Triple A syndrome: genotype-phenotype assessment

The triple A or Allgrove syndrome is an autosomal-recessive disease (MIM*231550) characterized by the triad of achalasia, alacrima and adrenocorticotropic hormone (ACTH)-resistant adrenal insufficiency. Associated features of the syndrome are neurological and dermatological abnormalities. Until the discovery of the AAAS gene as the responsible gene in triple A syndrome, the diagnosis was based on characteristic clinical features. Here we present the clinical and molecular genetic data which demonstrated the marked phenotypic variability in three unrelated patients with triple A syndrome. The final diagnosis of triple A syndrome was confirmed by molecular analysis. In one patient with isolated achalasia, the diagnosis of triple A syndrome could only be made on the basis of the molecular genetic analysis of the AAAS gene. We therefore suggest that the diagnosis of triple A syndrome should be considered in patients who exhibit only one or two of the main symptoms (i.e. alacrima, achalasia or adrenal insufficiency). These patients require careful neurological investigation, and mutation analysis of the AAAS gene should be performed.     

瞬目反射、脑干听觉诱发电位、经颅多普勒超声对椎基底动脉供血不足的诊断价值

目的：观察瞬目反射（ＢＲ）、脑干听觉诱发电位（ＢＡＥＰ）、经颅多普勒超声（ＴＣＤ）对椎基底动脉供血不足（ＶＢＩ）的诊断意义。方法：对４１例已经临床确诊的ＶＢＩ病人在间歇期进行ＢＲ、ＢＡＥＰ及ＴＣＤ检查。结果：ＴＣＤ、ＢＲ、ＢＡＥＰ异常率分别为８３％、８０％、６８％。ＢＲ提示脑桥损害１例、延髓损害１５例、广泛性脑干损害１７例；ＢＡＥＰ发现内耳听力减退２０例、脑干病变１３例；ＴＣＤ发现多血管流速异常１４例、一支流速改变１６例，有或伴有血管张力异常１３例。结论：由于ＢＲ、ＢＡＥＰ反射路径不同，检测结果不尽一致。联合检查有助于对病损部位进行定位。ＴＣＤ则有助于定性诊断     

Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats

The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.     

Androgen insufficiency in women: diagnostic and therapeutic implications

The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. The diagnosis of FAIS is made on the basis of these symptoms in the setting of a low serum free testosterone level. However, there is currently no readily available inexpensive assay which reliably measures free testosterone levels in the female range. The diagnosis of FAIS is further complicated by the lack of data demonstrating a minimum serum free testosterone level which, if below this, correlates with the symptoms of FAIS. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. There is a need for formulations of testosterone therapy specifically designed for use in women, along with clear guidelines regarding optimal therapeutic doses and long-term safety data.     

Electrophysiology of rat distal colon after partial nephrectomy

Previous in vivo studies in rat and man indicate that chronic renal insufficiency leads to an increase in the capacity of the large intestine for K secretion. The present studies were performed in isolated rat distal colon with conventional and K-sensitive microelectrodes to determine the cellular basis for enhanced colonic K secretion after 70% nephrectomy. The data revealed that in animals fed a regular diet, nephrectomy had no effect on the Na or K conductance of the apical membrane, or the kinetics of the basolateral membrane Na-K pump, but intracellular K activity decreased from 70±4 mmol/l to 58±4 mmol/l (P<0.005). In control (non-nephrectomised) animals, feeding a diet modestly (4-fold) enriched with K resulted in small but significant increases in the Na and K conductance of the apical membrane, no change in the kinetics of the basolateral membrane Na-K pump, and a rise in intracellular K activity from 70±4 mmol/l to 94±7 mmol/l (P<0.005). In contrast, in animals fed the K enriched diet, nephrectomy resulted in (i) large, amiloride-sensitive increases in transepithelial voltage and total tissue conductance (consistent with an appreciable degree of secondary hyperaldosteronism), (ii) marked increases in the Na and K conductance of the apical membrane, (iii) significant hyperpolarisation of the basolateral membrane, (iv) a 100% increase (P<0.02) in the maximum activity of the basolateral membrane Na-K pump, and (v) a rise in intracellular K activity from 94±7 mmol/l to 129±7 mmol/l (P<0.0025). These data suggest that the combination of modest dietary K enrichment and 70% nephrectomy stimulated an active K secretory process which reflected an increase in the K excretory load applied to the colonic mucosa, and the effects of aldosterone. In this model of renal insufficiency, enhanced K secretion by the transcellular and paracellular (potential-dependent) pathways results in a marked rise in the K excretory capacity of the colon.     

