低剂量激素替代治疗对绝经后妇女骨代谢的影响

目的 探讨低剂量结合型雌激素（ＣＥ）和安宫黄体酮（ＭＰＡ）联合应用对骨代谢的影响，方法３４例绝经后妇女随机分为两组，试验组１７例，ＣＥ０．６２５ｍｇ与ＭＰＡ２ｍｇ隔日口服交替应用，对照组１７例，口服ＣＤ０．６２５ｍｇ／ｄ，每月连续服用２５ｄ，后１０ｄ加用ＭＰＡ４ｍｇ。两组均连续服用４周期，于用药前后分别测定血碱性磷酸酶（ＡＬＰ）及尿Ｃａ／Ｃｒ比值。结果 实验组完成治疗者１６例，对照组完成治疗者１５     

超氧化物歧化酶和脂质过氧化物与溃疡病发病关系

目的：观察超氧化物歧化酶（ＳＯＤ）和脂质过氧化物（ＬＰＯ）在消化性溃疡（ＰＵ）治疗前后变化，以探索其对ＰＵ发病和愈合作用。方法：用ＳＵＮ法和于树玉法分别测定ＰＵ患者血及组织中铜锌超氧化物歧化酶（Ｃｕ ＺｎＳＯＤ）活性和ＬＰＯ含量。结果：１８０例十二指肠溃疡（ＤＵ）和４２例胃溃疡（ＧＵ）患者粘膜和红细胞中Ｃｕ ＺｎＳＯＤ活性比正常组显著降低（Ｐ＜０．０１～０．００１）。１３６例ＤＵ组织及血中和１５例ＧＵ组织中ＬＰＯ含量比正常组显著升高（Ｐ＜００１～０．００１）。用呋喃唑酮、雷尼替丁和洛赛克分别治疗５０、２０和２４例ＤＵ患者两周后组织中Ｃｕ ＺｎＳＯＤ活性比治疗前明显升高（Ｐ＜０．０１～０．００１）。组织中ＬＰＯ含量比治疗前明显降低（Ｐ＜０００５～０．００１）。组织和红细胞中Ｃｕ ＺｎＳＯＤ活性从活动期→愈合期→瘢痕期逐渐升高，而ＬＰＯ含量则逐渐降低。结论：粘膜组织中Ｃｕ ＺｎＳＯＤ活性和ＬＰＯ含量升降与消化性溃疡的愈合和发病密切相关。     

硒对二乙基亚硝胺诱发大鼠肝癌生长的抑制作用的观察

观察硒对二乙基亚硝胺诱发大鼠肝癌的影响。方法；在诱癌过程中，大鼠分别投予含０．２，１．０，３．０×１０＾－６硒的饲料，检测血，肝组织ＬＰＯ，ＧＳＨ－ＰＸ活性，观察诱癌率及癌结节面积。结果：补Ｓｅ后对诱癌率无显著影响，但补充３．０×１－０＾－６Ｓｅ可使癌结节面积显著减少。补Ｓｅ可显著地减轻诱癌早期血和肝组织中ＬＰＯ的形成及诱癌过程中血和肝组织中ＧＳＨ－ＰＸ活性的降低。     

烧伤后红细胞损伤的机制——过氧化脂质、维生素E与溶血的关系

本实验发现大鼠体表面积20％Ⅲ°烧伤后,皮肤内产生了大量丙二醛(MDA),第二天达最高,第七天有第二高峰,血浆和红细胞(RBC)MDA第三天达最高,血浆和RBC维生素E(VE)于伤后第二天后迅速下降,RBC溶血第三天最甚。对皮肤MDA、血浆MDA、RBCMDA、血浆VE、BBC VE、1％H_2O_2溶血进行相关分析后发现在不同时相,有不同的相关关系,但基本遵循烧伤皮肤MDA增加、血浆MDA增加、RBC MDA增加、血浆和RBC VE降低,溶血增加的规律。文中讨论了RBC损伤的机制。     

某些降压药对血脂的影响

报道52例高血压病人服降压药双氢克尿噻、心得安、复方降压片和硝苯啶1～2月后血脂的变化,结果显示,双克(25～50mg/日)对血脂的主要影响是升高TG,加用心得安(30mg/日)后,TG升高幅度更大;TC有上升趋势,HDL-C变化较小。复降片(3片/日)对血脂的影响较大。不仅TG明显升高、TC也有明显升高,而HDL-C则有显著下降、HDL-C/TC比值下降也十分显著。硝苯啶(30mg/日)对血脂也产生不利影响,血TG浓度上升,TC浓度增加,而HDL-C变化不大。这种变化已被看作为对长期接受这些药物治疗的病人外加了一个致动脉粥样硬化的危险因素。     

Almitrine bismesylate disposition in the human digestive tract

Summary The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker¹⁴C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected.Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time.The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.     

