复方丹参注射液联合伽马刀治疗对原发性肝癌患者免疫功能的影响

目的:探索伽马刀联合复方丹参注射液治疗对原发性肝癌患者免疫系统的影响。方法:将行伽马刀治疗的40例原发性肝癌患者随机分为试验组和对照组,每组各20例。试验组患者采用伽马刀联合丹参注射液治疗;对照组患者仅单纯接受伽马刀治疗。治疗期间观察两组患者T细胞亚群及血清免疫球蛋白的变化。结果:在治疗前后,试验组患者CD^3+T细胞、CD4^+T细胞和CD4^+T/CD8^+T细胞比值及血清免疫球蛋白IgM、IgG、IgA水平均有所上升,与对照组相比,差异均有统计学意义(均P<0.05)。结论:伽马刀联合丹参注射液治疗能有效提高原发性肝癌患者免疫球蛋白水平,刺激CD^3+T细胞和CD4^+T细胞的增殖,抑制CD8^+T细胞的产生。     

PPAR-γ agonist pioglitazone reduces microglial proliferation and NF-κB activation in the substantia nigra in the 6-hydroxydopamine model of Parkinson’s disease

BackgroundPeroxisome proliferator-activated receptor γ (PPAR-γ) agonists have received much attention in research because of their neuroprotective and anti-inflammatory effects that reduce cell death and halt the progression of neurodegeneration. Thus, this study observed the pioglitazone effects on the main inflammatory markers after 6-hydroxydopamine (6-OHDA) lesion.MethodsThe effects of a 5-day administration of the PPAR-γ agonist pioglitazone (30 mg/kg) in male Wistar rats that received bilateral intranigral infusions of 6-OHDA. After surgery, the rats were evaluated in the open-field test on days 1,7,14, and 21. Immediately after the behavioral tests on day 21, the rats were euthanized, and the substantia nigra was removed to analyze the expression of nuclear factor κB (NF-κB) and IκB by western blot. To immunohistochemical, animals were intracardially perfused, with brain removal that was frozen and sectioned, being selected slices of the SNc region to detect tyrosine hydroxylase (TH) immunoreactivity, microglia activation (Iba-1) and NF-κB translocation in the nucleus.ResultsPioglitazone protected rats against hypolocomotion and 6-OHDA-induced dopaminergic neurodegeneration on day 7. Decreases in the microglial activation and the NF-κB expression were observed, and the p65 activation was inhibited.ConclusionsThese results suggest that pioglitazone may be a potential adjuvant for the treatment of Parkinson`s disease because of its effects on pathological markers of the progression of neurodegeneration.     

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice

Backgroundβ₂-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β₂-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.MethodsSeizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals’ motor coordination and memory processes was also evaluated.ResultsSingle SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β₂-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals’ motor performance and memory after both single and 7 days administration.ConclusionsPresented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β₂-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.     

Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts

Background

Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage.

Methods

Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 μM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) expression were analyzed. As clinical validation of the in vitro findings, ECs of diabetic patients in optimized glycaemic control administered with a 3 weeks Simvastatin regimen were similarly processed.

Results

Simvastatin blunted the rise in PMN adhesion and ROS generation following stimulation of saphenous vein EC culture with AGEs in vitro. This effect was time dependent and was associated to an increase in PPAR-γ induction paralleled by a decrease in RAGEs expression. Parallely, data from diabetic patients administered with Simvastatin showed a similar significant reduction in PNM adhesion and ROS generation. Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance. Interference in the function of these two crucial pathways might be at the root of the statin antinflammatory and antithrombotic effect in the context of AGEs-associated damage.

Conclusions

Despite the recently raised warning on the use of statins in the diabetic population, this study elucidates their cornerstone position in endothelial homeostasis of saphenous grafts in patients with controlled diabetes.     

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.     

甲胎蛋白和GGT-Ⅱ联合检测在肝癌患者诊断中的意义

目的：探讨两种肝癌标志物甲胎蛋白（α-fetoprotein,AFP）和γ-谷氨酰转移酶同工酶Ⅱ（γ-glutamyltransferase isoenzymeII,GGT-Ⅱ）单独检测和联合检测原发性肝癌（primaryhepatocellularcar cinoma,PHC）的早期诊断价值。方法：GGT-Ⅱ检测采用聚丙烯酰胺凝胶电泳法,AFP检测采用电化学发光免疫分析法。分别对33例乙型肝炎患者,30例肝炎后肝硬化患者,44例原发性肝癌患者以及35名健康体检者进行GGT-Ⅱ和AFP检测,综合分析2项指标对PHC的诊断价值。结果：PHC组的GGT-Ⅱ和AFP的阳性率均明显高于肝硬化组、肝炎组和健康对照,差异有统计学意义（P〈O．01）,联合检测敏感性高于单一检测指标。结论：血清GGT-Ⅱ及AFP联合检测可提高PHC的诊断灵敏度,提高肝癌的早期检出率。     

Recent advances in the etiology and treatment of inflammatory bowel disease

Crohn’s disease and ulcerative colitis, together comprising the inflammatory bowel diseases, currently affect up to 2 million people in the western developed countries. The pathogenesis of the disease is a complex one in which genetic, immunogenic, microbial and environmental factors contribute to the etiology of the disease. Recent advances in understanding the molecular mechanisms that determine this complex entity have provided insight for promising new therapies.     

Interleukin-15 in the treatment of cancer

IL-15 is a 14–15 kDa member of the four α-helix bundle of cytokines that acts through a heterotrimeric receptor involving IL-2/IL-15R β, γc and the IL-15 specific receptor subunit IL-15R α. IL-15 stimulates the proliferation of T, B and NK cells, and induces stem, central and effector memory CD8 T cells. In rhesus macaques, continuous infusion of recombinant human IL-15 at 20 μg/kg/day was associated with approximately a 10-fold increase in the numbers of circulating NK, γ/δ cells and monocytes, and an 80- to 100-fold increase in the numbers of effector memory CD8 T cells. IL-15 has shown efficacy in murine models of malignancy. Clinical trials involving recombinant human IL-15 given by bolus infusions have been completed and by subcutaneous and continuous intravenous infusions are underway in patients with metastatic malignancy. Furthermore, clinical trials are being initiated that employ the combination of IL-15 with IL-15R α^+/- IgFc.     

Type 1 reaction in leprosy: a model for a better understanding of tissue immunity under an immunopathological condition

Type 1 reaction (T1R) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. Leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. Early diagnosis is a great challenge for effectively treating and managing T1R. There is an urgent need to identify the most significant biomarkers to prevent recurrent T1R and to differentiate late T1R from relapse. T1R continues to be treated with corticosteroids and complications due to iatrogenic treatment remain frequent. This review aims to provide a framework from which to approach the great challenges that still persist in T1R management and debate key issues in order to reduce the distance between basic research and the clinic.