Short-term treatment with estrone oleate in liposomes (Merlin-2) does not affect the expression of the ob gene in Zucker obese rats

Young female Zucker fa/fa rats of 370-430 g were implanted with osmotic minipumps releasing 3.5 mol/dayúkg of estrone oleate in liposomes (Merlin-2) into the bloodstream for up to 14 days. Merlin-2 induced a sustained loss of appetite, and a decrease in body weight of 3.5%, which contrasts with the 8.2% increase in controls during the period studied. Plasma insulin, glucose and urea decreased, and liver glycogen increased with Merlin-2 treatment. Plasma ACTH and corticosterone increased to a maximum at the end of the experiment. The expression of the ob gene in adipose tissue was unchanged, and plasma leptin levels were also unchanged by treatment. Estrone levels increased more than 1500-fold, and estrone oleate rose 100-fold during treatment. The fact that estrone oleate had no effect on the leptin levels or expression in obese rats, in contrast with the marked inhibition observed in the lean suggests that the functionality of the leptin receptor is essential for estrone oleate inhibition of the ob gene. This also suggests that leptin may control ob gene expression in white adipose tissue and that estrone oleate may activate this process. The slimming effect of estrone oleate is, thus, not directly dependent on leptin, since both normoleptinemic and hyperleptinemic animals lose fat following treatment nor are the effects on appetite and energy expenditure mediated by leptin. However, leptin levels and the expression of the ob gene are directly linked with estrone oleate function. A possible involvement of leptin in estrone oleate action is postulated. The results support the participation of estrone oleate in the control of body weight and hint at the complexity of its regulation by leptin and glucocorticoids.     

Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats

We investigated time-course changes in the expression of receptor activator of nuclear factor-kappaB (RANK), its ligand (RANKL), osteoprotegerin (OPG), bone-type alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRAP) in ovariectomized (OVX) rats. Samples of sera and coccyges were used for analysis of the enzyme activities and expression levels of proteins and mRNAs, and an immunohistochemical analysis was also performed. Serum BAP activity increased to 158.6% of the pre-operation value at 1 week after OVX, and then decreased to 38.7% at 8 weeks after OVX. On the other hand, the serum TRAP activity increased to 130.9% of the pre-operation level at 1 week after OVX, and was maintained at a high level, compared with the pre-operation level. The patterns of BAP and TRAP activity in the coccyges specimens were similar to those seen in the sera. The expression profiles of TRAP, RANK, and RANKL proteins in the coccyx specimens were similar to the pattern of serum TRAP activity, while the profiles of the BAP and OPG proteins were similar to the pattern of serum BAP activity in OVX rats. The changes in the mRNA expression levels of the osteogenic proteins were similar to those for protein expression. These biochemical changes in OVX rats were confirmed by immunohistochemical studies. Our results suggest that not only osteoclastogenesis accelerated but also osteoblastogenesis transiently increased during the early phase of osteoporosis.     

Effect of DHEA Glutamate Release from Synaptosomes of Rats at Different Ages

Dehydroepiandrosterone (DHEA) exerts multiple effects in the central nervous system. Most of them seem to be mediated through their nongenomic actions on neurotransmitter receptors, and these actions occur within seconds or milliseconds. DHEA increases neuronal excitability, enhances neuronal plasticity, and has neuroprotective properties. By investigating glutamate release from synaptosomes of rats at different ages (from 17 days to 12 months), we observed that (i) there is an increase in basal and K(+)-stimulated L-[3H] glutamate release in rats at 12 months old, when compared to other ages; and (ii) there is an inhibitory effect of DHEA on basal L-[3H] glutamate release in 12 months old. This inhibitory effect of DHEA could be related to its reported protective role against excitotoxicity caused by overstimulation of the glutamatergic system and ageing.     

Extracts ofPhellinus gilvus andPhellinus baumii inhibit pulmonary inflammation induced by lipopolysaccharide in rats

Compared to saline-challenged rats, rats exposed to 50 microg intratracheal lipopolysaccharide showed an increase of total white cells (from 0.3 x 10(6) to 2.4 x 10(6)), neutrophils (from 0.09 x 10(6) to 1.8 x 10(6)), the levels of tumor necrosis factor (TNF)-alpha (from 200 pg ml(-1) to 1200 pg ml(-1)), and interleukin (IL)-1beta (from 220 pg ml(-1) to 650 pg ml(-1)) in the bronchial lavage fluid. However, after pretreatment with extracts of Phellinus gilvus and Phellinus baumii, the total white cells, neutrophils, and the level of IL-1beta in lipopolysaccharide-challenged rats were similar to those in saline-challenged rats, except for TNF-alpha. The results indicate that extracts of P. gilvus and P. baumii may be useful in preventing acute pulmonary inflammation in human diseases.     

Intestinal permeability to lactulose and mannitol in growing rats with iron-deficiency anemia

Iron deficiency can have nonhematological manifestations, some of which may affect the gastrointestinal tract. The aim of this study was to determine if iron-deficiency anemia in growing rats affected small-bowel permeability as assessed by the urinary ratio of lactulose and mannitol. Thirty-seven male Harlan Sprague-Dawley rats (21 d of age) were randomly divided into two groups and fed either an iron-deficient (n=19) or an iron-sufficient diet (n=18) that contained either 13.5 or 43.8 mg of iron/kg diet, respectively. Animals were evaluated between 25 and 38 d of dietary treatment. Intestinal permeability was assessed by measuring the lactulose/mannitol urinary ratio following administration of a solution that contained the two sugars. At the end of the study, the mean body weight of rats fed the low-iron diet was approx 95% that of the controls. The mean hemoglobin (g/dL) was significantly lower in the low-iron diet group (11.2±1.4) than in the control group (16.9±0.8) (p=0.001). The liver iron concentration (μg/g) of the anemic group (41.4±4.7) was also statistically (p=0.001) lower than in the control group (116.6±18.2). The lactulose/mannitol ratio was lower in the anemic rats (2.0±0.7) than in the control group (2.6±0.7) (p=0.008), a finding that is not suggestive of intestinal mucosal atrophy, previously described in anemic children.     

