MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors

Summary The properties of MDL 72222 (1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate), a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones, are described.On the rabbit isolated heart, MDL 72222 was a potent antagonist of responses mediated through the receptors for 5-HT present on the terminal sympathetic fibres. The threshold for antagonism was approximately 0.1 nM and the negative logarithm of the molar concentration of MDL 72222 which reduced the chronotropic response of the isolated rabbit heart to twice an ED₅₀ of 5-HT to that of the ED₅₀ was 9.27. MDL 72222 was also highly selective since responses to the nicotine receptor agonist, dimethylphenylpiperazinum iodine (DMPP), were inhibited only at concentrations more than 1000 times those necessary to inhibit 5-HT.In the anaesthetised rat, MDL 72222 produced marked blockade of the Bezold-Jarisch effect of 5-HT. Again, inhibition was selective since much higher doses of MDL 72222 failed to alter the response to electrical stimulation of the efferent vagus nerves. In contrast, MDL 72222 proved only a weak and essentially non-selective antagonist of responses mediated by the 5-HT M-receptor present on the cholinergic nerves of the guinea-pig ileum.MDL 72222 does not block smooth muscle contractile responses elicited by oxytocin or mediated through 5-HT D-receptors, muscarinic or nicotinic cholinoceptors or histamine H₁-receptors except at relatively high concentrations. Similarly, in a number of radioligand binding assays carried out using brain tissue membranes, the displacing effects of MDL 72222 were absent or weak at sites identifying compounds with activity at ₁, ₂ or -adrenoceptors, 5-HT₁ or 5-HT₂ receptors, benzodiazepine receptors or histamine H₁-receptors.MDL 72222 is the first reported selective and potent antagonist of responses mediated through the 5-HT receptors present on the terminal sympathetic neurones of the rabbit heart and on the neurones subserving the afferent limb of the Bezold-Jarisch reflex. The compound should provide a useful means by which responses mediated through such sites can be distinguished.     

Animal models and treatment of prostate cancer

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The "Pollard tumors" provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.     

In vitro H-serotonin (5-HT) synthesis and release in BALBc and C57BL mice. II. Cell body areas

"In vitro" 3H-5-HT and 3H-5-HIAA, newly synthesized from 3H-TRP, are measured in the brainstem, the anterior raphe nuclei and the locus coeruleus of C57BL and BALBc mice. As found for the caudate nucleus and the hippocampus, higher synthesis and release are determined in C57BL than in BALBc, for the locus coeruleus and more globally, for the brainstem. But these differences disappear when the study is carried on the raphe dorsalis and the raphe centralis nuclei. Therefore the serotonergic activity could be independently regulated at the level of cell bodies and at those of terminals. However, the 5-HT metabolism of NRD of BALBc mice could be submitted to a specific autoinhibition which could explain a lower 5-HT synthesis and release at the corresponding terminal level, compared to C57BL.     

白细胞介素-1对大鼠离体胰岛B细胞分泌功能的影响

目的 :观察白细胞介素 1(IL 1)对大鼠胰岛B细胞分泌功能的影响并探讨其机制。方法 :采用胰岛细胞培养的方法 ,观察IL 1对胰岛素分泌和MTT还原的影响 ;通过分子杂交检测c fosmRNA并分析蛋白质合成的变化。结果 :IL 1作用后胰岛素分泌和MTT还原量明显减少 ,且有时间依赖性 ;IL 1诱导c fosmRNA ,从而使细胞蛋白质表达发生变化。结论 :IL 1可能通过改变胰岛细胞内基因表达 ,抑制细胞代谢 ,从而使胰岛素分泌减少     

