Gingival crevicular fluid levels of clindamycin compared with its minimal inhibitory concentrations for periodontal bacteria

Clindamycin concentrations in gingival crevicular fluid and in blood were determined over a 7-h period and were related to the minimal inhibitory concentrations of this agent for 340 bacterial strains isolated from diseased periodontal sites. The clindamycin levels after administration of single 300-mg oral doses were measured in gingival crevicular fluids by using an agar diffusion bioassay. Minimal inhibitory concentrations were determined by agar dilution techniques for 30 species of periodontal bacteria. With the exception of Eikenella corrodens and Actinobacillus actinomycetemcomitans, most of the bacteria were inhibited by a concentration of 1.0 microgram of clindamycin per ml or less. The peak concentrations in crevicular fluid (2.0 +/- 0.3 microgram/ml) and in blood (1.9 +/- 0.3 micrograms/ml) were approximately the same. However, crevicular fluid levels of 1.0 micrograms/ml and above were present for up to 6 h, whereas blood concentrations dropped below 1.0 micrograms/ml within 2 h after administration. Based on its minimal inhibitory concentrations, clindamycin at crevicular fluid levels of 1.0 micrograms/ml or above should inhibit most bacteria associated with diseased periodontal sites.     

2型糖尿病患者血浆中PAI-1及sVCAM-1水平与耳鸣的相关性研究

目的探讨2型糖尿病(T2DM)患者血浆相关指标预测耳鸣发生情况的意义。方法对64例T2DM并发耳鸣患者及148例单纯T2DM患者临床资料进行回顾性分析,分别将其纳入观察组与对照组。比较两组患者血浆相关指标纤维酶原激活物抑制物-1(PAI-1)、可溶性血管细胞黏附分子-1(sVCAM-1)、3-硝基酪氨酸(3-NT)、神经生长因子(NGF)水平,以受试者工作特征曲线(ROC曲线)分析上述指标单独或联合预测T2DM并发耳鸣的诊断效能,借助Pearson相关系数模型,探索观察组患者上述指标与耳鸣严重程度[耳鸣残疾度量化表(THI)]的相关性。结果观察组血浆PAI-1、sVCAM-1、3-NT、NGF水平均明显高于对照组,差异有统计学意义(P<0.05)。血浆PAI-1、sVCAM-1、3-NT、NGF单独预测T2DM患者并发耳鸣ROC曲线下面积(AUC)均大于0.5,Youden指数对应cut-off值分别为8.06 mmol/L、58.50 ng/mL、269.79 pg/mL、4.16 ng/mL;4个指标联合预测的ROC曲线AUC为0.796,均明显大于单独预测指标(P<0.05)。观察组患者血浆PAI-1、sVCAM-1、3-NT、NGF水平与THI评分均表现出显著正相关(r>0,P<0.05)。结论血浆PAI-1、sVCAM-1水平与T2DM患者并发耳鸣存在密切关系,可通过联合3-NT、NGF等指标开展较为准确的早期预测诊断,以期提高临床干预的目的性。     

2型糖尿病伴牙周病大鼠牙槽骨中转化生长因子β1 mRNA的表达

背景:研究表明糖尿病可以增加牙周病的发病风险,糖尿病可以引起骨代谢的紊乱并导致骨质疏松症,但其具体机制尚未阐明.目的:通过对大鼠牙槽骨转化生长因子β1 mRNA表达及根尖区骨密度变化的测定,探究2型糖尿病促进牙周病变的机制.方法:采用高糖高脂饮食喂养、小剂量链脲佐菌素、一次性腹腔注射及正畸结扎丝结扎的方法建立2型糖尿病伴牙周病SD大鼠模型.应用RT-PCR技术检测实验大鼠牙槽骨中转化生长因子β1 mRNA表达,并对大鼠牙槽骨进行骨密度测量及病理切片光镜观察.结果与结论:与正常对照组、2型糖尿病组、牙周病组比较,2型糖尿病伴牙周病组大鼠牙槽骨中转化生长因子β1 mRNA表达最高,骨密度值最低(P＜0.01).2型糖尿病伴牙周病组大鼠牙槽骨有骨质疏松倾向.结果提示2型糖尿病可能通过转化生长因子β1的过表达来促进牙槽骨骨质疏松,进而说明2型糖尿病可能通过转化生长因子β1的过表达来促进牙周病变.     

