Wk Group Research Articles

Evaluation of the Group Lifestyle Balance Program in a Military Setting: An Investment Worth Expanding.

The Diabetes Prevention Program (DPP) demonstrated that lifestyle intervention programs were effective in preventing or delaying the onset of diabetes. The Group Lifestyle Balance (GLB) program translated the DPP curriculum into a 12-wk group intervention for those at risk for diabetes. This retrospective evaluation examined clinical outcomes for patients in the Diabetes Center of Excellence GLB program located at Wilford Hall Ambulatory Surgical Center from 2009 to 2013. Objectives included determining rates of retention, demographic characteristics of program completers, and changes in metabolic surrogates of disease prevalence. Adults with prediabetes or metabolic syndrome (MetS) were referred to the GLB program. Updated participant metabolic data were collected at regular intervals during their participation. During the 5-yr study, 704 patients attended the initial class. Overall, 52% of all participants completed the program with the greatest decline in participation occurring by the fourth week (30%). Baseline prevalence of conditions of interest for those who completed the program was prediabetes (93.2%), obesity (56.1%), and MetS (31.5%). GLB completers were older and retired (p < 0.05). A significant number of active duty military members (44.9%, p < 0.01, n = 53) dropped out of the program before the fourth week. Furthermore, those who completed the program saw a 2.0% reduction in prediabetes prevalence (p < 0.001), obesity decreased by 8.7% (p < 0.001), and MetS decreased by 6.8% (p < 0.01). Significant differences were found for central obesity, triglycerides, and fasting blood sugar (p < 0.001). The GLB program is a valuable DPP and was effective at improving clinical outcomes and reducing the incidence of prediabetes, obesity, and MetS for participants who completed the program. Every effort should be made to support and encourage GLB participants to complete the program.

Effect of weaning age on growth performance, feed efficiency, nutrient digestibility and blood-biochemical parameters in Droughtmaster crossbred beef calves.

ObjectiveThe objective of this study was to determine the effect of weaning age on intake, performance, nutrition metabolism and serum parameters of beef calves.MethodsSixty Droughtmaster crossbred calves were assigned to 5 groups with 12 calves in each group. The calves in control group remained with the dams till the 22-week age, while the calves weaned at 28 d (4 wk), 42 d (6 wk), 56 d (8 wk), and 70 d (10 wk) of age were sent to group 4 wk, group 6 wk, group 8 wk, and group 10 wk, respectively, and then were fed on milk replacer till the 22-week age. Feed intake and body weight and size were record and blood metabolites were measured. And 24 calves of them (6 in each group) were picked randomly for digestion and metabolism trail. Feed, feces and urine sample were taken and measured.ResultsDry matter intake of calves in group 4 wk was significantly lower than those in the remaining groups from wk 17 to 22 (p<0.05). Feed efficiency of the calves was higher in groups 4 wk and 6 wk than those in groups 8 wk and 10 wk from 11 to 13 wk (p<0.05), and calves had higher feed efficiency in group 4 wk, group 6 wk, and group 8 wk than those in group 10 wk from wk 14 to wk 22. Calves in group 4 wk and 6 wk had lower body weight than group 8 wk and group 10 wk and control group at 10-week age (p<0.05) and 13-week age (p<0.05), and calves in group 6 wk had no significant difference in body weight with control group, group 8 wk and 10 wk (p>0.05) but was higher than that of group 4 wk (p<0.05). Calves in group 6 wk had higher final body weight and total gain than group 4 wk, but no difference of total gain with that of groups 8 wk, 10 wk, and control group. And weaning calves at 6-week age brought higher feed efficiency and average daily gain from wk 14 to wk 22, and higher dry matter and organic matter digestibility at 21 wk.ConclusionIt is concluded that the weaning of calves at 6 weeks of age gave positive results.

