Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day

Most atypical antipsychotic drugs (APDs), e. g. risperidone (RIS), produce more extensive blockade of brain serotonin (5-HT)(2A) than dopamine (DA) D-2 receptors. This distinguishes them from typical APDs, e.g. haloperidol (HAL). Our objective was to test the hypothesis that augmentation of low doses of RIS or HAL (2 mg/day) with pimavanserin (PIM), a selective 5-HT2A inverse agonist, to enhance 5-HT2A receptor blockade, can achieve efficacy comparable to RIS, 6 mg/day, but with lesser side effects. In a multi-center, randomized, double-blind, 6 week trial, 423 patients with chronic schizophrenia experiencing a recent exacerbation of psychotic symptoms were randomized to RIS2mg + placebo (RIS2PBO), RIS2mg + PIM20mg (RIS2PIM), RIS6mg + PBO (RIS6PBO), HAL2mg + PBO (HAL2PBO), or HAL2mg + PIM20mg (HAL2PIM). Improvement in psychopathology was measured by the PANSS and CGI-S. The reduction in PANSS Total Score with RIS2PIM at endpoint was significantly greater than RIS2PBO: -23.0 vs. -16.3 (p = 0.007), and not significantly different from the RIS6PBO group: -23.2 points. The percentage of patients with >= 20% improvement at day 15 in the RIS2PIM group was 62.3%, significantly greater than the RIS6PBO (42.1%; p = 0.01) and the RIS2PBO groups (37.7%; p = 0.002). Weight gain and hyperprolactinemia were greater in the RIS6PBO group than the RIS2PIM group but there was no difference in extrapyramidal side effects (EPS). HAL2PBO and HAL2PIM were not significantly different from each other in efficacy but HAL2PIM had less EPS at end point. Both HAL groups and RIS6PBO showed equal improvement in psychopathology at endpoint, indicating HAL 2 mg/day is effective to treat an acute exacerbation in chronic schizophrenia patients. In conclusion, a sub-effective RIS dose combined with PIM to enhance 5-HT2A receptor blockade provided faster onset of action, and at endpoint, equal efficacy and better safety, compared to standard dose RIS. These results support the conclusion that 5-HT2A receptor blockade is a key component of the action of some atypical APDs and can reduce EPS due to a typical APD. (C) 2012 Elsevier B.V. All rights reserved.

HEMATOLOGICAL ANALYSIS OF Micropogonias furnieri, DESMAREST, 1823, SCIANIDAE, FROM TWO ESTUARIES OF BAIXADA SANTISTA, SAO PAULO, BRAZIL

Hematological alterations in fish are considered a useful tool to evaluate pathological processes resulting from the exposure to environmental pollutants. The whitemouth croaker Micropogonias furnieri is a common species in estuarine areas and potentially exposed to many contaminants. In the present study, the hematological characteristics of fish collected at two sites in Baixada Santista (Santos Estuarine System - SES, a polluted site; and the Estuary of Itanhaem River - EIR, unpolluted site) del was analysed. The following blood descriptors were analyzed: number of Erythrocytes (Er), Hematocrit (Ht), Hemoglobin (Hb), Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin concentration (MCHC). Fish from SES exhibited significant lower levels of Ht and increase on MCHC and Hb. Such differences are likely related to the different contamination levels found in these estuaries.

Medial amygdaloid nucleus 5-HT2C receptors are involved in the hypophagic effect caused by zimelidine in rats

The medial amygdaloid nucleus (MeA) is a sub-region of the amygdaloid complex that has been described as participating in food intake regulation. Serotonin has been known to play an important role in appetite and food intake regulation. Moreover, serotonin 5-HT2C and 5-HT1A receptors appear to be critical in food intake regulation. We investigated the role of the serotoninergic system in the MeA on feeding behavior regulation in rats. The current study examined the effects on feeding behavior regulation of the serotonin reuptake inhibitor, zimelidine, administered directly into the MeA or given systemically, and the serotoninergic receptors mediating its effect. Our results showed that microinjection of zimelidine (0.2, 2 and 20 nmol/100 nL) into the MeA evoked dose dependent hypophagic effects in fasted rats. The selective 5-HT1A receptor antagonist WAY-100635 (18.5 nmol/100 nL) or the 5-HT1B receptor antagonist SB-216641 microinjected bilaterally into the MeA did not change the hypophagic effect evoked by local MeA zimelidine treatment. However, microinjection of the selective 5-HT2C receptor antagonist SB-242084 (10 nmol/100 nL) was able to block the hypophagic effect of zimelidine. Moreover, microinjection of the 5-HT2C receptor antagonist SB-242084 into the MeA also blocked the hypophagic effect caused by zimelidine administered systemically. These results suggest that MeA 5-HT2C receptors modulate the hypophagic effect caused by local MeA administration as well as by systemic zimelidine administration. Furthermore, 5-HT2C into the MeA could be a potential target for systemic administration of zimelidine. (C) 2012 Elsevier Ltd. All rights reserved.

DIFFERENTIAL INVOLVEMENT OF DORSAL RAPHE SUBNUCLEI IN THE REGULATION OF ANXIETY- AND PANIC-RELATED DEFENSIVE BEHAVIORS

A wealth of evidence indicates that the dorsal raphe nucleus (DR) is not a homogenous structure, but an aggregate of distinctive populations of neurons that may differ anatomically, neurochemically and functionally. Other findings suggest that serotonergic neurons within the mid-caudal and caudal part of the DR are involved in anxiety processing while those within the lateral wings (IwDR) and ventrolateral periaqueductal gray (vIPAG) are responsive to panic-evoking stimuli/situations. However, no study to date has directly compared the activity of 5-HT and non-5HT neurons within different subnuclei of the DR following the expression of anxiety- and panic-related defensive responses. In the present investigation, the number of doubly immunostained cells for Fos protein and tryptophan hydroxylase, a marker of serotonergic neurons, was assessed within the rat DR, median raphe nucleus (MRN) and PAG following inhibitory avoidance and escape performance in the elevated T-maze, behaviors associated with anxiety and panic, respectively. Inhibitory avoidance, but not escape, significantly increased the number of Fos-expressing serotonergic neurons within the mid-caudal part of the dorsal subnucleus, caudal and interfascicular subnuclei of the DR and in the MRN. Escape, on the other hand, caused a marked increase in the activity of non-5HT cells within the IwDR, vIPAG, dorsolateral and dorsomedial columns of the PAG. These results strongly corroborate the view that different subsets of neurons in the DR are activated by anxiety- and panic-relevant stimuli/situations, with important implications for the understanding of the pathophysiology of generalized anxiety and panic disorders. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

WATER HOMEOSTASIS, FRAILTY AND COGNITIVE FUNCTION IN THE NURSING HOME

Objective: - To develop and test a practical clinical method to assess frailty in nursing homes; - To investigate the relationship between cognitive status of the elderly and the balance between water compartments of their body composition. Design and subjects: Cross-sectional study, conducted at two nursing homes in Boston-MA. Methods: Body mass and height (Ht) were evaluated to calculate BMI (body mass index, in Kg/m(2)). The cognitive decline was evaluated based on the scores obtained from the Mini-Mental State Examination (MMSE); The extracellular to total body water ratio (ECW/TBW) was calculated after the analysis of TBW from deuterium and tritium dilution and ECW from bromide dilution. Single-frequency BIA analysis data were investigated for resistance (R) and reactance (Xc), plotted in an R/Ht Xc/Ht graph (vectorial analysis-BIVA). The BIVA results of nursing home residents were compared against the data obtained from the NHANES Ill study. TBW and ECW values were compared with a group of free-living elderly volunteers. Results: The ECW/TBW was significantly higher in nursing home residents than in the free-living individuals. BIVA analysis showed significantly higher Xc/Ht values in the reference subjects. The MMSE did not present a significant correlation with ECW/TBW for either gender. Conclusion: We proposed the ECW/TBW ratio and BIVA as surrogate methods for the clinical assessment of frailty. We tested successfully both approaches with nursing home patients and free-living volunteers and compared them to a national data base. The advent of new, portable instruments will enable field tests to further validate our proposed "Frailty Factor" in future studies. We found no correlation between frailty and cognitive decline in the nursing home.

Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation

Possa SS, Charafeddine HT, Righetti RF, da Silva PA, Almeida-Reis R, Saraiva-Romanholo BM, Perini A, Prado CM, Leick-Maldonado EA, Martins MA, Tiberio ID. Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation. Am J Physiol Lung Cell Mol Physiol 303: L939-L952, 2012. First published September 21, 2012; doi:10.1152/ajplung.00034.2012.-Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E-NO) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced E-NO concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-beta, NF-kappa B, IFN-gamma, and 8-iso-prostaglandin F2 alpha contents compared with the untreated group (P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.

Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study

Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.

Central, but not basolateral, amygdala involvement in the anxiolytic-like effects of midazolam in rats in the elevated plus maze

The role of the amygdala in the mediation of fear and anxiety has been extensively investigated. However, how the amygdala functions during the organization of the anxiety-like behaviors generated in the elevated plus maze (EPM) is still under investigation. The basolateral (BLA) and the central (CeA) nuclei are the main input and output stations of the amygdala. In the present study, we ethopharmacologically analyzed the behavior of rats subjected to the EPM and the tissue content of the monoamines dopamine (DA) and serotonin (5-HT) and their metabolites in the nucleus accumbens (NAc), dorsal hippocampus (DH), and dorsal striatum (DS) of animals injected with saline or midazolam (20 and 30 nmol/0.2 mu L) into the BLA or CeA. Injections of midazolam into the CeA, but not BLA, caused clear anxiolytic-like effects in the EPM. These treatments did not cause significant changes in 5-HT or DA contents in the NAc, DH, or DS of animals tested in the EPM. The data suggest that the anxiolytic-like effects of midazolam in the EPM also appear to rely on GABA-benzodiazepine mechanisms in the CeA, but not BLA, and do not appear to depend on 5-HT and DA mechanisms prevalent in limbic structures.

In vitro evaluation of combined hyperthermia and photodynamic effects using magnetoliposomes loaded with cucurbit[7]uril zinc phthalocyanine complex on melanoma

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTI method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p > 0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma. (C) 2012 Elsevier B.V. All rights reserved.

Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration

A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT(2C)Rs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT(2C)Rs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT(2C)Rs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT(2C)Rs accounts for the short-term aversive effect of antidepressants.

Sources of organic trace minerals in diets for weaned piglets

One hundred and twenty six piglets from a commercial genetic strain weaned at 21 days of age (6.11 +/- 0.42 kg) were used to evaluate the effects of supplementation levels of organic sources of trace minerals in the diets of weaned piglets on performance, occurrence of diarrhea, excretion of copper and zinc in the feces, and hematological parameters. A completely randomized block design was adopted, composed of six treatments (diets containing 100% of inorganic trace minerals premix at 3.00 kg/T; diets containing 0, 25, 50, 75 or 100% of organic trace minerals premix, equivalent to 0; 0.75; 1.50; 2.25 or 3.00 kg/T, respectively), seven replicates and three animals per plot. During the experimental period (from 21 to 63 days of age), the increasing levels of organic trace minerals premix in the diets determined a quadratic effect on daily weight gain (DWG), feed conversion (FC), percentage of hematocrit (Ht), hemoglobin (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), platelets (Pt), and a linear increase of Cu and Zn concentrations in feces. The comparison of means between the treatment with inorganic trace minerals premix and the other treatments showed that piglets fed diets without trace minerals premix had lower values of DWG, Ht, Hb, MCH, MCV, Pt and the worst FC value of piglets fed diets containing 25% of organic trace minerals premix presented lower values of Ht and Hb, in comparison with those fed diets with 100% of inorganic trace minerals premix. Inorganic trace minerals premix can be substituted by organic trace minerals premix at a lower level of inclusion in diets for weaned piglets.

Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment

We investigated the influence of angiotensin-converting enzyme inhibitor (ACEi) treatment and physical exercise on arterial pressure (AP) and heart rate variability (HRV) in volunteer patients with hypertension. A total of 54 sedentary volunteers were divided into three groups: normotensive (NT Group), hypertensive (HT Group) and HT volunteers treated with ACEi (ACEi Group). All volunteers underwent an aerobic physical-training protocol for 15 weeks. HRV was investigated using a spectral analysis of a time series of R-R interval (RRi) that was obtained in a supine position and during a tilt test. Physical training promoted a significant reduction in the mean arterial pressure of the HT group (113 +/- 3 vs. 106 +/- 1 mm Hg) and the ACEi group (104 +/- 2 vs. 98 +/- 2 mm Hg). Spectral analysis of RRi in the supine position before physical training demonstrated that the NT and ACEi groups had similar values at low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.5 Hz) oscillations. The HT group had an increase in LF oscillations in absolute and normalized units and a decrease in HF oscillations in normalized units compared with the other groups. The HT group had the lowest responses to the tilt test during LF oscillations in normalized units. Physical training improved the autonomic modulation of the heart rate in the supine position only in the HT group. Physical training promoted a similar increase in autonomic modulation responses in the tilt test in all groups. Our findings show that aerobic physical training improves cardiac autonomic modulation in HT volunteers independently of ACEi treatment. Hypertension Research (2012) 35, 82-87; doi:10.1038/hr.2011.162; published online 29 September 2011

