Species and sex differences of aflatoxin B1-induced glutathione S-transferase placental form in single hepatocytes.

Species and sex differences of aflatoxin B1 (AFB1)-induced glutathione S-transferase placental form (GST-P) positive single hepatocytes have been investigated 48 h after an intraperitoneal injection of AFB1 to young male and female Fischer rats (2 mg AFB1/kg body wt) and male Syrian golden hamsters (6 mg AFB1/kg body wt). The presence of GST-P positive hepatocytes was examined by the immunohistochemical method. Male rats formed three times as many AFB1-induced GST-P positive hepatocytes as females. Pretreatment of both male and female rats with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO) (4 mmol/kg body wt), 2 h and 4 h before AFB1 injection increased AFB1-induced GST-P positive hepatocytes by about 120% above the controls. Male hamsters formed several-fold less AFB1-induced GST-P positive hepatocytes than male rats. Pretreatment with BSO did not increase AFB1-induced GST-P positive hepatocytes in hamsters even though it produced an increase in hepatic necrosis. It appears that GSH and GSH S-transferases play an important role in modulating hepatic AFB1-DNA binding and AFB1-induced GST-P positive hepatocytes in rats and hamsters.     

Suppressive effect of vitamin E on lipid peroxidation in halothane-administered guinea pig liver.

The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation.     

Inhibitory effect of anti-platelet prostaglandin on liver metastasis of hamster pancreatic cancer

Coagulation system and platelets play an important role in the stage of lodgement of tumor cells. We examined abilities of human and hamster pancreatic cancer cell lines to aggregate platelets in vitro, and investigated the effect of prostaglandin E1, I2, on artificial liver metastases of pancreatic cancer in Syrian golden hamster. Platelet aggregating activities were found in five out of six human pancreatic cancer cell line and thromboplastin likes activity in five cell lines. Diisopropanolnitrosamine induced hamster pancreatic cancer cells (HPK-1) were able to aggregate platelets both in vitro and in vivo and these activities were inhibited by prostaglandin I2. Hamster was inoculated intraportally with 1 X 10(6) HPK-1 cells. After two weeks autopsy of these hamsters revealed multiple metastatic nodules on liver surface. In this model we administered prostaglandin E1, I2 into the portal vein five minutes before cell inoculation. Number of liver surface nodules were significantly decreased to 33.1 + 7.0, 11.0 + 9.6 in hamster given 100g PGE1 PGI2 before cell inoculation, compared with control group of hamsters (62.0 + 6.6 PH9.3, 66.1 + 13.9 PH7.4). But administration of prostaglandin after cell injection was not effective. In all cases none of extrahepatic metastases were noted. Inhibitory action of PGE1 PGI2 on liver metastasis is suspected to be related to inhibition of platelet aggregation.     

Presence of ghost cells and the Wnt signaling pathway in odontomas

BACKGROUND: Although it has been reported that ghost cells are present in odontomas, the generation mechanism of these cells is unclear. To evaluate the presence of ghost cells and involvement of the Wnt signaling pathway, we examined the expression of hard keratins, beta-catenin and Lef-1 in odontomas. METHODS: Sixty-nine cases of odontoma were examined immunohistochemically with the use of antibodies against human hair proteins, beta-catenin and Lef-1. RESULTS: Expression of hard keratins was found only in the cytoplasm of ghost cells in 46 (66.7%) of the 69 odontomas. Compound odontomas (78.8%) showed a higher incidence of ghost cells than complex odontomas (29.4%). Histopathologically, ghost cells were found within odontogenic epithelium adjacent to immature enamel and in the centre of Liesegang-ring-like calcified materials. Expression of beta-catenin and Lef-1 was observed in the cytoplasm and nucleus of odontogenic epithelial cells adjacent to the ghost cells in immature odontomas. CONCLUSION: These findings suggest that odontoma is a hard keratin-expressing tumor-like lesion, and that the Wnt signaling pathway may be involved in the formation of ghost cells in odontomas.     

Comparative in vitro and in vivo activity of rifabutin and rifampicin against Mycobacterium avium complex

In vitro antimicrobial activity of rifabutin and rifampicin against various mycobacteria, including the Mycobacterium avium complex, was evaluated by the agar dilution method, using 7H10 agar medium. The activity of rifabutin based on MIC50 and MIC90 was higher than that of rifampicin, against all the acid-fast organisms tested. Microbicidal activity of rifabutin against the M. avium complex phagocytosed in mouse peritoneal or alveolar macrophages was greater than that of rifampicin. Both rifabutin and rifampicin had therapeutic effects against murine infections induced by M. avium complex. Rifabutin was somewhat more effective than rifampicin in mice.     

A protocol for the successful long-term enzyme replacement therapy of scurvy in guinea pigs

Summary Gulonolactone oxidase, a key enzyme in the biosynthesis of ascorbic acid, is missing from guinea pigs and certain other scurvy-prone species. Weekly intraperitoneal injections of glutaraldehyde cross-linked immunoprecipitates of this enzyme have been shown to provide guinea pigs with the capability of synthesizing their own ascorbic acid and of surviving without an exogenous source of this vitamin. This protocol, however, was successful in only a small percentage of the animals tested. The reasons for the limited therapeutic success were investigated. Apparently, the gulonolactone oxidase-treated guinea pigs fed without ascorbic acid were receiving insufficient nutrition. By supplementing these enzyme-treated animals with vitamins A, B, D and E and selenium, we successfully maintained a high proportion of guinea pigs fed without vitamin C.     

Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.