The effect of SIRT1 protein knock down on PGC-1α acetylation during skeletal muscle contraction

[Purpose]

The purpose of this study was to investigate the effect of Sirtuin 1 (SIRT1) and General control nonderepressible 5 (GCN5) knock down on peroxisome proliferator- activated receptor gamma coactivator 1-alpha (PGC-1α) deacetylation during electrical stimulated skeletal muscle contraction.

[Methods]

Skeletal muscle primary cell were isolated from C57BL/6 mice gastrocnemius and transfected lentiviral SIRT1 and GCN5 shRNA. Knock downed muscle cell were stimulated by electrical stimulation (1Hz, 3min) and collected for PGC-1α deceatylation assays. Immunoprecipitation performed for PGC-1α deacetylation, acetyl-lysine level was measured.

[Results]

Our resulted showed SIRT1 knock down not influenced to PGC-1α deacetylation during electrical stimulation induced muscle contraction while GCN5 knock down decreased PGC-1α deacetylation significantly (p<0.05).

[Conclusion]

This study can be concluded that GCN5 is a critical factor for muscle contraction induced PGC-1α deacetylation.     

Genetic associations of body composition,flexibility and injury risk with ACE,ACTN3 and COL5A1 polymorphisms in Korean ballerinas

[Purpose]

The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea.

[Methods]

For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism).

[Results]

As results, the ACE DD genotype in ballerinas was associated with higher body fat and percentage of body fat than the ACE II and ID genotypes (p < 0.05). In the study on the ACTN3 polymorphism and ballerinas, the XX genotype in ballerinas had lower body weight and lower fat-free mass than the RR and RX genotype (p < 0.005). Also, the means of sit and reach test for flexibility was lower in the ACTN3 XX genotype of ballerinas than the RR and RX genotype of ballerinas (p < 0.05). Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no association with any factors including flexibility and injury risks.

[Conclusion]

In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with ballerinas'' performance capacity; COL5A1 was not associated with any factors of performance of Ballerinas. The results suggested that the ACE DD genotype is associated with high body fat, the ACTN3 XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury.     

Effects of active drinking practices on fluid consumption and sweat rate while exercising in a hot environment

[Purpose]

To examine the effects of active drinking practices on fluid consumption and sweat rate while exercising in a hot environment.

[Methods]

Nine men completed two experiments. Each consisted of 3 phases: pre-testing (pre), training period, and post-testing (post). During testing, the subjects ran on a treadmill at a moderate intensity for 90 min at 39 ± 1℃ followed by a 3-h recovery. They drank ad libitum. During training, they ran for 90 min for 7 days while either drinking actively (AH, 150% of weight loss) or passively (PH, 50% of weight loss).

[Results]

The actual volume consumed in training was three times greater during AH than during PH. In post during AH, the volume of drinking was two times greater than pre (1592 ± 953 and 855 ± 551 mL, respectively; p < 0.05). No difference in volume consumption during PH between pre and post was found. The sweat loss during exercise was greater in post (1377 ± 956 mL) than in pre (558 ± 642 mL) during AH (p < 0.05), but not during PH. Rectal temperature and heart rate decreased after training. Serum osmolality following exercise were not different than the baseline or between the conditions.

[Conclusion]

Active drinking practices while exercising in a hot environment induced greater voluntary fluid intake and sweat loss.     

Association between Oestrogens Receptor Expressions in Breast Cancer and Comorbidities: A Cross-Sectional,Population-Based Study

Background

Breast cancer with oestrogen receptor expression is common in older women. Several factors, such as age and reproductive hormone exposure, have been associated with oestrogen receptor expression in breast cancer. However, the association between comorbidities and the oestrogen receptor expression has been poorly studied. We hypothesized that there was an association between burden comorbidity and breast cancer with oestrogen receptor expression in older women.

Objective

To determine whether oestrogen receptor expression in breast cancer was associated with burden comorbidity in community-dwelling women.

