Therapeutic down-regulation of central and peripheral B-cell-activating factor (BAFF) production in pediatric opsoclonus-myoclonus syndrome

Opsoclonus-myoclonus syndrome (OMS) is an autoimmune, paraneoplastic, central nervous system disorder, characterized by cerebrospinal fluid (CSF) B-cell expansion and various putative autoantibodies. To investigate the role of B-cell activating factor (BAFF) in OMS and the effect of disease-modifying immunotherapies used to treat it, BAFF was measured by enzyme-linked immunoadsorbent assay in the CSF and serum of 161 children with OMS and 116 pediatric controls. The mean concentration of CSF BAFF and the CSF/serum BAFF ratio were significantly higher in untreated OMS compared to neurological controls. CSF and serum BAFF levels were significantly lower in children treated with ACTH or corticosteroids, as was the CSF/serum BAFF ratio. There was a strong, negative correlation between CSF or serum BAFF levels and ACTH dose. Monthly IVIg infusions had no net impact on BAFF levels, and the combination of IVIg with ACTH or steroids did not reduce or enhance their anti-BAFF effects. These data indicate that BAFF production is increased centrally, not peripherally, in OMS, implying astrocytic over production. The novel dose-related central and peripheral anti-BAFF properties of ACTH, especially, have implications for other BAFF-related autoimmune disorders, infectious diseases, and cancers.     

Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia

Hypoxic-ischemic encephalopathy (HIE) remains one of the most important neurologic complications in the newborn. Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage. Furthermore, recent data have suggested that platelet-activating factor (PAF) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury. The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia. In addition, we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid (CSF) after hypoxic-ischemic brain injury. The group of asphyxiated infants (Group 1) consisted of 21 full-term (gestational age >37 weeks). These infants were randomized and divided into either a standard therapy group (Group 1a; n=10) or cooling group (Group 1b; n=11). Head cooling combined with minimal hypothermia (rectal temperature 36.5-36 degrees C) was started as soon as practicable after birth. The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h. The control group (Group 2) consisted of seven full-term infants and none of these infants showed any sign of asphyxia. To measure PAF concentration in CSF, CSF with lumbar puncture was collected into tubes immediately before the cooling (1-3h after birth) and again after 36h. We had no evidence of severe adverse events related to hypothermia. In Group 1a, two infants died after 72h of life; however, all newborn infants in Group 1b survived. Convulsion required treatment in three infants of standard therapy group (1a); none of the infants in Group 1b had clinical seizure activity. Abnormal EEG patterns were found in four infants of Group 1a; no EEG abnormalities were noted in Group 1b (P<0.05). On admission (before cooling), PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control (P<0.001). Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups (Group 1a vs. 1b) (P>0.05). Obtained PAF level in CSF after 36h, showed a profound decline in cooling group of infants compared to Group 1a infants (P<0.01). In conclusion, the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging. Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants.     

Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia.

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, and plasma levels of CRH, ACTH and cortisol were determined in samples taken simultaneously from 28 patients with dementia including senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID), dementia following a cerebrovascular accident (CVD), and the borderline-to-normal state. CRH levels in CSF were significantly reduced in patients with SDAT and CVD, but not in those with MID, as compared with the borderline cases. ACTH levels in CSF were significantly reduced in the patients with SDAT compared to those with MID. Reduced CRH levels in CSF were found in the patients who showed severe dementia and poor activities of daily living (ADL). Plasma levels of CRH, ACTH and cortisol were normal and were not significantly different among the four groups of patients. CRH levels in CSF were positively correlated with ACTH levels in CSF, but not with the levels of plasma CRH, ACTH or cortisol. Plasma CRH levels were positively correlated with plasma ACTH levels. These results suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) CSF CRH is correlated with the severity of dementia and ADL; 3) the levels of CRH in CSF and plasma are independent, and 4) the plasma CRH reflects, at least in part, the activity of the hypothalamic CRH regulating the secretion of pituitary ACTH.     

血清CyPA、sCLU、HO-1与新生儿窒息复苏后发生脑损伤的关系研究

摘要 目的：探讨血清亲环素A（CyPA）、丛生蛋白（sCLU）、血红素氧化酶-1（HO-1）与新生儿窒息复苏后发生脑损伤的关系。方法：选择2020年6月至2023年3月湖北民族大学附属民大医院收治的172例窒息新生儿,根据复苏后是否发生脑损伤分为脑损伤组（80例）和无脑损伤组（92例）,复苏治疗前检测并对比两组血清CyPA、sCLU、HO-1水平。多因素Logistic回归分析新生儿窒息复苏后发生脑损伤的影响因素,受试者工作特征（ROC）曲线分析血清CyPA、sCLU、HO-1预测新生儿窒息复苏后发生脑损伤的价值。结果：脑损伤组血清CyPA、sCLU、HO-1水平高于无脑损伤组（P＜0.05）。胎盘早剥、母体妊娠高血压疾病、重度窒息、高水平CyPA、高水平sCLU、高水平HO-1是新生儿窒息复苏后发生脑损伤的危险因素（P＜0.05）。血清CyPA、sCLU、HO-1预测新生儿窒息复苏后发生脑损伤的曲线下面积为0.797、0.832、0.779,联合预测的曲线下面积为0.941,高于各指标单独预测。结论：新生儿窒息复苏后发生脑损伤的危险因素包括胎盘早剥、母体妊娠高血压疾病、重度窒息、CyPA升高、sCLU升高、HO-1升高,联合检测血清CyPA、sCLU和HO-1对新生儿窒息复苏后发生脑损伤具有较高的预测价值。     

Hormonal changes in patients with haematological malignancies

Levels of immunologically reactive insulin (IRI), growth hormone (GH), thyroxine, cortisol and ACTH in sera of patients with various haematological malignancies were determined. IRI and GH levels were increased in 80% of the patients regardless of the type of disease. IRI was more elevated in relapse than in remission. Cytostatic treatment returned IRI serum levels to normal. Thyroxine, ACTH and cortisol in serum were higher in only two percent of the patient with haematological malignancies.     

Insulin-like growth factor-1 and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration.

Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.     

替莫唑胺治疗垂体瘤患者的临床疗效及机制研究

目的:探讨替莫唑胺治疗垂体瘤患者的临床疗效及其机制。方法:选取我院收治的垂体瘤患者70例,随机分为实验组和对照组,每组35例。对照组患者进行显微镜下经鼻蝶窦手术治疗,并给予溴隐亭口服治疗;实验组在对照组治疗基础上联合替莫唑胺胶囊治疗。观察并比较治疗前后两组患者血清泌乳素、IGF-1、GH水平的变化及临床疗效。结果:与治疗前相比,两组患者治疗后的血清PRL、IGF-1、GH、TSH水平均降低,FT4、ACTH水平升高,差异具有统计学意义(P0.05);而与对照组比较,实验组的血清PRL、IGF-1、GH、TSH水平更低,FT4、ACTH水平更高(P0.05)。实验组的治疗总有效率显著高于对照组,差异具有统计学意义(P0.05)。结论:替莫唑胺治疗垂体瘤的临床疗效好,推测其机制与降低血清PRL、IGF-1水平有关。     

Some functional aspects of canine corticotrophs

To examine the regulation and functional significance of canine pituitary pars intermedia corticotrophs, ACTH and cortisol responses to CRF were studied in healthy dogs before and after treatment with dexamethasone. In addition the effects of the dopamine agonist bromocriptine and the dopamine antagonist pimozide were investigated. In the latter two instances prolactin concentrations were also measured. Finally the pituitaries were studied immunocytochemically for ACTH and alpha-MSH. No response of ACTH or cortisol to bromocriptine was observed. Pimozide caused a slight rise in ACTH levels in some dogs. However, prolactin levels significantly decreased with bromocriptine and increased with pimozide. Injection of synthetic ovine CRF to dogs was followed by sharp increases in ACTH and cortisol values. These responses were obliterated by prior treatment with dexamethasone. In 1 of 4 dogs given dexamethasone before euthanasia, there were few pars distalis cells with ACTH(1-24) immunopositivity, although persistence of ACTH(1-24) reaction was noted within cells of the pars intermedia. The results indicate that none of the CRF-induced ACTH secretion in dogs is derived from pars intermedia corticotrophs. Dosages of bromocriptine and pimozide that clearly alter prolactin secretion do not consistently affect ACTH levels.     

