EFFECTS OF LOSARTAN ON THE CARDIOVASCULAR SYSTEM, RENAL HAEMODYNAMICS AND FUNCTION AND LUNG LIQUID FLOW IN FETAL SHEEP

1. The angiotensin type 1 (AT₁) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125–132 days gestation). Losartan reduced the fetal systolic (P < 0.01) and diastolic (P < 0.01) pressor response to 5 μg angiotensin II (AngII) i.v. from 27.4 ± 1.5 to 7.4 ± 0.9 and from 17.5 ± 1.3 to 5.4 ± 0.6 mmHg, respectively, after 1h and to 6.1 ± 0.5 and 4.4 ± 0.5 mmHg, respectively, after 2h. Maternal pressor responses to 5 μg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P < 0.05) after losartan administration, but fetal heart rate did not change. 2. Fetal haematocrit increased (P < 0.05), fetal PO₂ decreased (P < 0.01), PCO₂ did not change and pH decreased (P < 0.01), as did plasma bicarbonate levels (P < 0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis. 3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P < 0.01) and an increase in blood flow (P < 0.05). Glomerular filtration rate decreased (P < 0.05); thus, filtration fraction decreased (P < 0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P < 0.01) and became negative. Urine flow decreased (P < 0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium:potassium ratio decreased (P < 0.05). There was a decrease in lung liquid flow (P < 0.05) following losartan. 4. It is concluded that the fetal renin-angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT₁ receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.     

Phosphate poisoning by ingestion of clothes washing liquid and fabric conditioner

A case of deliberate ingestion of clothes washing liquid and fabric conditioner is described. Tracheal intubation and controlled ventilation became necessary because of respiratory muscle dysfunction associated with hypocalcaemia. We suggest that the phosphate component of the clothes washing liquid was responsible for the dramatic metabolic upset and subsequent need for admission to the Intensive Care Unit.     

不同强度运动对女子游泳运动员性激素水平的影响及特点

本研究以放兔分析法观察不同强度运动前后19名女子游泳运动员血清促卵泡激素(FSH)、黄体生成素(LH)、雌二醇(E_2)、孕酮(P)、睾酮(T)及胰岛素(Ins)的变化。受试者在卵泡及黄体两期分别进行短时间高强度间歇运动——6×50m全速力竭性游泳和长时间持续运动——1000m全速力竭性游泳。在运动前5分钟及运动后即刻分别采集静脉血测定各种激素含量。主要结果如下:受试者从事6×50m最大速度间歇游泳后,卵泡期各种激素浓度的变化均显著高于运动前安静状态,黄体期变化不一,FSH、LH降低,E_2、P、T及Ins升高。从事1000m全速游泳后,激素变化表现为卵泡期FSH、LH、E_2、P均升高,T及Ins降低;黄体期E_2、P、T升高,Ins降低,FSH、LH无显著变化,两期相比黄体期运动成绩优于卵泡期。上述结果提示:①受试者月经周期的黄体期机体有氧能力强于卵泡期,运动能力的增强与黄体期E_2、P、T水平升高有关。②FSH、LH与E_2、P分泌变化并非同步一致,说明运动中E_2升高并非受制于促性腺激素,而主要是卵巢分泌量升高所致。③运动中E_2、P、T具有协同效应,可抵抗疲劳,提高人体运动能力。     

Quantitative determination of atracurium in human plasma using high-performance liquid chromatography

