镉对肾脏的毒作用

雄性Ｗｉｓｔａｒ大鼠２４只，随机等分为４组，皮下注射不同剂量的ＣｄＭＴ。结果显示镉接触组尿钙和尿蛋白都高于对照组；肾皮质钠泵和钙泵活性低于对照组，体外试验也显示镉能抑制钙泵活性，ＧＳＨ和半胱氨酸对这种抑制有保护作用；肾皮质ＧＳＨ含量低于对照组，ＭＤＡ含量则高于对照组，但肝脏的这两个指标无变化；高剂量组ｃＡＭＰ／ｃＧＭＰ的比值低于对照组。提示脂质过氧化和钙代谢障碍是镉引起肾损害的机理之一。     

Inhibition of GABA-gated chloride channel function by arachidonic acid

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.     

Involvement of synthesis of brain cell structural proteins in the action of antitheines on long-term memory

Academician S. V. Anichkov Department of Pharmacology, Research Institute of Experimental Medicine, Academy of Medical Sciences, St. Petersburg. (Presented by Academician of the Academy of Medical Sciences A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 5, pp. 506–508, May, 1992.     

兔心肌挫伤心功能障碍与心肌细胞内Ca2+和线粒体ATP酶的变化

目的：探讨心肌细胞内游离钙([Ca^2 ]i)和心肌ATP酶变化在心肌挫伤（MC）后心功能障碍发生机制中的意义。方法：随机选取兔36只，分为6组：正常对照、伤后2、4、8、12、24h，每组6只。经右颈总动脉插管至左心室测左室压力。采用BIM-II型生物撞击机致成MC模型。在上述时相点测定左室压力，并测定心肌细胞内[Ca^2 ]i和心肌匀浆组织及线粒体ATP酶活力。结果：心脏收缩/舒张功能受到损害，心肌细胞内[Ca^2 ]i升高，心肌匀浆组织及线粒体ATP酶下降，相关分析表明心功能障碍与心肌细胞内[Ca^2 ]i含量升高呈明显负相关，与ATP酶活性降低呈明显正相关。结论：MC后心脏功能下降，心肌细胞内[Ca^2 ]i含量升高和ATP酶活性下降可能是其原因之一。     

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.     

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

红景天苷对3T3-L1脂肪细胞糖代谢及细胞分化的影响

目的:观察红景天苷对脂肪细胞糖代谢和细胞分化的影响,分析其改善糖代谢的可能机制.方法:检测红景天苷干预的脂肪细胞对 3H-葡萄糖的摄取,对红景天苷干预分化的细胞进行油红O染色后通过比色法分析脂肪细胞分化程度.逆转录多聚酶联反应(RT-PCR)检测脂肪细胞分化相关基因过氧化物体增殖剂活化受体-γ(PPAR-γ)、CAAT/增强子结合蛋白-α(C/EBP-α) mRNA的表达. 结果:红景天苷组葡萄糖摄取率为110.4%,明显高于正常对照组 (P<0.01);红景天苷明显抑制细胞分化及PPAR-γ、C/EBP-α mRNA表达,与对照组比较,P<0.01.结论:红景天苷促进3H-葡萄糖摄取,可抑制脂肪细胞分化,下调分化相关基因的表达.     

Carbon blacks as EPR sensors for localized measurements of tissue oxygenation.

New electron paramagnetic resonance (EPR) oximetry probes were identified in the class of carbon black materials. These compounds exhibit very high oxygen sensitivity and favorable EPR characteristics for biological applications. At low pO(2), the linewidth is particularly sensitive to changes in oxygen tension (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was demonstrated in vivo: the pO(2) was measured in muscle in which the blood flow was temporarily restricted as well as in tumor-bearing mice during a carbogen breathing challenge. The responsiveness to pO(2) was stable in muscle for at least 3 months. No toxicity was observed using these materials in cellular experiments and in histological studies performed 2, 7, and 28 days after implantation. In view of their EPR characteristics (high sensitivity) as well as the well-characterized production procedure that make them available on a large scale, these probes can be considered as very promising tools for future developments in EPR oximetry.