Methods

A total of 1,707 women with breast cancer registered on the list of a breast cancer registry were included. The recorded data included: age, Charlson Comorbidity Index score≥1, breast cancer characteristics (coded according to the International Classification of Diseases for Oncology), and breast cancer pathological stage (the pathological-tumour-node-metastasis, Scarff Bloom Richardson, and hormonal status of oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor).

Results

Breast cancer with oestrogen receptor expression was identified in 1,378 patients (80·7%). The fully-adjusted logistic regression showed that oestrogen receptor expression was associated with Charlson Comorbidity Index score≥1 (odds ratio [OR] = 1·91,95%confidence interval [CI] = [1.01–3.61], P = 0·048), progesterone receptor expression (OR = 16·64, 95%CI = [11.62–23.81], P<0·001), human epidermal growth factor receptor (OR = 0·54, 95%CI = [0.34–0.84], P = 0·007), age (OR = 1.02, 95%CI = [1.00–1.03], P = 0.008), Scarff Bloom Richardson grade II and grade III (OR = 0·21with 95%CI = [0.10–0.44] and OR = 0·06 with 95%CI = [0.03–0.12], P<0·001).

Conclusion

Our findings provide new data showing an independent positive association between burden comorbidity and breast cancer with oestrogen receptor expression. This result confirms that evaluation of oestrogen receptor expression in breast cancer should not be limited to hormonal factors stratified by age.     

Effects of detraining on motor unit potential area,muscle function and physical performance based on CNTF gene polymorphism

[Purpose]

The purpose of this study was to identify the effect of detraining on motor unit potential area (SMUP), muscular function and physical performance, according to CNTF gene polymorphism.

[Methods]

For this study, GG (normal homozygote, n = 8) group and GA + AA (mutation heterozygote and homozygote, n = 10) group were divided by CNTF gene polymorphism and both groups were performed detraining for 4 weeks. The data was analyzed by two-way repeated measures ANOVA for verifying the differences between two groups and interaction using SPSS (ver. 20.0) statistical program.

[Results]

The results were as follows. First, changes in body composition were measured but there was no significant interaction effect between time and group. Seconds, changes in SMUP were measured by SEMG. Interaction effect between time and group was found lateral vastus during isokinetic exercise of 180°/sec (p < .05). Third, changes in isokinetic muscle strength of 60°/sec and 180°/sec were measured but there was no significant interaction effect. Fourth, significant statistical differences were not showed changes of sports performance after detraining.

[Conclusion]

In conclusion, there were no significantly differences between GG and GA + AA group after detraining, therefore, further study will be considered a matter in various its interventions such as serum levels of CNTF and changes in receptors and muscle fiber types.     

Effects of hippotherapy on brain function,BDNF level,and physical fitness in children with ADHD

[Purpose]

The purpose of this study was to examine the effects of hippotherapy on brain function and levels of blood-derived neurotrophic factor (BDNF) in children with attention deficit and/or hyperactivity disorder (ADHD).

[Methods]

The hippotherapy group (HRG) included twenty children with ADHD and the control group (CG) included 19 children. All participants’ physical fitness, fMRI brain scans, and blood BDNF levels were measured at baseline and after 32 weeks of participating in hippotherapy.

[Results]

After 32 weeks of participating in hippotherapy, the body fat of the HRG was significantly decreased (-1.12 ± 4.20%) and the body fat of the CG was increased (2.38 ± 6.35%) (p=0.049). There was no significant difference of physical fitness in both groups (p>0.05). Although there was a higher decrease in the activated insular area in the HRG (-1.59 ± 0.99) than in the CG (-1.14 ± 1.41), there was no significant difference between the two groups (p>0.05) Also, there was a higher increase in the activated cerebellum area in the HRG (1.97 ± 1.45) than in the CG (1.92 ± 1.81). However, there was no significant difference between the two groups (p>0.05). BDNF levels showed an increased tendency in the HRG (166.29 ± 277.52pg) compared to the CG (21.13 ± 686.33pg); otherwise, there was not any significant difference in these blood levels between the two groups (p>0.05). It can be assumed that big individual differences in the level of ADHD in the study participants might not cause any significant results, although there might be positive changes in the brain function of children with ADHD.

