新疆地区维吾尔族人群高血压患者microRNA表达谱分析

目的筛选新疆地区维吾尔族人群原发性高血压(EH)患者与健康者血浆中microRNA差异表达谱,为进一步探究microRNA与新疆维吾尔族人群原发性高血压发病的关系提供依据。方法选取4例维吾尔族原发性高血压患者和4名维吾尔族健康人的全血,用Agilent Human miRNA芯片检测血浆microRNA表达谱。对差异表达的microRNA进行聚类分析、靶基因预测、靶基因注释等生物信息学分析。另外选取独立验证样本(15例维吾尔族原发性高血压患者及15名维吾尔族健康人),对差异表达的microRNA进行q PCR验证。结果实验组与对照组相比,筛选获得257个差异表达microRNA,其中161个上调表达,97下调表达。通过Target Scan、PITA、microRNAorg数据库对差异表达microRNA进行靶基因预测,对3个数据库预测到的靶基因取交集,获得6 580个microRNA调控的靶基因系。最终筛选得到表达上调最多和下调最多的两个microRNA,hsa-miR-1183和hsa-miR-30e-5p。结论原发性高血压患者有着独特的microRNA表达谱,筛选获得的差异表达microRNA,可能是原发性高血压早期诊断的生物标志物和潜在的治疗靶点,同时对于后续研究原发性高血压的发病机制具有提示作用。     

Serum biochemical profile and performance of broiler chickens fed diets containing essential oils and pepper

Serum biochemical parameters and performance data were evaluated in broilers fed diets supplemented with antibiotics or essential oils from oregano, sage, rosemary, and pepper crude extract (OLES). Animals (n = 910) were distributed into five treatment groups, with seven replicates of 26 birds in each group: the control group (diet without additives); the group receiving an antibiotic growth promoter diet; and the groups T₅₀, T₁₀₀, and T₁₅₀ (feed supplemented with 50, 100, and 150 mg/kg of OLES, respectively). After 42 days, 55 animals were randomly selected for serum biochemical profile analysis involving pancreatic, renal, and hepatic functions (lipase, amylase, urea, uric acid, aspartate aminotransferase, gamma glutamyltransferase, total cholesterol, high-density lipoprotein, triglycerides, total protein, albumin, globulins, and albumin/globulins ratio). Growth performance of broilers (body weight, weight gain, feed intake, alimentary conversion, and mortality) was also evaluated throughout the experiment period. The increase in serum levels of lipase, uric acid, urea, and aspartate aminotransferase suggests that OLES may cause kidney and liver impairment, mainly, at the higher dose. The OLES dose of 100 mg/kg is suitable for a final body weight and a weight gain similar to those observed in broilers supplemented with antibiotic growth promoters.     

A case of Candida haemulonii osteitis: clinical features,biochemical characteristics,and antifungal resistance profile

We describe here the first case of osteitis caused by Candida haemulonii in a young immunocompetent patient. This patient presented a history of severe peripheral vascular disease associated with a lack of hygienic conditions as the only risk factors for such an uncommon infection. Clinical signs and histological examination allowed us to determine that it was a C. haemulonii infection and not colonization. The outcome was favourable with oral voriconazole therapy and surgical revascularization. An environmental cause of such infections is most probable, as C. haemulonii has previously been isolated from different non-human sources. Identification methods, results obtained with three in vitro antifungal susceptibility methods and clinical features are reported.     

Clinching the diagnosis: using the biochemical profile

The biochemical profile is an important extension of clinical evaluation and should include widely applicable tests for this purpose. Interpretation of results requires a proper understanding of what constitutes normality and abnormality and a knowledge of how changes may occur. The pathologist has a major responsibility in advising on interpretation in different clinical situations. This requires a familiarity with artefactual and drug-induced changes and a thorough knowledge of the pathophysiology of disease processes.     

Insulin resistance in essential hypertension

High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.     

Intracellular sodium and calcium in essential hypertension

Summary Intracellular sodium and calcium activities were measured by ion-selective electrodes in red blood cells of primary hypertensives and of normotensives with and without a familial disposition to hypertension. Intraerythrocytic sodium activity was markedly elevated in patients and normotensives with a familial disposition to hypertension (15.16±2.35 mmol/l in hypertensives and 9.74±1.43 mmol/l in normotensives, respectively, mean value±s_D) as compared to the corresponding group without such a history (8.35±2.08 mmol/l in hypertensives and 7.00±1.38 mmol/l in normotensives). Mean intraerythrocytic calcium activity showed the highest values in patients with hypertension (32.8±32.5 µmol/l in patients with and 25.3±19.0 µmol/l in those without a familial disposition to hypertension), whereas in normotensives mean calcium activity was much lower (9.6±9.7 and 4.8±4.5 µmol/l, respectively). Our results document that a disturbed intraerythrocytic sodium metabolism is limited to patients with essential hypertension and a familial disposition to hypertension and, to a lesser extent, to normotensives showing a familial disposition to hypertension. Thus, a genetically determined alteration in intracellular sodium can be assumed. Furthermore, the observation of an enhanced intraerythrocytic calcium in some essential hypertensives with and without a familial disposition suggests additional factors, other than sodium, responsible for the disturbed intracellular calcium balance in these patients.     

Personality characteristics and renin in essential hypertension

There may be specific personality differences between some if not all biochemically defined subgroups of patients with essential hypertension. A newly standardized projective test of reactions to frustration, a questionnaire related to such characteristics as aggressiveness and dominance, and a standardized interview were applied to 16 patients with established high renin essential hypertension and 21 patients of similar age with normal renin. High renin patients are significantly less assertive, fail to externalize their aggression, perceive frustration less and try to please others more; they have a stronger need to solve problems immediately yet tend to deny social conflicts. These tendencies are likely to create internal conflict and indicate a psychosomatic component in high renin essential hypertension.     

Transdermal clonidine application: Long-term results in essential hypertension

Summary Skin patches of a clonidine transdermal therapeutic system (clonidine-TTS) with a constant release rate of either 0.1 or 0.2 mg clonidine/24 h continuously over 7 days were used in 32 essential hypertensives. These self-adhesive drug delivery systems (3.5 cm²), which were affixed to the upper outer arm, were changed by the patients at weekly intervals.During a mean observation period of 7 months (range 1–19 months) transdermal clonidine reduced the blood pressure from 162±15/107±5 mmHg to normal values (diastolic 95 mmHg) in 63% of our patients. However, chronic use of clonidine-TTS was accompanied by a high frequency of contact dermatitis (type IV allergy) in nearly half of our patients (n=15, 47%). In 11 of these 15 patients transdermal clonidine administration had to be stopped because of intolerable local skin reactions (pruritus, erythema, vesiculation, and/or infiltration). Subsequent patch testing with all components of clonidine-TTS was performed in eight cases. Whereas in seven cases an allergic contact dermatitis to clonidine was found, only one patient showed an allergy to another component of clonidine-TTS (polyisobutylene).We conclude that this strikingly high incidence of local allergic skin reactions limits the use of clonidine-TTS in essential hypertension.     

Microarray analysis of differential gene expression profile in peripheral blood cells of patients with human essential hypertension

The polygenic nature of essential hypertension and its dependence on environmental factors pose a challenge for biomedical research. We hypothesized that the analysis of gene expression profiles from peripheral blood cells would distinguish patients with hypertension from normotensives. In order to test this, total RNA from peripheral blood cells was isolated. RNA was reversed-transcribed and labeled and gene expression analyzed using significance Analysis Microarrays (Stanford University, CA, USA). Briefly, Significance Analysis Microarrays (SAM) thresholding identified 31 up-regulated and 18 down-regulated genes with fold changes of ≥2 or ≤0.5 and q-value≤5% in expression. Statistically significantly gene ontology (GO) function and biological process differentially expressed in essential hypertension were MHC class II receptor activity and immune response respectively. Biological pathway analysis identified several related pathways which are associated with immune/inflammatory responses. Quantitative Real-Time RT-PCR results were consistent with the microarray results. The levels of C-reactive protein were higher in hypertensive patients than normotensives and inflammation-related genes were increased as well. In conclusion, genes enriched for "immune/inflammatory responses" may be associated with essential hypertension. In addition, there is a correlation between systemic inflammation and hypertension. It is anticipated that these findings may provide accurate and efficient strategies for prevention, diagnosis and control of this disorder.     

Hereditary angioedema: clinical and biochemical heterogeneity

Hereditary angioedema is a well defined entity for which we now have effective therapy. It is a condition however that can have different clinical presentations which require individualized therapeutic approaches. The recent advances into the molecular biology of this condition should provide further insights for its effective management.     

Meditation training and essential hypertension: A methodological study

Meditation training appears to be a promising psychological approach to the control of hypertension. However, most studies to date have had serious deficiencies. This study attempted to correct many of these deficiencies. Forty-one unmedicated hypertensives referred by general practitioners were randomly allocated to three groups. The treatment group (SRELAX) underwent training procedures based on Transcendental Meditation; a placebo control group (NSRELAX) underwent identical training but without a mantra. Both procedures were compared with a no-treatment control group. The results showed modest reductions in blood pressure in both SRELAX and NSRELAX groups, compared with the no-treatment controls, with diastolic percentage reductions reaching significance (p<0.05). There was considerable subject variation in response, with overall a mean decline in diastolic blood pressure of 8–10% on 3-month follow-up. Possible indicators to predict the response of subjects are considered and reasons for the similarity in the effectiveness of the SRELAX and NSRELAX conditions are discussed.This research was funded by a grant from the Auckland Medical Research Foundation.