大鼠实验性肝硬化时甲状腺激素水平及甲状腺形态学变化的研究

将Wistar大鼠分为三组：肝硬化组，给予四氯化碳等复合因素，给药组，除给CCl4等复合因素外，用赤栀黄合剂灌胃41天；正常组给以一般饮食及饮水。结果，与正常组及给药组相比，硬化组血T3、T4测定值低，甲状腺滤泡中胶质明显减少，滤泡细胞与胶质间空泡增多，滤泡上皮细胞内PAS阳性小滴数日增多。表明在实验性肝硬化期间甲状腺参与了抗疾病的代谢活动，其机理可能是肝硬化时肝细胞合成、转运T3，T4的蛋白质减少。运输中的T3，T4减少，活性甲状腺素不足，从而导致甲状腺代偿性功能活跃。赤栀黄合剂具有保肝，恢复甲状腺素水平的作用。     

Thoracic epidural analgesia in aortocoronary bypass surgery II: effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may – in part – be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS).
Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 μg–kg^-1) anaesthesia, the HF + TEA group with the same fentanyl dose + TEA with 10 ml bupivacain 5 mg ml^-1, followed by 4 ml every hour, and the LF + TEA group receiving fentanyl 15 μg kg^-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, Cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively.
A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and Cortisol was noticed in all groups, but the increase was delayed in the epidural groups.
Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.     

皮质类固醇对哮喘患者T淋巴细胞亚群的影响

应用Ｔ淋巴细胞亚群单克隆抗体对类固醇治疗前后哮喘患者外周血Ｔ淋巴细胞亚群的变化进行检测，结果提示：类固醇治疗后ＯＫＴ８较治疗前增高，ＯＫＴ４／ＯＫＴ８比值较治疗前降低并且接近正常，说明Ｔ淋巴细胞是类固醇作用的靶细胞，类固醇可直接影响Ｔ细胞亚群分布，发挥其非特异性抗炎作用。     

Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.     

Steroid receptor assay in various tissues and tumors

Four types of steroid receptors were assayed in 1715 tumors of various localization and in 101 normal tissue samples from the mammary gland, uterus, and endometrium; tissuespecific distribution of steroid receptors was demonstrated. Expression of steroid hormones (especially estrogen receptors) is enhanced in proliferating compared with resting tissues and in hormone-sensitive tumors compared with adjacent normal tissue. It is assumed that hormone sensitivity of the tumor reflects hormone sensitivity of parental organ. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 558–561, May, 1998     

丙氨瑞林治疗子宫内膜癌病人的性激素及有丝分裂指数的变化

目的：观察丙氨瑞林对子宫内膜癌的治疗作用。方法：对诊刮确诊的１７例子宫内膜癌病人，予丙氨瑞林７００μｇ，ｉｍ，ｑｄ×７ｄ，用药前后作性激素测定及组织学检查。结果：绝经妇女用药后血中ＦＳＨ和ＬＨ下降（Ｐ＜０．０１和＜０．０５），雌二醇、孕酮及睾丸酮变化不明显。其中１３例内膜样腺癌用药后有丝分裂指数明显下降（Ｐ＜０．０１），有丝分裂指数变化与癌周内膜之反应有关。呈增生反应癌周内膜癌组织有丝分裂指数下降值明显高于呈萎缩状态癌周内膜。结论：丙氨瑞林治疗子宫内膜癌后能降低ＦＳＨ和ＬＨ水平，对子宫内膜癌尤其是雌激素依赖性内膜癌有一定疗效。     

Left ventricle haemodynamics and vaso-active hormones during graded supine exercise in healthy male subjects