[Conclusion]

Therefore, this study suggests that hippotherapy training would need to be modified and developed to increase the efficacy of hippotherapy in children with ADHD.     

Arterial stiffness is inversely associated with a better running record in a full course marathon race

[Purpose]

Arterial stiffness is an independent predictor of cardiovascular risk and may contribute to reduced running capacity in humans. This study investigated the relationship between course record and arterial stiffness in marathoners who participated in the Seoul International Marathon in 2012.

[Methods]

A total of 30 amateur marathoners (Males n = 28, Females n = 2, mean age = 51.6 ± 8.3 years) were assessed before and after the marathon race. Brachial-ankle pulse wave velocity (ba-PWV) was assessed by VP-1000 plus (Omron Healthcare Co., Ltd., Kyoto, Japan) before and immediately after the marathon race. Pearson''s correlation coefficient was used to determine the relationship between race record and ba-PWV. In addition, Wilcoxon signed rank test was used to determine the difference in ba-PWV between before and after the race.

[Results]

There was no significant change in the ba-PWV of marathoners before and after the race (1271.1 ± 185 vs. 1268.8 ± 200 cm/s, P=0.579). Both the full course record (Pearson''s correlation coefficient = 0.416, P = 0.022) and the record of half line (Pearson''s correlation coefficient = 0.482, P = 0.007) were positively related with the difference in ba-PWV, suggesting that reduced arterial stiffness is associated with a better running record in the marathon.

[Conclusion]

These results may suggest that good vascular function contributes to a better running record in the marathon race.     

The Potential of a High Protein-Low Carbohydrate Diet to Preserve Intrahepatic Triglyceride Content in Healthy Humans

Background

Protein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.

Objective

To assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.

Design

Seven men and nine women [mean ± SD age: 24±5 y; BMI: 22.9±2.1 kg/m²] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by ¹H-magnetic resonance spectroscopy before and after the dietary intervention.

Results

IHTG content changed in different directions with the HPLC (CH₂H₂O: 0.23±0.17 to 0.20±0.10; IHTG%: 0.25±0.20% to 0.22±0.11%) compared with the HCLP diet (CH₂H₂O: 0.34±0.20 vs. 0.38±0.21; IHTG%: 0.38±0.22% vs. 0.43±0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).

Conclusions

A HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01551238","term_id":"NCT01551238"}}NCT01551238     

Dopamine-Induced Conformational Changes in Alpha-Synuclein

Background

Oligomerization and aggregation of α-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson''s disease [1]. However, α-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods [2], [3], [4]. A number of in vitro studies showed that dopamine can modulate the aggregation of α-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7].

Methodology/Principal Findings

Here, we show that α-synuclein adopts a variety of conformations in primary neuronal cultures using fluorescence lifetime imaging microscopy (FLIM). Importantly, we found that dopamine, but not dopamine agonists, induced conformational changes in α-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in α-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species.

Conclusion/Significance

Our results show, for the first time, a direct effect of dopamine on the conformation of α-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson''s disease.     

The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type

[Purpose]

The aim of this study was to investigate the effect of treadmill exercise on inflammatory response in streptozotocin (STZ)-induced animal model of Alzheimer’s disease (AD).

[Methods]

To induce the animal model of AD, Sprague-Dawley rats were injected into intracerebroventricular (ICV) injection with 1.5 mg/kg of STZ. Rats were divided into three groups as Sham-con group (n = 7), STZ-con group (n = 7) and STZ-exe group (n = 7). Exercise group ran on the treadmill for 30 min/day, 5 days/week during 6 weeks.

[Results]

The results of this study were as follows: First, STZ-exe group was improved on cognitive function when compared to STZ-con group in water maze test. Second, STZ-exe group help reduce the expression level of amyloid-beta (Aβ). In addition, Toll-like receptors-4 (TLR4), Nuclear factor-kB (NF-kB), Tumor necrosis factor-α (TNF-α) and Interleukin-1α (IL-1α) level of STZ-exe group was significantly decreased when compared to STZ-con group.

[Conclusion]

These results show that treadmill exercise had positive effect on cognitive function and reduced inflammatory response in STZ-induced animal model of AD.     

Serum Interleukin-18 Levels Are Associated with Physical Activity in Japanese Men

Objective

To investigate the link between serum interleukin-18 (IL-18) levels and physical activity in Japanese men.

Methods

A total of 81 men (45.7±17.6 years old) was enrolled in this cross-sectional investigation study. We assessed anthropometric and body composition parameters. Serum IL-18 levels, physical activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk parameters were also evaluated.

Results

Serum IL-18 levels were 179.4±84.7 pg/mL. Physical activity evaluated by Σ[metabolic equivalents × h per week (METs⋅h/w)]was significantly and negatively correlated with serum IL-18 levels (r = −0.252, p = 0.0235). These associations remained even after adjusting for age, peak oxygen uptake and other confounding factors.

Conclusion

Serum IL-18 levels were closely associated with physical activity independent of peak oxygen uptake in Japanese men.     

Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats

[Purpose]

The purpose of the study is to explore effect of 6 weeks treadmill exercise on brain insulin signaling and β-amyloid(Aβ).

[Methods]

The rat model of Alzheimer’s disease(AD) used in the present study was induced by the intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV-Sham(n=7), ICV-STZ CON(n=7), ICV-STZ EXE(n=7). Treadmill exercise was done for 30 min a day, 5 days a week for 6 weeks. Passive avoidance task was carried out before and after treadmill exercise.

[Results]

The results of this study show that treadmill exercise activated Protein kinase B(AKT)/ Glycogen synthase kinase 3α (GSK3α), possibly via activation of insulin receptor(IR) and insulin receptor substrate(IRS) and reduced Aβ in the brain of ICV-STZ rats. More interestingly, treadmill exercise improved cognitive function of ICV-STZ rats. Finally, physical exercise or physical activity gave positive influences on brain insulin signaling pathway.

[Conclusion]

Therefore, treadmill exercise can be applied to improve AD as preventive and therapeutic method.     

A Technique for Performing Electrical Impedance Myography in the Mouse Hind Limb: Data in Normal and ALS SOD1 G93A Animals

Objective

To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models.

Methods

An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups.

Results

The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ±1% and 12% ±2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18±0.6° for the healthy animals and 14±1.0° for the ALS animals, p = 0.0025).

Conclusions

With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals.

Significance

EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy.     

Effects of Serum Lipid Smoothness on the Progression and Vulnerability of Atherosclerotic Plaques in Rabbits

Objective

We aimed to explore the effects of lipid smoothness on the progression and vulnerability of atherosclerotic plaques.

Approach

24 rabbits were divided into three groups randomly. Group 1 was given standard chow diet; group 2 was fed with cholesterol-rich diet; for group 3, subjects were planned to take cholesterol-rich diet at the first phase for 12 weeks and during the second phase, low-fat and cholesterol-rich diet was then applied alternately every three weeks till the end of the experiment. Lipid profiles, inflammatory factors, endothelium functions, pathological and histological changes were examined. Expressions of matrix metalloproteinase-9 and lectin-like oxidized LDL receptor-1 were measured by immunohistochemical staining.

Results

According to data collected during the whole experiment, lipid smoothness index of group 3 was the lowest. Compared with group 2, statistics of the group 3 indicated that: the development of plaques progressed faster; the plaque area and plaque thickness (53.53[22.6]% vs 33.90[24.91]% , 800.38[98.25]µm vs 675.00[109.67]µm) were higher while the fibrous cap thickness (103.50[45.66]µm vs 295.83[97.90]µm) was lower; hs-CRP (0.53[0.07]mg/dL vs 0.45[0.06]mg/dL), interleukin-18 (186.01[8.41]ng/L vs 158.08[2.37]ng/L), OX-LDL (177.15[5.93]µg/L vs 139.57[2.35] µg/L) and endothelin-1 (164.66[9.54]ng/L vs 131.52[4.39]ng/L) were higher while nitric-oxide (22.41[1.69]µmol/L vs 27.23[1.36]µmol/L) was lower; expressions of matrix metalloproteinase-9 (IOD: 37375.87[5634.52] vs 20956.57[4616.93]) and lectin-like oxidized LDL receptor-1 (IOD: 45213.04[16653.81] vs 21921.68[6142.32]) were higher.