亚低温联合手术治疗对重型颅脑损伤患者血清ET-1、Ang-1、G-CSF及预后的影响

目的:研究亚低温联合手术治疗对重型颅脑损伤患者血清内皮素-1(endothelin-1,ET-1)、血管生成素-1(Angiopoietin-1,Ang-1)、粒细胞集落刺激因子(Granulocyte-colony stimulating factor,G-CSF)及预后的影响。方法:选取我院收治的118例重型颅脑损伤患者,按照抛硬币法分为治疗组和对照组,每组各59例。两组患者入院后均进行手术治疗,治疗组则在术后进行亚低温治疗。观察并比较两组患者临床治疗效果、治疗前后血清ET-1、Ang-1、G-CSF水平变化情况、不良反应发生情况以及预后情况。结果:治疗后,治疗组第1、3、7、14天的颅内压均显著低于对照组,两组组间比较差异显著(P0.05)。两组患者血清ET-1、Ang-1、G-CSF较治疗前显著下降,且治疗组血清各指标水平改善情况显著优于对照组(P0.05)。两组患者均发生脑梗死、脑积水、癫痫、肺部感染、切口脑脊液瘘以及应激性溃疡出血等并发症,但两组差异无统计学意义(P0.05)。治疗组患者的预后良好率达到49.15%,显著高于对照组的13.56%;而治疗组的死亡率(5.08%)则明显低于对照组(13.56%),两组差异显著(P0.05)。结论:亚低温联合手术治疗较单纯手术治疗可以更好的改善患者血清ET-1、Ang-1以及G-CSF水平,其不良反应发生率也更低,从而可以更好的改善患者的预后情况,值得在临床上推广应用。     

Effect of hydrocortisone on ACTH, growth hormone, insulin and glucose in the blood of bilaterally adrenalectomized patients

This study is aimed at elucidating the mechanism of paradoxical rise in plasma ACTH levels in response to glucocorticoids, observed by several authors in bilaterally adrenalectomized patients with Cushing's disease. Six control subjects and fourteen patients bilaterally adrenalectomized for Cushing's disease were given a dose of 200 mg hydrocortisone sodium succinate by 3-5 mm i.v. injection. Plasma ACTH (in 6 patients), serum cortisol, growth hormone (GH) and insulin and blood glucose levels were estimated at 0, 30, 60, 90, and 120 minutes. The administration of hydrocortisone significantly suppressed plasma ACTH levels only at 60 min. In one case a slight rise in ACTH level during the test was observed. A significant fall in blood glucose levels was found only in the adrenalectomized patients. No significant changes in serum insulin and GH levels were noted. The possible mechanisms are discussed, especially the potential role of transient glucose deficiency in the pathophysiology of plasma ACTH increase in response to hydrocortisone in the bilaterally adrenalectomized patients.     

Effect of soman (pinacolyl methylphosphonofluoridate) on the blood levels of corticosterone and adrenocorticotropin in mice

Mice were poisoned by an extremely toxic organophosphate anticholinesterase soman (pinacolyl methylphosphonofluoridate), 50 or 100 micrograms/kg at 1000, and the serum concentrations of corticosterone were determined fluorometrically at 3-h intervals for at least 24 h. The lower soman dose (50 micrograms/kg) produced a modest increase in serum corticosterone concentrations but by 24 h the levels were not significantly different from control. Following the higher soman dose (100 micrograms/kg) the serum corticosterone levels were elevated significantly (p less than 0.05), for at least 27 h. However, ACTH concentrations were not elevated. It is possible that the elevated levels of corticosterone were due to a reduced metabolism and excretion of corticosterone resulting from the intense hypothermia, following soman poisoning which may change cardiac output and organ (liver and kidney) perfusion and not due to an enhanced release from the adrenal gland.     

