Association Between NR3C1 Gene Polymorphisms and Toxicity Induced by Glucocorticoids Therapy in Saudi Children with Acute Lymphoblastic Leukemia

Background: Glucocorticoids (GCs) are key hormones used for the treatment of acute lymphoblastic leukemia(ALL) in children, but their cytotoxic effects are not well defined. The aim of this study was to evaluate the associationbetween polymorphisms in NR3C1 encoding for protein involved in the GCs metabolism and its role in the developmentof ALL and the toxicity outcome, in terms of liver toxicity, glucose abnormality and infections, in ALL Saudi children.Methods: The following polymorphisms BCII rs41423247, ER22/23 EK rs6189 and rs6190 and N363S rs6195 inNR3C1 were analyzed in 70 children with ALL treated according to the ALL 2000 study protocol in comparison to60 control subjects. Treatment toxicities and their association with genotypes were evaluated according to CommonToxicity Criteria (NCI-CTC). Results: This study demonstrated that the NR3C1 did not contribute to the developmentof childhood ALL. Homozygous ER22/23EK polymorphism was not found in both ALL patients and in control groupwhereas the heterozygous polymorphism was only observed in the control group (6.66%). The toxicology data inthis study showed a significant difference between ALL patients carrying N363S polymorphism and wild type (40%and 6.51% respectively, P= 0.009) and a high-risk factor in the toxicity of glucose abnormality (OR=10.167; 1.302-79.339).BCII shows increased risk factors towards the liver toxicity (OR=2.667; 0.526-7.330) as well as the glucoseabnormality (OR=7.5; 1.039-54.116). Conclusion: This study suggested that the polymorphisms in NR3C1 were notassociated with the development of ALL in children. N363S polymorphism was sensitive to glucocorticoids and it maycontribute to the glucose abnormality for these patients.     

糖皮质激素治疗3例重/危重型COVID-19患者有效性及安全性分析

目的：初步评估糖皮质激素治疗重/危重型COVID-19患者的有效性及安全性。方法：通过回顾性分析3例重/危重型COVID-19患者激素使用指征、使用时机、用法用量及疗程和不良反应，对比患者使用激素前后症状、体征，炎症因子、血氧饱和度、氧合指数及影像学等变化，分析激素使用的有效性和安全性。结果：有效性方面：3例患者有激素使用指征且使用后症状体征有一定好转，影像学有吸收；患者C病情反复并进行了气管插管。安全性方面：3例患者均出现了血糖升高；患者B的乙肝病毒被激活并继发了糠秕孢子菌毛囊炎；患者C细菌感染加重并出现了异常躁动。3例患者的排毒时间均大于35天，其中患者B排毒时间最长，为44.67天；3例患者住院时间均超过1个月，B患者长达47.46天。结论：激素应用是把双刃剑，应严格掌握使用指征和疗程，权衡利弊，重视激素使用后的不良反应。     

Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.     

Deflazacort alleviate pro-inflammatory cytokines expression,oxidative stress and histopathological alterations in collagen induced arthritis in Wistar rats

ObjectivesGlucocorticoids are important and frequently used class of anti-inflammatory drugs. Deflazacort (DFZ) is a glucocorticoid and an oxazolone derivative of prednisolone. As it has high anti-inflammatory and immunosuppressive potency, we studied inhibitory effect of DFZ on mediators regulating the pro-inflammatory response and oxidative stress induced in arthritis.MethodsFemale Wistar rats were immunized intradermally by collagen type II to induce collagen induced arthritis. Arthritic rats were treated with DFZ orally (6 mg kg⁻¹ body weight) until 28 days after the onset of clinical symptoms of disease. The effect of DFZ treatment in the rats was monitored by clinical scoring, biochemical parameters, immunohistochemistry and histopathological evaluation.ResultsDeflazacort significantly decreased the level of articular elastase, nitric oxide and lipid peroxidation whereas significantly increased the activity of catalase, superoxide dismutase and glutathione. Deflazacort down-regulated expression of pro-inflammatory molecules like TNF-α and COX-2. Histopathological evaluation revealed significant reduction of synovial hyperplasia and cellular infiltration in synovial membrane in DFZ treated group as compared to the diseased group.ConclusionsThis suggests that DFZ significantly down-regulates the expression of pro-inflammatory molecules such as TNF-α and COX-2 and alleviates the oxidative stress which make it a viable therapeutic option for treatment of arthritis.     

解析呼吸内科危重症哮喘的判断及治疗方法

目的对呼吸内科危重症哮喘的判断以及治疗方法进行分析。方法将2009年12月—2011年12月到该院呼吸内科进行危重症哮喘治疗的55例患者分别分成治疗组以及对照组进行比较,得出比较结果。结果项两组经过比较后,治疗组的治疗效果比对照组的治疗效果明显,两者差异具有统计学意义(P<0.05)。结论采用氨茶碱联合糖皮质激素雾化治疗危重症哮喘比单独使用氨茶碱治疗危重症哮喘的效果更为明显。     

糖皮质激素对记忆巩固的作用及其神经机制

背景 糖皮质激素(glucocorticoid,GC)在机体的作用范围比较广泛,对学习记忆也能产生影响. 目的 近年来关于GC增强记忆巩固的神经机制有了进一步的发展,现就近年的进展予以综述. 内容 在人体和动物的众多研究均提示,去甲肾上腺系统的激活在GC影响记忆的机制中发挥重要的作用,谷氨酸及其受体、内源性大麻素也参与其中.GC对记忆巩固的调节主要通过基底外侧杏仁核(the basolateral complex of the amygdale,BLA)及BLA与其他脑区的相互作用而实现,且不同的麻醉药物对应激反应的影响也不相同. 趋向 深入研究GC对人体认知功能的影响,有助于揭示认知功能障碍的发生机制,有利于临床工作者制定有效的预防及治疗方案.     

Endocrine systems in juvenile anadromous and landlocked Atlantic salmon (Salmo salar): seasonal development and seawater acclimation

The present study compares developmental changes in plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and cortisol, and mRNA levels of their receptors and the prolactin receptor (PRLR) in the gill of anadromous and landlocked Atlantic salmon during the spring parr-smolt transformation (smoltification) period and following four days and one month seawater (SW) acclimation. Plasma GH and gill GH receptor (GHR) mRNA levels increased continuously during the spring smoltification period in the anadromous, but not in landlocked salmon. There were no differences in plasma IGF-I levels between strains, or any increase during smoltification. Gill IGF-I and IGF-I receptor (IGF-IR) mRNA levels increased in anadromous salmon during smoltification, with no changes observed in landlocked fish. Gill PRLR mRNA levels remained stable in both strains during spring. Plasma cortisol levels in anadromous salmon increased 5-fold in May and June, but not in landlocked salmon. Gill glucocorticoid receptor (GR) mRNA levels were elevated in both strains at the time of peak smoltification in anadromous salmon, while mineralocorticoid receptor (MR) mRNA levels remained stable. Only anadromous salmon showed an increase of gill 11beta-hydroxysteroid dehydrogenase type-2 (11beta-HSD2) mRNA levels in May. GH and gill GHR mRNA levels increased in both strains following four days of SW exposure in mid-May, whereas only the anadromous salmon displayed elevated plasma GH and GHR mRNA after one month in SW. Plasma IGF-I increased after four days in SW in both strains, decreasing in both strains after one month in SW. Gill IGF-I mRNA levels were only increased in landlocked salmon after 4days in SW. Gill IGF-IR mRNA levels in SW did not differ from FW levels in either strain. Gill PRLR mRNA did not change after four days of SW exposure, and decreased in both strains after one month in SW. Plasma cortisol levels did not change following SW exposure in either strain. Gill GR, 11beta-HSD2 and MR mRNA levels increased after four days in SW in both strains, whereas only the anadromous strain maintained elevated gill GR and 11beta-HSD2 mRNA levels after one month in SW. The results indicate that hormones and receptors of the GH and cortisol axes are present at significantly lower levels during spring development and SW acclimation in landlocked relative to anadromous salmon. These findings suggest that attenuation of GH and cortisol axes may, at least partially, result in reduced preparatory upregulation of key gill ion-secretory proteins, possibly a result of reduced selection pressure for marine adaptations in landlocked salmon.     

Multidisciplinary protocol of preoperative and surgical management of patients with pituitary tumors candidates to pituitary surgery

The optimal planning of preoperative diagnosis, management and treatment of pituitary tumors (PT) candidates to pituitary surgery (PS) requires a multidisciplinary approach involving a team of endocrinologists, neurosurgeons, ENT, neuro-ophthalmologists and neuroradiologists with experience in pituitary diseases. Such teams improve surgical results, minimize complications and facilitate their correct treatment if occurring, and optimize the hormonal, ophthalmological and radiological preoperative and follow-up evaluation. We have developed a clinical practice protocol for patients with PT who are candidates to PS based on the most recent national and international guidelines and the relevant literature regarding PT published in the last years. The protocol has been elaborated by a multidisciplinary team of a Spanish Pituitary Tumor Center of Excellence (PTCE) that includes at least one neurosurgeon, ENT, neuroradiologist, neuro-ophthalmologist, endocrine pathologist and endocrinologist specialized in pituitary diseases. We elaborated this guideline with the aim of sharing our experience with other centers involved in the perioperative and surgical management of PT thereby facilitating the management of patients undergoing PS.