The effect of nicergoline on the lower urinary tract muscle

Summary Two series of experiments were performed to determine whether nicregoline possesses an alpha-adrenergic blocking action on the lower urinary tract musculature in dogs and humans. One series consisted of in vivo studies of urethral pressure profile recordings in 19 female dogs, and their responses to adrenergic stimulation with noradrenaline or methoxamine, alone and following administration of nicergoline. The other series consisted of in vitro isometric studies of 61 strips of human prostate, and the establishement of dose response curves to nor-adrenaline alone and in the presence of various concentrations of nicergoline. In both sets of experiments clear evidence of an alpha-adrenergic blocking effect was obtained. From the in vitro experiments, the Kb of nicergoline was calculated as 9x10^-9 M.     

Enzyme activities associated with the demyelinating phase of canine distemper

Summary Canine distemper, a naturally occurring viral disease of dogs which often terminates in parainfectious demyelination, was used as a model to study the role of acid proteinase, neutral proteinase and beta-glucuronidase in demyelination. These enzymes were higher in cerebella of dogs with distemper-associated demyelination than in age-matched controls. The highest elevations corresponded with the most severely demyelinated cerebella. The source of the increased enzymes activities was apparently unrelated to the lymphocytes present in areas of demyelination.The direct effect of distemper virus and serum on these enzymes was tested in canine glial monolayers. Virus infection resulted in lower enzyme activities in cells concomitant with the appearance of cellular lesions. There was a relative increase of beta glucuronidase activity in the media suggesting that distemper virus released pre-formed lysosomal enzymes. Serum which was obtained from dogs with distemper-associated demyelination and had previously demyelinated cerebellar explants, also decreased activities of all 3 enzymesin vitro.The 3 enzymes were measured in gerbil brains at various time intervals following unilateral cerebral infarction to determine if processes other than demyelination also caused these enzymes to be increased. Uncomplicated ischemic necrosis (24 h post infarction) did not alter the activities of these enzymes. Invasion of macrophages to ingest and digest necrotic tissue 10 days after infarction resulted in greatly increased acid proteinase and beta-glucuronidase, but unchanged neutral proteinase, activities.It was concluded that the increased activities of acid proteinase and beta-glucuronidase in demyelinated tissue probably are derived from macrophages ingesting damaged tissue. Neutral proteinase may be more specifically involved in the demyelinating process since this is partially located within myelin and can degrade the basic protein of myelin.Supported in part by Research grant Nos. GM 1052 and Al-09022 from National Institutes of Health Service, U.S. Public Health Service.     

正畸力作用下上颌尖牙生物组织应力的三维有限元分析

建立了包括牙齿、牙周膜、牙髓、牙槽骨的上颌尖牙三维有限元模型 ,对不同加力方式下牙周组织的应力分布进行对比研究。目的是用较为先进和准确的双螺旋 CT法建立尖牙的三维有限元应力分析模型 ,为正畸治疗提供更为准确的数据并为模拟尖牙在正畸力作用下移动过程的模拟初态建立更为精确的模型。     

Postnatal development of vascular β-adrenoceptor-mediated responses and the increase in the adrenaline content of the adrenal gland have a parallel time course

The present study was undertaken to analyse the relationship between postnatal development of vascular ₂-adrenoceptor-mediated responses and the content of adrenaline in the adrenal gland and its concentration in plasma. Dog saphenous vein tissue from newborn, two-weeks old and adult animals were either preloaded with ³H-noradrenaline (or ³H-adrenaline) to study prejunctional -adrenoceptor-mediated effects or mounted in organ baths to determine isoprenaline-induced relaxation of preparations contracted by phenylephrine to about 65010 of the maximum. The adrenal glands and samples of blood from the same animals were taken for estimation of adrenaline and noradrenaline.At birth, there were no -adrenoceptor-mediated effects pre- or postjunctionally. At two weeks, while the results at the prejunctional level were not significantly different from those obtained in newborns, at the postjunctional level there was a relaxant response to isoprenaline, which antagonised about 35010 of the previous contraction to 1.75 mol·l^–1 phenylephrine. In adults, isoprenaline (50 nmol·l^–1) increased by 24% tritium overflow evoked by electrical stimulation of tissues preloaded with ³H-noradrenaline but not that of tissues preloaded with ³H-adrenaline. On the other hand, propranolol (1 mol·l^–1) reduced by 21% the overflow of tritium evoked by electrical stimulation of tissues preloaded with ³H-adrenaline but not that of tissues preloaded with ³H-noradrenaline; postjunctionally, the maximal response to isoprenaline antagonised 70% of the previous contraction to 1.75 mol·l^–1 phenylephrine.At birth the catecholamine content of the adrenals was relatively low (2.9 ol·g^–1) and the adrenaline/noradrenaline ratio was 0.26; two weeks later, the catecholamine content was 14.5 mol·g-1and the adrenaline/noradrenaline ratio was 0.74; in adults, the catecholamine content was 24.5 mol·g^–1 and the adrenaline/noradrenaline ratio was 2.3. In plasma, the highest concentration of adrenaline was observed at birth (11.8 nmol·l^–1); two weeks later it was 5.5 nmol·l^–1 and in adulthood it fell to 3.1 nmol·l^–1.On the basis of these results, it is concluded that some link between the postnatal increase in adrenaline adrenal content and the development of ₂-adrenoceptor-mediated pre- and postjunctional effects may exist. Additionally it is suggested that circulating adrenaline may trigger the development of ₂-adrenoceptor-mediated responses as well as some hypertensive states occurring as a consequence of an overreactivity of the sympathoadrenal system. Correspondence to: S. Guimarães at the above address     

