Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle

1. Low-voltage electrical stimulation (LVES) in skeletal muscle at a level far below the threshold of muscle contraction has been reported to promote local angiogenesis. However, the mechanism underlying the promotion of local angiogenesis by LVES has not been fully elucidated. In the present study, we evaluated whether angiogenic factors, such as vascular endotherial growth factor (VEGF), hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), as well as other disadvantageous factors, such as inflammation (interleukin (IL)-6) and hypoxia (hypoxia-inducible factor (HIF)-1alpha), contribute to the local angiogenesis produced by LVES. 2. We completely excised bilateral femoral arteries of male Sprague-Dawley rats. After the operation, electrodes were implanted onto the centre of the fascia of the bilateral tibialis anterior (TA) muscles, tunnelled subcutaneously and exteriorized at the level of the scapulae. The right TA muscles of rats were stimulated continuously at a stimulus frequency of 50 Hz, with a 0.1 V stimulus strength and no interval, for 5 days. The left TA muscles served as controls. 3. We found that both VEGF and HGF protein were significantly increased by LVES in stimulated muscles compared with control. The VEGF level of the LVES group was 89.10 +/- 17.19 ng/g, whereas that of the control group was 65.07 +/- 12.88 ng/g, as determined by ELISA (P < 0.05). The HGF level of the LVES and control groups was 8.52 +/- 1.96 and 5.80 +/- 2.14 ng/g, respectively (P < 0.05). In contrast, there was no difference in FGF, IL-6 and HIF-1alpha between the LVES and control groups. 4. These results suggest that LVES in a hindlimb ischaemia model of rats increases not only VEGF, but also HGF, production, which may be the main mechanism responsible for the angiogenesis produced by LVES.     

封闭式负压吸引联合自体游离皮片移植治疗下肢静脉性溃疡的临床研究

目的 探讨封闭式负压吸引(VSD)联合自体游离皮片移植与传统皮片移植在治疗下肢静脉性溃疡(VLU)的疗效对比.方法 选择32例VLU病人,其中16例行VSD封闭引流联合自体游离皮片移植的方法进行治疗(观察组),16例采用传统皮片移植治疗(对照组),观察记录创面愈合情况、术后不良事件发生情况、换药次数、住院时间.结果 32例病人均溃疡愈合出院,观察组术后第7天溃疡愈合面积95%及以上者明显高于对照组(81.3% vs 43.8%,Uc=2.194,P<0.05);术后观察组皮片感染率明显低于对照组(0 vs 25%,χ2=4.6,P<0.05);住院期间,观察组换药次数少于对照组[(7.1±1.3)次 vs (19.1±5.5)次,χ2=12.0,P<0.05];总体住院时间明显缩短[(13.9±3.0) d vs (25.1±5.4) d,χ2=10.3,P<0.05].随访期间两组病人均无复发病例.结论 VSD联合植皮术在治疗VLU较传统植皮术具有明显优势,可明显提高溃疡面植皮愈合率,降低创面感染率,减少换药次数,缩短住院时间,值得在临床上推广应用.     

Reperfusion injury in the human forearm is mild and not attenuated by short-term ischaemic preconditioning

1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this model. 2. Healthy young adult volunteers (mean (+/-SEM) age 32+/-6 years) were studied on two occasions. During one visit, IR alone was induced by 10 min of upper arm cuff occlusion, whereas on another occasion a PC stimulus (three 3 min cuff inflations) preceded IR. Endothelial function in the ischaemic arm was assessed by measuring arterial flow-mediated dilatation (FMD) and by calculation of forearm blood flow at baseline and 15 and 60 min after IR. Systemic venous blood was sampled from the non-ischaemic arm at baseline, after PC and at 2, 15 and 30 min after IR to assess neutrophil/leucocyte (CD11b) and platelet (bound glycoprotein IIb/IIIa and fibrinogen) activation, as well as numbers of platelet-leucocyte complexes, which were determined by flow cytometry. Because of a lack of measurable effects, the IR experiment was repeated with 20 min ischaemia in six subjects. 3. Five females and eight males completed the study. Flow-mediated dilatation was significantly impaired 30 min after IR (4.1 vs 6.2% at baseline; P<0.05);however, this was not significantly attenuated by ischaemic PC (FMD reduction at 30 min compared with baseline was 2.1+/-0.5% with IR alone and 2.6+/-1.4% with IR after PC; NS). No significant effect was seen on the number of platelet-leucocyte aggregates or on white cell or platelet activation after IR alone or after IR with PC (P>0.6 for all comparisons). Similar results were obtained in six subjects studied subjected to 20 min ischaemia. 4. In conclusion, in healthy young adults, brief periods of skeletal muscle ischaemia lead to arterial endothelial dysfunction, but no significant platelet or white cell activation. Preconditioning does not attenuate this effect on the endothelium. Further experiments with longer ischaemia times and varying PC stimuli may be necessary to produce measurable effects; however, this may prove difficult in conscious human subjects.     

胶原海绵在慢性下肢溃疡中应用临床疗效观察

目的评价胶原海绵促进下肢慢性溃疡愈合的临床疗效及相关作用机制。方法将40例下肢慢性溃疡患者分为治疗组和对照组,每组各20例。治疗组给予以胶原海绵覆盖创面,对照组给予以凡士林纱布覆盖创面,疗程为4周。分别于治疗后2周、4周采用照相法计算创面愈合率;治疗后1、2、4周评价疮面肉芽积分。结果治疗组创面愈合率治疗后4周高于对照组,差异有统计学意义;疮面肉芽积分在2周与4周时达到统计学差异(P0.05或0.01)。结论胶原海绵可以促进慢性下肢溃疡肉芽生长,提高慢性疮面愈合率。     

胃喜康对大鼠胃溃疡愈合和细胞生长因子的影响

我们在临床上应用胃喜康治疗消化性溃疡取得了较好的疗效,且复发率低.但其机制尚不清楚,有研究表明一些与胃酸分泌、细胞移行、分化、增殖和细胞外基质形成及新生血管生成有关的细胞生长因子参与溃疡的愈合,故本课题旨在通过研究胃喜康对胃溃疡大鼠细胞生长因子EGF、TGF-α及受体的影响,试图探讨该中药抗胃溃疡的可能机制,为临床治疗提供理论根据.     

Effect of dopamine on the healing of acetic acid-induced gastric ulcers in rats

Dopamine, as a neurotransmitter in the brain, is also present in the gastroduodenal mucosa and has been implicated in several functions in these tissues. Recent study showed that dopamine acts as a potent antitumor/angiogenic activity through suppression of growth factor expression. Since growth factors are known to play a crucial role in the mechanism of wound healing, it is possible that dopamine has a deleterious influence on the healing of gastric ulcers. In the present study, we examined the effect of dopamine on the healing of acetic acid-induced gastric ulcers in rats. Gastric ulcers were induced in male SD rats by serosal application of acetic acid for 60 sec. Dopamine was subcutaneously given twice daily for 7 days, starting 3 days after ulceration. In some case, the osmotic mini-pump filled with dopamine was implanted into the dorsal subcutaneous space in rats for 7 days. VEGF and Flk-1 mRNA expressions were determined by RT-PCR. Dopamine (3, 10 and 30 mg/kg) given subcutaneously for 7 days did not significantly affect the healing of gastric ulcers. The expression of VEGF and Flk-1 mRNA in the ulcerated mucosa was up-regulated after ulceration, and these expressions were not affected by dopamine. Likewise, dopamine (0.6 mg/kg/hr) infused continuously using the osmotic mini-pump also had no effect on the healing of these ulcers. These results suggest that dopamine, although reportedly shows a potent antitumor/angiogenic activity, does not cause any influence on the healing of the pre-existing gastric ulcers in rats. Received 3 August 2006; accepted 10 November 2006     

