G-CSF enhances stem cell proliferation in rat hippocampus after transient middle cerebral artery occlusion

Granulocyte colony-stimulating factor (G-CSF) enhances the survival and stimulates the proliferation of neutrophil progenitors. Recently, the neurogenerative effect of G-CSF has been intensely investigated. In this study, we explored the possibility that G-CSF enhanced the cell proliferation in the rat dentate gyrus (DG) after focal cerebral ischemia, using a rat transient middle cerebral artery occlusion (tMCAO) model. At 7 days after tMCAO, the number of 5-bromodeoxyuridine (BrdU)-positive cells in the G-CSF-treated group was significantly increased compared with that in the vehicle-treated group in the ipsilateral SGZ (16.6 ± 5.5/mm² in the vehicle-treated group versus 33.0 ± 7.2/mm² in the G-CSF-treated group, **p < 0.01) and in the ipsilateral GCL (14.2 ± 2.8/mm² in the vehicle-treated group versus 21.0 ± 3.8/mm² in the G-CSF-treated group, *p < 0.05). This result showed the possibility of a neurogenerative role of G-CSF after tMCAO in rats.     

Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: Effect of healthy aging

We evaluated effect of aging, gender and eye (sighting) dominance on relationship between visual evoked flow response (VEFR) and visual evoked potential (VEP), which refers to neurovascular coupling. The VEFR was defined as a percentage increase of the ratio of mean blood flow velocity in the contralateral (according to the side of dominant eye processing) posterior cerebral artery P2 segment to those in ipsilateral middle cerebral artery from the baseline during half-field stimulation. Vasoneural coupling index (CI) was defined as “100 × VEFR/VEP P100 amplitude”. Compared to the healthy elderly subjects (n: 19; female/male: 6/13, mean age: 69.7 ± 7), younger participants (n: 28; female/male: 16/12; mean age: 31.1 ± 4.7) had significantly higher VEFR for both sides: 18.9 ± 6.7% versus 11.2 ± 6.7%, p < 0.001 and 17.3 ± 7.7% versus 11.8 ± 5.5%, p: 0.007, for the hemisphere contralateral to dominant and nondominant eye (D and ND side), respectively. Albeit absence of any correlation between their latencies, VEP and VEFR amplitudes were well correlated. However, this was significant only for younger subjects and more evident in D side. The CI was higher in young subjects compared to those in old ones (6.49 ± 2.79 versus 4.75 ± 2.35, respectively, p = 0.007). But, this age-related trend remained as borderline when sides were analyzed individually: In the young subjects CI was 5.99 ± 2.21 and 6.96 ± 3.22 for D and ND sides, while those were 4.27 ± 2.60 and 5.19 ± 2.07 in old ones. This study confirmed diminished visual evoked flow in relation with advancing age, and suggested that “weakened” neurovascular coupling (as evidenced by a decreased VEP and VEFR correlation along with decreased CI) as one of the underlying mechanisms.     

Slower eating rate is independent to gastric emptying in obese minipigs

The aim of our study was to investigate whether the altered eating behavior observed in the context of a diet-induced metabolic syndrome is related to changes of the gastric emptying and autonomic balance. Eight adult male Göttingen minipigs were subjected during 5 months to ad libitum Western diet (WD). Several factors were compared between the lean (before WD) and obese conditions: general activity and eating behavior, gastric emptying, adiposity, glycemia and insulinemia during IVGTT, and heart rate variability (HRV). In our model, obesity did not alter the gastric emptying (258 ± 26 vs. 256 ± 14 min, P > 0.10) but induced insulin resistance: increased basal insulinemia (12.6 ± 0.8 to 36.6 ± 6.1 mU/l, P < 0.02) and reduced insulin sensitivity (4.5E−4 ± 0.7E−4 to 2.5E−4 ± 0.2E−4 min⁻¹ per mU.l⁻¹ of insulin, P < 0.05). The HRV and sympathovagal balance were not significantly modified (P > 0.10). Fed ad libitum with WD, animals overate durably (P < 0.001). During a 30-min meal test though, the ingestion speed, the food ingested (1076 ± 48 vs. 520 ± 52 g) and energy intake decreased in the obese condition (P < 0.05), which can be explained by the fragmentation of the daily caloric intake. These data suggest that the slower eating rate and increased number of meals observed in obese minipigs without neuropathy is independent to gastric emptying. The explanation may be sought rather in central modifications induced by obesity that might modify the food perception and/or motivation.     

