大鼠实验性视网膜光损伤中的视细胞凋亡

目的 进一步探讨视网膜光损伤的发病机制。 方法 20只Wistar大鼠分为实验组、对照组,分别在光照后12,24,36小时摘除眼球,视网膜组织行HE染色和核苷酸末端转移酶介导的DUTP缺口翻译法(TdT-mediated dUTP nick end labelling method,TUNEL)标记凋亡细胞。 结果 光照后12小时,视杆细胞外节出现少量空泡变性;24小时后,外核层出现明显的细胞核破碎、浓染和DNA裂解;36小时后,视杆细胞内、外节溶解,外核层大量细胞核丢失。 结论 视细胞凋亡是大鼠实验性视网膜光损伤的重要机制之一。 (中华眼底病杂志, 1999, 15: 167-169)     

Statins and peripheral neuropathy

Within the past 3 years seven cases of reversible peripheral neuropathy apparently caused by statins have been reported. Here we report seven additional cases associated with long-term statin therapy, in which other causes of neuropathy were thoroughly excluded. The neuropathy was in all cases axonal and with affection of both thick and thin nerve fibers. The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to 1 year in four cases after statin treatment had been withdrawn. We suggest that long-term statin treatment may be associated with chronic peripheral neuropathy. Received: 6 July 1998 / Accepted in revised form: 1 October 1998     

Interactions between essential fatty acid,prostanoid, polyol pathway and nitric oxide mechanisms in the neurovascular deficit of diabetic rats

Summary Impaired -6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, highdose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, N^G-nitro-l-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p<0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg · kg^–1 · day^–1) and WAY121509 (0.2 mg · kg^–1· day^–1) for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p<0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p<0.001). High-dose WAY121509 (10 mg · kg^–1 · day^–1) and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p<0.001). However, these effects were abolished by flurbiprofen (5 mg · kg^–1 · day^–1) and N^G-nitro-l-arginine (10 mg · kg^–1 · day^–1) co-treatment (p<0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.Abbreviations ARI Aldose reductase inhibitor - EPO evening primrose oil - NCV nerve conduction velocity - NO nitric oxide - NOLA N^G-nitro-l-arginine     

The effect of trimethyltin on acetylcholine release in the guinea-pig trachea

The purpose of the present work was to characterise the effects of trimethyltin on the release of acetylcholine from parasympathetic nerves and its effect on the postjunctional cholinergic stimulation of a smooth muscle. The guinea-pig trachea has been used as a model. Prejunctionally, trimethyltin (3.0 × 10⁻³ M) significantly enhanced in a reversible manner the high K⁺ (75 mM) evoked release of endogenous acetylcholine and [³H]acetylcholine. The evoked release of endogenous acetylcholine and [³H]acetylcholine was released from a pool of acetylcholine being independent of extraneuronal Ca²⁺ in the presence, but not in the absence of trimethyltin. The effect of trimethyltin on the release was not inhibited by low Ca²⁺ (0 mM and 1.0 × 10⁻⁴ M) or by Ca²⁺ channel blockers (verapamil, 1.0 × 10⁻⁴ M, flunarizine, 1.0 × 10⁻⁴ M, ω-conotoxin GVIA, 2.0 × 10⁻⁷ M and ω-agatoxin, 2.0 × 10⁻⁷ M). The present results also demonstrate that trimethyltin induce emptying of a non-vesicular, probably a cytoplasmic storage pool of acetylcholine, since AH5183 (2.0 × 10⁻⁵ M), an inhibitor of the translocation of acetylcholine into synaptic vesicles, and -latrotoxin (1.0 × 10⁻⁸ M), a toxin from black widow spider venom inducing vesicle depletion, had no inhibitory effects on the release of [³H]acetylcholine evoked by trimethyltin (3.0 × 10⁻³ M). The release of [³H]acetylcholine was moreover enhanced by trimethyltin when the vesicular uptake of [³H]acetylcholine was inhibited by AH5183, probably as a result of a higher cytoplasmic concentration of [³H]acetylcholine. Trimethyltin also reduced the neuronal uptake of [³H]choline and this was probably due to a depolarising effect of trimethyltin on the cholinergic nerve terminals. A similar depolarisation induced by trimethyltin was observed during patch clamping of GH₄ C₁ neuronal cells. Postjunctionally, trimethyltin had no effect by itself or on the carbachol-induced smooth muscle contraction, indicating that trimethyltin did not have a general depolarising effect on smooth muscle cells or an effect on muscarinic receptors. Furthermore, the reduced electrical field-induced contraction and the subsequent increase in the basal smooth muscle tension that was observed by addition of trimethyltin was activity-dependent, and was most probably due to emptying of a nervous non-vesicular storage pool of acetylcholine, followed by rapid hydrolysis of acetylcholine by acetyl- and pseudocholinesterases.     

