Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats

The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801.     

Implantable Transvenous Pacing Leads:

With the dawn of a new millennium, physicians' demands for very thin transvenous leads able to be positioned in nontraditional sites like the Bachmann's bundle, the high and mid-right ventricular septum, and the His bundle have created new and exciting challenges for lead engineers. Bipolar leads can now be as thin and reliable as unipolar leads. Cathode electrodes are very small, porous, and demonstrate high impedance. To optimize stimulation thresholds, steroid-eluting passive- and active-fixation electrodes have become popular for use in the atrium and ventricle. To create thin lead body diameters, new insulation and conductor materials and lead body designs are necessary. Hybrid medical materials having the best features of silicone rubber and polyurethane will allow for reliable insulation. Conductor cables instead of helical coils permit strong thin diameter leads to be designed. Transvenous lead implantation using the traditional stylet may not be possible with thin diameter leads, necessitating the use of sophisticated workstations using steerable catheters to guide these new active-fixation leads to selective sites in the right heart. The pacing lead of the future may be very different from the one used today. Ironically, it will have features and implantation techniques similar to the transvenous leads designed prior to the use of the stylet. We are now approaching full circle in lead development, retracing the footprints of the early implanters of three and a half decades ago. (PACE 2004; 27[Pt. II]:887–893)     

Decision analysis model of incisional hernia after open abdominal surgery

Background The incidence rate of incisional hernias after open surgery has been reported to be higher than that of port site hernias after laparoscopic surgery. No studies have compared the costs for the health care system in treating those two types of hernia. Methods A systematic review was conducted to obtain the baseline data, and a decision analysis model was created to simulate the occurrence and recurrence of incisional and port site hernias. Results The overall risk of having incisional hernias was eight-times higher than that of having port site hernias (7.4% vs 0.9%). A cost savings of ￡93 per patient can be generated for the health care system in the UK. Similar results were obtained for Germany, Italy and France. Conclusions The additional treatment costs for incisional hernia should be taken into account when the costs of a surgery performed by open approach are compared with by laparoscopy.     

组织工程化表皮膜片构建及其在供皮区的应用研究

目的构建组织工程化表皮细胞膜片并应用于供皮区创面治疗。方法利用患者少量自体或同种异体正常皮肤分离、培养、扩增的表皮细胞,接种于壳聚糖明胶膜构建成表皮细胞膜片;将膜片移植于治疗组供皮区创面、适度加压,同时设立对照组:空白材料对照以及传统油纱布对照覆盖创面。于术后5～10d、30d、90d行大体观察、组织学检查、广谱角蛋白、外皮蛋白、层粘连蛋白、免疫组织化学检测以及Ⅰ、Ⅲ型胶原比值测定(偏光显微镜、RTPCR)。结果利用自体及异体表皮细胞和壳聚糖明胶膜能够构建出人表皮细胞膜片,应用于临床供皮区创面治疗15例,经过3个月随访,疗效肯定。移植膜片创面愈合时间(8.1±1.3)d,空白材料对照区为(16.2±3.8)d,空白油纱布对照区为(23.0±5.8)d。移植膜片存活良好,结构较完整、术后30d及90d观察:12例无明显增生,3例有轻度增生(20.0%),而空白油纱布对照区11例遗留增生性瘢痕(74.4%,χ2=8.127,P<0.01)。结论表皮细胞-壳聚糖明胶膜片能促进供皮区创面早期愈合并减少后期瘢痕增生,具有良好治疗效果。     

The effect of sucralfate,an agent for gastroprotection on the healing of split thickness skin graft donor sites

Skin is the most commonly used tissue for the transplantation. A meticulous care of the donor site is needed to prevent scarring, delayed healing, and pain. Various agents and dressing materials have been reported to help healing of skin graft donor sites. Sucralfate is an extensively used agent, which provides acute gastroprotection and acceleration of chronic ulcer healing. In this study, we assessed the effects of topical sucralfate on the healing of the split thickness skin graft donor sites in a prospective comparative way. The study was carried out on 32 randomly chosen patients undergoing surgery for various causes and requiring split thickness skin graft resurfacing. The upper halves of the skin graft donor sites on the thighs were simply covered with paraffin gauze and the lower half was covered with sucralfate-soaked paraffin gauzes. The day of full epithelization varied from 6 to 9 days and 8–12 days on the sucralfate-applied areas and on the control sites, respectively. The mean value of the healing was 7.01 days in the studied lower halves and 10.8 days in the upper halves. The healing rate was strikingly faster and less painful on the sucralfate-applied areas. We were able to discharge patients earlier than usual, and patients’ comfort increased. It seems that sucralfate is a promising topical agent to increase the healing rate and decrease the incidence of associated problems such as pain and hypertrophic scar.     

Rb1基因第16内含子内21个碱基缺失1例

目地研究双眼视网膜母细胞瘤患者Rb1基因杂合性突变的分子生物学特性。方法应用PCR—SSCP直接测序技术检测双眼视网膜母细胞瘤患者白细胞DNA中Rb1基因杂合性突变。结果50例证实有Rb1基因杂合性突变的病例中有1例发生于第16内含子中可以用3种定位方法解释、具有相同序列的21个碱基缺失。结论这种极为少见的Rb1基因突变方式可能是由于破坏了正常拼接位点的结构而激活了“隐蔽拼接位点”，导致异常的Rb1基因mRNA产生或由此影响整个拼接过程。     

Use of Fmoc-N-(2-hydroxy-4-methoxybenzyl) amino acids in peptide synthesis

The use of N, O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl) amino acid derivatives in the synthesis of peptides with difficult sequences has already been described. With these amino acid derivatives the reversible protecting group 2-hydroxy-4-methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced, and thus the aggregation due to hydrogen-bond interchain association is inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb backbone protection. These new monoFmoc derivatives were obtained in higher yield than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the same as those obtained with bisFmoc derivatives, under the TBTU/HOBt/DIEA conditions. We also compared different syntheses of a difficult peptide with the Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the backbone protection and optimized Boc chemistry approaches gave the desired product in excellent yield and purity. © Munksgaard 1997.     

D-Cycloserine enhances social behaviour in individually-housed mice in the resident-intruder test

D-Cycloserine (DCS) has been reported to affect the central nervous system in man. To investigate whether the compound produces specific behavioural effects, DCS was administered to male mice in a resident-intruder situation and the behaviour of the interacting mice assessed using ethological analysis. Resident mice given DCS (32.0–320.0 mg/kg PO, 60 min before testing) showed dose-dependent increases in social investigation, smaller increases in sexual behaviour and decreased aggressiveness. Defensive and flight behaviour were not affected. Intruder mice showed slight increases in sexual behaviour that were not dose-dependent, and small increases in social investigation. The increases in social investigation induced by DCS (320.0 mg/kg) in resident mice were not reversible with R-HA 966 (32.0 mg/kg IP, 30 min before testing), a blocker of the strychnine-insensitive glycine modulatory site associated with theN-methyl-D-aspartate receptor, but were blocked by the GABA antagonist bicuculline (0.56 mg/kg IP, 5 min before testing). The small DCS-induced increase in sexual behaviour in residents was reversed by R-HA 966. Within the parameters of the resident-intruder situation, DCS exerts socio-sexual behaviour-enhancing effects which are dependent upon the role of the interactant, and which are mediated by an action upon multiple substrates. DCS may be regarded as another example of a sociotropic (approach-promoting) agent.Some of these results have been presented at the 1^st International Congress on Hormones, Brain and Neuropsychopharmacology, Rodos, Greece, September 12–17, 1993     

糖尿病脑内胰岛移植临床初步研究(附三例报告)

本文报告胰岛细胞脑内移植治疗I型糖尿病共3例,分别经过3个月、4个月、6个月的临床观察,其临床症状明显改善或消失,空腹血糖由移植前平均12.38mmol/L下降至7.77mmol/L;3例患者普通胰岛素用量平均每日62.3~u,移植后第21～30天均完全停用胰岛素,其中1例已持续撤离胰岛素治疗达5个月。观察结果提示:胰岛移植物在患者的脑内成活,并具有良好的内分泌功能。     

What the structure of angiostatin may tell us about its mechanism of action

Summary.  Originally discovered in 1994 by Folkman and coworkers, angiostatin was identified through its antitumor effects in mice and later shown to be a potent inhibitor of angiogenesis. An internal fragment of plasminogen, angiostatin consists of kringle domains that are known to be lysine-binding. The crystal structure of angiostatin was the first multikringle domain-containing structure to be published. This review will focus on what is known about the structure of angiostatin and its implications in function from the current literature.