Abstract P292: Re-evaluation of the Relations of Egg Consumption to Serum Total Cholesterol, Cause-specific and All-cause Mortality

Background: We previously reported that egg consumption was related to age-adjusted serum total cholesterol (TCH), and all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group in women, whereas no such relations were noted in men, using 14 year follow-up of NIPPON DATA80. Re-evaluation of these relations in a different cohort is needed. Methods: We analyzed the relations of egg consumption to serum total cholesterol (TCH) and cause-specific and all-cause mortality by using the NIPPON DATA90 database with a 15-year follow-up. At the baseline in 1990, a nutritional survey was performed by using the food-frequency method, and data were collected on study participants, ages 30 years and over, from randomly selected areas in Japan. We followed 4,799 female participants without history of stroke or myocardial infarction (mean age 52.8 y) for 15 years. Results: The participants were categorized into 5 egg consumption groups on the basis of their responses to a questionnaire (seldom, 1-2/wk, 1/2 d, 1/d, and ≥2/d). There were 218, 1507, 1622, 1409, and 43 women in each of the 5 groups, respectively. Age-adjusted TCH was not related to egg consumption (206.4, 206.3, 207.0, 207.7, and 203.8 mg/dL in the 5 egg consumption categories, respectively, P=0.737, analysis of covariance). There were 199 cardiovascular disease (CVD), 221 cancer, and 642 all-cause mortality during follow-up. Cox analysis, adjusted for confounding factors, found that all-cause and cancer mortality in the ≥2/d group were significantly higher than that in the 1-egg/d group (HR in the ≥2/d vs the 1-egg/d group: all-cause, 1.88 [95%CI: 1.12-3.16]; cancer, 2.77 [1.32-5.80]), and that cancer mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group (0.70 [0.50-0.99]). Egg consumption was not associated with CVD mortality. Conclusions: Loss of the relation of egg consumption to TCH might be due to that hypercholesterolemic individuals avoided eating eggs. Positive association of egg consumption with cancer and all-cause mortality needs further evaluation, and it may indicate that limiting egg consumption has some health benefits, at least in women in Japan.

Efficacy of Indomethacin in Pharmacological Closure of PDA in Preterm Neonates: A Prospective Study from Tertiary Care Centre in Rural India

Background: Patent ductusarteriosus (PDA) is a fetal shunt necessary for intrauterine survival of the baby, however its closure at birth occurs as pulmonary vascular resistance drops and lungs get expanded for participating in ventilation. However, PDA remains patent in a large proportion of preterm babies and by day -7, 87% of babies <24 wk gestation have a PDA which hinders in ventilation and causes ductal steal to vital organs. Hence, we aimed to study pharmacological closure of ductus in preterm babies. Aims and Objectives: 1) To study the efficacy of COX inhibitor, Indomethacin in ductal closure in preterm babies <34 wk gestation. 2) To compare the symptomatology of PDA in different groups of preterm babies <34 wk GA. Methods: A Hospital-based prospective study was conducted in tertiary care NICU.A total of 104 consecutive, eligible preterm babies <34 wk with echocardiographically documented PDA. Indomethacin (COX inhibitor) was administered orally in a dose of 0.2 mg/kg 12 h for 3 doses and the babies underwent Echo study in first 48 h, after2 days, 7days, and weekly thereafter till PDA closure. A second cycle of indomethacin was repeated if PDA did not respond to the initial treatment. Results: 75/104 (72%) PDAs closed with indomethacin while 13(12.5%) did not respond, and 16(15.38%) showed a reduction in the calibre of PDA. 26–30 wk group showed a brisk response to ductal closure with indomethacin within 108.1±12.44 h, and a mean no. of cycles of indomethacin of 0.98±5.75. Conclusion: With indomethacin we achieved 72% (75/104) closure rates. The best response to indomethacin was noted in 30–32 wk GA group, while maximum nonresponders were in 32–34 wk; suggesting as gestation increases, response to PG inhibitors decreases. KEYWORDS: Patent ductusarteriosus, Cyclo-oxygenase, Indomethacin, Preterm Neonates, PG inhibitors, Ductus arteriosus, Ductal flow.

Contralateral Repeated Bout Effect of Eccentric Exercise of the Elbow Flexors.

