Research on athlete's aerobic and anaerobic exercise ability with balanced nutrition / Pesquisa sobre a capacidade de exercício aeróbio e anaeróbio do atleta com nutrição balanceada / Investigación sobre la capacidad de ejercicio aeróbico y anaeróbico de los atletas con una nutrición equilibrada

ABSTRACT Introduction: The need for a lactic acid cycle eliminates lactic acid produced during exercise. This process requires energy consumption. D-ribose supplementation can increase muscle cell energy, accelerate the synthesis of PRPP in the heart and skeletal muscle, and eliminate the pentose phosphate pathway in the low limit of glucose-6-phosphate dehydrogenase activity; it doubles the speed of ATP recovery, so supplementing ribose can improve exercise capacity and accelerate the elimination of lactic acid to improve recovery ability. Objective: Supplementing D-ribose can increase muscle cell energy and accelerate the regeneration of ATP in the myocardium and skeletal muscle. This experiment intends to explore the effects of anaerobic and aerobic exercise and anaerobic exercise capacity and recovery ability after supplementing D-ribose granules by observing the changes in exercise tests before and after nutritional supplementation and recovery indicators after exercise. Methods: The thesis used a paired design to randomly divide 24 male amateur tennis players into two groups (12 in each group): physical training group (control group), physical training + nutrition D-ribose group (test group), and the D- The effect of ribose on the aerobic and anaerobic exercise capacity of amateur tennis players. Results: The observation indexes of the two groups before the test were not statistically significant (P>0.05); after the test for eight weeks, the aerobic capacity indexes of the test group were higher than those of the control group (P<0.05), and also higher than those before the test (P<0.05)); The recovery of 3minHR and 5minHR of the experimental group after exercise was significantly faster than that of the control group (P<0.05). Conclusions: Nutritional D-ribose supplementation can enhance the aerobic training effect of amateur tennis players, improve aerobic and anaerobic exercise capacity, and accelerate heart rate recovery after exercise. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A necessidade de um ciclo de ácido lático elimina o ácido lático produzido durante o exercício. Este processo requer consumo de energia. A suplementação com D-ribose pode aumentar a energia das células musculares, acelerar a síntese de PRPP no coração e no músculo esquelético e eliminar a via da pentose fosfato no limite inferior da atividade da glicose-6-fosfato desidrogenase; ele dobra a velocidade de recuperação de ATP, portanto, a suplementação de ribose pode melhorar a capacidade de exercício e acelerar a eliminação de ácido láctico para melhorar a capacidade de recuperação. Objetivo: A suplementação de D-ribose pode aumentar a energia das células musculares e acelerar a regeneração de ATP no miocárdio e músculo esquelético. Este experimento pretende explorar os efeitos do exercício anaeróbio e aeróbio e da capacidade de exercício anaeróbio e capacidade de recuperação após a suplementação de grânulos de D-ribose, observando as mudanças nos testes de exercício antes e após a suplementação nutricional e indicadores de recuperação após o exercício. Métodos: A tese utilizou um desenho pareado para dividir aleatoriamente 24 tenistas amadores do sexo masculino em dois grupos (12 em cada grupo): grupo de treinamento físico (grupo controle), grupo de treinamento físico + nutrição D-ribose (grupo de teste) e o grupo D - O efeito da ribose na capacidade de exercício aeróbio e anaeróbio de tenistas amadores. Resultados: Os índices de observação dos dois grupos antes do teste não foram estatisticamente significantes (P> 0,05); após o teste por oito semanas, os índices de capacidade aeróbia do grupo teste foram maiores do que os do grupo controle (P <0,05), e também maiores do que aqueles antes do teste (P <0,05); A recuperação de 3minHR e 5minHR do grupo experimental após o exercício foi significativamente mais rápida do que a do grupo controle (P <0,05). Conclusões: A suplementação nutricional de D-ribose pode aumentar o efeito do treinamento aeróbio de jogadores de tênis amadores, melhorar a capacidade de exercício aeróbio e anaeróbio e acelerar a recuperação da freqüência cardíaca após o exercício. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La actividad física regular ayuda a mejorar las habilidades cardiovasculares y cerebrovasculares. Cómo evaluar la tensión nerviosa de los vasos cardiovasculares y cerebrovasculares a través del deporte es un tema candente. Objetivo: El artículo analiza la influencia de la participación regular en deportes sobre la función cardiovascular de las personas y los indicadores relacionados con la sangre. Métodos: Seleccionamos a 30 adultos mayores sanos que participan regularmente en deportes, registramos sus cambios en el ECG, presión arterial, frecuencia cardíaca y otros indicadores relacionados con la función cardiovascular, y analizamos la función sanguínea de los ancianos. Detección del recuento de glóbulos rojos (RBC), volumen de glóbulos rojos (MCV) y hemoglobina (Hb), creatinina sérica (Cr), glucosa en sangre (BGS), triglicéridos (TG), colesterol (TC), lipoproteínas de baja densidad (LDL) y se mide la lipoproteína de alta densidad (HDL). Resultados: Los adultos mayores que persisten en el ejercicio durante mucho tiempo tienen mejores indicadores que los que no lo hacen. Conclusión: El ejercicio aeróbico adecuado puede reducir la rigidez de los vasos sanguíneos en los ancianos. El ejercicio puede ayudar a los ancianos a aumentar la variabilidad de la frecuencia cardíaca y mejorar los indicadores sanguíneos y la masa corporal de la función nerviosa autónoma del corazón. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Methods Used to Make Lipid Nanoparticles to Deliver LNA Gapmers Against lncRNAs into Acute Myeloid Leukemia (AML) Blasts.

Developing strategies to target lncRNAs are needed. In this chapter, we describe in detail a method to deliver antisense oligonucleotides into acute myeloid leukemia cells using lipid nanoparticles tagged with the transferrin receptor. While this chapter is focused on the delivery method, we also discuss important considerations about the design of antisense oligonucleotides (ASOs). The strategy described here has been used successfully to deliver ASOs into leukemic blasts and stem cells.

Dual Inhibition of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells.

Colorectal cancer, one of the most commonly diagnosed cancers worldwide, is often accompanied by uncontrolled proliferation of tumor cells. Dyskerin pseudouridine synthase 1 (DKC1), screened using the genome-wide RNAi strategy, is a previously unidentified key regulator that promotes colorectal cancer cell proliferation. Enforced expression of DKC1, but not its catalytically inactive mutant D125A, accelerates cell growth in vitro and in vivo. DKC1 knockdown or its inhibitor pyrazofurin attenuates cell proliferation. Proteomics, RNA immunoprecipitation (RIP)-seq, and RNA decay analyses reveal that DKC1 binds to and stabilizes the mRNA of several ribosomal proteins (RPs), including RPL10A, RPL22L1, RPL34, and RPS3. DKC1 depletion significantly accelerates mRNA decay of these RPs, which mediates the oncogenic function of DKC1. Interestingly, these DKC1-regulated RPs also interact with HRAS and suppress the RAS/RAF/MEK/ERK pathway. Pyrazofurin and trametinib combination synergistically restrains colorectal cancer cell growth in vitro and in vivo. Furthermore, DKC1 is markedly upregulated in colorectal cancer tissues compared to adjacent normal tissues. Colorectal cancer patients with higher DKC1 expression has consistently poorer overall survival and progression-free survival outcomes. Taken together, these data suggest that DKC1 is an essential gene and candidate therapeutic target for colorectal cancer.

Effect of D-ribose supplementation on delayed onset muscle soreness induced by plyometric exercise in college students.

OBJECTIVE: Previous investigations suggest that appropriate nutritional interventions may reduce delayed onset muscle soreness (DOMS). This study examined the effect of D-ribose supplementation on DOMS induced by plyometric exercise. METHODS: For the purpose of inducing DOMS, 21 untrained male college students performed a lower-limb plyometric exercise session that involved 7 sets of 20 consecutive frog hops with 90-s of rest between each set. Muscle soreness was measured with a visual analogue scale 1-h before, 24-h after, and 48-h after exercise. Subjects were then randomly placed into the D-ribose group (DRIB, n = 11) and the placebo group (PLAC, n = 10) to assure equivalent BMI and muscle soreness. After a 14-d washout/recovery period, subjects performed the same exercise session, with DRIB ingesting a 200 ml solution containing 15 g D-ribose 1-h before, 1-h, 12-h, 24-h, and 36-h after exercise, and PLAC ingesting a calorically equivalent placebo of the same volume and taste containing sorbitol and ß-cyclodextrin. Muscle soreness and isokinetic muscle strength were measured, and venous blood was assessed for markers of muscle damage and oxidative stress 1-h before, 24-h and 48-h after exercise. RESULTS: In DRIB, muscle soreness after 24-h and 48-h in the second exercise session were significantly lower (p < 0.01) than was experienced in the first exercise session. In the second exercise, blood-related markers of muscle soreness, including creatine kinase, lactate dehydrogenase (LDH), myoglobin and malondialdehyde (MDA) in DRIB after 24-h were lower in DRIB after 24-h than in PLAC (MDA, p < 0.05; rest outcomes, p < 0.01). In addition, LDH and MDA in DRIB were significantly lower (p < 0.01) after 24-h in DRIB than in PLAC. No difference was found in isokinetic muscle strength and oxidative stress markers, including superoxide dismutase and total antioxidant capacity, between DRIB and PLAC after 24-h and 48-h. CONCLUSION: D-ribose supplementation reduces muscle soreness, improves recovery of muscle damage, and inhibits the formation of lipid peroxides. Young adult males performing plyometric exercise are likely to realize a DOMS reduction through consumption of D-ribose in 15 g/doses both before (1-h) and after (1-h, 12-h, 24-h, 36-h) exercise. These results suggest that appropriately timed consumption of D-ribose may induce a similar alleviation of exercise-induced DOMS in the general public.

Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice.

Ribose-cysteine is a synthetic compound designed to increase glutathione (GSH) synthesis. Low levels of GSH and the GSH-dependent enzyme, glutathione peroxidase (GPx), is associated with cardiovascular disease (CVD) in both mice and humans. Here we investigate the effect of ribose-cysteine on GSH, GPx, oxidised lipids and atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice. Female 12-week old apoE-/- mice (n = 15) were treated with 4-5 mg/day ribose-cysteine in drinking water for 8 weeks or left untreated. Blood and livers were assessed for GSH, GPx activity and 8-isoprostanes. Plasma alanine transferase (ALT) and lipid levels were measured. Aortae were quantified for atherosclerotic lesion area in the aortic sinus and brachiocephalic arch and 8-isoprostanes measured. Ribose-cysteine treatment significantly reduced ALT levels (p<0.0005) in the apoE-/- mice. Treatment promoted a significant increase in GSH concentrations in the liver (p<0.05) and significantly increased GPx activity in the liver and erythrocytes of apoE-/-mice (p<0.005). The level of 8-isoprostanes were significantly reduced in the livers and arteries of apoE-/- mice (p<0.05 and p<0.0005, respectively). Ribose-cysteine treatment showed a significant decrease in total and low density lipoprotein (LDL) cholesterol (p<0.05) with no effect on other plasma lipids with the LDL reduction likely through upregulation of scavenger receptor-B1 (SR-B1). Ribose-cysteine treatment significantly reduced atherosclerotic lesion area by >50% in both the aortic sinus and brachiocephalic branch (p<0.05). Ribose-cysteine promotes a significant GSH-based antioxidant effect in multiple tissues as well as an LDL-lowering response. These effects are accompanied by a marked reduction in atherosclerosis suggesting that ribose-cysteine might increase protection against CVD.

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effectiveness of a Food Supplement Containing Creatine and D-Ribose Combined with a Physical Exercise Program in Increasing Stress Tolerance in Patients with Ischemic Heart Disease.

The aim of this study is to establish whether a supplement of creatine and ribose combined with a physical exercise program can improve the total work capacity during exercise in a population of patients with known ischemic heart disease. A double-blind, six-month study was designed in which 53 patients were enrolled and randomized to take either a nutraceutical composition containing creatine, D-ribose, vitamin B1, and vitamin B6 (active treatment) or the placebo. Both the nutraceutical supplement and the placebo were supplied by Giellepi S.p.A. Health Science in Lissone, Italy. After six months of study, the cardiac double product at the peak of the load, the delta double product, and the chronotropic index were higher in the active treatment group than in the placebo group. We can conclude that a supplementation with creatine, D-ribose, vitamin B1, and vitamin B6, in addition to standard therapy and a physical exercise program, seems to be helpful in improving exercise tolerance compared to the placebo in a population with cardiovascular disease. However, this needs to be further studied, given that there is no clear evidence that the double product can be used as a surrogate measure of exercise tolerance.

Effects of quorum-sensing inhibition on experimental periodontitis induced by mixed infection in mice.

This study aimed to verify, in in vivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P. gingivalis and F. nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P. gingivalis and F. nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P. gingivalis and F. nucleatum.

D-ribose induces nephropathy through RAGE-dependent NF-κB inflammation.

Recently, aberrantly high levels of D-ribose have been discovered in type II diabetic patients. D-ribose glycates proteins more rapidly than D-glucose, resulting in the production of advanced glycation end products (AGEs). Accumulations of these products can be found in impaired renal function, but the mechanisms are poorly understood. The present study tested whether D-ribose induces renal dysfunction via the RAGE-dependent NF-κB signaling pathway. In vivo, administration of D-ribose was found to lower blood glucose and regulate insulin tolerance. Compared to controls, urine nitrogen and creatinine excretion were increased in mice receiving D-ribose and were accompanied by severe pathological renal damage. Furthermore, immunohistochemistry showed that NF-κB, AGEs, and receptor of AGEs (RAGE) increased in the kidneys of the mice with D-ribose treatment. In vitro, by western blot and immunofluorescent staining, we confirmed that D-ribose induced NF-κB activation and accumulation of AGEs and RAGE in mesangial cells. By co-immunoprecipitation, we found that the pull-down of RAGE remarkably increased the expression of NF-κB. Silencing the RAGE gene blocked the phosphorylation of NF-κB induced by D-ribose. These results strongly suggest that D-ribose induced NF-κB inflammation in a RAGE-dependent manner, which may be a triggering mechanism leading to nephropathy.

Diabetex: A novel approach for diabetic wound healing.

INTRODUCTION AND AIM: Wound healing is an orderly complex process involving inflammation, clotting, re-epithelialization, neovascularization and wound closure. In diabetic patients, such process is impaired and delayed, posing negative economic as well as social consequences. Diabetex, (patency# EP 0877617 A1) composed of L-alanine, d-ribose, nicotinic acid and calcium ascorbate, which was initially introduced to treat cancer is thought to have anti- diabetic effects. The present study was designed to investigate the therapeutic merit of diabetex as well as the cellular mechanisms involved in such effects and its safety profile compared to metformin in wounded diabetic rats. MAIN METHODS: Sixty adult male Sprague-Dawley albino rats were randomly divided into two major groups after induction of full thickness wound; control and treated groups. Liver and kidney function test, as well as cytokines (VEGF, TGF-ß, PDGF and MMP2), fasting blood sugar were measured in animal sera. Histopathological studies including hematoxyline and eosin, Masson's trichrome stains were performed on wounded tissue. KEY FINDINGS: Diabetex significantly improved wound healing, collagen formation, induced re-epithelialization and neovascularization. Moreover, cytokines involved in wound healing process were increased by the antidiabetic medication. Noteworthy, the drug exhibited a safe profile on liver and kidney function tests and significantly reduced fasting blood sugar. SIGNIFICANCE: The present study offers a novel approach for treating diabetic resistant wounds with a possible more economic, safe strategy.

Ribosylation triggering Alzheimer's disease-like Tau hyperphosphorylation via activation of CaMKII.

Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies.

(D)-Ribose supplementation in the equine: lack of effect on glycated plasma proteins suggesting safety in humans.

BACKGROUND: d-Ribose is a popular dietary supplement for humans and the equine because of its crucial role in cellular bioenergetics. However, as a reducing sugar, it has been suggested that ingestion of d-ribose might promote the formation of glycated proteins in vivo with potential adverse consequences. OBJECTIVE: The aim of this study was to examine if d-Ribose would promote the formation of glycated proteins in vivo following exercise in training thoroughbred racehorses. METHODS: Two groups of horses received the supplement (30 and 50 g d-Ribose daily) for 17 weeks, during which period the horses were subjected to low-intensity exercises followed by high-intensity exercises. Blood samples were analyzed for glycated plasma proteins at baseline and following the 2 exercise regimens. RESULTS: This study shows that long-term ingestion of d-Ribose at 30-50 g a day does not promote the formation of glycated plasma proteins in thoroughbred racehorses. Ribose supplementation also protected the horses from cramping while enhancing muscle recovery at the same time. No adverse effects were reported. CONCLUSION: Ribose supplementation is safe and does not cause glycation in vivo. This investigation also establishes safety of d-Ribose in thoroughbred racehorses, suggesting similar implications in humans as well.

D-ribose aids heart failure patients with preserved ejection fraction and diastolic dysfunction: a pilot study.

OBJECTIVES: The incidence of heart failure continues to escalate with >550,000 newly diagnosed patients annually worldwide. More than half of the patients with heart failure have preserved ejection fraction or isolated diastolic dysfunction, for which no current effective therapies for diastolic dysfunction exist. Every cell requires adequate levels of high energy phosphates to maintain integrity and function. Previous studies have demonstrated that diastolic function is energy dependent and supplemental D-ribose has shown to improve diastolic dysfunction. This study investigated what role D-ribose might play in congestive heart failure patients with preserved systolic function and diastolic dysfunction. METHODS: A total of 11 patients, New York Heart Association class II-IV, with clinical symptoms, normal left ventricular systolic function and echocardiographic evidence of diastolic dysfunction were enrolled after meeting inclusion criteria. Each patient received oral D-ribose (5 g/dose) for 6 weeks. Echocardiographic evaluation, cardiopulmonary metabolic testing and subjective questionnaire assessment were performed at baseline, 6 weeks and at 9 weeks (3 weeks after discontinuing D-ribose). RESULTS: An improvement in their tissue Doppler velocity (E'), which was maintained at 9 weeks, was demonstrated in 64% of the patients. Five patients showed an improvement in their ratio of early diastolic filling velocity (E) to early annulus relaxation velocity (E'). There was no appreciable difference in these measurements during valsalva or with leg raising and handgrip exercises. Four patients also had an improvement in their maximum predicted VO2 values; two demonstrated a worsening effect and no differences were noted in the remaining patients. Subjective assessment revealed a benefit in only one patient, worsening symptoms in one patient and no change in the remaining cohort. CONCLUSIONS: This pilot study revealed some beneficial trends with D-ribose even with this small cohort size. However, future investigations are necessary to further substantiate these observed benefits.

D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation.

Non-enzymatic glycation of proteins by reducing saccharides for instance D-glucose is an important post-translational modification regulating protein function. Already two centuries ago, D-glucose (Glc) was identified in the urine of diabetic patients. Recently, abnormally high level of D-ribose (Rib) in the urine of type 2 diabetics has been discovered, which is highly active in protein glycation, resulting in the production of advanced glycation end products (AGEs). Accumulation of AGEs leads to altered cellular function, for example AGE accumulation in the nervous system impairs cognitive ability, yet the mechanisms mediating this process for Rib are unknown. Here we found that treatment with Rib accelerated AGE formation in U251 and U87MG astrocytoma cells and in mouse brain, inducing upregulation of receptor for AGEs (RAGE). Astrocytoma cells with elevated levels of RAGE displayed enhanced activity of the proinflammatory nuclear transcription factor kappaB and increased expression of tumor necrosis factor alpha and glial fibrillary acidic protein. Moreover, injection of Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory abilities. These results indicate that mouse spatial cognitive impairment caused by Rib-derived AGEs is correlated with activation of an astrocyte-mediated, RAGE-dependent inflammatory response. This study may provide insights into the mechanism of Rib-involved cognitive impairments and diabetic encephalopathy.

Ribose Supplementation Alone or with Elevated Creatine Does Not Preserve High Energy Nucleotides or Cardiac Function in the Failing Mouse Heart.

BACKGROUND: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE). METHODS AND RESULTS: FOUR GROUPS WERE STUDIED: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8-14%) in all infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32-47% increased mass). Ejection fraction closely correlated with infarct size independently of treatment (r(2) = 0.63, p<0.0001), but did not correlate with myocardial creatine or TAN levels. CONCLUSION: Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically failing mouse heart and that alternative strategies to preserve TAN pool should be investigated.

Daily supplementation of D-ribose shows no therapeutic benefits in the MHC-I transgenic mouse model of inflammatory myositis.

BACKGROUND: Current treatments for idiopathic inflammatory myopathies (collectively called myositis) focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1), leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg) over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. RESULTS: Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. CONCLUSIONS: Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

Supplementation of creatine and ribose prevents apoptosis and right ventricle hypertrophy in hypoxic hearts.

BACKGROUND/AIMS: The simultaneous supplementation of creatine and D-ribose has been shown to reduce apoptosis in vitro in non-irreversibly injured cultured ischemic cardiomyocytes through down-regulation of the signaling mechanisms governing adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (Akt). Here, we test the hypothesis that an analogous mechanism exists in vivo when the challenge is chronic exposure to hypoxia. METHODS: Five week-old mice were exposed to an atmosphere containing 10% O2 for 10 days. Mice were gavaged daily with vehicle, creatine, D-ribose or creatine + D-ribose. After sacrifice, myocardial and pulmonary tissue were harvested for structural and biochemical analyses. RESULTS: Hypoxia induced right ventricle hypertrophy and left ventricle apoptosis. Both phenotypes were slightly reduced by either creatine or D-ribose, whereas the simultaneous administration of creatine + D-ribose almost completely reversed the effects of hypoxia. Furthermore, creatine + D-ribose diminished the hypoxia-induced increases in the activity of AMPK, Akt and JNK, but not of ERK. Finally, the hypoxia-induced pulmonary overexpression of endothelin-1 mRNA was markedly reduced by creatine + D-ribose. CONCLUSION: The simultaneous administration of creatine + D-ribose confers additional cardiovascular protection with respect to that observed with either creatine or D-ribose. The mechanism stems from the AMPK and Akt signaling pathways. These findings may form the basis of a paradigm to re-energize non-irreversibly damaged cardiomyocytes, counteracting injury by triggering specific signaling pathways.

Effects of a carbohydrate-, protein-, and ribose-containing repletion drink during 8 weeks of endurance training on aerobic capacity, endurance performance, and body composition.

This study compared a carbohydrate-, protein-, and ribose-containing repletion drink vs. carbohydrates alone during 8 weeks of aerobic training. Thirty-two men (age, mean ± SD = 23 ± 3 years) performed tests for aerobic capacity (V(O2)peak), time to exhaustion (TTE) at 90% V(O2)peak, and percent body fat (%fat), and fat-free mass (FFM). Testing was conducted at pre-training (PRE), mid-training at 3 weeks (MID3), mid-training at 6 weeks (MID6), and post-training (POST). Cycle ergometry training was performed at 70% V(O2)peak for 1 hours per day, 5 days per week for 8 weeks. Participants were assigned to a test drink (TEST; 370 kcal, 76 g carbohydrate, 14 g protein, 2.2 g d-ribose; n = 15) or control drink (CON; 370 kcal, 93 g carbohydrate; n = 17) ingested immediately after training. Body weight (BW; 1.8% decrease CON; 1.3% decrease TEST from PRE to POST), %fat (5.5% decrease CON; 3.9% decrease TEST), and FFM (0.1% decrease CON; 0.6% decrease TEST) decreased (p ≤ 0.05), whereas V(O2)peak (19.1% increase CON; 15.8% increase TEST) and TTE (239.1% increase CON; 377.3% increase TEST) increased (p ≤ 0.05) throughout the 8 weeks of training. Percent decreases in %fat from PRE to MID3 and percent increases in FFM from PRE to MID3 and MID6 were greater (p ≤ 0.05) for TEST than CON. Overall, even though the TEST drink did not augment BW, V(O2)peak, or TTE beyond carbohydrates alone, it did improve body composition (%fat and FFM) within the first 3-6 weeks of supplementation, which may be helpful for practitioners to understand how carbohydrate-protein recovery drinks can and cannot improve performance in their athletes.

Enhanced levels of non-enzymatic glycation and pentosidine crosslinking in spontaneous osteoarthritis progression.

OBJECTIVE: To test the hypothesis that heightened advanced glycation endproducts (AGEs) content in cartilage accelerates the progression of spontaneous osteoarthritis (OA) in the Hartley guinea pig (HGP) model. METHODS: Twenty-eight male, 3-month-old HGPs were used. Eight were left untreated as a baseline control group and sacrificed at 3 months of age (n = 4) and 9 months of age (n = 4; age-matched controls). The other 20 HGPs received intra-articular knee injections in the right knee whereas the left knees acted as contra-lateral non-injected controls. Injections consisted of 100 µl phosphate buffered saline (PBS; n = 10) or PBS+2.0 M D-(-)-Ribose (n = 10). Injections were given once weekly for 24 weeks. At the end of the treatment period, the tibiae were fixed with formalin, scanned with microCT for sub-chondral bone mineral density, and then histological slides were prepared, stained with Safranin-O with Fast Green counter stain and scored using the OARSI-HISTOgp scheme. Cartilage pentosidine (established biomarker for AGEs) content, collagen content (% dry mass), glucosaminoglycan GAG-to-collagen ratio (µg/µg), GAG-to-DNA ratio and DNA-to-collagen ratio were measured. RESULTS: Pentosidine content increased greatly due to PBS + Ribose injection (P < 0.0001) and reached levels found in cartilage from 80-year-old humans. Surprisingly, mean OARSI-HISTOgp scores for both the injected and contra-lateral controls in the PBS + Ribose group were not detectably different, nor were they different from the mean score for the age-matched control group. CONCLUSION: AGEs accumulation due to intra-articular ribose-containing injections in the HGP model of spontaneous knee OA did not enhance disease progression.

Evaluation of α-D-ribofuranose (D-ribose) toxicity after intravenous administration to rabbits.

Rapid intravenous administration of D-ribose may result in a significant reduction in cellular damage in patients with sudden ischemic insults. The development of an effective and clinically safe therapeutic regimen using the intravenous route in critically ill patients especially with cardiac diseases requires a comprehensive assessment of potential toxic effects of the drug in laboratory animals and in human beings. The potential clinical, behavioral, hematological, biochemical, gross pathological and histological toxic effects associated with the intravenous administration of D-ribose in rabbits for 28 days were evaluated in this study. Except for an increase in neutrophil percentage in male rabbits in the D-ribose-treated groups, there were no statistically significant toxic effects induced by daily intravenous administration of the drug in male and female rabbits. Results of this study suggest that D-ribose administered intravenously for 28 days in the rabbit exhibited no toxicity at 420 mg/kg.