Helical computed tomography of liver injuries: A trial of dual phase imaging

This study was performed to evaluate whether consecutive arterial phase and portal venous phase scans of the upper abdomen are contributory in the evaluation of the liver in patients with blunt abdominal trauma. The purpose of the study was to determine whether such dual acquisition using helical computed tomography (HCT) provides improved definition of injuries and significant information about the dynamics of posttraumatic hemorrhage.During a 10-month period, all patients referred for evaluation of blunt abdominal trauma were scanned using a dual phase imaging technique. Two consecutive and comparable scan clusters were programmed to study the upper abdomen, with a slice collimation of 10 mm and a 11 pitch. Intravenous contrast medium was delivered at a rate of 2 ml/sec for a total of 125 ml, with scan delays of 30 and 70 seconds (arterial and venous phases of hepatic enhancement).Thirty-two patients with hepatic lacerations were encountered, and the images from both acquisitions were compared and graded according to lesion conspicuity. The presence of contrast medium extravasation associated with parenchymal injuries was also recorded.In 23 (72%) of the 32 patients, the liver injuries were better defined in the portal venous phase, and in eight (25%) patients, the lesions were equally shown in both phases. In only one case, the lesion was better demonstrated in the arterial phase. Contrast medium extravasation was noted in two patients at the site of liver laceration. In three additional cases, contrast medium extravasation was also noted in associated splenic injuries. In all of these patients, the extravasation (bleeding laceration) was seen only in the images corresponding to the portal venous phase.Dual phase HCT of the upper abdomen does not provide significant additional information in the evaluation of patients with liver injuries resulting from blunt abdominal trauma. With a single scan cluster through the upper abdomen after a 70-second injection-scan delay, lesion definition is optimal, and vascular opacification remains adequate.     

Spinal accessory nerve palsy due to neurovascular compression. Report of a case diagnosed by magnetic resonance imaging and magnetic resonance angiography

The case of a young patient with left accessory nerve paralysis is reported. He had slight tilting of the head to the right side, developed over a period of about 6 months. On neurological examination hypotrophy of the left sternocleidomastoid and trapezius muscles was observed. MRI and MR-angiography imaged the presence of a neurovascular compression between the medulla oblungata, at the level of the nerve entry zone, and a vessel loop of an elongated left vertebral artery. In spite of the absence of a surgical demonstration it is our opinion that the neurovascular conflict is the cause of the accessory nerve palsy.     

Continuous infusion of rocuronium in a paediatric intensive care unit

Purpose  

To evaluate prospectively the efficacy and dose requirements of rocuronium administered by continuous infusion for neuromuscular blockade in a paediatric ICU population.     

Bilateral traumatic abducens nerve paralysis with cervical spine flexion injury

Bilateral traumatic abducens nerve palsy is a rare condition. We report a case associated with cervical spine flexion injury. This may be the first such case report, as no similar case was found in our review of the literature. The mechanisms of injury in this case are relevant to theories that explain hyperextension injuries.     

Methyldopa produces central inhibition of parasympathetic activity in the cat

Summary -Methyldopa (10–100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2–3h after injection. This -methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before -methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3–10.0 g/kg i.v.). These results suggest that -methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an -adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made.     

Fetal Krabbe leukodystrophy

Summary Two new cases of Krabbe disease were diagnosed prenatally in a family with two previous affected children. The activity of galactosylceramide--galactosidase was virtually absent in cultured amniotic cells.The prenatal diagnosis was confirmed enzymatically in cultured fibroblasts, brain, and visceral organs.Light and electron microscopy studies in both fetuses, 20 and 23 weeks of gestational age respectively, revealed the presence of typical globoid cells in the white matter of the spinal cord. Specific inclusions were also found in the brain stem and in peripheral nerves of the second fetus.A comparison with other Krabbe disease fetuses described in the literature contributes to the consensus that abnormal morphological findings can be expected in particular in the most actively myelinating areas of the nervous system.Although most of the cells containing the specific melusions are probably non-glial in nature, some of them could represent myelination glia.This work was supported by the FGWO (grants nos. 3.0033.77 and 3.0012.77), by the FRSM (grant no. 3.4542.79), and by the Baron Charles Bracht Foundation