To help the interpretation of causes of death, it is critical that the background incidence of factors contributing to death be recorded and archived. Information was gathered from the control groups of 19 rat carcinogenicity studies. All cases of death occurring within the 2-year period were reviewed. Out of 1124 males and 1084 females, 720 male (64.1%) and 689 female (63.6%) decedents were recorded. There was no difference in the probability of survival between two sexes. Analysis of factors contributing to death revealed that 400 males (48.7%) had neoplastic changes, 189 males (23.0%) had non-neoplastic lesions, and 232 males (28.3%) died from unknown causes.

The therapeutic efficacy of xylamine in the field of psychological medicine has been recognized for years and the drug is used to treat depression and some other conditions, but little is known about its mechanism of action on vascular system. Therefore, the present study was designed to investigate the influence of xylamine on the contractile responses of isolated rat thoracic arteries to phenylephrine(PE) and potassium chloride(KCl). Xylamine produced a concentration-dependent relaxation in PE-precontracted endothelium intact(+E) rat aortic rings, but not in a KCl-precontracted aortic rings.

This study investigated the potential effects of amitraz on the pre- and postnatal development, behavior, and reproductive performance of offspring of parent rats given amitraz during pre-mating, gestation, and lactation. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and lactation up to weaning. Based on fluid consumption, the male rats received an average of 0, 5.7 ± 1.33, 13.2 ± 2.08, and 35.8 ± 3.42 mg/kg/day amitraz, and the female rats received an average of 0, 8.7 ± 4.42, 20.1 ± 9.60, and 47.6 ± 22.38 mg/kg/day amitraz, respectively. At 360 ppm, an increase in the incidence of abnormal clinical signs, a suppression in the body weight gain, a decrease in the food consumption and litter size, an increase in the post-implantation loss, and a decrease in the seminal vesicle weight were observed in the parent animals. In addition, a suppression in the body weight gain, a decrease in the grip strength, a delay in the negative geotaxis, an increase in the pre- and post-implantation loss, and a decrease in the number of live embryos were observed in the offspring. At 120 ppm, suppressed body weight gain and reduced food consumption were observed in the parent rats. Suppressed body weight gain and decreased grip strength were also observed in the offspring. There were no signs of either reproductive or developmental toxicity at 40 ppm. Under these experimental conditions, the no-observed-adverse-effect level of amitraz for parent rats and their offspring was estimated to be 40 ppm in rats.

We have studied, by a nonisotopic in situ end-laveling(ISEL) technique, frequency of apoptosis in the external granular layer(EGL) of the cerebellum of immature mice by Y-rays irradiation from 60Co or diagnostic ultrasound exposure. The total number of normal cells and cells showing morphological features of apoptosis were counted. The frequency of apoptotic cells was expressed as a percentage of the total number of cells in EGL. The extent of changes following 200 cGy(1090 cGy/min) was studied at 2, 4, 6, 8, 12, or 24 hours after exposure. The maximal frequency was found 6~8 hours after exposure. The immature mice that received 18, 36, 54, 108, 198, 396, cGY of y-rays or diagnostic ultrasound(7.5MHz, 4.2mW, Ispta=7.9mW/cm2, Ispta=114.3W/cm2) for 10 or 30 minutes were examined 6 hours after irradiation. Measurements performed after y-ray irradiation showed a dose-related increase in apoptotic cells in each of the mice studied. The dose-response curves were analyzed by a linear-quadratic model;frequency of apoptotic cell in the EGL was y=(0.1349+_0.01175)D+(-0.0001522+_0.0000334)D2+0.048(r2=0.981, D-dose in cGy). In the experiment of ultrasound exposure, the frequency of apoptotic cell was 0.106+_0.130(10 minutes exposure) and 0.167+_0.220(30 minutes exposure). We estimated the relative dose of the yield from the experiment with ultrasound by substituting the yield from ultrasound exposure into the curve from the y-irradiation. The relative dose of ultrasound exposure compared with y-irradiation were 0.432 cGY(10 minutes exposure) and 0.885 cGY(30 minutes exposure). We have found that there is no evidence to indicate that diagnostic ultrasound involves a significant risk.

In order to study the effects of Jengjengamiyjintang on the duodenal ulcer induced by HCI-aspirin in rats, the changes of histological profiles, goblet cells(PAS-positive cells), and the distribution and frequency of cholecystokinin(CCK)-8 and serotonin-producing gastro-entero-endocrine cells were observed after oral administration of Jengjengamiyjintang. Histologically, very severe injury to duodenal epithelium were observed in control groups and theses injuries were increased with time intervals. But in the Jengjengamiyjintang administrated groups, no gross lesion of ulcer were demonstrated and histologically minor injury to the mucosal epithelium were observed. PAS-positive cells were increased in the Jengjengamiyjintang administrated groups compared to that of control groups. Severe degranulation of CCK-8- and serotonin-immunoreactive cells were observed in control groups but these phenomenon was seldom in the Jengjengamiyjintang administrated groups. Serotonin-immunoreactive cells were significantly decreased in control groups but increased in Jengjengamiyjintang administrated groups compared with control groups. According to these result, it is suggested that Jengjengamiyjintang would accelarat the healing of the duodenal ulcer but the functional mechanisms were unknown.