后路凸侧椎板楔形截骨经肋椎关节松解胸椎间隙治疗青少年重度脊柱侧后凸

【摘要】 目的：评价经后路凸侧椎板楔形截骨经肋椎关节松解胸椎间隙矫形治疗青少年重度脊柱侧后凸畸形的安全性和早期临床效果。方法：2014年5月~2016年12月对我院15例青少年重度脊柱侧后凸患者行经后路凸侧椎板楔形截骨经肋椎关节松解胸椎间隙手术治疗,术前仅1例严重脊柱侧后凸患者行头盆环牵引。男6例,女9例,年龄13～18岁（16.1±1.6岁）。其中先天性脊柱侧后凸3例,特发性11例,神经纤维瘤病性1例。术前侧凸Cobb角82°～144°（102.5°±17.6°）,侧凸的柔韧性为6.4％～28.5％[（21.56±5.70）%];后凸50°～95°（68.1°±15.3°）,冠状位躯干偏移距离（C7中垂线与骶骨中垂线距离）2.0～6.8cm（3.40±1.37cm）。术前四肢肌力及感觉均正常。观察治疗效果。结果：椎板楔形截骨5.20±0.56个（4~6个）,松解椎间隙5.20±0.56个（4~6个）,手术时间6.1～7.9h（7.00±0.51h）,术中出血量1050～2500ml（1450.0±521.3ml）。术后侧凸Cobb角18°～40°（28.0°±6.6°）,矫正率72.5%;后凸22°～42°（27.8°±6.1°）,矫正率58.4%;冠状位躯干偏移距离0～2cm（0.85±0.74cm）,矫正率72.8%。随访25～41个月（33.1±5.4个月）。末次随访时侧凸Cobb角19°～43°（30.0°±6.9°）,矫正率70.6%;后凸22°～42°（28.6°±6.5°）,矫正率57.2%;冠状位躯干偏移距离0.2～2.3cm（1.10±0.72cm）,矫正率71.3%。无胸膜破裂,无假关节形成,无内固定断裂及松动,矫正度无显著丢失。1例患者术前骨盆牵引发生钉道感染,经局部换药及抗生素应用,2周后感染控制;1例术后第3天发生十二指肠系膜上动脉综合征,采取禁食水、持续胃肠减压、维持水电解质平衡、左侧卧位,术后2周痊愈;1例T4左侧椎弓根螺钉侵入椎管压迫神经,术后5h发生左下肢不完全性瘫痪,术后8h去除T4左侧椎弓根螺钉,术后5个月左下肢功能完全恢复。结论：采用后路凸侧椎板楔形截骨经肋椎关节松解胸椎间隙治疗青少年重度脊柱侧后凸畸形,不需要剥离椎体侧方胸膜,手术解剖层次表浅和创伤小,不仅有助于增加脊柱柔韧性,而且可提供足够的压缩和闭合空间来矫正脊柱侧后凸,能获得良好的脊柱三维矫正。     

A mini-incision carpal tunnel release technique to prevent pillar pain: A technical note

Pillar pain represents one of the most common complications of classic open carpal tunnel release (CTR). This complication causes a sense of discomfort worse than the compression syndrome itself. We, herein, introduce a new treatment method for CTR through a mini-incision, which allows subcutaneously cutting the transverse carpal ligament (TCL) and releasing the median nerve without neurovascular complications. This mini-incision approach can allow the direct visualization and preservation of the thenar motor branch in those rare cases where it has an aberrant origin. For the past 10 years, we have consecutively performed this technique in the surgical treatment of 318 patients with the diagnosis of primary CTS, without developing any neurovascular and tendon injuries as well as pillar pain.     