Canine laryngeal transplantation: preliminary studies and a new heterotopic allotransplantation model

While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single long-term survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the longterm prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. In the dog, CsA alone is inadequate for the long-term prevention of transplant rejection while combined therapy with CsA, RS-61443 and methylprednisolone can provide long-term rejection-free larynx transplant survival. The newly developed heterotopic larynx transplant model allows studies of transplant viability, rejection mechanisms and neural regeneration and functional recovery to be performed with minimal animal morbidity and lowered research costs.Presented at the combined meeting of the Society of Head and Neck Surgeons and the European Organization for Research and Treatment of Cancer (EORTC), Paris, France, 25–28 May, 1994     

地尔硫卓对失血性休克犬肾脏的保护作用

目的：探讨地尔硫卓（Ｄｉｌｔｉａｚｅｍ,Ｄｉｌ）对失血性休克犬肾脏的保护作用及机理。方法：动脉放血,使血压降低至５３３～６６７ｋＰａ（４０～５０ｍｍＨｇ）,维持９０ｍｉｎ后回输血液进行复苏。在休克３０ｍｉｎ时,分别给动物输注盐水和（或）Ｄｉｌ。结果：Ｄｉｌ能明显提高失血性休克动物的平均动脉压（ＭＡＰ）;降低肾脏组织中的丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）的活性;保护肾脏组织的超微结构。结论：Ｄｉｌ对失血性休克犬的肾脏具有保护作用。     

Effects of molsidomine,nitroglycerin, and isosorbide dinitrate on the coronary circulation,myocardial oxygen consumption,and haemodynamics in anaesthetized dogs

Summary The effects of i.v. molsidomine administration on the coronary circulation, myocardial oxygen consumption, and haemodynamics were studied in open-chest dogs with non-constricted coronary arteries, and compared to those of nitroglycerin and isosorbide dinitrate. Molsidomine (50, 100, 250 g/kg) reduced coronary flow while nitroglycerin (5, 10, 20 g/kg) and isosorbide dinitrate (50, 100, 250 g/kg) augmented coronary flow indicating coronary dilatation. Coronary resistance remained unaffected by molsidomine but fell after both nitrates. Molsidomine decreased myocardial oxygen consumption whereas nitroglycerin and isosorbide dinitrate initially increased oxygen consumption followed by a reduction. A decrease in stroke work was calculated after all three drugs. Minute work fell after molsidomine and nitroglycerin but not after isosorbide dinitrate.Heart rate and contractility remained unchanged by molsidomine but were both significantly enhanced by both nitrates. Stroke volume and cardiac output fell after molsidomine but increased immediately after both nitrates when administered with a subsequent decrease. Peripheral resistance was unchanged by the low dose of molsidomine but significantly decreased by the two nitrates immediately after administration indicating precapillary vasodilatation. The fall in blood pressure after molsidomine followed the reduction in cardiac output as sequel of lowered preload and venous return to the heart. The same mechanism decreased heart work after both nitrates but in addition vasodilatation of the coronary arteries and arterial vessel occurred.The effects of the three compounds are mainly the consequence of extracardiac effects, i.e. increased capacity of postcapillary vessels (molsidomine) plus arteriolar vasodilatation of short (nitroglycerin) and long duration (isosorbide dinitrate), respectively. Whereas molsidomine exerts no effects on the heart and coronary circulation both nitrates dilate coronary arteries and change heart performance thus indicating direct effects on the entire heart.     

Tissue specific susceptibility of alpha-adrenoceptor mediated vasoconstriction to nifedipine

Summary The influence of the calcium antagonist nifedipine on ₁- and ₁-adrenoceptor vasoconstrictor effects was investigated in vitro. Changes in tension were monitored isometrically on helical strips of canine circumflex coronary and saphenous arteries suspended in 10 ml organ baths and of saphenous veins superfused with Krebs-Henseleit solution. Distinction between ₁- and ₂-adrenoceptor was made by using selective -adrenoceptor blocking drugs such as rauwolscine, yohimbine, corynanthine and prazosin, and the agonists noradrenaline, phenylephrine and guanfacine. In venous and both arterial vascular smooth muscles, the contractile process could be triggered by stimulation of both ₁- and ₂-like adrenoceptors. Nifedipine inhibited the venoconstrictor response to the ₂-agonist guanfacine, leaving that to the ₁-agonist phenylephrine unchanged. In saphenous arteries, nifedipine in addition to guanfacine also antagonized constrictor responses to phenylephrine, though to a significantly weaker extent. In circumflex coronary arteries, nifedipine was equally potent in antagonizing responses to both ₁- and ₂-adrenoceptor stimulation.It is suggested that the susceptibility of -adrenoceptormediated vasoconstrictor effects to blockade by calcium antagonists depends not only on the subtype of -adrenoceptor but, in addition, on the type and origin of vascular smooth muscle and may be a reflection of tissue variations in intracellular calcium stores.     

Fractographic Examination of Racing Greyhound Central (Navicular) Tarsal Bone Failure Surfaces Using Scanning Electron Microscopy

The greyhound is a fatigue fracture model of a short distance running athlete. Greyhounds have a high incidence of central (navicular) tarsal bone (CTB) fractures, which are not associated with overt trauma. We wished to determine whether these fractures occur because of accumulation of fatigue microdamage. We hypothesized that bone from racing dogs would show site-specific microdamage accumulation, causing predisposition to structural failure. We performed a fractographic examination of failure surfaces from fractured bones using scanning electron microscopy and assessed microcracking observed at the failure surface using a visual analog scale. Branching arrays of microcracks were seen in failure surfaces of CTB and adjacent tarsal bones, suggestive of compressive fatigue failure. Branching arrays of microcracks were particularly prevalent in remodeled trabecular bone that had become compact. CTB fractures showed increased microdamage when compared with other in vivo fractures (adjacent tarsal bone and long bone fractures), and ex vivo tarsal fractures induced by monotonic loading (P < 0.02). It was concluded that greyhound racing and training often results in CTB structural failure, because of accumulation and coalescence of branching arrays of fatigue microcracks, the formation of which appears to be predisposed to adapted bone. Received: 12 November 1999 / Accepted: 10 March 2000     

双异丙吡胺对犬右心室心外膜下细胞瞬间外向钾电流抑制作用的研究

目的：探讨双异丙吡胺对犬右心室心外膜下（Epi）细胞复极1期末4-氨基吡啶敏感的非钙依赖性瞬间外向钾电流（Ito1）的抑制作用，以期为临床药物治疗Brugada综合征等起源于右心室的恶性心律失常疾病提供必要的证据。方法：酶解分离犬右心室Epi单个心肌细胞，在全细胞钳制条件下，观察双异丙吡胺对犬右心室Epi细胞Ito1离子流的抑制作用。结果：（1）在刺激频率为0．2Hz、37℃和去极化试验电压＋70mv水平，在临床相关的治疗浓度范围内双异丙吡胺呈浓度依赖性有效地抑制犬Ito1离子流而无电压依赖性。（2）当刺激频率超过1Hz时，双异丙吡胺对Ito1离子流的抑制作用具有明显的快频率应用依赖性。（3）双异丙吡胺对Ito1离子流的抑制作用依赖于去极化试验电压脉冲提示双异丙吡胺属于通道开放状态阻滞剂。结论：在临床相关的治疗浓度范围内双异丙吡胺能以浓度依赖性方式抑制犬右心室Epi细胞的Ito1离子流，恢复Epi细胞间Ito1离子流的均衡性，因而对Brugada综合征等疾病所致的、以2相折返为基础的恶性心律失常可能有预防作用。