T3、T4试验对32例危重病人预后的推测

各种严重的非甲状腺疾病,可引起血清T_3,T_4浓度的降低,且T_3,T_4浓度的下降与病情的严重性有密切的关系。为此我们对32例危重病人的甲状腺功能进行前瞻性研究,以探讨其与预后的关系。一、临床资料 (一)观察对象:本组男20例,女12例;年龄29～81岁,平均61岁。32例均为住院危重病人,皆无甲亢或甲(?)的表现,也未曾服用可影响甲状腺激素分     

甲亢和甲减患者血脂和载脂蛋白的变化

本文观察35例Graves 甲亢(GD)和20例甲状腺功能减退(甲减)患者药物治疗前后血脂和载脂蛋白(APO)的变化,GD 患者治疗前血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和APOB 均明显降低,经抗甲状腺药物(ATD)治疗甲亢缓解后,上述指标恢复正常。治疗前后GD 患者血清甘油三脂(TG)及APOA 浓度无明显变化。治疗前血清TC、APOB 浓度与T_3,T_4水平呈负相关。甲减患者治疗前血清TC、TG 和LDL-C 高于对照组,替代治疗后,其浓度降至正常。患者APOB 浓度比治疗前下降,但治疗前后血清HDL-C 和APOA 水平无显著变化。治疗前血清T_c与血清T-3、T_4浓度呈负相关。     

三碘甲状腺原氨酸毒症临床探讨

甲状腺分泌两种具有生理活性的激素,即甲状腺素(T_4)和三碘甲状腺原氨酸(T_3),在甲状腺机能亢进症(简称甲亢)中,大多数血清T_4和T_3的浓度同时升高。但近年来已发现某些甲亢病人血清T_4浓度正常,而T_3增高,称“三碘甲状腺原氨酸毒症或T_3甲亢(T_3-toxicosis)。我院从1976年至1989年在确诊1000例甲亢中,发现41例T_3型甲亢,现报告如下: 临床资料一般资料:本文病例均系本院已确诊病人,男8例,女33例;年龄:16—53岁,平均36.4岁。     

肾病综合征血清T_3T_4的变化

肾脏不仅排泄体内的代谢产物,而且还参与体内水、电解质、酸硷度及内分泌的调节。当肾小球疾病。尤其是肾功能不全时,可引起其它器官的损害。甲状腺也不例外。我们对29例肾病综合征(以下简称肾综)患者血清T_3T_4的变化与疾病活动的关系,进行了研究,发现肾综活动期血清T_3T_4浓度下降明显,兹将结果报告如下:     

醋酸铅对大鼠血清T_3、T_4和甲状腺摄碘的影响

铅是一种对许多器官和组织具有毒作用的重金属,但是有关铅对甲状腺的毒性作用报道不多。本文观察了铅对大鼠血清T_3、T_4及甲状腺摄碘的影响,为铅对甲状腺的毒性作用提供实验资料。 材料和方法 取Wistan大鼠24只,由中国医科大学实验动物中心提供。体重220～250g,雌雄各半。     

老年肺心病急性期血清T_3、T_4测定

慢性肺原性心脏病期患者由于长期肺部反复感染、慢性缺氧,有的病人到后期可出现继发性肾上腺皮质功能不全,以致需要每日补充生理剂量的糖皮质激素,方能促使病人全身情况的好转。重症肺心病人,是否会有甲状腺功能低下,导致体内基础代谢下降,尚无报导。本文作者于1983年冬至1984年春在住院的部分重症肺心病患者中,抽血送查了血清T_3、T_4浓度;同期又在其它病种的病人中亦抽血送查血清T_3、T_4,进行对照观察。     

血清3、3′、5′一三碘甲状腺原氨酸(rT_3)在甲状腺机能亢进与减退症中的诊断价值

本文报道150例甲亢、85例甲减患者血清rT_3的测定结果,分析其诊断价值。两组rT_3的变化均非常明显(P<0.001),甲亢组rT_3升高小于T_3,大于T_4,诊断符合率86.7％,低于T_3和T_4;甲减组rT_3下降的程度及诊断符合率(94.2％)均超过T_3T_4,仅次于TSH,表明血清rT_3反映甲减比甲亢敏感,尤对早期甲减有重要意义。本结果提示,血清rT_3可作为诊断甲减较有价值的指标。     

