The participation of the sympathetic nervous system in thromboxane A2 release induced by limb ischemia

Our previous studies indicate that the blockade of the sympathetic nervous system by spinal anesthesia or epidural anesthesia inhibits the release of TXA2 induced by limb ischemia with thigh tourniquet in patients with lower limb surgery. The present study was undertaken to confirm this phenomenon in anesthetized dogs. Twenty one anesthetized dogs underwent 60 min occlusion of the abdominal aorta and the inferior vena cava, followed by reperfusion. They were randomized into three groups: no treatment group and pretreatment groups with either 2 ml of 0.5% bupivacaine intrathecally or 4 mg.kg-1 of labetalol intravenously. In no treatment group plasma TXB2 levels were increased significantly after reperfusion. However, prior treatments with bupivacaine intrathecally or labetalol intravenously inhibited the increases in plasma TXB2 levels after reperfusion. These results suggest that limb ischemia stimulates the TXA2 production, which may be influenced not only by endothelial cell damage and the generation of oxygen free radicals but also by the activation of the sympathetic nervous system.     

A case report of intracerebral tuberculoma during antituberculous therapy

A case of multiple intracerebral tuberculoma occurred in the course of anti-tuberculous therapy is reported. A 16-year-old high school boy had been treated with isoniagid, streptomycin and paramino-salicylic acid on the tuberculous pleulitis for 3 months previously. He was admitted to our hospital because of progressive headache associated with vomiting. Neurological examination revealed bilateral full papilledema and incomplete bilateral abducens palsy. An immediate CT study with contrast enhancement demonstrated two small ring-like mass with considerable perifocal edema in the left temporal and occipital lobe, respectively. Intracerebral tuberculoma was considered to be most likely, so the patient was given antituberculous therapy with steroid and mannitol. However, despite of medical decompression, he developed intracranial hypertension aggravated, leading to removal of tumor 7 days after admission. Initially left temporal tuberculoma, which had more extensive and prominent perifocal edema, was successfully excised. The specimen was a walnut-sized granuloma with hard capsule including pus inside. Numerous tuberculous bacilli were identified with Ziel-Nielsen staining technique from the pus. Postoperative course was gratifying, and other tumor in the left occipital lobe, which was also diagnosed as tuberculoma, was treated with continuing administration of isoniagid, ethanbutol and rifampicin. However, the former two drugs were forced to be discontinued because of agranulocytosis. Only rifampicin was maintained for 2 months thereafter but no decrease of the size was observed in serial CT studies. Then left occipital tuberculoma was removed. The pathology was tuberculoma with positive bacilli staining. He discharged 1 month later without any neurological deficit but was on antituberculous therapy (rifampisin) as an outpatient for 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased calcitonin levels during ovarian development in the eel, Anguilla japonica

Female silver eels (Anguilla japonica) were matured with repeated injections of chum salmon pituitary homogenate. Blood samples and ovaries were taken at various stages of ovarian development for the analysis of serum immunoreactive calcitonin (CT), Ca content, and gonadosomatic index. Serum CT levels gradually increased in accordance with an increase in gonadosomatic index and the highest level was observed at the time of ovulation. An increase in serum Ca level was also observed during ovarian development. These results suggest an involvement of CT in sexual maturation in the eel.     

Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters

Potential chemopreventive effects of naturally occurring agents were investigated using a new 16-week medium-term pancreatic carcinogenesis models in hamsters. Male 6-week-old Syrian hamsters were subcutaneously injected with 10mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) four times within a week, and fed a diet supplemented with 80ppm benzyl isothiocyanate (BITC), 80ppm sulforaphane (SFN) or 10ppm resveratrol (RES) during the initiation or post-initiation stages. For the initiation stage, each chemical was given for 3 weeks including 1 week before and after the BOP injections. With post-initiation exposure, the groups were changed from basal diet 1 week after the last BOP injection, and then fed each chemical for 14 weeks. All the animals were sacrificed after 16 weeks. The multiplicities of combined pancreatic lesions including atypical hyperplasias and adenocarcinomas were significantly decreased by BITC and SFN given in the initiation but not the post-initiation stage. On the other hand, RES, a naturally occurring inhibitor of cyclooxygenase-2 (COX-2) reported chemopreventive effects, failed to show significant effects on pancreatic carcinogenesis in either the initiation or post-initiation stages. Our data suggest that the naturally occurring isothiocyanates BITC and SFN can block BOP-initiation of hamster pancreatic carcinogenesis.     

Lack of enhancing effects of sodium nitrite on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female Sprague-Dawley rats

A number of heterocyclic amines (HCAs) have been shown to exert enhanced carcinogenic and mutagenic potential when given simultaneously with sodium nitrite (NaNO(2)). In the present experiment, effects of combined treatment with NaNO(2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most prevalent carcinogenic HCAs in the human environment, were assessed with regard to mammary tumor induction in female Sprague-Dawley (SD) rats. Animals at 6 weeks of age were given intragastric doses of 100mg/kg body weight of PhIP twice a week for 4 weeks, during which period 0 or 0.2% NaNO(2) was administered in the drinking water. Control rats received 0.2% NaNO(2) alone for the 4 weeks or non-supplemented water during the entire 48 week experimental period, without carcinogen treatment. The first tumor in the PhIP+NaNO(2) group appeared significantly later than with PhIP alone, and during the experimental period, the incidence, multiplicity and volume of mammary tumors in this group tended towards decreased, although values did not significantly differ at the terminal sacrifice. These results indicate that NaNO(2) does not enhance PhIP-induced rat mammary carcinogenesis, rather possessing some potential for inhibition.     

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42–75 years) were enrolled. Both cisplatin (40 mg/m²) and vinorelbine (20 mg/m²) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6–93.4%). The median survival time was 23 months (range, 4–43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3–4 neutropenia in 84.6% of patients, grade 3–4 thrombocytopenia in 3.8%, and grade 3–4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3–4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. Conclusion: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.