2型糖尿病患者血清单核细胞趋化蛋白1、白细胞介素18与颈动脉内膜中膜厚度相关性研究

目的 探讨2型糖尿病患者血清单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)、白细胞介素18(IL-18)水平与颈动脉内膜中膜厚度(carotid intima-media thickness,CIMT)的关系.方法 60例2型糖尿病患者分为大血管病变组30例和无大血管病变组30例,体检健康者为对照组30例.超声测定CIMT,酶联免疫吸附法测定血清MCP-1、IL-18水平.结果 2型糖尿病有、无大血管病变组血清MCP-1(无大血管病变组血清MCP-1除外)、IL-18、CIMT明显高于对照组,MCP-1(387.57±75.41)ng/L,(177.48±38.35)ng/L vs(122.51±8.98)ng/L,IL-18(54.76±16.31)ng/L、(35.08±8.83)ng/L vs(26.13±7.05)ng/L,CIMT(1.44±0.33)mm、(1.06±0.26)mm vs(0.68±0.12)mm(均P<0.01);大血管病变组上述指标又高于无大血管病变组(均P<0.01).直线相关分析显示2型糖尿痛患者血清MCP-1与空腹血糖(FPG)、餐后2小时血糖(2 hPG)、糖化血红蛋白、收缩压、低密度脂蛋白胆固醇、CIMT和IL-18呈正相关(P<0.01或<0.05);血清IL-18与FPG、2 hPG、甘油三酯、CIMT、MCP-1呈正相关(P<0.01或<0.05).多元线性回归分析显示年龄、MCP-1、IL-18是ClMT升高的危险因素(t=2.694、6.466、2.445,均P<0.01).结论 2型糖尿病患者血清MCP-1、IL-18与CIMT密切相关,提示两者可能是亚临床期动脉粥样硬化的危险因素.     

血液t-PA和PAI-1水平及活性与血液流变学指标的相关性分析

目的探讨血液t-PA和PAI-1的水平及活性与血流变指标间的相关性.方法随机选择30例40～60岁无心、脑血管意外病史健康体检者,进行血液t-PA和PAI-1浓度、活性、血流变指标常规测定.结果 t-PA浓度与PAI-1浓度高度相关(P＜0.001),t-PA浓度与血液黏度呈高度的正相关(P＜0.001),t-PA活性与血液黏度无相关关系(P＞0.05);PAI-1浓度、活性与血液黏度无相关关系(P＞0.05),PAI-1活性与血压呈正相关关系(P＜0.05).在不同性别之间外周血t-PA,OAI-1活性、浓度没有显著性差异(P＞0.05),不同性别间全血黏度、血还原黏度、血沉、红细胞压积、红细胞聚集指数具有非常显著的差异(P＜0.01),数值男性大于女性(血沉除外).40～49岁体检者与50～60岁年龄组间只有血压、红细胞压积、红细胞变形指数、红细胞电泳指数具有显著的差异(P＜0.01),除红细胞变形指数、红细胞电泳指数外,数值以年龄≥50岁组为高;其他无差异.结论血液t-PA浓度与PAI-1浓度高度相关(P＜0.001),t-PA浓度与血液黏度呈高度的正相关.     

