Glycation Endproducts, Soluble Receptor for Advanced Glycation Endproducts and Cytokines in Diabetic and Non-diabetic Pregnancies

Problem  Cytokines, advanced glycation end products (AGEs), and their receptor RAGE have been recently suggested to play a role in human pregnancy. In this study, we sought to determine the alterations of plasma AGEs, soluble RAGE (sRAGE), and proinflammatory cytokines in normal pregnancies and those complicated with type 1 diabetes mellitus.
Method of study  These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (HP), and pregnant diabetic (DP) women.
Results  In the first trimester, DP showed lower sRAGE and higher AGEs compared to HP. In the DP group, significant negative correlations were seen between TNF-α and lipopolysaccharide (LPS)-stimulated ΙL-6 in the first trimester and sRAGE in the third trimester. LPS-stimulated IL-12 was positively correlated with levels of AGEs in the third trimester.
Conclusion  We detected several differences in the levels of AGEs, sRAGE, and proinflammatory cytokines between euglycemic and diabetic pregnancies.     

非糖尿病患者糖化血红蛋白和胰岛素抵抗与 冠状动脉病变程度的相关性研究

目的 研究非糖尿病的冠心病患者中糖化血红蛋白（HbA1c）和胰岛素抵抗与冠状动脉病变严重程度的关系。方法 纳入临床疑诊冠心病并接受冠状动脉造影的非糖尿病患者184例,依据SYNTAX积分分为轻度狭窄组（0~22分）60例、中度狭窄组（23~32分）76例、重度狭窄组（≥33分）48例,采用Pearson相关性分析及多元线性逐步回归分析SYNTAX积分与HbA1c水平、稳态模型胰岛素抵抗指数（HOMA-IR）的关系。结果 三组间年龄、吸烟史、TC、LDL-C、HbA1c、HOMA-IR及CRP水平差异有统计学意义（P＜0.05）。相关性分析显示SYNTAX积分与HbA1c、HOMA-IR及CRP水平呈正相关,HbA1c与HOMA-IR呈正相关,多元线性逐步回归分析显示年龄、吸烟、HbA1c、HOMA-IR及CRP与冠脉病变程度独立相关。结论 在非糖尿病的冠心病人群中存在胰岛素抵抗,且胰岛素抵抗、HbA1c水平与冠状动脉病变严重程度密切相关。     

Non-diabetic retinal abnormalities in chronic pancreatitis.

To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.     

口服给药二房室模型吸收和消除速率常数与血药浓度关系的仿真研究

提出一种计算机仿真方法,研究血药浓度随吸收速率常数(Ka)和消除速率常数(K10)的变化规律。根据参考文献中的参数估计值,选取具有一级吸收速率的口服给药二房室模型,改变不同的参数值,利用MATLAB软件编程实现中心室血药浓度的仿真,结果以二维或三维图形显示。仿真结果中血药浓度随两个参数的变化规律与实际结果一致。从图中可以很清楚地观察两个参数和血药浓度之间的对应关系。计算机仿真技术可以用来模拟预测个体的血药浓度特性,并能得到大量个体数据,对新药的临床研究具有一定的参考价值。     

Constant Low Rate of Fungemia in Norway, 1991 to 1996

Since 1991 information on yeast isolates from blood cultures has been recorded prospectively from all microbiological laboratories (5 university and 16 county or local hospital laboratories) in Norway (population, 4.3 million). From 1991 to 1996 a total of 571 episodes of fungemia in 552 patients occurred (1991, 109 episodes; 1992, 81 episodes; 1993, 93 episodes; 1994, 89 episodes; 1995, 98 episodes; and 1996, 101 episodes). The fungemia rates per 10,000 patient days were 0.29 in 1991 and 0.27 in 1996. The average rates for the years 1991 to 1996 were 0.37 for the university laboratories and 0.20 for the other laboratories. These rates are low compared to the rate (0.76) in five Dutch university hospitals in 1995 and the rate (2.0) in Iowa in 1991. The four most frequently isolated species were Candida albicans (66%), Candida glabrata (12.5%), Candida parapsilosis (7.6%), and Candida tropicalis (6.4%). The incidences of both C. albicans (range, 63 to 73%) and C. glabrata (range, 8.4 to 15.7%) varied somewhat throughout this period, but no significant increase or decrease was noted. MICs of amphotericin B, flucytosine, and fluconazole were determined for 89% of the isolates. All were susceptible to amphotericin B, and only 29 (5.6%) strains had decreased susceptibility to flucytosine. All C. albicans isolates were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs, ≥16 μg/ml) did increase, from 9.6% in 1991 and 1992 to 12.2% in 1994, 16.1% in 1995, and 18.6% in 1996. This was largely due to increases in the percentages of resistant C. glabrata and Candida krusei strains in the last 2 years. Compared to the incidence in other countries, it is remarkable that Norway has such a low and constant incidence of fungemia. A possible reason for this difference might be a restricted antibiotic use policy in Norway.     

