We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male ...Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise.
Introduction
Inorganic nitrate ingestion has been posited to affect arterial blood pressure and vascular function.
Purpose
We sought to determine the acute effect of a red spinach extract (RSE) high ...in inorganic nitrate on vascular reactivity 1-h after ingestion in peripheral conduit and resistance arteries.
Methods
Fifteen (
n
= 15; males 8, females 7) apparently healthy subjects (aged 23.1 ± 3.3 years; BMI 27.2 ± 3.7 kg/m
2
) participated in this crossover design, double-blinded study. Subjects reported to the lab ≥2-h post-prandial and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture was performed on three occasions: baseline, 30-min post-ingestion and between 65 to 75-min post-ingestion. Baseline vascular measurements i.e., calf venous occlusion plethysmography, brachial artery flow-mediated dilation (FMD), 30-min of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up vascular measurements beginning at 40-min post-ingestion were also performed.
Results
Humoral nitrate following RSE ingestion was significantly higher at 30- (+54 %;
P
= 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %,
P
< 0.001) and PBO at the same time points (
P
< 0.05). No significant changes in BP or HR occurred in either condition. Peak reactive hyperemia (RH) calf blood flow increased significantly (+13.7 %;
P
= 0.016) following RSE ingestion, whereas it decreased (−14.0 %;
P
= 0.008) following PBO ingestion. No significant differential FMD responses were detected (
P
> 0.05), though RH was decreased following the baseline measure in both conditions.
Conclusions
RSE significantly increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e., resistance vasculature) reactivity increases were isolated to the lower limb and no appreciable change in brachial artery FMD was observed.
Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features.
To compare remission ...rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age.
Twelve-week, double-blind, randomized, controlled trial.
Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age (<60 or > or =60 years) (mean standard deviation (SD), 41.3 10.8 years in 117 younger adults vs 71.7 7.8 years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features.
Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio OR, 1.28; 95% confidence interval CI, 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean SD, 6.5 6.6 kg vs 3.3 4.9 kg, P = .001).
Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks.
clinicaltrials.gov Identifier: NCT00056472.
Summary
We examined if 6 weeks of progressive resistance‐loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational ...efficiency, ribosome biogenesis, and markers of proteolysis. For 6 weeks, 8 male Sprague‐Dawley rats (~9–10 weeks of age, ~300–325 g) rats were assigned to the progressive resistance‐loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel‐loading paradigm was as follows – days 1–7: free‐wheel resistance, days 8–15: wheel resistance set to 20%–25% body mass, days 16–24: 40% body mass, days 25–32: 60% body mass, days 33–42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p < .01), relative (body mass‐corrected) gastrocnemius mass (+16%, p < .001), raw plantaris mass (+13%, p < .05), and relative plantaris mass (+15%, p < .01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p < .01), a 125% increase in pan 4EBP1 levels (p < .001) and a 31% decrease in pan eIF4E levels (p < .05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c‐Myc protein levels (p < .05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F‐box protein 32 and poly‐ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p < .001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.
New Findings
What is the central question of this study?
Does 60 min of peristaltic pulse external pneumatic compression (EPC) alter gene and protein expression patterns related to metabolism, ...vascular biology, redox balance and inflammation in vastus lateralis biopsy samples?
What is the main finding and its importance?
A single bout of EPC transiently upregulates PGC‐1α mRNA, while also upregulating endothelial nitric oxide synthase protein and nitric oxide metabolite concentrations in vastus lateralis biopsy samples.
We investigated whether a single 60 min bout of whole‐leg, lower pressure external pneumatic compression (EPC) altered select vascular, metabolic, antioxidant and inflammation‐related mRNAs. Ten participants (eight male, two female; aged 22.0 ± 0.4 years) reported to the laboratory 4 h postprandial, and vastus lateralis muscle biopsies were obtained before (PRE) and 1 and 4 h after EPC treatment. Messenger RNA expression was analysed using real‐time RT‐PCR, and significant mRNA findings were investigated further by Western blot analysis of respective protein concentrations. Peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) mRNA increased by 77% 1 h following EPC compared with PRE levels (P = 0.005), but no change in protein concentration 1 or 4 h post‐EPC was observed. Increases in endothelial nitric oxide sythase (eNOS) mRNA (+44%) and superoxide dismutase 2 (SOD2) mRNA (+57%) 1 h post‐EPC as well as an increase in interleukin‐10 mRNA (+132%) 4 h post‐EPC compared with PRE levels were observed, but only approached significance (P = 0.076, 0.077 and 0.074, respectively). Interestingly, eNOS protein (+40%, P = 0.025) and nitrate and nitrite (NOx) concentrations (+69%, P = 0.025) increased 1–4 h post‐EPC. Moreover, SOD2 protein tended to increase from PRE to 4 h post‐EPC (+43%, P = 0.074), although no changes in tissue 4‐hydroxnonenal levels was observed. An acute bout of EPC transiently upregulates PGC‐1α mRNA, while also upregulating eNOS protein and NOx concentrations in vastus lateralis biopsy samples. Future research should characterize the origin of these responses (e.g. vascular or muscle fibre cells) and how the acute effects of EPC application on gene and protein expression observed herein are associated with functional improvements (e.g. metabolism, vascular function) in acute and chronic models.
New Findings What is the central question of this study? Does 60 min of peristaltic pulse external pneumatic compression (EPC) alter gene and protein expression patterns related to metabolism, ...vascular biology, redox balance and inflammation in vastus lateralis biopsy samples? What is the main finding and its importance? A single bout of EPC transiently upregulates PGC-1alpha mRNA, while also upregulating endothelial nitric oxide synthase protein and nitric oxide metabolite concentrations in vastus lateralis biopsy samples. We investigated whether a single 60 min bout of whole-leg, lower pressure external pneumatic compression (EPC) altered select vascular, metabolic, antioxidant and inflammation-related mRNAs. Ten participants (eight male, two female; aged 22.0 ± 0.4 years) reported to the laboratory 4 h postprandial, and vastus lateralis muscle biopsies were obtained before (PRE) and 1 and 4 h after EPC treatment. Messenger RNA expression was analysed using real-time RT-PCR, and significant mRNA findings were investigated further by Western blot analysis of respective protein concentrations. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNA increased by 77% 1 h following EPC compared with PRE levels (P = 0.005), but no change in protein concentration 1 or 4 h post-EPC was observed. Increases in endothelial nitric oxide sythase (eNOS) mRNA (+44%) and superoxide dismutase 2 (SOD2) mRNA (+57%) 1 h post-EPC as well as an increase in interleukin-10 mRNA (+132%) 4 h post-EPC compared with PRE levels were observed, but only approached significance (P = 0.076, 0.077 and 0.074, respectively). Interestingly, eNOS protein (+40%, P = 0.025) and nitrate and nitrite (NOx) concentrations (+69%, P = 0.025) increased 1-4 h post-EPC. Moreover, SOD2 protein tended to increase from PRE to 4 h post-EPC (+43%, P = 0.074), although no changes in tissue 4-hydroxnonenal levels was observed. An acute bout of EPC transiently upregulates PGC-1alpha mRNA, while also upregulating eNOS protein and NOx concentrations in vastus lateralis biopsy samples. Future research should characterize the origin of these responses (e.g. vascular or muscle fibre cells) and how the acute effects of EPC application on gene and protein expression observed herein are associated with functional improvements (e.g. metabolism, vascular function) in acute and chronic models.
We investigated whether a single 60-min bout of whole leg, peristaltic pulse external pneumatic compression (EPC) altered select growth factor-related mRNAs and/or various phospho(p)-proteins related ...to cell growth, proliferation, inflammation and apoptosis signalling (e.g. Akt-mTOR, Jak-Stat). Ten participants (8 males, 2 females; aged 22·2 ± 0·4 years) reported to the laboratory 4 h post-prandial, and vastus lateralis muscle biopsies were obtained prior to (PRE), 1 h and 4 h post-EPC treatment. mRNA expression was analysed using real-time RT-PCR and phosphophorylated and cleaved proteins were analysed using an antibody array. No changes in selected growth factor-related mRNAs were observed following EPC. All p-proteins significantly altered by EPC decreased, except for p-rps6 (Ser235/236) which increased 31% 1 h post-EPC compared to PRE levels (P = 0·016). Notable decreases also included p-BAD (Ser112; -28%, P = 0·004) at 4 h post-EPC compared to PRE levels. In summary, an acute bout of EPC transiently upregulates p-rps6 as well as affecting other markers in the Akt-mTOR signalling cascade. Future research should characterize whether chronic EPC application promotes alterations in lower-limb musculature and/or enhances exercise-induced training adaptations.
Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP are present in mature neutrophils. By ...indirect immunofluorescence, both eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4 ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic protein (MBP) was not detectable. Electron microscopic examination of immunogold-labeled buffy coat cells stained with EDN antibody showed that EDN is localized to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly purified neutrophils (0.001% eosinophil contamination) by the reverse transcription-polymerase chain reaction. We conclude that proteins that are either identical to or immunologically cross-reactive with EDN and ECP are present in neutrophils and that EDN is synthesized and localized to neutrophil granules. Thus, caution must be exercised in interpreting the presence of EDN and ECP as specific markers of eosinophil-associated inflammation in human disease.
Neuronal M2 muscarinic receptors inhibit acetylcholine release from pulmonary parasympathetic nerves but are dysfunctional in antigen-challenged animals and asthmatics. Deletion of pulmonary ...eosinophils protects M2 receptor function in antigen-challenged guinea pigs. Therefore, the association of eosinophils with airway nerves was investigated. Nerve-associated eosinophils were significantly increased in challenged animals compared with controls (0.75 +/- 0.05 vs. 0.28 +/- 0.05 eosinophils/nerve). In antigen-challenged animals, eosinophil density was greatest around airway nerves, suggesting recruitment to the nerves. M2 receptor function was inversely correlated with the number of eosinophils per nerve, thus eosinophils are associated with airway nerves in antigen-challenged guinea pigs, where they impair M2 receptor function. In airways from three patients with fatal asthma, 196 of 637 eosinophils (30%) were associated with nerves, and release of eosinophil major basic protein was evident; conversely, in three control patients 1 of 11 (9%) eosinophils were in contact with nerves. Thus eosinophils and their granule proteins are also seen in association with airway nerves in patients with asthma.
Recent evidence suggests that resistance training with light or heavy loads to failure results in similar adaptations. Herein, we compared how both training modalities affect the molecular, ...neuromuscular, and recovery responses following exercise. Resistance‐trained males (mean ± SE: 22 ± 2 years, 84.8 ± 9.0 kg, 1.79 ± 0.06 m; n = 15) performed a crossover design of four sets of leg extensor exercise at 30% (light RE) or 80% (heavy RE) one repetition maximum (1RM) to repetition failure, and heavy RE or light RE 1 week later. Surface electromyography (EMG) was monitored during exercise, and vastus lateralis muscle biopsies were collected at baseline (PRE), 15 min (15mPOST), and 90 min following RE (90mPOST) for examination of molecular targets and fiber typing. Isokinetic dynamometry was also performed before (PRE), immediately after (POST), and 48 h after (48hPOST) exercise. Dependent variables were analyzed using repeated measures ANOVAs and significance was set at P ≤ 0.05. Repetitions completed were greater during light RE (P < 0.01), while EMG amplitude was greater during heavy RE (P ≤ 0.01). POST isokinetic torque was reduced following light versus heavy RE (P < 0.05). Postexercise expression of mRNAs and phosphoproteins associated with muscle hypertrophy were similar between load conditions. Additionally, p70s6k (Thr389) phosphorylation and fast‐twitch fiber proportion exhibited a strong relationship after both light and heavy RE (r > 0.5). While similar mRNA and phosphoprotein responses to both modalities occurred, we posit that heavy RE is a more time‐efficient training method given the differences in total repetitions completed, lower EMG amplitude during light RE, and impaired recovery response after light RE.
Similar skeletal muscle mRNA and phosphoprotein responses to light versus heavy resistance exercise (RE) occurred. However, we posit that heavy RE is a more efficient training method given that significantly less total repetitions completed were completed to elicit similar physiological responses, lower skeletal muscle electromyography amplitude occurred during light RE, and an impaired functional recovery response occurred after light RE.
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