肺心病患者血清甲状腺激素监测及临床意义

用放免法测定46例肺心病患者血清甲状腺激素水平并与正常对照组比较,结果提示:肺心病患者血清T_3、T_4均明显低于正常组,尤以T_3为著(P<0.01),TSH与正常对照组比较差异无显著性。按病情轻重分为单纯肺心病组(单纯肺心组),呼吸衰竭组(呼衰组),肺性脑病组(肺脑组),其T_3、T_4均值逐渐依次下降,提示测定T_3、T_4值可综合判断肺心病患者病情程度及预后的关系。     

叶酸、维生素B6、维生素B12对大鼠同型半胱氨酸水平及阴茎组织内NOs的影响

目的:观察补充叶酸、维生素B6和维生素B12对高蛋氨酸(Met)喂饲所引起高同型半胱氨酸(Hcy)血症及阴茎组织内NOs的影响.方法:Wistar大鼠30只随机分成3组:对照组、模型组和干预组,每组10只,分别喂以普通鼠饲料、普通鼠饲料添加3% Met、普通饲料添加3% Met同时每只鼠每天添加叶酸0.5mg、维生素B6 2.5mg和维生素B12 50μg,喂养3个月.测定血浆总Hcy(tHcy)浓度、血清叶酸浓度及阴茎组织NOs的浓度.结果:实验前,血浆tHcy、血清叶酸浓度3组间无明显差异.实验后,干预组血清叶酸浓度明显高于实验前和模型组及对照组(P＜0.05);干预组血浆tHcy浓度低于模型组有显著性差异(P＜0.05),与对照组无显著差异;干预组阴茎组织内Nos浓度高于模型组(P＜0.05),与对照组无显著性差异.模型组NOs浓度低于正常对照组和干预组(P＜0.05).结论:补充叶酸、维生素B6和维生素B12可降低模型组摄入所致高Hcy血症,削弱后者引起的阴茎组织内NOs的浓度的影响.     

慢性肺源性心脏病患者血清内源性洋地黄样因子的临床观察

本文用放射免疫方法测定28例慢性肺源性心脏病急性期患者和20例正常人血清EDF 浓度,结果显示:慢性肺源性心脏病组血清 EDF 浓度明显低于正常对照组,P<0.01;随心功能不全程度加重,血清 EDF 浓度明显降低;合并有心房纤颤者血清 EDF 浓度明显低于窦性节律者,P<0.025;血清 EDF 浓度与血红蛋白浓度、右室流出道直径、血清 T_3、T_3浓度呈明显正相关,r 分别为0.5276、0.6242、0.6394、0.6383,P 分别<0.01、<0.01、<0.05、<0.05;慢性肺源性心脏病恢复期患者血清 EDF 浓度较急性期明显升高,P<0.05,但仍低于正常对照组水平,P<0.01。     

Modulation of hepatic CYP2A1, CYP2C11, and CYP3A9 expression in adult rats by neonatal administration of tamoxifen.

To examine the effect of neonatal administration of tamoxifen on adult expression of hepatic cytochrome P-450 (CYP) enzymes and steroid 5alpha-reductase, male and female Sprague-Dawley rats were injected s.c. with tamoxifen (20 microg) or peanut oil (control) once daily at days 1 to 5 of age and sacrificed at 3 months of age. Neonatal tamoxifen treatment did not affect b.wt. or liver weight of adult male and female rats, but decreased testicular weight by approximately 40% in adult male rats. Neonatal administration of tamoxifen decreased hepatic microsomal testosterone 6beta- and 7alpha-hydroxylase activities in adult female rats whereas it did not alter steroid 5alpha-reductase activity. The same treatment increased testosterone 7alpha-hydroxylase activity, but did not affect testosterone 6beta-hydroxylase or steroid 5alpha-reductase activity in adult male rats. Immunoblot analysis indicated that neonatal tamoxifen treatment decreased CYP2C11 protein level by 26% and increased CYP2A1 protein content by 2.6-fold in adult male rats, whereas it had no effect on CYP3A or CYP2B protein expression. The reduction in the CYP3A-mediated testosterone 6beta-hydroxylase activity in adult female rats was accompanied by a decrease in CYP3A9 mRNA expression. Analysis of serum hormone levels indicated that neonatal exposure to tamoxifen resulted in a decrease in serum 17beta-estradiol concentration in adult female rats, whereas it did not alter serum testosterone concentration in adult male rats. In summary, treatment of neonatal rats with tamoxifen produced a long-lasting effect on hepatic CYP2A1, CYP2C11, and CYP3A9 expression in addition to testicular weight and serum 17beta-estradiol concentration.     