Serum cathepsin K as a marker of bone metabolism in postmenopausal women treated with alendronate

Context

Cathepsin K is a member of the cysteine protease family that cleaves both helical and telopeptide regions of collagen I, the major type of collagen in bone. Measurement of circulating levels of cathepsin K may be useful to assay the number or function of osteoclasts.

Objective

The aim of the study was to evaluate the role of serum cathepsin K as a biochemical marker of bone metabolism in patients with postmenopausal osteoporosis before and after treatment with alendronate.

Design, setting and participants

The study was a case–control and prospective study with postmenopausal osteoporotic women including a total number of 86 subjects. Serum cathepsin K was determined in 46 women with postmenopausal osteoporosis before and after 3, 6 and 12 months of treatment with alendronate. Basal serum cathepsin K levels were also compared between premenopausal healthy women (n = 20), postmenopausal women without osteoporosis (n = 20) and osteoporotic women. In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) were measured.

Main outcome measure

Changes in cathepsin K serum levels after alendronate treatment.

Results

Serum cathepsin K levels were higher in postmenopausal women with osteoporosis (9.4 ± 11 pmol/L) compared with healthy postmenopausal women (6.8 ± 8.1 pmol/L; p < 0.01) and premenopausal women (6.3 ± 5.0 pmol/L, p < 0.01). Serum cathepsin K decreases gradually after alendronate treatment (17% at 3 months, 22% at 6 months and 41% at 12 months, p < 0.01). In contrast, the treatment resulted in early and sustained reductions in serum CTX.

Conclusion

We conclude that serum cathepsin K seems to provide additional information on bone metabolism in postmenopausal women treated with alendronate.     

Effect of dietary supplementation with collagen hydrolysates on bone metabolism of postmenopausal women with low mineral density

Collagen hydrolysates (CH), obtained by an enzymatic hydrolysis process of gelatins, have potential application as oral supplements. Objective: To evaluate the effects of diet supplementation with collagen hydrolysates on bone metabolism markers in postmenopausal women with low bone mineral density. Methods: A randomized double-blind clinical assay with postmenopausal women with osteopenia was planned. The volunteers ingested 10 g/day of CH or a placebo for a period of 24 weeks. The bone resorption markers (carboxyl-terminal collagen crosslinks—CTX) and bone formation markers (osteocalcin—OSCAL and bone-specific alkaline phosphatase—BAP) were determined at baseline and at 12 and 24 weeks of treatment. Results: The sample consisted of 35 placebo and 36 treated subjects (aged 57.3 ± 4.8 years and BMI of 27.4 ± 4.5 kg/m²). BAP levels showed no significant changes over the time. CTX levels showed a significant increase during the 24 weeks of treatment from 0.40 to 0.48 ng/mL in CH group and 0.47 to 0.57 ng/mL in placebo group (p < 0.0001). OSCAL levels also showed a increase during the 24 weeks from 24.8 to 29.0 ng/mL in CH group and 28.1 to 31.8 ng/mL in placebo group (p < 0.001). A comparison of levels of bone markers between CH and placebo group demonstrated no differences. Analysis of variance revealed no significant effect of dietary supplementation with collagen hydrolysates on biochemical bone markers. Conclusions: CH consumption did not produce any effects on bone metabolism as measured by biochemical indices of bone remodeling in postmenopausal women. The majority of patients exhibited inadequate calcium intake, as well as excess body weight.     

Mechanism of caspase-3 activation during hypoxia in the cerebral cortex of newborn piglets

