Night-time plasma cortisol secretion is associated with specific sleep stages

Polysomnographic recordings were obtained in 16 healthy male subjects in order to evaluate temporal interrelationships between concentrations of plasma cortisol and sleep at night. The pattern of nocturnal cortisol secretion appeared to be synchronized with the periodicity of sleep: rapid eye movement (REM) sleep was found to be primarily present when cortisol concentrations were decreasing, indicating a diminished or absent secretory activity of the adrenals at that time; wakefulness and Stage 1 sleep, by contrast, were associated with increasing plasma cortisol concentrations. Furthermore, the enhanced adrenal secretory activity usually preceded the occurrence of light sleep or wakefulness, which is in accord with a wakening effect of plasma cortisol. Just prior to the onset of the first pronounced rise in plasma cortisol during sleep, episodes of slow wave sleep (SWS) became more frequent. This suggests that the offset of episodes of SWS may act as a trigger for the first pronounced nocturnal rise in plasma cortisol.     

Normal growth of prepubertal nephrotic children during long-term treatment with repeated courses of prednisone

The growth of 21 prepubertal children with steroid-dependent frequently relapsing nephrotic syndrome was studied before and during treatment with repeated courses of oral prednisone for 4 y. The height and height velocity standard deviation scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06, respectively, at the onset of the disease and -0.12 and +0:05, +0:14 and +1:02, +0:21 and +0:78 and +0:17 and +0:66, respectively, thereafter yearly during the treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and 2081 mg/body area (m) at the first, second, third and fourth year, respectively. The nephrotic children grew normally for their age before onset of the disease and growth remained normal despite prednisone treatment.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Summary: Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35 ± 6 years vs 42 ± 9 years) and had worse histological scores for tubular atrophy (1.7 ± 0.7 vs 1.1 ± 0.5) and arteriolar hyperplasia (1.4 ± 0.7 vs 0.7 ± 0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9 ± 0.3 mg/dL to 2.5 ± 1.2) or reduction in creatinine clearances (52 ± 20mL/min to 52 ± 27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1 ± 0.5 mg/dL to 3.3 ± 1.1, P < 0.01) and a fall in creatinine clearances (51 ± 26 mL/min to 31 ± 22, P = 0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2 ± 1.2 g/day to 1.3 ± 1.1, non-treatment group: 1.9 ± 1.4 to 1.5 ± 1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.     

参三七皂甙Rg1对实验性血栓形成的影响及其机制探讨

用大鼠动静脉血栓形成模型,研究参三七皂甙Rg₁抗血栓作用。结果表明,参三七皂甙Rg₁可明显降低实验性血栓形成,对大鼠血浆纤溶系统亦有明显作用,可升高血浆中组织纤溶酶原激活物(t-PA)活性和活性型t-PA百分比,降低组织纤溶酶原激活物抑制剂(PAI)活性。同时利用培养大鼠血管内皮细胞实验,发现Rg₁可以剂量依赖性提高血管内皮细胞一氧化氮(NO)释放。提示Rg₁抗血栓作用与增强纤溶系统活性,促进血管内皮NO释放有关。     

Adrenocorticoid regulation of Na+, K+-ATPase in adult rat kidney: effects on post-translational processing and mRNA abundance

The mechanisms by which adreno-corticoid hormones regulate Na⁺, K⁺-ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na⁺, K⁺-ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0±0.8 vs. Adx = 7.1±0.7 μmol Pi mg^-1 protein h^-1) and in renal microsomes (C = 30.3 ± 1.9 vs Adx = 14.6 ± 1.3 μmol Pi mg^-1 protein h^-1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 μg kg^-1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na⁺, K⁺-ATPase activity. In cortical homogenate the protein level of α1 and β1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the α1 and β1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the α1 and β1 subunits was significantly lower (P < 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for α1 and β1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 μg kg^-1 body wt), a significant 2-fold increase in both α1 and β1 mRNAs was observed (P < 0.05 for both subunits). These data suggest that glucocorticoids can upregulate the mRNA of both Na⁺, K⁺-ATPase subunits but that the low renal Na⁺, K⁺-ATPase activity in adult Adx rats is mainly due to loss of glucocorticoid regulation of the post-translational processing of the enzyme.     

Effects of calcitonin on human auditory and visual evoked brain potentials

Besides its Ca⁺⁺-regulative effects, calcitonin is known to diminish sensitivity to painful stimuli. The present study aimed to clarify whether calcitonin has similar effects on stimulus processing in other modalities. Effects of calcitonin were assessed on brain potentials recorded from the human scalp which were evoked either by auditory clicks or visual checkerboard pattern-reversals. Twelve healthy men were tested in a double-blind intra-subject design receiving either 0.1 IU/kg salmon calcitonin (sCT) or 1.0 IU/kg sCT or saline solution during a 20 min IV infusion. sCT significantly increased latency of wave V of the brainstem auditory evoked potential (BAEP). Effects on BAEP wave V increased in magnitude with increasing dose of sCT and with decreasing intensity of the click stimulus. There was also a slight increase in latency of the N80 of the pattern-reversal visual evoked potential (PR-VEP). Additionally, subjects rated themselves as less activated following the high dose of sCT compared to placebo. The pattern of results is in accord with a slowing or inhibitory influence of calcitonin on auditory and visual sensory processing, thus paralleling findings concerning calcitonin effects on the perception of painful somatosensory stimuli.