Spermatogenesis in aged rats after prenatal 3,3',4,4',5-pentachlorobiphenyl exposure

We previously reported that prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126) had dose-related adverse effects on the spermatogenesis of 7(pubescent)- and 17(adult)-week-old rats, but the effects in middle and old age have been unclear. In this study, the spermatogenesis of male Sprague-Dawley rats whose dams had been injected (i.g.) with 25 pg, 2.5 ng, 250 ng, or 7.5 microg of PCB126/kg or the vehicle on days 13-19 post-conception was investigated at 52 and 90 weeks of age. At 52 weeks, the 7.5 microg group showed a significant decrease of preleptotene spermatocytes in stages VII-VIII seminiferous tubules, round spermatids increased at stages VI-VII and elongated spermatids decreased at stage VIII, while the spermatogenesis of the other PCB-treated groups were similar to that of the vehicle group. At 90 weeks, the 7.5 microg group showed a significant decrease of spermatogenic cells at many stages, and the 250 ng group showed a significant decrease of preleptotene spermatocytes at stages VII-VIII, and round spermatids increased at stages VI-VII, elongated spermatids decreased at stage VIII, and the spermatogenesis of the 2.5 ng and 25 pg groups were similar to those of the vehicle group. The present study showed that prenatal PCB126 exposure had dose-related adverse effects on spermatogenesis in aging rats and may have accelerated spermatogenic senescence. Because the serum testosterone levels of the PCB126 groups and the vehicle group were similar, a direct endocrine cause for the observed effects was unlikely.     

Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats: role of metallothionein and glutathione

The influence of aging on the sensitivity of the liver to the acute toxicity of cadmium has not been studied previously in adult rats. In this study hepatotoxicity caused by a single sc injection of CdCl(2) was compared in 5-, 18-, and 28-month-old male Fischer 344 rats. Doses of Cd were adjusted on the basis of the mean lean body mass for each age group of rats, and liver injury was evaluated 24 h after treatment. Cd treatment produced substantial increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities in 5- and 18-month-old rats, whereas no significant increases were observed in 28-month-old rats. Histologic examination of representative livers from each age group confirmed the findings for serum enzyme activity; hepatocellular necrosis was observed only in livers from 5- and 18-month-old rats. The attenuation of Cd hepatotoxicity in senescent rats did not appear to be related to pretreatment levels of metallothionein or glutathione. Likewise, resistance to Cd could not be explained on the basis of metallothionein induction, which decreased as a function of aging. Thus, the mechanisms that account for the postmaturational decline in sensitivity to Cd do not appear to be associated with alterations in levels of the major factors that protect against Cd-induced hepatotoxicity.     

Sex- and Age-Dependent Acetaminophen Hepato- and Nephrotoxicity in Sprague-Dawley Rats: Role of Tissue Accumulation, Nonprotein Sulfhydryl Depletion, and Covalent Binding

