Determinants of the effect of estrogen on the progression of subclinical atherosclerosis: Estrogen in the Prevention of Atherosclerosis Trial

OBJECTIVE: To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness (IMT) in postmenopausal women. DESIGN: A randomized, double-blind, placebo-controlled, single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein (LDL) cholesterol levels of 3.37 mmol/L or greater (> or = 130 mg/dL). Intervention was unopposed micronized 17beta-estradiol versus placebo. Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial. RESULTS: Progression of carotid IMT was inversely related to on-trial high-density lipoprotein (HDL) cholesterol (P = 0.04) and was directly related to on-trial LDL-cholesterol (P = 0.005). Compared with placebo, women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level. In contrast, fasting glucose, insulin, and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy, but the changes were not related to carotid IMT progression. On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression, jointly explaining 30% of the treatment effect of unopposed estrogen on the progression of carotid IMT. CONCLUSION: Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol. Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism, these factors did not play a significant role in carotid IMT progression.     

Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.     

Functional Capacity of Patients in the Early Period After the Embolization of Cerebrovascular Malformations: Preliminary Findings

ABSTRACT: Research into outcomes of endovascular intervention for cerebral blood vessel malformations has previously focused on the clinical picture of the disease, death rate, comparison of surgical methods, and the most common postoperative and postbleeding complications. From the nursing standpoint, the crucial elements in assessing postoperative patients are functional outcome defining patients' ability to function in life and recognition of impairments in which patients will be dependent on the nursing staff. The aim of the study was to assess functional capacity of patients before and after the embolization of cerebral blood vessel malformations in the aspect of nursing care. The study included 38 patients after embolization of cerebral blood vessels. The assessment of their condition using the Functional Capacity Scale was performed twice: before and after the surgical procedure. The research shows that on the day of admission to hospital, patients had greatest difficulty performing hygienic activities (p < .0001), satisfying physiological needs (p < .0001), and consuming their meals (p < .004). Headache (p < .002) and poor psychological state (p < .0001) manifesting itself through mild depression constituted other serious problems. After the surgery, vast majority of patients were independent in terms of self-care (p ≤ .03). Headache occurred in the case of 21% of patients, and psychological state improved in 34% of patients, which shows that there is a major demand for care in this sphere.     

Characterization of Graphite Oxide and Reduced Graphene Oxide Obtained from Different Graphite Precursors and Oxidized by Different Methods Using Raman Spectroscopy Statistical Analysis

In this paper, various graphite oxide (GO) and reduced graphene oxide (rGO) preparation methods are analyzed. The obtained materials differed in their properties, including (among others) their oxygen contents. The chemical and structural properties of graphite, graphite oxides, and reduced graphene oxides were previously investigated using Raman spectroscopy (RS), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). In this paper, hierarchical clustering analysis (HCA) and analysis of variance (ANOVA) were used to trace the directions of changes of the selected parameters relative to a preparation method of such oxides. We showed that the oxidation methods affected the physicochemical properties of the final products. The aim of the research was the statistical analysis of the selected properties in order to use this information to design graphene oxide materials with properties relevant for specific applications (i.e., in gas sensors).     

Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

Naloxone (NLX) has the ability to shift the immune response to a Th1 profile. Therefore, the adjuvant efficacy of NLX with recombinant P. vivax apical membrane antigen‐1(rPvAMA‐1) in BALB/c mice was evaluated. Mice were immunized subcutaneously with purified rPvAMA‐1 formulated with NLX (doses of 5 mg/kg body weight) alone or in combination with IFA. A significant increase in anti‐PvAMA‐1 IgG antibody after the second boost (mean OD₄₉₀ = 2·08 and 2·17, in groups received, rPvAMA‐1/NLX and rPvAMA‐1/NLX/IFA, respectively) was detected. IgG1 and IgG2b were the predominant isotypes in all immunized mouse groups. In immunized mice with rPvAMA‐1/NLX (mean: 1036 pg/mL) and with rPvAMA‐1/NLX/IFA (mean: 1024 pg/mL), IFN‐γ was elicited in response to rPvAMA‐1 after the second boost. No detectable IL‐4 secretion was determined in all tested groups. In conclusion, the administration of NLX alone or NLX/IFA with rPvAMA‐1 in BALB/c mice, which induced mixed Th1/Th2 immune responses, was comparable with that of the same recombinant antigen with CFA/IFA adjuvant. The results indicate that NLX alone may possibly not be considered as a potent Th1 adjuvant in PvAMA‐1‐based vaccine. However, in order to modulate immune responses from mixed Th1/Th2 to strong and protective Th1 response, further study is warranted on combination of NLX with other adjuvants such as CpG motifs or MPL in proper vaccine formulation. Additionally, dose–response study is necessary to determine the effect of different doses of antigen combined with NLX (at various doses) in Balb/c mice.     

Brain-derived neurotrophic factor blood levels are decreased in schizophrenia patients and associate with rs6265 genotypes

Objectives

A growing number of studies implicate brain-derived neurotrophic factor (BDNF), an important promoter of synaptic transmission and neural plasticity, in the pathogenesis of schizophrenia. However, the existing data are controversial, that may reflect population differences between studied groups.

Design and methods

In the present study we performed a comparative analysis of BDNF plasma levels and its relation with rs6265 (G196A; Val66Met) polymorphism of BDNF gene (BDNF) in schizophrenia-affected and healthy subjects (controls) of the Armenian population. To check the influence of antipsychotics on BDNF plasma levels both medicated and non-medicated patients were involved in this study. Patients with paranoid form of schizophrenia chronically treated with typical antipsychotics (n = 103), age- and sex-matched controls (n = 105), and 25 antipsychotic-naive first-episode schizophrenia patients were involved. The levels of BDNF in the blood plasma were measured with a solid-phase enzyme-linked immunosorbent assay.

Results

Decreased plasma levels of BDNF in both medicated and non-medicated schizophrenia patients compared to controls were observed. No significant difference in BDNF levels between medicated and non-medicated patients was detected. It was also detected that, compared to individuals homozygous for the standard allele (G/G) of rs6265, carriers of the rs6265 minor allele (A/G + A/A), which is significantly more frequent in schizophrenia patients than in controls, had decreased BDNF levels.

Conclusions

The data obtained suggested that the pathogenesis of schizophrenia is characterized by genetically predetermined decreased blood levels of BDNF. These results indicated that genetically determined alterations of neuroimmune modulators may be among the risk factors of schizophrenia and contribute to disease-specific pathologic changes in functional activity of both the neuronal synaptic plasticity and the immune system.     

Cognition,mood, and physiological concentrations of sex hormones in the early and late postmenopause

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (<6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.Nuclear and nonnuclear receptors for estrogens, androgens, and progesterone are widely distributed in the brain and expressed within discrete neural populations (1–5), and sex steroids may influence brain function through other mechanisms. Variations in the hormonal milieu after menopause have the potential to affect cognitive function and mood as well as physiological processes linked to cognitive aging and late-life disorders, such as Alzheimer’s disease (6, 7). A number of studies have examined associations between serum concentrations of sex steroids and cognition after menopause. Most have focused on 17β-estradiol (E2) (8), which is produced cyclically by the ovaries in women of reproductive age. After menopause, the depletion of ovarian follicles leads to permanent reductions in circulating levels of E2 as well as estrone (E1) and progesterone (P4). Findings related to cognition are inconsistent because of, in part, limited measures of cognitive abilities, measurement of only a single sex steroid, and restricted age range. Age is potentially quite important, because some hormonal effects on cognitive outcomes are proposed to vary by age or timing in relation to the final menstrual period (9–12). The timing, or critical window, hypothesis is best developed with regard to exogenous E2; no research has examined this hypothesis in relation to endogenous hormone concentrations.The ongoing Early versus Late Intervention Trial with Estradiol (ELITE) targets two groups of women: women in early postmenopause and women in late postmenopause (Protocol Plan). The randomized interventions are oral E2 or placebo, and the goal is to assess whether time since menopause (as represented by postmenopause group) modifies the effect of E2 therapy on specified health outcomes, including cognitive change (ELITE-Cog). This large trial provides the additional opportunity to test in a well-characterized cohort of postmenopausal women the hypothesis that the relation of endogenous E2 levels to cognitive skills differs by temporal proximity to menopause and assess other hormone associations with cognition and mood.In younger women, verbal episodic memory is reported to be sensitive to estrogen effects (13, 14), and verbal memory impairment is potentially important, given its association with Alzheimer’s disease risk (15). Episodic memory depends on integrity of the hippocampus and adjacent medial temporal lobe structures (16), and studies in rodents document robust effects of E2 on hippocampal synaptic plasticity, hippocampal long-term potentiation, and hippocampal-mediated cognitive behaviors (17, 18).Here, we report—for early and late postmenopausal women not using hormone therapy—prerandomization associations between verbal memory and other cognitive measures and serum concentrations of E2, E1, P4, and testosterone (T) as well as sex hormone binding globulin (SHBG). At the same time, we also examined the relation between serum hormone concentrations and mood or possible depression. Our primary hypothesis was that the association of E2 levels with verbal episodic memory would differ between postmenopause strata, with higher concentrations associated with better memory performance in the early group but not the late group.