In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated.     

Epidermal growth factor receptors in endometrial adenomatosis

The expression of the epidermal growth factor receptors (EGFR) and of progesterone and estrogen receptors (PR and ER, respectively) was studied in 31 women of a reproductive age with endometrial adenomatosis. The receptor phenotype EGFR+PR-ER-, indicating mainly local regulation of the proliferative processes, was detected in adenomatous endometrium three times more often than in normal endometrium. The metabolic endocrine disorders were less frequent in patients with endometrial adenomatosis with EGFR, but the disease ran a more severe course in these patients, which was proven by more numerous diagnostic scrapings performed within the same period. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 45–49, January, 1999     

Multiple sulphatase deficiency presenting at birth

A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalcificans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts.     

慢性肾小球肾炎病人白细胞糖皮质激素受体的变化

以氚标记的地塞米松(~3H-Dex)为配体,用一点分析法测定了23例慢性肾小球肾炎病人混合白细胞的糖皮质激素受体(GCR),平均为8825±2429位点/细胞((?)±SD)。与正常人5154±1635位点/细胞相比相差十分显著,P<0.01。其中16例并发尿毒症患者的GCR平均为9464±2571位点/细胞((?)±SD)。对这种变化的可能机制和临床意义进行了讨论。     

181例柯兴氏综合征的临床病理

本文收集自1957至1984年181例柯兴氏综合征的肾上腺标本,对30例作了电镜观察。对88例用电子计算机作逐步回归分析,结果表明治疗方式、病理类型、紫纹和性征异常对预后影响较大。并对肾上腺皮腺癌诊断标准的掌握、皮质增生中腺瘤样结节和皮质腺瘤间可能存在的转化关系、肾上腺皮质增生的诊断标准以及柯兴氏综合征病例肾上腺病损的超微结构进行了讨论。     

Reconstitution of humoral immunity during pregnancy

BACKGROUND: Recently, increasing attention has been paid to hormonal regulations of the immune system. MATERIALS AND METHODS: In this study, cord sera and the corresponding maternal sera were obtained at delivery. Sera from pregnant women were obtained at early, middle, and late stages of pregnancy. These sera were tested for titer and avidity of measles or mumps virus-specific immunoglobulin G (IgG) by means of a single-dilution, urea-denaturation enzyme-linked immunosorbent assay method. RESULTS: A positive and significant correlation was found between the titer and avidity of the virus-specific IgG, both in the cord sera and in the maternal sera. This correlation was established already at the early stage of pregnancy. There were no such correlations found in nonpregnant individuals. CONCLUSIONS: This is the first observation in human subjects that the avidity and concentration of the virus-specific IgG had a positive and significant correlation. Pregnancy must have some significant effects on the regulation of humoral immunity.     

Role of Apolipoprotein A-I in Steroid-Induced Activation of DNA and Protein Synthesis in Hepatocytes

It is demonstrated that anabolic effect of steroid hormones is produced by steroid-apolipoprotein A-I complexes. These complexes accelerate not only protein, but also DNA synthesis and produce both cell hypertrophy and hyperplasia. For realization of their anabolic effect steroid hormones are modified by - and -reductases in resident macrophages.     

Cell and cytokine profiles in nasal secretions from patients with nasal polyposis: effects of topical steroids and surgical treatment

BACKGROUND: Nasal polyposis (NP), a chronic inflammatory disease of the paranasal sinus mucosa, is frequently associated with asthma. Previous reports showed that surgical treatment for nasal polyps may influence asthma evolution. We hypothesized that sinus surgery may alter the cytokine network in nasal secretions. METHODS: We evaluated the characteristics (cells and mediators) of nasal lavages in nine patients with untreated NP (group A), 17 patients treated with topical steroids (group B), 21 patients treated by nasal surgery endonasal ethmoidectomy associated with topical steroids (group C), and 12 healthy subjects (controls). RESULTS: Percentages of both eosinophils and neutrophils were higher in NP patients than in controls. Percentages of eosinophils and interleukin-5 (IL-5) level were higher in group A than in group C and controls. There was a positive correlation between IL-5 and eosinophils. In marked contrast, IL-8, IL-10, and IL-1beta levels were significantly higher in group C than in groups A and B and controls; TNF-alpha concentration was significantly lower in group C than in groups A and B and controls; and there was a negative correlation between IL-10 and TNF-alpha. The percentage of eosinophils was higher in asthmatic patients with NP than in nonasthmatic patients. In addition, in group C, asthmatic patients also had a significantly higher level of IL-10 than nonasthmatic patients. CONCLUSIONS: Our study demonstrates that percentages of eosinophils and neutrophils, and IL-5 level were increased in nasal secretions from untreated patients with NP. Topical steroid treatment is associated with a decrease of inflammatory cells and mediators. In marked contrast, nasal surgery is associated with marked changes, in cytokine profile in nasal secretions, that are clearly different from those of controls and topical steroid-treated NP patients.     

Impaired Leydig Cell Function In Vitro in Testicular Tissue from Human Males with "Sertoli Cell Only" Syndrome

Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.