Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury

Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n = 6; CCI-Veh, n = 7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n = 7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p < 0.01) and from CCI-SP scores on days 4, 9 and 14 (p < 0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.     

Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

Objective

Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically.

Design and setting

We conducted a study in patients presenting to the emergency department at the University Hospital Bern. In this retrospective case series analysis of prospectively gathered data, over a 2-year period we identified 10,823 adult (≥50 years) outpatients with a measured baseline serum sodium, at admission to the hospital. OF patients were compared to a control group without fractures using standard statistical methods.

Results

Four hundred and eighty (5%) patients had 547 OF. The OF group had a higher mean age (73 vs. 68 years, p < 0.0001), smaller proportion of men (37% vs. 58%, p < 0.0001), higher hospitalisation rate (83% vs. 62%, p < 0.0001) and longer hospital stay (8 vs. 6 days, p < 0.0001). Any diuretic agent (p < 0.0001), loop diurietics (p = 0.02), spironolactone (p = 0.02) and amiloride (p < 0.01) were used significantly more in OF patients, but not thiazides (p = 0.68). The prevalence of hyponatremia increased significantly (p < 0.0001) with the number of diuretics taken. Advanced age (odds ratio [OR] 1.04, p < 0.0001), hyponatremia (OR 1.46, p = 0.011) higher serum creatinine (OR 1.53, p = 0.0001), furosemide use alone (OR 1.40, p = 0.01) and co-treatment with amiloride (OR 2.22, p = 0.02) were associated with a higher risk for OF.

Conclusions

This study highlights the clinical association of hyponatremia during the use of certain diuretics (i.e. furosemide or in combination, i.e. amiloride) with an increased risk of osteoporosis associated fractures. Although evidence-based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients.     

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO₂ sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO₂ sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO₂ exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/(kg day)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p > 0.05), although tidal volume (V_T) was reduced in BN rats (p < 0.05). There were also minimal effects of fluoxetine on CO₂ sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and V_T during hypercapnia in BN rats (p < 0.05). The augmented CO₂ response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p < 0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO₂ sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO₂ sensitivity in the BN rat.     

Whole-blood culture is a valid low-cost method to measure monocytic cytokines — A comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes

Whole-blood and peripheral blood mononuclear cell (PBMC) cultures are used as non-validated surrogate measures of monocytic cytokine production. The aim of this investigation was to compare ex vivo cytokine production from human whole-blood and PBMC with that from isolated monocytes. We also assessed the intra- and inter-individual variation in cytokine production. In 64 healthy men (age 19-40 years) IL-6, TNF and IL-10 were measured by enzyme-linked immunosorbent assay in supernatants from whole-blood, PBMC and monocytes cultured 24 h with lipopolysaccharide (LPS) or UV-killed L. acidophilus. Cytokines produced from whole-blood was found to be more strongly correlated with monocytic cytokines than cytokines from PBMC, particularly after LPS-stimulation: r = 0.57, P < 0.001 versus r = 0.33, P = 0.01 for IL-6 and r = 0.43, P < 0.001 versus r = 0.30, P = 0.02 for TNF-α. Adjustment for a preceding 8-week dietary fatty acid-intervention did not change any of the associations. Based on measurements at three time-points 8 weeks apart the intra-individual variation was ≥ 50% smaller than the inter-individual variation (P < 0.05) in most whole-blood cytokine responses and LPS-stimulated IL-6 from PBMC. We conclude that whole-blood cultures are well-suited low-cost proxy-measures of monocytic cytokine production. Moreover, large inter-individual variation in cytokine production was demonstrated whereas the individual responses in whole-blood were reproducible even over long time-periods.     

Cardiovascular responses after brisk finger movement and their dependency on the “eigenfrequency” of the baroreflex loop

The baroreflex is mainly involved in short-term blood pressure regulation and strongly influenced by activations of medullary circulation centres in the brain stem and higher brain centres. One important feature of the baroreflex is its strong preference for oscillations around 0.1 Hz, which can be seen as resonance or “eigenfrequency” (EF) of the control loop (so-called Mayer waves). In the present study we investigated beat-to-beat heart rate intervals (RRI) and arterial blood pressure (BP) changes after brisk finger movement and their relationship to the “eigenfrequency” determined by cross spectral analysis between RRI and arterial blood pressure time series of 17 healthy subjects. The analyses revealed significant correlations between BP response magnitude (r = 0.63, p < 0.01) respectively RRI response magnitude (r = 0.59, p < 0.05) and EF. This can be interpreted in such a way that subjects with a “high” EF (>0.10 Hz) elicit larger BP responses as well as larger RRI responses when compared to subjects with a “low” EF (<0.10 Hz).     

Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis

Vitamin D receptor (VDR) genotypes have been shown to be associated with differential susceptibility or resistance to tuberculosis. The influence of FokI, BsmI, ApaI and TaqI variants of VDR gene on 1, 25(OH)₂ D₃ modulated granzyme A expression of cytotoxic lymphocytes induced by culture filtrate antigen (CFA) of Mycobacterium tuberculosis was studied in 40 pulmonary tuberculosis (PTB) patients and 49 normal healthy subjects (NHS) by flow cytometry. In both the study groups, addition of 1, 25(OH)₂ D₃ (10^− 7M) significantly reduced the percentage of granzyme A positive cells in both unstimulated (NHS, p < 0.0001; PTB, p = 0.02) and stimulated culture conditions (CFA, NHS, p < 0.0001; PTB, p = 0.0001) which correlated positively with the IFN-γ levels (unstimulated, p = 0.01; CFA stimulated, p = 0.004) in NHS. The ApaI aa genotype and bbaaTT extended genotype were associated with a significantly decreased percentage of granzyme A positive cells in NHS (p < 0.05). Our results suggest that 1, 25(OH)₂ D₃ suppresses granzyme A probably by down-regulating Th1 cytokine response. Moreover, the VDR gene variants might regulate cytotoxic T-cell response via 1, 25(OH)₂ D₃ mediated suppression of granzyme A expression in tuberculosis.     

M-ficolin in children with cancer

Objectives

M-ficolin (ficolin-1) is a complement-activating pattern-recognition molecule structurally related to mannan-binding lectin. It is produced by monocytes and neutrophils, and is found in serum. Its biological role is largely unknown. We assessed M-ficolin concentration in serum from pediatric cancer patients. The aim of this study was to explore association of M-ficolin with clinical and hematological parameters, and to investigate whether the risk of chemotherapy-related infections was related to M-ficolin concentrations in serum.

Methods

M-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis and was correlated with peripheral blood counts and bone marrow examinations performed at the same time.

Results

Median M-ficolin concentration in 94 children with cancer was 1.6 μg/mL (interquartile range, 0.57-2.7; range, 0.055-25.8), and was not different from age-matched controls (median, 1.7 μg/mL; p = 0.92). M-ficolin was strongly associated with absolute counts of neutrophils (Spearman's rho, 0.45; 95%-CI, 0.26-0.65; p < 0.001), monocytes (0.34; 0.12-0.55; p < 0.001), and thus phagocytes (0.42; 0.20-0.63; p < 0.001) in peripheral blood. Similarly, M-ficolin correlated strongly with neutrophils (0.36; 0.14-0.59; p = 0.002) and phagocytes (0.31; 0.08-0.54; p = 0.009) in bone marrow. Low serum M-ficolin (≤0.5 μg/mL) was not associated with an increased incidence of fever in neutropenia during chemotherapy (multivariate Poisson rate ratio, 1.04; 95%-CI, 0.68-1.60; p = 0.85).

Conclusions

The concentration of M-ficolin in serum from children with cancer was strongly associated with neutrophil and monocyte counts in blood and bone marrow. These results suggest that M-ficolin concentrations in serum reflect the pool of phagocytes.     

The differential effects of equipotent doses of isoflurane and desflurane on hippocampal acetylcholine levels in young and aged rats

The differential effects of age-adjusted equipotent doses of isoflurane (Iso) and desflurane (Des) on hippocampal acetylcholine (ACh) levels were examined using cerebral microdialysis in young (12–16 weeks old) and aged (16–18 months old) Fischer 344 rats. An 80 min exposure to 1 minimum alveolar concentration (MAC) of isoflurane and desflurane produced similar maximal decreases in hippocampal ACh levels in both age groups: to 36.3 ± 13.9% (Iso) and 28.6 ± 12.9% (Des) of baseline in aged rats versus 32.5 ± 18.7% (Iso) and 29.6 ± 12.5% (Des) of baseline in young rats. Compared to isoflurane, the onset of this maximal decrease was delayed in both age groups with desflurane. Furthermore, following the end of anesthesia in aged rats, hippocampal ACh levels returned to control levels faster with desflurane (within 20–40 min) than isoflurane (within 60–80 min). These data demonstrate that age-adjusted equipotent doses of isoflurane and desflurane produce similar maximal decreases in hippocampal ACh levels in a manner that is independent of age. However, compared to isoflurane, desflurane is associated with a slower decrease in and a faster restoration of hippocampal ACh levels following anesthesia in this rat model of aging. Hence, in the aged, the administration of age-adjusted equipotent doses of an inhalational anesthetic with low blood and tissue solubility, such as desflurane, may provide a viable pharmacotherapeutic strategy for minimizing the duration of the attenuation of hippocampal cholinergic outflow observed following anesthesia.     

Cognitive task performance causes impaired maximum force production in human hand flexor muscles

The purpose of this study was to investigate effects of demanding cognitive task performance on intermittent maximum voluntary muscle contraction (MVC) force production. Participants performed either a modified Stroop or control task for 22 min. After the first min and at 3-min intervals thereafter, participants rated fatigue, perceived mental exertion and performed a 4-s MVC handgrip squeeze. A mixed ANOVA showed a significant interaction, F(7, 259) = 2.43, p = .02, with a significant linear reduction in MVC force production over time in the cognitively depleting condition (p = .01) and no change for controls. Ratings of perceived mental exertion, F(7, 252) = 2.39, p < .05, mirrored the force production results with a greater linear increase over time in the cognitive depletion condition (p < .001) compared to controls. Findings support current views that performance of cognitively demanding tasks diminishes central nervous system resources that govern self-regulation of physical tasks requiring maximal voluntary effort.     

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

Objectives

The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status.

Methods

In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women.

Results

Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β = 0.339, p < 0.001) and DXA-assessed total and percentage body fat (β = 0.366, p < 0.001 and β = 0.412, p < 0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β = 0.408, p < 0.001), after taking the potential confounders (including body mass index) into account.

Conclusion

Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.     

Participating in a virtual reality balance exercise program can reduce risk and fear of falls

Objective

The objective of this study was to quantify the effectiveness of virtual reality balance games (VRBG) to decrease risk and fear of falls among women.

Methods

Thirty six community dwelling women aged 56 and above were randomly divided into experimental (exercises using VRBG focus on improving balance) and control (conventional balance exercises) groups. Both groups attended a twice 6 weekly exercise session for an hour. Risk and fear of falls were measured with Physiological Profile Approach (PPA) and Activity Specific Balance Scale (ABC-6). Pre and post intervention differences between the groups were examined using two way repeated measures ANOVA.

Results

Both VRBG and conventional balance exercise groups had significant decrease in PPA (p < 0.001) and ABC-6 (p < 0.01) after the interventions. However, no significant effects were demonstrated between the groups in PPA (p = 0.18) and ABC-6 (p = 0.25) post intervention. Time and group interaction effect were not significant for PPA (p = 0.18) and ABC-6 (p = 0.45).

Conclusions

Practising VRBG can increase balance confidence and decrease risk of falls among community dwelling women.     

Effects of supervised whole body vibration exercise on fall risk factors,functional dependence and health-related quality of life in nursing home residents aged 80+

Objective

To test the feasibility and effectiveness of whole-body vibration (WBV) therapy on fall risk, functional dependence and health-related quality of life in nursing home residents aged 80+ years.

Design

Twenty-nine 80–95 years old volunteers, nursing home residents were randomized to an eight-week WBV intervention group) (n = 15) or control group (n = 14). Functional mobility was assessed using the timed up and go (TUG) test. Lower limb performance was evaluated using the 30-s Chair Sit to Stand (30-s CSTS) test. Postural stability was measured using a force platform. The Barthel Index was used to assess functional dependence and the EuroQol (EQ-5D) was used to evaluate Health-Related Quality of Life. All outcome measures were assessed at baseline and at a follow-up after 8 weeks.

Results

At the 8-week follow up, TUG test (p < 0.001), 30-s CSTS number of times (p = 0.006), EQ-5Dmobility (p < 0.001), EQ-5DVAS (p < 0.014), EQ-5Dutility (p < 0.001) and Barthel index (p = 0.003) improved in the WBV intervention group when compared to the control group.

Conclusions

An 8-week WBV-based intervention in a nursing home setting is effective in reducing fall risk factors and quality of life in nursing home residents aged 80+.     

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax] < 70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO₂ test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11 ± 0.03 l min⁻¹ Torr⁻¹) than those with preserved inspiratory muscle strength (0.07 ± 0.03 l min⁻¹ Torr⁻¹, p = 0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r = −0.57, p = 0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r = −0.46, p = 0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.     

NO-mediated activation of Src kinase during hypoxia in the cerebral cortex of newborn piglets

The present study aims to investigate the mechanism of Src kinase activation during hypoxia and tests the hypothesis that the hypoxia-induced activation of Src kinase, as determined by Src kinase phosphorylation, in the cerebral cortical membranes of newborn piglets is mediated by NO derived from neuronal nitric oxide synthase (nNOS). Fifteen piglets were divided into normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-treated with nNOS inhibitor I (Hx-nNOSi) groups. Hypoxia was induced by decreasing FiO₂ to 0.06 for 1 h. nNOS inhibitor I (selectivity >2500 vs eNOS and >500 vs iNOS) was administered (0.4 mg/kg, i.v.) 30 min prior to hypoxia. Cortical membranes were isolated and phosphorylation of Src kinase was determined by Western blot analysis. Src kinase activity was determined by radioactive assay using immunopurified enzyme. Membrane proteins were separated by 12% SDS–PAGE and probed with anti-phospho (pTyr⁴¹⁸)-Src kinase antibody. Protein bands were detected, analyzed by densitometry and expressed as absorbance (OD × mm²). Density (OD × mm²) of phosphorylated Src kinase was 111.7 ± 21.1 in Nx, 234.5 ± 23.8 in Hx (p < 0.05 vs Nx) and 104.7 ± 18.1 in Hx-nNOSi (p < 0.05 vs Hx, p = NS vs Nx). Src kinase activity (pmol/mg protein/ h) was 2472 ± 75 in Nx, 4556 ± 358 in Hx (p < 0.05 vs Nx) and 2259 ± 207 in Hx-nNOSi (p < 0.05 vs Hx, p = NS vs Nx). The data show that pretreatment with nNOS inhibitor prevents the hypoxia-induced increase in tyrosine phosphorylation and the activity of Src kinase. We conclude that the mechanism of hypoxia-induced increased activation of Src kinase is mediated by nNOS derived NO. We propose that NO mediated inhibition of protein tyrosine phosphatases SH-PTP-1 and SH-PTP-2 leads to increased tyrosine phosphorylation and activation of Src kinase in the cerebral cortex of newborn piglets.     

Tyrosine phosphorylation of neuronal nitric oxide synthase (nNOS) during hypoxia in the cerebral cortex of newborn piglets: The role of nitric oxide

The present study aims to investigate the mechanism of activation of nNOS during hypoxia and tests the hypothesis that the hypoxia-induced increased tyrosine phosphorylation of nNOS in the cerebral cortical membranes of newborn piglets is mediated by nNOS-derived nitric oxide (NO). Fifteen newborn piglets were divided into normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-pretreated with nNOS inhibitor I (Hx-nNOSi) groups. Hypoxia was induced by an FiO₂ of 0.07 for 60 min. nNOS inhibitor I (selectivity > 2500 vs endothelial NOS and >500 vs inducible NOS) was administered (0.4 mg/kg, i.v.) 30 min prior to hypoxia. Cortical membranes were isolated and tyrosine phosphorylation of nNOS determined by Western blot. Membrane protein was immunoprecipitated with nNOS antibody, separated on 12% SDS-PAGE and blotted with anti-phosphotyrosine antibody. Protein bands were detected by enhanced chemiluminescence, analyzed by densitometry and expressed as absorbance (OD × mm²). Density (OD × mm²) of tyrosine phosphorylated nNOS was 51.66 ± 14.11 in Nx, 118.39 ± 14.17 in Hx (p < 0.05 vs Nx) and 45.56 ± 10.34 in Hx-nNOSi (p < 0.05 vs Hx, p = NS vs Nx). The results demonstrate that pretreatment with nNOS inhibitor prevents the hypoxia-induced increased tyrosine phosphorylation of nNOS. We conclude that the mechanism of hypoxia-induced increased tyrosine phosphorylation of nNOS is mediated by nNOS-derived NO.     

Circulating IL-35 in pancreatic ductal adenocarcinoma patients

IL-35 is a novel inhibitory cytokine that is mainly produced by regulatory T-cells (Tregs) and is required for Treg-mediated immunosuppression. However, the plasma levels of IL-35 in patients with pancreatic ductal adenocarcinoma (PDAC) have never been investigated. In this study, we found that plasma IL-35 levels more significantly increased in PDAC patients than in normal controls (134.53 ± 92.45 pg/mL vs. 14.26 ± 6.56 pg/mL). IL-35 mRNA levels were positively correlated with plasma IL-35 levels (EBI3, R = 0.925, p < 0.01; p35, R = 0.916, p < 0.01). Furthermore, IL-35 expression levels were associated with lymph node metastasis (p = 0.001) and late tumor stage (p = 0.002). For the resected patients, high IL-35 expression levels were associated with large tumor size (p < 0.01), higher TNM classification T staging (p < 0.05), and late tumor stage (p < 0.05). In conclusion, circulating IL-35 in PDAC patients significantly increased, suggesting that regulating the expression of IL-35 may provide a new possible target for the treatment of PDAC patients, especially for the resectable ones.     

Labisia pumila extract regulates body weight and adipokines in ovariectomized rats

Objective

We investigated the effects of a standardized water extract of Labisia pumila var. alata (LPva), and compared to estrogen replacement (ERT), on body weight gain, uterus weight, adipose tissue mRNA and protein levels of adipokines in ovariectomized (OVX) rats.

Methods

Eight-week-old OVX Sprague-Dawley rats were administered orally with either 10 mg/kg/day (LPva10), 20 mg/kg/day (LPva20) or 50 mg/kg/day (LPva50) of LPva for 30 days. Sham-operated (Sham) and estrogen-treated OVX rats (ERT, 0.625 mg/kg/day) served as controls. Plasma adipokines were measured, and mRNA expressions of the adipokines were determined in the adipose tissues.

Results

ERT- and LPva50-treated OVX rats showed significantly less (p < 0.05) weight gain compared to untreated OVX rats. Ovariectomy caused plasma leptin levels to decrease significantly (p < 0.05), but when treated with LPva or ERT, plasma leptin increased significantly to levels higher or comparable to that seen in the Sham group. The mRNA expression of leptin was higher in the LPva-treated animals than in all other groups. In contrast, the elevated plasma resistin concentrations in OVX rats were significantly reduced in rats given ERT (p < 0.05) and LPva extracts (p < 0.05). There was no difference in adiponectin levels in all groups. The uterus to body weight ratio of untreated OVX rats was significantly low compared to Sham (p < 0.05), but showed dose-dependent increase upon treatment with LPva.

