• 약학회지
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• 제41권4호
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• pp.492-497
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• 1997

A difference in ethanol metabolism between premature and young adult rats was examined. Female SD rats, either 4wk or 12wk old, were injected with a single dose of ethanol (1.5g /kg) through jugular vein and the blood ethanol level was monitored for 300 min using a gas chromatographic method. Reduction of blood ethanol level per unit of time was less and the area under the blood concentration-time curve (AUC) was significantly greater in young adults compared to premature rats. Activity of hepatic alcohol dehydrogenase was not influenced by the age increase. Total cytochrome P-450, cytochrome $b_5$. or aminopyrine N-demethylation was not different between premature rats and young adult rats. However, p-nitrophenol hydroxylation and p-nitroanisole O-demethylation activities were significantly higher in premature rats. The relative liver weight was 45% greater in premature rats leading to an overall increase in ethanol metabolizing activity in these animals. The results indicate that the reduction in ethanol elimination in young adult rats appears to be mostly associated with the decrease in relative liver weight as the age of animals increases.

• 한국식품위생안전성학회지
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• 제11권4호
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• pp.291-297
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• 1996

The role of cytochrome P-450 2E1 (P450 2E1) in the early phase of alcoholic fatty liver was examined. Female rats were pretreated with either allyl sulfide (200 mg/kg, po), disulfiram (500 mg/kg, po), YH 439 (250 mg/kg, po) or pyrazine (200 mg/kg/day$\times$2 days, ip). Marked changes in carbon tetrachloride-induced hepatotoxicity and caboxyhemoglobin (COHb) elevation due to dichloromethane administration were observed in rats treated with one of the P450 2E1 modulators. A single dose of ethanol (6 g/kg, po) increased the hepatic triglyceride contents approximately 2 fold, which was inhibited completely by YH 439 pretreatment. However, the other P450 2E1 modulators failed to alter the ethanol-induced hepatic triglyceride accumulation. In vitro hepatic microsomal enzyme activity was determined in 4 week old premature and 12 week old adult rats. Aminopyrine-N demethylation was not different, but p-nitrophenol hydroxylation and p-nitroanisole O-demethylation were significantly higher in premature rats. However, no difference in the triglyceride accumulation induced by an intraperitoneal dose of ethanol (3 g/kg) was noted between premature and adult rats. The results suggest that the P450 2E1 activity dose not play an important role in the induction of acute alcoholic fatty liver.

• Molecules and Cells
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• 제37권12호
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• pp.865-872
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• 2014

Premature ovarian failure (POF) is a long-term adverse effect of chemotherapy treatment. However, current available treatment regimens are not optimal. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues, but the homing and restorative effects of BMSCs on chemotherapy injured ovaries are still not clear. In this study, we found that granulosa cell (GC) apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells (GCs) in vitro. Chemotherapy-induced POF was induced by intraperitoneal injection of cisplatin in rats. BMSCs labeled with enhanced green fluorescent protein (EGFP) were injected into the rats via the tail vein to investigate the homing and distribution of BMSCs in vivo. The number of BMSCs in the ovarian hilum and medulla was greater than in the cortex, but no BMSCs were found in the follicles and corpus lutea. In addition, the BMSCs treatment group's antral follicle count and estradiol levels increased after 30 days, compared with the POF group. Hence, our study demonstrates that intravenously delivered BMSCs can home to the ovaries, and restore its structure and function in POF model rats.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.439-444
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• 2000

Tricyclic antidepressant clomipramine or selective serotonin reuptake inhibitors (SSRIs) have been commonly used for the treatment of premature ejaculation. In the present study, we analyzed the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the medial preoptic area (MPOA) of the hypothalamus by awakening animal microdialysis following administration of clomipramine and various SSRIs. We then compared the serotonin metabolism and clinical effects of clomipramine and SSRIs on premature ejaculation. Basal extracellular serotonin level in the MPOA was higher than other brain regions and it was significantly increased by clomipramine and the SSRIs. The rank order of the concentration of serotonin at the MPOA was clomipramine, sertraline, paroxetine and fluoxetine and the concentrations of 5-HIAA was vice versa. The changes in serotonin concentration at the MPOA appeared closely associated with the clinical effects of these drugs on premature ejaculation. These results suggest that the serotonergic neuronal activity in the MPOA may have an selective inhibitory influence on ejaculation, and the effects of clomipramine and SSRIs on erectile function are mainly mediated by MPOA of the hypothalamus.

• Journal of Nutrition and Health
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• 제31권3호
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• pp.243-252
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• 1998

This study was conducted to investigated the short-term effects of early weaning and protein intake on organ and cell growth, nitrogen metabolism and physiological functions of rats. Five groups of early weaned rats separated from the dam on the 15th day postpartum were each given one five diets consisting of either one of the three levels of casein-low(8%), -normal (16%), and -high(32%), or a normal level (16%) of isolated soy protein(ISP) or egg yolk protein, for 7 days. The normal weaned rats were fed maternal breast milk for three weeks from birth. On the 22nd day postpartum , all the rats were sacrificed . The weight gain of the early weaned rats, especially the ones fed high protein, was observed to be significantly lower than that of the normal weaned rats. By the 15th day, of early weaning and especially in the ISP-fed rats, the total DNA contents of liver and kidney, which may be said to represent an index of cell numbers, significantly decreased, but their fresh and dry weight and protein/DNA ratio, allegedly representing an index of cell size, significantly increased , not affecting the cell number and cell size of brain. There were no differences in total serum protein and albumin concentrations between early and normal weaned rats. In the early weaned rats observed , the serum urea N and $\alpha$-amino N concentrations significantly increased in high protein-fed rats, and decreased in low protein-fed rats. Another observation was that no significant difference was noticed as regards to serum GOT activity, total bilirubin, uric acid, and creatinine concentration, which may represent indices of liver and kidney functions, among rat groups, GPT activity was an exception . These results suggest that premature weaning and the quality and quantity of dietary protein significantly affect organ and cell growth and nitrogen metabolism but does not seriously affect physiological functions in the neonatal development of rats.