This study compared the magnitude of the repeated bout effect (RBE) for different time intervals between two bouts of eccentric exercise of the elbow flexors to better understand the contralateral RBE (CL-RBE). Untrained young men (22.0 ± 1.8 yr) were allocated to either a control or one of seven CL-RBE groups (n = 13 per group). The CL-RBE groups performed exercise consisting of 30 maximal isokinetic (30°·s) eccentric contractions of the elbow flexors (ECC1) with either dominant or nondominant arm followed 0.5 h, 6 h, 12 h, 24 h (1 d), 7 d (1 wk), 28 d (4 wk), or 56 d (8 wk) by the same exercise (ECC2) using the opposite arm. The control group used the nondominant arm for ECC1 and ECC2 separated by 2 wk. Maximal voluntary concentric contraction torque, peak torque angle, range of motion, upper arm circumference, muscle soreness, ultrasound echo intensity, and plasma creatine kinase activity and myoglobin concentration changed (P < 0.05) after ECC1, without significant difference among the groups. Changes in all variables after ECC2 were smaller (P < 0.05) than those after ECC1 for the control, 1 d, 1 wk, and 4 wk groups, indicating the RBE. However, the changes were not significantly different between ECC1 and ECC2 for the 0.5 h, 6 h, 12 h, and 8 wk groups. The difference in the changes in all variables between ECC1 and ECC2 was smaller for the 1 d (70%), 1 wk (55%), and 4 wk (36%) than the control group (91%), and the magnitude of the CL-RBE was reduced with increasing the time between bouts from 1 d to 4 wk (P < 0.05). These results suggest that the CL-RBE lasts shorter than the ipsilateral RBE (>8 wk) and requires a day to be conferred.

Walking and Calcified Atherosclerotic Plaque in the Coronary Arteries: The National Heart, Lung, and Blood Institute Family Heart Study.

Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification. In a cross-sectional design, we studied 2971 participants of the National Heart, Lung, and Blood Institute Family Heart Study without a history of myocardial infarction, coronary artery bypass grafting, or percutaneous transluminal angioplasty. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute walking metabolic equivalent hours. CAC was measured by cardiac computed tomography. We defined prevalent CAC and aortic calcification using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios. Mean age was 55 years, and 60% of participants were women. Compared with the ≤3.75-Met-h/wk group, prevalence ratios for CAC after adjusting for age, sex, race, smoking, alcohol use, total physical activity (excluding walking), and familial clustering were 0.53 (95% confidence interval, 0.35-0.79) for >3.75 to 7.5 Met-h/wk, 0.72 (95% confidence interval, 0.52-0.99) for >7.5 to 15 Met-h/wk, and 0.54 (95% confidence interval, 0.36-0.81) for >15 to 22.5 Met-h/wk, (P trend=0.01). The walking-CAC relationship remained significant for those with body mass index ≥25 (P trend=0.02) and persisted with CAC cutoffs of 300, 200, 150, and 50 but not 0. When examined as a continuous variable, a J-shaped association between walking and CAC was found. The walking-aortic calcification association was not significant. Our findings suggest that walking is associated with lower prevalent CAC (but not aortic calcification) in adults without known heart disease.

Coadministration of calcium chloride with lead acetate can improve motility of cauda epididymal spermatozoa in Swiss white mice

Lead is an industrial heavy metal that can decrease sperm motility. The aim was to investigate the protective effects of calcium against lead on motility of spermatozoa. In total 40 adult male Swiss white mice were randomly divided into 5 groups (control, lead of 1(st) wk, lead of 2(nd) wk, lead/calcium of 1(st) wk and lead/calcium of 2(nd) wk). The lead groups of mice were injected by a single dose of lead acetate (200 mg/kg) intraperitoneally. Lead/calcium groups of mice were injected by a single same dose of lead acetate along with three doses of 80 mg/kg calcium chloride. The control group of mice was injected only with same volume of distilled water through the same route. Mice of 1(st) and 2(nd) wk groups were sacrificed through cervical dislocation one and two weeks after injections respectively. Mean of the progressive motile spermatozoa of cauda epididymis in lead/calcium group of the first week was higher than the lead group of the first week and this difference was significant. There was not any significant difference among weight of testes and epididymides of all groups. It can be concluded that calcium can decrease the effects of lead on sperm motility.

