The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway

We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10–100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10–100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemitransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.     

Stress-responsive protein kinases in redox-regulated apoptosis signaling

Both extra- and intracellular stimuli elicit a wide variety of responses, such as cell survival, proliferation, differentiation, and apoptosis, through regulation of cell signaling. Recent studies have revealed that stress-responsive signal transduction pathways are strictly regulated by the intracellular redox state. The redox state of the cell is a consequence of the precise balance between the levels of oxidizing and reducing equivalents, such as reactive oxygen species (ROS) and endogenous antioxidants. The generation of ROS fluctuates in response to alterations of both external and internal environment and, in turn, triggers specific signaling cascades, including mitogen-activated protein kinases, which determine cell survival or cell death. This review focuses on the regulatory mechanisms of stress-responsive protein kinases and their involvement in oxidative stress-induced apoptosis. It also provides recent findings on the molecular mechanisms by which redox signaling cross-talks with stress-responsive protein kinase cascades.     

Differences in regional wash-in and wash-out time constants for xenon-CT ventilation studies

Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO-WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon. RESULTS: WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO-WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI-WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh-Taylor instabilities set up at interfaces between two gases of different densities.     

Isolation,characterization and chromosomal mapping of an actin gene from the primitive red alga Cyanidioschyzon merolae

Based on the results of cytological studies, it has been assumed that Cyanidioschyzon merolae does not contain actin genes. However, Southern hybridization of C. merolae cell-nuclear DNA with a yeast actin-gene probe has suggested the presence of an actin gene in the C. merolae genome. In the present study, an actin gene was isolated from a C. merolae genomic library using a yeast actin-gene probe. The C. merolae actin gene has no intron. The predicted actin is composed of 377 amino acids and has an estimated molecular mass of 42003 Da. Southern hybridization indicated that the C. merolae genome contains only one actin gene. This gene is transcribed at a size of 2.4 kb. When Southern hybridization was performed with C. merolae chromosomes separated by pulsed-field gel electrophoresis, a band appeared on unseparated chromosomes XI and XII. A phylogenetic tree based on known eucaryote actin-gene sequences revealed that C. merolae diverged after the division of Protozoa, but before the division of Fungi, Animalia and Chlorophyta.     

The course of aggressive behavior induced by a single injection of delta 9-tetrahydrocannabinol and its characteristics

Female, Wistar King A rats subjected to one day of isolated housing, during which all food was withheld for 22 hr and supplied for only 2 hr, and then given a single dose of Δ⁹-tetrahydrocannabinol (THC) markedly exhibited muricide and rod-attack behavior. This continued for 100 days after treatment as far as the animals remained in isolation. They displayed rat pup-killing behavior as well, although normal virgin female rats did not show such behavior. When the rats were transferred from isolated housing to group housing 60 days after THC treatment, rod-attack behavior disappeared completely in all rats and muricide disappeared in 13 of the 28 rats which exhibited muricide. However, when these rats were returned to isolation after a 15 day period of group housing, rod-attack behavior and muricide identical to that observed previously reappeared. It is concluded that housing condition plays a crucial role in the occurrence and maintenance of THC-induced aggression including muricide.     

Elevated binding activity of CD8+ cells with phytohaemagglutinin by asbestos fibre in vitro.

Asbestos fibres are known to depress the mitogenic stimuli of phytohaemagglutinin (PHA) to lymphocytes. We examined effects of asbestos (chrysotile) fibre on the proliferation of PHA-stimulated lymphocytes and the PHA binding activity of lymphocytes in vitro. The incorporation of 3H-thymidine and the expression of interleukin-2 receptor were depressed when the cells were exposed to 50 micrograms/ml of chrysotile fibre. The PHA binding activity of lymphocytes was significantly enhanced after chrysotile fibre exposure, as compared with non-exposed group. These results indicate that the depression of PHA stimuli with chrysotile fibre was not due to blocking of PHA binding to lymphocytes. The enhancement of PHA binding activity by chrysotile fibre was observed on CD8+ but not on CD4+ cells. It is possible, therefore, that treatment of peripheral blood mononuclear cells with chrysotile fibre induces increased reactivity of CD8+ cells with PHA, and that intensely activated CD8+ cells suppress proliferation of lymphocytes.     

Clinical diagnosis of gliomatosis cerebri by radioimages

Gliomatosis cerebri (GC) is a rare clinical entity characterized by diffuse and infiltrative overgrowth of the tumor cells. Most of the previously reported cases of GC were autopsy cases because the clinical diagnosis of GC has been difficult. The authors report four cases diagnosed clinically as GC. Cases 1 and 2 are females aged 19 and 69. Cases 3 and 4 are males aged 47 and 50. In the first three cases, CT findings were almost normal. MRI study, especially on its T2 weighted image (T2W1), clearly demonstrated the wide extent of the infiltration of the tumor cells along the white matter. The last case occurred in the pre-MRI era, but contrast enhanced CT showed a bilateral periventricular high density area accompanied by diffuse low density white matter. Three of them underwent echo-guided needle biopsy, and one underwent partial excision of the lesion. Histological diagnosis was glioblastoma in Cases 1 and 4, and anaplastic astrocytoma in Cases 2 and 3. Difficulty in the clinical diagnosis of GC has been based on the fact that traditional imaging studies, including CT, can not clearly show the extent of tumor cell infiltration. MRI study is a very sensitive imaging technique which can easily demonstrate the area infiltrated by glioma cells. So we may be able to make clinical diagnosis of GC, coupling the data from MRI study and brain biopsy. The authors expect that accumulation of clinical experiences of GC may give useful information for the investigation of "invasion", which is one of the major problems in the treatment of malignant gliomas.