• 한국동물학회지
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• 제19권1호
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• pp.7-14
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• 1976

본인은 생후 24일 된 쥐에 PMS와 더불어 estradiol을 처리하면 排卵이 예정보다 24시간 앞당겨 일어남을 보고한 바 있다. 본 실험은 이의 계속 연구로 腦下垂體前葉에서 분비되는 preovulatory LH surge가 PMS 처리 후 51$\\sim$56시간에 일어남을 보았다. 그러나 estradiol을 PMS와 동시에 처리하면 예정보다 24시간 단축된다. 卵巢를 제거한 쥐에 0, 24, 48시간에 $2.5\\sim 40\\mu g$의 estradiol을 처리하면 51$\\sim$56시간에 腦下垂體의 LH가 증가되지 않는다. 그러나 estradiol을 처리하고 이어 48시간에 1mg의 progesterone을 처리하면 卵巢를 제거한 쥐에서도 腦下垂體의 LH level은 증가된다. 본 실험의 결과로 estradiol처리가 PMS로 유도한 排卵을 24시간 앞당기는 사실은 estrogen이 progesterone과 길항작용으로 腦下垂體에서 LH분비를 24시간 앞당겨 일으키고, 따라서 排卵도 24시간 단축되는 것이라고 생각된다.

• 한국발생생물학회지:발생과생식
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• 제14권1호
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• pp.35-41
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• 2010

Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

• Journal of Nutrition and Health
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• 제30권1호
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• pp.3-11
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• 1997

This study was conducted to investigate the effects of protein levels and casein/whey ratios on organ growth and protein metabolism in early weaned rats. Premature rats weaned by the 17th day were fed six semipurified synthetic, isocaloric and gel diets that contained three levels (low, medium and high) and two different combinations(casein/whey ; 80 : 20 or 20 : 80) of milk protein for 8 days. On the 25th day postpartum, frest weigth and DNA, RNA and milk protein contents in brain, liver, kidney and muscle were determined to ascertain organ and cellular growth. Futher, with a view to ascertain protein metabolism and renal functions, serum total protein, $\alpha$-amino N, urea N, and creatinine and creatinine and urinary urea N, creatinine and hydroxproline were determined. Total DNA contents of brain, liver and kidney, which may represent as an index of cell numbers in those organs were significantly decreased in the rats fed diets containing low level protein regardless of casein/whey ratio. However, as fat as the rats fed high protein diets were concerned, their fresh weight, protein contents and GFR of kidney were significantly increased. Furthermore, nitrogen components, $\alpha$-amino N, urea N and creatinie in serum and urine were also increassed. Another observation was that high casein/whey ratio significantly facilitated accumulation of porteins in muscle and kidney and urinary hydorxyproline excretion, not affecting the DNA content of those organs. This study showed that low(8%) or high(32%) contents of protein had less desirable effects either on protein metabolism or on organ cellular growth in prematurely weaned rats, whereas there were no effects on general growth and bone strength.

• 대한소아치과학회지
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• 제7권1호
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• pp.75-83
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• 1980

Rickets is not the deposite of minerals in the skeletal tissue and the retardation of skeletal growth in growing in growing animals. This study was undertaken to investigate the histologic effects of experimental rickets on the dental structure of the albino rats, and to show the relationship between the histological effects and the pulpal disease which induced premature loss of the primary teeth. This study was based on material obtained from 40 white rats that were placed on a rachitogenic diet for a period 1 to 56 days after weaning (at 24 days). In addition, a study was made of 25 litter mates, 24 to 80 days, that were fed a normal diet. The following results were obtained: 1. Enamel formation and calcification showed no significant changes and no hypoplasia. 2. Dentin formation and calcification was retarded and disturbed. In the experimental group, predentin/calcified dentin was remarkablly increased. 3. Newly formed dentin showed interglobular texture (less homogenous calcification) and the predentin was significantly wider and thicker, and there was an irregular wave in the basal portion of the rat's incisors. 4. In cementum, Matrix formed at almost a normal rate but calcification was defective. So cementoid tissue was increasesd. 5. The formation of the alveolar bone was at almost a normal rate but calcification was retarded. The trabecular bone was filled with osteoid tissue and thicker than in normal groups.

• Clinical and Experimental Pediatrics
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• 제57권6호
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• pp.251-256
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• 2014

Severe intraventricular hemorrhaging (IVH) in premature infants and subsequent posthemorrhagic hydrocephalus (PHH) causes significant mortality and life-long neurological complications, including seizures, cerebral palsy, and developmental retardation. However, there are currently no effective therapies for neonatal IVH. The pathogenesis of PHH has been mainly explained by inflammation within the subarachnoid spaces due to the hemolysis of extravasated blood after IVH. Obliterative arachnoiditis, induced by inflammatory responses, impairs cerebrospinal fluid (CSF) resorption and subsequently leads to the development of PHH with ensuing brain damage. Increasing evidence has demonstrated potent immunomodulating abilities of mesenchymal stem cells (MSCs) in various brain injury models. Recent reports of MSC transplantation in an IVH model of newborn rats demonstrated that intraventricular transplantation of MSCs downregulated the inflammatory cytokines in CSF and attenuated progressive PHH. In addition, MSC transplantation mitigated the brain damages that ensue after IVH and PHH, including reactive gliosis, cell death, delayed myelination, and impaired behavioral functions. These findings suggest that MSCs are promising therapeutic agents for neuroprotection in preterm infants with severe IVH.