Conclusion

The present study provides first evidence that LPva exerts uterotrophic effect and regulates body weight gain by modulating secretion of leptin and resistin, and expression of the adipokines in adipose tissues.     

Correlates and predictors of self-rated health and ambulatory status among elderly women – Cross-sectional and 10 years population-based cohort study

Aim

To investigate the correlates and predictors of self-rated health (SRH) and self-reported ambulatory status (AMB) among elderly women.

Subjects and methods

A random sample of 1620 postmenopausal women aged 53–66 years in 1994 was selected from Osteoporosis Risk Factor and Prevention (OSTPRE) – study cohort in Finland. SRH and AMB were assessed in baseline (1994) and after 10-year follow-up (2004). A prognostic model was developed to predict the probability of good 10-year SRH and AMB.

Results

Full AMB was correlated with and predicted by good SRH (OR = 4.3, p < 0.001). Good quality of life (QoL) was both correlate and predictor of good 10-year SRH (OR = 2.0, p < 0.001) and full AMB (OR = 2.6, p < 0.001). Low BMI was associated with good SRH (OR = 0.97, p < 0.049) and full AMB (OR = 0.92, p < 0.001), good grip strength with good SRH (OR = 2.7, p < 0.001) and ability to squat down with full AMB (OR = 1.7, p = 0.002). Cardiovascular diseases, arthritis and back pain were common significant negative correlates (p < 0.001) of baseline AMB and SRH out of variety of chronic diseases with significant association with either one. The significant (p < 0.05) baseline predictors in final prognostic model for good 10-year SRH included baseline AMB and SRH, QoL, age, BMI, grip strength and psychiatric diseases (C-index = 0.81) and for full 10-year AMB ability to squat, baseline AMB and SRH, QoL, BMI, hypertension and arthritis (C-index = 0.81). These risk scores had better predictive power in comparison to that of baseline SRH and AMB alone (p < 0.001 in univariate Z-score test).

Conclusions

Among elderly women AMB is strongly linked to SRH. SRH and AMB are affected mostly by musculoskeletal, cardiovascular and psychiatric diseases as well as body anthropometry, muscle strength and subjective QoL. The present study provides a novel algorithm for predicting probability of full AMB and good SRH in postmenopausal women.     

Low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression

Objectives

To investigate the low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression.

Methods

Cross-sectional study with 180 women aged between 19 and 60 years who admitted to our outpatient clinic. Sexual function was assessed by female sexual function index and clinically significant depression was measured by Beck depression inventory test.

Results

The rate of low sexual function was 85.9% in postmenopausal (OR 2.9, 95% CI 1.8–4.8) and 47.7% in premenopausal women (OR 0.4, 95% CI 0.3–0.5) (p < 0.0001). The postmenopausal group reported significantly lower desire, arousal, lubrication, orgasm, satisfaction and pain scores than controls (p < 0.0001, for all of them). Low sexual function was positively correlated with age (r = 0.37, p < 0.0001), menopausal status (r = 0.40, p < 0.0001), gravidity (r = 0.44, p < 0.0001), parity (r = 0.43, p < 0.0001), abortion rates (r = 0.27, p = 0.001) and marriage period (r = 0.40, p < 0.0001). There were also significant negative correlations between low sexual function and education (r = −0.39, p < 0.0001) and family income (r = −0.29, p < 0.0001). However, multivariate regression analysis demonstrated that education, family income and menopausal status were the only independent variables for low sexual function after adjusted for age, gravidity, parity, abortion, marriage period and menopausal status.

Conclusion

Low sexual function was relatively high in postmenopausal women without clinically significant depression. Education, family income and menopausal status were the independent risk factors for low sexual function. Investigation of female sexuality was essential for these patients.