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1.
Ceramide synthases (CerS) synthesise ceramides of defined acyl chain lengths, which are thought to mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed a significant elevation of CerS2 and its products, C24-ceramides, in CD11b+ cells (monocytes and neutrophils) isolated from blood. This result correlates with the clinical finding that CerS2 mRNA expression and C24-ceramide levels were significantly increased by 2.2- and 1.5-fold, respectively, in white blood cells of MS patients. The increased CerS2 mRNA/C24-ceramide expression in neutrophils/monocytes seems to mediate pro-inflammatory effects, since a specific genetic deletion of CerS2 in blood cells or a total genetic deletion of CerS2 significantly delayed the onset of clinical symptoms, due to a reduced infiltration of immune cells, in particular neutrophils, into the central nervous system. CXCR2 chemokine receptors, expressed on neutrophils, promote the migration of neutrophils into the central nervous system, which is a prerequisite for the recruitment of further immune cells and the inflammatory process that leads to the development of MS. Interestingly, neutrophils isolated from CerS2 null EAE mice, as opposed to WT EAE mice, were characterised by significantly lower CXCR2 receptor mRNA expression resulting in their reduced migratory capacity towards CXCL2. Most importantly, G-CSF-induced CXCR2 expression was significantly reduced in CerS2 null neutrophils and their migratory capacity was significantly impaired. In conclusion, our data strongly indicate that G-CSF-induced CXCR2 expression is regulated in a CerS2-dependent manner and that CerS2 thereby promotes the migration of neutrophils, thus, contributing to inflammation and the development of EAE and MS. 相似文献
2.
Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?
《Sleep medicine》2021
Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients. 相似文献
3.
We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control. 相似文献
4.
James R. Westphal 《International journal of mental health and addiction》2007,5(2):123-140
Introduction Recent reviews found problem gamblers are heterogeneous and recommended subtyping gamblers in treatment studies.
Objective Review factors (stage of change, preferred gambling activity, co-occurring disorder, and temporal instability of symptoms)
for subtyping by evaluating the evidence for their effects on gambling treatment.
Methods Literature review, evidence grading.
Results Evidence is limited that any of the reviewed factors affects gambling treatment. Substantial evidence from prospective studies
and other evidence from cross-sectional studies and the strong placebo response among pathological gamblers support the temporal
instability of gambling symptoms.
Conclusions Multiple studies are needed to develop the evidence base needed to subtype gamblers in treatment. Changes in the diagnostic
criteria of pathological gambling may be necessary, especially to specify the persistence of gambling-related symptoms. 相似文献
5.
为了探讨增产菊胺酯引起小鼠精了生成障碍的可能机理,本文研究了增产菊胺酯对雄性小鼠卵泡刺激素(FSH)、黄体生成素(LH)及睾酮(T)的影响。小鼠经口染毒,隔天一次,连续10次,第35天处死。检验因清FSH、LH没有明显变化,而睾丸组织睾酮含量出现剂理依赖性降低,高剂量组与对照组比较有显著性差异(P〈0.05),结果表明,增产菊胺酯不影响FSH、LH,而影响T的合成和分泌。这可能是增产菊胺酯对小鼠精 相似文献
6.
Takashi Ito Kazuo Shimamura Kiyoshi Shoji Akira Akatsuka Yasuyoshi Kiryu Norikazu Tamaoki Yoshiyuki Osamura 《Virchows Archiv : an international journal of pathology》1993,422(6):487-490
A rare case of urinary bladder carcinoma with granulocyte colony stimulating factor (G-CSF) production was reported. In an 83-year-old female, marked neutrophilia in the peripheral blood decreased from 132,500/mm3 to 3,300/mm3 after tumour resection. The tumour was a transitional cell carcinoma. The serum G-CSF level reduced from 238 pg/ml pre-operatively to normal (60 pg/ml) after the operation. Immunohistochemical investigation of the resected tumour with monoclonal antibody specific for G-CSF revealed positive staining in the carcinoma cells, confirming G-CSF secretion. 相似文献
7.
This experiment was undertaken to provide a pharmacological characterization of performance on a task involving food-related instrumental and consummatory behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or approaching and consuming a less-preferred food (Lab Chow). The lever pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever pressing schedule. Previous work has shown that injection of dopamine (DA) antagonists, or depletion of DA in the nucleus accumbens, caused a substantial shift in behavior such that lever pressing was reduced but chow consumption increased. In the present study it was shown that the DA antagonist haloperidol decreased lever pressing and increased chow consumption at doses of 0.1 and 0.15 mg/kg. The D1 antagonist SCH 23390 (0.05, 0.1 and 0.15 mg/kg) and the non-selective DA antagonistcis-flupenthixol (0.3 and 0.45 mg/kg) decreased lever pressing and produced substantial increases in chow consumption. The D2 antagonist sulpiride decreased lever pressing, but produced only slight increases in chow intake at the highest dose. Pentobarbital reduced lever pressing and increased chow consumption at 10.0 mg/kg. The muscarinic agonist pilocarpine produced dose-related decreases in lever pressing, but failed to increase chow consumption. Amphetamine produced dose-related decreases in both lever pressing and chow consumption. These results indicate that low/moderate doses of the DA antagonists haloperidol,cis-flupenthixol and SCH 23390 can suppress lever pressing in doses that leave the animal directed towards food acquisition and consumption. 相似文献
8.
目的 :观察血清保存方法对促甲状腺激素 (TSH)结果的影响。方法 :将甲状腺功能正常、异常患者共 10份血清 ,采用不同血清量、不同条件分组保存后测定 TSH。结果 :保存方法对 TSH结果有一定的影响。结论 :用于 TSH血清的保存量要多、要密封管口、低温保存。 相似文献
9.
The effect of a systemic (IP) treatment with 1.0, 3.0 and 9.0 mg/kg U-50,488H (U50), a highly selective kappa-agonist, on spontaneous, nocturnal ingestive behavior of the rat was studied using a microcomputer controlled data acquisition system. The latency to initiate drinking was increased and drinking behavior was suppressed in the first hour after injection in a dose-dependent manner. The consummatory indices of drinking were not affected. After this period of adipsia, a phase of polydipsia, that was probably due to the diuretic effect of U50, was evident. The prophagic effect of U50 was evident only at the dose of 3 mg/kg and was accompanied by an increased duration of feeding episodes but not by a reduced latency to feed. These results suggest that kappa-receptors play a pivotal role in modulating spontaneous drinking in the normally hydrated rat and that this control is mainly exerted on the motivational aspect of drinking. 相似文献
10.
全身(全淋巴)照射后100例医源性急性放射病的临床分析 总被引:1,自引:1,他引:0
在造血干细胞移植治疗肿瘤过程中用全身照射(TBI)或全淋巴照射(TLI)预处理,研究受照不同剂量患者发生医源性急性放射病严重程度,治疗方法和造血恢复及相关合并症。方法100例患者(白血病91例,其他肿瘤9例)接受500~1000cGyTBI或TLI和超大剂量化疗作预处理。结果均发生医源性急性放射病,白细胞降至(0~0.15)×109/L,骨髓空虚,合并各种感染和出血。经造血干细胞移植,抗感染,应用GM-CSF或G-CSF积极支持治疗及保护隔离措施,92例造血恢复,8例死于不同感染和出血。结论造血干细胞的移植起主要治疗作用,不同造血因子用于治疗急性放射病,可能是一种有希望的方法 相似文献