Development Of Disease In Women Research Articles

Residential proximity to agricultural pesticide use and cardiovascular disease risk factors among adult Latina women in California's Salinas Valley.

Cardiovascular disease is a leading cause of death worldwide. There is limited evidence that exposure to current-use pesticides may contribute to cardiovascular disease risk. We examined the association between residential proximity to the application of agricultural pesticides and cardiovascular risk factors among 484 adult women in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a cohort based in an agricultural region of California. Outcome assessment was completed between 2010 and 2013. Using participant residential addresses and California's Pesticide Use Reporting database, we estimated agricultural pesticide use within one km of residences during the 2-year period preceding outcome assessment. We used Bayesian Hierarchical Modeling to evaluate associations between exposure to 14 agricultural pesticides and continuous measures of waist circumference, body mass index, and blood pressure. Each 10-fold increase in paraquat application around homes was associated with increased diastolic blood pressure (β=2.60 mm Hg, 95% Credible Interval (CrI): 0.27-4.89) and each 10-fold increase in glyphosate application was associated with increased pulse pressure (β=2.26 mm Hg, 95% CrI: 0.09-4.41). No meaningful associations were observed for the other pesticides examined. Our results suggest that paraquat and glyphosate pesticides may affect cardiovascular disease development in women with chronic environmental exposure.

Lifestyle and the hypertensive disorders of pregnancy in nulliparous women in the United States: a secondary data analysis of the nuMom2b

BackgroundHypertensive disorders of pregnancy are a leading cause of maternal and fetal morbidity and mortality and a significant risk factor for future cardiovascular disease development in women. This study aimed to explore lifestyle wellness-related variables and how they impact the risk of hypertension in pregnancy.MethodsThis is a secondary analysis of data from the prospective cohort study Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b). Data was collected through questionnaires, clinical evaluations, and medical records review at 8 academic medical centers in the United States. Four study visits were scheduled throughout the participant’s pregnancy (visits one–four): 60–136, 160–216, and 220–296 weeks gestation and birth. A series of statistical modeling and logistical regression were performed using 15 lifestyle variables related to sleep, nutrition, resilience, illness avoidance, and physical activity were selected as predictor variables with an outcome variable of hypertension.ResultsOf 9289 nulliparous participants considered for inclusion in our analyses, 1464 had any HDP during study participation, and 554 participants had complete data available for the study and were included in our final sample. Results were statistically significant at a level of p < 0.05. Of the sleep variables, snoring at visit 1 increased the risk of hypertension in pregnancy. Greater vegetable consumption reported at visit one decreased risks of hypertension in pregnancy. Physical activity reported at visit two and visit three were associated with decreased risk of hypertension. Physical activity reported at visit three combined with more hours of sleep each night, or through napping habit reported at visit one decreased hypertension risk. Increased fish oil consumption combined with more hours of sleep at visit one increased odds of hypertension in pregnancy.ConclusionsOur results support that lifestyle wellness-related variables relating to sleep, physical activity and nutrition affect hypertension in pregnancy. The studied variables and others should be considered in future research and intervention development to reduce hypertension in pregnancy and improve maternal wellness.

Glycemic index and heart disease , ,

A diet high in carbohydrates with high glycemic indexes (GI) and glycemic load were linked to risk of coronary heart disease development in women in a large prospective study. Two cross-sectional studies showed that low-GI diets are associated with high HDL-cholesterol concentrations, especially in women. In a tightly controlled study of patients with type 2 diabetes, serum total cholesterol, LDL cholesterol, and apolipoprotein B concentrations fell more significantly after a low-GI diet than after a high-GI diet. In the same study, plasminogen activator inhibitor-1 concentrations were reduced by 58% after the low-GI diet. Insulin-stimulated glucose uptake by adipocytes was significantly higher in patients undergoing coronary artery bypass graft surgery after 4 wk of consuming a low-GI diet than after consuming a high-GI diet. The effects of low-GI diets may be mediated by changes in postprandial fatty acid concentrations or by hormonal signals from adipocytes, but a possible association of low-GI diets with some other dietary factor such as chromium must not be excluded. Proof of the clinical value of low-GI diets awaits prospective trials, which should include short-term observations covering periods of metabolic stress induced by surgery as well as long-term trials with clinical endpoints.

Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS

Background and aimsElevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change. MethodsWe used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS). ResultsThe probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women. ConclusionsSimilar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

Psychological factors and atherosclerotic cardiovascular disease development in women: A narrative review

Cardiovascular disease (CVD) is the leading cause of mortality, with rising evidence of differences between women and men, worldwide. Data from the literature indicate the presence of gender-specific differences both in biological responses and in lifestyle behaviors to psychological stress. There is evidence suggesting that women experience higher levels of psychological problems, such as anxiety and depression. The connection between psychological factors and CVD can be explained by behavioral and biological risk factors, as well as underlying mechanisms, such as the sympathetic nervous system overactivity and the hypothalamic-pituitary-adrenal function impairment. Moreover, some psychosocial factors may place women at particular risk of CVDs. Given these hypotheses, the present review summarizes the existing knowledge about psychological factors and CVD connection in women, highlighting the sex differences.

Результати вивчення факторів ризику розвитку цереброваскулярних хвороб у жінок міста Києва

Cerebrovascular diseases in the leading countries of the world occupy the second place among all the causes of death and become the main cause of disability of the population in working age. Preventive measures for the development of cerebrovascular disease are directed at eliminating or reducing the impact of risk factors of disease. The objective: to define risk factors for the development of cerebrovascular disease in women under the age of 40 years residing in Kyiv. Materials and methods. 420 women under the age of 40 years residing in Kyiv were questioned with the use of sociological method. A universal adapted questionnaire was used to conduct the research. The results were processed with the application of statistical method and the method of structural-and-logical analysis. Results. It has been defined that up to 32.0% of women have risk factors for developing cerebrovascular diseases of medical nature, up to 69.0% – of hereditary nature, up to 69.0% – of those associated with lifestyle and 32.0% – of socio-economic nature. Among women who did not have a diagnosis of cerebrovascular disease 24.6±2.2% of the polled have hypertensive disease. At the same time, 21.9±2.1% of them do not follow the doctor’s recommendations on healthy lifestyle and 13.8±1.7% of them do not follow the recommendations of the doctor on taking medications. Among women who have been diagnosed with cerebrovascular disease 31.7±2.3% of the polled have hypertensive disease. At the same time, 48.7±2.5% of them do not follow the doctor’s recommendations on healthy lifestyle and 38.5±2.4% do not follow the recommendations of the doctor regarding the intake of medicines. All that leads to high risks of developing a cerebral stroke. Conclusions. A high level of risk factors for cerebrovascular disease was defined among women aged up to 40 years of life residing in Kyiv that requires the introduction of comprehensive information and sanitary preventive programs. Keywords: Kyiv, women, cerebrovascular diseases, risk factors.

Major risk factors for chronic venous disease development in women: is childbirth among them?

ABSTRACTMany studies have reported that Chronic venous disease (CVD) occurs more in females than males, due to pregnancy. The study was conducted over the period 2014–2015 at the Dermatovenereological clinic, Novi Sad, Serbia. We performed a cross-sectional study of 554 women. According to Clinical-Etiology-Anatomy-Pathophysiology (CEAP) staging, the sample was divided into three groups: Mild CVD (classes 1–3 by CEAP) – n = 72; Severe CVD (classes 4–6 by CEAP) – n = 122 and a Control (no CVD) – n = 360 patients. The age range of participants was 18 to 93 years (average 54.92 years). Most important CVD risk factors were examined in detail. Out of 554 examinees, 22.03% had severe CVD, and 12.99% had mild CVD. Bivariate analyses showed a significantly higher proportion of women who had deliveries in the severe CVD and mild CVD groups, compared with the control group. Other significantly related factors were older age, family history of varicose veins, standing job position and hypertension. After performing multiple logistic regression analysis, older age, standing job position and family history of varicose veins remained significant, while childbirth lost its significance. Our results suggest that childbirths are not associated with the occurrence of CVD

Comparative assessment of primary and paraneoplastic gout in lung cancer

Introduction. Lung cancer (LС) is the most common cause of the so-called paraneoplastic syndrome (PNPS) development, caused by the complex immunoinflammatory, degenerative and vascular distant changes. The risk of LC development is increased in patients with gout which proves the connection between violations of purine metabolism and carcinogenesis. Paraneoplastic (neoplastic) gout is one of the relatively frequent manifestations of LC, but such a relationship of the diseases requires further study. The objective of the study: to compare the clinical and laboratory course of primary gout and disease in the LC patients compared with the tumor process clinical course in the other signs of PNPS presence and to identify risk factors. Materials and methods. 113 patients with gout (97 men and 16 women aged 33 to 79 years) were observed. They were divided into two groups: the first group consisted of 54 patients with primary gout and the second group consisted of 59 patients with paraneoplastic variant of LC. Whereas in the 1st group the ratio of men and women was 26:1, in the 2nd – only 3: 1, and the average age was 50 and 59 years, respectively. The clinical course of gout and tumor process in the 2nd (main) group was compared with that in 199 LC patients with PNPS (comparison group), which was diagnosed in 15.5 % of LC observations. Purine metabolism was assessed by blood levels of uric acid and oxypurinol, their renal clearance, serum activity of xanthine oxidase, xanthine deaminase, adenosine deaminase, and 5-nucleotidase. Results. Paraneoplastic (neoplastic) gout develops in 3.5 % of the LC patients and in 22.9 % of those with PNPS. It differs from the primary (idiopathic) gout by the greater frequency of the disease development in women, the hand joints involvement and the metabolic type of hyperuricemia, but less often observed urolithiasis, peripheral tophi, chronic form of arthritis and the absence of renal type of purine metabolism impairment. Patients with tumorous gout differ from other LC patients with PNPS by the absence of bilateral and median lobe localization of the lung process, but relatively frequent occurrence of Pancoast tumor, high levels of uric acid and xanthine oxidase in the blood. The development of paraneoplastic gout depends on the clinical course of the LC (tumor invasion into the thoracic wall and pericardium, the number of distant organs metastasis) and the power of chemotherapy, the use of alkylating antineoplastic agents and alkaloids. Treatment-associated myelodepression, radiation pneumofibrosis and acute thrombophlebitis development depends on paraneoplastic gout. The presence of gout does not worsen the survival of LC patients with PNPS. LC patients with hyperuricemia (> 420 μmol / l in men and > 360 μmol / L in women) should be prescribed with xanthine oxidase inhibitor - allopurinol in the complex of therapeutic measures. Conclusions . Paraneoplastic gout is a frequent PNPS manifestation in LC, its course has peculiarities compared with the primary gout and is closely related to the tumor process character and the power of chemotherapy, it can determine the complications development in the course of therapeutic interventions. The data presented in the study require further comparative analysis of the other signs of PNPS, comparison of tumor and idiopathic variants of the musculoskeletal system lesion, cutaneous vasculitis and autoimmune systemic syndromes, which might assist in developing of the additional prognostic criteria for the tumor process clinical course, increasing the efficiency of therapy and its control quality.

Abstract 656: Histological and 3D morphological evaluation of mammary cancers and primary cells from genetically engineered mice with only one copy of Brca1 disrupted in combination with Trp53 haploinsufficiency

