阴茎勃起及勃起功能障碍的研究进展

勃起功能障碍的基础研究须近十年来取得了较大进展,一氧化氮－cGMP(NO-cGMP)通路的发现使得阴茎平滑肌松驰的机制进一步阐明。一氧化氮合酶（NOS）、磷酸二酯酶（PDEs）的研究为勃起功能障碍的临床治疗提供了坚实的基础,进而促使了万艾可的问世。目前,勃起功能障碍的基因治疗停留在实验室阶段,但随着分子生物学的深入研究,转基因疗法可能成为临床上治疗勃起功能障碍的有效方法之一。     

Protein glycation and endothelium dysfunction

Advanced glycation end-products (AGE) are a group of heterogeneous molecules found in higher levels during diabetes, end stage renal failure and aging. Vascular alteration is correlated with their accumulation as during retinopathy or glomerulosclerosis. Glycation of extracellular matrix proteins is associated with diabetic angiopathy. AGE stimulate endothelial cell via the interaction with the receptor RAGE, leading to an inflammatory state with increased adhesion molecule expression, chemoattractant factor and tissue factor production. RAGE activation by AGE triggers reactive oxygen species production by NADPH oxydase. Agents that inhibit AGE formation, stimulate their degradation or neutralize their binding to RAGE represent new approaches to limit the deleterious activities of AGE.     

二甲基精氨酸二甲基氨基水解酶与内皮功能异常

非对称二甲基精氨酸（asymmetric dimethylarginine,ADMA）是一氧化氮合酶（NOS）的内源性竞争性抑制物,竞争性抑制NOS使NO含量减少,引起一系列血管异常效应。二甲基精氨酸Z-甲基氨基水解酶（dimethylarginine dimethylaminohydrolase,DDAH）是主导ADMA代谢的催化酶。DDAH减少或活性降低会使ADMA在体内积累,导致内皮功能异常。本文介绍了DDAH引起内皮功能异常的机制,并对有关影响DDAH活性或表达的药物研究作一概述。     

Cardiovascular complications and related risk factors underlying opium consumption

Opium is considered as the second most abused addictive compound in worldwide. It seems that one of the causes for common consumption of opium in many countries is a traditional belief, even among medical personnel, through which opium might have advantageous influences on cardiovascular events and be beneficial in controlling hypertension, dyslipidemia, and diabetes. According to several investigations, it is thought that opium not only has no beneficial effects on cardiovascular events, but it might have deleterious influences on these settings. As a result, people need to be trained with regard to the adverse effects of opium on cardiovascular events. In this review, we try to go through the understanding of the effects of opium cardiovascular disorders and related complications such as blood pressure, blood sugar, lipid circumstances, and finally atherosclerosis.     

Leg disorders in broiler chickens: prevalence, risk factors and prevention

Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which quantifies the risk factors for poor locomotion in broiler chickens. We assessed the walking ability of 51,000 birds, representing 4.8 million birds within 176 flocks. We also obtained information on approximately 150 different management factors associated with each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit (second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide approximately 2 x 10(10) broilers are reared within similar husbandry systems. We identify a range of management factors that could be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and production. A debate on the sustainability of current practice in the production of this important food source is required.     

Biomarkers of endothelial dysfunction,cardiovascular risk factors and atherosclerosis in rheumatoid arthritis

Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-α. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima–media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-α, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P ≤ 0.04). Five patients had diabetes. Differences in endothelial function were no longer significant between patients and controls (P = 0.08) only after both traditional and nontraditional cardiovascular risk factors were controlled for. In the 74 RA patients, IL-6 predicted levels of all three biomarkers (P ≤ 0.03), and rheumatoid factor titres and low glomerular filtration rate (GFR) both predicted levels of VCAM-1 and ICAM-1, independent of traditional cardiovascular risk factors (P ≤ 0.02). VCAM-1 was associated with common carotid artery intima–media thickness (P = 0.02) and plaque (P = 0.04) in RA. Patients had impaired endothelial function, less favourable traditional cardiovascular risk factor profiles, and higher circulating concentrations of hs-CRP and cytokines compared with healthy control individuals. Both traditional and nontraditional cardiovascular risk factors contributed to the differences in endothelial function between RA patients and healthy control individuals. IL-6, rheumatoid factor titres and low GFR were independently predictive of endothelial dysfunction in RA. Disease-modifying agents that effectively suppress both cytokine and rheumatoid factor production, and interventions aimed at preserving renal function may attenuate cardiovascular risk in RA.     

Cardiovascular risk factors in subjects with Helicobacter pylori infection

Background. It has been proposed that Helicobacter pylori infection is related to cardiovascular disease, although this has not been fully investigated. The aim of this study was to investigate whether H. pylori in‐fection is associated with cardiovascular risk factors. Subjects and Methods. One thousand six hundred and fifty people undergoing annual medical checks at Shimane Institute of Health Science between September 1998 and August 1999 were enrolled. Gender, age, body mass index, habitual smoking and drinking, systolic and diastolic blood pressure, serum level of total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDLC), blood glucose, leukocyte count and hemoglobin were compared between H. pylori seropositive and seronegative cases. Results. In H. pylori seropositive individuals, HDLC was significantly lower than that in seronegative individuals. After adjustment for possible confounding factors (gender, age, BMI, smoking and drinking habits), mean HDLC in H. pylori‐seropositive and seronegative individuals were 56.1 and 58.2 mg/dl, respectively (p < .005). The percentage of the elderly (over 50 years old) individuals with HDLC < 35 mg/dl in H. pylori seropositive and seronegative groups were 7.4% and 4.7%, respectively (p < .001). In addition, the lower HDLC level was accompanied by an increased leukocyte count. Conclusion. Long‐term infection with H. pylori may have an important role in decreasing the serum HDLC concentration.     

Cardiovascular risk factors in a tourist town: association with job-related factors

Previous studies have shown that mortality from cardiovascular diseases in fishing villages was lower than that in farming villages. In contrast, few reports on the population living in a tourist village have appeared. Then, we report here the characteristic features of a tourist town, and that in fishing and farming towns. The rural farming town in Gunma prefecture had a population of 15,100. The population working in the primary industry was 17.1%, and the farming population was 17.0%. The fishing town in Shizuoka prefecture had a population of 11,700. The population working in the primary industry was 11.0%, and the fishing population was 10.2%. The rural tourist town in Shizuoka prefecture had a population of 17,800. The population working in the tertiary industry was 60.2%, and the wholesaling or retailing population was 16.6%. Standardized mortality ratios of cardiovascular diseases in the tourist town reported by Shizuoka health officials were higher than the fishing town. The rate of participation at ages of 50-59 years for the basic health examination in the tourist town was lower than the fishing and the farming towns. From the results of the health examination of residents at ages of 50-59 years, the high prevalence of obesity and hypertension in men and high prevalence of hypertension in women were found in the tourist town. In the tourist town, self-employed women at ages of 50-59 years had irregular time of meals and insufficient care of diet in comparison with employed women. Furthermore, the prevalence of hypertension in self-employed women was also higher than that of employed women. We could suggest that health status in communities might be associated with job-related factors.     

Cardiovascular disease and risk factors: the role of growth hormone

Clinical studies in patients with acromegaly have shown that growth hormone (GH) exerts both short- and long-term effects on the structure and function of the heart. Moreover, chronic growth hormone deficiency (GHD) has been associated with impaired cardiac performance, low heart rate and impaired left ventricular systolic function. Exercise capacity in patients with GHD is significantly reduced and in some severely affected individuals, dilated cardiomyopathy and heart failure has been reported. GHD has also been associated with a number of risk factors for cardiovascular disease. Altered lipoprotein metabolism and elevated fibrinogen and plasminogen activator inhibitor-1 activity are associated with GHD, and the risk of hypertension is increased in GH-deficient men. Subcutaneous and intra-abdominal fat mass have also been found to be abnormally high in these patients. These effects may contribute to an increased risk of death from cardiovascular disease. GH is therefore an important factor in the development and function of the cardiovascular system. In this paper, the effects of GH on the physiological mechanisms of the cardiovascular system are discussed, including the effect of GHD on cardiovascular disease risk. We will also discuss the effects of long-term GH replacement therapy in this patient population.     

Trehalose protects the endothelium from cadmium-induced dysfunction

The objective of the present study is to identify the possible regulatory role of trehalose (Tre) against cadmium chloride (CdCl₂)-induced endothelial cell dysfunction. To screen the dose-dependent effect of both Tre and CdCl₂, a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was performed. Interestingly, MTT assay results have shown that co-incubation of Tre (1 mM) with CdCl₂ significantly decreased the CdCl₂ (5 µM) cytotoxicity. Nitric oxide (NO) measurement using Griess assay and 4-amino-5-methylamino-2ʹ,7ʹ-difluorofluorescein fluorescence probe results have shown that CdCl₂ decreases NO production in endothelial cells. Western blotting analysis results showed that CdCl₂ decreases endothelial nitric oxide synthase (eNOS) and phospho endothelial nitric oxide synthase (peNOS) expression. The present study results have also observed that CdCl₂ treatment increases reactive oxygen species (ROS) production. However, combination treatment (Tre + CdCl₂) could restore the NO production in CdCl₂-treated cells. In addition, combination treatment could also restore eNOS and peNOS expression in endothelial cells. Moreover, Tre treatment was found to decrease CdCl₂-induced ROS production. Collectively, the present study results demonstrate that Tre possesses a significant protective action against CdCl₂-mediated endothelial dysfunction by increasing NO production, eNOS and peNOS expression, and by decreasing oxidative stress.     

Cardiovascular risk factors in a small urban community in central Croatia

The aim of this study was to determine in Karlovac (southern part of central Croatia) the most important risk factors for coronary heart diseases in men and women according to age < or = 59 and > or = 60 on the basis of their prevalence in 558 non-coronary patients and 442 symptomatic coronary patients. In younger male coronary patients (< or = 59 years of age) in relation to the control study, the statistically significant more frequent risk factors were hypercholesterolemia (p < 0.001), smoking (p < 0.01) and diabetes (p < 0.01). In older male patients (> or = 60 years of age) there was no statistically significant difference in a single risk factor. In younger female coronary patients, the statistically significant more frequent risk factors were hypercholesterolemia (p < 0.001) and diabetes (p < 0.001) and in older female patients diabetes (p < 0.05). This population sample showed higher prevalence of cardiovascular risk factors in younger coronary patients. The most frequent risk factors were diabetes, hypercholesterolemia and smoking. The difference is slighter in older coronary patients where it is diabetes, which is the most important for women.