次声暴露对大鼠脾、肝脏某些酶活性的影响

目的:观察8 Hz,130 dB次声暴露不同时间对大鼠脾、肝脏某些酶活性的影响.方法:35只SD大鼠随机分为5组,即对照组,1周,2周,3周,4周组.每天次声暴露1次,每次2 h.实验后,观察大鼠脾、肝脏组织中MAO,GSH-px,SOD活性和MDA含量的变化.结果:大鼠脾脏MAO活性1周,2周时显著增高(P＜0.01),3周下降,4周时又显著增加(P＜0.05).肝脏组织MAO活性变化不明显(P＞0.05).脾脏组织中GSH-px活性在4周时明显增高(P＜0.05),肝脏组织中GSH-px活性在1周时就有显著性增高(P＜0.05).脾脏SOD活性在1周至4周均有显著性增高(P＜0.05).肝脏组织在实验期变化不明显(P＞0.05).脾脏组织中MDA含量在3周至4周时有显著性增高(P＜0.05).肝脏组织在1至2周时有非常显著的增高(P＜0.01),在3周时下降,到4周时又显著高于对照组(P＜0.05).结论:8Hz,130 dB次声暴露,大鼠脾、肝脏组织活性氧自由基、脂质过氧化物增高,抗氧化能力降低,造成对组织的损伤.     

α<Subscript>1A</Subscript>- adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat

To determine which subtype of α_1-adrenergic receptors plays a role in the regulation of blood pressure, with α_1--adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various aradrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED₅₀, Dr) of α_-1adrenoceptor selective antagonist (prazosin, Dr 13.5 ± 3.6 vs. 15.1 ± 4.3, n = 11), /ga_1A-adrenoceptor selective antagonist (5-methyl-urapidil, Dr 2.4 ± 0.9 vs. 3.7 ± 2.3, n = 12; RS-17053, Dr 3.2 ± 1.6 vs. 4.4 ± 3.3, n =12) and α_1D- adrenoceptor selective antagonist (BMY7378, Dr 1.9 ±0.9 vs. 2.2 ± 0.8, n = 8) on phenylephrineinduced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial blood pressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4 ± 0.6 vs. 4.3 ± 0.9, n = 5; BMY7378, Dr 1.7 ± 0.5 vs. 1.7 ± 0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by α_1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.     

Production of transgenic rats by ooplasmic injection of spermatogenic cells exposed to exogenous DNA: a preliminary study

The aim of the present study was to investigate the efficiencies of producing transgenic rats by the ooplasmic injection of sperm heads (intracytoplasmic sperm injection: ICSI) and elongating spermatids (elongating spermatid injection: ELSI) exposed to the EGFP DNA solution. A slightly lower proportion of ICSI oocytes using sperm heads exposed to a concentration of 0.5 microg/ml DNA solution for 1 min developed into offspring (13.3%, 48/361) when compared to that of oocytes injected with nontreated sperm heads (19.4%, 32/165). Eight ICSI offspring were found to be EGFP-carrying transgenic rats (16.7% per offspring; 2.2% per embryo). After a 1-min exposure of the elongating spermatids to 5 microg/ml of DNA solution, 8.8% (45/511) of the ELSI oocytes developed into offspring while 12.7% (22/173) of the ELSI oocytes using nontreated spermatids developed. Six ELSI offspring carried the EGFP DNA (13.3% per offspring; 1.2% per embryo). The conventional pronuclear microinjection of 5 microg/ml of DNA solution resulted in the higher production of offspring (29.7%, 104/350) and the birth of three transgenic rats (2.9% per offspring; 0.9% per embryo). Thus, sperm heads and elongating spermatids were practically useful as the vector of exogenous DNA if the DNA-exposed spermatogenic cells were microinseminated into rat oocytes.     

Germination,Viability and Clearance of Stachybotrys chartarum in the Lungs of Infant Rats

Observing that the conidia of Stachybotrys chartarum can germinate in the lung of infant rats, it became important to ascertain whether an infection can ensue. Viable conidia of S. chartarum were instilled into the lungs of 4 and 14 day-old rat pups. Germination was observed frequently in the lungs of 4 day-old but rarely in the 14 day-old pups. In the 4 day-old pups, pulmonary inflammation with hemorrhagic exudates was observed and resulted in about 15% mortality rate compared to 0% for the controls instilled with phosphate buffered saline. Acute neutrophilic inflammation and intense interstitial pneumonia with poorly formed granulomas observed three days following exposure were associated with fungal hyphae and conidia. The surviving experimental pups showed significantly slower weight gain for seven days. Dilution plating and quantitative PCR analysis were used to follow total fungal load in the rat pups lung homogenates. In the 4 day-old rat pups viable fungi decreased rapidly and were less than 1% by day seven. Similarly, fungal DNA decreased exponentially and was only 0.03% by fourteen days after exposure. However, 14 day-old rat pups showed neither the lethal effects of exposures to viable conidia of S. chartarum nor the slower weight gain, and the fungal load decreased even more rapidly. We conclude that S. chartarum conidia can initially germinate and form hyphae but even in the immature rat pups do not establish an effective infection, although a very limited persistence cannot be excluded.This revised version was published online in October 2005 with corrections to the Cover Date.     

Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats

In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.