呼吸功能不全综合实验改革的探索

目的:为了探索如何在一次教学实验中将生理学、病理生理学和药理学三个机能学科的实验有机地结合起来, 形成综合性实验以培养学生的综合思维和实验研究能力。方法:在病理生理学的呼吸功能不全实验的基础上, 增加了呼吸的生理调节和不同类型的呼吸衰竭采用不同的针对性药物治疗, 并且采用启发式教学方法。结果:学生学习兴趣明显提高, 学生不仅学到了更多的研究方法, 而且综合分析和科研创新能力都有明显提高。结论:这种改进明显提高了实验课的教学水平和教学质量。     

Serum creatinine concentration and renal interstitial volume

Summary Renal biopsies of 44 patients with endocapillary acute glomerulonephritis (gn) and 64 patients with moderately severe mesangioproliferative gn were investigated morphometrically (point-counting-method, tubulometry).In both gn's statistically significant positive correlations between relative interstitial volume and the concentration of serum creatinine at the time of biopsy were found.Despite severe glomerular lesions the serum creatinine concentration is not increased in most cases of endocapillary acute gn, providing the relative interstitial volume is not increased by more than 15%.Increased serum creatinine concentration without a markedly enlarged interstitium was found in 11 cases of endocapillary acute gn with clinically and morphologically proven acute renal failure. In these cases the glomerular function is probably impaired by the Thurau-mechanism.In all other patients, especially in those with moderately severe mesangioproliferative gn, the serum creatinine concentration rises with an enlargement of relative interstitial volume. This reduction of renal function may be explained by a decrease to the total cross-sectional area of postglomerular vessels, caused by interstitial fibrosis. That may possibly lead to diminished renal blood flow and glomerular filtration with an increase of the serum creatinine concentration.Supported by the Deutsche Forschungsgemeinschaft     

Pharmacokinetics of high doses of piretanide in moderate to severe renal failure

Summary The pharmacokinetics of piretanide was studied in 10 patients with chronic renal failure. After administration of a high oral dose (12 to 192 mg) of piretanide the kinetics behaved according to an open 2-compartment model. The elimination constant in the first phase () ranged from 0.385 to 0.756 h^–1 and in the second phase () from 0.079 to 0.274 h^–1. The corresponding elimination half-lives ranged from 55 to 108 min (t_1/2 ) and from 152 to 524 min (t_1/2 ). Only an average of 2.8% of the orally administered drug was recovered in 24 h urines. Nevertheless, a good correlation was found between urinary recovery or renal clearance of the drug and residual renal function. The elimination of piretanide by non-renal mechanisms appeared to be increased when renal function was greatly diminished.     

基于数据挖掘的早发性卵巢功能不全动物模型分析

目的：研究早发性卵巢功能不全动物模型的造模特点,为早发性卵巢功能不全动物模型制备的规范化提供参考,为该病发病机制及诊疗研究提供更好的研究基础。方法：通过检索中国知网、万方、维普、中国生物医学文献及PubMed数据库获取近十年早发性卵巢功能不全动物实验文献,归纳实验动物种类、造模方式、给药剂量、给药方案、成模标准及检测指标,应用Excel软件进行频数分析,应用SPSS Modeler 18.0进行关联规则分析并运用Cytoscape 3.6.1对结果进行可视化升级。结果：共纳入文献281篇,建立早发性卵巢功能不全动物模型多选用SD大鼠或BALB/c小鼠,造模方式多选用医源性诱导,造模药物以环磷酰胺为主,成模标准多选用动情周期紊乱,检测指标多选用卵巢组织形态学变化、雌二醇、卵泡刺激素及动情周期以从多方面综合评价模型。结论：早发性卵巢功能不全动物实验多选用SD大鼠,以环磷酰胺首次腹腔注射给药50 mg·kg-1,第2天起以8 mg·kg-1·d-1维持14 d诱导造模,具有简便易行、成模率高且符合疾病发生过程等优点,可为该病基础动物实验研究提供参考。     

Vitamin D Status in Adolescents during COVID-19 Pandemic: A Cross-Sectional Comparative Study

Vitamin D has been claimed to be effective in the response to infections, including the respiratory syndrome coronavirus 2 (SARS-CoV-2). It is supposed that lockdown measures and fear of SARS-CoV-2 infection might reduce vitamin D levels through the modification of lifestyle. However, very few data exist on the association between lockdown measures and vitamin D status in humans. For this cross-sectional comparative study, adolescents (n = 298) aged 18 to 19 years were enrolled during the compulsory military fitness-for-duty evaluation between July and December 2020 in Southern Switzerland. Beyond anthropometric measurements, participants filled in a structured questionnaire about their lifestyle and a blood specimen was sampled for the determination of total 25-hydroxy-vitamin D. The obtained data were compared with those of 437 adolescents enrolled at the military fitness-for-duty evaluation during the same period of the year in the context of the CENERI study (2014–2016). The anthropometric measures were similar between the two study groups. The levels of vitamin D were also comparable (77 (64–91) vs. 74 (60–92) nmol/L, p = 0.50; median and interquartile range). A total of 38 (13%) and 43 (9.8%) subjects presented insufficient (<50 nmol/L) levels of vitamin D (p = 0.42) during the current pandemic and in the CENERI study, respectively. These data do not support the hypothesis that during the SARS-CoV-2 pandemic, late adolescents are at higher risk of vitamin insufficiency.