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991.
Rosella Micheletti Daniela Oliva Pietro Belfiore Antonio Giachetti Simonetta Nicosia 《Inflammation research》1985,16(5):291-294
The activity of a number of compounds belonging to the novel class ofN-imidazolylphenyl-N'-alkyl-formamidines on histamine-sensitive adenylate cyclase was evaluated. All substances inhibited histamine-dependent adenylate cyclase activation. The compounds which were investigated in a wider concentration range, i.e. DA 4360, DA 4577, and DA 4626, behaved as simple competitive antagonists, yielding apparentK
B
values comparable with those estimated in conventional H2-receptor assays. These results provide further evidence for the highly selective H2-receptor antagonism of these new molecules, and confirm the suitability of the histamine-stimulated adenylate cyclase assay in guinea-pig gastric cells as a functionally reduced system for the study of H2 antagonists. 相似文献
992.
Enrico Zammarchi Luca Filippi Claudio Fonda P. Alberto Benedetti Daniela Pistone M. Alice Donati 《Child's nervous system》1996,12(7):413-416
The authors report the cases of two patients with neonatal onset of hypoketotic hypoglycemia with hyperinsulinism and a poor response to diazoxide. Pancreatic venous sampling showed a diffuse pancreatic hyperplasia in one patient and a focal lesion in the other. The second patient, diagnosed after a significant delay, suffered severe long-term neurological sequelae, despite having more limited hyperplasia; the brain MRI also showed severe pathological changes in cortex and white matter, predominantly in the parietooccipital region. Early and accurate diagnosis is critical in these patients in whom hypoglycemia is compounded by a lack of the ketone bodies which represent a vital alternative source of energy for the central nervous system. 相似文献
993.
G A Skowronski M S Abdel-Rahman S E Gerges K M Klein 《Journal of applied toxicology : JAT》1985,5(2):97-103
Alcide, a liquid sterilizer, was evaluated for teratogenic potential in rats and mice. Sodium chlorite and lactic acid, the active ingredients of this compound, form chlorine dioxide when mixed. Pregnant rats and mice were administered 1 ml and 0.1 ml, respectively, of Alcide liquid by gavage on days 6-15 of gestation. The general health of the dams was evaluated and the fetuses examined for external, visceral and skeletal malformations. There was no evidence of maternal toxicity among treated rats and mice. Fetal viability, weight, length and number of resorptions were comparable with control groups. Teratogenic toxicity was not detected in either species. There was some incidence of skeletal and visceral anomalies; however, these variances were not significantly different from control animals. 相似文献
994.
Buccione R Baldassarre M Trapani V Catalano C Pompeo A Brancaccio A Giavazzi R Luini A Corda D 《European journal of cancer (Oxford, England : 1990)》2005,41(3):470-476
The naturally occurring phosphoinositide metabolite, glycerophosphoinositol 4-phosphate, has recently been shown to induce rearrangements in the actin cytoskeleton through modulation of the small GTPases, Rac and Rho. Since this is directly linked to cell spreading and remodelling, we have evaluated the potential role of glycerophosphoinositol 4-phosphate and related metabolites in tumour cell invasion. The biological effects of these compounds were tested in a number of cellular activities related to cell spreading, including cell migration and cell invasion. We find that unlike other inositol-containing molecules, such as the inositol phosphates, glycerophosphoinositol and glycerophosphoinositol 4-phosphate prevent the invasion of epithelium-derived MDA-MB-231 breast carcinoma and A375MM melanoma cell lines through the extracellular matrix; this is due to a decreased ability to degrade matrix components. These data identify a specific activity of the glycerophosphoinositols that can be exploited for their development as novel anti-invasive drugs. 相似文献
995.
Viola M Libra M Callari D Sinatra F Spada D Noto D Emmanuele G Romano F Averna M Pezzino FM Stivala F Travali S 《International journal of oncology》2005,27(4):1071-1077
Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating normal cells (PHA-stimulated lymphocytes) could be linked to a possible BS-RNase effect on telomerase activity. In BS-RNase-treated HT29 cells (Na-butyrate-differentiated or not) and human lymphocytes (proliferating or not), we investigated cell vitality (MTT method) and morphology (SEM), BS-RNase localization (immunofluorescence), telomerase activity (TRAP-ELISA method), hTR mRNA expression (RT-PCR), and hTERT levels (western blot). While no BS-RNase effect was detectable on not proliferating cells, a clear relationship was noticed between the diminished number of vital elements of both proliferating cell populations after treatment (48 h and 72 h for HT29 and PHA-stimulated lymphocytes, respectively) with 50 microg/ml BS-RNase and the decrease of their telomerase activity. At the same time, we found that hTR levels, the RNA subunit of telomerase, in proliferation-inhibited BS-RNase-treated cells were diminished. Moreover, by immunofluorescence technique, we detected BS-RNase in the HT29 cell nucleolus after 3-h treatment. Therefore, as hTR has been recently proven to co-fractionate with nucleoli, we hypothesize that a BS-RNase direct action on the telomerase hTR subunit could be a possible mechanism of action by which BS-RNase exerts its pro-apoptotic effects only on proliferating cells. 相似文献
996.