Acetaminophen (APAP) produces sex-dependent nephrotoxicity andhepatotoxicity in young adult Sprague-Dawley (SD) rats and age-dependenttoxicity in male rats. There is no information re garding thesusceptibility of aging female SD rats to APAP toxicity. Therefore,the present studies were designed to determine if sex-dependentdifferences in APAP toxicity persist in aging rats and to elucidatefactors contributing to sex- and age-dependent APAP hepatotoxicityand nephrotoxicity. Young adult (3 months old) and aging (18months old) male and female rats were killed from 2 through24 hr after receiving APAP (0–1250 mg/kg, ip) containing[ring-¹⁴C]APAP. Trunk blood was collected for determinationof blood urea nitrogen (BUN) concentration, serum alanine aminotransferase(ALT) activity, and plasma APAP concentration; urine was collectedfor determination of glucose and protein excretion; and liverand kidneys were removed for determination of tissue glutathione(GSH) concentration, APAP concentration, and covalent binding.APAP at 1250 mg/kg induced nephrotoxicity (as indicated by elevationsin BUN concentration) in 3-month-old females but not males,whereas APAP induced hepatotoxicity (as indicated by elevationsin serum ALT activity) in 3-month-old males but not females.Sex differences in APAP toxicity were no longer apparent in18-month-old rats. APAP at 750 mg/kg ip produced liver and kidneydamage in 18-month-old but not 3-month-old male and female rats.No consistent sex- or age-dependent differences in serum, hepatic,and renal APAP concentrations were observed that would accountfor differences in APAI toxicity. No sex- or age-dependent differencesin tissue GSH depletion or covalent binding of radiolabel fromAPAP in livers or kidneys were observed following APAP administration.Utilizing an affinity-purified polyclonal antibody raised againstAPAP, arylated proteins with electrophoretic mobility similarto those observed in mice were prominent in rat livers followingAPAP administration to 3- and 18-month-old rats of both sexes.In contrast, no arylated proteins were detected in any rat kidneysfollowing APAP administration. Absence of immunochemically detectableproteins in rat kidney following APAP administration is in directcontrast to observations in mice and supports the hypothesisthat mechanisms of APAP hepatotoxicity and nephrotoxicity inrats and mice are distinctly different. In conclusion, sex differencesin APAP toxicity are observed only in young adult (3-month-old)rats and sex differences are organ-specific with males moresusceptible to hepatotoxicity and females more susceptible tonephrotoxicity. Aging rats are more susceptible to APAP-induceddamage to both the liver and the kidney than are 3-month-oldrats but sex differences are no longer apparent in 18-month-oldrats. The mechanisms contributing to sex- and age-dependentdifferences in APAP toxicity cannot be attributed to differencesin tissue APAP concentrations, GSH depletion, or covalent binding.     

Aging and drug metabolism: alteration of liver drug metabolizing ability in male rats. Is it functional deterioration or feminization of the liver?]

The profiles of hepatic drug metabolism were obtained by using young and old male and female rats. The profile obtained from old male rats was completely different from that from young male rats, while it was almost identical to those of females of any ages. This was due to the selective decrease in male hepatic enzyme activities showing higher activities than females to the activity levels of females which did not alter much with aging. Castration of young adult male rats caused a decrease in enzyme activities but did not result in the feminization of the metabolic profile. Administration of testosterone to old male rats resulted in the recovery of the profile of young male rats, but the levels of activities were not as high as young male rats. Plasma testosterone levels were found to decrease in parallel with drug metabolizing activities of male rats during aging. These results suggest that sex hormones play important roles in the alteration of drug metabolizing activities in male rats with aging. The loss of male characteristics in profile of drug metabolism during aging was evaluated by use of antibody to the male specific cytochrome P-450, P-450 m1. Anti-P-450 ml strongly inhibited imipramine N-demethylase activity, which showed marked sex (male greater than female) and age (young greater than old) differences, while this did not inhibit imipramine 2-hydroxylase activity, which showed no sex or age differences. The portion of N-demethylase activity inhibited by this antibody decreased in old rats while the portion not inhibited did not decrease with age. These results indicate that the decrease of sex specific cytochrome P-450 is responsible for the age-associated decrease in at least one of the drug metabolizing enzyme activities in male rats. It is suggested that some processes of the control mechanism of the gene expression of male specific cytochrome P-450 may be altered with old age.     

羟乙基淀粉130/0.4不同复苏方案对失血性休克大鼠肺损伤的早期影响及机制

目的探讨不同剂量6%羟乙基淀粉溶液(hydroxyeth-ylstarch,HES)130/0.4和林格液复苏对失血性休克大鼠急性肺损伤(acute lung injury,ALI)的早期影响及机制。方法24只♂SD大鼠,随机分为4组,每组6只:sham组,林格液组(RS组),33mlHES组(H1组),50mlHES组(H2组)。RS组输注3倍失血量的林格液;H1组、H2组分别输注33、50ml的HES130/0.4和一定量的林格液(林格液的量为3倍最大的放血量减去相应剂量的羟乙基淀粉)。测定休克前(T0),复苏前(T1),复苏后2(T4)、3h(T5)血气分析、CD11b和CD18的表达;观察肺组织超微结构变化。结果与T0比较,PaO2RS组T1、H1组T1～5、H2组T5升高;复苏组PaCO2T1～5降低;除H1组外,各液体复苏组pH于T4、5降低。RS组肺组织超微结构受损;H1组除线粒体结构轻微改变外基本正常;H2组核周间隙轻度扩张,粗面内质网轻度扩张,有脱颗粒。各液体复苏组于T1、T4、T5CD11b和CD18的表达增强;与RS组比较,H1、H2组于T4、T5CD11b和CD18的表达降低;与H1组比较,H2组于T4、T5CD11b和CD18的表达增强。结论6%HES130/0.433ml·kg-1复合一定量的林格液复苏可减轻失血性休克大鼠早期肺炎性损伤,其机制与抑制外周血白细胞CDllb和CD18的表达有关。     