Correlation between Ribosome Biogenesis and the Magnitude of Hypertrophy in Overloaded Skeletal Muscle

External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size.

Effects of sphincter of Oddi motility on the formation of cholesterol gallstones.

To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs. Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation. The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups. A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer.

AIMTo investigate the prognostic effect of a delayed interval between neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer.METHODSWe evaluated 87 patients with locally advanced mid- or distal rectal cancer undergoing total mesorectal excision following an interval period after neoadjuvant CRT at Şişli Hamidiye Etfal Training and Research Hospital, Istanbul between January 2009 and January 2014. Patients were divided into two groups according to the interval before surgery: < 8 wk (group I) and ≥ 8 wk (group II). Data related to patients, cancer characteristics and pathological examination were collected and analyzed.RESULTSWhen the distribution of timing between group I (n = 45) and group II (n = 42) was viewed, comparison of interval periods (median ± SD) of groups showed a significant difference of as 5 ± 1.28 wk in group I and 10.1 ± 2.2 wk in group II (P < 0.001). The median follow-up period for all patients was 34.5 (9.9-81) mo. group II had significantly higher rates of pathological complete response (pCR) than group I had (19% vs 8.9%, P = 0.002). Rate of tumor regression grade (TRG) poor response was 44.4% in group I and 9.5% in group II (P < 0.002). A poor pathological response was associated with worse disease-free survival (P = 0.009). The interval time did not show any association with local recurrence (P = 0.79).CONCLUSIONDelaying the neoadjuvant CRT-surgery interval may provide nodal down-staging, improve pCR rate, and decrease the rate of TRG poor response.

Dietary vitamin D dose-response in healthy children 2 to 8 y of age: a 12-wk randomized controlled trial using fortified foods

Vitamin D is fundamental for bone health. A high proportion of Canadian 2- to 8-y-olds do not meet the Estimated Average Requirement (EAR) of 400 IU/d. The objective was to determine whether vitamin D intakes consistent with the EAR or Recommended Dietary Allowance (RDA), through fortification of additional dairy products, would result in higher vitamin D status in young children. Participants aged 2-8 y (n = 77; Montreal, Canada) were randomly assigned to 1 of 3 dietary vitamin D targets (control; EAR: 400 IU/d; or RDA: 600 IU/d) for 12 wk (January to April 2014). Anthropometric measurements, demographic characteristics, dietary intakes, fasting serum parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], and ionized calcium were compared by using mixed-model ANOVA. Participants' mean ± SD age was 5.1 ± 1.9 y; 54.5% were boys with body mass index z scores of 0.50 ± 0.85. Compliance was 85% overall. No differences were observed in baseline dietary vitamin D intakes or serum 25(OH)D. At 12 wk, the EAR and RDA groups had significantly higher vitamin D intakes [median (IQR): control, 227 (184-305) IU/d; EAR, 410 (363-516) IU/d; and RDA, 554 (493-653) IU/d; P < 0.05] and serum 25(OH)D concentrations (control: 55.8 ± 12.3 nmol/L; EAR: 64.1 ± 10.0 nmol/L; and RDA: 63.7 ± 12.4 nmol/L; P < 0.05) than the control group. Ninety-six percent of children in the EAR and RDA groups and 67% of the control group had 25(OH)D concentrations ≥50 nmol/L. Increasing the vitamin D intakes of young children through fortification of alternative dairy products results in significantly higher serum concentrations of 25(OH)D and a significantly greater proportion of children with serum 25(OH)D ≥50 nmol/L during periods of minimal ultraviolet B radiation exposure. This trial was registered at clinicaltrials.gov as NCT02097160 and had Health Canada Temporary Marketing Authorization Letters for both products (TM-13-0432 and TM-13-0433).

Fish oil supplementation during chemotherapy increases posterior time to tumor progression in colorectal cancer

abstractThe authors evaluated clinical outcomes during and after chemotherapy in colorectal cancer patients supplemented with fish oil during the first 9 wk of treatment. Thirty individuals never submitted to chemotherapy were randomized into supplemented group (SG), which received 2 g/day of fish oil (0.6 g/day of EPA and DHA) for 9 wk or control group (CG), which received neither fish oil nor placebo. Outcomes assessed were number of chemotherapy cycles administered; days undergoing chemotherapy; number of delays and interruptions in the administration of chemotherapy; number of hospitalizations during chemotherapy; tumor progression; values of carcinoembryonic antigen (CEA); days until events (death and progression); and 3 yr survival. Time to tumor progression was significantly longer in SG [S593 days (±211.5)] vs. CG [330 days (± 135.1); P = 0.04], other outcomes did not differ between groups. Subjects with advanced cancer who received fish oil presented longer time to tumor progression and lower CEA values after chemotherapy; however these differences were not statistically significant. Supplementation with 2 g/day of fish oil for the first 9 wk of chemotherapy may contribute to delay in tumor progression in colorectal patients, possibly by enhancing the antineoplastic action of the chemotherapeutic drug.

Wheat Type (Class) Influences Development and Regression of Colon Cancer Risk Markers in Rats

We previously found red wheat more effective than white wheat in reducing colon cancer risk in rats when fed during initiation and postinitiation stages. Here we examine the effect of wheat on colon cancer risk in early and late postinitiation stages in carcinogen-treated rats. Four groups were fed a basal diet, 1 group a red wheat diet, and 1 group a white wheat diet. After 6 wk, 1 basal, the red and white groups were killed (early postinitiation stage). Of the remaining basal groups, 1 continued on the basal diet, 1 was switched to red and another to white wheat for 8 more wk (late postinitiation stage). Red and white wheat significantly reduced morphological [aberrant crypt foci (ACF)] and biochemical (β-catenin accumulated crypts) markers in both early and late postinitiation stages. Both wheat diets reduced dysplasia markers (sialomucin-expressing ACF and mucin depleted foci), compared to the basal diet, during the late postinitiation stage, but red wheat more so. Only red wheat significantly reduced the number of metallothionein-positive crypts, a stem cell mutation marker, in both stages. Overall, red wheat flour reduced risk markers more than white wheat flour, and this was more pronounced in the late post-initiation stage.

Different subtypes of Guillane-Barré syndrome in children

Guillan-Barre syndrome (GBS) is a debilitating illness with different subtypes depending on geographical area. In this study we review the GBS subtypes in Iranian children. One hundred and eight children below 15 yr entered the study during 7 yr (1998-2005), they were evaluated in 1 st (95 cases) and 2 nd wk (13 cases) diagnosed clinically, electrodiagnostically and their cerebrospinal fluid (CSF) were analyzed. Patients were divided into demyelinating and axonal forms. Data were analyzed by t test for continuous measures and the Fisher's exact test for categorical variables in SPSS 16. P less 0.05 was significant. The means age ± SD of affected patients are 4.8 ± 2.7 yr (minimum 1 yr, maximum 14.5 yr). CSF protein and pleocytosis were more common in 2 nd wk group (77 mg/dL in first week versus 63 mg/dL in second week); 2% (first week) and 30% CSF pleocytosis occurred (second week). Demyelinating form happens in 47% of patients, axonal 40% and combined form of axonal and de- myelinating form happened in 9%. Normal electrodiagnostic tests in spite of clinically confirmed GBS were observed in 4%. CSF protein was higher in demyelinating compared to axonal form (71 mg/dL and 54 mg/dL). There is no sex predilection for GBS affection (59 males, and 49 females). Peak incidence of GBS in children is below age of 5 yr (65%) ;axonal form of GBS (sensory and motor) make a considerable proportion of GBS in children (40%) with lower CSF protein compared to demye- linating type, but it is not statistically significant (P > 0.05).

