DNA疫苗的细菌内毒素检测

目的 :考察DNA疫苗细菌内毒素的检查方法的可行性及DNA疫苗的干扰作用。方法 :干扰试验和对比试验。结果 :供试品阴性对照系列样品溶液无干扰作用 ,与家兔法结果一致。结论 :将疫苗稀释 2倍可用灵敏度为 0 5EU ml的鲎试剂作细菌内毒素检查。     

Levels of Circulating DNA in Blood Serum and DNA Damage in Leukocytes of Healthy Donors of Different Genders and Ages

We studied the levels of extracellular nuclear and mitochondrial DNA of blood serum and DNA damage in leukocytes of healthy donors of different sex and age groups. The baseline levels of DNA damage in leukocytes and serum DNA levels were shown to vary greatly among different donors. The baseline level of DNA damage in leukocytes was not associated with the presence of chronic deceases or an occupational health risk for elderly donors. It was found that extracellular DNA concentrations were generally higher in men than in women. There is a tendency towards an increase in the relative mitochondrial DNA copy number determined by ΔCt in women but not in men: the relative mtDNA copy number in elderly individuals varies significantly in both sexes, possibly due to age-related physiological changes. It is necessary to consider the gender and age of patients when using an indicator such as the level of extracellular DNA of blood serum for diagnosis and monitoring.

     

IL-10、IL-18和内毒素在肝硬化患者自发性细菌性腹膜炎中的作用

目的:探讨由肝硬化合并自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)患者血清中IL-10、IL-18及内毒素的水平及其临床意义.方法:采用ELISA方法检测各组血清IL-10、IL-18水平,采用偶氮显色基质法检测内毒素水平.结果:SBP患者血清中IL-10、IL-18及内毒素的水平明显高于正常对照组,P＜0.05,SBP患者治疗后血清中IL-10、IL-18及内毒素的水平都明显降低,P＜0.05.结论:检测血清中IL-10、IL-18及内毒素在肝硬化患者自发性细菌性腹膜炎中的诊断及预后中具有一定指导意义.     

Self-Efficacy in Overweight Individuals with Binge Eating Disorder

MILLER, PETER M., JULIA A. WATKINS, ROGER G. SARGENT, AND EDWARD J. RICKERT. Self-efficacy in overweight individuals with binge eating disorder. Obes Res. Objective: To evaluate the relationship between self-efficacy judgments in obese individuals with binge eating disorder, “borderline” binge eating disorder, and no binge eating problems. Research Methods and Procedures: Before participation in a residential weight management program, 79 male and female subjects were administered the Weight Efficacy Lifestyle Questionnaire (WEL) and the Binge Eating Scale (BES). Based on DSM-IV diagnostic questions, subjects were categorized as BED, Borderline BED, or non-BED. Results: Krusal-Wallace Rank-Order analysis of variance revealed significant negative associations between binge eating and total WEL scores as well as the subscales of Negative Emotions, Social Pressure, Physical Discomfort, and Positive Activities. Differences were significant between the BED and the Borderline BED groups with the exception of the Social Pressure scale and the Total WEL scores. BED diagnosis as well as severity of binge eating were strongly associated with low self-efficacy ratings. Discussion: These results indicate that obese individuals with binge eating disorder demonstrate lower self-efficacy than those without this condition and that self-efficacy is related to the severity of binge eating.     

Serum Copper and Zinc Levels in Healthy Greek Children and Their Parents

The aim of this study was to investigate whether there is a correlation between copper (Cu) and zinc (Zn) levels in children and their parents, considering their nutritional habits. Cu and Zn concentrations were measured by flame atomic absorption spectrophotometry in the serum of 66 healthy children, aged 3–14 years, and their parents, residing in a region of Greece (Thrace). Cu levels were higher in mothers than those in fathers, but they were lower in both parents than those in children. They also tended to decrease with age in both parents and children, whereas Zn levels significantly increased with age in children. There was a positive correlation between children's and mothers' Zn levels, as well as children's and both parents' Cu levels. Children used to eat meat, fish, vegetables, and legumes as frequently as their parents, but they were consuming more eggs, milk, and fruits than the latest. Regarding parents' diet, higher Zn levels were depended on the consumption of meat and milk, whereas higher Cu levels were depended on the consumption of milk. Consequently, children’s Cu and Zn levels are related to their parents’ levels, which can be influenced by their nutritional habits.     

Occult Endotoxin in Bacterial Protoplasm

Protoplasm separated from disrupted cells of gram-negative bacteria was extracted with hot phenol-water or was precipitated with ethyl alcohol after digestion with Pronase. These methods recovered about 10 times more endotoxin than was detectable in the untreated protoplasm. Inactivation of endotoxin by protoplasm also occurred in vitro when the endotoxin was first dissociated into subunits before reaction with protoplasm. Despite this increased yield from another source, the major proportion of endotoxin was still found in the cell walls.     