Generation of the Antibody Repertoire in Individuals with Multiple Immunoglobulin Heavy Chain Constant Region Gene Deletions

Antibodies against protein antigens are largely restricted to the IgG1 subclass in man, whereas anti-carbohydrate antibodies, at least in adults, are almost exclusively confined to the IgG2 subclass. In IgG2-deficient donors where the C gamma 2 gene is retained in the genome, antibodies against most polysaccharide antigens are absent. We therefore undertook a study of the antibody repertoire in 11 adult donors with immunoglobulin heavy chain constant region gene deletions, homozygous or heterozygous defects, encompassing the C gamma 2 gene. In all cases, antibodies against polysaccharide antigens were present and restricted to the remaining subclasses (IgG1 and/or IgG3). These results suggest an unrestricted use of the available VH gene repertoire in donors lacking the C gamma 2 gene, and imply that the limited antibody repertoire found in IgG2-deficient individuals with a retained C gamma 2 gene may be a consequence of an altered regulatory mechanism or a structural VH gene defect. However, furthermore, the deletion of multiple C gamma heavy chain constant region genes did not appear to decrease the IgG switch probability as such, since total serum levels of IgG appear to be normal.     

Cardiovascular and Electrodermal Response Patterns in Heart Rate Reactive Individuals During Psychological Stress

The goal of this research was to examine the cardiovascular and electrodermal response patterns of heart rate reactive and nonreactive individuals to psychological stress. Sixty males were tested while resting, listening to tones, identifying tone patterns, and performing mental arithmetic. Dependent variables were blood pressure, heart rate (HR), and skin conductance responses. Based on the change in HR from baseline to the first minute of mental arithmetic, two extreme reactivity groups of 15 subjects each were formed. Results indicated that HR reactive subjects had higher systolic blood pressure and HR than nonreactives. Reactives showed greater HR lability during all the tasks and a phasic acceleration to tones, while nonreactives showed a deceleration. Finally, comparisons of skin conductance responses indicated that subjects who were nonreactive when measuring HR were more reactive when measuring skin conductance. The HR reactivity seen in these subjects has been linked to predisposition to psychosomatic illness, and the current findings are discussed in that light.     

GAD65-Reactive T cells in a Non-diabetic Stiff-man Syndrome Patient

GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. Still, only 30% of SMS patients also have type 1 diabetes. To study regulation of T cell responsiveness to GAD65, we investigated a non-diabetic SMS patient with HLA-DR3/7 (predisposing to type 1 diabetes) and high levels of type 1 diabetes-associated autoantibodies against GAD65 and islet cells, and compared the results with those of her diabetic son and two other SMS patients. T cell responses to GAD65 were repeatedly absent in primary stimulation, whereas IA-2, islet antigen and tetanus toxoid induced significant T cell proliferation. However, after in vitro restimulation, GAD65 reactive T cell lines and clones were obtained that were HLA-DR3 restricted, and cross-reactive with a homogenate of purified human pancreatic islets. These T cells produced the immunoregulatory cytokine IL-10 in combination with IFN-gamma and IL-4 (Th0). The dominant T cell epitope was mapped to the central region of GAD65. Although no primary response to whole GAD65 was detectable, the naturally processed GAD65 peptide epitope was recognized vigorously in the primary stimulation assay. The lack of detectable primary T cell responses to GAD65, together with the GAD65-specific cytokine production of restimulated T cells, suggest that GAD65-specific cellular autoimmunity in this patient is suppressed and may be related to the absence of diabetes despite humoral autoreactivity and genetic predisposition.     