Schultze-Mosgau A Griesinger G Altgassen C von Otte S Hornung D Diedrich K 《Expert opinion on investigational drugs》2005,14(9):1085-1097
Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer. 相似文献
997.
Viganò D Rubino T Vaccani A Bianchessi S Marmorato P Castiglioni C Parolaro D 《Psychopharmacology》2005,182(4):527-536
The aim of this work was to study the mechanism of cross-modulation between cannabinoid and opioid systems for analgesia during
acute and chronic exposure. Acute coadministration of ineffectual subanalgesic doses of the synthetic cannabinoid CP-55,940
(0.2 mg/kg i.p.) and morphine (2.5 mg/kg i.p.) resulted in significant antinociception. In chronic studies, a low dose of
CP-55,940 (0.2 mg/kg, i.p.) that per se did not induce analgesia in naive animals produced a significant degree of antinociception
in rats made tolerant to morphine, whereas in rats made tolerant to CP-55,940, morphine challenge did not produce any analgesic
response. To identify the mechanism of these asymmetric interactions during chronic treatment, we investigated the functional
activity of cannabinoid and μ opioid receptors and their effects on the cyclic AMP (cAMP) cascade. Autoradiographic-binding
studies indicated a slight but significant reduction in cannabinoid receptor levels in the hippocampus and cerebellum of morphine-tolerant
rats, whereas CP-55,940-stimulated [35S]GTPγS binding showed a significant decrease in receptor/G protein coupling in the limbic area. In CP-55,940 exposed rats,
μ opioid receptor binding was significantly raised in the lateral thalamus and periaqueductal gray (PAG), with an increase
in DAMGO-stimulated [35S]GTPγS binding in the nucleus accumbens. Finally, we tested the cAMP system's responsiveness to the cannabinoid and opioid
in the striatum and dorsal mesencephalon. In vivo chronic morphine did not affect CP-55,940's ability to inhibit forskolin-stimulated
cAMP production in vitro and actually induced sensitization in striatal membranes. In contrast, in vivo chronic CP-55,940
desensitized DAMGO's efficacy in inhibiting forskolin-stimulated cAMP production in vitro. The alterations to the cAMP system
seem to mirror the behavioral responses, indicating that the two systems may interact at the postreceptor level. This might
open up new therapeutic opportunities for relief of chronic pain through cannabinoid–opioid coadministration. 相似文献
998.
Roesch-Ely D Scheffel H Weiland S Schwaninger M Hundemer HP Kolter T Weisbrod M 《Psychopharmacology》2005,178(4):420-430
Rationale Executive control (EC) has different subcomponents, e.g., response inhibition (measured, for example, by the Stroop task) and working memory (WM—measured, for example, by delayed response tasks, DRT). EC has been associated with networks involving the prefrontal cortex (PFC). Moreover, there is evidence that dopamine agonists, especially those with a D1 profile, may modulate EC, since in the PFC D1 subtype receptors are more abundant.Objective This study aimed to selectively distinguish whether D1 versus D2 dopamine agonism differentially influences EC related to the inhibition of irrelevant information and WM. Because of its D1 component, we predicted that the administration of pergolide (mixed D1/D2 agonist), in comparison with bromocriptine (D2 selective agonist) and placebo, would enhance performance in both EC tasks. Using a lateralized Stroop task, we predicted a decrease in the interference effect, as well as error rates, while no increase in facilitation effects. For the DRT task, we predicted fewer error scores in the delay condition.Methods Forty male healthy subjects participated in this randomized, double-blind, placebo-controlled, crossover study.Results For the Stroop task no superiority of pergolide was found; however, with bromocriptine, decreased interference was found. No modulation of lateralization effects was shown in interference measures. Moreover, subjects on pergolide showed an absence of facilitation effects. No effects of either agonist were found for the DRT.Conclusion Our findings suggest that dopamine agonists modulate two EC tasks differently. Furthermore, there seems to be a selective modulation of different aspects of the Stroop task. 相似文献
999.
Lang PA Kempe DS Akel A Klarl BA Eisele K Podolski M Hermle T Niemoeller OM Attanasio P Huber SM Wieder T Lang F Duranton C 《Naunyn-Schmiedeberg's archives of pharmacology》2005,372(3):228-235
Osmotic shock, oxidative stress and Cl− removal activate a non-selective Ca2+-permeable cation conductance in human erythrocytes. The entry of Ca2+ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine
mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells.
Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we
explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced
by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated
from forward scatter in FACS analysis. Removal of Cl− enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the β agonist isoproterenol (IC50 approx. 1 μM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca2+ activity following Cl− removal, an effect again significantly blunted by isoproterenol exposure (10 μM). Whole-cell patch-clamp experiments performed
in Cl− free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol
exposure (10 μM). Phenylephrine (IC50<10 μM), dobutamine (IC50 approx. 1 μM) and dopamine (IC50 approx. 3 μM) similarly inhibited the effect of Cl− removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl− removal-activated Ca2+ entry into erythrocytes, thus preventing increase of cytosolic Ca2+ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte
phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood. 相似文献
1000.
Recurrent central neurocytomas 总被引:4,自引:0,他引:4