Serum Uric Acid Levels and Risk of Metabolic Syndrome in Healthy Adults

ObjectiveTo investigate the relationship between hyperuricemia and metabolic syndrome in a population of healthy subjects.MethodsWe studied 1,573 healthy adults (25 to 64 years old) in the population laboratory of the Tehran University of Medical Sciences. The study was designed according to the World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) project with use of the National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome.ResultsThe crude prevalence of the metabolic syndrome was 29.9% (age-adjusted, 27.5%). The rate of metabolic syndrome significantly increased in higher quartiles of serum uric acid in both sexes but especially in women (P < .0001 versus P = .026). The bivariate correlation was significant between uric acid levels and age, total serum cholesterol, high-density lipoprotein cholesterol, triglycerides, body mass index, waist and hip circumferences, waist-to-hip ratio, and systolic and diastolic blood pressures; however, there was not a significant correlation between serum uric acid concentrations and fasting plasma glucose.ConclusionThese data indicate that an independent relationship exists between hyperuricemia and the metabolic syndrome. Moreover, hyperuricemia is significantly correlated with hypertriglyceridemia, hypertension, and visceral obesity. Early detection of hyperuricemia seems to be essential for prevention of the metabolic syndrome. (Endocr Pract. 2008;14:298-304)     

An Eighteen Serum Cytokine Signature for Discriminating Glioma from Normal Healthy Individuals

Glioblastomas (GBM) are largely incurable as they diffusely infiltrate adjacent brain tissues and are difficult to diagnose at early stages. Biomarkers derived from serum, which can be obtained by minimally invasive procedures, may help in early diagnosis, prognosis and treatment monitoring. To develop a serum cytokine signature, we profiled 48 cytokines in sera derived from normal healthy individuals (n = 26) and different grades of glioma patients (n = 194). We divided the normal and grade IV glioma/GBM serum samples randomly into equal sized training and test sets. In the training set, the Prediction Analysis for Microarrays (PAM) identified a panel of 18 cytokines that could discriminate GBM sera from normal sera with maximum accuracy (95.40%) and minimum error (4.60%). The 18-cytokine signature obtained in the training set discriminated GBM sera from normal sera in the test set as well (accuracy 96.55%; error 3.45%). Interestingly, the 18-cytokine signature also differentiated grade II/Diffuse Astrocytoma (DA) and grade III/Anaplastic Astrocytoma (AA) sera from normal sera very efficiently (DA vs. normal–accuracy 96.00%, error 4.00%; AA vs. normal–accuracy 95.83%, error 4.17%). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using 18 cytokines resulted in the enrichment of two pathways, cytokine-cytokine receptor interaction and JAK-STAT pathways with high significance. Thus our study identified an 18-cytokine signature for distinguishing glioma sera from normal healthy individual sera and also demonstrated the importance of their differential abundance in glioma biology.     

细菌内毒素研究进展

内毒素（endotoxin）是一种革兰阴性细菌细胞壁外膜的主要组成成分,其化学本质为脂多糖（lipopolysaccharide,LPS）,是诱发炎症反应过程中主要的致病成分。本文就细菌内毒素的信号通路、检测方法及抗内毒素药物的研发进行了综述。     

Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5×10⁻⁷). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations.     

Changes in Serum Copper and Zinc Levels in Peripartum Healthy and Subclinically Hypocalcemic Dairy Cows

The objective of this study was to determine the levels of serum copper and zinc in subclinically hypocalcemic peripartum dairy cows in comparison to healthy animals. Blood samples were taken from 219 multiparous Holstein cows near parturition (from 4 weeks prepartum to 4 weeks postpartum) and 51 cows with subclinical hypocalcemia. The results showed that the serum copper concentration increased gradually at 1 week prepartum and remained high for the first 4 weeks postpartum in the healthy periparturient dairy cows. The serum zinc concentration reached a nadir at 1 week postpartum and subsequently increased gradually to baseline. The serum zinc concentration was significantly decreased (P?<?0.01) in dairy cows with subclinical hypocalcemia compared with healthy cows. There was no significant difference in the serum copper concentration between cows with subclinical hypocalcemia and healthy cows. These data demonstrate that the concentrations of copper and zinc in serum change dramatically during the peripartum period in dairy cows, which is a tremendous challenge for the body and for the maintenance of dairy cow health. The present study further suggests that a decreased serum zinc concentration could be a cause of decreased productive performance and increased susceptibility to other diseases due to immunosuppression in dairy cows with subclinical hypocalcemia. Additionally, this decreased zinc concentration may be involved in the pathogenesis of subclinical hypocalcemia.     

Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

BackgroundCytokines are humoral molecules that elicit regulatory function in immunologic pathways. The level and type of cytokine production has become critical in distinguishing physiologic from pathologic immune conditions. Cytokine profiling has become an important biomarker discovery tool in monitoring of the immune system. However, the variations in cytokine levels in individual subjects over time in healthy individuals have not been extensively studied. In this study, we use multiplex bead arrays to evaluate 27 analytes in paired serum samples taken seven days apart from 144 healthy individuals in order to assess variations over a short time period.MethodsFluorescent bead-based immunoassay (Luminex) was used to measure 27 analytes in serum samples. Measurements were performed on matched samples from 144 healthy donors. To assess inter-plate variability, one arbitrarily selected serum sample was analyzed on each of the first ten plates as bridge sample. ResultsUsing the bridge sample, we showed minimal inter-plate variations in the measurement of most analytes. In measurement of cytokines from the 144 patients at two time points, we found that three cytokines (IL-2, IL-15 and GM-CSF) were undetectable and five analytes (RANTES, MCP-1, VEGF, MIP-1β and PDGF-BB) showed significant difference in concentrations at Day 0 compared to Day 7. ConclusionsThe current study demonstrated higher variations in cytokine levels among individuals than were observed for samples obtained one week apart from identical donors. These data suggest that a serum sample from each subject for use as a baseline measurement is a better control for clinical trials rather than sera from a paired cohort.     

Daily Variations of Homocysteine Concentration May Influence Methylation of DNA in Normal Healthy Individuals

The regulation of genetic expression is tightly controlled and well balanced in the organism by different epigenetic mechanisms such as DNA methylation and histone modifications. DNA methylation occurring after embryogenesis is seen mainly as an irreversible event. Even small changes in genomic DNA methylation might be of biological relevance, and several factors influencing DNA methylation have been identified so far, one being homocysteine. In this study, genomic DNA methylation was analyzed and homocysteine plasma levels were measured over a 24 h period in 30 healthy students (15 males and 15 females) exposed to a standard 24 h regime of daytime activity alternating with nighttime sleep. Plasma homocysteine concentrations were measured using HPLC detection. DNA was extracted from whole EDTA blood, and genomic DNA methylation was assessed by fluorescently labeled cytosine extension assay. Both homocysteine and DNA methylation showed 24 h variation. Homocysteine showed a significant daily rhythm with an evening peak and nocturnal nadir in all subjects (p<0.001). Males showed higher overall homocysteine levels compared to females (p=0.002). Genomic DNA methylation showed a significant rhythm with increased levels at night (p=0.021), which was inverse to plasma homocysteine levels.     

Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals

Objectives

We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.

Methods

Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.

Results

The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.

Conclusions

In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.     

Comparison of Serum Changes of Interleukin-17A and Interleukin-21 Between Schizophrenic Patients and Healthy Individuals

Background:Immunological alterations in schizophrenic patients have been considered during last decade. There are no remarkable reports on the changes of IL-17A and IL-21 in schizophrenic patients. Therefore, the purpose of this study was to evaluate changes of serum IL-17A and IL-21 in schizophrenic patients in comparison with healthy controls.Methods:In the present study serum levels of IL-17A and IL-21 in 30 patients with schizophrenia before treatment and three months after treatment were measured by enzyme-linked immunosorbent assay (ELISA) and compare to 30 match healthy control group.Results:Serum levels of IL-21 in schizophrenic patient was significantly higher than control group (P= 0.001). Serum levels of IL-17A in the schizophrenic patients had no significant changes than the control group (P= 0.4). Serum levels of IL-17A in patients with schizophrenia three months after treatment than before treatment had no significant change (P=0.7) and IL-21 serum levels in schizophrenic patient three month after treatment was not significant changed in comparison with this group before treatment (P= 0.06).Conclusion:The serum levels of interlukine-21 is elevated in schizophrenic. Results of this study showed that IL-21 might be involved in the pathologic mechanism of schizophrenia.Key Words: Immunity, Interleukin-17A, Interleukin-21, Schizophrenia     

The Effects of Rosuvastatin on the Serum Cortisol,Serum Lipid,and Serum Mevalonic Acid Levels in the Healthy Indian Male Population

In this open-label, balanced, randomized, placebo-controlled, parallel study, healthy male volunteers were randomly divided into two groups. Each group received either a single oral dose of rosuvastatin 20 mg or placebo. Estimations were done at predose on day 1 of dosing (baseline) and 24 h postdose after days 7 and 14. Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid (MVA) levels were measured using validated liquid chromatography–tandem mass spectrometry method. Rosuvastatin produced a statistically significant (P < 0.05) decrease in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides. However, the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group. The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent, without any significant change in serum cortisol level in the healthy Indian male population.