Angiopoietin-1 promotes functional neovascularization that relieves ischemia by improving regional reperfusion in a swine chronic myocardial ischemia model

Summary This study investigates the long-term angiogenic effects of ANG-1 and VEGF in a swine chronic myocardial ischemia model. Four-weeks after gradual occlusion of the left circumflex coronary artery by ameroid constrictor, animals were injected with recombinant adenoviral vectors carrying either human ANG-1 (n=9), human VEGF₁₆₅ (n=10) or empty vector (n=7) into the left ventricle free wall supplied by the constricted artery. Left ventricular perfusion in animals that received AdANG-1 (3.25±0.16 ml/min/g, p<0.05) recovered robustly 4 weeks after gene transfer while ischemia persisted in the AdVEGF (1.09±0.13 ml/min/g) and empty vector (1.20±0.03 ml/min/g) groups. Microvascular densities in the left ventricles of animals that received AdANG-1 (19.61±1.76/0.572 mm² myocardial tissue, p<0.05) and AdVEGF (18.17±1.43/0.572 mm² myocardial tissue, p<0.05) were significantly higher than animals that received empty vector (13.53±0.92/0.572 mm² myocardial tissue) 12 weeks after gene transfer. ANG-1, but not VEGF, contributed to enhanced regional perfusion by increasing arteriolar density (1.9±0.4/0.572 mm² myocardial tissue vs. 0.7±0.2/0.572 mm² myocardial tissue, p<0.05) of large-sized (50–100 μm) arterioles. These data demonstrate that gene transfer of ANG-1 and VEGF enhances angiogenesis, but ANG-1 promotes sustained improvement of ventricular perfusion that expedites recovery of ischemic myocardium via arteriogenesis.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg^–1 I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7–8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg^–1 urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 ± 16.9 mg dl^–1, n= 6, prior to insulin and 42.0 ± 8.4 mg dl^–1, n= 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg^–1, I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 ± 14.0 mg dl^–1, n= 10, prior to insulin and 386.6 ± 43.6 mg dl^–1, n= 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation. (Mol Cell Biochem 261: 105–110, 2004)     

Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist‐to‐hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. Results: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = ?0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist‐to‐hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross‐sectional area (r = 0.37, p < 0.001). Discussion: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Global DNA methylation (LINE-1) associated with exposure to arsenic-contaminated environment and with type of arsenical skin lesions in Thailand

The effects of chronic arsenic exposure mode on DNA methylation and skin lesion type are unclear. These relationships were investigated in an arsenic-contaminated area of southern Thailand. Cases with arsenical skin lesions (n = 131) and lesion-free controls (n = 163) were selected from an arsenic-contaminated sub-district, as well as 105 controls from a non-contaminated area. Type and severity of skin lesions and salivary global DNA methylation (LINE-1) were determined. Arsenic exposure was characterized as occupational, domestic and current (toe-nail arsenic). Associations were explored using logistic regression. Cases and controls had lower LINE-1 methylation and higher toenail arsenic than external controls (74.65% and 74.61% vs 76.05%, p < 0.001 for each). Cases were more likely to have been exposed domestically (OR_total 1.76, 95% ci 1.00, 3.11; and 2.22, 95% ci 1.22, 4.03; P_trend = 0.005 for exposure <36 and ≥36 years). More severe spotty hyperpigmentation was related to higher LINE-1 methylation (P_trend=0.006). LINE-1 methylation was positively associated with toenail arsenic only among non-symptomatic exposed subjects (OR 1.31, 95% ci 1.06, 1.64; p = 0.014). Exposure to an arsenic-contaminated environment results in global DNA hypomethylation. However, among symptomatic subjects, increased global DNA methylation was associated with increased severity of spotty hyperpigmentation.     

IGFBP-3 and IGFBP-10 (CYR61) up-regulation during the development of Barrett's oesophagus and associated oesophageal adenocarcinoma: potential biomarkers of disease risk

Dys-regulation of the insulin-like growth factor (IGF) system increases the risk of a number of malignancies. The aim of this study was to investigate the role of members of the IGF binding protein (IGFBP) superfamily in the development of oesophageal adenocarcinoma (EAC) and their possible use as markers of disease risk. Expression of IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 was assessed using Real-Time-polymerase chain reaction (PCR) and immunohistochemistry in oesophageal tissues from Barrett's oesophagus (BE) patients with and without associated EAC, and in control subjects. IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 mRNA levels were up-regulated in Barrett's (n=17) and tumour tissue of EAC patients (n=18) compared with normal tissue of control subjects without BE or EAC (n=18) (p<0.001). Over-expression of IGFBP-3 and IGFBP-10/CYR61 proteins was observed in Barrett's, dysplastic and tumour tissue of EAC cases (n=47 for IGFBP-10; n=39 for IGFBP-3) compared with adjacent normal epithelium (p<0.050). Notably, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 expression in Barrett's tissue of EAC cases (n=17) was significantly (p<0.001) higher than in Barrett's tissue of BE patients with no sign of progression to cancer (n=15). Overall, the results suggest that members of the IGFBP superfamily are up-regulated during oesophageal carcinogenesis and merit further investigation as markers of EAC risk.     

Heterogeneity of hemoglobin A1d: assessment and partial characterization of two new minor hemoglobins, A1d3a and A1d3b, increased in uremic and diabetic patients, respectively

We have separated and quantified two new minor hemoglobins named HbA_1d3a and HbA_1d3b. The level of HbA_1d3a was significantly higher in uremic than in non-uremic patients (3.00 ± 0.50% vs. 1.28 ± 0.26% of total hemoglobin). It correlated well with carbamylated hemoglobin (r=0.80, n=81, p<0.002) and with plasma urea concentration (r=0.78, n=81, p<0.002). These data and the electrospray ionization mass spectrometric analysis provide strong evidence that HbA_1d3a is an α-chain modified by carbamylation. The HbA_1d3b level in the diabetic patients was found to be 1.6-fold that in non-diabetic subjects (3.00 ± 0.49 vs. 1.90 ± 0.33). This was attributed to HbA_1d3 modified by glycation. Indeed HbA_1d3b correlated significantly with HbA_1c (r=0.71, p<0.002) and with serum glucose level (r=0.62, p<0.002). These two new minor hemoglobins may serve as complements for the objective assessment of averagd long-term uremia and glycemia in uremic and diabetic patients.     

Insulin Sensitivity,Cardiorespiratory Fitness,and Physical Activity in Overweight Hispanic Youth

Objective: To determine whether cardiorespiratory fitness and/or physical activity (PA) were related to measures of insulin sensitivity and secretion independent of body composition in overweight Hispanic children. Research Methods and Procedures: Ninety‐five Hispanic children (n = 55 boys; n = 40 girls; 8 to 13 years old) participated in this investigation. The frequently sampled intravenous glucose tolerance test was used to determine the insulin sensitivity index (SI), the acute insulin response, and the disposition index. Cardiorespiratory fitness [maximal oxygen uptake (Vo_2max)] was evaluated using a treadmill protocol, and PA was determined by an interviewer‐administered questionnaire. Body composition was measured using DXA. Results: Unadjusted correlations indicated that Vo_2max (milliliters of O₂ per minute) was negatively related to SI (r = ?0.46, p < 0.05) and disposition index (r = ?0.31, p < 0.05) and positively associated with fasting insulin (r = 0.29, p < 0.05), but these relationships were no longer significant once gender, Tanner stage, fat mass, and soft lean tissue mass were included as covariates (all p > 0.05). Multivariate linear regression analysis showed that body fat mass explained 53% of the variance in SI and that Vo_2max (milliliters of O₂ per minute) was not independently related to SI. Cardiorespiratory fitness was positively related to both fat mass (r = 0.43, p < 0.001) and soft lean tissue mass (r = 0.89, p < 0.001). PA was not related to any measure of insulin sensitivity and secretion. Discussion: Cardiorespiratory fitness, as determined by Vo_2max (milliliters of O₂ per minute), was not independently related to insulin sensitivity or secretion, suggesting that Vo_2max influences insulin dynamics indirectly through fat mass.     

A resistance band increased internal hip abduction moments and gluteus medius activation during pre-landing and early-landing

An increased knee abduction angle during jump-landing has been identified as a risk factor for anterior cruciate ligament injuries. Activation of the hip abductors may decrease the knee abduction angle during jump-landing. The purpose of this study was to examine the effects of a resistance band on the internal hip abduction moment and gluteus medius activation during the pre-landing (100 ms before initial contact) and early-landing (100 ms after initial contact) phases of a jump–landing–jump task. Thirteen male and 15 female recreational athletes (age: 21.1±2.4 yr; mass: 73.8±14.6 kg; height: 1.76±0.1 m) participated in the study. Subjects performed jump–landing–jump tasks with or without a resistance band applied to their lower shanks. During the with-band condition, subjects were instructed to maintain their movement patterns as performing the jump-landing task without a resistance band. Lower extremity kinematics, kinetics, and gluteus medius electromyography (EMG) were collected. Applying the band increased the average hip abduction moment during pre-landing (p<0.001, Cohen?s d (d)=2.8) and early-landing (p<0.001, d=1.5), and the average gluteus medius EMG during pre-landing (p<0.001, d=1.0) and early-landing (p=0.003, d=0.55). Applying the band decreased the initial hip flexion angle (p=0.028, d=0.25), initial hip abduction angle (p<0.001, d=0.91), maximum knee flexion angle (p=0.046, d=0.17), and jump height (p=0.004, d=0.16). Applying a resistance band provides a potential strategy to train the strength and muscle activation for the gluteus medius during jump-landing. Additional instructions and feedback regarding hip abduction, hip flexion, and knee flexion may be required to minimize negative changes to other kinematic variables.     

High Expression of Complement Components in Omental Adipose Tissue in Obese Men

Objective: Accumulation of visceral fat is recognized as a predictor of obesity‐related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. Research Methods and Procedures: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real‐time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. Results: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue (～2‐, 4‐, 17‐, 10‐, and 7‐fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). Discussion: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra‐abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.     

Postural stability during static strain before and after a submaximal aerobic bicycle test in athletes

Control of static balance was studied in wrestlers (n = 31) in the normal state and against the background of physical fatigue, i.e., before and after a bicycle PWC ₁₇₀ test, respectively. The static balance was evaluated using a Ritm force platform (Russia) during normal basic stance (BS) and static strain (half-squatting position (HS) with the eyes open). Before physical exercise, i.e., during BS, the differences in postural control of the center of pressure (CP) between athletes and control subjects (n = 40) were nonsignificant. In the HS position, both linear and angular sway velocities of CP (LSV and ASV, respectively) were significantly lower in wrestlers (p < 0.001), and these parameters were negatively correlated with the PWC ₁₇₀ index (r = −0.454 and r = −455, p < 0.001 for LSV and ASV, respectively), which suggests that up to 20% of the sway velocity variance during static strain is dependent on the working capacity of the subjects. After the PWC ₁₇₀ test, the sway velocities of CP increased in both groups during BS (p < 0.01) and HS (p < 0.001), which testifies to the important role of muscular fatigue in the decrease in postural stability in both groups. During BS, an increase in LSV and ASV was about the same in both groups; however, during HS, an increase in the sway velocities of CP after PWC ₁₇₀ was lower in wrestlers (the intergroup differences at p = 0.037 and p = 0.008 for LSV and ASV, respectively); this parameter was negatively correlated with the recovery of the heart rate (HR) after the bicycle test (r = −0.378, p < 0.001 and r = −0.265, p < 0.05 for LSV and ASV, respectively), which suggests that rapid recovery contributes to a certain extent (about 6.5–14.2%) to the postural stability during static strain of wrestlers against the background of their physical fatigue.     

Seasonal Variation in Onset of Myocardial Infarction—A 7‐year single‐center study in Italy

Like many other serious acute cardiovascular and cerebrovascular events, acute myocardial infarction (AMI) shows seasonal variation, being most frequent in the winter. We sought to investigate whether age, gender, and hypertension influence this pattern. We studied 4014 (2259 male and 1755 female) consecutive patients with AMI presenting to St. Anna Hospital of Ferrara, Italy between January 1998 and December 2004. Some 1131 (28.2%) of the AMI occurred in persons <65 yrs of age, and 2883 (71.8%) in those ≥65 yrs of age. AMI was over‐represented in males (82% in the <65 yr group vs. 56.6% in the ≥65 yr group (χ²=13.99; p<0.001). Hypertension had been previously documented in 964 (24%) of the cases. There were 691 (17.2%) fatal case outcomes; fatal outcomes were significantly higher among the 3054 normotensive (n=614 or 20.1%) than the 964 hypertensive cases (n=77 or 8%; χ²=74.94, p<0.001). AMIs were most frequent in the winter (n=1076 or 26.8% of all the events) and least in the summer (n=924 or 23.0% of all the events; χ²=12.36, p=0.007). The greatest number of AMIs occurred in December (n=379 or 9.44%), and the lowest number in September (n=293 or 7.3%; χ²=11.1, p=0.001). Inferential chronobiological (Cosinor) analysis identified a significant annual pattern in AMI in those ≥65 yrs of age, with a peak between December and February—January for the total sample (p<0.005), January for the sample of males (p=0.014), February for fatal infarctions (p=0.017), and December for non‐fatal infarctions (p=0.006). No such temporal variations were detected in any of these categories in those <65 yrs of age. The annual pattern in AMI was also verified by Cosinor analysis in the following hypertensive subgroups: hypertensive males (n=552: January, p=0.014), non‐fatal infarctions in hypertensive patients (n=887: January, p=0.018), and elderly normotensives (n=1556: November, p=0.007).     

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.     

Children’s Beliefs about Animal Minds (Child-BAM): Associations with Positive and Negative Child–Animal Interactions

Children and animals can have a great impact on each other’s lives, yet little is known about the underpinnings of these relationships. Children’s interactions with animals may be influenced by their belief in animal minds, that animals are sentient and experience thoughts and feelings. This study introduces a newly developed measure of children’s beliefs about animal minds (Child-BAM) and investigates associations between it and factors relating to positive and negative interactions with animals. Using a questionnaire-based survey of over 1,000 6- to 13-year-olds in the UK, the results show that Child-BAM was associated with higher attachment to pets (p < 0.001), compassion (p < 0.001), humane (p < 0.001) and caring behavior (p < 0.001) toward animals, emotional attachment to animals (p = 0.003), and positive attitudes toward animals (p < 0.001). Child-BAM was also associated with less acceptance of intentional animal cruelty (p = 0.001), unintentional animal cruelty (p = 0.007), and animal neglect (p = 0.01). There was a significant difference in Child-BAM between children with pets (p = 0.013), children who had a pet of their own (p = 0.016), and age group (p < 0.001). This study enhances our understanding of the psychological underpinnings of child–animal relationships and highlights the implications for animal welfare education and for preventing childhood animal cruelty.     

Effects of halothane,isoflurane, sevoflurane and desflurane on contraction of ventricular myocytes from streptozotocin-induced diabetic rats

Various clinically used volatile general anaesthetics (e.g. sevoflurane, halothane, isoflurane and desflurane) have been shown to have significant negative inotropic effects on normal ventricular muscle. However, little is known about their effects in ventricular tissue from diabetic animals. Streptozotocin (STZ)-induced diabetes is known to induce changes in the amplitude and time course of shortening and one report suggests that the inotropic effects of anaesthetics are ameliorated in papillary muscles from diabetic animals. The aim of these studies was to investigate this further in electrically stimulated (1 Hz) ventricular myocytes. Cells were superfused with either normal Tyrode (NT) solution or NT containing anaesthetic (1 mM) for a period of 2 min (at 30–32°C). Myocytes from STZ rats were shown to have a significantly longer time to peak shortening (p > 0.001, n= 50) and the amplitude of shortening tended to be greater but this was not significant (p= 0.13, n= 50). Halothane, isoflurane, desflurane and sevoflurane significantly (p < 0.05) reduced the magnitude of shortening of control cells by 72.5 ± 3.2%, 46.5 ± 9.7%, 28.9 ± 4.3% and 22.8 ± 5.6%, respectively (n > 11 per group) but their steady-state negative inotropic effect was found to be no different in cells from STZ-treated rats (73.0 ± 4.8%, 40.7 ± 4.7%, 25.0 ± 5.2% and 19.8 ± 5.2%, respectively, n > 10 per group). Therefore, we conclude that the inotropic effects of volatile anaesthetics were not altered by STZ treatment. (Mol Cell Biochem 261: 209–215, 2004)     

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague–Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (DEG; n = 8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). The levels of t-PI3-K, p-PI3-K, and p-CREB, and the p-CREB/t-CREB ratio significantly increased in the NEG (p < 0.001, respectively). The p-PI3-K/t-PI3-K ratio significantly increased in the DEG (p < 0.001). The p-Erk1/t-Erk1 ratio significantly increased in the NEG (p < 0.001), whereas the p-Erk2/t-Erk2 ratio significantly decreased in the DCG and DEG (p < 0.001). The caspase-3 level significantly increased in the DCG compared with that in the DEG (p < 0.001). These results suggest that treadmill exercise increases NGF levels and accelerates p-PI3-K activation in order to suppress apoptotic cell death in the soleus muscle of diabetic rats.     

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.     

Reduction-oxidation (Redox) and vascular tissue level of homocyst(e)ine in human coronary atherosclerotic lesions and role in extracellular matrix remodeling and vascular tone

Hyperhomocyst(e)inemia in patients with coronary and peripheral arterial occlusion has been demonstrated by others. Redox-state of homocyst(e)ine causes dysfunction of endothelial cells and promote growth of vascular smooth muscle cells. The role of tissue, protein bound and unbound, oxidative mixed disulfides in the development of fibrous plaque in atherosclerotic lesion is not known. Redox-state around the fibroblasts and vascular smooth muscle cells modulates the expression of extracellular matrix (ECM) components (Tyagi et al. 1996, J Cell Biochem, 61: 139-151). To determine the role of tissue homocystine in fibrotic atherosclerotic plaque development, coronary arteries were isolated from ischemic explanted hearts (n = 10). Apparently normal vascular tissue was obtained from idiopathic cardiomyopathic explanted hearts (n = 10). Tissue extract were prepared from atherosclerotic lesions and from normal arteries devoid of adventitia. Interaction of homocystine with Ellman's reagent (5, 5-dithio-bis-2-nitro benzoic acid) catalyzed by limiting amount of reducing agent (catalyst) generated change in optical density (OD) at 412 nm in dose dependent fashion. We have generated a standard curve between change at 412 nm and amount of homocystine. The change in OD at 412 nm with increasing amount (0-25 g) of homocystine demonstrated linearity. The protein-bound oxidized disulfides were precipitated by trichloroacetic acid (TCA) and free-oxidative disulfides in the supernatant were collected. The pathophysiological amount of protein-bound disulfide in atherosclerotic tissue (1.0 ± 0.2g/mg total protein) was 10 times that in normal tissue (0.1 ±0.01 g/mg, p < 0.001). The amount of free oxidative disulfide in atherosclerotic tissue (1.5 ± 0.3g/mg) was 15 times that in normal tissue (0.12 ± 0.02 g/mg, p < 0.001). To determine the role of homocystine in ECM expression, ECM collagenase activity in the presence and absence of homocystine was measured by zymography. The effect of homocysteine on collagenase activity was biphasic, increased at < [0.01 mM] and inhibited at > [0.1 mM]. To determine whether homocystine regulates vascular tone, isometric measurements were carried out using normal coronary rings. Results suggested that homocystine induced endothelial-modulated vasoconstriction in coronary vessels. Tissue oxidative disulfides and the homocystine may contribute to the development of fibrotic atherosclerotic lesions and vascular dysfunction.     

Eveningness associates with smoking and sleep problems among pregnant women

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness–eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.     

Sociodemographics of Pet Ownership among Adolescents in Great Britain: Findings from the HBSC Study in England,Scotland, and Wales

The aim of this study was to assess the prevalence of pet ownership among adolescents in Great Britain and identify any sociodemographic differences between pet owners and non-pet owners. A total of 14,328 11-to 15-year-old adolescents from England, Scotland, and Wales were included in the analysis. Results revealed 15-year-old adolescents were significantly more likely than 11-year-old adolescents to own dogs (OR = 1.146, p < 0.001) but less likely to own fish, reptiles, or amphibians (OR = 0.629, p < 0.001), and small mammals (OR = 0.630, p < 0.001). Thirteen-year-olds were significantly more likely than 11-year-olds to own dogs (OR = 1.240, p = 0.021) and birds (OR = 1.299, p = 0.010), but significantly less likely to own fish, reptiles, or amphibians (OR = 0.795, p < 0.001). No gender differences were found. White adolescents were more likely than non-white adolescents to own all pet types. Those living in single-parent families were significantly more likely than those living with two parents to own dogs (OR = 1.186, p = 0.013) and cats (OR = 1.319, p < 0.001). Furthermore, those who reported living in stepfamilies were also more likely to own cats (OR = 1.428, p < 0.001). Adolescents with siblings were more likely to own cats (OR = 1.391, p = 0.001), fish, reptiles, or amphibians (OR = 1.220, p = 0.037) than adolescents without siblings. Adolescents with employed parents (both or one) were significantly more likely than those with unemployed parents to own dogs (OR = 1.414, p = 0.002) and birds (OR = 1.523, p = 0.018). Adolescents from high-affluence families were less likely than adolescents from low-affluence families to own dogs (OR = 0.888, p = 0.037), small mammals (OR = 0.832, p = 0.005), and birds (OR = 0.801, p = 0.046). Furthermore, family affluence differences were found in different pet types. Differences in all pet types and siblings were also found in a proxy measure of attachment to pets. This study provides evidence that pet ownership is related to several sociodemographic factors. These are relevant to take into account when performing HAI studies on adolescents.