We have previously shown that the activity and the expression of caspase-9 and caspase-3 were increased during hypoxia in the cerebral cortex of newborn piglets. The present study was conducted to test the hypothesis that the hypoxia-induced activation of caspase-3 in the cerebral cortex of newborn piglets is mediated by caspase-9. Twenty-two newborn piglets were randomly assigned to four groups: normoxic (Nx), normoxic pretreated with a selective caspase-9 inhibitor, Z-Leu-Glu(OMe)-His-Asp(OMe)-Fluoromethyl ketone (Z-LEHD-FMK) (Nx + LEHD), hypoxic (Hx), and hypoxic pretreated with Z-LEHD-FMK (Hx + LEHD). Cerebral tissue hypoxia was confirmed biochemically by measuring ATP and phosphocreatine. Caspase-9 and -3 activities were determined spectrofluorometrically. The expression of caspase-9 and -3 proteins was measured by Western blot analysis using active enzyme specific antibodies. Cytosolic caspase-9 activity (nmol/mg protein/h) was 3.70 ± 0.40 in Nx, 3.56 ± 0.31 in Nx + LEHD (p = NS versus Nx), 4.99 ± 0.64 in Hx (p < 0.05 versus Nx), and 3.73 ± 0.80 in Hx + LEHD (p < 0.05 versus Hx, p = NS versus Nx). Cytosolic caspase-3 activity (nmol/mg protein/h) was 7.80 ± 1.17 in Nx, 8.15 ± 0.87 in Nx + LEHD (p = NS versus Nx), 13.07 ± 0.78 in Hx (p < 0.05 versus Nx), and 10.05 ± 2.09 in Hx + LEHD (p < 0.05 versus Hx) The density (OD × mm²) of active caspase-9 protein was 18.52 ± 1.89 in Nx, 20.53 ± 1.12 in Nx + LEHD (p = NS versus Nx), 32.36 ± 5.03 in Hx (p < 0.05 versus Nx), and 19.94 ± 3.59 in Hx + LEHD (p < 0.05 versus Hx, p = NS versus Nx). The density (OD × mm²) of active caspase-3 protein was 55.87 ± 8.73 in Nx, 55.69 ± 8.18 in Nx + LEHD (p = NS versus Nx), 94.10 ± 12.05 in Hx (p < 0.05 versus Nx), and 56.12 ± 14.56 in Hx + LEHD (p < 0.05 versus Hx, p = NS versus Nx). These data show that administration of a selective caspase-9 inhibitor, Z-LEHD-FMK, prior to hypoxia prevents the hypoxia-induced increase in caspase-3 activity and the expression of active caspase-3 protein. We conclude that the hypoxia-induced activation of caspase-3 during hypoxia in the cerebral cortex of newborn piglets is mediated by caspase-9.     

Autonomic function and change in insulin for exercising postmenopausal women

Purpose

Obesity, physical inactivity and altered estrogen metabolism play an integrated role contributing to the disease risk profiles of postmenopausal women. These same risk factors also affect modulation of the autonomic nervous system (ANS).

Methods

We examined 332 postmenopausal, overweight, previously sedentary women (mean ± SD; age, 57.6 ± 6.3 years; weight, 84.3 ± 11.9 kg; BMI, 31.7 ± 3.7 kg/m²) participating in a 6-month, moderate intensity, aerobic exercise training intervention to determine the relationship between heart rate variability (HRV) derived autonomic function and fasting insulin. We analyzed quartiles of change in time and frequency domain indices of ANS activity and changes in insulin for between and within group differences using ANCOVA and Tukey post hoc tests adjusted for age, ethnicity, randomization group, change in fitness, and change in weight.

Results

We observed at baseline that insulin was positively correlated with body anthropometry (body weight, r² = 0.34; BMI, r² = 0.39; waist circumference, r² = 0.29; all, P < 0.001), and inversely associated with rMSSD (r² = −0.12) and SDNN (r² = −0.18; all, P < 0.01). After the intervention, changes in rMSSD (r² = −0.21, P < 0.002) and SDNN r² −0.19, P < 0.0001) were inversely correlated to insulin change. Further ANCOVA analysis revealed that rMSSD and SDNN were both significant (P < 0.0001); however, only rMSSD exhibited a step-wise pattern of improvement when quartiles of rMSSD were compared to corresponding insulin reductions: Q1 (referent group, 8.41 ± 3.2 uIU/ml), Q2 (−3.30 ± −3.2 uIU/ml), Q3 (−5.66 ± −3.2 uIU/ml; P < 0.02), and Q4 (−9.60 ± −3.2 uIU/ml; P < 0.006).

Conclusion

Our study shows that changes in autonomic function are associated with changes in insulin and that exercise training may influence this relationship in postmenopausal women.     

Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life

Objective

To use the Menopause-Specific Quality of Life Questionnaire (MENQOL) to assess the impact of menopausal symptoms on health-related quality of life in a large US population-based study.

Methods

Participants were recruited from the US population through random-digit-dialing and probability sampling. Analyses included 2703 postmenopausal women 40–65 years old in our Menopause Epidemiology Study. Respondents answered a 30-min questionnaire, including the MENQOL.

Results

Scores for each domain were: vasomotor: 3.2 ± 2.2; psycho-social: 3.3 ± 1.8; physical: 3.5 ± 1.5; sexual: 2.9 ± 2.1. There were significant differences in the MENQOL scores by age, smoking, exercise, education, employment status and BMI. Women aged 60–65 years (p < 0.0001), with a bachelor’s degree or higher level of education (p < 0.0001), who exercised at least 3 days a week (p < 0.0001), who had never smoked (p < 0.0001), with a body mass index ≤25 kg/m² (p < 0.0001), and who had significantly lower scores indicating better quality of life. Hot flashes affected work (46.0%), social activities (44.4%), leisure activities (47.6%), sleep (82.0%), mood (68.6%), concentration (69.0%), sexual activity (40.9%), total energy level (63.3%) and overall quality of life (69.3%).

Conclusion

Symptoms experienced during menopause and socio-demographic characteristics affect the quality of life in postmenopausal women. Hot flashes impact the daily activities of most postmenopausal women, especially those with more frequent/severe symptoms. Treatments that safely and effectively treat these symptoms could improve quality of life among postmenopausal women.     

Fitness alters fluid regulatory but not behavioural responses to hypohydrated exercise

Dehydration is typical during prolonged exercise. Because training stimulates numerous adaptations, some involving fluid regulation, it is conceivable that training involves adaptations to dehydration. This study tested the hypothesis that trained individuals have altered fluid regulatory, but not behavioural or perceptual responses to exercise when hypohydrated. Six trained (V.O_{2 peak}: 65 ± 8 mL kg^− 1 min^− 1) and six untrained (V.O_{2 peak}: 45 ± 4 mL kg⁻¹ min⁻¹) males cycled for 40 min at 70%V.O_{2 peak}, once whilst euhydrated (EUH) and once whilst hypohydrated by ~ 2% body mass (HYPO), before a 40-min performance trial with euhydration (in EUH) or ad libitum drinking (in HYPO), in temperate conditions (24.3 °C, 50% rh). Baseline hydration was achieved by complete or partial rehydration from exercise + heat stress on the previous evening. Body mass was reduced (− 1.8 ± 0.1%) and plasma osmolality was increased (5 ± 1 mosmol kg^− 1) similarly between fitness groups in HYPO compared to EUH (P < 0.05). During exercise, plasma [AVP] rose more in HYPO than EUH; the elevation was greater in the Untrained (4.1 ± 1.7 vs. 2.0 ± 0.8 pmol L^− 1, P < 0.01) than Trained (1.4 ± 0.6 vs. 1.1 ± 0.5 pmol L^− 1, P < 0.01; P = 0.02). Increases in plasma [AVP] relative to osmolality were higher in Untrained than Trained (0.47 ± 0.06 vs. 0.025 ± 0.05 pmol mosmol^− 1, P = 0.03). Fitness groups had equivalent thirst ratings during fixed exercise but Trained were thirstier than Untrained when self regulating in HYPO (4.0 ± 1.5 vs. 2.7 ± 1.2; P = 0.05); thus Trained tended to consume more fluid (1.20 ± 0.16 vs. 0.88 ± 0.16 L; P = 0.19), but maintained similar hypohydration consistent with their greater sweat rate during HYPO. In conclusion, aerobic fitness attenuates the neuroendocrine ([AVP]) response to hypohydrated exercise, but not perceptual (thirst) or behavioural (ad libitum drinking) responses.     

Comparative study of the effects of laser photobiomodulation and extract of Brassica oleracea on skin wounds in wistar rats: A histomorphometric study

The objective of this study was to investigate the effect of a photobiomodulation laser and Brassica oleracea on tissue morphology in skin wounds. The parameters analyzed were type I and III collagen fibers, and thickness and surface density of the epithelial tissue, as well as how quickly the wound closed. Five skin wounds 12 mm in diameter were made on the backs of the animals, which were randomized into four groups (8 animals each). Saline Group: 0.9% saline solution; Ointment Group (extract of Cabbage, B. oleracea, 10% lanolin); Balsam Group (10% glycolic extract of B. oleracea emulsion oil); L60 Group (laser GaAsAl 60 J/cm²). The applications were made daily during a 20-day treatment, and every 4 days tissue from different wounds was removed. The reduction in the size of the wounds on the 4th, 8th, 12th and 16th days was significantly greater in the treated groups compared to the control group. At all the time points analyzed, there was a greater proportion of collagen in the Balsam and L60 groups (p < 0.05). There was also a greater proliferation of epithelial cells in the L60 and Balsam groups after 20 days of treatment (p < 0.05). The healing extract and laser 60 j/cm² exerted a great effect on collagen proliferation in stimulating scar tissue maturation.     

Fibrocytes are associated with the fibrosis of coronary heart disease

Fibrocytes contribute significantly to fibrosis in many cardiac diseases. However, it is not clear whether fibrocytes are associated with the fibrosis in coronary heart disease (CHD). The aim of this study was to determine whether fibrocytes are involved in cardiac fibrosis in CHD. We identified the presence of fibrocytes in CHD heart by immunofluorescence and confocal microscopy, examined the collagen volume fraction by Masson's Trichrome staining, and evaluated the correlation between fibrocytes and cardiac fibrosis. In conjunction, we examined the location of CXCL12, a homing factor and specific ligand for CXCR4, by immunohistochemistry. Fibrocytes were identified in 26 out of 27 CHD hearts and in 10 out of 11 normal hearts. Combinations, including CD34/αSMA, CD34/procollagen-I, CD45/αSMA, CXCR4/procollagen-I and CXCR4/αSMA, stained significantly more fibrocytes in CHD hearts as compared with those in normal hearts (p < 0.05). There were positive correlations between the collagen volume fraction and the amount of fibrocytes (r = 0.558; p = 0.003 < 0.01) and between the number of CXCR4⁺ fibrocytes and the CXCL12⁺ cells (r = 0.741; p = 0.000 < 0.01) in CHD hearts. Based upon these findings, we conclude that fibrocytes, likely recruited through the CXCR4/CXCL12 axis, may contribute to the increase in the fibroblast population in CHD heart.     

The immunomodulation of a novel tumor necrosis factor (CgTNF-1) in oyster Crassostrea gigas

Tumor necrosis factor (TNF) is one of the most important cytokines involved in many processes in both vertebrate and invertebrate. In the present study, a new tumor necrosis factor with a typical TNF domain was identified in oyster Crassostrea gigas (designated CgTNF-1). CgTNF-1 shared low sequence identity and similarity with the TNF superfamily members from other vertebrate and invertebrate. After LPS stimulation, the mRNA expression of CgTNF-1 in haemocytes increased significantly and peaked at 12 h (1.39 ± 0.12, P < 0.05) post treatment, and the expression of CgTNF-1 protein in haemolymph also increased obviously during 6–12 h. When the oyster haemocytes were incubated with rCgTNF-1, its apoptosis and phagocytosis rate were both effectively induced and peaked at 12 h post the treatment of rCgTNF-1 with the concentration of 100 ng mL⁻¹ (23.3 ± 3%, P < 0.01), 50 ng mL⁻¹ (5.3 ± 0.6%, P < 0.05) and 10 ng mL⁻¹ (6.7 ± 1.2%, P < 0.05), respectively. After the co-stimulation of LPS and rCgTNF-1, the apoptosis and phagocytosis rate of oyster haemocytes, and the activities of PO and lysozyme in the haemolymph all increased significantly, and reached the peak at 12 h (apoptosis rate 26.7 ± 1.5%, P < 0.01), 12 h (phagocytosis rate 8.3 ± 0.6%, P < 0.01), 6 h (PO 1.11 ± 0.01 U mg prot⁻¹, P < 0.01) and 12 h (lysozyme 168.9 ± 8.3 U mg prot⁻¹, P < 0.05), respectively, which were significantly higher than that in the LPS group. Furthermore, the anti-bacteria activity in the LPS + TNF group was significantly higher than that in the LPS group during 6–12 h. All the results collectively indicated that CgTNF-1 was involved in the oyster immunity and played a crucial role in the modulation of immune response including apoptosis and phagocytosis of haemocytes, and regulation of anti-bacterial activity as well as the activation of immune relevant enzymes.     

In vitro protection of adipose tissue-derived mesenchymal stem cells by erythropoietin

Mobilization of stem cells and their differentiation into cardiomyocytes are known to have protective effects after myocardial infarction. The integrity of transplanted mesenchymal stem cells for cardiac regeneration is dependent on cell–cell or cell–matrix interaction, which is adversely affected by reactive oxygen species in an ischemic environment. Treatment with erythropoietin was shown to protect human adipose tissue derived mesenchymal stem cells in an ischemic injury in vitro model. The analyses indicated that expression of erythropoietin receptors played a pivotal role in erythropoietin mediated cell survival. In this study, the anti-apoptotic effect of erythropoietin on stem cells was analyzed in apoptosis-induced human mesenchymal stem cells. Apoptosis was induced in cultured adult human adipose tissue derived mesenchymal stem cells by hydrogen peroxide. A group of cultured cells was also treated with recombinant human erythropoietin in a concentration of 50 ng mL⁻¹. The degree of apoptosis was analyzed by flow-cytometry and immunohistochemical staining for Caspase 3. The average percentages of apoptotic cells were significantly higher in H₂O₂-induced stem cells than in cells co-cultured with erythropoietin (63.03 ± 4.96% vs 29 ± 3.41%, p < 0.01). We conclude that preconditioning with erythropoietin suppresses apoptosis of mesenchymal stem cells and enhances their survival.     

Infiltration and activation of acidophilic granulocytes in skin lesions of gilthead seabream, Sparus aurata, naturally infected with lymphocystis disease virus

Light, ultrastructural and immunocytochemical investigations were carried out on the skin of gilthead seabream, Sparus aurata L., naturally infected with lymphocystis iridovirus, to assess pathology and host cellular responses. Of 220,000 young seabream examined, 32,400 (14.7%) had clinical signs of lymphocystis and within 6 months of disease appearance, 45% of clinically affected fish had died. A subsample of 20 S. aurata (80.0 ± 12.5 mm total length, mean ± S.D.), including 10 with lymphocystis on the skin and 10 clinically normal, were examined via immunohistochemistry. Affected skin displayed macroscopic, wart-like clusters of hypertrophic fibroblasts which arose from the dermis and were covered by the epithelium. Clusters were encountered on the head, trunk and fins, but there was no evidence of visceral lymphocystis. The lymphocysts were surrounded by numerous granular cells that were positive for the antimicrobial peptide (AMP) piscidin 3 and underwent intense degranulation. To identify the type of granular cells involved in this viral disease, a double immunohistochemical staining with the monoclonal antibody G7 (mAb G7), which is specific for seabream acidophilic granulocytes (AGs), and with anti-histamine (as a marker for mast cells, MCs) was applied to the skin sections of the 10 clinically normal fish and 10 fish with lymphocystis. In infected skin, the number of G7-positive cells (i.e., AGs) (18.5 ± 10.5, mean number of cells per 20,000 μm² ± S.D.) was significantly higher compared to their density in uninfected skin (1.4 ± 2.2) (t test, p < 0.01). Notably, the AGs that infiltrated the skin lesions of infected animals were found to be degranulated and to produce the pro-inflammatory cytokine interleukin-1β. No histamine-positive granular cells (i.e., MCs) were encountered in the lymphocystis lesions. The present study shows the response of skin to lymphocystis disease virus (LCDV) and provides evidence that AGs, but not MCs, are recruited and activated in response to this skin infection.     

Differential hippocampal pharmacokinetics of phenobarbital and carbamazepine in repetitive seizures induced by 3-mercaptopropionic acid