Conclusions

Lipids fluctuation could accelerate the progression and vulnerability of atherosclerotic plaques through worsening arterial endothelium dysfunction and inflammatory reactions.     

Effects of low calorie diet-induced weight loss on post-exercise heart rate recovery in obese men

[Purpose]

Heart Rate Recovery (HRR) after maximum exercise is a reactivation function of vagus nerve and an independent risk factor that predicts cardiovascular disease and mortality. Weight loss obtained through dietary programs has been employed as a therapy to reduce risks of cardiovascular disease and obesity.

[Methods]

Eighteen subjects of middle aged obese men (age 44.8 ± 1.6 yrs, BMI 29.7 ± 0.5 kg/m²) were selected for this study. As a weight loss direction, the nutritional direction of low-calorie diet mainly consisted of carbohydrate, protein, and fat has been conducted for 3 months. Blood pressure was measured after overnight fasting, and blood samples were collected from the antecubital vein before and after weight loss program. All the pre- and post-exercise ‘HRR decay constant’s were assessed by using values of HRR (heart recovery rate; 2 minutes) and HR measured after reached to the maximal oxygen uptake (VO₂max) exploited the bicycle ergometer.

[Results]

After the completion of weight loss program, body weight and BMI were significantly decreased, but the Heart Rate (HR) after maximum exercise and in steady state were not changed significantly (p > 0.05). The post-exercise HRR after the weight loss did not show significant changes in perspectives of 30 seconds (-16.6 ± 2.3 to -20.2 ± 2.1 beats/min, p > 0.05) and 60 seconds (-33.5 ± 3.4 to -34.6 ± 2.8 beats/min, p > 0.05) respectively but in perspectives of 90 seconds (-40.9 ± 2.6 to -48.1 ± 3.1 beats/min, p < 0.05) and 120 seconds (-48.6 ± 2.6 to -54.3 ± 3.5 beats/min, p < 0.05), they were decreased significantly. Pre-’HRR decay constant’s of 0.294 ± 0.02 %/second were significantly increased to post-values of 0.342 ± 0.03 %/second (p = 0.026). Changes in ‘HRR decay constant’ were significantly correlated with changes in blood glucose (r = -0.471, p < 0.05) and maximal oxygen consumption (VO₂max, r = 0.505, p < 0.05) respectively.

[Conclusions]

The low-calorie diet directed to obese middle aged men for 3 months significantly improved the HRR after maximum exercise, and this improvement in cardiovascular autonomic nerve system was estimated to be involved with improvements in blood glucose and maximal oxygen consumption.     

Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial

Background

Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.

Methods

The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC₂₀₁₀) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.

Results

58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29).

Conclusion

Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01012557","term_id":"NCT01012557"}}NCT01012557.     

Changes in αB-crystallin,tubulin, and MHC isoforms by hindlimb unloading show different expression patterns in various hindlimb muscles

[Purpose]

αB-crystallin is a small heat shock protein that acts as a molecular chaperone under various stress conditions. Microtubules, which consist of tubulin, are related to maintain the intracellular organelles and cellular morphology. These two proteins have been shown to be related to the properties of different types of myofibers based on their contractile properties. The response of these proteins during muscular atrophy, which induces a myofibril component change, is not clearly understood.

[Methods]

We performed 15 days of hindlimb unloading on rats to investigate the transitions of these proteins by analyzing their absolute quantities. Protein contents were analyzed in the soleus, plantaris, and gastrocnemius muscles of the unloading and control groups (N = 6).

[Results]

All three muscles were significantly atrophied by hindlimb unloading (P < 0.01): soleus (47.5%), plantaris (16.3%), and gastrocnemius (21.3%) compared to each control group. αB-crystallin was significantly reduced in all three examined unloaded hindlimb muscles compared to controls (P < 0.01) during the transition of the myosin heavy chain to fast twitch muscles. α-Tubulin responded only in the unloaded soleus muscle. Muscle atrophy induced the reduction of αB-crystallin and α-tubulin expressions in plantar flexor muscles with a shift to the fast muscle fiber compared to the control.

[Conclusion]

The novel finding of this study is that both proteins, αB-crystallin and α-tubulin, were downregulated in slow muscles (P < 0.01); However, α-tubulin was not significantly reduced compared to the control in fast muscles (P < 0.01).     

Exercise Training suppresses vascular fibrosis in aging obesity induced rats

[Purpose]

The aim of this study was to investigate the effects of exercise training (ET) on vascular fibrosis in aging model rats with diet-induced obesity.

[Methods]

Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9 weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8 weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses.

[Results]

The exercise training significantly decreased levels of AT-1, TGF-ß and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a reduced collagen accumulation in the aorta media compared to AHF group.

[Conclusion]

These results suggest that ET could protect the aging obesity aorta against down-regulation of fibrotic factors (AT-1, TGF-ß and Coll-1 gene) and fibrosis by inhibition of collagen accumulation in the aorta media.     

NAMPT regulates mitochondria biogenesis via NAD metabolism and calcium binding proteins during skeletal muscle contraction

[Purpose]

The purpose of this study was to investigate the effect that muscle contraction induced NAD metabolism via NAMPT has on mitochondrial biogenesis.

[Methods]

Primary skeletal muscle cells were isolated from the gastrocnemius in C57BL/6 mice. The muscle cells were stimulated by electrical current at 1Hz for 3 minutes in conditions of normal or NAD metabolism related inhibitor treatment. NAD/NADH level, Sirt1 and mitochondria biogenesis related signal factor’s changes were examined in normal or NAD metabolism related inhibitor treated cells.

[Results]

Electrical stimulation (ES) induced muscle contractions significantly increased NAD/NADH levels, NAMPT inhibitor FK-866 inhibited ES-induced NAD formation, which caused SIRT1 expression and PGC-1α deacetylation to decrease. Moreover, NAMPT inhibition decreased mitochondrial biogenesis related mRNA, COX-1 and Tfam levels. Along with AMPK inhibitor, compound C decreases SIRT1 expression, PGC-1α deacetylation and muscle contraction induced mitochondrial biogenesis related mRNA increment. These results indicated that the AMPK-NAMPT signal is a key player for muscle contraction induced SIRT1 expression and PGC-1α deacetylation, which influences mitochondrial biogenesis. Inhibition of the AMPK upregulator, Camkkβ, STO-609 decreased AMPK phosphorylation and SIRT1 expression but did not decrease PGC-1α deacetylation. However, CAMKII inhibition via AIP decreased PGC-1α deacetylation.

[Conclusion]

In conclusion, the results indicate that NAMPT plays an important role in NAD metabolism and mitochondrial biogenesis. However, mitochondrial biogenesis is also controlled by different calcium binding protein signals including Camkkβ and CAMKII. [Keyword] Muscle contraction, NAD metabolism, SIRT1, PGC-1 α, mitochondria biogenesis.     

Differences in HCV Viral Decline between Low and Standard-Dose Pegylated-Interferon-Alpha-2a with Ribavirin in HIV/HCV Genotype 3 Patients

Background

The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment.

Methods

Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG) included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model.

Results

One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1∶1.72±0.74 log₁₀ IU/mL versus 1.78±0.67 log₁₀ IU/mL, p = 0.827; week 2∶2.3±0.89 log₁₀ IU/mL versus 3.01±1.02 log₁₀ IU/mL, p = 0.013; week 4∶3.52±1.2 log₁₀ IU/mL versus 4.09±1.1 log₁₀ IU/mL, p = 0.005). The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4.

Conclusions

Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.