Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptor α-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation

AIM: To explore the effect of recombinant human interleukin-11 (rhIL-11) on the expressions of interleukin-11 receptor α-chain (IL-11Rα) and an additional signal transducer glycoprotein 130 (gp130) in intestinal epithelium cell line-6 (IEC-6) after neutron irradiation.METHODS: Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis.RESULTS: The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h (P ＜ 0.01), IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells (P ＜ 0.05). In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation (P ＜ 0.01) and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL-11Rα expression was higher than that of irradiated cells (P ＜ 0.05). When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein (P ＜ 0.05) in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells (P ＜ 0.05).CONCLUSION: rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.     

Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters

Bromocriptine, a potent dopamine D2 receptor agonist, suppresses lipogenesis and improves glucose intolerance and insulin resistance. Recent evidence suggests that bromocriptine may produce these effects by altering central nervous system (CNS) regulation of metabolism. To determine whether or not the CNS plays a critical role in these bromocriptine-mediated effects on peripheral metabolism, we compared the metabolic responses to bromocriptine when administered peripherally versus centrally in naturally obese and glucose intolerant Syrian hamsters. Male hamsters (BW 194 +/- 5 g) were treated with bromocriptine or vehicle either intraperitoneally (i.p., 800 microgram/animal) or intracerebroventricularly (i.c.v., 1 microgram/animal) daily at 1 h after light onset for 14 days while held on 14-hour daily photoperiods. Glucose tolerance tests (GTTs, 3 g glucose/kg BW) were conducted after treatment. Compared to control animals, bromocriptine i.p. significantly reduced weight gain (11.7 vs. -2.4 g) and the areas under the glucose and insulin GTT curves by 29 and 48%, respectively. Similarly, compared with vehicle-treated controls, bromocriptine i.c.v. at 1 microgram/animal substantially reduced weight gain (8.7 vs. -6.3 g), the areas under the glucose and insulin GTT curves by 31 and 44% respectively, and the basal plasma insulin concentration by 41% (p < 0.05). Furthermore, both treatments significantly improved insulin-mediated suppression of hepatic glucose production during a hyperinsulinemic-euglycemic clamp. Thus, daily administration of bromocriptine at a very low dose i.c.v. replicates the metabolic effects of bromocriptine administered i.p. at a much higher dose. This finding demonstrates for the first time that the CNS is a critical target of bromocriptine's metabolic effects.     

不同日摄氟量对人体健康影响的研究

以日摄氟量作为评价环境氟对人体健康影响的指标,比单一用空气、饮水和食物等的含氟量进行分析要合理。日摄氟量的计算各家不一,我们是将各点大气、饮水、粮食、蔬菜的实测含氟量分别乘大气12m~3、饮水3L、粮食0.6kg、蔬菜0.5kg,其和即是。研究结果表明:(1)成人的尿氟与日摄量呈非常显著的正相关(r=0.8809,P<0.01)。(2)成人的牙齿,各调查点的斑釉率和斑釉指数均随日摄氟量的增加而上升,二者分别与日摄氟量呈高度显著和显著的正相关(r=0.9048,p<0.01;r=0.8154,p<0.05)。(3)成人的胫腓骨、尺挠骨和骨盆的X线改变,以骨质增生、骨质的密度、结构改变和骨周肌腱韧带附着处钙化为主要表现,其改变的总阳性率与日摄氟量有一定的关系。     

黄芪、莪术配伍对胃癌细胞COX-2表达的调节作用

目的:观察黄芪、莪术配伍对MKN-45细胞COX-2、PPlAR-Y、NF-KB的影响.方法:以黄芪、莪术配伍作用于MKN-45细胞,并设塞莱希布组、罗格列酮组、黄芪组、莪术组和空白组相对照.用MTT法观察各组药物对胃癌细胞的抑制率,用RT-PCR以及Western blot方法检测给药后人胃癌细胞COX-2、PPARy、NF-KB基因及COX-2蛋白表达的变化.结果:各组对COX-2和NF-KB的mRNA表达均有抑制作用,除莪术外对PPARy mRNA均有促表达作用,其中以塞莱希布组和配伍组对COX-2 mRNA表达的抑制作用最为明显,且配伍组作用明显强于黄芪组和莪术组,以罗格列酮组和配伍组对NF-KB mRNA的表达抑制作用和对PPARy表达的促表达作用都是最明显.结论:黄芪、莪术配伍能起到增效作用,对细胞的抑制效应明显,对COX-2的抑制作用大于黄芪、莪术的单独效应,与塞莱希布相近,其对COX-2的抑制作用可能是通过PPARy/NFKB信号途径发挥作用的.     

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Background and objectives

Patients with CKD are more likely than others to have abnormalities in serum potassium (K⁺). Aside from severe hyperkalemia, the clinical significance of K⁺ abnormalities is not known. We sought to examine the association of serum K⁺ with mortality and hospitalization rates within narrow eGFR strata to understand how the burden of hyperkalemia varies by CKD severity. Associations were examined between serum K⁺ and discontinuation of medications that block the renin-angiotensin-aldosterone system (RAAS), which are known to increase serum K⁺.

Design, setting, participants, & measurements

A cohort of patients with CKD (eGFR<60 ml/min per 1.73 m²) with serum K⁺ data were studied (n=55,266) between January 1, 2009, and June 30, 2013 (study end). Serum K⁺, eGFR, and covariates were considered on a time-updated basis. Mortality, major adverse cardiovascular events (MACE), hospitalization, and discontinuation of RAAS blockers were considered per time at risk.

Results

During the study, serum K⁺ levels of 5.5–5.9 and ≥6.0 mEq/L were most prevalent at lower eGFR: they were present, respectively, in 1.7% and 0.2% of patient-time for eGFR of 50–59 ml/min per 1.73 m² versus 7.6% and 1.8% of patient-time for eGFR<30 ml/min per 1.73 m². Serum K⁺ level <3.5 mEq/L was present in 1.2%–1.4% of patient-time across eGFR strata. The median follow-up time was 2.76 years. There was a U-shaped association between serum K⁺ and mortality; pooled adjusted incidence rate ratios were 3.05 (95% confidence interval, 2.53 to 3.68) and 3.31 (95% confidence interval, 2.52 to 4.34) for K⁺ levels <3.5 mEq/L and ≥6.0 mEq/L, respectively. Within eGFR strata, there were U-shaped associations of serum K⁺ with rates of MACE, hospitalization, and discontinuation of RAAS blockers.

Conclusions

Both hyperkalemia and hypokalemia were independently associated with higher rates of death, MACE, hospitalization, and discontinuation of RAAS blockers in patients with CKD who were not undergoing dialysis. Future studies are needed to determine whether interventions targeted at maintaining normal serum K⁺ improve outcomes in this population.     

心理社会因素在溃疡性结肠炎中的作用

目的:探讨心理社会因素在溃疡性结肠炎(UC)中的作用.方法:UC患者30例,正常对照组30例.采用明尼苏达多相人格调查表(MMPI)、汉米尔顿抑郁量表(HAMD)、汉米尔顿焦虑量表(HAMA)、生活事件量表(LES)、社会支持量表(ss)、多伦多述情障碍量表(TAS)对uC患者及正常人进行评定.结果:UC患者在Hs(t=4.39,P＜0.01)、D(t=4.48,P＜0.01)、Pt(t=2.67,P＜0.05)、Sc(t=2.55,P＜0.05)和HAMD(t=4.19,P＜0.01)、HAMA(t=3.48,P＜0.01)、TAS(t=3.81,P＜0.01)量表的评分高于正常对照组. 结论:UC患者的人格因素及述情方式有明显异常.     

Left stellate ganglion and vagal nerve activity and cardiac arrhythmias in ambulatory dogs with pacing-induced congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the patterns of autonomic nerve activity in congestive heart failure (CHF). BACKGROUND: The relationship between autonomic nerve activity and cardiac arrhythmias in CHF is unclear. METHODS: We implanted radiotransmitters in 6 dogs for continuous (24/7) simultaneous monitoring of left stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and electrocardiography before and after pacing-induced CHF. RESULTS: Congestive heart failure increased both SGNA and VNA. The SGNA but not VNA manifested a circadian variation pattern. There was extensive sinus node fibrosis. We analyzed 2,263 episodes of prolonged (>3 s) sinus pauses (PSP) and 1,420 long (>10 s) episodes of paroxysmal atrial tachycardia (PAT). Most (95.3%) PSP episodes occurred at night, and 56% were preceded by a short burst of SGNA that induced transient sinus tachycardia. Long PAT episodes were typically (83%) induced by simultaneous SGNA and VNA discharge, followed by VNA withdrawal. Premature ventricular contractions and ventricular tachycardia were preceded by elevated SGNA. CONCLUSIONS: The reduction of sympathovagal balance at night in ambulatory dogs was due to reduced sympathetic discharge rather than a net increase of vagal discharge. The tachybrady syndrome in CHF might be triggered by an intermittent short burst of SGNA that resulted in tachycardia and sinus node suppression. Simultaneous sympathovagal discharge is a cause of long PAT episodes. These data indicate that there is an association between the specific patterns of autonomic nerve discharges and cardiac arrhythmia during CHF.     

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.