Our previous research has identified granulin (grn) and p130 genes as sex steroid-inducible genes in the rat hypothalamus, which might be involved in sexual differentiation of the brain. Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to di-n-butyl phthalate (DBP), diisononyl phthalate (DINP) and di-2-ethylhexyl adipate (DEHA) affects hypothalamic sex steroid-inducible genes. The present study assessed the effects of perinatal exposure to DBP, DINP and DEHA on sex steroid hormones levels and hypothalamic gm and p130 mRNA expressions at postnatal day (PND) 3 and 7. Pregnant rats were fed a soy-free diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to GD 3 or 7. At PND 3 and 7, perinatal exposure to these chemicals did not substantially affect serum concentrations of testosterone and estradiol. At PND 3, the expression of grn mRNA levels in males was decreased by DEHA, and that of p130 was decreased by DBP, DINP and DEHA, though the effects were not dose-dependent. At PND 7, the expression of gm gene in female pups was increased by higher doses of DBP and all the doses, except for 4,000 ppm, of DINP, while that in male pups decreased by 480 and 12,000 ppm of DEHA. Hypothalamic expression of p130 mRNA in males was increased by lower doses of DBP and all the doses of DINP, whereas that of females was decreased by 480 and 2,400 ppm of DEHA. These results suggest that these chemicals may affect the expression of gm and p130 genes by directly acting on the hypothalamus, thus leading to inappropriate expression of these genes.
This experiment was performed to study the morphological responses of the epidermis of the rat scalp, following X-ray irradiation. Male rats were divided into normal and experimental groups. Rats anesthetized with sodium thiopental, were exposed only on their head areas with a single dose of 3,000rads or 6,000rads, respectively. Radiation was produced by Mitsubishi Linea Accelerator ML-4MV at the speed of 200rads/min. The target distance was 80cm. Animals were sacrificed on six hours, two days and six days following irradiation. By the perfusion fixation through the heart, rats were fixed with 1% glutaraldehyde-1% paraformaldehyde solution. Pieces of the tissue taken from the scalp were refixed in 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide, and embedded within araldite mixture. The sections were cut on a LKB-V ultratome, stained with uranyl acetate and lead citrate, and were observed with JEM 100CX-II electron microscope. The results were as follow; 1. Six hours after exposure to 3,000rads of X-ray. Disrupted intercellular spaces, within which some amorphous materials were filled, disrupted mitochondria, and vacuoles in the keratinocytes were frequently observed, but six days after exposure to 3,000rads of X-ray, Morphology of the keratinocytes was generally restored. 2. Many of the morphological changes were seen on the six days after exposure to 6,000rads of X-ray. 3. Widened intercellular spaces and thickened dense plaques of the desmosomes were frequently observed after exposure to 6,000rads of X-ray. 4. In the experimental groups, the Langerhans and the Merkel cells were damaged, similarly to the keratinocyte. Above results suggest that head irradiation with the dose of 3,000rads temporarily damaged the epidermis of the scalp, though most of the structures recover within six days, whereas with the dose of 6,000rads it severely damaged the epidermis without showing any recovering tendency.
Kim, Jun-Soo;Park, Jin-Uk;Choi, Seok-Hwa;Kim, Gon-Hyung
Journal of Veterinary Clinics
/
v.27
no.3
/
pp.240-245
/
2010
Osteonecrosis of the femoral head is an idiopathic and progressive disease. It was reported that several animal models have been used for the research of osteonecrosis. However, no standardized animal model for the study of osteonecrosis has been developed to date. This study was conducted to compare the degree of osteonecrosis of three surgically induced osteonecrosis models in rats. Twenty Sprague-Dawley rats (24 weeks old, male) were divided into three experimental groups and a control group, five heads each. Three groups were surgically induced into osteonecrosis; the ligamentum teres were cut and the periosteum of the femoral neck was stripped (Group S), the steel wire was ligated to the neck of the femoral head (Group W), and the femoral neck was tied up with a wire in the same way as in the W group, and burned by attaching the electrode tip to the wire and then the wire was removed (Group B). After two weeks, rats were sacrificed and the femoral head and neck were collected. Histological findings were evaluated with H/E stains, Safranin-O and TUNEL for osteonecrotic lesions in the bones and cartilages of the femoral head. Osteonecrosis was induced successfully in all groups (Group S, W and B) in two weeks, a short period of time. Significant necrotic changes of the cartilage were detected only in Group B. In the modified cautery model in particular, the method of removing the wire after cautery was completed in the experimental model of osteonecrosis more efficiently than any other method.