Left ventricle systolic and diastolic functional parameters were measured by gated equilibrium radionuclide cardiography in 12 healthy men (age 33–51 years) at rest and during graded supine exercise. The leftventricle end-diastolic volume showed an initial small (11%) increase during low submaximal exercise [from mean 163 (SD 40) at rest to mean 181 (SD 48) ml], while left ventricle end-systolic volume decreased successively [from mean 59 (SD 19) to mean 39 (SD 21) ml] with increasing exercise. Stroke volume was therefore elevated at all exercise levels compared with rest [mean 104 (SD 23) ml], and the peak value [mean 128 (SD 33) ml] was found at the lowest exercise level, contributing 40% to the initial increase in cardiac output. Cardiac output increased from mean 6.2 (SD 1.4) at rest to mean 20.2 (SD 5.0) 1 · min^–1 at maximum. Left ventricle peak ejection and peak filling rates increased from mean 449 (SD 89) and mean 442 (SD 85) ml · s^–1 at rest to mean 996 (SD 227) and mean 1255 (SD 333) ml · s^–1, respectively, at maximum. The myocardium oxygen consumption, assumed to be proportional to the sum of the stroke work and the potential energy, increased fourfold, but absolute values were twice as high as expected, indicating that extrapolation from data obtained in dog hearts (as we have done) cannot be directly applied to humans. Selected vaso-active hormones were measured at all exercise intensities. Noradrenaline (NA), adrenaline (A) and angiotensin II (AII) concentrations showed a very pronounced increase at maximal exercise compared with the preceding lower intensites, while atrial natriuretic factor (ANF) and cyclic guanosinemonophosphate (cGMP) concentrations showed a more continuous increase, and dopamine (DA) remained almost unchanged. This speaks in favour of a crucial role for NA, A and AII in preserving blood pressure at maximum exercise, while DA probably has no importance for the cardiovascular homeostasis during exercise. Increases in concentrations of ANF and cGMP were highly correlated (r = 0.86). Our data supported the opinion that there is a cardiac limitation to maximal performance connected to the cardiac pumping capacity.     

Endocrinology: Immunohistochemical sex steroid receptor distribution in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle

The bleeding problems experienced by users of subdermal levonorgestrelimplants (Norplant) remain unexplained. The aim of the presentstudy was to investigate the oestrogen (ER) and progesteronereceptor (PR) distribution in levonorgestrel-treated endometrialbiopsies from 31 subjects recruited in Jakarta, Indonesia, andto compare the sex steroid receptor immunostaining with thatof endometrium from 58 normally cycling women from Melbourne,Australia. Sex steroid receptor immunoreactivity was additionallycompared with days of exposure to subdermal levonorgestrel,serum oestradiol and progesterone levels and days of bleedingduring a 90-day reference period. An immunohistochemical techniquewith an alkaline phosphatase anti-alkaline phosphatase (APAAP)detection system for use in formalin-fixed paraffin wax embeddedendometrial tissue was employed. Significantly greater meanimmunostaining scores of stromal PR were observed in Norplantcompared with control endometrium at all stages across the cycle.No significant correlations were demonstrated between sex steroidreceptor immunostaining and days of exposure to subdermal levonorgestrel,serum oestradiol or progesterone concentrations or days of bleedingduring a 90-day reference period. Whether the elevated stromalPR immunostaining in Norplant-treated endometrium is a consequenceof increased synthesis or reduced turnover of receptor remainsunclear. As yet it is undetermined whether increased PR immunoreactivitycorresponds to an increase in number of functional PR.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

THE EVOLUTIONARY ANTECEDENTS TO LOVE

Behaviors are adaptations to the physical, biotic, and social environments. Great diversity exists among vertebrates in reproductive behaviors and the neuroendocrine mechanisms underlying these behaviors. Study of this diversity illuminates species, population, and sex differences in hormone–brain-behavior relations. It also can provide insights into how and why certain neuroendocrine mechanisms evolved. Discoveries in evolution and ecology, neuroscience and endocrinology, are complementary and interrelated, and when applied in behavioral neuroscience, the investigator's perspective is less constrained by existing dogma. Naturally-occurring organisms not typically studied can be especially useful as their unusual adaptations illustrate alternative solutions to particular problems. Indeed, they ‘often force one to abandon standard methods and standard points of view’ with the result that, ‘in trying to comprehend their special and often unusual adaptation, one often serendipitously stumbles on new insights’ (Bartholomew, 1982). Thus, to ignore comparative research would greatly limit our understanding of the evolution of hormone-behavior relations. As Bullock (1984) admonishes, “without due consideration of the neural and behavioral correlates of differences between higher taxa and between closely related families, species, sexes, and stages, we cannot expect to understand our nervous systems or ourselves”. © 1998 Elsevier Science Ltd. All rights reserved.