Sonographic evaluation of endothelial function in letrozole and tamoxifen users

Objectives

Studies have shown that women previously treated for breast cancer present fewer cardiovascular events, indicating a possible protective effect of tamoxifen treatment. The effects of these aromatase inhibitors on cardiovascular protection remain controversial. The aim of this study was to compare some cardiovascular risk markers among breast cancer survivors following treatment with tamoxifen group (TMXg), letrozole group (LTZg) or no endocrine treatment group (NETg).

Methods

A total of 103 breast cancer survivors: 35 using TMXg, 34 using letrozole group (LTZg) and 34 using no endocrine treatment group (NETg) were evaluated. Ultrasonographic evaluation of brachial artery flow-mediated dilation (FMD), carotid intima–media thickness (IMT) and stiffness index (β); blood total cholesterol, HDL and triglycerides were assessed.

Results

All three groups presented similar values of HDL and IMT. TMXg showed the lowest total cholesterol (219.29 ± 36.31 mg/dL vs. 250.59 ± 38.37 mg/dL vs. 245.09 ± 35.35 mg/dL; TMXg vs. LTZg vs. NETg, respectively; p < 0.01—ANOVA), the highest triglycerides (139.34 ± 41.82 mg/dL vs. 111.35 ± 28.22 mg/dL vs. 122.09 ± 33.42 mg/dL; p < 0.01), the highest FMD (6.32 ± 2.33% vs. 4.10 ± 2.06% vs. 4.66 ± 2.52%; p < 0.01) and the lowest stiffness index (β) (5.08 ± 1.68 vs. 6.28 ± 1.75 vs. 5.99 ± 1.86; p = 0.01). LTZg did not differ significantly from NETg on any evaluated parameter.

Conclusions

We did not observe any effect of LTZg on the evaluated cardiovascular risk parameters compared to NETg. As such, the observed difference on lipid values, stiffness index (β) and FMD between women receiving tamoxifen and letrozole might be best attributed to the beneficial effect of tamoxifen than to a detrimental effect of letrozole.     

Managing menopausal symptoms and depression in tamoxifen users: implications of drug and medicinal interactions

Objective

Tamoxifen, a medication used in the treatment of breast cancer, often induces menopausal symptoms. Certain medications and natural supplements taken or prescribed to alleviate tamoxifen-induced hot flashes and depressive states in women with breast cancer interact with tamoxifen. This paper reviews potentially problematic interactions and offers treatment recommendations.

Methods

Medline (1950-June 1, 2010), Embase Classic + Embase (1947-June 1, 2010) and PsycINFO (1967-June 1, 2010) were searched through Ovid. The word “tamoxifen” was searched with “depression” and then with “menopaus*” and “symptoms”, with “treatment” as a limit. “Tamoxifen” was later searched with the MeSH terms “drug interaction” or “drug incompatibility”.

Results

Venlafaxine is efficacious for the treatment of hot flashes and depression and safe to use in combination with tamoxifen. Gabapentin is also efficacious in treating tamoxifen-induced hot flashes and, since it does not interact with cytochrome P450 system, is likely safe to use in patients using tamoxifen. Desvenlafaxine and pregabalin may be alternatives to venlafaxine and gabapentin, respectively, although desvenlafaxine has not yet been studied in this population. Paroxetine, fluoxetine and bupropion are strong CYP2D6 inhibitors which should be avoided in tamoxifen users. Fluvoxamine and nefazodone both inhibit CYP3A, which could potentially affect the metabolism of tamoxifen. Clonidine can be an alternative agent but may carry significant side effects. Evidence of medicinal products for the treatment of tamoxifen-induced hot flashes is equivocal at best.

Conclusions

Clinicians should remain cautious about using strong inhibitors and/or inducers of cytochrome 2D6 and 3A4 concomitantly with tamoxifen. Use of natural menopausal supplements and diets rich in isoflavones should not be encouraged in tamoxifen users until more data is available. There are however safe treatments for hot flashes and depression in tamoxifen users.     