Cardiac Protection from Ischemia-Reperfusion Injury in Swimming Mice

PURPOSE:The purpose of this study was to determine whether cardiac protection from ischemia could be afforded with a forced-swimming as a higher intensity and stress model of exercise. We hypothesised was that higher-intensity training via forced swimming might invoke additional protective mechanisms or pathways than those previously reported in response to lower intensity voluntary activity such as wheel running. METHODS: Male C57Bl/6 mice swam for 90 min twice a day for 1 or 2 wk before randomly assigned to either 1) molecular analysis of cardiac pro-survival kinases with Phospho-Receptor Tyrosine Kinase (P-RTK) Proteome arrays and Western Immunoblotting, 2) transcriptional adaptations via qRT-PCR, or 3) global ischemia-reperfusion injury assessment via Langendorff isolated heart preparation with 25-min ischemia/45-min reperfusion. RESULTS: Hearts exhibited physiological hypertrophy (15.44% and 22% increase in Heart:Body weight ratio compared to sedentary controls in 1 and 2 wk groups respectively). Langendorff perfusion revealed left ventricular developed pressure (LVDP) improved (61.46% ± 5.7 vs. 44.35% ± 3.7, P<0.01) and end diastolic pressure was reduced (EDP mmHg: 12.68 ± 1.8 vs. 27.40 ± 1.8, P<0.01) following 2 wks of swim training. Subsequent gene and protein expression showed differential signaling in pro-survival kinases and other cardioprotective mechanisms. Pooled sample proteome arrays within the 2-week group showed exercised mice exhibited greater phosphorylation of various growth factors such as Insulin receptor, IGF-1R, FGF, HGF, PDGF. Protein expression of NFKB was reduced in exercised groups. CONCLUSIONS: These data indicate that swimming mice exhibited significant cardioprotection compared to the sedentary group after 2 weeks of exercise. Subsequent proteomic screening showed that in the 2-week group, a number of P-RTK growth factor receptors were activated in response to exercise. The anti-inflammatory and activation of pro-survival kinases due to the hormetic effect of exercise warrants further investigation.

SIRT1 Plays a Protective Role in Intervertebral Disc Degeneration in a Puncture-induced Rodent Model.

Experimental animal study of treatment of intervertebral disc (IVD) degeneration. This report aims to evaluate the in vivo effects of SIRT1 on IVD biology and to explore its potential mechanism. Silent mating type information regulator 2 homolog 1 (SIRT1) has attracted immense attention because of its functions in a variety of aging-related diseases. Despite previous studies indicated that SIRT1 showed a unique expression with degeneration in some in vitro study, there is no in vivo research on the role SIRT1 plays in IVD and its mechanism. Coccygeal discs were punctured to induce disc degeneration. Sixteen C57BL/6J mice received either Carboxy methocel (Vehicle) or Resveratrol (RES) gavage. Eight SIRT1 mice and their SIRT1 littermates were also used in this study. At 2 and 6 weeks after puncture, magnetic resonance images were obtained. The mice were subsequently killed, and the spine was extracted for further evaluation. Coccygeal disc puncture caused IVD degeneration in the mice. A SIRT1 activator, RES, markedly ameliorated this pathological change, as demonstrated by stronger signal intensity in the T2-weighted images, as well as a significantly lower magnetic resonance imaging grade (at 2 wk vs. Vehicle group P < 0.001). Histological analysis also revealed an improvement in the RES group compared with the Vehicle group (P < 0.05). Genetic ablation of 1 allele significantly enhanced the level of damage relative to the wild-type mice. In addition, SIRT1 activation suppressed the expression of p16 and at the same time, promoted proliferating cell nuclear antigen and type II collagen expression in disc cells, whereas genetic ablation of 1 allele SIRT1 exhibited the opposite consequence. The SIRT1 activator RES protects against puncture-induced disc injury whereas SIRT1 deficiency aggravates tissue injury; the protective role of SIRT1 is partly mediated by suppressing p16, which plays a role in elevating the decreased proliferative ability of the senescent nucleus pulposus cells. N/A.

Effect of daily lithium chloride administration on bone mass and strength in growing broiler chickens,

The objective was to determine the effects of oral lithium chloride supplementation on bone strength and mass in broiler chickens. Ninety-six broilers were assigned to 1 of 2 treatment groups (lithium chloride or control; n = 48/treatment). Beginning at 1 or 3 wk of age, chickens were administered lithium chloride (20 mg/kg body weight) or water daily by oral gavage. At 6 wk of age, chickens were euthanized and bone and muscle samples were collected. A 24 h lithium chloride (20 mg/kg body weight) challenge determined that serum lithium chloride increased within 2 h and cleared the system within 24 h, demonstrating the effective delivery of lithium chloride. Treatment did not influence body weight (P ≥ 0.20) or feed intake (P ≥ 0.81), demonstrating that lithium chloride did not negatively affect broiler growth. To determine bone strength, 3-point bending was performed on the femora and tibiae obtained from control and lithium chloride-treated birds in the 1 wk group. Lithium chloride-treated birds had a 22% reduction in stiffness compared with control in the femora (P = 0.02) without a corresponding reduction in elastic modulus. No differences were observed in yield or ultimate load and in the corresponding calculations of stresses (P ≥ 0.26). The toughness of tibiae was not altered in lithium chloride compared with control (P = 0.11). Bone length and micro-CT imaging were performed on the tibiae of control and lithium chloride groups. No differences (P ≥ 0.52) in bone length, cortical or trabecular bone volume, trabecular thickness, number, or spacing were observed. Lithium chloride treatment did not affect pectoralis muscle color or lipid oxidation (P > 0.05). In conclusion, lithium chloride treatment in broilers did not negatively affect growth or meat quality. A reduction in bone stiffness of the femur with lithium chloride treatment was observed, however unlike the mouse model, the dosages of lithium chloride used in the current study did not result in anabolic effects on broiler long bones.

Upregulation of TRPC1/6 may be involved in arterial remodeling in rat

BackgroundHypertension and its complications are associated with arterial remodeling. Transient receptor potential cationic channels (TRPCs) are important nonselective cationic channels that regulate calcium homeostasis in mammalian cell membranes. We aimed to study the expression of various TRPC isoforms in spontaneously hypertensive rat (SHR) carotid arterial remodeling and explore the relationship between SHR carotid arterial remodeling and TRPC expression. Materials and methodsThirty male SHRs were randomly divided into three groups and sacrificed at ages 4, 8, and 18 wk, respectively, with matching control male Wistar-Kyoto rats (n = 10). Caudal artery systolic blood pressure (SBP) was measured every 2 wk. Carotid artery remodeling parameters including carotid artery wall thickness (MT), lumen diameter (LD), medial area, collagen area rate, and average nuclear area in media cells were determined after histologic staining. Real-time polymerase chain reaction and immunoblot assays were performed to assess TRPC expression. Carotid artery remodeling and TRPC expression were reevaluated after ginsenoside Rb1 treatment from eighth to eighteenth week. ResultsCarotid artery remodeling of SHRs was aggravated gradually with age and SBP, as well as MT, LD, MT/LD, medial area, average nuclear area in media cells, and collagen deposition, most obvious at 18 wk. Interestingly, expression of TRPC1, 3, and 6 increased with age and SBP, with TRPC1/6 showing significant differences between the Wistar-Kyoto and 18 wk groups; TRPC4/5 expression was unchanged and TRPC7 was barely detected. Importantly, after ginsenoside Rb1 treatment, TRPC1/6 expressions were significantly inhibited, SBP decreased, and the carotid artery remodeling in SHRs relieved. ConclusionsUpregulation of TRPC1 and TRPC6 may be involved in carotid arterial remodeling in SHRs.

