摘要:

To investigate the metabolic consequences of germinal matrix hemorrhage(GMH) we used volume-selective1H magnetic resonance spectroscopy in the striatal region in 12 preterm infants with predominantly small GMH. Both sides of the brain were investigated twice. Metabolite indices were calculated as the metabolite signal, recorded with TR = 1.6 s and TE = 272 ms, divided by the fully relaxed water signal corrected for transverse relaxation time constant (T2) decay. At the first investigation, when the infants were 32.5 ± 2.0 (mean ± SD) wk postmenstrual age, the hemorrhage was unilateral or markedly asymmetrical in size in 10 of 12 infants. The lactate index was higher (p< 0.01) and the phosphocreatine + creatine(Cr) (p< 0.05) andN-acetyl-L-aspartate (NAA)(p< 0.05) indices lower in the side with the larger hemorrhage. At the second investigation, 54.1 ± 2.7 wk postmenstrual age, no sign of a previous GMH could be seen on magnetic resonance imaging in three of 10 infants. Lactate could be detected in two of 10 infants only, and the Cr and NAA indices did not differ between sides. However, the choline index was significantly higher in the side with the larger hemorrhage (p< 0.01). We conclude that GMH is initially followed by lactate accumulation and possibly a delay in maturation as indicated by the transiently low Cr and NAA indices. Moreover, an increased choline index at the corrected age of 3 mo indicates a more persistent metabolic change after small GMH.Abbreviations: Cho,choline-containing compounds;GMH,germinal matrix hemorrhage;1H MRS,proton magnetic resonance spectroscopy;MRI,magnetic resonance imaging;NAA,N-acetyl-L-aspartate;Cr,phosphocreatine + creatine;T1,longitudinal relaxation time constant;T2,transverse relaxation time constant

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Subarachnoid hematoma produces cerebral vasoconstriction that may lead to death or permanent disability. After hematoma, enhanced pial arteriolar responses to vasoconstrictor agents have been reported in newborn pigs. The present study was designed to address the hypothesis that 5-hydroxytryptamine(5-HT) constricts piglet pial arterioles, and hematoma augments this constriction. Piglets (1-3 d old) anesthetized with ketamine and acepromazine received either 3 mL of artificial cerebrospinal fluid (control) or autologous nonheparinized blood (hematoma) injected onto the cortical surface. Four days after injection, closed cranial windows were implanted over the injected area under α-chloralose anesthesia. Vascular reactivity to 5-HT was examined. In control piglets, topical application of 5-HT (10-9, 10-7, and 10-5M) induced very mild, dose-dependent constriction of pial arterioles (-6 ± 1, -10 ± 2, and -12 ± 4%, respectively). These constrictions were substantially augmented in piglets with hematoma (-12± 2, -19 ± 1, and -30 ± 2%, respectively). After topical application of 5-HT, cerebrospinal fluid samples were collected from under the window to determine the effects of 5-HT on the levels of 6-keto-prostaglandin F1α and thromboxane B2. The baseline levels of 6-keto-prostaglandin F1α and thromboxane B2before 5-HT were 1791 ± 387 and 434 ± 74 pg/mL, respectively, in the control. 5-HT application had no significant effects on these prostanoid levels (levels at the highest concentration of 5-HT had a corresponding value of 1175 ± 301 and 288 ± 74 pg/mL for 6-keto-prostaglandin F1α and thromboxane B2, respectively). However, indomethacin (5 mg/kg, i.v.) treatment of the control piglets potentiated the constriction in response to 5-HT (-11 ± 1, -15 ± 2, and -24± 3%, respectively) sufficiently to produce constriction similar to that in the hematoma group. 5-HT has little effect on normal pial arterioles of newborn piglets but is a more potent cerebral vasoconstrictor in conjunction with cerebral hematoma.Abbreviations: 5-HT,5-hydroxytryptamine;aCSF,artificial cerebrospinal fluid;ET-1,endothelin-1;LTC4,leukotriene C4;TXB2,thromboxane B2