Tumor-associated prognostic factors of the plasminogen activator family: determination and clinical value of u-PA, t-PA, PAI-1, and PAI-2

Proteolytic factors belonging t the plasminogen activator family (plasmin, u-PA, t-PA, u-PAR, PAI-1, and PAI-2), which usually are involved in blood clotting and degradation of blood clots, are also present in healthy and diseased tissue of the kidney, lung, liver, gastro-intestinal tract, breast, prostate, ovary, and brain. These factors are engaged in brain development, angiogenesis and vascular invasion, wound healing as well as in placenta development and embryogenesis. Plasminogen activators u-PA and t-PA, their inhibitors PAI-1 and PAI-2, and the u-PA-receptor (u-PAR, CD87) are often elevated in solid malignant tumour tissues compared to their normal counterparts. In breast cancer patients, an elevated tumour tissue extract antigen content of u-PA, PAI-1, and u-PAR is associated with increased tumour aggressiveness and poor prognosis; in contrary, an elevated content of t-PA and PAI-2 indicates a favourable prognosis. For clinical relevant determination of these proteolytic factors in tumour tissue extracts, only enzymo-immunometric tests (ELISA) are recommended. Enzymometric and enzymographic tests are actually conducted only in an experimental, preclinical context.     

血清黏附分子和细胞因子与2型糖尿病患者血管病变的关系

目的 探讨2型糖尿病（T2DM）患者血清黏附分子与细胞因子水平以及与血管病变的关系.方法 选择96例T2DM患者按照血管病变情况分为无血管病变组（28例）、微血管病变组（33例）、大血管病变组（35例）,选择同期健康体检者30名作为对照组,ELISA法检测血清细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）,细胞因子包括白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）和假性血友病因子（vWF）浓度,同时检测治疗半个月后T2DM患者黏附分子和细胞因子的表达.结果 与对照组比较,T2DM患者不同血管病变组ICAM-1、VCAM-1、IL-6和TNF-α水平都明显增高,差异有统计学意义（P均＜0.05）,且随着患者血管病变的严重,其表达也有升高趋势,差异有统计学意义（P均＜0.05）;治疗半个月后,患者血清ICAM-1、VCAM-1、IL-6和TNF-α水平显著性降低,差异具有统计学意义（t值分别为16.281、8.712、7.697、8.445,P均＜0.05）,各指标分别从治疗前（505.34±56.42） μg/L,（570.85±59.54）μg/L,（94.51±18.04） ng/L,（70.57±18.34） ng/L降到治疗后（390.53±45.23） μg/L,（482.93±69.85） μg/L,（77.31±15.49） ng/L,（50.45±12.66） ng/L;T2DM患者血清ICAM-1、VCAM-1、IL-6及TNF-α水平与vWF的表达都呈明显的正相关（r值分别为0.482、0.453、0.576、0.534,P均＜0.05）.结论 黏附分子和细胞因子共同参与了T2DM恶化以及血管病变的发生发展.     

IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease.

The capacity of peripheral blood mononuclear cells (PBMC) from patients with treated Parkinson's disease (PD) to produce interleukin (IL) IL-1 beta IL-2, IL-6, tumor necrosis factor (TNF)-alpha and the proliferative response to mitogens, was compared with that from cells from healthy subjects. The production of IL-2 and the mitogen response were significantly lower in PD patients, whereas the secretion of IL-1 beta, IL-6 and TNF-alpha were significantly enhanced. To evaluate the role of levodopa in creating immunological alterations, PBMC of patients and controls were incubated with concentrations of the drug extrapolated from those used in clinical practice. Levodopa caused an inhibition of mitogen-induced proliferation, stimulation of IL-6 and TNF-alpha production, whereas the secretion of IL-1 beta and IL-2 was not affected. The results of the study provide a further support for the interrelationship between the central nervous and immune system. In addition, the data indicate that the immunological alterations found in PD may be partially attributed to levodopa administration.     

Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease

OBJECTIVE

Low levels of fetuin-A, a systemic calcification inhibitor, are linked to mortality in patients on dialysis. In contrast, elevated fetuin-A is associated with cardiovascular events in non-renal patients. We investigated fetuin-A in patients with type 2 diabetes and peripheral arterial disease (PAD).

RESEARCH DESIGN AND METHODS

We studied fetuin-A in 76 patients with PAD and normal glucose metabolism (NGM-PAD) and in 129 patients with PAD and type 2 diabetes (type 2 diabetes–PAD). Additionally, 40 patients with diabetes without any complications (type 2 diabetes–non-PAD) were examined.

