Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic l-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.) 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, byt not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat. The finding that the presence of an unestrous female produced an enhanced demand on tyrosine hydroxylase activity in the medial prefrontal neocortex demonstrates that the sexual incentive provided by the estrous female may not be the only factor responsible for all the effects observed in the present study. In fact, there is a distinct possibility that the intense challenge produced by sexually significant stimuli is but an endpoint, and that the changes found in forebrain monoamine synthesis is a reflection of an environmental challenge not necessarily specifically linked to the sexual behavior.     

Deficient corpus callosum in hybrids between ddN and three other abnormal mouse strains.

The mouse strain ddN from Japan was crossed with three other inbred strains prone to absence of the corpus callosum (BALB/cWah1, I/LnJ and 129/ReJ), and at least one brain with abnormally small corpus callosum was observed in offspring from each F1 hybrid cross. Data for several polymorphic protein markers revealed that the four strains are not closely related genetically. Nevertheless, they share common genetic causes of an absent corpus callosum, which helps to understand why anatomical studies of ddN and BALB/c have yielded similar results. The hippocampal commissure is abnormally small in I/LnJ mice and the anterior commissure is often malformed in BALB/c mice, but both commissures in hybrids were normal, which suggests a different genetic basis for these defects and the absent corpus callosum.     

Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity

Several studies have emphasized the significance of neoangiogenesis for tumor growth and progression, but few have focused on malignant hematological disorders. We studied vascular density and architecture in bone marrow samples of patients with chronic myeloproliferative disease (MPD). Vascular structures were immunostained (for von Willebrand factor/FVIII-RAG, CD 31/PECAM or Ulex europeus I for vessels and for vascular endothelial growth factor, VEGF) in samples from patients with polycythemia vera (PV) (n = 7), chronic myelocytic leukemia (CML) (n = 9), and myelofibrosis (MF) (n = 6) when diagnosed and were compared with normal bone marrow specimens (n = 9). We observed that the mean (+/- SD) vessel count per high-power microscopy field (HPF) was 5.3 (+/- 2.1) in normal bone marrow, 5.9 (+/- 2.1) in PV, 10.8 (+/- 3.2) in CML, and 14.4 (+/- 5.5) in MF (P < 0.001 for CMP and MF versus controls). Confocal microscopy, including three-dimensional reconstructions of the blood vessel architecture, confirmed this increased vessel density and revealed tortuous vessel architecture and increased branching in the MPD, particularly in CML and MF. Furthermore, the number of VEGF-positive bone marrow cells was increased in CML and, particularly, in MF. Numbers of VEGF-positive cells and vessels per HPF correlated significantly (r = 0.41; P = 0. 037). Thus the myeloproliferative diseases PV, CML, and MF exhibit neoangiogenesis that is related to diagnosis.     

Concentrations of the flame retardant 2,2',4,4'-tetrabrominated diphenyl ether in human adipose tissue in Swedish persons and the risk for non-Hodgkin's lymphoma

Concentrations of the flame retardant 2,2',4,4'-tetrabrominated diphenyl ether (2,2',4,4'-TeBDE) in the adipose tissue of 77 individuals from Sweden were determined. The subjects were recruited during the time period 1995-97 and encompassed both men and women ranging from 28 to 85 years in age. Of the subjects included, 19 patients had non-Hodgkin's lymphoma (NHL), 23 patients had malignant melanoma, 8 patients had other cancers or in situ changes, and 27 persons had no cancer diagnosis. The mean concentration of 2,2',4,4'-TeBDE was 5.1 ng/g lipid (range 0.6-27.5) for the 27 persons without malignancies. For NHL patients the mean concentration was 13.0 ng/g lipid (range 1.0-98.2). A nonsignificantly elevated risk with dose response was found for NHL when the cases and controls were compared in the two highest concentration groups (2.05-< 5.43 ng/g lipid and > or = 5.43 ng/g lipid) with the lowest group (< 2.05 ng/g lipid) yielding odds ratio (OR) 1.9 with 95% confidence interval (CI) 0.3-14 and OR 3.8, CI 0.7-26, respectively. The results for the patients with malignant melanoma did not differ from the controls.     

Death following ingestion of MDMA (ecstasy) and moclobemide

Four deaths following the ingestion of moclobemide and MDMA ('ecstasy') are described. The probable cause of death in each case was serotonin syndrome as a result of an interaction between the two drugs. As none of the victims had been prescribed moclobemide it seems that each had taken the drug to enhance the effects of MDMA, with fatal consequences. Warnings are needed against misinformed attempts to potentiate the pharmacological effects of illicit drugs.