Abstract 2681: 4-methylumbelliferone: Dietary supplement turned chemo-preventive and anti-metastatic agent for prostate cancer

Abstract INTRODUCTION: Hyaluronic acid (HA), a glycosaminoglycan, is associated with prostate cancer (PCa) progression and metastasis. 4-methylumbelliferone (4-MU) is dietary supplement that inhibits HA-synthesis. In this study we evaluated chemopreventive and therapeutic efficacy of 4-MU to prevent PCa growth and metastasis in three PCa models. METHODS: Efficacy of daily oral gavage of 4-MU was evaluated in 3 PCa models: Model 1: TRAMP mice (n = 8-20/group) were treated with vehicle or 4-MU (450 mg/kg) by starting stage-specific treatment at 8 (PIN stage), 12 (adenocarcinoma) and 22 (invasive carcinoma) wks of age. Model 2: Mice were treated with 4-MU (200 mg/kg or 450 mg/kg) following intracardiac injection of Luciferase expressing PC3-ML cells. 3. Palpable DU145 xenografts were treated with 4-MU (200 and 450 mg/kg). Effect of 4-MU on EMT markers, HA receptors was evaluated by Q-PCR, immunoblotting and/or immunohistochemistry in PCa cells and xenograft tissues. HA add back and overexpression studies were conducted to evaluate the mechanism of action of 4-MU. RESULTS: In the TRAMP model, at 28 wks, 100% of vehicle treated mice developed PCa, but tumor growth and progression was inhibited in all 4-MU treated groups; P+SV weight (g): vehicle: 3.2±2.9; 8 wk: 0.43±0.14; 12 wk: 0.35±0.04; 22 wk: 1.0±0.35 g. The P+SV weight in TRAMP mice at 22 wks of age was 0.9±0.04, showing that late stage administration of 4-MU halted further tumor progression. Animals in 8, 12 and 22 wk groups remained tumor free until 52, 44 and 34 wks respectively, even after stopping treatment at 28 wks. While 55% of vehicle treated animals developed metastasis, none of the treated groups had metastasis. In the PC3-ML intracardiac model, 100% of the mice in the vehicle group but none in the treatment group developed skeletal metastasis. In the DU145 model, 4-MU inhibited tumor growth. No serum/organ toxicity or weight loss was observed in any treatment groups. In all models, 4-MU treatment downregulated HA, HA receptors (CD44, RHAMM) and EMT markers (β-catenin, Zeb2) by &amp;gt;2-fold) but up-regulated E-cadherin. HA addition and overexpression of myristoylated AKt inhibited 4-MU effects. CONCLUSION: 4-MU is a potent non-toxic, oral chemopreventive agent, which inhibits PCa growth and metastasis by abrogating HA-signaling and reversing EMT. Support: R01 CA 123063-04 (VBL); R01 CA 72821-11 (VBL) Note: This abstract was not presented at the meeting. Citation Format: Travis Yates, David Alonzo, Soum Lokeshwar, Kelly Hoye, Luis E. Lopez, Marie Hupe, Vinata Lokeshwar. 4-methylumbelliferone: Dietary supplement turned chemo-preventive and anti-metastatic agent for prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2681. doi:10.1158/1538-7445.AM2014-2681

Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide, gastrin and cholecystokinin octapeptide.

To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs. Thirty-four adult male Hartley guinea pigs were divided randomly into two groups: the control group and pigment stone group. The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice, and were fed a pigment lithogenic diet and sacrificed after 3, 6, 9 and 12 wk. SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage. Serum vasoactive intestinal peptide (VIP), gastrin and cholecystokinin octapeptide (CCK-8) were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay. The incidence of pigment gallstone formation was 0%, 0%, 16.7% and 66.7% in the 3-, 6-, 9- and 12-wk group, respectively. The frequency of myoelectric activity decreased in the 3-wk group. The amplitude of myoelectric activity had a tendency to decrease but not significantly. The frequency of the SO decreased significantly in the 9-wk group. The SO basal pressure and common bile duct pressure increased in the 12-wk group (25.19 ± 7.77 mmHg vs 40.56 ± 11.81 mmHg, 22.35 ± 7.60 mmHg vs 38.51 ± 11.57 mmHg, P < 0.05). Serum VIP was significantly elevated in the 6- and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group. Pigment gallstone-causing diet may induce SO dysfunction. The tension of the SO increased. The disturbance in SO motility may play a role in pigment gallstone formation, and changes in serum VIP and CCK-8 may be important causes of SO dysfunction.