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e.iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), α-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.)Nω-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/iv; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p< 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI,p< 0.05), but remained stable in NLA lambs. α-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 ± 0.9versus4.2 ± 0.7 μM(NLA-40),p< 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 ± 017versus0.44 ± 0.05 μM (NLA-40),p< 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity.Abbreviations: AA/DHA ratio,ascorbic acid/dehydroascorbic acid ratio;CONT,control;HI,hypoxic-ischemic;MABP,mean aortic blood pressure;NLA,Nω-nitro-L-arginine;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A new animal experimental model of human neuroblastoma is described. The model involves xenotransplantation of a poorly differentiated human neuroblastoma cell line (SH-SY5Y) to the subcutaneous tissue in the hind leg of nude rats (WAG rnu/rnu). Injection of 20 million cells suspended in 0.2 mL of medium in each hind leg yielded an 89% tumor take (41/46) in 23 nude rats. Tumor take was evident after 2 wk. The tumors grew exponentially and reached a volume of 5.2 ± 1.6 mL 4 wk after transplantation. The tumor cells retained their morphologic phenotype at the ultrastructural level after transplantation and were immunohistochemically positive for neuron-specific enolase and for chromogranins A and B. Subcutaneous injections of the angiogenesis inhibitor TNP-470 (10 mg/kg of body weight) every other day gave a treated/control quotient for mean tumor volume of 0.34 after 12 d of treatment. This implies that angiogenesis inhibition may be of value as a complement to chemotherapy in the treatment of human neuroblastoma. The presented animal experimental model is designed for investigations of the effects of chemotherapy, angiogenesis inhibitors, radiotherapy, and/or surgery on the growth rate of human neuroblastoma.Abbreviations: BW,body weight;CgA,chromogranin A;CgB,chromogranin B;NSE,neuron-specific enolase;T/C,treated/control

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The increased incidence of infection in preterm neonates has been related in part to their relative deficiency of most complement components, because complement is known to participate in the defense against bacterial and viral infections. In a prospective study, complement activation products were determined in 52 preterm infants. Twenty preterm infants suffered from proven early onset infection, 11 infants were presumed to suffer from infection, which could not be confirmed. Twenty-one preterm infants without infection or perinatal asphyxia formed the control group. EDTA plasma was obtained within the first 6 h after birth, and follow-up examinations were done in 15 patients with proven infection during the next 24 h. The complement activation products C3a-desArg, C3bBbP, and sC5b-9 were measured with enzyme immunoassay systems. In preterm neonates with early onset infection, a significant elevation of C3a-desArg was found in the very early course of the disease. C3a-desArg generation resulted from alternative pathway activation as shown by a concurrent increase of C3bBbP concentration. In addition, significantly higher concentrations of sC5b-9 predicted infection in the first few hours after birth. Thus, despite very low levels of native complement proteins, preterm babies are able to generate remarkable amounts of activation products of the complement cascade. The elevation of these activation products preceded by hours significant changes of routine laboratory markers of infection, such as leukocyte count, differential blood count, and C-reactive protein. Thus they might help to identify preterm neonates with severe systemic infection earlier than other laboratory parameters.Abbreviations: CRP,C-reactive protein;TCC,terminal complement complex;I/T ratio,ratio of immature to total neutrophilic leukocytes;EIA,enzyme immunoassay