Endocrine patterns before and after examination stress in males and females

Plasma levels of cortisol, adrenocorticotropin (ACTH), and growth hormone (GH), were determined by radioimmunoassay in medical students just before (Exp.1) plasma values of cortisol were higher than their control values in both sexes, statistically significantly, however, only in males. The difference of cortisol behavior between the sexes was not significant. The males' ACTH values were lower than their control levels, but there was no such difference in the females. Plasma levels and differences of growth hormone varied greatly in both sexes. After the examination (Exp.2) plasma values of cortisol were unaffected compared with their control values in both sexes. The ACTH values were lower than the control values in both sexes, significantly though only in the males. The GH values were higher than control values in the males but not in the females. The results are in line with previous observations suggesting that psychological stress is associated with slightly different hormonal effects in males and females.     

Reports of two cases of selective adrenocorticotropin (ACTH) and growth hormone (GH) deficiency: differential diagnosis from cases with isolated ACTH deficiency associated with transient GH insufficiency

An acquired partial pituitary insufficiency with selective ACTH and GH deficiency was demonstrated in two men aged 47 and 54, for which the clinical course over many years corresponds to Addison's disease. In one of the 2 cases, antibodies to anterior pituitary cell membrane, assayed by an immunofluorescence method with GH3 cells (rat GH and prolactin secreting cell) and AtT-20 cells (mouse ACTH secreting cell) as antigens, were positive. We also present a 55-year-old man with isolated ACTH deficiency associated with transient GH deficiency. In this case, hydrocortisone replacement corrected his subnormal, pre-therapy GH response to insulin tolerance and glucagon propranolol tests, although there was no response of serum GH to L-dops and arginine stimulation test before therapy. Selective ACTH and GH deficiency are very rare and the finding of transient GH insufficiency in a patient with isolated ACTH deficiency suggests that repeated testing while on hydrocortisone replacement therapy is of great diagnostic importance in order to distinguish between selective ACTH and GH deficiency and isolated ACTH deficiency accompanied by transient GH insufficiency.     

急性心肌梗死患者血清外连素、MEG3、HSP-70水平与心肌损伤标志物及心血管不良事件的关系研究

目的:研究急性心肌梗死(AMI)患者血清外连素、母系表达基因3(MEG3)、热休克蛋白70(HSP-70)水平与心肌损伤标志物及心血管不良事件的关系。方法:选取2015年1月-2020年1月期间我院接受治疗的AMI患者200例作为AMI组,另选取同期在我院健康体检的人群100例作为对照组,对比对照组、AMI组心肌型肌酸激酶同工酶(CK-MB)、肌红蛋白(Myo)、心肌肌钙蛋白Ⅰ(cTnI)、外连素、MEG3 RNA、HSP-70。对比心血管不良事件与非心血管不良事件患者的CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70水平。采用Pearson相关性分析AMI患者血清外连素、MEG3 RNA、HSP-70水平与心肌损伤标志物的关系。结果:AMI组CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70均高于对照组(P<0.05)。随访过程中,有59例发生心血管不良事件纳为心血管不良事件组,剩余141例未发生心血管不良事件纳为非心血管不良事件组。心血管不良事件组患者的CK-MB、Myo、cTnI、外连素、MEG3 RNA、HSP-70均高于非心血管不良事件组(P<0.05)。AMI患者外连素、MEG3 RNA、HSP-70水平与CK-MB、Myo、cTnI均呈正相关(P<0.05)。结论:AMI患者中外连素、MEG3 RNA、HSP-70均呈现异常高表达,且与心肌损伤标志物密切相关,可考虑作为AMI患者早期确诊的新型标志物。     

Detection of antibodies to Angiostrongylus cantonensis in serum and cerebrospinal fluid of patients with eosinophilic meningitis

Adult and young adult antigens of Angiostrongylus cantonensis were purified by immuno-affinity chromatography and used to detect antibody in serum and cerebrospinal fluid (CSF), by enzyme-linked immunosorbent assay (ELISA), in cases of human eosinophilic meningitis or meningoencephalitis. The levels of IgG, IgA, IgM and IgE antibodies to A. cantonensis in these patients were higher than levels in control subjects. Antibodies in patients detected against adult and young adult worm antigens of A. cantonensis did not differ significantly. Significantly higher IgM and IgE antibody levels were observed in serum compared with CSF from infected patients (Student's t-test, P less than 0.05). Both adult and young adult A. cantonensis antigens proved to be highly sensitive in ELISA for serum antibodies; however, the sensitivity was significantly lower in tests on CSF.     