Soluble Levels of Receptor for Advanced Glycation Endproducts (RAGE) and Progression of Atherosclerosis in Individuals Infected with Human Immunodeficiency Virus: ACTG NWCS 332

Identification of biomarkers and/or mediators of cardiovascular disease (CVD) associated with HIV infection would be of diagnostic and therapeutic value. As soluble receptor for advanced glycation endproducts (sRAGE) and endogenous secretory (esRAGE) have been implicated in vascular complications in other settings, we investigated whether either soluble form of RAGE was associated with changes in carotid intima-media thickness (CIMT) in HIV-infected patients and HIV-uninfected controls. We found no differences in sRAGE, esRAGE, or CIMT among groups at study entry, or in yearly rates of change in sRAGE, esRAGE, or CIMT by HIV-serostatus (all p?>?0.10). However, yearly rates of change in sRAGE (p?=?0.07) and esRAGE (p?<?0.001) were higher in those taking protease inhibitors, and lower baseline esRAGE levels (p?=?0.06) were associated with increased odds of CIMT progression in HIV-infected individuals. Although esRAGE was not altered by HIV-serostatus (p?=?0.17), its inverse relationship with CIMT progression in HIV-infected patients suggests a possible role as a mediator of CVD in HIV-infected persons.     

Non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus.

The diagnosis of diabetic nephropathy (DN) is almost always based on clinical grounds. The diagnosis is supported by a long history of diabetes, evidence of target organ damage and proteinuria preceding azotemia. The validity of this clinical approach is well established in insulin dependent diabetes mellitus but not in non-insulin dependent diabetes mellitus (NIDDM). It is thus important to determine which patients with NIDDM accompanied by non-diabetic renal disease (NDRD) should have a biopsy. However, factors clinically associated with NDRD in patients with NIDDM remain unclear. Therefore we reviewed clinical data, laboratory data and renal biopsies from 22 NIDDM patients who underwent renal biopsy between 1992 and 1998 in Wonju Christian Hospital. From this data, we identified important features that would discriminate between DN and NDRD. There were 8 women and 14 men. Age ranged from 33 to 68 (51.2 +/- 10.7) years. The duration of diabetes at biopsy ranged from 0 to 13 (4.2 +/- 4.2) years. Nephrotic syndrome was present in 13 patients. The patients with NDRD (n = 14) and DN (n = 8) had comparable 24-hour proteinuria, 24-hour albuminuria, creatinine clearance, serum creatinine, albumin, as well as incidences of neuropathy and hypertension. The significant factors that predict the NDRD included a short duration of the diabetes mellitus, the presence of dysmorphic red blood cells in urine, the absence of retinopathy and HbA1c below 9% (p < 0.05, respectively). NDRD included IgA nephropathy (n = 6), minimal change disease (n = 3), membranous nephropathy (n = 3), membranous lupus nephritis (n = 1) and acute interstitial nephritis (n = 1). Multiple logistic regression analysis revealed that the short duration of DM and the absence of retinopathy were factors significantly associated with NDRD. In summary, when there is a short duration of diabetes mellitus, or an absence of retinopathy seen in patients with NIDDM, then renal biopsy in diabetic patients aids in the detection of NDRD.     

非糖尿病尿路感染患者在治疗中监测血糖的价值分析

目的 通过动态监测非糖尿病患者尿路感染治疗前后空腹血糖(Glu)和外周血中白细胞(WBC)变化,了解该类患者Glu升高是异常升高还是急性泌尿系感染的应激反应所致.方法 收集153例确诊尿路感染患者的资料,包括89例血糖正常患者以及64例血糖调节受损(IGR)患者,分别统计入院时、采集尿培养时以及好转出院时的Glu和WBC结果,80例健康体检者作为正常对照.结果 89例血糖正常患者中,46例院内感染患者入院时与出院时以及正常体检人群的Glu和WBC差异无统计学意义(P＞0.05),采集尿培养时的Glu和WBC结果均高于入院以及出院和体检人群(P ＜0.05);43例入院时即尿培养阳性的患者Glu和WBC均高于出院及正常体检人群(P＜0.05);89例患者采集尿培养时的Glu和WBC升高比值成一定的正相关,相关系数r=0.801(P ＜0.05).64例IGR患者中,30例院内感染患者入院时与出院时的Glu和WBC差异无统计学意义(P＞0.05),但Glu高于正常对照组(P＜0.05),采集尿培养时的Glu和WBC结果均高于入院以及出院和体检人群(P＜0.05);34例入院时即尿培养阳性的患者Glu和WBC均高于出院及正常体检人群(P＜0.05);64例患者采集尿培养时的Glu和WBC升高比值成一定的正相关,相关系数r=0.658(P ＜0.05).结论 非糖尿病尿路感染患者Glu升高可能是应激反应所致,Glu检测可作为非糖尿病尿路感染患者监测病情,评估预后的一种方法.     