Diaphragmatic Breathing Training Program Improves Abdominal Motion During Natural Breathing in Patients With Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

Yamaguti WP, Claudino RC, Neto AP, Chammas MC, Gomes AC, Salge TM, Moriya HT, Cukier A, Carvalho CR. Diaphragmatic breathing training program improves abdominal motion during natural breathing in patients with chronic obstructive pulmonary disease: a randomized controlled trial. Arch Phys Med Rehabil 2012;93:571-7. Objective: To investigate the effects of a diaphragmatic breathing training program (DBTP) on thoracoabdominal motion and functional capacity in patients with chronic obstructive pulmonary disease. Design: A prospective, randomized controlled trial. Setting: Academic medical center. Participants: Subjects (N=30; forced expiratory volume in Is, 4270 +/- 13% predicted) were randomly allocated to either a training group (TG) or a control group (CG). Interventions: Subjects in the TG completed a 4-week supervised DBTP (3 individualized weekly sessions), while those in the CG received their usual care. Main Outcome Measures: Effectiveness was assessed by amplitude of the rib cage to abdominal motion ratio (RC/ABD ratio) (primary outcome) and diaphragmatic mobility (secondary outcome). The RC/ABD ratio was measured using respiratory inductive plethysmography during voluntary diaphragmatic breathing and natural breathing. Diaphragmatic mobility was measured by ultrasonography. A 6-minute walk test and health-related quality of life were also evaluated. Results: Immediately after the 4-week DBTP, the TG showed a greater abdominal motion during natural breathing quantified by a reduction in the RC/ABD ratio when compared with the CG (F=8.66; P<.001). Abdominal motion during voluntary diaphragmatic breathing after the intervention was also greater in the TG than in the CG (F=4.11; P<.05). The TG showed greater diaphragmatic mobility after the 4-week DBTP than did the CG (F=15.08; P<.001). An improvement in the 6-minute walk test and in health-related quality of life was also observed in the TG. Conclusions: DBTP for patients with chronic obstructive pulmonary disease induced increased diaphragm participation during natural breathing, resulting in an improvement in functional capacity.

Synthesis and characterization of a diruthenium(II,III)-ketoprofen compound and study of the in vitro effects on CRC cells in comparison to the naproxen and ibuprofen derivatives

A new diruthenium(II,III) complex, of formula [Ru2Cl(ket)(4)], Ruket, containing the non-steroidal anti-inflammatory drug ketoprofen was synthesized and mainly characterized by electrospray ionization mass spectrometry (ESI-MS), UV-Vis-IR electronic spectroscopy and FTIR and Raman vibrational spectroscopies. The four drug-carboxylato bridging ligands stabilize a Ru-2(II,III) mixed valent core in a paddlewheel type structure as confirmed by ESI mass spectra, electronic and vibrational spectroscopies and magnetic measurements. Ruket and the analogous compounds containing ibuprofen, Ruibp, and naproxen, Runpx, were tested for the biological effects in the human colon carcinoma cells HT-29 and Caco-2 expressing high and low levels of COX-2 respectively. All compounds only weakly affected the proliferation of the colorectal cancer cells HT-29 and Caco-2, and similarly only partially inhibited the production/activity of MMP-2 and MMP-9 by HT-29 cells, suggesting that COX-2 inhibition by these drugs can only partially be involved in the pharmacological effects of these derivatives. (c) 2012 Elsevier Ltd. All rights reserved.

Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan (R) PCR. APOE epsilon 2/epsilon 3/epsilon 4 genotyping was performed using PCR-RFLP. Total cholesterol (TC). LDL-c and apoB were reduced after each treatment (p<0.001). Triglycerides, VLDL-c and apoAl were reduced only after atorvastatin (p<0.05), whereas triglycerides and VLDL-c were increased after HT (p=0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT+AT groups (p<0.05). APOE mRNA expression was reduced after atorvastatin treatment (p=0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms, however the reduction on APOE expression was more pronounced in epsilon 3 epsilon 3 than in epsilon 3 epsilon 4 carriers. Atorvastatin down-regulates APOE mRNA expression and it is modified by APOE genotypes in PBMC from postmenopausal women. (C) 2011 Elsevier Ltd. All rights reserved.