Regulation of muscle protein synthesis in neonatal pigs during prolonged endotoxemia

In adults, protein synthesis in skeletal muscle is reduced by as much as 50% after a septic challenge, and is associated with repression of translation initiation. Neonates are highly anabolic and their muscle protein synthesis rates are elevated and uniquely sensitive to amino acid and insulin stimulation. In the present study, neonatal piglets were infused with Endotoxin (lipopolysaccharide, LPS) for 20 h at 0 (n = 6) and 13 microg/kg*h (n = 8). During the last 2 h, dextrose and an amino acid mixture were infused to attain fed plasma concentrations of amino acids, glucose, and insulin. Fractional protein synthesis rates and translational control mechanisms were examined. LPS reduced protein synthesis in glycolytic muscles by only 13% and had no significant effect in oxidative muscles. This depression was associated with reductions in the phosphorylation of 4E-BP1 (-31%) and S6 K1 (-78%), and a decrease in eIF4G binding to eIF4E (-62%), an event required for formation of the active mRNA binding complex. By comparison, LPS increased protein synthesis in the liver (+29%), spleen (+32%), and kidney (+27%), and in the liver, this increase was associated with augmented eIF4G to eIF4E binding (+88%). In muscle and liver, LPS did not alter eIF2B activity, an event that regulates initiator met-tRNA(i) binding to the 40S ribosomal complex. These findings suggest that during sustained endotoxemia, the high rate of neonatal muscle protein synthesis is largely maintained in the presence of substrate supply, despite profound changes in translation initiation factors that modulate the mRNA binding step in translation initiation.     

Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal

Protein synthesis (PS) increases after a meal in neonates, but the time course of the changes in PS in different tissues after a meal is unknown. We aimed to evaluate the changes in tissue PS, mammalian target of rapamycin complex 1 (mTORC1) activation, and proportion of ribosomal protein (rp) mRNAs in polysomes over 4 h after a bolus meal in neonatal pigs (n = 6/group; 5- to 7-d-old). The results show a more sustained increase in PS in glycolytic compared with mixed fiber type muscles and no changes in oxidative muscles. PS increased in liver, jejunum, and pancreas but not in kidney and heart. Feeding did not affect AMP-activated protein kinase or RAS-related GTP binding B activation. Phosphorylation of tuberous sclerosis complex 2, proline-rich Akt substrate of 40 kD, mTOR, eukaryotic initiation factor 4E binding protein, and rp S6 kinase 1 increased in all tissues after feeding. The proportion of mRNAs encoding rp S4 and S8 in liver polysomes increased within 30 min postfeeding. These results suggest that feeding stimulates mTORC1 signaling in muscle and viscera, but mTORC1 activation alone is not sufficient to stimulate PS in all tissues.     

Developmental regulation of protein kinase B activation is isoform specific in skeletal muscle of neonatal pigs

The postprandial activation of the insulin signaling pathway that leads to translation initiation is enhanced in skeletal muscle of the neonate and decreases with development in parallel with the developmental decline in muscle protein synthesis. Our previous study showed that the activity of protein kinase B (PKB), a major insulin signaling component, was higher in 7- than in 26-d-old pigs. To examine the molecular mechanisms involved, we determined PKB isoform abundance and phosphorylation state, the abundance of its kinases, and PKB's association with its kinases. The abundances of total PKB, PKBalpha, and PKBgamma were higher in muscle of 7- than in 26-d-old pigs whereas PKBbeta abundance was similar in the two age groups. PKB phosphorylation at Thr308 was higher in 7- than in 26-d-old pigs but PKB phosphorylation at Ser473 was similar in both age groups. The association of PKB with 3'-phosphoinositide-dependent kinase-1 (PDK-1), a kinase that phosphorylates PKB at Thr308, and PDK-1 abundance were higher in 7- than in 26-d-old pigs. Moreover, PDK-1 phosphorylation at Ser-241, a site that is crucial for PDK-1 activation, was higher in 7- than in 26-d-old pigs. However, the association of PKB with integrin-linked kinase (ILK), a kinase that potentially phosphorylates PKB at Ser473, and ILK abundance were similar in both age groups. The result suggests that the developmental change in PKB activation is isoform specific and involves regulation by PDK-1.     

Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia

Sepsis has been associated with tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) overproduction, insulin resistance, and a profound suppression of muscle protein synthesis. However, lesser suppression of muscle protein synthesis in neonatal pigs occurs in response to endotoxin (LPS) when glucose and amino acids are provided. We hypothesize that the LPS-induced TNF-alpha and NO overproduction down-regulates insulin signaling pathway activation in neonatal pigs in the presence of fed levels of insulin, glucose, and amino acids. In skeletal muscle, inducible NOS activity was increased in response to LPS infusion, but phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), p42/p44 mitogen-activated protein kinase (MAPK), and protein kinase B, the association of IRS-1 with phosphatidylinositol 3-kinase (PI 3-kinase), and constitutive NOS activity were not altered. In liver, activation of the insulin receptor, IRS-1, and PI 3-kinase were not affected by LPS, but p42 MAPK phosphorylation was increased. The absence of a down-regulation in the insulin signaling cascade in muscle despite the LPS-induced increase in TNF-alpha and muscle iNOS, may contribute to the near-maintenance of muscle protein synthesis rates in the presence of glucose and amino acids in LPS-infused neonatal pigs.     

Synthesis of alpha-fetoprotein, albumin and total serum protein in neonatal pigs.

Studies on the incorporation of 3H-leucine established that synthesis of alpha-fetoprotein (AFP) does occur in the neonatal pig. This synthesis probably accounts for the increase in AFP concentration from 0.46 mg/ml on the day after birth to the maximum value of 1.02 mg/ml found 5 days after birth. After the 5th day, the concentration decreases successively and AFP cannot be detected by electroimmunoassay in the sera of 8-week-old pigs. During the first 3 weeks of extrauterine life, the albumin concentration in serum increases from 3 mg/ml to approximately 30 mg/ml due mainly to increased synthesis of albumin. The concentration of AFP in the fetal pig serum decreases from 3 mg/ml at 6.5 cm crown-to-rump (CR) length to 0.8 mg/ml at 28 cm CR length, whereas the albumin concentration increases from 0.2 mg/ml at 6.5 cm CR length to 1.0 mg/ml at 28 cm CR length. The total serum protein content in the fetus is approximately 20 mg/ml irrespective of gestational age. During the first day after birth there is a marked increase in both the synthesis and the concentration of total serum proteins. The concentration rises to 70 mg/ml during the first day and then slowly declines to 65 mg/ml during the 3 weeks following birth.     

Pancreatic development in newborn guinea pigs fed intact or low-hydrolyzed protein formulas

AIM: To evaluate pancreatic development in newborn guinea pigs fed since birth intact or low-hydrolyzed protein formulas compared with breast milk. METHODS: Forty-five newborn guinea pigs were allocated to three feeding regimens: breast milk (n=15) and two isocaloric isonitrogen milk formulas containing intact (n=15) or low-hydrolyzed proteins (n=15). Body weight and food consumption were recorded every day. After 8 days, one third of pups from each group was killed, and the remaining animals were weaned. Another third was killed on day 14, and the remainders were killed on day 20. Zymogen storage was evaluated on pancreatic sections, whereas DNA and RNA concentrations were measured by a fluorometric method. RESULTS: Compared with breast fed pups, both groups of artificially fed animals showed lower weight gain during the first 2 weeks of life but not after weaning. Both formulas fed groups had significantly lower amount of zymogen granules in pancreatic acinar cells at 8 and 14 days of life. This reduction was still present at day 20 in intact protein formula but not in low-hydrolyzed protein formula fed animals in which higher RNA/DNA ratio was also observed compared with breast fed pups. CONCLUSION: In newborn guinea pigs, artificial feeding is associated with reduced zymogen storage at days 8 and 14 of life. After weaning, cellular content of zymogen granules is comparable with breast fed pups only in low-hydrolyzed protein formula fed animals, even in the presence of some evidence of pancreatic hypoplasia.     

Arginine and mixed amino acids increase protein accretion in the growth-restricted and normal ovine fetus by different mechanisms

Protein metabolism may be perturbed in intrauterine growth restriction (IUGR). Arginine is indispensable for growth and nitrogen balance in young mammals. Fetuses with IUGR therefore may benefit from arginine supplementation. The purpose of this study was to determine 1) the effects of IUGR on protein metabolism in the ovine fetus and 2) the effects of arginine or mixed amino acid (AA) infusion on protein metabolism in these fetuses. Pregnant ewes and their fetuses were catheterized at 110 d gestation and randomly assigned to control or IUGR groups. IUGR was induced by repetitive placental embolization. Parameters of fetal protein metabolism were determined from [ring-(2)H(5)]phenylalanine kinetics at baseline and in response to a 4-h infusion of either arginine or an isonitrogenous AA mixture. There were no differences in protein metabolism between control and IUGR groups either at baseline or in response to arginine or AA treatment. Both arginine and AA infusion increased fetal protein accretion in both groups. Arginine did this by decreasing protein turnover, synthesis, and breakdown. AAs increased protein turnover and synthesis while decreasing protein breakdown. AA infusion resulted in a significantly higher increase in protein accretion than arginine infusion. Thus, in the ovine fetus, placental embolization has no clear effect on protein metabolism. Arginine and AAs both stimulate protein accretion but do so in distinctly different ways. Mixed AA infusion has a greater effect on protein accretion than arginine alone and therefore may be a better strategy for stimulating fetal growth.     

Pharmacokinetics and metabolism of trimethoprim in neonatal and young pigs

The pharmacokinetics and metabolism of trimethoprim (TMP) was studied in newborn, 1 and 8-week-old piglets after intravenous administration of 5 mg/kg. Kinetic parameters were calculated using a two-compartment open model. Steady-state volume of distribution increased from 0.78 L/kg at birth to 1.32 L/kg at 1 week, and 1.83 L/kg at 8 weeks due to changes in plasma protein binding and tissue accumulation. Elimination half-life decreased from 485 minutes at birth to 224 minutes at 1 week, and 120 minutes at 8 weeks leading to a rise in body clearance from 1.18 to 11.8 ml/min/kg during the same period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both metabolic capacity and renal function. Metabolism was the main contributor to the elimination of TMP at all ages, although the major metabolic pathway, O-demethylation and subsequent conjugation, was only slightly developed at birth. The capacity to form conjugates with either glucuronic acid or sulphate appeared to be at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in all groups.     

前白蛋白及视黄醇结合蛋白对不同窒息程度新生儿肝功能损害的诊断意义

目的探究前白蛋白(PAB)及视黄醇结合蛋白(RBP)对于鉴别轻、重度窒息新生儿的肝损害诊断价值。方法回顾性分析185例窒息新生儿,依据Apgar评分,分为轻度和重度窒息组,对不同窒息程度早产儿(84例)、足月儿(101例)的PAB、RBP、谷丙转氨酶、谷草转氨酶进行比较,并进行ROC曲线分析。结果与轻度窒息组比较,重度窒息组早产儿的谷草转氨酶较高,PAB、RBP较低(P0.05);重度窒息组足月儿的PAB较低(P0.05)。与治疗前比,治疗后早产儿重度窒息组的PAB,足月儿轻度窒息组的AST、PAB和重度窒息组的PAB均明显好转(P0.05)。ROC曲线显示,前白蛋白对于窒息足月儿、早产儿肝功能损害评价均有较好的灵敏度及特异度。结论前白蛋白可作为评价新生儿窒息肝损害的指标,并可以用于判断窒息程度的不同。     

Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.

As cocaine use during pregnancy has become increasingly recognized, there also has been increased concern about the toxic and teratogenic properties of cocaine on the fetus. A significant literature exists describing the adverse fetal and neonatal outcomes associated with in utero cocaine exposure. However, specific causality by cocaine on outcome in the human is difficult to ascertain because of multiple confounding variables associated with substance abuse including social factors and polydrug use as well as difficulty in confirming timing, dose and frequency of cocaine exposure. Most literature suggests that prenatal cocaine exposure is associated with developmental risk to the fetus. What is currently unknown is the extent of risk, the additive and/or synergistic factors contributing to cocaine's toxicity and the reversibility of the injury. In this paper we review the pharmacologic properties of cocaine as related to a model of mechanisms for developmental injury secondary to cocaine exposure and the published literature on the adverse fetal and neonatal outcomes associated with cocaine use during pregnancy. Specific attention has been focused on the structural, neurobehavioral and respiratory control teratogenesis.     