妊娠期高血压疾病患者的血管内皮功能评价

目的探讨妊娠期高血压疾病(HDCP)患者的血管内皮功能变化。方法对孕晚期50例妊娠期高血压疾病患者(研究组)和30例正常孕妇(对照组),检测两组患者的血清内皮素(ET)、一氧化氮(NO)水平,超声测量肱动脉血流介导的舒张功能(FMD)。结果 (1)研究组ET高于对照组并有统计学差异(P<0.05),而研究组的NO、FMD低于对照组并均有统计学差异(P<0.05)。(2)在研究组内,重度子痫前期组的ET高于轻度子痫前期组并有统计学差异(P<0.05),而重度子痫前期组的NO、FMD低于轻度子痫前期组并均有统计学差异(P<0.05)。结论 HDCP患者存在血管内皮损伤,超声等检查能有效检测其内皮损伤程度。     

Cognitive function in HIV-1-infected drug users

Loss of cognitive ability, the most common neuropsychological complication in HIV-1 disease, may influence compliance with treatment and has been associated with decreased functional capacity, as well as an increased risk of mortality. In HIV-1-infected drug users, cognitive impairment affecting attention, memory, planning of complex tasks, information processing, and motor processes, has been reported, similar to findings in predominantly HIV-1-infected nondrug-using cohorts. The issue of whether early signs of cognitive dysfunction can be identified in asymptomatic HIV-1-infected drug users remains controversial. Evaluation of potential confounding factors, such as drug abuse, age, education, nutritional status, which may influence cognitive function, is essential for determining the dominant cause of neuropsychological abnormalities. There is evidence for a time-limited, protective effect against the development of AIDS dementia with zidovudine therapy. The potential ability of other therapies (e.g., antioxidants, B-complex vitamins) to prevent neuronal damage and protect the brain remains to be determined.     

水通道蛋白1与内皮细胞功能

 水通道蛋白1（AQP1）是目前唯一发现在内皮有表达的水通道蛋白,在肾脏尿浓缩机制、小肠吸收乳糜微粒和角膜内皮的液体平衡中有重要作用;在血管内皮细胞中促进NO和CO2转运,调节血管舒缩功能,与心肌缺血后水肿和坏死关系密切,促进内皮细胞迁移,影响血管形成和肿瘤播散。     

Health behaviors and endothelial function

An unhealthy lifestyle, including excess caloric intake, lack of exercise, smoking, and excessive alcohol consumption, increases one’s risk of developing cardiovascular disease (CVD). However, the exact mechanisms by which these behaviors influence the development and progression of CVD have yet to be determined. Endothelial function (EF) has been shown to be a potent predictor of CVD, yet the effects of health behaviors on EF are not clear. The literature assessing the role of four health behaviors, obesity (a proxy of excess caloric intake), smoking, physical inactivity, and alcohol consumption, on the development of endothelial dysfunction is reviewed. Potential mechanisms through which these behaviors may influence EF are discussed. Smoking, being overweight or obese, and physical inactivity are all associated with decreased EF. A direct causal relationship between these measures and EF is suggested by the fact that improvements in these behaviors leads to parallel improvements in EF. The influence of alcohol consumption is somewhat more contentious, with some studies indicating a dose−response relationship such that those with greater consumption have poor EF. However, other studies have shown that those who drink moderately have the best EF. Although there is a growing body of literature implicating poor health behaviors in the development of endothelial dysfunction, more work is needed to establish the exact mechanisms by which this occurs. To our knowledge, there are no studies that have assessed the impact of multiple health behaviors or the interaction of health behaviors on EF.     

Vascular endothelial function in health and diseases

The vascular endothelium constitutes approximately 1% of body mass (1 kg) and has a surface area of approximately 5000 m². The endothelium is a multifunctional endocrine organ strategically placed between the vessel wall and the circulating blood, and has a key role in vascular homeostasis. The endothelium is both a target for and mediator of cardiovascular disease. The endothelium releases several relaxing and constricting factors, which can affect vascular homeostasis. Endothelial dysfunction, whether caused by physical injury or cellular damage, leads to compensatory responses that alter the normal homeostatic properties of the endothelium. In this review, we summarized some physiological aspects of endothelial function and then we discussed endothelial dysfunction during some pathological conditions.     

Sonographic versus clinical evaluation as predictors of residual trophoblastic tissue

BACKGROUND: The study aims to compare the diagnostic accuracy of sonographic evaluation versus clinical estimation in women suspected to have retained trophoblastic fragments. METHODS: The study group consisted of 68 consecutive patients admitted to our department due to suspected residual trophoblastic tissue. Each woman underwent ultrasound and physical examination by expert clinicians. The clinicians performing the physical examination were not informed of the sonographic findings, and vice versa. RESULTS: Patients were divided into three subgroups: clinical suspicion only of residual trophoblastic tissue (n = 8), sonographic suspicion only (n = 44) and combined sonographic and clinical suspicion of residual trophoblastic tissue (n = 16). In the latter group, in 14 out of 16 women (87.5%) retained trophoblastic tissue was confirmed by histological examination, a significantly higher rate compared to ultrasonographic (45.5%, P < 0.002) or clinical suspicion only (62.5%, P = 0.07). The specificity and positive predictive value of the clinical examination were significantly higher compared to ultrasonographic evaluation (P < 0.05), while the sensitivity of the ultrasonographic evaluation was higher than the clinical estimation (P < 0.05). There was no statistically significant difference in the negative predictive value or in diagnostic accuracy between the two methods. CONCLUSIONS: Based on our current experience, it seems that the combination of both clinical and ultrasonographic evaluation is recommended before uterine curettage is performed, thus lowering the rate of unnecessary invasive procedures.     

Human endothelial function and microvascular ageing

Age is a primary risk factor for cardiovascular disease, and this is an increasingly important public health concern because of an increase in the absolute number and proportion of the population at an older age in many countries. A key component of cardiovascular ageing is reduced function of the vascular endothelium, and this probably contributes to the impaired microvessel function observed with ageing in multiple vascular beds. In turn, impaired microvessel function is thought to contribute to the pathophysiology of cardiovascular and metabolic diseases. Here we review evidence that the first signs of altered endothelial and microvessel function can appear in childhood and at all stages of the human lifespan; low-birth-weight babies have reduced endothelial function in skin microvessels at 3 months, and by age 10 years their brachial artery endothelial function is reduced in comparison with normal-birth-weight babies. In overweight/obese adolescent children with clustering of traditional cardiovascular disease risk factors, endothelial function is reduced compared with normal-weight children, and this appears to persist into early adulthood. Adult ageing is associated with impaired microvessel endothelial function and an increase in capillary blood pressure. Biological and lifestyle factors that influence microvessel function include body fat and visceral adiposity, sex hormone status, diet and physical activity. The mechanisms underlying age-associated changes in microvessel function are uncertain but may involve alterations in nitric oxide, prostanoid, endothelium-derived hyperpolarizing factor(s) and endothelin-1 pathways.     

Selenium-dependent enzymes in endothelial cell function

Glutathione peroxidases and thioredoxin reductases are the main selenoproteins expressed by endothelial cells. These enzymes reduce hydroperoxides, their role in endothelial cell physiology, however, by far exceeds prevention of oxidative damage. Reactive oxygen and nitrogen species, especially superoxide, hydroperoxides, and nitric oxide, are crucial signaling molecules in endothelial cells. Their production is regulated by vascular NAD(P)H oxidases and the endothelial nitric oxide synthase. Their metabolism and physiological functions are coordinated by glutathione peroxidases and the thioredoxin/thioredoxin reductase system. Endothelial selenoproteins are involved in the regulation of the vascular tone by maintaining the superoxide anion/nitric oxide balance, of cell adhesion by controlling cell adhesion molecule expression, of apoptosis via inhibition/activation of apoptosis signal-regulating kinase-1, and of eicosanoid production by controlling the activity of cyclooxygenases and lipoxygenases. Accordingly, they regulate inflammatory processes and atherogenesis. The underlying mechanisms are various and differ between individual selenoproteins. Scavenging of hydroperoxides not only prevents oxidative damage, but also interferes with signaling cascades and enzymes involved. Modulation of proteins by hydroperoxide-driven thiol/disulfide exchange is a novel mechanism that needs to be further investigated. A better understanding of the complex interplay of selenoproteins in regulating endothelial cell functions will help to develop a rationale for an improvement of health by an optimum selenium supply.     

Evaluation of vascular endothelial function

Endothelial function was evaluated in renal and forearm vessels from patients with essential hypertension. First, the increase in renal blood flow evaluated by the clearance of para-aminohippurate, serum c-GMP and urinary NOx during L-arginine infusion was significantly attenuated in essential hypertension. This attenuated endothelium-dependent vasodilation was improved by angiotensin converting enzyme inhibitor, but unchanged by calcium antagonist. Second, the increase in forearm blood flow evaluated by plethysmography during acetylcholine infusion or reactive hyperemia was attenuated in essential hypertension. This attenuation was abolished by NO synthesis inhibitor. Forearm endothelial function was improved by angiotensin converting enzyme inhibitor, daily aerobic exercise and body weight reduction by low calorie diet. In conclusion, endothelium-dependent vasodilation was attenuated in renal and forearm vasculature of essential hypertensives via reduction of NO synthesis. This attenuation can be improved by several treatments.     

内皮衍生微粒诱导内皮细胞氧自由基产生损伤内皮功能

目的： 探讨内皮衍生微粒（EMP)诱导内皮功能失调的机制和氧自由基(O-·2)在EMP诱导内皮功能失调中所起的作用。方法: 从人血纤维蛋白溶酶原激活抑制剂-1刺激的人脐静脉内皮细胞中提取EMP,(1)采用牛主动脉内皮细胞（BAEC）做细胞培养,分成3组。第1组不做预处理,第2组EMP (1×108/L),第3组EMP(1×108/L) + L-nitroarginiemethylester(L-NAME, 1 mmol/L),预处理BAEC 30 min后,用超氧化物歧化酶(SOD)可抑制的铁细胞色素C还原法,测量O-·2的产生情况。(2) 从小鼠中分离面动脉,分成4组。第1组不做预处理,第2组EMP (1×108/L),第3组EMP(1×108/L) + SOD (2×105 U/L),第4组EMP (1×108/L)+聚乙烯羟乙酸盐超氧化物歧化酶(PEG-SOD, 2×105 U/L) 预处理血管10 min后做乙酰胆碱（ACH）诱导下的内皮依赖血管舒张功能试验。结果:（1）EMP明显增加BAEC O-·2产生,L-NAME可以抑制50% EMP导致的 O-·2产生增加。 (2) EMP明显损伤ACH诱导的血管舒张功能,SOD处理未能清除EMP对血管舒张功能的损伤,PEG-SOD可部分恢复EMP处理后的血管舒张功能。结论: EMP诱导血管内皮功能失调至少部分是通过诱导细胞内产生的O-·2所致,为将来寻找包括清除O-·2在内的综合治疗方法提供理论依据。     

Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus

INTRODUCTION:

Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy.

METHODS:

We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation).

RESULTS:

Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P =  0.257), HbA_1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P = 0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P = 0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P = 0.888).

CONCLUSIONS:

Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.     

Human cytomegalovirus, endothelial function and atherosclerosis

Human cytomegalovirus (HCMV) serology is linked to several measures of endothelial dysfunction. There is substantial evidence for HCMV having an aetiological role in transplant arterial disease and accumulating evidence for HCMV in the origins of preeclampsia. However, whether HCMV is a clinically significant cause of atherosclerosis in the general, immunocompetent population remains to be seen.