RESULTS

Type 2 diabetes–PAD subjects (399 ± 155 μg/ml) had significantly higher fetuin-A levels than type 2 diabetes–non-PAD subjects (247 ± 42; P < 0.001). In NGM-PAD subjects (376 ± 144), fetuin-A was significantly higher than in type 2 diabetes–non-PAD subjects (P < 0.001). Type 2 diabetes–PAD patients with mediasclerosis had lower fetuin-A than subjects without (P < 0.03). Regression analysis in type 2 diabetes–PAD subjects revealed that glycated A1C (P < 0.001) and mediasclerosis (P = 0.004) were the strongest predictors of fetuin-A. Multivariate regression revealed that a 1-SD increase in fetuin-A was associated with an odds ratio (OR) of 2.1 (95% CI 1.1–3.3; P < 0.001) for the prevalence of PAD and an OR of 1.4 (1.0–1.7, P = 0.039) for the prevalence of myocardial infarction.

CONCLUSIONS

In contrast to previous findings, fetuin-A was higher in type 2 diabetes–PAD patients than in type 2 diabetes–non-PAD patients. In NGM-PAD patients, fetuin-A was also higher than in type 2 diabetes–non-PAD patients. In type 2 diabetes–PAD patients, fetuin-A was inversely associated with mediasclerosis—the calcification process pathognomonic for diabetic PAD. This association persisted in multivariate regression, which is in line with the calcification inhibition in coronary heart or renal disease.Patients suffering from type 2 diabetes and peripheral artery disease (PAD) (type 2 diabetes–PAD) have a five times higher risk for cardiovascular mortality than patients with one disease alone (1–3). Furthermore, the risk of lower-extremity amputation is higher than in patients without diabetes (3).Fetuin-A, also known as α2-Schmid Heremans glycoprotein (ASHG), is a potent systemic calcification inhibitor (4). Fetuin-A knockout mice develop severe calcification of various organs (4). In a cross-sectional study, low levels of fetuin-A were associated with cardiovascular mortality in patients on dialysis (5). In addition, low fetuin-A has been linked to vascular calcification (6) and flow-limiting aortic stenosis (7).Fetuin-A interacts with the insulin receptor tyrosine kinase and induces insulin resistance in rodents (8,9). Stefan et al. (10) demonstrated in a prospective case-cohort study that elevated fetuin-A is an independent risk factor for developing diabetes. Contrariwise to renal (dialysis) patients, several studies showed that high levels of fetuin-A were associated with atherosclerosis and its manifestations in non-renal patients (11–13). Likewise, high levels of fetuin-A were linked to myocardial infarction and ischemic stroke (12). This possible involvement of fetuin-A in the pathogenesis of cardiovascular disease has been confirmed by a recent trans-European cohort study with 2,520 patients (13). Thus, it seems that high levels of fetuin-A are associated with atherosclerosis and its manifestations in non-renal patients.In contrast to the latter findings, a recent article (14) suggested that fetuin-A levels in a non-dialysis condition are lower in type 2 diabetes–PAD patients (n = 38) than in patients with diabetes alone.However, the role of fetuin-A and its involvement in atherosclerosis seems to be very complex and yet not understood. The situation is even more complex in patients with type 2 diabetes–PAD, who generally suffer from advanced/systemic atherosclerosis (1–3,15). In those high-risk patients, up to 30% show mediasclerosis (2,15). The aim of this study was to investigate fetuin-A levels in patients with type 2 diabetes with or without PAD in comparison with PAD patients with diabetes.     

Clearance of t-PA, PAI-1, and t-PA-PAI-1 complex in an isolated perfused rat liver system

The role of physiologic inhibitors of tissue-type plasminogen activator (t-PA) in its clearance has not yet been defined. In this study, the clearance of t-PA, plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex was determined in an isolated perfused rat liver system. The clearance of t-PA-PAI-1 complex was twice as fast as that of t-PA, whereas PAI-1 was cleared slowly. The half-lives for t-PA, determined by a two-compartmental pharmacokinetic model, were: alpha, 20.1 minutes, and beta, 120.0 minutes. The corresponding values for t-PA-PAI-1 complex were: alpha, 9.7 minutes, and beta, about 7 hours. The model microconstants were computed for t-PA and t-PA-PAI-1 complex and the marked difference between the "on" microconstants k12 for t-PA (0.026 +/- 0.001 min-1) and t-PA-PAI-1 complex (0.090 +/- 0.025 min-1) suggests that the effect on binding to liver cells is the most important factor in the faster clearance of t-PA-PAI-1 complex when compared with t-PA.     

2型糖尿病合并非酒精性脂肪肝患者同型半胱氨酸及血脂特点分析

目的探讨在2型糖尿病(T2DM)合并非酒精性脂肪性肝病患者中检测空腹血清同型半胱氨酸(tHCY)的临床意义。方法将210例2型糖尿病患者分为不合并非酒精性脂肪性肝病组(A组)108例,合并非酒精性脂肪性肝病组(B组)102例,分别测定身高、体质量,抽空腹血检查同型半胱氨酸(tHCY)、总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)等,计算体质指数(BMI)。结果 B组的BMI、TG、TC、LDL-C及tHCY均明显高于A组(P<0.05)。而年龄,HDL-C明显小于A组(P<0.01),tHCY与BMI、TG、TC、LDL-C、HDL-C的相关分析:tHCY与TG﹙r=0.245,P<0.05﹚、BMI﹙r=0.216,P<0.05﹚、LDL-C﹙r=0.223,P<0.05﹚呈正相关,与HDL-C呈负相关﹙rs=-0.222,P<0.05﹚。结论血脂紊乱及血清同型半胱氨酸是T2DM合并非酒精性脂肪性肝病的危险因素,并且TG、BMI、HDL-C及LDL-C与血清同型半胱氨酸水平具有相关性。     

2型糖尿病非酒精性脂肪性肝病与胰岛素抵抗的相关性分析

目的探讨在2型糖尿病(T2DM)合并非酒精性脂肪性肝病与胰岛素抵抗的关系。方法将195例2型糖尿病患者分为单纯糖尿病组(A组)83例,合并非酒精性脂肪肝组(B组)60例及合并非酒精性脂肪性肝炎组(C组)52例,分别测定身高、体质量,抽空腹血检查总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、糖化血红蛋白(HbA1C)、空腹血糖(FBG)及空腹胰岛素(FINS)等。计算体质量指数(BMI)及胰岛素抵抗指数(HOMA-IR)。结果 BMI、TG、TC、LDL-C、ALT、AST、GGT、FINS、HOMA-IR水平显示:B组均明显高于A组(P<0.05),C组均明显高于B组(P<0.05)。而HDL-C水平显示:B组均明显低于A组(P<0.05),C组均明显低于B组(P<0.05)。3组间HbA1C、FBG及年龄比较,差异无统计学意义。相关分析显示:HOMA-IR与BMI、TG、TC、LDL-C呈显著正相关(P<0.01),与HDL-C呈显著负相关(P<0.01)。结论胰岛素抵抗是T2DM合并非酒精性脂肪性肝病的危险因素,并且与BMI、TG、TC、LDL-C、HDL-C水平具有相关性。     

Serum 1,5-anhydroglucitol levels in patients with fulminant type 1 diabetes are lower than those in patients with type 2 diabetes

ObjectivesWe investigated clinical relevance of serum 1,5-anhydroglucitol (1,5-AG) levels in fulminant type 1 diabetes mellitus (FT1DM) patients, because 1,5-AG is known to reflect short term glycemic control.Design and methodsSubjects comprised 7 patients with FT1DM and 32 patients with type 2 diabetes mellitus (T2DM) with HbA1c < 8.5%. All of them have never been treated for diabetes.ResultsHbA_1C showed no significant difference between both groups. On the other hand, serum 1,5-AG levels were significantly lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG levels were < 5.0 μg/ml in 6 of 7 (86%) FT1DM patients, compared with only 1 of 32 (3%) T2DM patients.ConclusionsSerum 1,5-AG levels were lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG, but not HbA_1C, reflects short-term exacerbation of glycemia in patients with FT1DM.     

一氧化氮在2型糖尿病周围神经病变中的作用

目的：初步了解2型糖尿病伴周围神经病变患者血清一氧化氮水平的变化及其关系。方法：测定100例2型糖尿病患者和50例健康人的血清一氧化氮水平，分析其与2型糖尿病相关指标及胫后神经传导速度的相关性。结果：①2型糖尿病患者血清一氧化氮水平与病程显著负相关；②伴有糖尿病周围神经病的2型糖尿病患者，血清一氧化氮水平较无糖尿病周围神经病者显著降低（P〈0．01）；伴轻度糖尿病周围神经病者与中、重度者相比，血清一氧化氮水平无显著性差异（P〉0．05）。结论：①2型糖尿病患者血清一氧化氮水平的变化是一个随病程变化的过程。②血清一氧化氮水平与糖尿病周围神经病的发生密切相关；与糖尿病周围神经病的发展无明显关系。     

Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease

The purpose of this study was to evaluate whether IL-1 beta (IL-1beta promoter and IL-1beta exon 5), IL-1 receptor antagonist (IL-1 Ra), and IL-4 (IL-4 promoter and IL-4 intron 3) gene polymorphisms act as markers of susceptibility to Kawasaki disease (KD), or of the severity of the disease. The study included 107 KD patients and 103 normal controls. Polymorphisms for cytokine genes were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for cytokine gene polymorphisms in both groups were compared. No significant difference was observed in the genotypes and allelic frequencies of cytokines between patients with coronary aneurysm and without. In addition, there was no significant association in the genotype and allelic frequencies of IL-1 beta, IL-4, and IL-6 in patients with KD. The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD.     

Serum levels of tumor necrosis factor and IL-1 alpha and IL-1 beta in diabetic patients

OBJECTIVE: To determine whether chronic hyperglycemia causes increased levels of serum tumor necrosis factor (TNF) and interleukin 1 alpha (IL-1 alpha) and IL-1 beta. RESEARCH DESIGN AND METHODS: Sera were obtained from 59 diabetic patients, 44 chronically ill nondiabetic patients, and 34 age-matched healthy control subjects. Mononuclear cells were isolated from a subgroup of diabetic patients and healthy control subjects. RESULTS: Except for a modest increase in the prevalence of detectable serum TNF levels in diabetic patients, the serum cytokines measured in this study did not appear to be altered in diabetes. In vitro TNF production by mononuclear cells was not altered in diabetic patients. However, in vitro IL-1 beta secretion, in response to lipopolysaccharides, was reduced. CONCLUSIONS: Diabetes mellitus is not associated with significant changes in serum levels of TNF, IL-1 alpha, or IL-1 beta. In vitro secretion of IL-1 beta in response to lipopolysaccharides may be reduced in diabetes.     

健康老人血液纤溶能力测定值报告

为了解我国老年人血液纤溶能力状态，对９２位健康老人（７２．０±８．６岁）血浆组织型纤溶酶原激活剂（ｔＰＡ）及其快速抑制剂（ＰＡＩ～１）和血浆纤溶酶原（ＰＬＧ）进行了测定并据此确定了参考值范围。ｔＰＡ：６８０±１６０ＩＵ／Ｌ（４２０～９４０ＩＵ／Ｌ）；ＰＡＩ－１：１１．９６±１．５６ｆＵ／Ｌ（８．９１～１５．０１ＦＵ／Ｌ）；ＰＬＧ：１０７．２％±１６．９％（７４．１％～１４０．３％）。上述结果与年轻组相比ｔＰＡ与ＰＬＧ活性降低而ＰＡＩ－１活性增高（Ｐ＜０．００１），说明老年人纤溶系统功能有明显减退。