性别对缺氧缺血性脑损伤新生大鼠脑发育的影响

目的探讨不同性别缺氧缺血性脑损伤(HIBI)新生大鼠脑发育的差异。方法2018年1月1日至12月31日,新生7日龄SD大鼠60只(雌性30只、雄性30只),按随机数字表法将大鼠分为HIBI组40只(雄性20只、雌性20只),对照组20只(雌性10只、雄性10只)。HIBI组大鼠采用Rice-Vannucci方法制作缺氧缺血性脑损伤模型,分离左侧颈总动脉,双重结扎后切断,再置于8%O2和92%N2的混合气体的缺氧箱中90 min;对照组不进行任何处理。缺氧缺血处理后2周,应用步迹分析评价各组大鼠21日龄运动发育功能,头颅磁共振成像(MRI)测量大鼠脑组织的残存脑容量,透射电镜下分析运动区域神经元突触结构的破坏程度。采用方差分析和χ^2检验进行组间统计学比较,同组步长及趾间距比较采用配对t检验。结果HIBI-雄性组大鼠的病死率明显高于HIBI-雌性组[20%(4/20)比10%(2/20),χ^2=40.000,P=0.001];HIBI-雄性组和HIBI-雌性组大鼠脑损伤对侧(右侧)步长及趾间距均明显小于对照组[(7.5±0.3)和(7.9±0.5)比(8.2±0.5)cm,(0.9±0.1)和(1.0±0.0)比(1.1±0.1)cm,F=9.605、71.437,P均<0.01];且HIBI-雄性组均明显小于雌性组(P均<0.01)。HIBI-雄性组和HIBI-雌性组大鼠右侧步长及趾间距均明显小于同组左侧步长[(8.3±0.4)和(8.3±0.5)cm,t=5.289、10.580,P=0.001、0.010]及趾间距[(1.1±0.1)和(1.1±0.1)cm,t=7.953、6.435,P均<0.01]。HIBI-雄性组与HIBI-雌性组的残存脑容量明显小于对照组[(67±4)%和(75±5)%比100%,F=406.122,P<0.01],其中HIBI-雄性组小于HIBI-雌性组(t=-5.281,P<0.01)。HIBI-雄性组和HIBI-雌性组左侧中央前回神经元突触间隙均明显大于对照组[(23.4±1.3)和(19.7±1.6)比(18.9±0.6)nm,F=71.719,P<0.01],其中HIBI-雄性组大于HIBI-雌性组(t=7.645,P<0.01)。结论雄性新生大鼠更易受到HIBI的危害,具有更严重的脑损伤程度及偏瘫症状,对不同性别HIBI患儿应采用不同的更合适的治疗策略。     

不同吸氧方式对新生鼠视网膜血管发育的影响

目的：吸氧是早产儿视网膜病的高危因素之一,目前吸入氧浓度、吸氧方式等与早产儿视网膜病的关系仍有争议。该实验通过研究不同吸氧方式对新生鼠视网膜血管发育的影响,为早产儿临床合理用氧提供实验依据。方法：选择7日龄C57BL/6 J新生小鼠144只,随机分为6组,每组24只。实验组1:吸入氧浓度(F iO2)由30%逐渐升高至75%后突然中断吸氧;实验组2:F iO2由75%逐渐降低直至停氧;实验组3:吸75%高氧5天后骤然停氧;实验组4:吸75%高氧5天后逐渐降低F iO2直至停氧;实验组5:第1天吸75%高氧,第2天吸空气氧,交替进行,连续6 d;对照组:置于同实验条件下的空气中。实验组1,2,3,5和对照组分别于P12(生后第12天),P14,P17视网膜铺片(ADP酶染色法),实验组4于P14,P17,P22视网膜铺片,各组均在P17行视网膜切片(苏木素-伊红染色法)观察视网膜血管的增生和发育情况。结果：①视网膜铺片显示:对照组:P12见少量无灌注区,周边血管结构清晰,P14无灌注区消失,血管形态基本正常,P17血管形态全部正常。实验组1,3,5:P12视网膜中央部有大片无灌注区,血管收缩、闭塞,P14新生血管开始形成,P17大量新生血管形成。实验组4:P14视网膜中央部大片无灌注区,有少量新生血管形成,P17无灌注区缩小,血管走行基本正常,深层血管有阻塞,P22血管发育基本正常。实验组2:铺片显示视网膜血管形态与对照组相似。②视网膜切片显示:实验组1,2,3,4,5小鼠突破视网膜内界膜的新生血管内皮细胞核的数目分别为49.50±1.36,5.17±0.67,47.68±4.70,5.74±2.37,29.15±2.48个,对照组为1.22±0.20个。实验组1,3,5与对照组相比差异均有显著性(P<0.05),实验组2,4与对照组相比差异无显著性(P>0.05)。结论：不同吸氧方式对视网膜血管发育产生不同的影响,吸入氧浓度波动较大、吸入高浓度氧后突然停氧可严重影响新生鼠视网膜血管的发育,产生类似早产儿视网膜病的病变。因此临床上应尽早稳定早产儿的生命体征,减少氧疗,严密监测用氧情况,采取逐渐降低氧浓度的吸氧方式,并尽量避免氧浓度波动过大。     

