3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone

An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg gamma-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP.     

Alterations in synaptosomal neurotransmitter amino acids in “petit-mal” rats at a daytime and a nighttime

The synaptosoma fractions of 6 brain areas-olfactory tubercles (OT), frontal cortex (FC), striatum (Sr), amygdala (A), thalamus (Th), hypothalamus (Hy)-have been analyzed for their neurotransmitter amino acids (AA) content in Wistar rats exhibiting petit-mal epilepsy (PM-E) and in controls (C). The analysis was carried out at 11 p.m. (nighttime corresponding to the acrophase for the hourly number of spike-wave complexes) and at 11 a.m. (daytime). A day versus night rhythmicity is recorded for synaptosomal inhibitory AA in control and in PM-E rats. However, day versus night variations are more frequent and more prominent in C rats than in PM-E rats. Two day versus night variations exist only in PM-E rats: increases of GABA level in Sr and of Asp in Hy. Differences between PME-and C in synaptosomal AA content are more likely to be present during the nighttime. During this period lower AA values for PM-E rats are found for one or several inhibitory AA in OT, Th, and FC. It seems that the differences between PM-E and C concerning the inhibitory AA correlate with the number of spike-wave discharges. Only in one brain area is there a similar difference for PM-E and C during daytime and nighttime: a decreased GABA content for PM-E rats in OT. The decrease is larger in nighttime than in daytime. This difference may serve as a marker for this epileptic disorder. Moreover, it is in OT that the greatest number of PM-E versus C differences in synaptosomal neurotransmitter AA are observed. In view of these and former data, the existence of different alterations in synaptosomal neurotransmitter AA for different types of epilepsy is suggested.Abbreviations used GABA 4-aminobutyrate - Tau taurine - Gly glycine - Asp aspartate - Glu glutamate - Gln glutamine - OT offactory tubereles - FC fronto-parietal cortex - Sr striatum - A amygdala - Th lateral thalamus - Hy lateral hypothalamus - AA neurotransmitter amino acids - I inhibitory - E excitatory - C control rats - PM-E petit-mal rats     

The chicken dystrophin cDNA: striking conservation of the C-terminal coding and 3'' untranslated regions between man and chicken.

Dystrophin is a very large muscle protein (approximately 400 kd) the deficiency of which is responsible for Duchenne muscular dystrophy. Its function is unknown at present. In order to know whether different domains of the protein are differentially conserved during evolution, we have cloned and sequenced the chicken dystrophin cDNA. The protein coding sequence has almost the same size as in man. The N-terminal region that resembles the actin binding domain of alpha actinin, as well as the large spectrin like domain show 80% and 75% conservation respectively between chicken and man. In contrast, the C-terminal region shows 95% identity over 627 aa suggesting that it is an important region of interaction with other proteins. Comparison of the amino acid sequence of this C-terminal region to other protein sequences shows only marginally significant similarities. Finally we have found a striking conservation of three segments of the 3' untranslated sequence (85% homology over a total of 920 nt) between chicken and man. These also appear to be conserved in other mammals. This high conservation is not linked to open reading frames.     

Chromosome localization and polymorphism of an oestrogen-inducible gene specifically expressed in some breast cancers

Summary The BCEI gene codes for a small secreted protein and is expressed in the human mammary tumour cell line MCF7 under oestrogen control and in some breast cancers. We have mapped the gene to chromosome 21 using a panel of somatic hybrid lines, and in situ hybridization has allowed a precise assignment to band 21q223. Two restriction fragment length polymorphisms (RFLP) are described that should be of use in linkage or population studies to test a possible involvement of the BCEI gene in genetic predisposition to breast cancer. This gene should also be a useful marker for the genetic and physical mapping of chromosome 21, and for a better definition of the region involved in the clinical phenotype of Downs syndrome.     

Sorbitol Gum in Xerostomics: The Effects on Dental Plaque pH and Salivary Flow Rates1

Adequate salivary flow is important for patient comfort and maintenance of oral health. Xerostomia, or dry mouth, is a common clinical complaint. Masticatory and gustatory activity can stimulate salivary flow from functional salivary tissue and the use of sugarless mints and gums have been recommended to individuals who complain of xerostomia, but there are minimum clinical data. A clinical study assessing the effect on salivary flow rates and dental plaque pH of a sorbitol-sweetened chewing gum in subjects with the complaint of xerostomia was conducted. The chewing of the gum in this present study stimulated salivary flow in the subjects with xerostomia. Statistically significant stimulated whole mouth and parotid salivary flow rate increases were found when compared to unstimulated whole mouth and parotid salivary flow rates. Chewing of the sorbitol-sweetened gum also effectively reduced the drop in pH seen following the exposure to a fermentable carbohydrate. The findings of this present study indicate that chewing of a sorbitol-sweetened gum may be of benefit to patients with the complaint of xerostomia.     

Ethanolamine base exchange enzymatic activities in spontaneous transformed glial cell lines. Effect of dibutyryl cyclic AMP treatment

Cultured astrocytes derived from neonatal rats (normal cells) displayed maximal ethanolamine base exchange enzymatic activity (EBEE) when cultures reached confluency and cells almost ceased to divide. At this stage, ethanolamine phosphotransferase (EPT) and choline base exchange enzyme (CBEE) activities reached a plateau. In spontaneously transformed glial cells, no differential activity variation either between EPT and CBEE, or between EPT and EBEE was observed. The EBEE activity was mainly localized in the microsomal fraction and was completely absent from plasma membranes. Dibutyryl cyclic AMP (db-cAMP) treatment of the transformed cells reversed the pattern of these activities to that of normal cells. Moreover, treatment of the transformed cells with medium conditioned by normal astroblasts markedly increased EBEE activity. This study demonstrates that (i) variation of EBEE activity during cell growth differs in normal and in transformed cultured glial cells. (ii) EBEE activity may be modulated via both db-cAMP and normal cell conditioned medium. Our findings suggest a possible implication of EBEE in the maturation and contact inhibition of cell growth.     

NAD+ Glycohydrolase of the Plasma Membrane Prepared from Glial and Neuronal Cells

NAD+ glycohydrolase (EC 3.2.2.5) activity was detected in the plasma membrane prepared from the primary culture of rat astrocytes. The enzyme has a broad optimum pH range. From the kinetic analysis, a Michaelis constant of 91.2 microM and a maximum velocity of 0.785 mumol/min/mg protein were obtained. ADPribose exhibited a competitive inhibition with respect to NAD. The inhibition by nicotinamide was shown to be of a non-competitive type. ATP and GTP were found to be competitive inhibitors. NAD+ glycohydrolase activity was not detected in the plasma membrane prepared from the primary culture of neuronal cells of chick embryos.