心脏手术前,后甲状腺功能的变化

测定心脏病手术前、后血清甲状腺激素及皮质醇浓度。结果显示：与术前相比，术后Ｔ３、ＦＴ３明显下降，ｒＴ３和皮质醇明显升高，心脏病术后血清甲状腺激素变化的主要特点为低Ｔ３综合征，其与内源性糖皮质激素分泌增多有关。     

牛膝多糖对幼年哮喘大鼠气道壁嗜酸性粒细胞和肥大细胞的影响

目的观察幼年哮喘大鼠气道壁嗜酸性粒细胞(EOS)及肥大细胞(MC)的变化并探讨牛膝多糖(ABPS)对其的影响。方法清洁级♂SD大鼠50只,随机分为5组:哮喘组(A)、正常对照组(C)、牛膝多糖(ABPS)治疗组(T1、T2、T3),每组10只。采用鸡卵清蛋白(OVA)复制幼年大鼠哮喘模型。将动物处死后取肺组织,石蜡切片,HE及甲苯氨蓝染色,镜下观察EOS及MC数量、MC脱颗粒等情况,TUNEL法检测气道壁EOS的凋亡情况。结果①哮喘组(A)气道壁炎症细胞总数和EOS数为最多(EOS的百分率达73.4%±8.5%),ABPS治疗组T1、T3明显减少(EOS的百分率为56.1%±19.3%、57.3%±18.2%),与A组相比差异有显著性(P<0.05),T2组亦有减少,但与A组比较差异无显著性;②A组EOS凋亡率为5.3%±2.2%,而C组为15.9%±2.4%(P<0.01)。用药T1、T3组EOS凋亡率分别为8.7%±2.9%、9.8%±2.2%,与A组相比差异均有显著性(P<0.05);③ABPS治疗组T1、T3的MC数量,脱颗粒百分率均低于哮喘组,与A组相比差异均有显著性(P<0.05),药物(ABPS)抑制率(T1、T2、T3)分别是26.7%、11.8%和35.3%。结论哮喘大鼠气道壁EOS和MC明显增多,牛膝多糖能减少哮喘大鼠气道EOS和MC的数量,促进EOS的凋亡,抑制MC颗粒的释放,从而达到治疗哮喘作用。     

Changes in enzymes of the cholinergic system and acetylcholine release in the cerebra of aging male Fischer rats

The functional decline of memory in the aging human brain has been partially attributed to defects in cholinergic transmission. Therefore, we have investigated various components of the cholinergic system in cerebra of Fischer 344 male rats, ages 3-33 months. Choline acetyltransferase (ChA), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activities were determined in homogenates of the cerebra using specific radiometric assays. For measuring the release of acetylcholine (ACh), cerebral slices were incubated for one hour in Krebs buffer containing 3H-choline chloride to label ACh formed in situ, washed, and transferred to a microbath for superfusion. 3H-ACh released into the superfusate was determined. The levels of ChA in the cerebra of 9- to 27-month-old rats were lower (33%) than those in 3-month-old rats. Only 1% of these rats survive to the age of 33 months. In rats of this age, there was no decrease in ChA levels. AChE decreased while BChE increased with advancing age. The rate of spontaneous release of 3H-ACh decreased gradually by 63% from 3 to 33 months of age. The evoked release of ACh decreased by 50% in 33-month-old rats. Alterations in the levels of ChA, AChE (or BChE) and cholinergic receptors are not large enough to account for losses in cholinergic transmission in the cerebrum. The large decreases in the rates of spontaneous or evoked release of ACh in the aging cerebrum indicates that the functional defect in the cholinergic transmission of the aging cerebrum is possibly due to a defective release mechanism of this transmitter.