The effect of the β-carboline FG 7142 on the behaviour of male rats in a living cage: An ethological analysis of social and nonsocial behaviour

The effects of FG 7142, a -carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n=8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self-grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the -carboline inverse agonist.     

Species differences in the relative analgesic potencies of some classical opiates and opioid peptides

The analgesic ED₅₀ values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). -Endorpin, d-Met², Pro⁵-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of - and -receptors in mediation of the analgesic effect induced by different types of opioids.     

Effects of several 5′-carboxamide derivatives of adenosine on adenosine receptors of human platelets and rat fat cells

Summary The effects of several 5-carboxamide derivatives of adenosine on stimulatory (R _a) adenosine receptors of human platelets and inhibitory (R _i) adenosine receptors of rat fat cells have been compared. 5-N-Cyclopropylcarboxamidoadenosine (CPCA) and 5-N-ethylcarboxamidoadenosine (NECA) most potently inhibited ADP-induced aggregation of human platelets as shown by IC₅₀-values of 0.24 and 0.34 mol/l. 5-N-Methylcarboxamidoadenosine (MECA; IC₅₀ 0.81 mol/l) and 5-N-carboxamidoadenosine (NCA; IC₅₀ 2.1 mol/l) were less potent, whereas adenosine, 2-chloroadenosine and (-)N⁶-phenylisopropyladenosine [(-)PIA] exhibit IC₅₀-values of about 1.5 mol/l. Nearly the same rank order of potency was obtained for stimulation of adenylate cyclase activity of platelet membranes and for inhibition of [³H]NECA binding to human platelets. In order to examine the effects of the carboxamide analogues on R _i adenosine receptors of rat fat cells inhibition of lipolysis and adenylate cyclase were studied. (-)PIA was the most potent inhibitor of lipolysis as shown by an IC₅₀ of 0.5 nmol/l, followed by CPCA (IC₅₀ 1.1 nmol/l) and NECA (IC₅₀ 1.3 nmol/l), whereas MECA (IC₅₀ 17.9 nmol/l) and NCA (IC₅₀ 20.1 nmol/l) were much less potent than NECA in inhibiting lipolysis. Similar results were obtained for inhibition of adenylate cyclase activity of fat cell membranes and for competition with [³H]PIA binding to fat cell membranes. The relative potencies of the adenosine analogues at both receptor subclasses were calculated from the ratio of the IC₅₀-values for inhibition of platelet aggregation and of lipolysis. (-)PIA showed the highest selectivity for R _i receptors as indicated by a 2,900-fold lower IC₅₀ for the antilipolytic than for the antiaggregatory effect. The R _a/R _i activity ratio for NECA was about 260, for CPCA 220, for NCA 105 and for MECA 45. These results indicate that all 5-carboxamide adenosine derivatives are more potent agonists at R _i receptors than at R _a receptors. Since MECA has a higher selectivity for R _a receptors than NECA, it may be useful for the characterization of stimulatory adenosine receptors in different tissues.     

Comparative effects ofβ 2-adrenoceptor agonists on intracranial self-stimulation,Sidman avoidance,and motor activity in rats

The effects of -adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on leverpressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS leverpressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although -adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.     

Hypotensive brain stem necrosis in a stillborn

Summary Hypotensive brain stem necrosis is reported in a stillborn. Additional postmortem findings included evidence of intrauterine distress, shock, and a pure blood culture of group B -hemolytic streptococci. These findings suggest group B -hemolytic streptococcal sepsis in utero, with a subsequent episode of transitory circulatory failure prior to intrauterine demise.     

Birch Pollen Related Pear Allergy: A Single-Blind Oral Challenge TRIAL with 2 Pear Cultivars