Abstract Background: Previously established genetically engineered mouse (GEM) models with spontaneous mammary cancer development have both Brca1 alleles disrupted withTrp53 haploinsufficiency (Brca1f11/f11/MMTV-Cre/Trp53+/-). Cell culture plates with nanoimprinted scaffolds (SCIVAX Life Sciences, Inc) purportedly increase concordance between in vitro/in vivo results but reports are limited to human cancer cell lines. Here we characterized hyperplasia and cancer development in Brca1f11/WT11/MMTV-Cre/Trp53+/- mice and established conditions for 3D culture of primary mammary epithelial cells (MEC) using the imprinted plates. Methods: Time-course of mammary hyperplasia and cancer development was defined in female Brca1f11/WT11/MMTV-Cre/Trp53+/- (n = 23) and Brca1f11/f11/MMTV-Cre/Trp53+/- (n = 13) mice euthanized at age 6 and 12 months (m) or when largest tumor reached 1 cm3. Mammary tissue was taken at necropsy for histology (age 6/12m) and primary MEC culture (age 6m) using EpiCult-B (StemCell Technologies) on nanoimprinted scaffold plates. Primary normal (wild-type, n = 2) and precancerous MEC (Brca1f11/f11/MMTV-Cre/Trp53+/-, n = 2; Brca1f11/WT11/MMTV-Cre/Trp53+/-; n = 2) were cultured. Optimal conditions for spheroid growth were established by comparison of spheroid formation from thoracic vs. inguinal mammary glands with different numbers of plated cells and percentage FBS after 7 days culture. Endpoints included sphere number, size and presence/absence of concurrent monolayer growth. Spheres were harvested for histological examination. Hematoxylin and eosin (H&amp;E) stained sections were read for histology and immunohistochemistry (IHC) for Pan-Cytokeratin (Pan-CK) and Ki67 performed for in vivo/in vitro comparisons. Results: Forty-two percent of Brca1f11/WT11/MMTV-Cre/Trp53+/- mice developed mammary cancer by age 12m compared to 100% of Brca1f11/f11/MMTV-Cre/Trp53+/- mice. Cancers appeared by age 6m only in Brca1f11/f11/MMTV-Cre/Trp53+/- mice. Mammary cancers in both models were carcinomas of either adeno, anaplastic or sarcomatoid types. All were Pan-CK positive and proliferation rates were similar between the two genetic models. Spheres developed from all primary MEC attempted. Optimal conditions for sphere formation were plating of 10,000 cells obtained from inguinal mammary gland per well in 5% FBS EpiCult-B. Conclusions: Here we report development of spontaneous mammary cancers in Brca1 insufficiency mice that are more representative of disease development in women who carry only one allele with a BRCA1-mutation and established conditions for use of cell culture plates with nanoimprinted scaffolds for 3D culture of normal and preneoplastic primary murine mammary epithelial cells. Supported by NCI, NIH 1RO1CA112176 (PAF). Citation Format: Sahar J. Alothman, Weisheng Wang, Bhaskar V. Kallakury, Priscilla Furth. Histological and 3D morphological evaluation of mammary cancers and primary cells from genetically engineered mice with only one copy of Brca1 disrupted in combination with Trp53 haploinsufficiency. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 656.

Effects of the lifestyle habits in breast cancer transcriptional regulation.

Through research carried out in the last 25 years about the breast cancer etiology, it has been possible to estimate that less than 10 % of patients who are diagnosed with the condition are carriers of some germline or somatic mutation. The clinical reports of breast cancer patients with healthy twins and the development of disease in women without high penetrance mutations detected, warn the participation more factors in the transformation process. The high incidence of mammary adenocarcinoma in the modern woman and the urgent need for new methods of prevention and early detection have demanded more information about the role that environment and lifestyle have on the transformation of mammary gland epithelial cells. Obesity, alcoholism and smoking are factors that have shown a close correlation with the risk of developing breast cancer. And although these conditions affect different cell regulation levels, the study of its effects in the mechanisms of transcriptional and epigenetic regulation is considered critical for a better understanding of the loss of identity of epithelial cells during carcinogenesis of this tissue. The main objective of this review was to establish the importance of changes occurring to transcriptional level in the mammary gland as a consequence of acute or chronic exposure to harmful products such as obesity-causing foods, ethanol and cigarette smoke components. At analyze the main studies related to topic, it has concluded that the understanding of effects caused by the lifestyle factors in performance of the transcriptional mechanisms that determine gene expression of the mammary gland epithelial cells, may help explain the development of this disease in women without genetic propensity and different phenotypic manifestations of this cancer type.

Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes.

In the vast majority of cardiovascular diseases (CVDs), there are well-described differences between women and men in epidemiology, pathophysiology, clinical manifestations, effects of therapy, and outcomes.1–3 These differences arise on one hand from biological differences among women and men, which are called sex differences. They are due to differences in gene expression from the sex chromosomes and subsequent differences in sexual hormones leading to differences in gene expression and function in the CV system, e.g. in vascular function and NO signalling, in myocardial remodelling under stress, or metabolism of drugs by sex-specific cytochrome expression. Sex differences are frequently reproducible in animal models. In contrast, gender differences are unique to the human. They arise from sociocultural processes, such as different behaviours of women and men; exposure to specific influences of the environment; different forms of nutrition, lifestyle, or stress; or attitudes towards treatments and prevention. These are equally important for CVDs. Both sex and gender (S&G) influence human development ( Figure 1 ). Since it is almost impossible to distinguish properly between effects of S&G in the medical field, the EUGenMed writing group decided to discuss both of them together and to use the term S&G for all medical relevant differences between women and men in the present review. Figure 1 Interaction between sex and gender during lifetime: societal conditions (upper) as well as biological facts (lower) affect germ cells, the newborn, the adult, and the development of disease in women and men. In its current research framework programme ‘Horizon 2020’, the EU calls for the inclusion of the gender dimension into biomedical research since ‘it helps improve the scientific quality …

A role of oestrogen in aggravating SLE-like syndrome in C4-deficient mice.

As one of the epigenetic factors, oestrogen is considered to be a predisposing factor that is associated with a susceptibility to autoimmune disease development in women including systemic lupus erythematosus (SLE). Here, we proposed that oestrogen is also imparted in a post-lupus symptomatic enhancement as studied in the C4-deficient (C4-/-) mice model known to develop SLE-like symptoms. Fifty-six C4 knockout mice were ovariectomised (OVX) to eliminate the effect of endogenous feminine hormones followed by 17-β oestradiol (E2) administration in both dose- and time-dependent manners. Histopathological features of kidneys and spleens were studied by histological and immunofluorescent staining. The relative expression levels of IgG and IgM were measured densitometrically on their immunoreactive bands and the level of IgG-anti-double stranded (ds) DNA was measured by ELISA. E2-treated mice displayed a gradual increase in immune complex deposition (both IgG and IgM) in glomeruli and proximal convoluted tubules. An increased reactivity of autoantibodies against dsDNA correlated with increasing doses and longer exposure to E2 treatments. In addition, enlargement of the spleen (splenomegaly) was also observed in E2-treated mice. Our results support the hypothesis that oestrogen aggravates severity of the SLE-like symptoms in C4-deficient mice.

Abstract 2286: Spontaneous mammary cancer development in genetically engineered mice with only one copy of Brca1 disrupted in combination with Trp53 haploinsufficiency

Abstract Background: Women carrying one mutated copy of BRCA1 are disposed to developing breast cancer. BRCA1-mutation-related cancers often harbor TRP53 mutations. Previously established genetically engineered mouse (GEM) models with spontaneous mammary cancer development have both copies of Brca1 disrupted in combination with Trp53 haploinsufficiency. Here we characterized cancer development in GEM with only one copy of Brca1 disrupted in mammary epithelial cells using Cre-Lox technology in combination with germ-line Trp53 haploinsufficiency. Methods: From our Brca1f11fT11/MMTV-Cre/Trp53+/− breeding program we noted mammary cancer development in female Brca1f11/WT11/MMTV-Cre/Trp53+/− mice. The time-course of mammary hyperplasia and cancer development was characterized in these mice. Mice were euthanized at age 6 months (n = 9) or when the largest tumor reached 1 cm3 or at 12 months if no tumor developed (n = 12). Cancers were resected, inguinal mammary glands processed for histology and thoracic mammary glands flash frozen or processed for primary cell culture. Hyperplastic alveolar nodules (HANs) and branching patterns were detected using inguinal mammary gland whole mounts. Histology was read on H&amp;E stained slides and immunohistochemistry (IHC) performed for ERα, PGR and HER2 on cancer specimens. Results: Thirty-three percent of the mice developed palpable mammary tumors by age 12 months. Forty-four percent of the mice exhibited HANs at age 6 months and 56% at age 12 months. One mouse developed a female reproductive tract cancer. Three mice developed single palpable mammary adenocarcinomas. One mouse developed two cancers, one palpable spindloid and one non-palpable anaplastic carcinoma. Two adenocarcinomas have completed IHC studies and are ER/PGR/HER2 negative. Multilayered ductal hyperplasia was present only in 12-month-old mice (89%). Two-layered lobular-type hyperplasia was found in 33% of 6-month-old and 100% of 12-month-old mice. Primary cell cultures were established from both cancers attempted. Conclusions: Here we report development of a Brca1 insufficiency mouse model more representative of disease development in women who carry only one allele with a BRCA1-mutation. Similar to models with both Brca1 copies disrupted, Trp53 haploinsufficiency was required for cancer progression. The spectrum of mammary cancer histology was similar to that previously reported when both Brca1 alleles were disrupted. This model represents a tool for investigation of preventive strategies in the face of Brca1 and Trp53 haploinsufficiency and study of possible interactions between this genetic background and genetic and environmental factors that may promote cancer development. Citation Format: Sahar Alothman, Svenja Groeneveld, Ahmad Alamri, Bhaskar Kallakury, Priscilla A. Furth. Spontaneous mammary cancer development in genetically engineered mice with only one copy of Brca1 disrupted in combination with Trp53 haploinsufficiency. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2015-2286

Abstract 659: Curcumin Ameliorates Cardiac Dysfunction in the Ovariectomized Diabetic mRen2.Lewis Rat by Inhibiting Renin Angiotensin System

Diabetes is a well-recognized independent risk factor for the development of cardiovascular disease in women. Moreover, hypertension and loss of estrogen are additional complicating factors to diabetic heart disease. Curcumin, an active compound in the widely used spice turmeric, exerts therapeutic potential in diabetes mellitus; however, the underlying mechanisms are not fully understood. The present study was designed to investigate the potential of curcumin to ameliorate early cardiac dysfunction in insulin- and estrogen-depleted hypertensive mRen2.Lewis rats by altering the renin angiotensin system as one of the major contributors to the development of diabetic cardiomyopathy. Ovariectomy (OVX) was performed at 10 weeks of age and diabetes (D) subsequently induced at 11 weeks with streptozotocin (65 mg/kg). Only animals that showed hyperglycemia greater than 200 mg/dl were considered diabetic. OVX-D rats were given curcumin at a dose of 200 mg/kg/day (OVX-D &amp; CUR; n=7) or vehicle (OVX-D &amp; VEH; n=8) by gastric gavage starting two days after streptozotocin injection. Intact non-diabetic mRen2.Lewis rats served as controls (C; n=9). After four weeks, concomitant insulin and estrogen depletion induced systolic and diastolic dysfunction, indicated by decreased fractional shortening (FS; C: 60.0 ± 1.5 vs OVX-D &amp; VEH: 43.7 ± 2.2 %; p&lt;0.05) and Tissue Doppler velocity at the level of mitral annulus (e’; C: 75.0 ± 3.4 vs OVX-D &amp; VEH: 58.6 ± 5.6 mm/s; p&lt;0.05) that was associated with increased blood pressure (BP; C: 131 ± 3 vs 179 ± 2 mmHg; p&lt;0.05), elevated plasma angiotensin II (Ang II; C: 20 ± 4 vs 32 ± 2 pg/ml; p&lt;0.05), and cardiac expression of Ang II type 1 receptor (AT1; C: 100 ± 12 vs 206 ± 33 %; p&lt;0.05). Curcumin treatment did not affect BP (164 ± 6 mmHg; p&gt;0.05) but attenuated cardiac systolic (FS: 53 ± 3%, p&lt;0.05) and diastolic dysfunction (e’: 74 ± 3 mm/s; p&lt;0.05) while reducing AT1 expression (120 ± 12 %; p&lt;0.05) in the diabetic heart. It also decreased plasma Ang II to the levels not different from the controls (21.6 ± 3 pg/ml; p&gt;0.05). In conclusion, the present study suggests that curcumin treatment, in a blood pressure independent manner, may ameliorate early cardiac dysfunction in estrogen- and insulin-depleted mRen2.Lewis rats by reducing Ang II signaling pathway.

Cuprizone induces similar demyelination in male and female C57BL/6 mice and results in disruption of the estrous cycle

Multiple sclerosis is a demyelinating neurological disease that is influenced by gender, primarily reflected in greater susceptibility to disease development in women than in men. Cuprizone intoxication, an animal model that is used to study demyelination and remyelination, has been extensively characterized in male C57BL/6 mice. Here, we have undertaken a comprehensive characterization of the morphological and cellular processes that occur in female C57BL/6J mice during cuprizone-induced demyelination and subsequent remyelination and compared them with age-matched male mice. We find that the pattern of demyelination and remyelination is similar between genders and that there is little or no difference in the loss or repopulation of mature oligodendrocytes or accumulation of reactive glia. Furthermore, examination of alphaERKO and betaERKO mice suggests that estrogen receptors do not affect the outcome for demyelination or remyelination. Interestingly, we found that cuprizone treatment disrupts estrous cyclicity in female mice, possibly interfering with potential hormone influences on demyelination and remyelination. Therefore, cuprizone-induced demyelination in C57BL/6J mice may have limitations as a model for the study of sex differences.

Raised serum thyrotrophin in women with peripheral arterial disease.

Women with symptomatic peripheral arterial disease were screened for impaired thyroid function using a sensitive immunoradiometric assay for thyrotrophin (TSH). The arterial disease in the aortotibial segment was documented by an abnormal brachial/ankle pressure index in 80 patients. An age-matched control group of elderly women (n = 30) with a normal pressure index was established. In the control group the mean serum TSH was 1.6 +/- 1.1 milliunits/l, median 1.5 milliunits/l and this established a normal range of 0.2-3.9 milliunits/l. Seven patients (8.8 per cent) were already receiving treatment for myxoedema. In the remaining patients, the overall distribution of serum TSH was skewed to higher levels; the mean was 3.7 milliunits/l, median 2.4 milliunits/l, P less than 0.001 compared with controls and 15 (19 per cent) had a serum TSH greater than 4 milliunits/l, compared with only one (3.3 per cent) of the controls. Therefore 22 patients (28 per cent) had myxoedema or a raised serum TSH. For all subjects with a normal TSH, there was a positive correlation of serum TSH with serum cholesterol, r = 0.68, P less than 0.001. For patients with a raised TSH, there was a continuing, but non-linear, increase of serum cholesterol with TSH. These results suggest that a raised serum TSH may be one of the risk factors for the development of peripheral arterial disease in women, possibly by increasing cholesterol levels.

Glycemic index and heart disease , ,

A diet high in carbohydrates with high glycemic indexes (GI) and glycemic load were linked to risk of coronary heart disease development in women in a large prospective study. Two cross-sectional studies showed that low-GI diets are associated with high HDL-cholesterol concentrations, especially in women. In a tightly controlled study of patients with type 2 diabetes, serum total cholesterol, LDL cholesterol, and apolipoprotein B concentrations fell more significantly after a low-GI diet than after a high-GI diet. In the same study, plasminogen activator inhibitor-1 concentrations were reduced by 58% after the low-GI diet. Insulin-stimulated glucose uptake by adipocytes was significantly higher in patients undergoing coronary artery bypass graft surgery after 4 wk of consuming a low-GI diet than after consuming a high-GI diet. The effects of low-GI diets may be mediated by changes in postprandial fatty acid concentrations or by hormonal signals from adipocytes, but a possible association of low-GI diets with some other dietary factor such as chromium must not be excluded. Proof of the clinical value of low-GI diets awaits prospective trials, which should include short-term observations covering periods of metabolic stress induced by surgery as well as long-term trials with clinical endpoints.

Risk factors in the development of coronary heart disease in women

Risk factors in the development of coronary heart disease in women

Pregnancy related changes in some cardiovascular risk factors

Certain risk factors for development of ischemic heart disease are influenced by pregnancy related changes of female sex hormone levels. As a part of the cardiovascular risk factor studies in Finnmark county, Norway, 1974-75 and 1977-78, cross-sectional clinical and non-fasting laboratory data were obtained prior to conception (n = 463), during pregnancy (n = 335), and following delivery (n = 451). Compared with prepregnancy values, total cholesterol was on average 7% lower in the first trimester (p < 0.001), and 30% higher at the end of gestation (p < 0.001). High density lipoprotein cholesterol was 38% higher at mid-pregnancy (p < 0.001), but only 14% higher in the last trimester (p < 0.01). Serum triglycerides were 18% lower in the first (p < 0.001) and 123% higher in the third trimester (p < 0.001). Blood glucose was 5% lower than baseline in mid-pregnancy (p < 0.001). Except for the second trimester, when only 27% of women smoked, more than 40% of the women examined were smokers. Postpartum values were similar to prepregnancy levels, except serum triglycerides which remained 35% higher (p < 0.001) and blood glucose (p < 0.05). The major serum lipid fractions, and blood glucose, were significantly different during pregnancy and postpartum, which may influence the risk of cardiovascular disease development in women.

Estrogen and coronary heart disease in women

We review herein the evidence that estrogen is protective against the development of cardiovascular disease in women. To our knowledge, no studies in women have looked at endogenous estrogen levels as predictors of cardiovascular disease. Studies of surrogate measures of endogenous estrogen such as parity, age at menarche, and age at menopause have provided inconsistent results. Current use of oral contraceptives increases risk in older women who smoke cigarettes, but most studies of past use show no increased risk. Most, but not all, studies of hormone replacement therapy in postmenopausal women show around a 50% reduction in risk of a coronary event in women using unopposed oral estrogen. These important observations need to be confirmed in a double-blind, randomized clinical trial, since the protection is biologically plausible and the magnitude of the benefit would be quite large if selection factors can be excluded. ( JAMA . 1991;265:1861-1867)