Central suppressive effect of octreotide on the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive

Somatostatin (SRIH) and its analog have been reported to act within the central nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D-glucose (2-DG) injection or cold-swim stress is well demonstrated to be closely associated with an increase in hypothalamic noradrenergic neuronal activity (NNA). To evaluate whether the suppression of the hypothalamic NNA response could be involved in the central mechanism whereby a SRIH analog inhibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricle of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were analyzed, and the ratio of DHPG to NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreatment with octreotide suppressed the 2-DG-induced increase in hypothalamic NNA, accompanied by the inhibition of the serum glucose, NA and adrenaline responses. This suppressive effect of octreotide was dose-dependent. Similarly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA response to cold-swim stress, accompanied by a blockade of the increases in serum glucose, NA and adrenaline. A close relationship between hypothalamic NNA and serum glucose emerged from these studies. Intraperitoneal pretreatment with octreotide had no significant effect on the hyperglycemic or hypothalamic NNA response to 2-DG injection. These findings suggest that the inhibitory effect of octreotide on the hypothalamic NNA response to 2-DG injection or cold-swim stress is associated with the simultaneous suppression of the hyperglycemic response. Supporting the concept that hypothalamic NNA contributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at least in part, involved in the central mechanism by which octreotide inhibits the hyperglycemic response to 2-DG injection or cold-swim stress.     

A case of intratubular germ cell tumor giving rise to seminoma in a subfertile man

A 34-year-old man visited our hospital with the complaint of right scrotal swelling. Right high orchiectomy was performed under the diagnosis of testicular tumor. Pathological examination was seminoma, pT2pN0pM0 and 3 courses of chemotherapy (cisplatin, vinblastine, bleomycin) were performed. The patient had undergone testicular biopsy for infertility at another hospital 6 years before this visit. Re-examination of the biopsy specimen revealed a intratubular germ cell tumor. No evidence of recurrence or metastasis was found 2 years after surgery.     

Progression of PDMT is accompanied by lack of Fas and intense expression of Bcl-2 and PKC-epsilon

Recent study has demonstrated the development of pregnancy-dependent mammary tumors (PDMTs) in GR/A mice during pregnancy and their regression by apoptotic cell death after parturition. In the present study, we examined the molecular machinery of PDMTs before and after parturition and in progression. The death associated-cell surface molecule Fas was expressed only when apoptosis occurred, and no expression could be determined after progression. Interestingly, death suppressor Bcl-2 showed down-regulation when apoptosis occurred, and intense expression after progression. Examination of the possible involvement of PKC isozymes showed that only PKC-epsilon showed drastic changes in expression: expression was not detected in normal mammary gland cells and PDMTs, but was instead seen only when PDMTs progressed to malignant tumors. On the basis of these results, we suggest that PDMT-regression is due to Fas-mediated apoptosis, and that lack of Fas, persistent expression of Bcl-2, and new expression of PKC-epsilon are essential events for tumor progression.      

A new bioactive triene aldehyde from the marine sponge Leucetta microraphis

A new triene aldehyde, (2E,6Z,9Z)-2-methyl-2,6,9-icosatrienal (1), was isolated from a MeOH extract of the Okinawan marine sponge Leucetta microraphis. The structure of 1 was determined by spectroscopic analysis. Three imidazole alkaloids, leucettamine B, preclathridine A, and (9E)-clathridine 9-N-(2-sulfoethyl)imine, were also obtained and identified. Compound 1 showed moderate growth-inhibitory activity toward HeLa S3 cells.     

Overproduction of IL-8 results in suppression of bone metastasis by lung cancer cells in vivo

HARA-B cells were established from the bone lesion in nude mice formed after an intracardiac inoculation of the human lung cancer-derived cells (HARA), and production of IL-8 in HARA-B cells was decreased as compared to that in the parental HARA cells. This suggests a possible relationship between IL-8 production and bone metastasis. Thus, we examined the effect of IL-8 on bone metastasis using HARA-B cells transfected with experimental (IL-8-cDNA) and/or control plasmid in the experimental bone metastasis model in nude mice. Growth rates of both cells in vitro were similar. Control cells developed radiologically detectable bone metastases in 50% of nude mice tested, whereas experimental cells did not develop bone metastases. Osteoclastic bone resorption is an important step in the process of bone metastasis, and IL-8 possesses an inhibitory effect on osteoclastic bone resorption. These results suggest that IL-8 suppresses bone metastasis, which might be attributed to the inhibitory effect of IL-8 on osteoclastic bone resorption.     

Functional connectivity between forearm and digits representations in human somatosensory area 3b.

OBJECTIVE: We compared the effects of tactile interference to the forearm on magnetic responses evoked by electric stimulation of the little finger (D5) and the thumb (D1). METHODS: Electric stimulation was delivered to D5 or D1 individually. In each stimulus session, magnetic recordings were conducted with or without concurrent tactile interference to the radial side of the anterior forearm. RESULTS: With forearm interference, the amplitude of the primary response (N20m) following D5 stimulation was reduced to 90.7% of the control value without interference, while that following D1 stimulation was not affected (100.7%). CONCLUSIONS: In human somatosensory area 3b, the representation of the forearm is immediately adjacent to that of the D5, and distant from that of the D1. Thus, the result suggests that the tactile interference effect on N20m depends on the cortical distance between electrically and mechanically activated 3b areas. SIGNIFICANCE: Intrinsic synaptic connections between the 3b hand representation and its surroundings have been hypothesized as a neural basis for plastic changes of the human brain, such as a phantom hand phenomenon. The present finding implies that these connections may play some physiological roles even in normal adult humans.     

Acute promyelocytic leukemia after living donor partial orthotopic liver transplantation in two Japanese girls

Organ transplant recipients are generally considered to be at greater risk for developing malignant disorders because of prolonged immunosuppression for organ grafting, but acute leukemia is a rare complication after organ transplantation (0.2 - 2.5%). We encountered two girls with acute promyelocytic leukemia (APL) after living donor partial orthotopic liver transplantation. In one patient, APL developed 21 months after liver transplantation for ornithine transcarbamylase deficiency. She had been administered tacrolimus for prophylaxis of graft-versus-host reaction. In the other patient, APL was diagnosed 46 months after liver transplantation for congenital biliary atresia. Both patients were successfully treated by chemotherapy including all-trans retinoic acid (ATRA), and after reaching complete remission, they have subsequently been in continuous remission. Although leukemia after liver transplantation is generally thought of as a rare complication, increases in survival rate following liver transplantation is likely to lead to more such cases, and documentation of these cases is therefore of importance.