舒洛地希治疗下肢静脉溃疡的疗效和安全性

目的：研究舒洛地希治疗下肢静脉溃疡的疗效和安全性.方法：把114例患者随机分为对照组（n=53）和治疗组（n=61）,对照组患者采用伤口护理和压力绷带包扎法进行局部治疗,治疗组患者采用相同的局部治疗的同时,肌肉注射舒洛地希60 mg/d,共30 d.结果：20 d的治愈率：对照组为18.9%,治疗组为36.1%,有显著性差异（P＜0.05）;30 d的治愈率：对照组为32.0%,治疗组为52.5%,有显著性差异（P＜0.05）.治疗组溃疡面积的降低明显快于对照组.治疗过程中,所有患者均未出现严重不良反应.结论：舒洛地希治疗下肢静脉溃疡安全和有效.     

Effects of bepridil and lidocaine on the intravenctricular conduction in acutely ischaemic and infarcted canine myocardium

Summary Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans. Send offprint requests to H. Hashimoto at the above address     

Role of p38-mitogen-activated protein kinase in ischaemic preconditioning in rat heart

1. Activation of p38-mitogen-activated protein kinase (MAPK) has been implicated in the signalling cascade leading to protection by ischaemic preconditioning. This, however, is controversial and there is a plethora of conflicting data in the literature. Although many experimental differences may contribute to this, two in particular may be confounding: (i) the failure to account for p38-MAPK activation during aerobic perfusion; and (ii) the use of the anti-oxidant dimethylsulphoxide (DMSO) as the vehicle for the commonly used p38-MAPK inhibitor SB203580. We have investigated the effects of aerobic perfusion, ischaemia and preconditioning on p38-MAPK activation. In addition, we have used water-soluble SB203580 hydrochloride (SB203580.HCl) and DMSO to probe the role of p38-MAPK in preconditioning and ischaemic injury. 2. Activation of p38-MAPK in rat isolated hearts was assessed using a dual phosphospecific antibody during cannulation, aerobic perfusion and index, autolytic and preconditioned ischaemia. The effect of SB203580.HCl (10 mmol/L) in ischaemic preconditioning and ischaemia/reperfusion was tested using recovery of function and tetrazolium (TTC) staining as end-points. 3. Aerobic perfusion induced rapid activation (34% of maximal ischaemia-induced increase; P < 0.05) of p38-MAPK after 2 min that returned to baseline after 30 min. Index, autolytic and preconditioned ischaemia activated p38-MAPK, with index ischaemia peaking after 15 min (520% of basal; P < 0.05) before declining. SB203580.HCl blocked p38-MAPK activity, but did not block ischaemic preconditioning when bracketing the trigger phase and was not protective when given during ischaemia. 4. In the rat isolated heart, activation of p38-MAPK is neither a unique feature of preconditioning nor a prerequisite. Previous studies using SB203580 may have been complicated by failure to account for the activation of p38-MAPK by the protocol itself and the anti-oxidant properties of the most commonly used vehicle DMSO.     

Inflammation in ischaemic brain injury: Current advances and future perspectives

1. Numerous studies have indicated that inflammation plays a key role in ischaemic brain injury. Brain ischaemia–reperfusion‐induced inflammatory responses include increased microglial and astrocyte activity, increased production of cytokines, chemokines, adhesion molecules and metalloproteinases and the infiltration of monocytes and leucocytes into injured brain regions. 2. Although a significant proportion of the inflammatory response appears to exacerbate ischaemic brain injury, certain inflammatory responses are beneficial to ischaemic brains. It is necessary to further identify the detrimental and beneficial inflammatory responses so that therapeutic strategies can be designed for stroke patients to selectively inhibit detrimental responses while enhancing beneficial responses. 3. Increasing evidence also indicates significant changes in the peripheral immune system of stroke patients and animals that undergo cerebral ischaemia. It is worth elucidating the effects of these changes in ischaemic brain damage. 4. There are complex interactions in the ischaemic brain between microglia and other cell types, including neurons, astrocytes, endothelial cells and stem cells. It is of particular interest to determine the mechanisms underlying the roles of high‐mobility group box‐1, advanced glycation end‐products receptors (RAGE), S100B and NADPH oxidase in these interactions. 5. Because brain ischaemia‐induced inflammation is a relatively long‐lasting event with profound effects on brain injury, it is of considerable importance to further investigate the mechanisms underlying inflammation in ischaemic brains.     

积雪苷治疗下肢难愈性皮肤溃疡的疗效观察

目的 探讨积雪苷治疗下肢难愈性皮肤溃疡的疗效及安全性.方法 92例下肢难愈性皮肤溃疡患者随机分为积雪苷外用组(n=30)、积雪苷外用加口服联合治疗组(n=31)和外用康复新液对照组(n=31).外用组:积雪苷霜涂抹于患处,一日3次;联合治疗组:外用积雪苷霜联合口服积雪苷片,外用方法同外用组,口服给药为一日3次,每次2片;对照组:外用康复新液外敷于患处,一日1次.总疗程均为6周.观察比较3组溃疡面评分情况、愈显率以及不良反应.结果 联合治疗组疮面渗出和疮面大小以及疼痛评分较对照组和外用组改善显著(P＜0.05).外用组、联合治疗组及对照组的愈显率分别为60.00％、80.64％和58.07％.各组均未见明显不良反应.结论 积雪苷霜联合积雪苷片治疗下肢难愈性皮肤溃疡安全有效.     

胃喜康提高大鼠胃溃疡愈合质量的实验研究

研究资料显示，完全治愈的溃疡其复发率很低，因此，溃疡愈合质量(QOUH)逐渐引起人们的重视。随着生长因子研究的进展，生长因子对消化道的修复作用日益受到人们的关注。为此我们设计了本课题，试图探讨胃喜康对表皮生长因子（EGF）及其受体（EGFR）的影响以及与QOUH的关系，为临床治疗提供理论根据。     

Sulphydryl-containing agents stimulate the healing of duodenal ulceration in man.

This prospective randomized double-blind study examined whether sulphydryl-containing agents stimulate the healing and prevent the recurrence of duodenal ulceration in man. To this end, DL-methionine methyl sulphonium chloride (MMSC, 500 mg four times daily) or DL-cysteine (200 mg four times daily) were orally administered with cimetidine. Symptomatic endoscopy-proven duodenal ulcer patients who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg b.d.), cimetidine (400 mg b.d.) with MMSC, or cimetidine (400 mg b.d.) with cysteine. These patients were then kept on their respective oral regimens (except for cimetidine which was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 65 patients (74%) given cimetidine alone but in all the patients given MMSC (n = 87) or cysteine (n = 86) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%) given cimetidine at night relapsed. Addition of MMSC or cysteine to cimetidine incurred a significantly (p less than 0.001) lower relapse rate. During the year following maintenance therapy, the relapse rate in the group that had been previously treated with cimetidine alone (63%, n = 51) was significantly (p less than 0.001) higher than that in the groups previously treated with MMSC and cimetidine (6%, n = 67) or cysteine with cimetidine (6%, n = 64). The results suggest that sulphydryl-containing agents stimulate the healing and protect against the recurrence of duodenal ulceration.     