Flexor Tenosynovectomy for Recurrent Carpal Tunnel Syndrome: A Retrospective Case Series of 108 Hands

Background: The etiology of recurrent carpal tunnel syndrome (CTS) is unclear, and outcomes following secondary surgery in this demographic have been poorer than primary surgery. Fibrosis and hypertrophy have been identified in the flexor tenosynovium in these patients. The authors use flexor tenosynovectomy (FTS) for recurrent CTS after primary carpal tunnel release and present a review of these patients. Methods: A retrospective chart review was performed of 108 cases of FTS for recurrent CTS from 1995 to 2015 by 4 attending surgeons at one institution. Demographic information, symptoms, and outcomes were among the data recorded. A phone survey was conducted on available patients where the shortened version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and satisfaction were assessed. Results: Average office follow-up was 12 months. Average age was 57.5 years. A total of 104 (96%) reported symptom improvement and 48 (44%) reported complete symptom resolution. Forty patients were available for long-term follow-up at an average 6.75 years postoperatively via phone interview. Average QuickDASH score was 31.2 in these patients. Thirty-six (90%) of 40 patients were initially satisfied at last office visit, and 31 (78%) of 40 were satisfied at average 6.9 years, a maintenance of satisfaction of 86%. Satisfied patients were older (58 years) than unsatisfied patients (51 years). Conclusion: Both long-term satisfaction and QuickDASH scores in our cohort are consistent with or better than published results from nerve-shielding procedures. The authors believe a decrease in both carpal tunnel volume and potential adhesions of fibrotic or inflammatory synovium contributes to the benefits of this procedure. This remains our procedure of choice for recurrent CTS.     

Sonographic Follow-Up of Patients With Cubital Tunnel Syndrome Undergoing in Situ Open Neurolysis or Endoscopic Release: The SPECTRE Study

Background:The measurement of cross-sectional area (CSA) is a diagnostic tool to detect entrapments syndrome. The aim of this study was to compare the clinical outcome in elbows undergoing endoscopic and “in situ” open cubital tunnel release for cubital tunnel syndrome (CuTS) using ultrasound-related changes in the largest CSA of the ulnar nerve. The purpose is to determine the association between clinical outcome and CSA. Methods: From May 2011 to April 2016, 60 patients with CuTS were prospectively followed and not randomly divided in two groups: 30 patients undergoing an endoscopic release (ER) and 30 patients with “in situ” open neurolysis (OR). A sonographic examination was performed by the senior authors at baseline and 3, 6, and 12 months after surgical decompression. Results: CSA values were statistically significantly lower in the ER. Hand grip strength difference with Jamar test was not statistically significant a 12 months (39 kg vs 27 kg). Static-2 point discrimination test difference was only statistically significant lower in the endoscopic group at 3, 6 and 12 months but not clinically relevant (5 mm vs 6 mm). The American Shoulder and Elbow Surgeons—Elbow questionnaire (ASES-e) function score, ASES-e Pain score, and ASES-e Satisfaction score were not statistically significant different between the two groups at 3, 6, and 12 months post operatively. Conclusions: The study confirms that in spite of lower values of CSA in the ER, there is not a statistically significant difference between the two techniques in terms of subjective outcomes. Ultrasound (US) measurements seem to have a limited value in clinical results of patients treated for entrapment neuropathy of the ulnar nerve.Type of study/LOE: Prognostic Level III     

内镜下全腹膜外Sublay修补在腹壁疝中的应用

目的评价腹壁疝内镜下全腹膜外Sublay(TES)手术的效果并总结经验。方法回顾性总结国内10所医院自2016年3月至2019年7月115例腹壁疝内镜下TES手术的患者资料。分析患者情况、疝的特点、手术经过和结果。结果115例计划实施TES的患者中,因严重腹膜破损中转为IPOM修补患者1例,其余均成功手术。可以缝合缺损患者108例(94.74%),需要永久补片固定患者15例(13.16%)。放置引流患者76例(66.67%),中位手术时间为144 min,术中无严重并发症发生。随访时间3~45个月,总并发症发生率为20例(17.54%),其中出现血清肿患者5例(4.38%)。绝大多数患者术后仅出现轻微疼痛,未出现慢性疼痛。结论在腹壁疝的治疗中,对熟悉腹壁解剖的外科医师而言,TES是一种有效、安全的修复手段。在熟悉手术的基础上适应症可逐步拓展。