Exposure to 1-bromopropane causes ovarian dysfunction in rats.

Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.     

Clinicopathologic study of mass-screened neuroblastoma with special emphasis on untreated observed cases: a possible histologic clue to tumor regression

Spontaneous regression and maturation of neuroblastoma (NB) are well documented and occur frequently in infants, including those detected by mass screening. To seek histologic clues for regression/maturation in mass-screened NB, clinicopathologic features of 12 tumors that were resected after 2 to 18 months of untreated observation were reviewed. Unobserved screened and age-matched unscreened patients were also studied. To evaluate the possible important role of apoptosis, apoptotic cells were detected by in situ deoxyribonucleic acid (DNA) nick end labeling and immunohistochemical stain for activated caspase-3. Nests with a varying degree of reduced cellularity ("less cellular" and "hypocellular" nests) were common in patients younger than 18 months of age, and were rare in older patients. Two characteristic cells, which have not been focused previously, were frequent, especially in the hypocellular nests. One showed amorphic eosinophilic cytoplasm with pyknotic nuclei and the other contained plump cytoplasm with well-maintained nuclei. These cells were also observed in 89% of the unobserved screened NBs and 79% of the age-matched unscreened patients with good outcome, whereas they could not be confirmed in any of the age-matched unscreened NBs with poor outcome. The amorphic and plump cells were negative for activated caspase-3 and in situ DNA nick end labeling. From these results, the authors hypothesize that these cells most likely represent a degenerative process, in either a state before the activation of caspase-3 or a caspase-independent form of cell death. The presence of less cellular and hypocellular nests with amorphic/plump cells may serve as one of the important clues in predicting tumor prognosis.     

Effect of an antioxidant, ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates

BACKGROUND: Oxidation and/or free radical reactions after subarachnoid hemorrhage (SAH) may be involved in the development of chronic cerebral vasospasm. The inhibition of these reactions is thought to be one of the therapeutic strategies for prevention of cerebral vasospasm. We investigated the effect of Ebselen, a synthetic seleno-organic compound, which exhibits anti-oxidation by glutathione peroxidaselike activity to inhibit free radical reactions by lipid peroxidation on the development of chronic cerebral vasospasm in a primate model. METHODS: Seventeen monkeys were used. SAH was produced by introduction of a blood clot around the right middle cerebral artery and the right side of the circle of Willis in all animals. The monkeys were randomly divided into three groups according to Ebselen dosage: 1) no dosage or non-treated group; 2) high-dose Ebselen group; and 3) low-dose Ebselen group. The drug was administered at 10 mg/Kg in the high-dose group and 5 mg/Kg in the low-dose group twice a day in each group for 7 days after SAH. The vessel diameter was evaluated on angiograms before the induction of SAH and at Day 7 following SAH.RESULTS:In the untreated group, the angiograms showed significant (p < 0.05) reductions of the mean vessel caliber of the right internal carotid (ICA) (38 +/- 10% reduction) and the middle cerebral artery (MCA) (56 +/- 9.7%) compared with the baseline value before SAH. In the high-dose Ebselen-treated group, the mean percent reduction in vessel caliber of the right ICA (16 +/- 11%) and MCA (28 +/- 9.5%) on Day 7 angiograms were significantly (p < 0.05) lower than those in the nontreated group, whereas the mean percent reduction of these vessels in the low-dose Ebselen-treated group showed no significant difference compared with the untreated group. CONCLUSIONS: Chronic cerebral vasospasm was inhibited in the animals in which a relatively large amount of Ebselen was administered for 7 days after SAH. The results suggest that the oxidation or free radical reaction by lipid peroxidation after SAH might be involved in the pathogenesis of vasospasm, and that inhibition of these reactions by drugs, such as Ebselen, may have a promising effect for prevention of vasospasm.     

Chronic unilateral ureteral obstruction represented as renin-dependent hypertension

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.     

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11

 The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P<0.01 and P<0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy. Received: 6 October 1995/Accepted 29 June 1996     

Technical aspects of venous stenting in high-grade stenoses using a long guidewire between dual venous access sites

We describe the technical benefits of the dual-access technique for venous stenting in high-grade stenosis. Stents were implanted successfully with this technique in all patients, although the preceding transfemoral interventions had failed. The dual-access technique is useful to facilitate the intervention when the stenoses are too severe to place the stent through just a single access point. Received: 21 October 1998; Revised: 23 February 1999; Accepted: 3 May 1999