Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter

Aims/hypothesis Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and also in improving blood flow. We hypothesised that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus for nitric oxide production. Methods Erythrocytes obtained from rabbits (n = 11) and both healthy and type 2 diabetic humans (n = 7) were incubated with C-peptide in the absence and presence of Fe²⁺ and Cr³⁺, and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of GLUT1, and also of mannose, a glycolysis inhibitor. To determine glucose transport, ¹⁴C-labelled glucose was added to erythrocytes in the presence and absence of the C-peptide–metal complex and the aforementioned inhibitors. Results The release of ATP from the erythrocytes of patients with diabetes increased from 64 ± 13 to 260 ± 39 nmol/l upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe²⁺, which was extended upon binding to Cr³⁺. The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr³⁺, the amount of glucose transferred into the erythrocyte increased by 31%. Conclusions/interpretation When complexed to Fe²⁺ or Cr³⁺, C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through GLUT1.     

镍铬铍合金烤瓷冠修复中铍离子对口腔常见细菌及牙周组织的影响

【目的】探讨镍铬铍合金烤瓷冠修复中铍离子对口腔两种龈下细菌生长的影响及修复后对患者牙周组织的影响。【方法】本研究分为两个部分：①体外实验分为三组,实验组（含有铍离子的人工唾液0．5 mL ＋口腔链球菌悬液／牙龈卟啉单胞菌悬液0．5 mL）、阳性组（人工唾液0．5 mL ＋口腔链球菌悬液／牙龈卟啉单胞菌悬液0．5 mL）、阴性组（人工唾液0．5 mL ＋ BHI 培养基0．5 mL）,口腔链球菌实验培养24 h ,牙龈卟啉单胞菌培养48 h 。②选取20例接受镍铬铍合金烤瓷冠修复的患者,分别测定修复前、修复后3个月牙龈沟液（GCF）、天冬氨酸转氨酶（GCF‐AST）、碱性磷酸酶（GCF‐ALP）的活性水平。【结果】实验组的6个铍离子浓度下（1．25、2．5、5、10、20、40 ppm）口腔链球菌悬液、牙龈卟啉单胞菌菌落计数均显著的低于阳性组（ P ＜0．05）;实验组随着铍离子浓度下增加,口腔链球菌悬液、牙龈卟啉单胞菌菌落计数呈现出显著的减少趋势（ P ＜0．05）。20例接受镍铬铍合金烤瓷全冠修复的患者,修复后6个月的 GCF 量、GCF‐AST 、GCF‐ALP 活性水平与修复前比较差异均无统计学意义（ P ＞0．05）。【结论】镍铬铍合金中铍离子对口腔链球菌悬液、牙龈卟啉单胞菌生长具有一定的抑制作用,镍铬铍合金烤瓷冠修复对患者牙周组织影响小。     

奈达铂联合多西他赛治疗晚期非小细胞肺癌的临床疗效观察

【目的】观察比较奈达铂联合多西他赛化疗方案与顺铂联合多西他赛化疗方案治疗晚期非小细胞肺癌（NSCLC ）的近期疗效及不良反应。【方法】本院70例晚期NSCLC患者根据使用化疗药物不同分为两组,分别为奈达铂联合多西他赛治疗36例,顺铂联合多西他赛治疗34例。具体用药方案为奈达铂组：采用奈达铂25 mg/（m^2· d）,d1～3给予,多西他赛75 mg/m^2,d1。顺铂组：采用顺铂25 mg/（m^2· d）,d1～3给予,21 d为1个周期,化疗2个周期后按WHO标准评价疗效及不良反应。【结果】奈达铂组：完全缓解（CR）1例,部分缓解（PR）14例,稳定（SD）18例,进展（PD）3例,有效率（RR）为41．7％（15/36）;顺铂组：CR 1例,PR 13例,SD 18例,PD 2例,有效率（RR）41．2％（14/34）,两组有效率比较差异无显著性（ P ＞0．05）。消化道反应：奈达铂组和顺铂组分别为5．6％（2/36）和29．4％（10/34）,两组相比较差异有显著性（ P ＜0．01）;肾毒性分别为0（0/36）和5．9％（2/34）（ P ＜0．05）;骨髓抑制：白细胞减少奈达铂组为72．2％（26/36）,顺铂组为70．6％（24/34）,两组相比较差异无显著性（ P＞0．05）。【结论】奈达铂联合多西他赛方案治疗晚期NSCLC的有效率不低于顺铂联合多西他赛方案,胃肠道毒性较顺铂联合多西他赛组轻,不良反应主要为骨髓抑制,两组白细胞下降无差异,但血小板下降较顺铂联合多西他赛组明显。     