Bisphenol A, an everywhere chemical, is applied as a plasticizer in polycarbonate plastics, which often used in our everyday products and in epoxy resins as protective coatings and linings for food and beverage cans for decades. Human exposure to BPA may lead to adverse effects by interfering with oestrogen receptors. Our present study was conducted to investigate the protective effects of selenium (Se) and vitamin E (Vit E) on BPA-induced damage in the liver of male rats. Animals were randomly divided into four groups: the first group received olive oil and served as control. The second group received both (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet). The third one treated orally by (10 mg/kg b.w.) of BPA. The last group received (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet) concomitantly with (10 mg/kg b.w.) BPA. Exposure to BPA for three weeks engendered a hepatic disorder. An increased AST and ALT enzymatic activity was noticed in BPA-treated group as compared to other groups. Furthermore, a change in glucose, cholesterol, LDL-C, HDL-C, albumin, and bilirubin level was remarkable. Moreover, exposure to BPA increased malondialdehyde levels while reduced gluthatione content was decreased in the liver homogenate. A decrease in glutathione peroxidase, glutathione s-transferase and catalase activities was observed in the same group. Administration of selenium and vitamin E through the diet in BPA treated rats ameliorated the biochemical parameters cited above. In addition, an improvement in activities of liver enzymes was recorded. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between BPA-induced hepatotoxicity and its alleviation by natural antioxidants like selenium and vitamin E.
Kim, Sung-Sik;Byeon, Jun-Hee;Yoo, Gyeol;Han, Ki-Taik
Archives of Plastic Surgery
/
v.32
no.1
/
pp.12-18
/
2005
The Transverse rectus abdominis musculocutaneous (TRAM) flap has been commonly used for autologous breast reconstruction. Despite these clinical usefulness, the TRAM flap is prone to partial flap or fat necrosis in especially pedicled flap. To improve flap survival, the surgical delay procedures and pharmacological treatments have been developed. In many studies for the pharmacological treatment, Lipo-$PGE_1$ has demonstrated a marked ability to improve flap survival and it's effect has been proved similar to surgical delay procedure. The purpose of this study is to determine the most effective route of Lipo-$PGE_1$ administration as a pharmacological treatment in TRAM flap of the rat. Fifty male Sprague-Dawley rats weighing 300-350 gm were divided into five groups, One week before flap elevation, Lipo-$PGE_1$($2{\mu}g/kg$) was injected three times in a week and than the left inferior epigastric vessel based TRAM flap ($5.0{\times}3.0cm$) elevated; group I: no procedure before flap elevation; group II: intraperitoneal injection; group III: intravenous injection; group IV: subcutaneous injection; group V: topical application. A flap was assessed at postoperative 7 days by comparison of flap survival rate, vessel counts(H-E stain), and vascular endothelial growth factor(VEGF) protein expressed by Western blot. The results demonstrated that the mean percentages of the flap survival area in group III were significantly higher than that of any other group(p<0.05). The vessel counts of all experimental groups were statistically higher than that of control group(p<0.05). Only in group III, the VEGF protein expression was increased significantly than control group and there are no difference in other experimental groups. In conclusion, the intravenous administration of the Lipo-$PGE_1$ is the most effective on flap survival, and the VEGF induced by Lipo-$PGE_1$ has some positive effects on new vessel formation and flap survival.
Alcoholism and alcohol abuse are major public health concerns. This is linked to the injury of many organs, especially liver. Experiments were peformed to know the acute effects of LeeKwaDoo (LKD) induced by two-third partial hepatectomy (PH) in rats. In liver samples, regeneration parameters and histological assessment were performed. For the blood biochemical study, the blood were assayed with AST, ALT. The portal branch of liver lobes was ligated in the male Sprague-Dowley rats, two-thirds partial hepatectomies were also performed. It was estimated bodyweight and relative liver weight for the index of liver mass. For the marker of blood chemistry, we investigate the serum sample of rats and demonstrated the level of AST, ALT. Remaining tissues of liver developed as microscopic structures. Resection of the lobes in PH+LKD group resulted in a marked change of liver weight, blood chemistry and histological changes. The initiation of the proliferative response in PH group stimulated as well as reduction of the liver mass. On the other hands, the Initiation of the proliferative response in PH+LKD group delayed. Eventually, both PH group and PH+LKD group was restored relative liver weigh after 7 day. In conclusion, the acute adminstration of LKD seems to inhibit the initial response of liver regeneration through alcohol effects.
This study was designed to investigate the optimal period of pedicles implantation in the prefabricated periosteofascial flap with a vascular tissue transfer. The flap prefabrication was prepared with a transposition of left occipital pedicles on the calvarial fascia of male Sprague-Dawley rats. Thirty flaps were divided into five groups of six flaps, including control group (group I) of the conventional periosteofascial flap based on the lateral border of the rat calvarium. The prefabricated flap was elevated as an $1{\times}1cm$ sized island flap based on the implanted pedicle at 1, 2, 3, and 4 weeks after the pedicles transfer in groups II, III, IV, and V, respectively. After the completion of creating a critical-sized calvarial defect and implanting with hydroxyapatite granules, the flap was sutured back for covering the defect and kept isolated from surrounding tissues. Six weeks after flap repositioning, the osseous changes of the defect were examined with simple radiographic findings, radiodensitometric analysis, and histological studies. By simple radiographic findings, specimens of the control, groups IV and V showed homogeneous radioopacity within the defect. But in groups II and III, focal radiolucency was observed in the defect. In the radiodensitometric analysis, the control group and the group V showed significant increased radiodensites statistically. Histologically, the implanted hydroxyapatite was absorbed partly in the defect in groups II, III, and IV. In the defects of the control group and the group V, the implanted hydroxyapatite was kept in its volume and the deposition of the bone cells was observed sparsely. In conclusion, the prefabricated periosteofascial flap can be created with a vascular tissue transfer and the pedicles should be implanted at least for 4 weeks to bring out positive osseous changes in the calvarial defect.
Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.
The disposition of Brazilin including plasma concentration-time profiles, excretions via urine and bile, and plasma protein binding was investigated after intravenous or oral administration of radio labeled Brazilin ($^3H-Brazilin$) to male Wistar rats. The main pharmac:okinetic parameters were as follows; $t\;_{ 1/2}$, 13.71 hr; AUC, $53.38\;\mu\textrm{g}{\cdot}hr/ml$; AUMC, $1013.4I\;\mu\textrm{g}{\cdot}hr^2/ml$, MRT, 18.95 hr; Vss, 17778 mllkg and CL, 936.77 ml/hr.kg. The 2nd peak was found in the plasma concentration-time profiles indicating potential enterohepatic circulation. The enterohepatic circulation was supported by the bile excretion. After oral administration, about 64.4 % of administered radioactivity was excreted into the bile within 10 hours and its excretion rate reached maximum at 3 hours after administration. The Vss was extremely high, 17.8 l/kg indicating distribution of brazilin in most organs (tissues) with high concentration of brazilin in some organs. Brazilin was distributed into most of organs (spleen, adrenal, pancreas, kidney, thymus, lung, heart, liver, prostate, epididymus, testis, fat, muscle and done) except brain. High concentration of Brazilin was detected especially in liver, kidney, epididymus and testis. Approximately, 62.9% and 44.1% of the dose was excreted for intravenous and oral administration, respectively. About 80% of the dose eventually excreted into urine was excreted within 24 hr after dosing. Plasma protein binding of brazilin resulted in $40\;{\pm}\;4%$ by ultrafiltration method.
The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic ${\alpha}$-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, $10.0{\mu}g/kg$ BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of $10.0{\mu}g/kg$ body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p < 0.05). Although there was no statistically significant, the ${\alpha}$-amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down-regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.
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