Insulin involvement in intestinal macromolecular transmission and closure in neonatal pigs

The involvement of insulin in the intestinal transmission of macromolecules to blood and the cessation of this transport (intestinal closure) was studied in neonatal pigs by measuring the serum levels of the markers bovine serum albumin and fluorescein isothiocyanate labelled dextran 70,000 (FITC-D) at 4 h after gavage feeding. In naturally suckled pigs, intestinal closure at 18 h was shown to be associated with an increase in serum immunoreactive insulin (IRI) levels. Similarly, intestinal closure obtained at 18 h, by gavage feeding unsuckled pigs a total of 48 g lactose/kg, was accompanied by an increase in serum IRI levels. Neither high serum IRI levels nor closure were observed in fasted pigs or in pigs gavage fed a total of 12 g lactose/kg. The effect of exogenous insulin on intestinal macromolecular transmission was studied by injecting 5 IU insulin/kg subcutaneously at 3 and 6 h, respectively, in newborn pigs gavage fed 10 ml sow colostrum/kg at 3 h intervals. This resulted in a reduction in the transmission of the markers when tested at 12 h, in comparison to littermates receiving the same amount of colostrum and littermates suckling the sow. It appears as if insulin, reflected as high serum levels over an extended period of time, is involved in the regulation of macromolecular transmission and intestinal closure in neonatal pigs. It was speculated that insulin may be involved in these processes by initiating the synthesis of membrane structural proteins in the enterocytes.     

脑缺氧缺血损伤新生大鼠热休克蛋白70的合成研究

目的：观察热休克蛋白70（HSP70）在缺氧缺血（HI）新生大鼠脑内的表达。方法：应用免疫组化法检测正常对照组以及HI组不同时间点的脑海马和皮质部位的HSP70阳性细胞数。结果：正常脑组织内未观察到明显HSP70阳性细胞，HI后阳性细胞明显增加。HI后2h即可观察阳性细胞，48h,72h达到高峰，7d时已经明显下降，结论：HI是脑HSP70合成及极为敏感的诱因，且HSP70的生成量随HI后时间增加呈动态变化过程。     

Growth, digestion, and protein metabolism in neonatal pigs given diets containing whey as the predominant or only source of milk protein

Milk substitutes containing ratios of casein/whey protein ranging from 80:20 to 0:100 were given to neonatal pigs. A ratio of 60:40 gave maximum growth rate, efficiency of feed utilization and nitrogen retention, and the lowest concentration of urea in blood plasma. This ratio is close to that in sow's milk, suggesting the hypothesis that in each species the milk may be adapted to the protein requirements of their young; by analogy, a casein/whey protein ratio of 20:80 in humanized milk formula might lead to more efficient protein utilization by the infant. In general, changes in the proportion of casein and whey proteins in the diet produced similar effects on the free amino acids in blood plasma as were found in clinical studies reported in the literature, providing further evidence of similarities in the protein metabolism of infants and neonatal pigs. The amount of nitrogen in the digesta remaining in the stomach at 1 h after a meal indicated that whey proteins empty from the stomach more rapidly than casein.     

新生儿脐血维生素K缺乏诱导蛋白与胎龄及地区的关系

目的 探讨新生儿脐血维生素K缺乏诱导蛋白(PIVKA-Ⅱ)水平是否与胎龄及地区有关。方法采集405例足月儿(平均胎龄39.31周,城镇259例,乡村146例)及142例早产儿(平均胎龄35.90周,城镇116例,乡村26例)脐血,用酶联免疫吸附法测定其PIVKA-Ⅱ水平,≥2μg/ml为阳性。结果 不同胎龄新生儿脐血PIVKA-Ⅱ阳性率无显著差异(P>0.05);城镇足月儿脐血PIVKA-Ⅱ阳性率32.82％,显著低于乡村65.75％(P<0.01),而城镇与乡村早产儿脐血PIVKA-Ⅱ阳性率(42.24％,46.15％)无显著差异(P>0.05)。结论新生儿脐血PIVKA-Ⅱ水平与胎龄无关,与地区有关。     

不同途径换血治疗新生儿重度高胆红素血症及其对内环境的影响

目的　 探讨不同途径换血治疗新生儿重度高未结合胆红素血症及其对内环境的影响。 方法 　对 5 3例符合换血指征的新生儿重度高未结合胆红素血症进行换血治疗 ,根据不同的换血途径分为桡动脉组 (A组 )和脐静脉组 (B组 )。除换血途径外 ,两组患儿的换血方法相同。换血前后行血常规、血气分析、生化、胆红素、血培养等检查 ,并分别进行比较。 结果 　两组患儿的总胆红素和未结合胆红素的换出率分别为A组 49 2 5 %和 5 0 2 8%、B组 49 64 %和 5 1 2 3% ,换血前后比较均有显著差异 (P <0 0 1) ,但两组间无显著差异 (P >0 0 5 )。A组换血前后血糖、离子钙、白细胞、血小板水平有显著变化 ,除上述外B组 ,钾离子、氯离子、镁离子亦有显著变化。 结论 　两种途径换血治疗新生儿重度高未结合胆红素血症的疗效相似 ,经挠动脉换血治疗对内环境的影响较少。     

美金胺对脑缺氧缺血新生大鼠热休克蛋白70合成的影响

为评估非竞争性：NMDA受体美金胺(Memantine)对缺氧缺血(HI)的脑保护作用，将HI模型鼠(结扎右侧颈总动脉后予8％氧2h)随机分为对照(NC,n=15)组、缺氧缺血(HI，n=25)组，HI前应用美金胺组(PRE，n=25)、HI后应用美金胺组(POST，n=24)。应用免疫组织化学方法观察各组海马及皮质部位热休克蛋白(HSP)70阳性细胞数，进一步从分子水平评估美金胺的脑保护效果。结果显示PRE组和POST组脑HSP70生成量明显低于HI组。提示HI是HSP70生成的强烈诱导剂，美金胺的应用则明显减少了HSP70的生成，具有一定的缺氧缺血脑保护作用。     

Lactate genesis by rat liver and muscle during development

Lactate has been shown to be an important fuel for brain metabolism during early postnatal development (1). In an attempt to identify the source(s) of lactate in the postnatal rat, we have studied the in vitro catabolism of glucose, galactose, fructose, alanine, glycerol, and octanoate in liver and muscle minces prepared from suckling rat pups. Whereas galactose, fructose, and octanoate were found to be lactagenic (lactate generating) in liver, glucose was the sole lactate precursor in muscle. Galactose was most effective as a hepatic lactate source at 3 d of age. Thereafter, the production of lactate from galactose decreased to reach control levels by 15 d of age. In contrast, fructose or octanoate were lactagenic throughout development. Lactate formation from galactose was completely halted by iodoacetate, inhibited by high galactose concentrations, and suppressed by fasting. The absence of oxygen increased lactate production from either fructose or octanoate, but it did not affect lactagenesis from galactose. Muscle minces produced lactate from glucose in an age-dependent manner similar to the development pattern of lactate formation from galactose by liver. Because lactose-derived galactose is readily available during suckling, it is suggested that galactose-based hepatic lactagenesis serves a unique role in maintaining the supply of lactate during early postnatal development. This hepatic capability may augment glucose-based muscle lactate synthesis at a time when lactate is a major brain fuel.     

��������Ϊ�۲����������СӤ���Է��������е�Ӧ��

??Brain development in preterm and little infants is immature. They are particularly vulnerable to various environmental stress factors??resulting in neurobehavioral abnormalities. However??due to the brain plasticity of preterm and little infants??early detection and intervention can reduce or eliminate neurobehavioral abnormalities. Neonatal behavior observation??NBO?? is an observation - intervention tool??which has a unique advantage in the early assessment and intervention of neurobehavioral abnormalities in preterm and little infants. NBO is cost-effective??practical??efficient??easily implemented??flexible and satisfactory. NBO has been widely used in many affiliated hospitals and preventive care organizations??and has achieved satisfactory results in clinical work.