Ethanol withdrawal in rats is attenuated by intracerebroventricular administration of neuropeptide Y

AIMS: The effects of intracerebroventricular administration of neuropeptide Y (NPY) on ethanol withdrawal were studied in rats. METHODS: Ethanol was administered intragastrically five times daily for 4 days. At 16-17 h after the last infusion of ethanol, rats were rated for withdrawal using a score based on three signs: irritability, tremor and rigidity. Subsequently, the rats received an injection of NPY (12 or 24 nmol) or vehicle and were rated for signs of withdrawal. RESULTS: At both doses, NPY significantly reduced ethanol withdrawal, the effect of the larger dose being more pronounced. CONCLUSIONS: Our results are consistent with the concept that NPY receptors are centrally involved in the regulation of neuronal excitability and might form a novel therapeutic target for treatment of ethanol withdrawal and other states of neuronal hyperexcitability.     

Duck cerebellum participates in regulation of food intake via the neurotransmitters serotonin and neuropeptide Y

Abstract

Two important neurotransmitters, serotonin (5-hydroxytryptamine, 5-HT) and neuropeptide Y (NPY), have been confirmed to be involved in food intake regulation. To clarify whether the cerebellum participates in modulation of food intake through these two neurotransmitters, we investigated the distribution and expression levels of 5-HT and NPY in cerebellum of the duck. Our results showed that 5-HT and NPY were distributed only at the Purkinje cell layer of the duck cerebellum. Moreover, the expression level of 5-HT in fasted (4 h) and tryptophan (100–200 mg/kg)-treated ducks was significantly higher than that in control animals (P < 0.01), whereas the expression of NPY was significantly decreased (P < 0.01). Therefore, our results indicated that inhibitory regulation of food intake respectively increased and decreased cerebellar 5-HT and NPY in the duck.     

Duck cerebellum participates in regulation of food intake via the neurotransmitters serotonin and neuropeptide Y

Two important neurotransmitters, serotonin (5-hydroxytryptamine, 5-HT) and neuropeptide Y (NPY), have been confirmed to be involved in food intake regulation. To clarify whether the cerebellum participates in modulation of food intake through these two neurotransmitters, we investigated the distribution and expression levels of 5-HT and NPY in cerebellum of the duck. Our results showed that 5-HT and NPY were distributed only at the Purkinje cell layer of the duck cerebellum. Moreover, the expression level of 5-HT in fasted (4 h) and tryptophan (100-200 mg/kg)-treated ducks was significantly higher than that in control animals (P<0.01), whereas the expression of NPY was significantly decreased (P<0.01). Therefore, our results indicated that inhibitory regulation of food intake respectively increased and decreased cerebellar 5-HT and NPY in the duck.     

Zinc regulation of food intake: new insights on the role of neuropeptide Y

The role of neuropeptide Y (NPY) in feeding behavior and zinc deficiency-induced anorexia has been controversial because hypothalamic NPY levels are elevated in both zinc deficiency and food restriction. A recent report shows that while NPY is released from terminals in the paraventricular nucleus of the hypothalamus of food-restricted animals, this release is significantly impaired in zinc-deficient animals. Zinc deficiency may therefore cause anorexia by inhibiting the release of NPY that is required for receptor activation.     

ICP患者胎盘中NPY的表达及意义

目的 探讨妊娠肝内胆汁淤积症患者胎盘中神经肽表达的变化.方法 采用SABC免疫组织化学染色方法及图像分析技术检测妊娠肝内胆汁淤积症患者胎盘中神经肽的表达及定量.结果 ①光镜下发现妊娠肝内胆汁淤积症患者胎盘绒毛水肿、绒毛间隙狭窄、绒毛血管合体膜增厚;②妊娠肝内胆汁淤积症患者胎盘和正常孕妇胎盘中均有神经肽的表达,但妊娠肝内胆汁淤积症患者胎盘中神经肽的表达增强,随病情加重而着色加深;图像分析神经肽在正常组、轻度妊娠肝内胆汁淤积症、重度妊娠肝内胆汁淤积症的平均光密度值(OD值)分别为0.7230±0.1452、1.0873±0.1394、1.6300±0.1281,统计学分析:轻度、正常组之间＞0.05,重度、正常组之间P＜O.O1,轻度、重度组之间P＜O.05.结论 妊娠肝内胆汁淤积症患者胎盘中神经肽的表达异常可能是导致妊娠肝内胆汁淤积症胎盘病理改变及胎儿不良预后的一个原因.     

The effect of sex steroids on insulin binding by target tissues in the rat

The effect of estradiol, progesterone and norgestrel on serum insulin and glucose levels and on insulin binding to adipocytes, hepatocytes and diaphragm muscle cell membranes has been evaluated in castrated male rats. Estradiol administration (5 μg/day × 6) significantly increased basal plasma insulin levels and the amount of insulin bound to fat and liver cells as well as muscle cell membranes. Progesterone treatment (5 mg/day × 6) caused a slight increase of basal insulin levels and a decrease of insulin binding to fat cells. Norgestrel treatment (5 mg/day × 6) decreased both insulin levels and the amount of insulin bound to adipocytes; a much lower dose of norgestrel, 6 μg/day × 7, also caused a decline in adipocyte insulin binding due to an apparent increase in the dissociation constant of the high affinity binding sites. These studies demonstrate that ovarian sex steroids have a significant effect on insulin binding to target cells. This animal model would assist in determining the mechanisms involved in changes of carbohydrate metabolism which occur during the menstrual cycle, pregnancy, the menopausal state and with the use of oral contraceptives.     

子宫内膜癌309例临床及围手术期分析

目的:分析子宫内膜癌患者临床及围手术期特征。方法:选取吉林大学第一医院手术治疗子宫内膜癌患者309例,将并存各种并发症的148例患者(合并症组)与同期无合并症的161例子宫内膜癌患者(对照组)的临床资料进行比较分析。结果:子宫内膜癌常见的合并症为高血压(97例)、糖尿病(52例),冠心病(12例)等,合并症组平均年龄(57.2±8.4)岁,对照组平均年龄(50.2±7.2)岁,合并症组的年龄明显高于对照组(P<0.01)。合并症发生情况与手术范围、肿瘤分期、分化程度和病理类型无关,而合并症者发生术后近期并发症的比例高于对照组(P<0.05)。结论:子宫内膜癌常合并高血压、糖尿病、冠心病等,合并症对治疗过程有一定的影响,治疗时要控制合并症,但合并症存在与否对预后无明显影响。     

Glutathione turnover is increased during the acute phase of sepsis in rats

Glutathione metabolism during infection has been poorly documented. Glutathione concentrations and synthesis rates were studied in infected rats (2 d after infection) and in pair-fed controls. Glutathione synthesis rates were determined in liver, spleen, lung, small and large intestine, skeletal muscle, heart and blood by a 4-h or 6-h (15)N cysteine infusion. The activities of four hepatic enzymes involved in glutathione metabolism were also determined. Glutathione synthesis rates were significantly greater in liver (+465%), spleen (+388%), large intestine (+109%), lung (+100%), muscle (+91%) and heart (+80%) of infected rats compared with pair-fed controls. Glutathione concentrations were also greater in these tissues but were unaffected in small intestine and lower in blood. In keeping with the stimulation of liver glutathione synthesis, the activities of liver gamma-glutamyl-cysteine synthetase and glutathione reductase were significantly greater in liver of infected rats than of pair-fed rats. From the present study, we estimate that glutathione synthesis accounts for at least 40% of the enhanced cysteine utilization during infection. This increased utilization may be the primary cause of an enhanced cysteine requirement in infection.     

Up-regulation of neuropeptide Y receptors in the hypothalamus of monosodium glutamate-lesioned Sprague-Dawley rats

Monosodium-glutamate (MSG) is neurotoxic for brain regions devoid of blood-brain barrier when it is injected at high doses during the neonatal period. Neuropeptide Y (NPY) neurons in the arcuate nucleus are particularly sensitive to MSG treatment. But, despite of the large decrease of this potent orexigenic peptide, feeding behavior is only slightly affected. We hypothesized that the hypothalamic NPY receptor system might be modified in these rats. The present study characterizes hypothalamic NPY and NPY receptors in normal and MSG-treated rats. MSG-treated rats were lighter (p < 0.01) and ate 17% less than the control rats (p < 0.01). NPY levels in the mediobasal and mediodorsal hypothalamus were reduced in MSG-treated rats compared to normal rats (-26% and -43%, p < 0.05 and p < 0.01, respectively). Combined hypothalamic Y1 and Y5 NPY receptor density was increased in MSG-treated rats compared to normal rats (+25%, p < 0.04), but affinity remained unaltered. Blockade with a selective Y1 antagonist showed that the Y1 receptor subtype represented more than 90% of the combined Y1 and Y5 receptor populations. The up-regulation of the NPY receptors is an element necessary to maintain food intake at a sufficient level to allow survival and growth of the lesioned rats.     

Declines in physical performance by sex and age among nondisabled community-dwelling older Japanese during a 6-year period

Background

Few studies have examined whether declines over time in hand-grip strength (HGS) and fast walking speed (FWS) differ by sex and age among non-Western community-dwelling older adults. This study aimed to quantify changes in HGS and FWS over the 6-year period from 1994 to 2000 and examine whether these changes differed by sex and baseline age among older individuals in a Japanese community.

Methods

We conducted a community-based prospective cohort study. The participants were 513 nondisabled men and women aged 67 to 91 years at the 1994 survey. Independent variables regarding time since baseline, in addition to various time-dependent and time-independent covariates, were obtained in 1994, 1996, 1998, and 2000. The outcome variables were HGS and FWS assessed at each survey. All data on independent and dependent variables that were collected at each survey were simultaneously analyzed using a linear mixed-effects model.

Results

The linear mixed-effects model revealed significant declines in both HGS (−0.70 kg/year, P < 0.001) and FWS (−0.027 m/sec/year, P < 0.001) among nondisabled older participants who had analyzable data in any survey during the 6-year period. Sex was significantly associated with the rate of decline in HGS (P < 0.001), but not FWS (P = 0.211).

Conclusions

In this analysis of nondisabled older Japanese, a mixed-effects model confirmed a significant effect of aging on declines in HGS and FWS and showed that men had a significantly steeper decline in HGS than did women during a 6-year period.Key words: aged, aging, hand-grip strength, walking speed, longitudinal study     

Oocyte developmental competence is reduced in sows during the seasonal infertility period

The modern domestic sow exhibits a period of impaired reproductive performance during the late summer and early autumn months, known as 'seasonal infertility'. A reduction in farrowing rate due to pregnancy loss is the most economically important manifestation of seasonal infertility. The aim of the present study was to determine whether there are changes in oocyte developmental competence associated with season. Ovaries were collected in pairs from sows sourced from commercial piggeries and slaughtered 4 days after weaning during winter and summer-autumn. Following oocyte IVM and parthenogenetic activation, the ability of oocytes from large follicles to form blastocysts was greater in winter (54.94 ± 6.11%) than in summer (21.09 ± 5.59%). During winter, the proportion of oocytes developing to the blastocyst stage from large follicles was significantly higher (54.94 ± 6.11%) than those oocytes from small follicles (23.17 ± 6.02%). There was no effect of season on the proportion of oocytes developing to the blastocyst stage from small follicles. There was no effect of follicle size on blastocyst formation from those oocytes recovered during summer. Blastocysts derived from small follicles during summer had the lowest number of cells (24.25 ± 1.48) compared with blastocysts derived from large follicles during winter (37.5 ± 1.3; P < 0.05). The mean progesterone concentration in follicular fluid collected from small follicles was greater in winter than summer (1235.55 ± 164.47 v. 701.3 ± 115.5 nmol L(-1), respectively; P < 0.001). The mean progesterone concentration in the follicular fluid of large follicles was also greater in winter than in summer (2470.9 ± 169.1 v. 1469.2 ± 156.5 nmol L(-1), respectively; P < 0.001). Regression analysis revealed a positive correlation between progesterone concentration and oocyte developmental competence. The results indicate that porcine oocytes fail to reach their full developmental potential during the period of seasonal infertility, suggesting that the pregnancy losses observed at this time of year may be due to reduced oocyte developmental competence.     

The 1258 G>A polymorphism in the neuropeptide Y gene is associated with greater alcohol consumption in a Mediterranean population

Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. In the Spanish Mediterranean population, this variant is not polymorphic. Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruited. Alcohol consumption, and demographic and lifestyle variables were measured. Nucleotide sequence determination and SNP analyses were carried out. Only one exonic SNP was detected by direct sequencing (1258 G>A or rs9785023; allele frequency 0.47). From the intronic markers chosen (483 A>G or rs13235938, 2517 A>G or rs4722342, and 7065 A>G or rs4722343), only the two latter ones were polymorphic (allele frequencies 0.46 and 0.04, respectively), and none of them were associated with alcohol consumption. However, the 1258 G>A SNP was associated (recessive pattern) with higher alcohol intake. This association was particularly relevant in men with high alcohol intake (59.1 ± 5.0 g/day in AA as opposed to 40.6 ± 7.5 in the G carriers, P = .022) and women with moderate alcohol intake (7.3 ± 5.5 g/day in AA as opposed to 4.6 ± 3.9 g/day in G carriers, P = .048). The 1258 G>A polymorphism in the NPY is associated with higher alcohol consumption in the Mediterranean population.     

Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium

Changes in diet greatly affect the mucosal immune system, particularly in diseases such as Crohn's disease and necrotizing enterocolitis. This review examines the hypothesis that alterations in the luminal environment of the intestine regulate the expression of genes in the epithelium responsible for signaling to immune cells. Increasing chemokine expression in the mouse intestinal epithelium using transgenic techniques enhances the recruitment of neutrophils and lymphocytes into the intestine. Furthermore, SCFA concentrations in the intestinal lumen vary markedly with diet. SCFAs alter chemokine expression by inhibiting histone deacetylase activity in the enterocyte. The review therefore describes a molecular pathway explaining how changes in diet may alter leukocyte recruitment by regulating enterocyte gene expression. It is likely that other similar pathways remain to be discovered.     