Previous evidence has shown that chronic 3-mercaptopropionic acid (MP) administration induced brain P-glycoprotein (P-gp) overexpression altering target site accumulation of phenytoin. The aim of the present work was to assess the involvement of P-glycoprotein in carbamazepine and phenobarbital hippocampal pharmacokinetics in an experimental model of epilepsy, induced by repetitive MP administration. Seizures were induced in Wistar rats by injection of MP (45 mg kg⁻¹, i.p.) during 10 days. Control rats (C) were injected with saline solution. In order to monitor extracellular brain antiepileptic levels, a concentric probe was inserted into the hippocampus. Animals were administered with carbamazepine (10 mg kg⁻¹, i.v.) or phenobarbital (20 mg kg⁻¹, i.v.) 30 min after intraperitoneal administration of vehicle or nimodipine (2 mg kg⁻¹), a well known P-glycoprotein inhibitor. No differences were found in hippocampal concentrations of carbamazepine comparing all groups. In vehicle pre-treated rats, hippocampal phenobarbital concentrations were lower in MP (maximal concentration, C_max: 6.0 ± 0.6 μg ml⁻¹, p < 0.05) than in C animals (C_max: 9.4 ± 0.9 μg ml⁻¹). Control rats pre-treated with nimodipine showed similar results (C_max: 10.7 ± 0.6 μg ml⁻¹) than those pre-treated with vehicle. Nimodipine pre-treatment in MP rats enhanced hippocampal phenobarbital concentrations (C_max: 10.2 ± 1.0 μg ml⁻¹, p < 0.05) as compared with vehicle pre-treatment.     

Impact of laparoscopic surgery on thoracoabdominal mechanics and inspiratory muscular activity

Objective

To evaluate the effect of laparoscopic surgery on pulmonary volume distributions and inspiratory muscles activity. Respiratory consequences associated with postoperative pain were also evaluated.

Methods

This study enrolled 20 patients without lung disease performed spirometry and chest wall kinematic analyses (i.e., chest wall, upper and lower ribcage and abdominal volumes), and measured the activity of inspiratory muscular before and 2 days after laparoscopic surgery. Pain was also assessed.

Results

After laparoscopy, the patients demonstrated decreased volumes in all three thoracoabdominal compartments: abdomen (ABD), upper and lower rib cage (URC and LRC, respectively) compared with the pre-operative measurements: ABD = 0.38 ± 0.20 L vs. 0.55 ± 0.25 L; URC = 0.45 ± 0.18 L vs. 0.55 ± 0.21 L; and LRC = 0.31 ± 0.18 L vs. 0.41 ± 0.23 L; p < 0.05. A reduction in the inspiratory muscular activity after surgery was also observed (sternocleidomastoid: 10.6 ± 5.1 × 10⁻³ mV vs. 12.8 ± 6.3 × 10⁻³ mV; intercostals: 16.8 ± 12.4 × 10⁻³ mV vs. 25.1 ± 21.3 × 10⁻³ mV; p < 0.05). In addition, lower volumes during deep breathing were observed in patients who reported significant pain than those who did not (0.51 ± 0.17 L vs. 0.79 ± 0.29 L; p < 0.05, respectively).

Conclusion

Laparoscopic surgery reduces chest wall ventilation and inspiratory muscular activity during deep breathing. The effects appear to depend on the patient's reported pain level.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity

Telomere length (TL), a measure of replicative senescence, decreases with aging, but the factors involved are incompletely understood. To determine if age-associated reductions in TL are related to habitual endurance exercise and maximal aerobic exercise capacity (maximal oxygen consumption, VO₂max), we studied groups of young (18-32 years; n = 15, 7 male) and older (55-72 years; n = 15, 9 male) sedentary and young (n = 10, 7 male) and older (n = 17, 11 male) endurance exercise-trained healthy adults. Leukocyte TL (LTL) was shorter in the older (7059 ± 141 bp) vs. young (8407 ± 218) sedentary adults (P < 0.01). LTL of the older endurance-trained adults (7992 ± 169 bp) was ∼900 bp greater than their sedentary peers (P < 0.01) and was not significantly different (P = 0.12) from young exercise-trained adults (8579 ± 413). LTL was positively related to VO₂max as a result of a significant association in older adults (r = 0.44, P < 0.01). Stepwise multiple regression analysis revealed that VO₂max was the only independent predictor of LTL in the overall group. Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the “anti-aging” effects of maintaining high aerobic fitness.     

Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index

Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa.The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514 ± 2.03) and I-GCa (6.836 ± 2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071 ± 2.07; p = 0.0005, p < 0.0001). In addition, the mean GCRI for the I-GCa group was significantly greater than that for the D-GCa group (p < 0.005). The GCRI-positive rate was significantly higher in subjects with GCa than in H. pylori-positive controls (D-GCa: p < 0.005, I-GCa: p < 0.0001).Many H. pylori-positive Japanese still carry a high risk for gastric cancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI.