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[Lipid profile of hyperandrogenic women undergoing treatment with ketoconazole and its relationship with the evolution of the hormone pattern].

BACKGROUND: Previous studies have demonstrated changes in the lipidic profile following treatment with ketoconazole. However, the possible influence in patients with hyperandrogenism treated with this drug and its possible relation with the evolution of the hormonal pattern is unknown. RESULTS: Thirty-seven women with no tumoral hyperandrogenism treated with ketoconazole for 9 months (400 mg/day) were studied during treatment and one month after suppression of the medication. The study included the evaluation of total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol and hormonal determinations of estradiol, androstenedione, testosterone, dehydroepiandrosterone, sulphate and sex hormone binding globulin. RESULTS: A rapid and significant decrease of LDL cholesterol and total cholesterol was observed (p < 0.01) which was reversible upon discontinuation of treatment. The HDL cholesterol levels and triglycerides did not modify. The final hormonal profile was more favorable with a significant reduction of testosterone and dehydroepiandrosterone sulphate (p < 0.01) and an increase in estradiol (p < 0.01). No statistical correlation was observed between the changes of sexual steroids and the changes in the lipidic pattern. CONCLUSIONS: In patients with non tumoral hyperandrogenism treated with ketoconazole the modifications of the steroid hormone profile do not appear to be related with changes in lipidic metabolism.

Adolescent↗

The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients.

Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.

Adult↗

Andrea Prader Award. Clinical Steroidology. Coming of age.

The determination of steroid concentrations in urine and plasma is an indispensable part of the diagnostic work-up in endocrinology. Since the description of the color reaction for determination of 17-ketosteroids by Zimmermann in 1935, a vast amount of work has been invested in the specialty of clinical chemistry, which we called 'clinical steroidology'. Until the early fifties, color reactions for block determinations of C19 and C21 steroids in urine and plasma were the strongholds of steroid clinical chemistry. Around 1952, paper chromatography, and later on column chromatography were added, which afforded fractionation and individual determinations of steroids in body fluids. The final achievement and almost absolute quantification of almost 50 steroid metabolites ('profile') in urine was achieved by capillary glass column chromatography-mass spectrometry (GC-MS), which came into clinical usage around the mid-eighties. For estimation of plasma steroids radioimmunoassays (RIA) were introduced during the sixties. A whole body of physiology and pathology was erected on the basis of steroid RIAs. Recent investigation, however, revealed that steroid RIAs yield unreliable results at low concentrations due to cross reactions and interferences by impurities of samples. The newly (nineties) developed method of isotope dilution/GC-MS produced highly accurate values of small amounts of steroids and became the gold standard of plasma steroid determinations. Thus 'clinical steroidology' has certainly come of age.

Awards and Prizes↗

Retention of NADPH-linked quinone reductase activity in an aldo-keto reductase following mutation of the catalytic tyrosine.

Aldo-keto reductases (AKR) are monomeric oxidoreductases that retain a conserved catalytic tetrad (Tyr, Lys, Asp, and His) at their active sites in which the Tyr acts as a general acid-base catalyst. In rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD, AKR1C9), a well-characterized AKR, the catalytic tyrosine is Tyr 55. This enzyme displays a high catalytic efficiency for a common AKR substrate 9,10-phenanthrenequinone (9,10-PQ). Surprisingly, Y55F and Y55S mutants of 3alpha-HSD reduced 9,10-PQ with high kcat values. This is the first report whereby the invariant catalytic tyrosine of an AKR has been mutated with retention of kcat values similar to wild-type enzyme. The Y55F and Y55S mutants displayed narrow substrate specificity and reduced select aromatic quinones and alpha-dicarbonyls. kcat versus pH profiles for steroid oxidoreduction catalyzed by wild-type 3alpha-HSD exhibited a single ionizable group with a pK= 7.0-7.5, which has been assigned to Tyr 55. This group was not evident in the kcat versus pH profiles for 9, 10-PQ reduction catalyzed by either wild-type or the Tyr 55 mutant enzymes, indicating that the protonation state of Tyr 55 is unimportant for 9,10-PQ turnover. Instead, wild-type and the active-site mutants Y55F, Y55S, H117A, D50N, K84R, and K84M showed the presence of a new titratable group with a pKb = 8.3-9.9. Thus, the group being titrated is not part of the tetrad. All the mutants decreased kcat/Km considerably more than they decreased kcat. Thus, the K84R mutant demonstrated a 30-fold decrease in the pH-independent value of kcat but 2200-fold decrease in the pH-independent value of kcat/Km. This suggests that all the tetrad residues influence quinone binding and that Lys 84 plays a dominant role in maintaining proper substrate orientation. Using wild-type enzyme, the energy of activation (Ea) for 9,10-PQ reduction was approximately 11 kcal/mol less than steroid oxidoreduction. The Ea for 9,10-PQ reduction was unchanged in the Tyr 55 mutants, suggesting that the reaction proceeds through the same low-energy barrier in the wild-type enzyme and these mutants. The retention of quinone reductase activity in this AKR in the absence of Tyr 55 with kcat versus pH rate profiles and activation energies identical to wild-type enzyme suggests that quinone reduction occurs via a mechanism that differs from 3-ketosteroid reduction. In this mechanism, the electron donor (NADPH) and acceptor (o-quinone) are bound in close proximity, which permits hydride transfer without formal protonation of the acceptor carbonyl by Tyr 55. This represents a rare example where one enzyme can catalyze the same chemical reaction (carbonyl reduction) by either acid catalysis or by a propinquity effect and where these two mechanisms can be discriminated by site-directed mutagenesis.