Approximately 70% of birch pollen allergic patients in Europe experience hypersensitivity reactions to Immunoglobulin E (IgE) cross-reactive food sources. This so-called pollen-food syndrome (PFS) is defined by allergic symptoms elicited promptly by the ingestion of fruits, nuts, or vegetables in these patients. So far, in the literature, less attention has been given to Bet v 1 cross-reactive symptoms caused by pear (Pyrus communis). In the Netherlands, pears are widely consumed. The primary objective of this study was to measure the type and severity of allergic symptoms during pear challenges in birch pollen allergic patients, with a positive history of pear allergy, using two different pear varieties. Fifteen patients were included, skin prick test (SPT), prick-to-prick test (PTP), specific Immunoglobulin E (sIgE), and single-blind oral challenges were performed with two pear (Pyrus communis) varieties: the ‘Cepuna’ (brand name Migo^®) and the ‘Conference’ pears. All patients were sensitized to one or both pear varieties. A total of 12 out of 15 participants developed symptoms during the ‘Cepuna’ food challenge and 14/15 reacted during the ‘Conference’ challenge. Challenges with the ‘Cepuna’ pears resulted in less objective symptoms (n = 2) in comparison with challenges with ‘Conference’ pears (n = 7). Although we did not find significance between both varieties in our study, we found a high likelihood of fewer and less severe symptoms during the ‘Cepuna’ challenges. Consequently selected pear sensitized patients can try to consume small doses of the ‘Cepuna’ pear outside the birch pollen season.     

胃癌前病变及癌组织中CD44v6的表达

目的 :探讨CD44v6蛋白表达与胃癌发生发展的关系。方法 :采用免疫组化SP法检测CD44v6蛋白在各级胃粘膜病变和胃癌组织中的表达。结果 :CD44v6蛋白阳性表达率胃癌组织高于胃炎及不典型增生病变组织(P <0 .0 5 ) ,进展期胃癌显著高于早期胃癌组织 (P <0 .0 5 ) ,伴淋巴结转移和肝转移的胃癌组织明显高于无转移的胃癌组织 (P <0 .0 5 )。结论 :CD44v6蛋白表达与胃癌的发生发展密切相关 ,其检测有助于胃癌的早期诊断 ,转移预测和预后判断     

CD44v6在骨肉瘤的表达与临床意义

目的 研究骨肉瘤组织中CD44V6的表达情况,探讨它与骨肉瘤侵袭的关系及临床意义。方法 应用免疫组织化学方法对70例骨肉瘤、15例骨软骨瘤患者和15例正常人的骨组织进行CD44V6、ki－67检测;对60例有随访资料的病例进行生存分析。结果 CD44V6在骨肉瘤中普遍呈阳性表达,明显高于软骨瘤及正常骨组织,与预后无明显相关,与细胞增殖指数ki－67无明显相关。结论 CD44V6可作为骨肿瘤恶性表型的标志,并可作为骨肉瘤诊断的辅助指标;CD44V6不是决定肿瘤细胞增殖、侵袭的唯一因素。     

CD44v6和nm23-H_1的表达对大肠癌淋巴结转移的影响

目的　探讨CD44v6和nm2 3-H1基因产物表达与大肠癌淋巴结转移的关系。方法　应用SP免疫组化染色法 ,对 76例大肠癌标本进行CD44v6和nm2 3-H1基因产物测定。结果　CD44v6基因产物的高表达和nm2 3-H1基因产物的低表达与大肠癌淋巴结转移有关 (P <0 .0 1)。大肠癌CD44v6和nm2 3-H1表达无相关性 (P >0 .0 5 ) ,但CD44v6阳性表达伴nm2 3-H1阴性表达的患者发生淋巴结转移的可能性大。结论　CD44v6和nm2 3-H1与大肠癌淋巴结转移密切相关 ,两者在淋巴结转移中起协同作用 ,联合检测对判断大肠癌淋巴结转移是一个有用的指标。     

Helicase Hmi1 stimulates the synthesis of concatemeric mitochondrial DNA molecules in yeast Saccharomyces cerevisiae

Hmi1p is a helicase in the yeast Saccharomyces cerevisiae required for maintenance of the wild-type mitochondrial genome. Disruption of the HMI1 ORF generates ^– and ⁰ cells. Here we demonstrate that, in ^– yeast strains, Hmi1p stimulates the synthesis of long concatemeric mitochondrial DNA molecules associated with a reduction in the number of nucleoids used for mitochondrial DNA packaging. Surprisingly, the ATPase negative mutants of Hmi1p can also stimulate the synthesis of long concatemeric ^– mitochondrial DNA molecules and support the maintenance of the wild-type mitochondrial genome, albeit with reduced efficiency. We show that, in the mutant hmi1–5 background, the wild-type mitochondrial DNA is fragmented; and we propose that, in hmi1 yeast cells, the loss of the wild-type mitochondrial genome is caused by this fragmentation of the mitochondrial DNA.