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Studies in humans and animals indicate that peripheral insulin sensitivity is decreased after puberty. Although glucose, after its uptake and phosphorylation, will be diverted to either the glycolytic or glycogen synthesis pathway, these pathways have not been characterized after the transition to puberty. Thus, we examined the changes in the pathways of glucose utilization in conscious (n= 22) prepuberty (81 ± 3 g), and postpuberty (258 ± 9 g) Sprague-Dawley rats. Insulin stimulated(by insulin clamp 18 mU/kg/min) glucose uptake [rate of glucose disappearance(Rd)] was decreased by ≈30% postpuberty (from 339 ± 22 to 239 ± 28 μmol/kg/min;p< 0.001). Although glycolysis (estimated by the rate of conversion of [3H]glucose to3H2O) decreased by ≈15% (p< 0.05), glycogen synthesis decreased by ≈40% (from 200 ± 17 prepuberty to 122± 22 μmol/kg/min postpuberty;p< 0.001), and accounted for ≈80% of the decrease inRdpostpuberty. Decrease in the capacity to store glycogen in response to insulin was also confirmed by≈40% decrease in both glycogen levels, and in3H accumulation into glycogen (from3H-glucose) at the end of the clamp study. This occurred in the absence of any changes in either theKmor theVmaxof glycogen synthase nor in the activity of glycogen phosphorylase. We conclude that the postpubertal decrease in insulin responsiveness is characterized by decreased ability to store muscle glycogen. We propose that high capacity for muscle glycogen synthesis may be required to sustain the increased metabolic requirements during peripubertal growth.Abbreviations: GS,glycogen synthase;GP,glycogen phosphorylase;HPG,hepatic glucose production;Rd,rate of diffusion

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Glucose, an essential substrate for brain oxidative metabolism, is transported across the blood-brain barrier and into neuronal and glial cells via Glut 1 and Glut 3 facilitative glucose transporter isoforms. To examine the effect of excessive circulating glucose on fetal brain glucose transporter expression, we investigated the effect of streptozotocin-induced maternal diabetes (SEVERE-D;n= 29) on the 20-d gestation fetal rat brain Glut 1 and Glut 3. We studied the effect of streptozotocin alone (STZ-ND;n= 12) in a nondiabetic state as well, along with vehicle injected controls (C;n= 24). In the presence of fetal hyperglycemia (12.63± 0.82 nM- SEVERE-Dversus2.35 ± 0.28-STZ-ND and 2.42± 0.16-C;p< 0.001) and hypoinsulinemia (0.38 ± 0.03 nM-SEVERE-Dversus0.50 ± 0.07-STZ-ND and 0.55 ± 0.06-C;p< 0.02), no detectable change in fetal brain Glut 1 and Glut 3 pretranslational expression (transcription/elongation rates and corresponding steady state mRNA levels) was noted when stimultaneously compared with the STZ-ND and C groups. In contrast, a trend toward a decline in Glut 1 (≈25 to 30%,p= 0.05) and a substantive decrease in Glut 3 (≈35 to 50%,p= 0.0006) protein concentrations was present in both the STZ-ND and SEVERE-D groups when compared with C group. These observations support a chemical effect of streptozotocin independent of maternal diabetes upon the translation or postranslational processing of fetal brain glucose transporters. Maternal diabetes with fetal hyperglycemia, however, failed to substantively alter fetal brain glucose transporters independent of the streptozotocin effects upon neuroectodermally derived tissues. We conclude that maternal diabetes with associated overt fetal hyperglycemia does not significantly change fetal brain glucose transporter levels.Abbreviations: Glut,glucose transporter;STZ-ND,streptozotocin-treated nondiabetic;SEVERE-D,streptozotocin-treated severely diabetic;C,vehicle control;NOD,nonobese diabetic;ANOVA,analysis of variance