Modulation of morphological changes of endometrial surface epithelium by administration of composite root extract in albino rat

In the present investigation, we attempted to study the modulation of morphological changes of endometrial surface epithelium by Scanning Electron Microscope (SCEM) in the adult albino rat after oral administration of roots extract. The origin of this experiment lies in the fact that the dry powdered roots of five plants, i.e., Plumbago rosea, Borassus flabellifer, Carica papaya (male), Dolichos lablab, and Shorea robusta in mixed form, has been traditionally used by the folk women of this region through oral route during the first seven days of a menstrual cycle to prevent conception. Ethanolic crude extract of these roots in composite form which has been referred to here as composite root extract (CRE) was administered to the adult female albino rat in a dose of 1000 mg/kg body weight/day through oral route continuously for 12 days starting from proestrous. The observations under SCEM showed that administration of the CRE induced morphological changes of the endometrial surface epithelium in albino rat uterus. The characteristic smooth regular pattern of normal epithelium appears to have been changed at places by haphazardly oriented groups of cells and loss of microvilli indicating a disorganized picture. This structural disparity has been thought to affect the smooth functioning of nidatory preparation in the endometrium.     

Supplementation of sows with L-carnitine during pregnancy and lactation improves growth of the piglets during the suckling period through increased milk production

Recent studies showed that piglets of sows fed diets supplemented with L-carnitine grow faster during the suckling period than piglets of control sows fed diets without L-carnitine. This study was undertaken to investigate the effect of L-carnitine supplementation in sows on milk production and milk constituents. An experiment was performed in which two groups of 20 gilts each were fed diets with or without supplemental L-carnitine during pregnancy (0 vs. 125 mg L-carnitine daily/sow) and lactation (0 vs. 250 mg L-carnitine daily/sow). The experiment was continued over two reproductive cycles. L-carnitine-treated sows had larger litters (P<0.01) and higher litter weights (P<0.05) than control sows. Piglets of L-carnitine-treated sows had lower birth weights (P<0.05) but grew faster during the suckling period (P<0.01) and were heavier (P<0.05) at weaning than piglets of control sows. L-carnitine-treated sows had higher milk yields on d 11 and 18 of lactation than control sows (P<0.05). Milk of L-carnitine-treated sows had higher concentrations of total and free carnitine than milk of control sows (P<0.001); concentrations of fat, protein and lactose and the amounts of gross energy in the milk did not differ between the two groups of sows. The amounts of protein (P<0.05) and lactose (P<0.05) were higher in L-carnitine-treated sows than in control sows; the amount of energy secreted with the milk tended to be higher in carnitine-treated sows than in control sows (P<0.10). The study suggests that piglets of carnitine-treated sows grow faster during the suckling period than those of control sows because they ingest more nutrients and energy with the milk.     

Effects of ethanol consumption on vasopressin and neuropeptide Y immunoreactivity and mRNA expression in peripheral and central areas related to cardiovascular regulation.

Results from previous studies have demonstrated that ethanol influences central neural mechanisms involved in the control of blood pressure. We studied the effects of ethanol consumption on vasopressin and neuropeptide Y immunoreactivity and mRNA expression in the nucleus tractus solitarius and paraventricular hypothalamic nucleus, as well as in the petrosal and nodose ganglia of rats. The ethanol-fed rats received liquid diet ad libitum containing 37.5% ethanol-derived calories (6.7% volume/volume), and the pair-fed rats received the same volume of diet containing isocaloric amounts of maltose-dextrin substituted for ethanol for 3 or 28 days. Arterial blood pressure was evaluated in a separate group of rats, which was unchanged by 3 days, but elevated by 21% after 28 days of ethanol consumption. Vasopressin immunoreactivity and mRNA signal were not detected in the ganglia, nor were they changed in the nucleus tractus solitarius and paraventricular hypothalamic nucleus, by 3 days of ethanol consumption. However, after 28 days of ethanol liquid diet consumption, vasopressin-positive terminals were decreased in the nucleus tractus solitarius and vasopressin immunoreactivity cell bodies and mRNA signal were decreased in the paraventricular hypothalamic nucleus. Neuropeptide Y-immunoreactive terminals were increased in the nucleus tractus solitarius only after 28 days of ethanol liquid diet consumption, but they were decreased in the paraventricular hypothalamic nucleus in rats treated with ethanol for 3 or 28 days. We concluded that the levels of both vasopressin and neuropeptide Y neurotransmitters are changed by long-term ethanol consumption in the neuronal pathways related to control of blood pressure.