The authors have established a new method for extraction and determination of atracurium in human plasma that employs a reversed phase high-performance liquid chromatography (HPLC). This method made use of a fluorescent spectrophotometer at an excitation wavelength of 240nm and an emission wavelength of 310nm. The mobile phase was made of a phosphate buffer, distilled water and acetonitrile (20V:30V:50V). The analytical column used was a Little Champ C₁₈.In a Bond Elute C₁₈ extraction column, which had been prewashed with a phosphate buffer and a 50% methanol solution, atracurium was extracted from acidified plasma samples using a mixture of methanol and phosphate buffer. A standard curve was prepared by the internal standard method using metocurine. A high linear correlation between atracurium concentration and the ratio of the atracurium peak height to the metocurine peak height was observed (r = 0.9994). The lowest threshold for detection of atracurium was 15ng/ml. When the plasma concentrations of atracurium were determined in 2 clinical cases, t_1/2 was 2.10 and 1.73min and t_1/2 was 15.57 and 21.57min, respectively. These results indicate that this method of extraction and determination is appropriate for studying the pharmacokinetics of atracurium because it allows a high reproducibility, and provides an extremely accurate, simple and quick analysis.(Okutani R, Kono K, Frederic M. deBros et al.: Quantitative determination of atracurium in human plasma using high-performance liquid chromatography. J Anesth 2: –, 1988)     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Formulation of Vaccine Adjuvant Muramyldipeptides (MDP). 1. Characterization of Amorphous and Crystalline Forms of a Muramyldipeptide Analogue

A relatively nonhygroscopic crystalline form of the glycopeptide, N-acetylmuramyl-L--aminobu-tyryl-D-isoglutamine (I), containing approximately one molecule of water was prepared from amorphous material. The crystalline material, consisting of a mixture of the and anomers, exhibited better physical and chemical stability than the lyophilized amorphous material. The /-anomer ratios of I in both the crystalline and the amorphous state were approximately equal but different from that in solution.     

康复新液联合奥美拉唑对HP阴性胃溃疡的疗效分析

目的分析康复新液联合奥美拉唑治疗幽门螺杆菌(HP)阴性胃溃疡患者的疗效。 方法选取HP阴性胃溃疡患者108例,随机均分为对照组和联合组。对照组接受奥美拉唑针剂治疗,联合组接受康复新液联合奥美拉唑针剂治疗。比较两组临床疗效、血清胃蛋白酶原(PG)、高迁移率族蛋白B1(HMGB1)、细胞炎症因子水平及不良反应发生率。 结果联合组治疗总有效率高于对照组(P＜0.05)。与治疗前比较,两组治疗后PGⅠ、PGⅡ、HMGB1、白细胞介素-6、肿瘤坏死因子-α及C反应蛋白均有降低,且联合组较对照组降低更明显(P＜0.05)。两组患者治疗期间总不良反应发生率比较,差异无统计学意义(P＞0.05)。 结论康复新液联合奥美拉唑针剂可提高HP阴性胃溃疡患者的临床疗效,值得临床应用推广。     

Soman intoxication-induced changes in serum acute phase protein levels,corticosterone concentration and immunosuppressive potency of the serum

We have studied the effect of soman intoxication on serum acute phase reactants (APR) levels, and the relationship of the APR and corticosterone concentrations and the immunosuppressive activity of the serum. One day after the injection of 1.8 LD₅₀ soman the concentrations of ₂-macroglobulin (₂-MG) and ₁-acid glycoprotein (AGP) in the serum of antidote protected rats increased 4- and 7-fold, respectively, whereas those of hemopexin (Hx), haptoglobin (Hp) and cysteine protease inhibitor (CPI) were two to three times higher than in the controls. A similar magnitude of increase of serum acute phase reactants levels was observed when 0.3 LD₅₀ soman was administered at 24-h intervals over the 5-day period. The relationship of changes in the APR concentration, corticosterone level and immunosuppressive activity of the serum was also comparable to that observed in the acute phase response to tissue injury.     

A reevaluation of the status of cholesterol in erythrocytes infected by Plasmodium knowlesi and P. falciparum

The cholesterol synthesis of rhesus monkey erythrocytes parasitized by Plasmodium knowlesi and human erythrocytes infected by P. falciparum, as measured by incorporation of [1-¹⁴C]acetate and ³H₂O, was almost undetectable, concordant with very low levels of measurable 3-hydroxy-3-methyl glutaryl-CoA reductase activity. In addition, both types of infected cells exchanged cholesterol with the plasma at the same rate as uninfected cells. The data do not exclude the possibility of cholesterol transfer from uninfected to infected cells.