Neuroprotection and thrombolysis: combination therapy in acute ischaemic stroke

The administration of oral aspirin within 48 h and tissue plasminogen activator within 3 h of ischaemic stroke onset remain the only treatments that have been shown to have clinical benefit. There has been much excitement about neuroprotection over the last two decades, as it may minimise the harmful effects of ischaemic neuronal damage. Although each step along the ischaemic cascade offers a potential target for therapeutic intervention, and neuroprotection has shown benefit in animal studies, this has been difficult to translate to humans. Some hope has been offered by the recent finding that the free radical scavenger NXY-059 may improve outcomes in patients presenting within 6 h of onset of ischaemic stroke. There is logic to the idea that neuroprotection may be most effective when reperfusion has occurred with thrombolysis, as the neuroprotectant will have greater access to ischaemic tissue and the opportunity is presented to minimise free radical-mediated reperfusion injury. Numerous studies in animal models support this view, but the concept has not, as yet, been rigorously tested in humans.     

Effects of prostaglandins on baroreflex during reperfusion of the ischaemic myocardium

1. The present study was planned to: (i) determine whether the baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) was attenuated during reperfusion of short-term ischaemic myocardium; and (ii) study whether blockade of prostaglandin synthesis with indomethacin reversed the inhibitory baroreflex. 2. Arterial pressure was lowered with intravenous sodium nitroprusside before coronary occlusion and 3 min after release of a 5 min occlusion of the left circumflex coronary artery in anaesthetized rabbits. The protocol was repeated 20 min after indomethacin (5 mg/kg, i.v.) or indomethacin vehicle (50 mmol/L tris(hydroxymethyl)aminomethane buffer, pH 8.4) treatment. In addition, this study was performed in a group of vagotomized rabbits. 3. Before indomethacin treatment, the slope of the mean arterial pressure (MAP)-RSNA relationship decreased from -3.3+/-0.77 to -2.01+/-0.69% change in RSNA/mmHg (P < 0.05) during reperfusion of ischaemic myocardium in intact rabbits. The decrease in the slope was reversed by administration of indomethacin. However, the decrease in the slope was not reversed by indomethacin vehicle. Furthermore, the reduction in the slope of the MAP-RSNA relationship during reperfusion of ischaemic myocardium was abolished in vagotomized rabbits. However, there was no inhibition of the slope of the MAP-HR relationship during reperfusion of ischaemic myocardium in either intact or vagotomized rabbits. 4. In conclusion, our data suggest that prostaglandins released by ischaemic myocardium can attenuate the baroreflex-mediated response of RSNA to lowered arterial pressure via vagal afferents during reperfusion of short-term ischaemic myocardium.     

An evaluation of the bile acid binding and antacid properties of hydrotalcite in hiatus hernia and peptic ulceration

Summary

The bile acid binding and antacid properties of hydrotalcite were studied in 25 patients with hiatus hernia or peptic ulceration. Hydrotalcite was found to have significant bile acid binding properties in the presence of free acid in the stomach. There was a definite antacid effect in both pathological entities. These results suggest that hydrotalcite may be an effective therapeutic agent in upper gastro-intestinal ulceration, warranting further investigation in lesions which are thought to involve both hydrochloric acid and bile acids in their pathogenesis.     

Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain

A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg (n = 36), acetaminophen 1000 mg (n = 37), and placebo (n = 38) in postpartum patients who had moderate to severe pain after episiotomy. At regular intervals over 4 hours, patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial. Both active agents were effective compared with placebo (P less than .05). Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference, total pain relief, and reduction of pain by more than 50% (P less than .05), suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg. No adverse effects were reported. Based on the results of this conventional postpartum episiotomy pain model, both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg.     

美宝创面速愈贴治疗压疮的疗效观察

目的观察美宝创面速愈贴治疗压疮的临床效果。方法 125例患者随机分为观察组65例和对照组60例。观察组给予美宝创面速愈贴治疗,对照组给予磺胺嘧啶银软膏治疗。观察2组的临床疗效。结果 观察组总有效率为98.5%高于对照组的88.3%,痊愈时间为(17.6±2.4)d短于对照组的(23.8±2.8)d,差异均有统计学意义(P<0.05)。结论美宝创面速愈贴治疗压疮效果显著,值得临床推广应用。