2, CO2production;Vo2, O2consumption;NOLD,nonoxidative leucine disposal

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effect of the route of nutrient administration on the relative rates of leucine and phenylalanine kinetics was examined in 30 low birth weight (LBW) infants using L-[1-13C]leucine, L-[2H5]phenylalanine, and L-[2H2]tyrosine tracers. The infants received special premature formula (PF,n= 10, 117 ± 8 kcal·kg-1·d-1and 3.2 ± 0.2 g protein·kg-1·d-1) or fortified human milk (HM,n= 10, 106 ± 6 kcal·kg-1·d-1and 3.0 ± 0.2 g protein·kg-1·d-1), or parenteral nutrition (PN,n= 10, 80 ± 25 kcal·kg-1·d-1and 1.8 ± 0.3 g protein·kg-1·d-1). The rate of appearance(Ra) of leucine (RaLeu), was significantly higher in group PF as compared with groups HM and PN (434 ± 51versus377 ± 33 and 359 ± 50μmol·kg-1·h-1,p< 0.05). TheRaof phenylalanine (RaPhe) was lower in group HM as compared with group PF (94 ± 18versus115 ± 16,p< 0.05),RaPhein group PN (108 ± 24μmol·kg-1·h-1) was in between group PF and HM. The relative rate ofRaPheandRaLeuexpressed asRaPhe/RaLeuratio was lower in all groups than that expected from reported whole body protein composition and from that reported in adults. The ratio of phenylalanine hydroxylation to leucine decarboxylation was 0.202 in group PF, 0.212 in group HM, and 0.161 in group PN, suggesting a higher rate of decarboxylation of leucine relative to hydroxylation of phenylalanine. We conclude that:1) the higherRaLeucompared with theRaPhemay be the result of either a higher turnover of a body protein enriched in leucine or the consequence of higher leucine intake in infant nutrition and2) whole body protein kinetics calculated from a single amino acid tracer do not adequately represent whole body protein metabolism.Abbreviations: LBW,low birth weight;Ra,rate of appearance;NOD,nonoxidative disposal;PF,preterm formula;HM,fortified human milk;PN,parenteral nutrition;KIC,ketoisocaproate

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We assessed the relative importance of lipid, apo B, lipoprotein(a)[Lp(a)], and total homocysteine (tHcy) levels in children in relation to premature cardiovascular disease in family members. Parents of 381 girls and 375 boys age 8-12 y completed family history questionnaires. Nonfasting serum lipids and lipoproteins and plasma tHcy and cysteine levels were measured in the children. Serum folate and vitamin B12levels were determined in a random subsample of 23% of the children, who participated in a food frequency interview. Children whose parents reported hypercholesterolemia had higher total and non-HDL cholesterol and apo B levels than the rest, but these levels were not associated with cardiovascular disease. tHcy levels were similar in girls and boys. tHcy was higher in children whose father, grandfather, or uncle died at age ≤55 y of myocardial infarction or sudden cardiac arrest(n= 42) than in control children [5.92 μmol/L (95% confidence interval [CI] of 5.47-6.36)versus5.25 μmol/L (95% CI, 5.16-5.34)], also after adjustment for socioeconomic group. Intake and serum levels of vitamin B12and folate were within recommended or reference ranges. In a stepwise multiple regression analysis, serum folate (negative correlation), plasma creatinine, and sugar intake as percent of dietary energy(positive correlations) were significantly associated with tHcy (multipler= 0.44, adjustedr2= 18%; 95% CI, 5-30%). Our data show that a modest elevation in tHcy in children was related to premature cardiovascular death in their male relatives and may partly account for the contribution of family history to risk of cardiovascular disease. tHcy may be modifiable through the diet, even in children with apparently adequate vitamin nutriture.Abbreviations: tHcy,total homocysteine;tCys,total cysteine;Lp(a),lipoprotein(a);CI,confidence interval

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Creatine kinase (CK) has been implicated in the maintenance of skeletal muscle intracellular energy supply via its ATP buffering capacity. We examined the postnatal expression of CK activity and isoform phenotype in four skeletal muscles [diaphragm (DIA), intercostal (IC), external abdominal oblique (EAO), and the soleus (SOL)] of the rat. Moreover, we correlated CK activity during development with postnatal changes in myosin heavy chain (MHC) phenotype, the latter an index of relative changes in the energetic demands of muscle contractile proteins. CK activity was lowest in the immediate newborn period and increased in all muscles during postnatal development; the highest levels of CK activity were observed in the adult IC and EAO. CK activity did relate to the MHC phenotype as indexed by the ratio of adult MHC isoform content(slow + IIa + IIx + IIb) to developmental MHC isoform content (slow + neonatal;r2= 0.93,p< 0.001). Stepwise regression revealed that type IIb MHC expression alone accounted for 79% of the developmental variance in CK activity. We conclude that CK activity increases during postnatal development in a muscle specific fashion and relates to the energetic demands of the muscle contractile proteins as reflected by MHC isoform composition. We speculate that the role of CK as an energy buffer is greatest in muscles expressing the IIb MHC isoform.Abbreviations: CK,creatine kinase;DIA,costal diaphragm muscle;IC,intercostal muscle;EAO,external abdominal oblique muscle;SOL,soleus muscle;MHC,myosin heavy chain;MHC neonatal,neonatal MHC isoform;MHC slow,slow MHC isoform;MHC IIa-2A, MHC IIx-2X, and MHC IIb-2B,MHC isoforms;Bis,N,N'-methylene-bis-acrylamide

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID