Skeletal Muscle Electrical Stimulation Prevents Progression of Disuse Muscle Atrophy via Forkhead Box O Dynamics Mediated by Phosphorylated Protein Kinase B and Peroxisome Proliferator-Activated Receptor gamma Coactivator-1alpha.

Although electrical muscle stimulation (EMS) of skeletal muscle effectively prevents muscle atrophy, its effect on the breakdown of muscle component proteins is unknown. In this study, we investigated the biological mechanisms by which EMS-induced muscle contraction inhibits disuse muscle atrophy progression. Experimental animals were divided into a control group and three experimental groups: immobilized (Im; immobilization treatment), low-frequency (LF; immobilization treatment and low-frequency muscle contraction exercise), and high-frequency (HF; immobilization treatment and high-frequency muscle contraction exercise). Following the experimental period, bilateral soleus muscles were collected and analyzed. Atrogin-1 and Muscle RING finger 1 (MuRF-1) mRNA expression levels were significantly higher for the experimental groups than for the control group but were significantly lower for the HF group than for the Im group. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNA and protein expression levels in the HF group were significantly higher than those in the Im group, with no significant differences compared to the Con group. Both the Forkhead box O (FoxO)/phosphorylated FoxO and protein kinase B (AKT)/phosphorylated AKT ratios were significantly lower for the Im group than for the control group and significantly higher for the HF group than for the Im group. These results, the suppression of atrogin-1 and MuRF-1 expression for the HF group may be due to decreased nuclear expression of FoxO by AKT phosphorylation and suppression of FoxO transcriptional activity by PGC-1alpha. Furthermore, the number of muscle contractions might be important for effective EMS.

Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of progressive osteoarthritis with subchondral bone collapse.

Objective: To establish an animal model of modified cuff tear arthropathy (mCTA) in order to better replicate the pathophysiology associated with rotator cuff tear-induced humeral head collapse. Design: mCTA was induced by transection of the rotator cuff, the long head of the biceps brachii (LHB), and superior half of the joint capsule in the right shoulder of 12-week-old rats; the left shoulder underwent sham surgery. The severity of CTA was quantitated using the Murine Shoulder Arthritis Score (MSAS). The trabecular bone of the humeral head and metaphysis was analyzed using bone histomorphometry. The expression of proinflammatory cytokines and catabolic enzymes was evaluated immunohistochemically. Results: In the mCTA model, the MSAS increased starting from 2 weeks after induction, and there was notable subchondral bone collapse with fibrous cells at 4 weeks. The mCTA cartilage exhibited positive staining for TNF-α, IL-1ß/6, MMP-3/13, and ADAMTS5. The trabecular bone volume was reduced not only in the subchondral bone but also in the metaphysis of the humeri, and bone resorption was enhanced in these areas. In the collapsed subchondral bone, both bone formation and resorption were increased. The fibrous cells showed expression of TNF-α, IL-6, and MMP-13, along with specific markers of mesenchymal stem cells. Furthermore, the fibrous cells showed osteoblastic characteristics (RUNX2-positive) and expressed RANKL. Conclusions: The LHB and the capsuloligamentous complex are critical stabilizers of the glenohumeral joint, serving to prevent the advancement of CTA following massive rotator cuff tears. Fibrous cells appear to play a role in the humeral head bone resorption.

CD204⁺ tumor-associated macrophages are associated with clinical outcome in canine pulmonary adenocarcinoma and transitional cell carcinoma.

Tumor-associated macrophages are abundant infiltrating cells in the tumor microenvironment (TME). Macrophages can be classified into several types of subsets based on their immune responses. Among those subsets, M2 macrophages contribute to anti-inflammatory responses and create an immunosuppressive environment that promotes tumor cell proliferation. In a previous study, human cancer patients with high M2 macrophages showed a worse prognosis for many types of tumors. However, studies examining the relationship between M2 macrophages and clinical outcomes in canine tumors are limited. In the previous human and canine studies, CD204 has been used as the marker for detecting M2 macrophages. Then we evaluated CD204+ and total macrophages infiltration and its association with clinical outcomes in canine solid tumors. In this study, we examined dogs with oral malignant melanoma (OMM), pulmonary adenocarcinoma (PA), hepatocellular carcinoma (HCC), and transitional cell carcinoma (TCC). Compared to healthy tissues, CD204+ and total macrophages were increased in OMM, PA, and TCC, but not in HCC. High CD204+ macrophage levels were significantly associated with lung metastasis in TCC (P = 0.030). Kaplan-Meier analysis revealed that high CD204+ macrophage levels were associated with shorter overall survival (OS) in canine patients with PA (P = 0.012) and TCC (P = 0.0053). These results suggest that CD204+ macrophages contribute to tumor progression and could be a prognostic factor in dogs with PA and TCC.

Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2.

It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID50 per ml by 1·375 mg ml-1 black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml-1 , green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries.

In vitro evidence of propagation of superoxide dismutase-1 protein aggregation in canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disorder that has been linked to mutations in the superoxide dismutase 1 (SOD1) gene. The accumulation of misfolded protein aggregates in spinal neurons and astrocytes is implicated as an important pathological process in DM; however, the mechanism of protein aggregate formation is largely unknown. In human neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), cell-to-cell propagation of disease-relevant proteins has been demonstrated. Therefore, in this study, propagation of aggregation-forming property of mutant SOD1 protein in DM in vitro was investigated. This study demonstrated that aggregates composed of canine wild type SOD1 protein were increased by co-transfection with canine mutant SOD1 (E40K SOD1), indicating intracellular propagation of SOD1 aggregates. Further, aggregated recombinant SOD1 proteins were released from the cells, taken up by other cells, and induced further aggregate formation of normally folded SOD1 proteins. These results suggest intercellular propagation of SOD1 aggregates. The hypothesis of cell-to-cell propagation of SOD1 aggregates proposed in this study may underly the progressive nature of DM pathology.

The Warburg effect and tumour immune microenvironment in extramammary Paget's disease: overexpression of lactate dehydrogenase A correlates with immune resistance.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant skin cancer. One of the hallmarks of cancers, including EMPD, is an enhancement of aerobic glycolysis, which is also known as the Warburg effect. In the last step of glycolysis, the enzyme lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactic acid, the accumulation of which contributes to the creation of an acidic tumour microenvironment. This in turn results in immunosuppression in various types of cancers. However, the contribution of these pathways has not been well-studied in EMPD. OBJECTIVE: To investigate the significance of the Warburg effect and its contribution to the tumour immune microenvironment in EMPD. METHODS: The mRNA expression levels of molecules involved in glycolysis and immune-related cytokines were examined by ddPCR. The number of immune cells was assessed by immunohistochemistry (IHC). RESULTS: The levels of two glycolytic enzymes, HK2 and LDHA, in tumour tissues were significantly increased compared to those in paired-normal tissues. IHC analyses revealed increased numbers of PD-L1+ , PD-1+ , CD163+ M2 macrophages, Iba1+ macrophages and Foxp3+ Tregs that were associated with high LDHA levels in EMPD. ddPCR demonstrated that multiple cytokines including IL-4, IL-6, IL-10, TGF-ß and CCL-2 were upregulated and associated with high LDHA levels in EMPD. Statistical analyses showed that IL-6 mRNA expression correlated with the number of CD163+ , Iba-1+ and Foxp3+ cells. CONCLUSION: The Warburg effect contributes to immunomodulation in the tumour microenvironment and further elucidation may lead to better understanding of the pathogenesis of EMPD.

COPD as an independent risk factor for osteoporosis and fractures.

Fractures are common in individuals with COPD and occur at higher bone mass values than expected. COPD appears to be an important risk factor for bone fragility. INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis and fractures, but screening and prophylactic measures to prevent both disorders are often neglected in this population. This case-control study assessed the prevalence of osteopenia, osteoporosis, and fractures in patients with COPD, and identified potential risk factors for fractures in this population. METHODS: Overall, 91 patients with COPD (COPD group; COPDG) and 81 age- and sex-matched controls (control group; CG) were assessed with bone mineral density (BMD), thoracic/lumbar spine radiographs, and serum PTH and 25-hydroxyvitamin D (25[OH]D) levels. The occurrence of prior fractures was retrieved from clinical history. RESULTS: The prevalence of total fractures in the COPDG was 57.1% (odds of fracture 4.7 times greater compared with the CG), and the femoral neck T-score emerged as the best predictor of fractures. Compared with the CG, the COPDG had lower spine and femoral BMD (p ≤ 0.01) and 25(OH)D levels (p = 0.01) and 2.6 times greater odds of osteoporosis. Among men, vertebral fractures were more prevalent in the COPDG versus CG (25.9% vs. 6.5%, respectively, p = 0.01). The odds of fracture increased with femoral neck T-scores ≤ - 2.7 in the CG and ≤ - 0.6 in the COPDG. CONCLUSION: These results add robust evidence to an increased odds of osteoporosis and fractures in COPD. Fractures in the COPDG occurred at higher BMD values than expected, suggesting that COPD may be an independent marker of fracture risk, reinforcing a need for regular osteoporosis screening with BMD measurement and prophylaxis of fractures in patients with this disorder.

Duodenal expression of antimicrobial peptides in dogs with idiopathic inflammatory bowel disease and intestinal lymphoma.

Although antimicrobial peptides (AMPs) play an integral role in the regulation of intestinal microbiota and homeostasis, their expression in canine gastrointestinal diseases, including idiopathic inflammatory bowel disease (IBD) and intestinal lymphoma, remains unknown. The objective of this study was to investigate the intestinal expression of AMPs in dogs with IBD or intestinal lymphoma. IBD was diagnosed in 44 dogs, small cell intestinal lymphoma in 25 dogs, and large cell intestinal lymphoma in 19 dogs. Twenty healthy beagles were used as normal controls. Duodenal mRNA expression of six representative AMPs - lactoferrin, lysozyme, cathelicidin, secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability increasing protein (BPI), and canine beta defensin (CBD103) - was quantified by real-time reverse transcription polymerase chain reaction. The relative expression of BPI, lactoferrin, and SLPI was significantly higher in dogs with IBD and intestinal lymphomas than in healthy controls. Interestingly, the expression patterns of AMPs differed between dogs with IBD and those with intestinal lymphomas, especially small cell lymphoma. Increased expression of BPI differentiated IBD from dogs with small cell intestinal lymphoma, with a sensitivity of 93.2%, a specificity of 100%, and an area under the curve of 0.955. These results suggest that the expression patterns of AMP aid in the diagnosis of canine IBD and intestinal lymphoma, although it remains uncertain whether the altered AMP expression is the cause or effect of mucosal inflammation.

Expression of apoptosis inhibitor of macrophages in tissue macrophages, leukocytes and vascular endothelial cells of dogs.

Apoptosis inhibitor of macrophages (AIM) is a protein which plays important roles in controlling the immune response and inflammation in human and mice. In dogs, AIM is reported to be expressed in cancerated macrophages and regulate the survival of these tumor cells. In this study, to elucidate the physiological expression pattern of AIM in dogs, systemic expression and distribution of AIM of dogs were investigated. Mature healthy Beagles were used. Various tissues, peripheral blood cells, and bone marrow cells of normal dogs were collected for in situ hybridization, real-time RT-PCR, and immunohistochemistry. AIM mRNA and protein were expressed in tissue macrophages of the spleen, liver, lungs, and lymph nodes, but not in the microglia of the cerebrum. Proximal tubules in the kidney also expressed AIM protein. Monocytes and B lymphocytes in circulating blood and a part of microvasculature endothelial cells showed AIM expression at both the mRNA and protein levels. In the bone marrow, early-stage monocyte progenitor-like cells expressed AIM mRNA and protein. These results clarified that AIM is expressed in more cell types than previously reported in human and mice. These data spread the possibility of AIM physiological functions and implies the relationship of AIM to the maturation of macrophage-strain cells in dogs and other species.

Local membrane charge regulates ß2 adrenergic receptor coupling to Gi3.

The ß2 adrenergic receptor (ß2AR) signals through both Gs and Gi in cardiac myocytes, and the Gi pathway counteracts the Gs pathway. However, Gi coupling is much less efficient than Gs coupling in most cell-based and biochemical assays, making it difficult to study ß2AR-Gi interactions. Here we investigate the role of phospholipid composition on Gs and Gi coupling. While negatively charged phospholipids are known to enhance agonist affinity and stabilize an active state of the ß2AR, we find that they impair coupling to Gi3 and facilitate coupling to Gs. Positively charged Ca2+ and Mg2+, known to interact with the negative charge on phospholipids, facilitates Gi3 coupling. Mutational analysis suggests that Ca2+ coordinates an interaction between phospholipid and the negatively charged EDGE motif on the amino terminal helix of Gi3. Taken together, our observations suggest that local membrane charge modulates the interaction between ß2AR and competing G protein subtypes.

Hyperglycaemia augments lipopolysaccharide-induced reduction in rat and human macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein pathway.

BACKGROUND: Macrophage phagocytosis constitutes an essential part of the host defence against microbes and the resolution of inflammation. Hyperglycaemia during sepsis is reported to reduce macrophage function, and thus, potentiate inflammatory deterioration. We investigated whether high-glucose concentrations augment lipopolysaccharide-induced reduction in macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein (CHOP) pathway using animal and laboratory investigations. METHODS: Peritoneal macrophages of artificially ventilated male Wistar rats, divided into four groups based on target blood glucose concentrations achieved by glucose administration with or without lipopolysaccharide, were obtained after 24 h. Human macrophages were also cultured in normal or high glucose with or without lipopolysaccharide exposure for 72 h. Changes in the phagocytic activity, intranuclear CHOP expression, and intracellular Akt phosphorylation status of macrophages were evaluated. These changes were also evaluated in human macrophages after genetic knock-down of CHOP by specific siRNA transfection or resolvin D2 treatment. RESULTS: Lipopolysaccharide impaired phagocytosis, increased intranuclear expression of CHOP, and inhibited Akt phosphorylation in both rat peritoneal and human macrophages. Hyperglycaemic glucose concentrations augmented these changes. Genetic knock-down of CHOP restored phagocytic ability and Akt phosphorylation in human macrophages. Furthermore, resolvin D2 co-incubation restored the inhibited phagocytosis and Akt phosphorylation along with the inhibition of intranuclear CHOP expression in human macrophages. CONCLUSIONS: These findings imply that controlling endoplasmic reticulum stress might provide new strategies for restoring reduced macrophage phagocytosis in sepsis-induced hyperglycaemia.

Serum cell-free DNA levels are a useful marker for extramammary Paget disease.

BACKGROUND: Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. OBJECTIVES: To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. METHODS: cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. RESULTS: Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. CONCLUSIONS: Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.

Effects of resistance training on arterial compliance and plasma endothelin-1 levels in healthy men.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Association of tumour-infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours.

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour-infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)-positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3-positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3-positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.

Intellectual disability is a risk factor for delayed emergence from total intravenous anaesthesia.

BACKGROUND: Previous studies have suggested that ID influences the depth of general anaesthesia (GA) and delays emergence from GA. In this retrospective cohort study, we investigated whether ID affects the time taken to emerge from GA. METHODS: We selected dental patients who underwent GA at the Department of Dental Anaesthesiology, Okayama University Hospital, using predefined inclusion and exclusion criteria, before dividing the selected participants into ID and non-ID (control) groups. Relevant data were collected from electronic anaesthesia records. Emergence time, the time from the discontinuation of propofol and remifentanil to tracheal extubation, was recorded for each patient. We compared the data of the ID group and control group. The association between ID and the emergence time was tested for statistical significance. Multivariate linear regression analysis was used to control for confounders. RESULTS: A total of 97 cases (control = 50, ID = 47) were included in the study. The emergence time was significantly longer in the ID group (ID group: 15.8 ± 6.6 min, control group: 10.8 ± 3.6 min). The ID group included more men and lower propofol and remifentanil infusion rates. The treatment time was longer, and the mean bispectral index was lower in the ID group. Sevoflurane inhalation was used only for anaesthesia induction in the ID group. In the multivariate linear regression analysis, ID was found to be significantly associated with a longer emergence time. CONCLUSION: Our results suggest that ID is associated with a longer emergence time from GA.

Effect of habitual exercise on urinary liver-type fatty acid-binding protein levels in middle-aged and older adults.

The purpose of this study was to examine the effect of habitual exercise on urinary liver-type fatty acid-binding protein (L-FABP), which can reflect the degree of various stresses on renal proximal tubule related to the progression of renal disease, in middle-aged and older adults. Cross-sectional and interventional approaches were used to comprehensively achieve this purpose. In the cross-sectional study, we investigated the relationship between physical activity levels and urinary L-FABP levels in 130 middle-aged and older adults. In the interventional study, subjects (n=31) were divided into two groups: exercise (n=19) and control group (n=12), whereby we examined the effects of 12-week aerobic exercise training on urinary L-FABP levels. The cross-sectional study showed that the urinary L-FABP levels were significantly lower in the higher physical activity group than in the lower physical activity group (P<.05). In the interventional study, 12-week aerobic exercise training significantly decreased urinary L-FABP levels (P<.01). Furthermore, the relative changes in urinary L-FABP levels were significantly correlated with the relative changes in physical activity levels and mean arterial pressure after intervention (r=-.374 and r=.530, respectively). Our results revealed that the urinary L-FABP levels were lower in the higher physical activity individuals, and aerobic exercise training decreased urinary L-FABP levels. These results suggest that habitual exercise appears to be associated with a decrease in the degree of several stresses on renal proximal tubule and to be beneficial for kidney health in middle-aged and older adults.

Effects of Aerobic and Resistance Training Combined with Fortified Milk on Muscle Mass, Muscle Strength, and Physical Performance in Older Adults: A Randomized Controlled Trial.

OBJECTIVES: Fortified milk and resistance training (RT) increase muscle mass, muscle strength, and physical performance in older adults, but it remains unclear whether RT combined with aerobic training (AT) would have stronger effects on these outcomes. The purpose of this study was to examine the effects of aerobic and resistance training (ART) combined with fortified milk consumption on muscle mass, muscle strength, and physical performance in older adults. DESIGN: Open-labeled randomized controlled trial. SETTING: University of Tsukuba. PARTICIPANTS: Fifty-six older adults aged 65-79. INTERVENTION: Participants were randomly allocated into resistance training (RT + fortified milk, n = 28) and aerobic and resistance training (ART + fortified milk, n = 28) groups. All participants attended supervised exercise programs twice a week at University of Tsukuba and ingested fortified milk every day for 12 weeks. Skeletal muscle index ([SMI]: appendicular lean mass/height2) was assessed using dual-energy X-ray absorptiometry as a muscle mass measure. One-repetition maximum strength was measured using four kinds of resistance training machines (chest press, leg extension, leg curl, and leg press) as muscle strength measures. Sit-to-stand and arm curl tests were also assessed as physical performance measures. MEASUREMENTS: The primary measurements were muscle mass and strength. The secondary outcomes were physical performance, blood samples, habitual diet, habitual physical activity, and medication use. RESULTS: Although the muscle strength and physical performance measures significantly improved in both groups, SMI significantly improved in only the RT group. There was no significant difference in the change in SMI and muscle strength measures between the two groups. However, the change in sit-to-stand and arm curl measures in the ART group were significantly higher than those in the RT group. CONCLUSIONS: These results suggest that AT before RT combined with fortified milk consumption has similar effects on skeletal muscle mass and strength compared with RT alone, but it may be a more useful strategy to improve physical performance in older adults. Although the mechanism of our intervention is uncertain, our program would be an effective prevention for sarcopenia in older adults.