To characterize and compare maxillary incisor lesions caused by various antitumor drugs, male BALB/c mice were given a single intravenous injection of an estimated 10% lethal dose (LD10)) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MMC), vinblastine sulfate (VBL). taxotere (TXR), irinotecan hydrochloride (CPT-11), DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals were sacrificed, and the maxillary incisors were examined microscopically. The dental lesions observed were classified into 4 different types on the basis of their morphological features. The lesion due to 5-FU was characterized by focal defects in the dentin, and this injury was reversible (transient dentin injury). ADR- or MMC-induced lesions were defined by abnormal structure of the apical aspect of the tooth and irregular odontogenesis, lasting for a long period (persistent apical injury). Treatment with VBL or TXR showed irregular enamel formation and abnormal dentinogenesis. Their targets were considered to be both immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT-11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the epithelial sheath on day 3, but no prominent dental abnormalities were seen thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety of dental lesions that vary temporally and spatially, making histopathological examination of the maxillary incisor an important component of the safety assessment process for novel antitumor drugs.

Animals↗

PubMedDate not supplied

The effects of intraperitoneal injection of 6-hydroxydopamine on the turnover and the levels of the brain catecholamines and the levels of plasma corticosterone in rats.

1. The effects of intraperitoneal injection of 6-hydroxydopamine (6-OHDA) on the levels and the turnover of brain catecholamines and the levels of plasma corticosterone were studied in rats. 2. Two weeks after intraperitoneal injection of 6-OHDA (150 mg/kg) a virtually complete disappearance of cardiac noradrenaline was observed. 3. An increment and an accelerated turnover of noradrenaline in the hypothalamus was observed 2 weeks after peripheral administration of 6-OHDA (150 mg/kg). 4. There was no change in the levels and the turnover of noradrenaline in the cortex of the rats so treated. 5. There was not change in the levels and the turnover of dopamine in either the hypothalamus or the cortex of the 6-OHDA-treated rats. 6. An increment and an accelerated turnover of hypothalamic noradrenaline were not associated with any change in plasma corticosterone.

Animals↗

PubMedDate not supplied

Bioartificial endocrine pancreas (Bio-AEP) for treatment of diabetes: effect of implantation of Bio-AEP on the pancreas.

Recently, we described a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP). Pancreatic islet cells in the Bio-AEP device were isolated from the immune system of the host by an artificial barrier, while nutrients, electrolytes, oxygen, and bioactive secretory products were exchanged across this barrier. This experiment was designed to evaluate whether the diffusion chamber could be useful as a Bio-AEP in the treatment of diabetes. Six streptozotocin (STZ)-induced diabetic rats each received a diffusion chamber containing 8 x 10(6) MIN6 cells as a xenograft Bio-AEP. In the STZ diabetic rats with Bio-AEPs, a return to normoglycemia was observed up to 30 weeks after implantation, without the use of any immunosuppressant. A gradual increase in the body weight of the rats was also observed. In three STZ diabetic rats, diffusion chambers without MIN6 cells were implanted as a sham operation. The fasting blood glucose levels in these three rats remained higher than 600 mg/dl, after implantation, and they lost weight. Thirty-five weeks after implantation, the pancreata were removed from the rats that underwent xenoimplantation, those that had the sham operation, and the normal control rats. In the sham-operated animals, the exocrine tissues of the pancreata were vacuolated and pancreatic B cells were not seen in the islets. In contrast, in the pancreata from the xenoimplantation, the exocrine tissues were normal, and a few pancreatic B cells were seen in the islets. These results indicated that xenoimplantation using the Bio-AEP might retard the progress of diabetes.

Animals↗

PubMedDate not supplied

Leptin resistance conferred by a combination of single nucleotide polymorphism and the adoption of a Western lifestyle in urban areas of Thailand.

OBJECTIVES: An increasing number of lifestyle disorders have emerged in response to the rapid urbanization that has occurred in Thailand. Recently, leptin resistance has been nominated as a possible marker for the onset of metabolic disorders in Asian countries. The research aimed to assess the relationship between leptin-resistance and environmental and/or genetic factors by comparing urban and rural inhabitants in Thailand. METHODS: A total of 212 age- and sex-matched subjects from an urban area (Bangkok) and from rural areas (Sai Noi) participated in the study. Anthropometric measurements, blood biochemistry, single nucleotide polymorphism analyses, and interviews concerning lifestyles and dietary habits were conducted individually. Backward elimination multiple regression analyses and least trimmed sum of square methods were used to estimate the effects of possible factors. RESULTS: A transition of staple food from rice to bread (decreased rice intake; p < 0.01 and increased bread intake; p < 0.05) was significant in urban areas. Leptin levels were higher in urban groups, with a significant difference in women (p < 0.001 in women and p = 0.06 in men), but not in men. Predictors selected for leptin-resistance in women were genotypes of UCP2, PPARg2, bread intake, living area, and smoking habit (r = 0.510); in men, genotypes of UCP2 and UCP3p, smoking habit, and rice intake (r = 0.315). CONCLUSIONS: Urban women with del/del type of UCP2 exhibited significant leptin resistance. A combination of urbanization and UCP2 genotype were considered to be responsible.

Anthropometry↗

PubMedDate not supplied

Antithrombotic and vasodilating effects of OP-41483, a prostacyclin derivative.

Anti-platelet and vasodilating actions of OP-41483, a derivative of prostacyclin, were studied experimentally and clinically. The ADP-induced human platelet aggregation was significantly inhibited in vitro, the rate being 59% with a dose of 3 micrograms/ml, 75% with 6 micrograms/ml and over 90% with 18 micrograms/ml or more. A significant reduction in deposition of platelet and mural thrombi on the chemically injured luminal surface of the canine femoral vein was observed by treatment with topical administration of the solution (10 micrograms/ml) and/or intravenous infusion (10 ng/kg/min). The blood flow rate of the normal canine femoral artery and the anterior or posterior tibial artery of patients with peripheral arterial occlusive disease at the ankle was moderately increased in cases of intravenous infusion of the compound at a rate of 10 ng/kg/min.

Adenosine Diphosphate↗