The insulin-like growth factor-I(IGF-I) is an important metabolic factor involved in cell growth and metabolism. Although secretion of IGF-I in rat liver is regulated by growth hormone, the effects of forskolin, adenylate cyclase activator, on secretion of IGF-I have not been reported. Therefore, a modified perfused rat liver model was used to investigate the regulatory effects of forskolin on IGF-I secretion in this experiment. The results were summerized as follows: 1. Modified perfused rat liver model was not changed to aspartate aminotransferase(AST), alanine aminotransferase(ALT) and lactic dehydrogenase(LDH) secretion in time. 2. The IGF-I secretion in hepatic cell was increased by forskolin(10-5, 10-6 and 10-7M) in a dose-dependent manner as compared with those of the controls, and significantly increased by 10-5 and 10-6M forskolin(p0.05). 3. Secretion of glucose in hepatic cell significantly was decreased by 10-5M forskolin as compared with those of controls(p0.05). These results suggest that forskolin may be involved in the regulation of IGF-I secretion in the perfused rat liver.

This study was carried out to compare the distribution pattern of the bombesin immunoreactive neurons of the hypothalamic nucleus in the rat and Mongolian gerbil. The bombesin immunoreactive neurons in the rat were located in the dorsal part of the dorsomedial hypothalamic nucleus, but in the Mongolian gerbil inthe compact part of dorsomedial hypothalamic nucleus. From this results, we could get an evidence that there were some differences in the distrbution of peptidebetween rat and Mongolian gerbil.

Ischemic preconditioning (IPC), i.e., a preliminary brief episode of ischemia and reperfusion, has been shown to reduce the cell damage induced by long ischemia and reperfusion. Superoxide radical which is produced during reperfusion after ischemia was recongnized as a factor of the ischemic injury and it is dismutated into H2O2 and O2 by two types of intracellular superoxide dismutase (SOD), Cu,Zn-SOD in cytoplasm and Mn-SOD in mitochondria. Recently oxygen free radicals are suggested to induce the apoptosis, however mechanism of the reduced apoptosis by ischemic precondition was unknown, while many studies performed in mammalian heart indicated that ATP-sensitive K+(K atp) channel activation related with the protective effects. The aim of present study is toinvestigate 1)whether IP upregulate the Cu,Zn-SOD and Mn-SOD activities, and 2)whether ischemic preconditioning decreases apoptosis via K atp channel activation in timely reperfused skeletal muscle after long ishemia. The experimental animals, Sprague-Dawley rats weighing 250~300g, were divided into 8 group; 1)control group, 2)ischemic preconditioning only groups, 3)pinacidil, a K atp channel opener, treatment only groups, 4)glibenclamide, a K atp channel blocker, treatment only groups, 5)ischemia groups, 6)ischemia after IPC groups, 7)ischemia and pinacidil treatment groups, and 8)IP and ischemia after glibenclamide pretreatment groups. Animals of the control group were administered with the vehicle (DMSO) alone. Pinacidil (1mg/kg) was administred intravenously 5 minutes after initiation of ischemia, and glibenclamide(0.5mg/kg) was injected intravenously 20 minutes before IPC. In rats that were ischemic preconditioned, the left common iliac artery was occluded for 5 minutes followed by 5 minutes of reperfusion by three times usign vascular clamp. Ischemia was done by occlusion of the same artery for 4 hours. The specimens of left rectus femoris muscle were obtained immediately (0 hours), 12 hours, 24 horus after drug administrations, IP or ischemia and reperfusion. The immunoreactivities of SOD and its alterations were observed by use of sheep antihuman Cu,Zn-SOD and Mn-SOD antibodies onthe 10 micro meter cryosections. The incidencies of apoptosis were observed by TUNEL methods with in situ apoptosis detection kit on 6 micro meter paraffine section. The results obtained were as follows: 1. After IPC, immunoreactivities of Cu,Zn-SOD mainly in the small-sized fibers were increased by 24 hours, that of Mn-SOD at 0 hour and 24 hours. 2. No significant changes in immunoreactivities of SDO was observed in the pinacidil and in the glibenclamide treatment only groups, and in the ischemia only groups. 3. The immunoreactivities of the Cu,Zn-SOD were incresed in the ischemia after IPC groups and the ischemia and pinacidil treatment groups. 4. The immunoreactivities of the Cu,Zn-SOD in the IPC and ischemia after glibenclamide pretreantment groups were not increased except for the 12 hours reperfusion group. But, Mn-SOD immunoreactivities were incresed in to 0 hours, 12 hours and 24 hours after reperfusion. 5. In the control group, the IPC only groups, and the pinacidil treatment only groups, negative or trace apoptotic reactions were observed, but the positive apoptotic reaction occured in the glibenclamide treatment groups. 6. Moderate or many number of apoptosis were revealed in the ischemia groups, and also the IPC and ischemia after glibenclamide pretreatment group except for 12 hours and 24 hours after reperfusion. However, the incidence of apoptosis was decreased in the ischemia after IPC groups and in theischemia and pinacidil treatment groups. 7. There is a coincidence between the increase of Cu,Zn-SOD immunoreactivities and the decrease of apoptosis in thepresence of ischemia and reperfusion. These results suggest that the protective effects of ishemic preconditioing may related to the SOD activation, and the ischemic preconditioning decreases the apoptosis partially via K atp channel activation in timely reperfused rat skeletal muscle. It is also suggested that inhibition of apoptosis by IPC may related with the SOD activation.

Severe hypertension (greater than 180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-oldhowever, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their agematched control Wistar-Kyoto (WKY) rats following developmental stages.

The present study was carried out to investigate the potential adverse effects of amitraz on pregnant dams after maternal exposure during the gestational days (GD) 1 through 19 in Sprague-Dawley rats. The test chemical was administered orally to pregnant rats at dose levels of 0, 3, 10, or 30 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights and reproductive findings on GD 20 were examined. In the 30 mg/kg group, an increase in the incidence of abnormal clinical signs and death, a suppression in the body weight gain, and a decrease in the food consumption were observed.