3-Hydroxysteroid Dehydrogenases↗

Steroid biochemistry of virilising adrenal tumours in childhood.

Steroid excretion in urine of 12 infants with virilising adrenal tumours has been determined using gas chromatography. In six children, (Group A, five female, one male) aged 2.8-5.3 years, very high urinary excretions of 17 oxosteroids (greater than 40 mumol/24 h) were largely accounted for by dehydroepiandrosterone (DHA). In one of the girls, the pattern of steroids excreted in urine was similar to that of newborn infants, with high excretions of 16-oxygenated derivatives of DHA. The histology of this tumour suggested a neoplasia of fetal-type adrenocortical cells. Very large tumours were found in three of the infants, two of whom have died and one has multiple metastases. From the other three children, small, well-encapsulated adenomas were successfully removed. Six children (Group B), had moderately elevated 17-oxosteroid excretions (8-17 mumol/24 h). In five of these cases (four female, one male) aged 0.8-5 years, 11 beta-hydroxyandrosterone was a consistently prominent urinary steroid. In one boy, aged 7.7 years, 17-oxosteroid excretion was 15 mumol/24 h and the major steroids in urine were metabolites of pregnenolone. These six children have survived with no clinical evidence of recurrent tumour. The in vivo functional activities of the tumours can be deduced from the different profiles of steroids in urine. These have revealed heterogeneous patterns of steroid biosynthesis.

17-Ketosteroids↗

Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor.

New N-substituted arylthiohydantoin antiandrogens were synthesized. These compounds presented exceptionally high relative binding affinities (RBAs) for the rat androgen receptor (AR): up to 3 times that of testosterone (T) and 100 times the RBAs of non-steroidal antiandrogens such as flutamide, Casodex and Anandron. Furthermore, unlike available markers for AR, they were totally devoid of any binding to the other steroid receptors. RU 59063, the molecule with the highest RBA, was tritiated. When it was compared to [3H]T for the assay of rat, mouse, hamster and human AR, it gave rise to the same number of binding sites but its K alpha (6 x 10(9) M-1) for rat and human AR were, respectively 3 and 8 times higher than that of T. Moreover RU 59063, unlike T, was devoid of any specific binding to human plasma. In vivo, these compounds displayed antiandrogenic activity while being devoid of any agonistic effect. Thus, RU 56187, given orally in castrated male animals, prevented in a dose-dependent manner the effects of 3 mg/kg testosterone propionate (TP) on mouse renal ornithine decarboxylase (acute test) and of 0.5 mg/kg TP on rat prostate weight (chronic test). In these two models, its ED50 was 0.6 and 1 mg/kg, respectively. In the intact rat, when given alone, it inhibited dose-dependently the effect of endogenous androgens on the seminal vesicles (ED50 approximately 1 mg/kg) and prostate (ED50 approximately 3 mg/kg) weights. These results suggest that these new compounds may be useful as specific markers for the androgen receptor as well as for the treatment of androgen-dependent diseases or disorders such as prostate cancer, acne, hirsutism and male pattern baldness.