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Intestinal fructose transport typically increases 3-fold after completion of weaning (>28 d of age) in rats allowed to wean normally. Precocious enhancement of fructose transport has been demonstrated in rats fed high fructose diets during early weaning. To determine the role of corticosterone in the enhancement of fructose uptake by diet, we fed 17-d-old rat pups, previously adrenalectomized or sham-operated at 10 d of age, high (65%) fructose or fructose-free diets for 3 d. Corticosterone levels in 20-d-old sham-operated and unoperated controls were 2.2-3.3-fold higher than those in adrenalectomized littermates and in unoperated 10-d-old pups. Fructose uptake per mg and per cm were each 2.0-2.5-fold higher in adrenalectomized and sham-operated pups fed high fructose diets compared with those in adrenalectomized and sham-operated littermates fed fructose-free diets or to those in unoperated littermates allowed to wean normally with the dam. An increase in levels of GLUT5 mRNA in pups fed high fructose diets paralleled the increase in rates of fructose uptake. Intestinal glucose uptake was independent of corticosterone levels and of diet. Thus, the corticosterone surge is not necessary for the precocious enhancement of intestinal fructose transport and of GLUT5 mRNA expression by dietary fructose during weaning.Abbreviations: ANOVA,analysis of variance;HF,high fructose;NF,fructose-free;MMC,mother's milk and chow;GLUT5,intestinal fructose transporter isoform.;GAPDH,glyceraldehyde-3-phosphate dehydrogenase

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Neurotransmitters are thought to influence cell development in their target tissues. In the current study, neonatal rats were given 6-hydroxydopamine to produce permanent sympathetic denervation, and the effects on cardiac and hepatic DNA and protein synthesis were assessed. Lesioned animals showed deficits in cardiac DNA synthesis over the first 8 d postpartum, a period in which sympathetic innervation is sparse and synaptic norepinephrine concentrations are low; the effect of lesioning was also evident for protein synthesis. Subsequently, DNA synthesis in control animals declined precipitously during the second to third postnatal week, the phase associated with ingrowth of the majority of sympathetic terminals and sympathetic hyperactivity. Neonatal lesioning delayed the ontogenetic decline in DNA synthesis; this effect was not shared by protein synthesis. In the liver, a tissue whose cells, unlike the heart, maintain the ability to divide into adulthood, there was no effect of 6-hydroxydopamine on DNA synthesis and only minor changes in protein synthesis. These results suggest that neural input provides two distinct trophic signals to the developing heart: an early promotion of cell replication associated with low levels of stimulation, and a subsequent promotion of the switchover from cell replication, to cell differentiation and enlargement, associated with high levels of stimulation. In light of the precipitous rise in circulating catecholamines at parturition, and of the subsequent development of sympathetic innervation, catecholamines are likely to play a trophic role in the establishment of the proper pattern of cardiac cell development.Abbreviations: ANCOVA,analysis of covariance;ANOVA,analysis of variance;6-OHDA,6-hydroxydopamine

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Oral glucose induces a greater insulin response than i.v. glucose, a difference apparently due to the secretion of gut factors(“incretins”). Studies examining the mechanisms of this finding in human subjects are limited, however, because of differences in glucose profiles. To overcome this obstacle, we studied eight young nonobese subjects using the hyperglycemic clamp with and without superimposed ingestion of oral glucose. In both studies, glucose was acutely raised by 125 mg/dL above fasting values by the infusion of i.v. glucose and maintained at this level for 180 min. During the experimental study, but not the control, each subject ingested oral glucose (30 g) at 120 min, and the glucose infusion was adjusted to maintain the plasma glucose plateau. Plasma insulin responses were nearly identical during both studies until oral glucose was added. After oral glucose, both plasma insulin and C-peptide levels sharply increased by 45-55% above control values (p< 0.001), indicating a potentiation of insulin secretion rather than decreased hepatic extraction of insulin. Plasma gastric inhibitory polypeptide (GIP) levels increased significantly in response to oral glucose, whereas plasma levels of glucagon-like peptide-1(7-37) were not affected. The time course of the rise in plasma GIP and insulin was nearly identical. We conclude that the GIP response to a modest oral glucose load may play an important physiologic role in glucose-stimulated insulin secretion in healthy young subjects.Abbreviations: GIP,gastric inhibitory polypeptide;GLP1(7-37),glucagon-like peptide-1(7-37 amide);VIP,vasoactive intestinal peptide

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID