F2-isoprostanes in Alzheimer and other neurodegenerative diseases

Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical- mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F2-Isoprostanes (F2-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F2-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid beta (Abeta) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F2-IsoPs are not reproducibly elevated in aged mouse models of cerebral Abeta amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F2-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F2-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F2-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD.     

High levels of cynical distrust partly predict premature mortality in middle-aged to ageing men

The aim of this study was to evaluate the effect of cynical distrust on mortality in middle-aged and aging men. The analysis is based on Kuopio Ischemic Heart Disease study, follow-up from 1984 to 2011. Sample consisted of 2682 men, aged 42–61 years at baseline. Data on mortality was provided by the National Death Registry, causes of death were classified by the National Center of Statistics of Finland. Cynical distrust was measured at baseline using Cynical Distrust Scale. Survival analyses were conducted using Cox regression models. In crude estimates after 28 years of follow-up, high cynical distrust was associated with 1.5–1.7 higher hazards for earlier death compared to low cynical distrust. Adjusted for conventional risk factors, high cynical distrust was significantly associated regarding CVD-free men and CVD mortality, while non-CVD mortality in study sample was consistently but not significantly associated. The risk effects were more expressed after 12–20 years rather than in earlier or later follow-up. To conclude, high cynical distrust associates with increased risk of CVD mortality in CVD-free men. The associations with non-CVD mortality are weaker and not reach statistical significance.     

Homocysteine and folate levels in postmenopausal women

OBJECTIVES: To assess total homocysteine (tHcy) and folate levels in postmenopausal women and investigate whether age, menopause duration, kind of menopause and tobacco use had an effect on these levels. METHODS: Total homocysteine and folate levels were measured in fasting blood samples of 200 postmenopausal women with normal thyroid and renal function tests. Patients were not receiving vitamins or hormone replacement therapy. RESULTS: Total homocysteine levels increased significantly after 60 years while folate levels showed a decrease trend after 65 years. Menopause duration had no effect on folate levels and increased significantly tHcy levels after >180 months duration. The kind of menopause did not influence tHcy and folate levels. Tobacco use reduced significantly folate levels. CONCLUSIONS: Age seems to be the principal factor influencing tHcy levels. We believe that decreased folate levels also reflect an age-associated inadequate dietary intake. Tobacco use did not alter tHcy levels; however, we found smoking to lower folate levels.     

Prolonged exercise,lymphocyte apoptosis and F2-isoprostanes

Exercise induces a post-exercise decline in the number of circulating lymphocytes. The aim of the present study was to investigate whether strenuous exercise induces lymphocyte apoptosis and generation of reactive oxygen species. Eleven healthy male subjects exercised for 2.5 h on a treadmill. Apoptotic lymphocytes were defined by being annexin positive and 7-aminoactinomycin-D negative. Measurement of F₂-isoprostanes was used as a marker of oxidant stress in vivo. An increase (60%, P<0.05) in the percentage of apoptotic circulating lymphocytes was found 2 h post-exercise, whereas the total number of apoptotic cells did not change in relation to exercise. The concentration of plasma F₂-isoprostanes increased approximately 1.6-fold in response to exercise, but declined towards pre-exercise values within the 1st h of recovery. The plasma concentrations of adrenaline, noradrenaline and cortisol increased during exercise. In conclusion, the results of the present study demonstrate that even in a study design in which high levels of apoptosis-inducing factors are generated, such as cortisol and isoprostanes, lymphocyte apoptosis does not contribute to post-exercise lymphocytopenia. Electronic Publication     

Hormone replacement therapy and urinary prostaglandins in postmenopausal women

The objective of the study was to observe the effects of hormone replacement therapy upon urinary prostaglandin E₂ and prostaglandin F_2α levels in postmenopausal patients. A total number of 55 women were enrolled in this study and 15 premenopausal (PreM) healthy subjects constitute the control group. A total of 40 patients at least 12 months after their natural menopause were divided into two groups: 15 of them was not medicated hormone replacement therapy (which composed NRHRT group) while 25 of the rest, received conjugated estrogen (Premarin) 0.625 mg/day orally plus medroxyprogesterone acetate (Farlutal) 10 mg/day orally built up the RHRT group. PGE₂ and PGF_2α levels were measured with PGE₂ [¹²⁵I] and PGF_2α [³H] RIA kits. Statistical significance was analyzed by Student’s t-test for impaired data. NRHRT and RHRT patients had had increased urinary PGE₂ levels when compared with PreM (P<0.001). HRT caused a significant decrease in PGE₂ levels in menopausal women (P<0.001). Urinary PGF_2α values of NRHRT and RHRT were significantly lower (P<0.001) in comparison with PreM group. There was no difference in PGF_2α values between two postmenopausal groups. HRT given to postmenopausal patients might have a positive impact on prostaglandins and therefore on bone turnover in a series of various mechanisms.     

Serum Mg and Zn levels in postmenopausal women

Approximately 30% of a woman's life is spent in the postmenopausal period. This is when steroid hormone deficiency is often accompanied by mineral homeostasis perturbations and deficiencies that could be related to the intensity of any clinical symptoms. The aim of this study was to assess how serum Mg and Zn levels in postmenopausal women correlate with climacteric symptoms, body mass index (BMI), and the time interval since the final menstruation. The study involved 171 healthy, postmenopausal women, who had had their final menstruation at least one year prior to the study and who did not use menopausal hormone therapy. Both hypomagnesaemia and hypozincaemia were detected in the postmenopausal women involved in this study. The analysis revealed statistically significant differences between serum Mg levels, depending on the time interval since the final menstruation (p<0.05). No statistically significant differences were found in serum Mg and Zn levels between women as regards the severity of the climacteric symptoms or BMI (p>0.05). In conclusion, serum Mg and Zn concentrations in postmenopausal women, not using MHT, were low. The average serum Mg levels decreased considerably with the time since the final menstruation. No correlation between BMI and worsening of climacteric symptoms and serum Mg and Zn concentrations in postmenopausal women, not using MHT was found.     

Vitamin D metabolism and cardiovascular risk factors in postmenopausal women

Objectives

The purpose of this review is to focus on the association of vitamin D and cardiovascular risk factors in postmenopausal women.

Methods

Review of the relevant literature and results from recent clinical studies as well as critical analysis of published results concerning the association of vitamin D and cardiovascular risk factors in postmenopausal women obtained from both a PubMed and individual searches.

Results and discussion

Both basic science and clinical studies support the protective role of vitamin D on cardiovascular health, although there are controversial results in the literature. Hypovitaminosis D is associated with disturbed glucose metabolism and pancreatic β-cell dysfunction, lipoprotein alterations, hypertension, overweight and obesity. The evidence highlights the importance of improving vitamin D status in the general population for the prevention of adverse long-term health risks, including cardiovascular health. The optimal vitamin D dose remains to be determined. However, correction of low vitamin D itself does not guarantee the prevention of these conditions.     

Ambulatory cardiovascular functioning in healthy postmenopausal women with victimization histories

Criminal victimization is a prevalent stressor among women, with potentially long-lasting emotional consequences. The present study examined associations among severity of lifetime victimization, current posttraumatic stress disorder (PTSD) symptoms, and ambulatory blood pressure (ABP) and heart rate (AHR) levels and variability. Thirty-nine healthy post-menopausal women who endorsed a history of criminal victimization completed a measure of PTSD symptom severity and participated in an average of 18 h of ambulatory cardiovascular monitoring. PTSD symptom clusters were associated with AHR. Symptom clusters and lifetime victimization severity jointly predicted ABP, with ABP the highest among severely victimized women with high levels of current intrusions. Given the prevalence of criminal victimization, biopsychosocial research on women's cardiovascular disease risk may benefit from increased attention to this stressor and its psychological sequelae.     

Waist circumference predicts metabolic cardiovascular risk in postmenopausal Chinese women

OBJECTIVE: The purpose of the study is to compare the differences in metabolic cardiovascular risk factors among postmenopausal Chinese women with or without abdominal obesity. DESIGN: The study is a cross-sectional, population-based, comparative cohort study. Each participant received anthropometric measurements and a 75-g oral glucose tolerance test after an overnight fast. The homeostasis model assessment for insulin resistance and the insulin sensitivity index, ISI, were used as measures of insulin resistance. A "metabolic cardiovascular risk score" was calculated from fasting insulin, glucose, lipids, and blood pressure. General linear models (GLM) were fit to examine the relation of waist circumference (WC) to insulin resistance and metabolic risk scores.(0,120). RESULTS: According to the International Obesity Task Force obesity criteria for Asians, 57 women had abdominal obesity (WC >/= 80 cm), and 58 had WCs less than 80 cm. The two groups were comparable in demographic variables and body mass index (BMI). The women with larger WCs were more insulin-resistant than their counterparts. The metabolic risk scores were significantly higher in women with abdominal obesity than in those without it. The results from the GLM showed that WC was an independent predictor of insulin resistance and metabolic risk scores after controlling for demographic variables (0.06- and 0.29-unit increases in homeostasis model assessment for insulin resistance and metabolic risk scores per 1 cm change in WC). Moreover, BMI neither correlated with metabolic risk scores nor affected the WC effects on insulin resistance and metabolic risk scores in the GLM. CONCLUSIONS: Postmenopausal Chinese women with abdominal obesity may carry higher metabolic cardiovascular risk than those without it. It is WC, not BMI, that predicts metabolic cardiovascular risk factors in these women.     

Hormone levels and cognitive function in postmenopausal midlife women

Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.     

Relationship between urinary endogenous steroid metabolites and lower urinary tract function in postmenopausal women

To investigate the relationship between the endogenous steroid hormones and the lower urinary tract function in postmenopausal women. Thirty postmenopausal volunteer women who did not have lower urinary tract symptoms or hormone replacement therapy were enrolled in this study. Urodynamic studies included uroflowmetry, multi-channel cystometry, and urethral pressure profilometry were conducted. Gas Chromatography- Mass Spectroscopy(GC-MS) was used to measure the urinary endogenous steroid hormone metabolites. The relationship between the urinary profile of the endogenous steroids and the urodynamic parameters of these patients were investigated. The mean ages of the patients were 60.6 +/- 5.5 years, and the Body Mass Index (BMI) averaged 24.56 +/- 2.23 (kg/m2). Of the progesterone metabolites, pregnandiol was significantly related to the residual volume in the uroflowmetry and the functional urethral length parameters (R=0.98, p=0.000; R= -0.65, p=0.04). Pregnantriol was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.64, p=0.04; R=0.82, p=0.01; R=0.04, p=0.04; R=- 0.79, p=0.01). In the androgen metabolites, androstenedione, 5-AT, 11- keto Et, 11-betahydroxy Et, THS, and THE were significantly related to the residual volume in uroflowmetry (R=0.92, p=0.001; R=0.84, p=0.008; R=0.99, p=0.000; R=0.72, p=0.03; R=0.97, p=0.000; R=0.85, p=0.00). beta-THF/alpha-THF was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.76, p=0.02; R=0.67, p=0.04; R=0.74, p=0.02; R=-0.92, p=0.000). alpha-cortol was significantly related to the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=0.81, p=0.01; R=0.71, p=0.03; R=-0.87, p=0.000). Of the estrogen metabolites, estrone (E1) was significantly related to the normal desire to void (R=0.68, p=0.04) and 17beta-estradiol/estrone was also significantly related to the normal and strong desire to void (R=-0.70, p=0.03 and R=-0.74, p=0.02, respectively). The urinary progesterone and androgen metabolite concentrations were positively related to the residual volume in uroflowmetry and positively or negatively related to MUCP and FUL. However, the urinary estrone concentration was positively related to the normal desire to void and 17beta-estradiol/estrone was significantly related to the normal and strong desire to void.     

Hormone levels and cognitive function in postmenopausal midlife women

Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.     

Association between urinary incontinence and urinary tract infections, and fractures in postmenopausal women

Objective: The association between urinary disorders, such as ongoing urinary incontinence (UI), history of urinary incontinence (HIST-UI) and urinary tract infactions (UTI), and fractures in peri- and postmenopausal women was assessed in an epidemiological study. Subjects and methods: The sample consisted of 10 000 women from seven birth cohorts, born between 1900 and 1940, who were investigated regarding urinary disorders, fractures and reproductive history by means of a postal questionnaire. Results: The overall response rate was 74.6%. The respondents (n = 7459) represented 53% of the total population from the respective birth cohorts. There was a significant independent correlation between UI, HIST-UI and UTI, respectively, and fractures after the age of 30. In subjects with HIST-UI, tobacco smokers compared to non-smokers had significant more fractures in both the 1930 and 1940 birth cohorts (P < 0.01). Logistic multiple regression in the 1930 and 1940 cohorts demonstrated that age (P < 0.001), HIST-UI (P < 0.001) and tobacco smoking (P < 0.05), respectively, had an independent explanatory value for fractures. Conclusion: The prevalence of fractures increased with increasing age, in smokers compared to non-smokers and in women with a history of UI.