Effect of vagotomy on plasma levels of growth hormone, free fatty acids and glucose in the pigeon

Plasma levels of growth hormone (GH), free fatty acids (FFA) and glucose were measured in vagotomized (VgX) and sham-operated (VgS) control pigeons. In VgX pigeons, GH level was significantly lower whereas FFA and glucose levels were higher than in VgS pigeons. The depression in GH level in VgX pigeons has been attributed to the significantly high levels of norepinephrine (NE) and corticosterone in these Birds. The higher plasma FFA concentration in VgX pigeons was therefore due to adipokinetic hormonal action other than of GH. It has been suggested that the adrenocorticotrophic hormone (ACTH) and/or NE could have produced the increase in plasma FFA in VgX pigeons. The pronounced hyperglycemia seen in VgX pigeons has been attributed to catecholamine action in the absence of the vagal tone.     

Effect of dexamethasone on the release of pituitary hormones in monolayer cultures of rat pituitary cells

The effect of dexamethasone on the release of ACTH, GH, PRL, LH and TSH was studied in monolayer cultures of rat pituitary cells in 4-hour incubation. With or without the addition of rat hypothalamic extract, the release of GH was significantly inhibited by dexamethasone at concentrations higher than 10(-9) M, although less remarkably than that of ACTH. Intracellular ACTH and GH were unchanged. PRL, LH and TSH were not affected. These results indicate that dexamethasone, when exerted for 4 hours, suppressed the release of GH as well as ACTH, at least in part, at the pituitary level.     

窒息新生儿血清miR-21、miR-210及miR-199a的表达及临床意义

目的:探讨窒息新生儿血清mi RNA-21、mi RNA-210及mi RNA-199a的表达及临床意义。方法:选取2015年9月1日到2017年7月31日我院新生儿科收治的窒息新生儿40例作为观察组,另选取同期在我院出生的健康新生儿40例作为对照组,根据阿氏(Apgar)评分将观察组的新生儿分为重度窒息组(12例)和轻度窒息组(28例)。检测所有新生儿血清中mi RNA-21、mi RNA-210及mi RNA-199a的表达水平,并比较观察组与对照组、重度窒息组与轻度窒息组血清中mi RNA-21、mi RNA-210及mi RNA-199a水平,并分析其相关性。结果:观察组的血清mi RNA-21、mi RNA-210水平高于对照组,mi RNA-199a水平低于对照组,差异有统计学意义(P0.05)。重度窒息组的血清mi RNA-21、mi RNA-210水平均高于轻度窒息组,mi RNA-199a水平低于轻度窒息组,差异有统计学意义(P0.05)。观察组血清mi RNA-21与mi RNA-210呈正相关(P0.05),血清mi RNA-21、mi RNA-210与mi RNA-199a水平呈负相关(P0.05)。结论:窒息新生儿血清中mi RNA-21、mi RNA-210呈现高表达,mi RNA-199a呈现低表达,且其表达水平与窒息严重程度相关。     

Reduction of baclofen-, but not sodium valproate-induced growth hormone release in type I diabetic men.

The effects of sodium valproate (a drug enhancing endogenous gamma aminobutyric acid (GABA)-ergic activity) and of the GABA analog baclofen (a GABA B receptor agonist) on serum GH levels was tested in 8 type I diabetic men and 8 normal controls. Sodium valproate (800 mg) or baclofen (10 mg) were given by mouth at 08.30 h on the experimental day. Control tests with a placebo were performed on different occasions. Basal GH levels were similar in controls and diabetic patients. Sodium valproate induced a 7 fold increase in serum GH concentrations in both groups. In contrast, baclofen-induced GH rise was significantly higher in normal controls (mean peak was 3.4 times higher than baseline) than in diabetic patients (mean peak was only 2.1 times higher than basal value). Serum GH levels did not change after placebo administration in any groups. These data suggest the presence of diabetes-induced alterations of a GABAergic pathway mediated by B receptors in the control of GH secretion. Alternatively, the data might indicate a change in diabetic men of other baclofen-sensitive neurotransmissions, different from GABA.