Hemoglobin solutions in experimental cardioplegia

The addition of stroma-free hemoglobin solution to a standard St. Thomas Hospital cardioplegic solution significantly protected the heart from ischemic damage compared to the effect of the same solution without added hemoglobin. An experimental model of rat heart cardioplegia and transplantation comprising heart arrest for three hours at 20 degrees C was used. The number of hearts performing strong contractions after cardioplegia with iso-oncotic oxyhemoglobin prior to transplantation was close to the results with histidine-buffered cardioplegic solution according to Bretschneider. Comparative biochemical model experiments in vitro confirmed that the positive effect of oxyhemoglobin was due predominantly to its buffering capacity. The role of oxygen transport to tissues by hemoglobin was limited only to the first minutes of cardioplegia since neither recirculation nor reoxygenation took place in the present experimental setting.     

Hemoglobin stability in bull sharks

No significant differences in oxyhemoglobin affinity, or electrophoretic patterns of hemoglobin were found in 18 bull sharks collected in selected regions of Lake Nicaragua, the Rio San Juan, and the Caribbean Sea. The half-saturation of hemoglobin with oxygen (P₅₀) was 11 and 17 mm Hg at pH 7.4 and 6.8, respectively (25° C, 3% hemoglobin solution, potassium phosphate buffer, 0.3 ionic strength). Electrophoresis resolved the hemoglobin into a minor and a major band. Planimetry of densitometric recordings showed that the major band constituted 54% of the total hemoglobin; the minor band, 46%. On the basis of these hemoglobin studies, no subspeciation of bull sharks in Lake Nicaragua was identified, although marine bull sharks have free access to the lake and have been there, at least, since 1535; the synonymy of Carcharhinus nicaraguensis with C. leucas was confirmed.     

Hemoglobin quantitation in subarachnoid hemorrhage

Summary The amount of hemoglobin in cerebrospinal fluid was quantitated in 15 patients with subarachnoid hemorrhage and in 35 subjects without subarachnoid hemorrhage (controls). The photometric determination of the hemoglobin content in cerebrospinal fluid indicated that patients with subarachnoid hemorrhage in contrast to controls showed a significant increase (P>0.01) of hemoglobin (Mann-Whitney test). In 5 of the patients with subarachnoid hemorrhage it was possible to determine the amount of hemoglobin in cerebrospinal fluid over a period of time. Possible correlations between clinical course and hemoglobin concentration as well as the use of hemoglobin quantitation in late diagnosis of subarachnoid hemorrhage are discussed.Abbreviations CSF Cerebrospinal fluid - Hb Hemoglobin - SAH Subarachnoid hemorrhage     

Hemoglobin S in the Venezuelan population

Hemoglobin variants were introduced in Venezuela mainly by the descendants of African slaves; their distribution is determined by the flow of these populations into the country. The most prevalent hemoglobin variants are Hb S and Hb C. Hb S has a frequency between 0 and 7% depending on the African component of the region. The study of beta s gene linked haplotypes has been used to investigate the origins of African populations in America. In Venezuela, the beta s mutation is associated with the Benin and Bantu haplotypes (CAR) with a high frequency. According to these results the Africans transported to Venezuela were of Bantu origin as it has been showed by the historical records.     

糖尿病患者红细胞膜蛋白糖基化与巯基氧化作用

非胰岛素依赖型糖尿病(NIDDM)患者,红细胞膜蛋白的糖基化水平与巯基氧化作用呈正相关(r=0.55)。与正常人红细胞膜的体外糖基化结果类似。为了证明糖基化能提高膜蛋白中巯基氧化的敏感性,在体外用Aspirin乙酰化封闭红细胞膜蛋白中可被糖基化的部位,可使糖基化抑制50％,氧化作用抑制33％;反之用维生素E代替Aspirin,则膜蛋白氧化作用降低44％,而糖基化仅降低12％。上述结果提示,糖基化可能引起膜蛋白构型改变,使硫氢基暴露,从而加速其氧化作用。膜蛋白的糖基化和氧化作用与糖尿病并发症及老年病密切相关。