• Journal of Chest Surgery
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• v.42 no.1
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• pp.1-8
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• 2009

Background: The pathophysiology of acute respiratory distress syndrome with sepsis is acute lung injury (ALI) that's' caused by endotoxin (LPS). We evaluate effects of moxifloxacin on LPS-induced ALI in a rat model. Material and Method: The rats were divided into 3 groups as the control group (C), the LPS insult group (L), and the LPS+moxifloxacin treated group (L-M). ALI was induced by endotracheal instillation of E.coli LPS, then moxifloxacin was given in 30 minutes. Five hours later, we checked the lung weight/body weight ratio(the L/BW ratio), the protein & neutrophils in the bronchoalveolar lavage fluid (BALF), the myeloperoxidase (MPO) activity & the malondialdehyde (MDA) content, the expressions of cytosolic and secretory phospholipase $A_2$ (c, $sPLA_2$), and the morphology of the lung with using a light microscope. Result: The L/BW ratio, the protein content and the neutrophil count in the BALF, and the MPO activity and the MDA content in lung were significantly increased in group L compared to group C, and these factors were markedly decreased in group L-M compare to group L. The $cPLA_2$ expression and the $sPLA_2$ expression were increased in group L and the $cPLA_2$ expression was decreased in group L-M. Yet the $sPLA_2$ expression was not changed in group L-M. Morphologically, many inflammatory findings were observed in group L, but not in group L-M. Conclusion: Many of the inflammatory changes of ALI that were caused by LPS insult were ameliorated by moxifloxacin treatment.

• Development and Reproduction
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• v.15 no.2
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• pp.179-185
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• 2011

Some phytoestrogens in soy and red wine, for example, might have beneficiary rather than adverse effects. In particular, dietary soy intake seems to be highly correlated with protection of breast cancer, osteoporosis and cardiovascular disorders. However, questions persist on the potential adverse effects of the main soy constituent genistein (GS) on female reproductive physiology. Previously we found that prepubertal exposure to GS could activate the reproductive system of immature female rats leading to precocious puberty onset, and intracerebroventricularly (ICV) injected GS could directly activate hypothalamic kisspeptin-GnRH neuronal circuits in adult female rats. The present study was performed to examine the hypothalamus-specific GS effects in prepubertal female rats and which subtype of estrogen receptor is mediated in this GS effect. Prepubertal female rats (PND 30) were anaesthetized, treated with single dose of GS (3.4 ${\mu}g$/animal), and sacrificed at 2 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 lowered the transcriptional activities of mTOR (1:$0.361{\pm}0.058$ AU, p<0.001) but increased that of GAD67 (1:$1.285{\pm}0.099$ AU, p<0.05), which are known to act as an upstream modulator of kisspeptin and GnRH neuronal activities in the hypothalamus, respectively. GS administration enhanced significantly the mRNA levels of KiSS-1(1:$1.458{\pm}0.078$ AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1:$1.29{\pm}0.08$ AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1:$0.379{\pm}0.196$ AU, p<0.05). There was no difference in the mRNA level of $ER{\alpha}$ in the GS-treated group compare to control group (1:$1.180{\pm}0.390$ AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of $ER{\beta}$ (1:$4.209{\pm}0.796$ AU, p<0.01, Fig. 3B). Taken together, the present study indicated that the acute exposure to GS could directly alter the hypothalamic GnRH modulating system in prepubertal female rats. Our study strongly suggested the involvement of $ER{\beta}$ pathway in GS's hypothalamus-specific action, and this idea is consistent with the GS's well-known $ER{\beta}$-mediated protective action in breast cancer.

• Development and Reproduction
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• v.14 no.4
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• pp.297-306
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• 2010

Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease testicular function by causing apoptosis in the testis, but this mechanism is not fully understood. Thus, in this study we examined whether TBT induces adipogenesis of the Leydig cells to find out the correlation between adipogenesis and apoptosis in the testis. Three week old SD male rats were orally administrated with sesame oil, 1 mg/kg of TBT, or 10 mg/kg of TBT daily for 1 week and weighed after administration. The testes obtained on day 8 were weighed and stained with BODIPY and TUNEL kit. Using total RNA extracted from the isolated Leydig cells, adipogenesis and apoptosis-related genes were analyzed by real-time PCR. The testicular weights of the rats treated with 10 mg/kg TBT were significantly decreased compared to those in the control rats treated with sesame oil. As a result of BODIPY staining, the number of Leydig cells stained with BODIPY was increased in the rats treated with 10 mg/kg TBT compared with the control rats. Similar to BODIPY staining results, the TUNEL assay showed that the apoptosis of Leydig cells was increased in TBT treated rats. The results of the gene expression analysis in the Leydig cells showed that the expression of adipogenesis-related genes (PPAR${\gamma}$, aP2, Perilipin, CD36) and apoptosis-related genes (TNFRSF1A, TNFSF10) was increased after TBT administration. The present study demonstrates that TBT induces the expression of adipogenesis-related and apoptosis-related genes in the Leydig cells leading to adipogenesis and apoptosis in the testes. These results suggest that the dysfunction of Leydig cells by TBT exposure may cause a loss in testicular function.

• Development and Reproduction
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• v.14 no.4
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• pp.281-286
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• 2010

Recent evidence has revealed that the intratesticular injection of hypertonic saline(20%) resulted in a chemically castrated state such as nadir testosterone levels in rats. To confirm the efficacy of this simple saline-injection method further, we investigated the changes in the gross and microscopic anatomy of testis. Our study comprised three groups; intact(control) group, orchidectomy group and saline-injection (experimental) group. Single dose of hypertonic saline (sterilized, $750{\mu}{\ell}/testis$) were directly administered into both testis of adult rats (about 300 g BW). Bilateral orchidectomy was performed at the same day of saline injection. Following 30 days post-injection, reproductive tissues were surgically removed, weighed and fixed for histological examination. The body weights were not changed in both orchidectomy group and saline-injection group when compared to those in intact group. The wet weights of testis were significantly decreased in saline-injection group when compared to those in intact group. The wet weights of epididymis and seminal vesicle and prostate were significantly decreased in orchidectomy group and saline-injection group when compared to those in intact group. Macroscopically, the testes exerted slight atrophy and the tunica albuginea seemed to be intact in saline injection group. Histologically, however, larger parts of testicular tissue underwent necrosis and were barely recognizable after hematoxylin-eosin staining. In the same section, only the opposite part of the injection site was stained showing abnormal state of cell layers mostly fibrosis and infiltrated leukocytes. Sloughing of immature germ cells from the basement membrane along with shedding cells in the intraluminal space was notable in most seminiferous tubules from the saline injected testis. The present study confirmed that the direct injection of hypertonic saline into testis can induce a castration-like, testosterone-depriving effects on accessory sex organs. Our findings suggest that the efficacy of this less expensive and minimally invasive method seems to be almost even with that of conventional orchidectomy and chemical castration, though more in-depth evaluation should be supported.

• Applied Biological Chemistry
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• v.44 no.3
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• pp.148-152
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• 2001

This study investigated the role of excitatory amino acid systems in the initiation of organophosphate-induced seizures and brain damages in rats through quantitative in vivo microdialysis. Microdialysates were collected from the hippocampus of rat brain, treated with diisopropylfluorophosphate (DFP; 2.67 mg/kg, s.c.) alone, and/or atropine sulfate (15 mg/kg, i.m.) and procyclidine (30 mg/kg, i.m.). The protective effects of atropine, a muscarinic blocker, and/or procyclidine, a N-methyl-D-aspartate and cholinergic antagonist, against DFP were examined. DFP treatment increased the levels of aspartate (Asp) and glutamate (Glu) significantly in the hippocampal persuate with the induction of seizures. Treatment of procyclidine could effectively block the increase of Asp and Glu levels. Atropine treatment showed no significant anticonvulsive effects against DFP-induced seizures. The increases of Asp and Glu levels by DFP were also completely blocked through the combined treatment of atropine and procyclidine. Histopathological findings on the hippocampus confirmed the above results. More effective protection was observed through the treatments of procyclidine alone or of both procyclidine and atropine than atropine alone against DFP-induced brain damage. Procyclidine was shown to be effective in DFP-induced seizures.

• Applied Microscopy
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• v.35 no.1
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• pp.31-39
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• 2005

Synapses are contact points where one neuron communicates with another. The morphological change of synapses under various physiological or pathological conditions has long been hypothesized to modify their functional properties. 3-dimensional (3-D) reconstruction of synapses with serial ultrathin sections has contributed to the understanding of ultrastructural dimensions and compositions of synapses. The 3-D reconstruction procedures, however, require a great amount of expertise as well as include prohibitively timeconsuming processes. Here, we introduce efficient 3-D reconstruction technique using high-voltage electron microscopy (HVEM). Primarily, we established an optimal section thickness and staining condition to observe synaptic structures in detail under HVEM. The result showed that synaptic profiles were preserved at the section thickness of 250 nm without the overlapping of synaptic ultrastructures. An increase in the reaction time of en bloc staining was most efficient to enhance contrast than the extension of postembedding staining or the addition of uranyl acetate during dehydration. Then, 3-D reconstruction of parallel fiber-Purkinje cell synapses in the rat cerebellum was carried out with serial HVEM images and reconstruction software. The images were aligned and the contours of synapses were outlined on each section. 3-D synapses were finally extracted from the section files by grouping all the synaptic contours. The reconstructed synapse model clearly demonstrated the configuration of pre and postsynaptic components. These results suggest that 3-D reconstruction of synapses using HVEM is much efficient and suitable for massive quantitative studies on synaptic connectivity than conventional TEM approach using numerous ultrathin sections.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.47-62
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• 1981

d-amphetamine이 사람에서 paranoid schizophrenia와 아주 유사한 model psychosis를 일으키며 또한 사람과 실험동물에서 실제 정신분열증에서 뚜렷이 관찰되는 behavioral perservation을 일으킬 수 있음이 관찰되었다. 이에 많은 학자들은 이러한 양상의 행동변화가 정신분열증의 원인 추구에 중요한 의미를 주는 뇌변화를 반영할지도 모른다는 생각에 많은 연구를 거듭하여 왔다. 지금까지는 주로 catecholamine기전에 대하여 집중적 연구가 수행되어져 왔으나 최근에는 d-amphetamine의 약리기전의 일부는 5-HT기전이 차지하고 있으며, 여러 행동변화에는 catecholaimin 보다 5-HT 가 더 중요하게 관계하고 있다는 주장이 나오고 있다. 또한 d-amphetamine은 시험관내에서 MAO 특히 신경전달물질 분해요소인 A type를 가역적으로 억제할 수 있음이 보고되어 많은 흥미를 끌어왔으나 생체내에서의 억제여부는 직접적으로 확인이 되고 있지 않다. 그러나 최근에 Braestrup(1977)과 El Hait(1978)등은 간접적인 방법으로 생체내에서도 억제시킬 수 있음을 보고하고 있다. 이에 저자는 d-amphetamine에 의해 야기되는 행동변화와 그 밑바탕을 이루는 생화학적 기전에 5-HT가 차지하는 역할을 알아보기 위해서 다음의 실험을 시행하였다. 첫째, d-amphetamine의 급성, 만성 투여가 5-HT의 5-HIAA 로의 turnover와 MAO활성도에 어떤 영향을 미치며, 더 나아가서 이 양자사이에 어느 정도 상관관계가 있는지를 알아보기 위해서 d-amphetamine을 투여한 후 시간 경과에 따라서 뇌내 5-HT, 5-HIAA, 5-HT turnover rate와 MAO 활성도를 측정하였다. 둘째, d-amphetamine, 5-HT 합성을 증가시키는 약물과 합성을 억제시키는 약물을 투여하고, 위의 생화학적 실험과 행동관찰을 병합 실시하여 비교분석하였다. 그 결과는 다음과 같다. 1) d-amphetamine (6 mg/kg)을 급성투여시, 뇌내 5-HT함량이 투여 1시간 후에 최고로(대조치의 123%, p<0.001) 증가되다가 이후 감소하며, 5-HIAA 함량은 처음 15분부터 감소하기 시작하다가 30분에 최저로 떨어지며(대조치의 78%, p<0.005) 이후 증가하여 24시간째는 약간 대조치 이상으로 회복되었다. 미토콘드리아 MAO활성도는 1시간째에 최저로 떨어지다가(대조치의 89%, p<0.05)이후 회복하기 시작하여 24시간째에 약간 대조치 이상으로 회복되었다. 5-HT의 turnover rate는 MAO활성도 변화와 거의 같은 변화를 보였다. 2) 만성투여시 (하루 2번, 14일간 투여)는 5-HT 함량, 5-HIAA 함량, MAO 활성도 및 5-HT turnover rate 모두가 중등도로 감소되었다. (각각 대조치의 87%, 69%, 80%, 79%). 3) MAO 활성도와 5-HT turnover rate 사이에는 높은 상관관계가 있었다. (r=0.866, p<0.001, N=94). 4) MAO 활성도의 역동학 실험에서는 대조치에 비해 투여군에서 Km 값은 의미가 있는 증가가 있었으나 $V_{max}$값은 큰 변동이 없었다. 5) d-amphetamine을 급성 투여할때는 sleeping과 lying components는 상당한 감소를 보인 반면, locomotor activity 는 1시간까지는 상당한 증가를 보였으며 용량이 적을수록 더 큰 증가가 있었다. 반면 stereotypy는 1시간까지 용량이 증가할수록 더 큰 증가가 나타나서 locomotor activity에서 stereotypy 의 증가로 이행을 나타내었다. 만성 투여시는 locomotor activity는 점차적인 감소를 보였으나 stereotypy는 점차적인 증가가 나타나서 14일쯤에는 평형에 도달하였다. 6) PCPA 단독 투여군(400 mg/kg, 3번)에 있어서는 5-HT와 5-HIAA 함량의 상당한 감소가 나타났으나 MAO 활성도와 행동에는 큰 변화를 나타내지 않았다. PCPA전 처치군에 있어서도 5-HT와 5-HIAA 함량은 마찬가지로 상당한 감소를 나타내었으나 gnawing, sniffing과 locomotor activity는 더 증가를, stereotyped head weaving, forepaw treading과 hindlimb abduction은 상당한 감소를 나타내었다. 7) L-tryptophan(100 mg/kg)단독 투여시는 5-HT 함량은 약간 증가를 나타내었으나 5-HIAA 함량은 상당한 증가를 보였다. MAO활성도나 행동은 큰 변화없었다. L-tryptophan 전처치군에 있어서는 5-HT 함량은 더 큰 증가를 보였으나, 5-HIaa 함량은 MAO 활성도는 별 변화없었으며 stereotypedlateral head waving, forepaw treading 과 hindlimb abduction은 증가를, locomotor activity, gnawing과 sniffing components는 감소를 나타내었다. 8) d-amphetamine 단독투여, 혹은 L-tryptophan 전처치, PCPA 전처치후 측정한 5-HT 함량과 stereotyped head weaving, forepaw treading, hinilimb abduction components 사이에는 높은 상관관계가 있었다(r=0.789, p<0.001). 반면 5-HT 함량과 locomotor activity, stereotyped gnawing과 sniffing components 사이에는 약한 음성의 상관관계가 있었다. (r=0.554, p <0.005). 이상의 결과로 미루어 볼때 5-HT의 5-HIAA 로의 turnover rate 는 주로 MAO 활성도에 의해서 조절되며 5-HT 기전이 d-amphetamine에 의해서 야기된 여러 행동변화 중 상당한 부분에서 중요한 역할을 하리라고 생각된다.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.43-54
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• 1982

Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.

• Journal of the Korean Society of Food Culture
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• v.17 no.4
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• pp.456-464
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• 2002

This study was designed to investigates the effects of Korean pueraris radix water extract in Cd(cadmium) administered rats. Forty male Sprague-Dawley rats weighing $100{\pm}10g$ were used for this experiment and divided into following 4 groups; control group, 3% pueraria radix in water extract group, 50 ppm Cd group, 50ppm Cd group with 3% pueraria radix in water extract group. The Cd administered rats were given 50 ppm of $CdCl_2\;{\cdot}\;2H_2O$ disolved in the distilled water. The Cd content in the rats tissue of Cd administered group was lower than in the rats tissue of Cd group with 3% pueraria radix in water extract group. Plasma levels of renin activity was increased by Cd administration group, compared with 3% pueraria radix in water extract group and Cd administred group. Glutamate oxaloacetate transaminase(GOT) and Glutamate pyruvate transaminase(GPT) were increased in Cd-administered group and lower in the 3% extracts of pueraria radix in water extract group. Lactate dehydrogenase(LDHase) was lower in the 3% extracts of pueraria radix-Cd group than in the Cd group. This results suggested that pueraria radix in water extract group, has a lowering effects on the accumulation of Cd and it is belived that the pueraria radix in water extract group has some protective effects to Cd administered in rats, but the mechanism of these effects was obscure.

• Journal of Food Hygiene and Safety
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• v.31 no.2
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• pp.113-118
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• 2016

Proprotein convertase subtilisin/kexin type 9 (PCSK9), is a protein mainly secreted by a liver. The PCSK9 plays an important role in low density lipoprotein (LDL) metabolism acting as a repressor of LDL receptor through transportation of the LDLR to the lysosome for degradation. Thus, the PCSK9 inhibitor suppresses PCSK9-regulated degradation of the LDL receptor as a LDL-lowering medicine. However, little is known about the role of PCSK9 in the reproductive system. Therefore, in the present study, we investigated Pcsk9 expression in male reproductive tracts including penises, prostates and testes using rats in response to their diets between a normal diet and a high-fat diet with cholesterol. Based on our previous study, the high-fat diet elevates concentration of total cholesterol and LDL in serum whereas it reduces the concentration of plasma high density lipoprotein (HDL). In addition, it dramatically affects to morphological changes of the male reproductive organs. Consistent with these results, the expression of Pcsk9 was substantially decreased in the penile tissues (P < 0.001) from rats fed a high fat diet as compared to a normal diet. Moreover, it slightly reduced in the prostate and testes (P < 0.05) of rats in response to a high fat diet. Localization of Pcsk9 was predominantly detected in urethral epithelium of penises, cylinder-shaped cells of prostate glands, and spermatogonia, spermatocytes and spermatid of testes of rats. Collectively, results of current study provide invaluable insights into the Pcsk9 gene with respect to its tissue- and cell-specific expression by a high fat diet with cholesterol.