Methionine-induced acidosis in the weanling rat

Whole body balances of non-metabolizable base (NB) were studied in weanling rats fed a cereal-based diet with or without added l -methionine. In response to l -methionine loading (2.5 mmol day^-1) the rats exhibited a significant reduction in rates of food intake (109 vs. 160 g per 8 days) and body growth (3 vs. 52 g per 8 days); fractional oxidation of absorbed dietary amino acid sulphur increased from 0.28 to 0.64; and mean urinary sulphate excretion increased from 2.3 to 14.8 mmol per 8 days. Mean rates of renal excretion of NB and filtered titratable organic acid decreased from 20 to ?11 mmol per 8 days and from 22 to 8 mmol per 8 days. Balances of calcium and NB remained at reference values despite a decrease in whole blood ‘base excess’ from ?1.0 to ?6.4 mmol 1–¹. The concentration of NB in plasma rose but slightly. It is concluded that L-methionine loading in the weanling rat leads to extracellular non-carbonic acidosis subject to renal compensation. This acidosis is due not to retention of H⁺ released by ionization of endogenous sulphuric acid but possibly to accumulation of (acid) organic metabolites of methionine which are efficiently conserved by the kidneys. The rise in sulphuric acid production leads to an adaptive decrease in fractional reabsorption of filtered sulphate. Even during inhibited growth, absorbed dietary NB is retained and deposited in the skeleton, probably as calcium carbonate.     

Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers

The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.     

Relationship of sperm superoxide dismutase-like activity with other sperm-specific enzymes and experimentally induced lipid peroxidation in infertile men

Summary. Superoxide dismutase-like activity (SOD-like), isoenzyme lactate dehydrogenase-C4 (LDH-C4) and NADH-diaphorase activities in spermatozoa have been investigated from 58 normozoospermic and 27 oligozoospermic men. Significantly higher SOD-like, LDH-C4 and diaphorase activities ( P <0.01, P <0.005 and P <0.0001, respectively) were detected in spermatozoa from oligozoospermic men, compared to the activities found in normozoospermic samples. SOD-like activity (mean±SE) in oligozoospermic samples amounted to 8.3±1.6 U 10⁻⁸ spermatozoa, while in spermatozoa in normozoospermic men with a sperm concentration above 20 million of spermatozoa per ml amounted to 4.2±0.5 U 10⁻⁸. There was a close correlation between the SOD-like activity and biochemical indicators of the presence of residual cytoplasm i.e. isoenzyme LDH-C4 and NADH-diaphorase (r = 0.53 and r = 0.66 in normozoospermic and r = 0.63 and r = 0.54 in oligozoospermic men, respectively). A positive relationship between SOD-like activity and experimentally-induced lipid peroxidation was detected in 54 infertile men (r = 0.30; P <0.05). These findings suggest that a higher level of superoxide dismutase-like activity may reflect a defect in the development or maturation of spermatozoa and, thereby, a decreased fertility potential. Hence, determination of SOD-like activity may give information on the state of maturity of human spermatozoa, while its role in the antioxidative protection remains to be determined.     

Andrology: Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma

The addition of luminol to unprocessed semen samples resultedin the generation of chemiluminescent signals, the intensityof which was highly correlated with the level of leukocyte contamination.Despite the spontaneous oxidant-generating capacity of seminalleukocytes, no correlations were observed between leukocytecontamination and the fertility status of the subjects or anyaspect of the semen profile, including the motility of the spermatozoaor their performance in a hyaluronate penetration assay. Luminol-dependentchemiluminescence and leukocyte contamination were also correlatedin washed sperm suspensions prepared either by repeated centrifugationor on discontinuous Percoll gradients. However, in such spermsuspensions, the spontaneous generation of oxidants by contaminatingleukocytes (>2x10⁴ leukocytes/ml) was invariably associatedwith a decreased capacity for movement. Moreover, causativeassociations between leukocyte contamination, reactive oxygenspecies generation, lipid peroxidation and impaired sperm motilitywere revealed by experiments involving the selective additionor removal of activated leukocytes. From these observationswe can conclude that low concentrations of leukocytes are acommon feature of the human ejaculate and can impair sperm function,particularly in the absence of seminal plasma. These findingshave implications for our understanding of the importance ofleukocytospermia in defining the fertility of human spermatozoain vivo and in vitro.