Androgen Antagonists↗

[A method for the quantitative analysis of steroid hormones by HPLC/RIA].

To solve the problem of cross-reaction in immunoassay and determine various steroid hormones simultaneously in a small amount of sample, a method for the quantitative analysis of steroid hormones was developed. This method is a combination of high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). The purpose of the study is the comprehensive analysis of steroid hormones profiles in normal subjects and adreno-cortical diseases. One hundred microliters of plasma was extracted by ether and the ether layer was evaporated. The residue was redissolved and separated by HPLC. Then fractions of steroid hormones were taken and determined by RIA. In this study, cortisol (F), androstenedione (A), 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T), progesterone (P), estrone (E1) and estradiol (E2) were analyzed in normal adults, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Cushing's syndrome. Results in normal adults were similar with those had been previously reported. In CAH, F was remarkably low and 17-OHP, A, T and P were remarkably high before treatment. During treatment some cases showed that 17-OHP, A, T and P were high, and 17-OHP and P tended to be within normal range, if F had been kept higher than about 20 micrograms/dl. In the analysis of Cushing's syndrome before treatment, there were definite differences between adenoma and hyperplasia. A, 17-OHP, T, E1 and E2 were higher in hyperplasia than those in adenoma. It is suggested that it is possible to diagnose the type of Cushing's syndrome with a small amount of plasma using this method. As a mass screening method of CAH at present, 17-OHP in dried blood on filter paper is determined, therefore the quantitative analysis of 17-OHP in dried blood on filter paper (9 mm disc) was attempted. The quantitative analysis proved to be possible, and it was considered to be applied as the secondary screening method of CAH by the use of dried blood on filter paper.

Adrenal Cortex Hormones↗

Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders.

The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i.m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8-week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass.

Adult↗

Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone.

The two [3H]aldosterone-binding proteins of rat brain cytosol were characterized by a dextran-coated charcoal method. With molybdate present to stabilize receptors, the affinities of the two sites for [3H]aldosterone in adrenalectomized perfused rat brain cytosols were 0.28 and 18.0 nM at 4 C. High affinity sites comprised 15% of the total receptor number. A small contamination of perfused brain cytosol preparations with corticosteroid-binding globulin (CBG) was found. However, due to the very high affinity of CBG for corticosterone at 4 C, this slight contamination resulted in significant alterations in the apparent affinity of steroids competing for aldosterone-binding sites. Selective precipitation of cytosol receptors with 36% (NH4)2SO4 reduced CBG concentrations to negligible levels. After blockade of low affinity sites with a highly selective glucocorticoid (RU 26988), the order of steroids in competing for the high affinity receptor was desoxycorticosterone greater than fludrocortisone greater than corticosterone greater than aldosterone greater than progesterone greater than dexamethasone. Readdition of a small quantity of dialyzed serum to cytosol preparations yielded a profile of steroid binding similar to that of the kidney mineralocorticoid receptor (aldosterone greater than desoxycorticosterone greater than corticosterone). The distribution of both receptors in brain regions of adrenalectomized rats was determined. Both receptors were at greatest density in the hippocampus and lowest density in the hypothalamus. The high affinity site was at greatest density in limbic regions, whereas the low affinity receptor, apparently identical to the glucocorticoid type II receptor, was at greatest density in cortex and cerebellum. It is concluded that the high affinity aldosterone receptor of rat brain, which had been identified in preliminary studies as a mineralocorticoid receptor, may bind either corticosterone or aldosterone in vivo.

Adrenalectomy↗

Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urine.

Anabolic-androgenic steroids are some of the most frequently detected drugs in amateur and professional sports. Doping control laboratories have developed numerous assays enabling the determination of administered drugs and/or their metabolic products that allow retrospectives with respect to pharmacokinetics and excretion profiles of steroids and their metabolites. A new metabolite generated from metandienone has been identified as 18-nor-17beta-hydroxymethyl,17alpha-methyl-androst-1,4,13-trien-3-one in excretion study urine samples providing a valuable tool for the long-term detection of metandienone abuse by athletes in sports drug testing. The metabolite was characterized using gas chromatography/(tandem) mass spectrometry, liquid chromatography/tandem mass spectrometry and liquid chromatography/high-resolution/high-accuracy (tandem) mass spectrometry by characteristic fragmentation patterns representing the intact 3-keto-1,4-diene structure in combination with typical product ions substantiating the proposed C/D-ring structure of the steroid metabolite. In addition, structure confirmation was obtained by the analysis of excretion study urine specimens obtained after administration of 17-CD(3)-labeled metandienone providing the deuterated analogue to the newly identified metabolite. 18-Nor-17beta-hydroxymethyl,17alpha-methyl-androst-1,4,13-trien-3-one was determined in metandienone administration study urine specimens up to 19 days after application of a single dose of 5 mg, hence providing an extended detection period compared with commonly employed strategies.

Adult↗

Steroid hormone metabolism in women with pelvic organ prolapse.

OBJECTIVE: To identify whether endogenous steroid hormone metabolism in women with pelvic organ prolapse (POP) is different from that in normal women and the relationship between endogenous steroid hormone metabolites and POP stage. STUDY DESIGN: Twenty postmenopausal women who were clinically diagnosed as having POP and 20 volunteer postmenopausal women without prolapse were included in the study. We compared the urinary profiles of endogenous steroids between the two groups and investigated the relationship between urinary profiles of endogenous steroids and degree of prolapse. Urinary profiles of endogenous steroids were assayed by gas chromatography/mass spectrometry. RESULTS: The ages of the patients and control group were 64.6 +/- 6.5 and 63.5 +/- 3.9 years, and the body mass index was 23.96 +/- 3.14 and 24.11 +/- 2.73 kg/m2 in patients and normal subjects, respectively. The number of patients were 4 at stage I, 4 at stage II, 6 at stage III and 6 at stage IV. 5-Androstene-3 beta,16 beta,17 beta-triol (5-AT), 11 beta-hydroxy an and 17 beta-estradiol were significantly increased in the POP group as compared with the control group (0.76 +/- 0.67 vs. 0.06 +/- 0.03 mumol/g creatinine, P = .002, 1.16 +/- 0.83 vs. 0.65 +/- 0.23 mumol/g creatinine, P = .04; and 15.08 +/- 9.81 vs. 8.53 +/- 6.19 mumol/g creatinine, P = .04). However, tetrahydrocortisone (THE) was significantly increased in the control group as compared with the patient group (9.80 +/- 6.21 vs. 5.22 +/- 4.89 mumol/g creatinine, P = .04). Androgen metabolites 5-AT and THE significantly correlated with the pelvic organ prolapse quantitation (POP-Q) stage (R = .418; P = .027; R = .46, P = .016). Among the estrogen metabolites, 17 beta-estradiol correlated with POP-Q stage, but not significantly so (R = .38, P = .05), and the 17 beta-estradiol/estrone ratio weakly correlated with stage (R = .14, P = .49). CONCLUSION: The metabolites of endogenous steroid hormones could be contributing factors in the pathogenesis of POP.

Aged↗

Steroid injections in the management of trigger fingers.

OBJECTIVES: The most commonly used primary treatment for trigger fingers is corticosteroid injection in the flexor tendon sheath, followed by surgical release if unsuccessful. This study examines the surgical and nonsurgical treatment of patients with trigger fingers presenting to a large Canadian tertiary referral center. The treatment success and side-effect profile of steroid injection therapy and surgical release were examined in the context of comorbid illness, specifically, diabetes mellitus. DESIGN: Retrospective review of all patients with trigger finger who were seen by the senior authors between January 1999 and June 2004. RESULTS: In the study period, 118 trigger digits were treated. This study included 92 nondiabetic, 21 type 2 diabetic, and five type 1 diabetic trigger fingers. Of the 89 digits that received at least one steroid injection, 46 (52%) resolved completely and 42 (47%) were improved. Nondiabetic digits were treated successfully in 40 out of 70 digits (57%) with steroid injection therapy. Diabetic patients had a success rate of 6 of 19 (32%) with steroid injections, which is significantly lower than nondiabetics (P = 0.04). All type 1 diabetics (n = 5) required surgical treatment. Surgical treatment was successful in 71 of 72 (99%) digits. No side effects of steroid injection were noted, and short-term postoperative side effects were noted in 26 of 72 surgical patients (36%). No statistically significant differences were found in surgical complication rates in diabetics vs. nondiabetics or type 1 diabetics vs. type 2 diabetics. CONCLUSIONS: Steroid injection therapy should be the first-line treatment of trigger fingers in nondiabetic patients. In diabetics, the success rate of steroid injection is significantly lower. Injection therapy for type 1 diabetics was ineffective in this study. Surgical release of the first annular (A1) pulley is most effective overall in diabetics and nondiabetics alike, with no higher rates of surgical complications in diabetics.

Adult↗

Role of sex steroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoylphosphate synthase (ammonia) and arginase activity in rat liver ontogenesis.

The effects of sex steroid hormones on the development changes of carbamoylphosphate synthase and arginase activity, and DNA content in rat liver were investigated. After birth, administration of estradiol causes an increase in carbamoylphosphate synthase and arginase activity at high dosages only. Progesterone strongly inhibits or even reverses these stimulatory effects of estradiol. Administration of progesterone alone had no effects in the 1st postnatal week, a stimulatory effect in the 2nd postnatal week, and slightly inhibitory effects on enzyme activities thereafter. Testosterone hardly affected enzyme activities in the 1st postnatal weeks and slightly decreased them from the 3rd postnatal week onwards. No differences in the response of either sex to these hormone treatments were observed. During the last 4 prenatal days and during the 1st postnatal week progesterone partially inhibited the prednisolone-induced enzyme accumulation and decrease in DNA content. Testosterone had such effects during the 1st 2 postnatal week. Comparison of these and previous experimental results with the developmental profiles of carbamoylphosphate synthase (ammonia) and arginase activity and DNA content on the one hand and with the developmental profile of steroid hormone levels on the other shows that only glucocorticosteroids influence enzyme activity and DNA content profiles, while progesterone and testosterone modulate the profiles by antagonizing the effects of glucocorticosteroids. No role for estrogens could be established.

Aging↗

17-Beta-estradiol and progesterone modulate an intrinsic opioid analgesic system.

It has been demonstrated in rats as well as in humans, that pregnancy and parturition are associated with an opioid-mediated maternal analgesia. This analgesia has been shown to involve a spinal cord dynorphin/kappa-opioid system. In the present study, simulation of the pregnancy blood profile of 17-beta-estradiol (E2) and progesterone (P) in non-pregnant, ovariectomized rats resulted in a statistically significant elevation in pain thresholds. The temporal pattern and magnitude of this analgesia was strikingly similar to that which has been observed during actual gestation. Administration of pregnancy levels of either E2 or P alone or E2 with the delayed addition of P (starting with dose 3, the dose at which the onset of analgesia occurred) was not sufficient to produce the increase in pain threshold. Therefore, the entire pregnancy profile of steroid hormones is responsible for the manifestation of analgesia. Chronic administration of the narcotic antagonist naltrexone blocked the increase in pain threshold associated with hormone-simulated pregnancy, indicating that it is mediated via an endogenous opioid system(s), as is the analgesia of actual pregnancy. The striking similarities between the analgesia of hormone-simulated pregnancy and actual gestation strongly suggest that the profile of change in plasma E2 and P is a parameter of the pregnant condition essential for the manifestation of elevated pain thresholds. These data also indicate the existence of an opioid analgesic system that is subject to modulation by ovarian sex steroids.

Analgesia↗

Asthma: where beyond steroids?

The prevalence of asthma is increasing dramatically despite major changes in monitoring and treatment of this disease. Currently available bronchodilators and anti-inflammatory drugs are effective in most patients, although these can have side effects and are mainly symptomatic. Many drugs are now in development for the treatment of asthma. Most of these new therapies are aimed at inhibition of the inflammatory components, with better safety profiles than steroids.

3',5'-Cyclic-AMP Phosphodiesterases↗

Unveiling the molecular basis of gonadal development: Multi-omics uncovers sex-related genes and steroid pathways in Sinonovacula constricta.

The razor clam Sinonovacula constricta is an economically important cultured mollusk in China, but the molecular mechanism of its gonadal development and sexual differentiation remains unclear. This study integrated gonadal transcriptomic, proteomic, and metabolomic analysis to identify key sex-related molecules. Transcriptome analysis identified 2795 DELs and 6497 DEGs between sexes, including the sex-related genes Fem-1b, Fem-1c, GUCY1B2 and FAT4, as well as a regulatory network of 39 lncRNA-mRNA pairs involving Tektin-4, Ropporin-1, Histone H1, and FoxN4. Proteomic analysis revealed 3217 DEPs: Tektin family members, Ropporin-1 and Tssk proteins were upregulated in the testis, while histone H1 and FAT4 were upregulated in the ovary. Metabolomic analysis detected 409 DEMs, with uridine identified as a potential sex differential marker (upregulated in the ovary), and 23 gonadal development-related DEMs showed sex-specific upregulation. Integrative transcriptome-proteome analysis identified 1543 co-expressed DEGs/DEPs enriched in nucleosome assembly, oxidative phosphorylation, and carbon metabolism, including key sex-related genes AKAP14, Tektin/Tssk families, Histone H1, and FAT4. Transcriptome-metabolome integration identified 32 shared KEGG pathways (e.g., biosynthesis of unsaturated fatty acids, pyrimidine metabolism), while proteome-metabolome integration revealed 5 (positive ion) and 6 (negative ion) co-enriched pathways, with alanine, aspartate and glutamate metabolism and oxidative phosphorylation being functionally relevant to gonadal development. Collectively, these results reveal the molecular basis of gonadal development, highlight critical sex-related genes and steroid metabolic pathways, and provide valuable resources for future reproduction and breeding in S. constricta.

Animals↗

Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse.

BACKGROUND/AIM: Although clinical and immunological findings in steroid-sensitive nephrotic syndrome (SSNS) favor an immunopathogenesis, many issues remain unsolved. Comprehensive studies analyzing cellular and humoral immunity in SSNS are scarce, and few studies addressed the effect of steroids on immunological factors. METHODS: We therefore performed a cross-sectional study of T and B lymphocyte populations in 89 children during the different stages of the disease and related the findings to parameters of humoral immunity and treatment with steroids. RESULTS: In untreated relapse, an increase in the proportion of activated CD3+ lymphocytes with a concomitant reduction of CD19+ B cells was noted compared to healthy controls. Conversely, patients with steroid dependency, relapsing on alternate-day steroids, showed a decline of the absolute numbers as well as proportion of CD4+ lymphocytes but a relative increase in CD19+ B cells, compared to healthy controls. Also untreated remission was characterized by an absolute and relative decrease in CD4+ lymphocytes compared to healthy controls which was accompanied by a significant increase in the proportion of CD8+ and also activated CD3+ lymphocytes. Steroid-induced remission resulted in suppression of absolute and relative CD4+, while absolute and relative B cells were upregulated in this group compared to untreated remission. SUMMARY AND CONCLUSION: Alterations of lymphocyte populations in SSNS are not limited to relapse but seem to be more pronounced in remission and show a different profile with steroid treatment. Changes of lymphocyte populations do not only affect T but also B lymphocytes, which may be of relevance in the pathogenesis of this disorder.

Adolescent↗

Persistent high activity of the fetal adrenal cortex in preterm infants: is there a clinical significance?

BACKGROUND: In preterm infants, the activity of the fetal adrenal cortex continues until term. Dehydroepiandrosterone sulphate can block the synthesis of surfactant in vitro. The incidence of pulmonary disease is higher in male than in female preterm infants. OBJECTIVE: To investigate the relationship between urinary excretion of fetal zone steroids (3beta-OH-5-ene-steroids) and the severity of lung disease in preterm infants with respect to gender. PATIENTS AND METHODS: 3beta-OH-5-ene-steroids were profiled by gas chromatography-mass spectrometry in 24-h urinary samples in 61 preterm infants of less than 30 weeks gestational age. RESULTS: The incidence of respiratory distress syndrome treated with surfactant in females (n = 30) was 47% and in males (n = 31) 71%, p = 0.07. Medians of total excretion rates of fetal zone steroids (microg/kg/d) in female (male) preterm infants were at day 1: 1,317 (895); day 2: 3,154 (7,723), p = 0.03; day 3: 5,502 (9,494), p = 0.08; day 5: 7,140 (10,407); week 2: 8,731 (9,720); week 3: 8,571 (10,079); week 4: 7,620 (7,825). Regression analysis did not reveal a significant influence of maximum excretion rates of fetal zone steroids or gender on the incidence of respiratory distress syndrome treated with surfactant. CONCLUSIONS: Excretion rates of fetal zone steroids were 4-fold higher than previously reported indicating a persistent high activity of the fetal adrenal zone in preterm infants. Excretion rates of fetal zone steroids were significantly higher in male preterm infants compared to females at day 2 (trend at day 3) but did not have a significant influence on the incidence of respiratory distress syndrome.

Adrenal Cortex↗