Histamine H1 receptors in rat dorsal raphe nucleus: pharmacological characterisation and linking to increased neuronal activity

In this work we studied the presence of histamine H(1) receptors in the rat dorsal raphe nucleus (DRN) and the effect of their activation on the activity of presumed serotonergic DRN neurones. [(3)H]-Mepyramine bound to DRN membranes with best-fit values of 107+/-13 fmol/mg protein for maximum binding (B(max)) and 1.2+/-0.4 nM for the equilibrium dissociation constant (K(d)). In DRN slices labelled with [(3)H]-inositol and in the presence of 10 mM LiCl, histamine stimulated the accumulation of [(3)H]-inositol phosphates ([(3)H]-IPs) with maximum effect 172+/-6% of basal and EC(50) 3.2+/-1.3 microM. [(3)H]-IPs accumulation induced by 100 microM histamine (162+/-5% of basal) was markedly, but not fully blocked by the selective H(1) antagonist mepyramine (300 nM; 64+/-6% inhibition). The simultaneous addition of mepyramine and the selective H(2) antagonist ranitidine (10 microM) abolished histamine-induced [(3)H]-IPs accumulation. The presence of H(2) receptors was confirmed by [(3)H]-tiotidine binding and by the determination of histamine-induced [(3)H]-cyclic AMP formation. Extracellular single-unit recording in brain stem slices showed that the exposure to histamine resulted in a marked increase in the firing rate of DRN presumed serotonergic neurones (471+/-10% of basal), that was dependent on the concentration of the agonist (EC(50) 4.5+/-0.3 microM). The action of histamine was not affected by the H(2) antagonist tiotidine (2 microM) but was fully prevented by 1 microM mepyramine. Taken together, our results indicate that histamine modulates the firing of DRN presumed serotonergic neurones through the activation of H(1) receptors coupled to phosphonositide hydrolysis.     

Differential responses in central dopaminergic activity induced by apomorphine in IPL nude rat

The IPL nude rat, derived by spontaneous mutation from the Sprague-Dawley strain, presents alterations in the prolactin synthesis and secretion due to an increased dopaminergic inhibition. However, there are no reports concerned to central dopamine activity. The corpus striatum is a brain area involved in the development of stereotyped behavior after the activation of mesolimbic and/or nigro-striatal dopamine pathways. In order to identify possible mesolimbic and/or nigro-striatal dysfunctions in the IPL nude rat, we study the spontaneous oral behaviors and the effects of apomorphine-induced dopaminergic activation on stereotyped behavior and neurochemical changes. Males from both strains were injected with saline or apomorphine (2 and 5 mg/kgs.c.) and evaluated during 30 min in a stereotypes oral tests. The corpus striatum and nucleus accumbens were used to measure dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by HPLC. The concentrations were expressed as synthesis rate (DA/DOPA) and turnover rate (DOPAC/DA). We observed that the spontaneous gnaw movements were significantly different between the untreated IPL nude and Sprague-Dawley (SD) rats. Apomophine injection decreased the amount of stereotyped gnawing in IPL nude rats at the two doses used, but it induced an increase in SD rats. Apomorphine also caused an enhancement in the number of biting and sniffing without modifying the licking behavior. In addition, modifications of the dopaminergic activity were also observed. Synthesis rate in the striatum of IPL nude rats was higher than in SD rats after the injection of saline. Apomorphine caused a reduction of the synthesis rate in both strains. Turnover rate was significantly lower in the striatum of IPL nude rats than in the SD rats injected with saline. Apomorphine caused an increase in the turnover rate in both strains. Contrary to observed in the striatum, the 2 mg/kg dose of apomorphine caused a significant increase in the DA synthesis rate in nucleus accumbens, while 5 mg/kg decrease it in both strains. The DA turnover rate in the same area was lower in IPL nude than in SD rats after saline injection. Apomorphine enhances the DA turnover rate in both strains. We conclude that the modifications of the oral spontaneous and induced stereotypical patterns observed in the IPL nude rats could be related to the differential responses in dopaminergic activity in the two brain areas examined.     

Can we prevent in-stent restenosis?

Nowadays stent placement has replaced balloon angioplasty as the most commonly performed percutaneous coronary interventional procedure, mainly because of its better acute and chronic outcome. As a result, in-stent restenosis (ISR) has become a widespread problem. The incidence of ISR varies from 10% to 50% and depends on the absence or presence of several risk factors, such as small vessel size, longer lesions, and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly caused by neointimal proliferation; consequently, this pathologic process has become the target of many preventive and therapeutic approaches. This article provides an overview of such management strategies, highlighting the rather disappointing experiences with mechanical and systemic drug therapies; the relative merits and disadvantages of intracoronary radiation; and the exciting yet realistic promise, embodied by the recent advancements in drug-eluting stent technology, of potentially eradicating ISR in the near future.     

Good results with unreamed nail and bone grafting for humeral nonunion: a retrospective study of 21 patients

21 patients with humeral shaft nonunions were treated by retrograde nailing with the unreamed humeral nail. In all cases, we reamed the fracture site and performed a bone graft. Union of the fracture occurred in every case. The mean healing time was 4.2 (4-6) months. The range of motion of the shoulder and elbow was excellent in 14 patients, that of the shoulder moderate in 6 and poor in 1, and that of the elbow moderate in 7. The functional results were excellent in 13 patients, good in 5 and fair in 3. Given the good functional results in this series, retr grade locked nailing and bone grafting appears to be a good method for treating humeral shaft nonunions.     

Failures of open reduction in developmental dislocation of the hip

Eight patients with the same number of developmental dislocated hips were initially treated with open reduction through an anterolateral approach. The hips then became dislocated again. There were six girls, with a mean age at first open reduction of 13.3 months. We treated the hips with a new open reduction through an anteromedial approach. A constricted anteromedial capsule was always found as the main factor; all had an intact anteromedial capsule, there was an inverted transverse ligament in three cases and a very tight psoas tendon in another three cases. All were reduced, without complications and with only one simultaneous bone procedure. Risk of avascular necrosis and residual dysplasia could not be evaluated with this follow-up. We conclude that in any open reduction for developmental dislocation of the hip the surgeon must consider a release of the anteromedial capsule, which we have found to be the most important factor in technical failures.     

角膜内植入物并发基质内上皮混浊

目的：报告应用角膜内植入物矫正远视眼后发生角膜周边部上皮性混浊的新的并发症。设计：前瞻性观察研究。参加者：7例患者的11只眼行角膜内植入矫正远视。方法：应用显微角膜板层刀制作一个蒂在下方的角膜瓣，将角膜内移植物植入角膜基质床中。