RCC1、RCA1在152例晚期NSCLC中的表达及其临床意义

目的 探讨ERCC1和BRCA1在晚期非小细胞肺癌(NSCLC)中的表达,分析ERCC1和BRCA1与铂类化疗近期疗效之间的关系.方法 采用免疫组化法对152例晚期NSCLC中ERCC1和BRCA1的表达进行检测分析.结果 ERCC1和BRCA1的表达与各临床特征之间均无关(P>0.05),ERCC1基因蛋白表达阴性者,应用含铂方案化疗,其近期疗效明显高于表达阳性的NSCLC患者(P<0.05),BRCA1的表达与含铂化疗近期疗效无关(P>0.05).结论 结果提示ERCC1可预测NSCLC对含铂联合化疗方案的敏感性.     

脂蛋白脂酶活化剂1886对食饵性高糖高脂猪血胰岛素和胰组织中铬和钒的影响

为观察脂蛋白脂酶活化剂NO-1886对高糖高脂猪血浆胰岛素和胰组织中微量元素铬钒含量的影响。将15头贵州小香猪随机分为3组:对照组喂基础猪饲料,糖脂组喂高脂高蔗糖饲料,NO-1886组前3个月喂高脂高蔗糖饲料,从第4个月开始在高脂高蔗糖饲料里加1％NO-1886。动物分栏喂养,每月末抽空腹静脉血测血糖、血脂、胰岛素浓度,第8月末在测量上述指标后处死动物,取胰组织,用酸消化,等离子体原子发射光谱仪检测铬钒的含量。结果发现,对照组、糖脂组和NO-1886组的血胰岛素在加NO-1886前,分别是11.4±2.7 mU/L、21.0±4.8 mU/L和21.9±6.6 mU/L,与对照组比较,后两纽升高(P<0.05);加NO-1886后,至实验结束时分别是11.4±6.2 mU/L、20.4±2.3 mU/L和15.4±1.8 mU/L。与加NO-1886前比较,对照组与糖脂组的变化差异无统计学意义,而NO-1886组降低(P<0.05)。胰岛素敏感试验发现,对照组与NO-1886组的血胰岛素变化规律基本一致,糖脂组血胰岛素含量降低(与对照组比较,第30 min时P<0.05,第90 min时P<0.01)。实验结束时,三纽动物胰组织中钒含量分别是0.8±0.8 ng/g、0.7±0.1 ng/g和0.8±0.3 ng/g;铬的含量分别是2.3±1.2 ng/g,g、1.9±0.6ng/g和2.1±0.9 ng/g。与对照组比较,糖脂组钒铬含量降低(P<0.05),NO-1886组无显著性差异(P>0.0     

The determination of pyridinium crosslinks in urine and serum as a possible marker of cartilage degradation in rheumatoid arthritis

Summary The determination of the collagen crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpyd) seems to be a successful way of characterizing topic destructive processes in rheumatoid arthritis (RA). Dpyd is a specific marker of collagen I resorption in bone, whereas Pyd is released from types I and II collagen in bone and cartilage. Both crosslinks were examined in 38 RA patients concurrently by RP-gradient-HPLC in urine and serum. A positive correlation was found between the inflammatory activity (measured by CrP) and the level of collagen crosslinks in urine. A correlation between serum and urine concentrations was demonstrable for Pyd, but not for Dpyd. Different elimination kinetics for fragments containing either Pyd or Dpyd are a possible explanation for this observation. The ratio of Pyd/Dpyd is known to be a useful marker to distinguish between destruction of cartilage and bone collagen. Because the Pyd/Dpyd ratio in urine does not necessarily correspond to that in serum, probably as a result of metabolic or elimination processes, the usefulness of the relationship between the crosslinks in urine as a method of differentiating between cartilage and bone degradation must be questioned.     

In vivo transcutaneous penetration of nicotinates and sensitive skin

Proclivity to develop irritant reactions and transcutaneous penetration of nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non-reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl nicotinate compared to reactors. Nicotinate-induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin.