P.119 Is NO synthase pathway involved in ornithine α-ketoglutarate beneficial effects on muscle wasting?

1998 ◽  
Vol 17 ◽  
pp. 62
Author(s):  
P. Pernet ◽  
C. Coudray-Lucas ◽  
C. Gillet ◽  
A. Jardel ◽  
M.P. Vasson ◽  
...  
Keyword(s):  
Muscle Wasting ◽  
No Synthase ◽  
Beneficial Effects

scholarly journals Pentoxifylline Prevents Autoimmune Mediated Inflammation in Low Dose Streptozotocin Induced Diabetes

2001 ◽  
Vol 8 (3-4) ◽  
pp. 213-221 ◽  
Author(s):  
Stanislava D. Stošic-Grujicic ◽  
Danijela D. Maksimovic ◽  
Marija B. Mostarica Stojkovic ◽  
Miodrag L. Lukic
Keyword(s):  
Cell Activation ◽  
Mononuclear Cells ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
No Synthase ◽  
Protective Effects ◽  
Endothelial Cell Activation ◽  
Susceptible Host ◽  
Xanthine Derivative ◽  
Beneficial Effects

Xanthine derivative, pentoxifylline (PTX), has been recently shown to exert a protective effects in certain animal models of autoimmunity, including diabetes in NOD mice. In the present study, the immunomodulatory potential of PTX was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-SZ) in genetically susceptible CBA/H mice (tested with 40 mg SZ/kg b.w. for 5 days) and DA rats (tested with 20 mg/kg b.w. for 5 days). In both species, 2 – 3 weeks following the MLD-SZ treatment, sustained hyperglycemia developed, as an outcome of inflammatory reaction with endothelial cell activation and accumulation of mononuclear cells. Although there was no evidence of typical insulitis in early disease development (day 10), in both rats and mice, macrophages, CD4+and CD8+cells were present in the islets of Langerhans as diffuse mononuclear infiltrates with the expression of IFN-γ and inducible NO synthase (iNOS). Administration of PTX (200 mg/kg/day for 10 days) in combination with MLD-SZ reduced insulitis and the production of mediators tested, and prevented the development of hyperglycemia. These results suggest that beneficial effects of PTX involve down-regulation of local proinflammatory cytokine-mediated NO synthase pathway. They also demonstrate that in addition to ameliorating spontaneous autoimmunity in NOD mice, PTX may be effective in downregulating an inflammatory autoimmune process triggered in susceptible host by an external agents, such as streptozotocin.

scholarly journals L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

1998 ◽  
Vol 9 (2) ◽  
pp. 203-210 ◽  
Author(s):  
U Haberstroh ◽  
K Stilo ◽  
J Pocock ◽  
G Wolf ◽  
U Helmchen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Northern Blotting ◽  
No Synthase ◽  
In Vivo Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Cell Infiltrate ◽  
Beneficial Effects

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

scholarly journals The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting, a Systematic Review—Gut Permeability as Potential Treatment Target

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1115
Author(s):  
Sandra J. van Krimpen ◽  
Fleur A. C. Jansen ◽  
Veerle L. Ottenheim ◽  
Clara Belzer ◽  
Miranda van der Ende ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Wasting ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Lactobacillus Species ◽  
Potential Treatment ◽  
Gut Permeability ◽  
Beneficial Effects ◽  
Gut Function ◽  
Lactobacillus Spp

Muscle wasting is a frequently observed, inflammation-driven condition in aging and disease, known as sarcopenia and cachexia. Current treatment strategies target the muscle directly and are often not able to reverse the process. Because a reduced gut function is related to systemic inflammation, this might be an indirect target to ameliorate muscle wasting, by administering pro-, pre-, and synbiotics. Therefore, this review aimed to study the potential of pro-, pre-, and synbiotics to treat muscle wasting and to elucidate which metabolites and mechanisms affect the organ crosstalk in cachexia. Overall, the literature shows that Lactobacillus species pluralis (spp.) and possibly other genera, such as Bifidobacterium, can ameliorate muscle wasting in mouse models. The beneficial effects of Lactobacillus spp. supplementation may be attributed to its potential to improve microbiome balance and to its reported capacity to reduce gut permeability. A subsequent literature search revealed that the reduction of a high gut permeability coincided with improved muscle mass or strength, which shows an association between gut permeability and muscle mass. A possible working mechanism is proposed, involving lactate, butyrate, and reduced inflammation in gut–brain–muscle crosstalk. Thus, reducing gut permeability via Lactobacillus spp. supplementation could be a potential treatment strategy for muscle wasting.

scholarly journals Is Exercise Training Appropriate for Patients With Advanced Heart Failure Receiving Continuous Inotropic Infusion? A Review

2018 ◽  
Vol 12 ◽  
pp. 117954681775143 ◽  
Author(s):  
Eisuke Amiya ◽  
Masanobu Taya
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Vascular Function ◽  
Muscle Wasting ◽  
Severe Heart Failure ◽  
Advanced Heart Failure ◽  
Autonomic Balance ◽  
Beneficial Effects ◽  
Rehabilitation Programs ◽  
Patients With Heart Failure

Exercise-based rehabilitation programs have been reported to have beneficial effects for patients with heart failure. However, there is little evidence about whether this is the case in patients with more severe heart failure. In particular, there is a question in the clinical setting whether patients with advanced heart failure and continuous inotropic infusion should be prescribed exercise training. In contrast, many studies conclude that prolonged immobility associated with heart failure profoundly impairs physical function and promotes muscle wasting that could further hasten the course of heart failure. By contrast, exercise training has various effects not only in improving exercise capacity but also on vascular function, skeletal muscle, and autonomic balance. In this review, we summarize the effectiveness and discuss methods of exercise training in patients with advanced heart failure receiving continuous inotropic agents such as dobutamine.

scholarly journals Targeting the Activin Receptor Signaling to Counteract the Multi-Systemic Complications of Cancer and Its Treatments

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 516
Author(s):  
Juha J. Hulmi ◽  
Tuuli A. Nissinen ◽  
Fabio Penna ◽  
Andrea Bonetto
Keyword(s):  
Poor Prognosis ◽  
Muscle Wasting ◽  
Preclinical Models ◽  
Systemic Complications ◽  
Activin Receptor ◽  
Downstream Signaling ◽  
Beneficial Effects ◽  
Tumor Bearing

Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting quality of life and overall survival in cancer patients. Pre-clinical studies have shown that blocking activin receptor type 2 (ACVR2) or its ligands and their downstream signaling can preserve muscle mass in rodents bearing experimental cancers, as well as in chemotherapy-treated animals. In tumor-bearing mice, the prevention of skeletal and respiratory muscle wasting was also associated with improved survival. However, the definitive proof that improved survival directly results from muscle preservation following blockade of ACVR2 signaling is still lacking, especially considering that concurrent beneficial effects in organs other than skeletal muscle have also been described in the presence of cancer or following chemotherapy treatments paired with counteraction of ACVR2 signaling. Hence, here, we aim to provide an up-to-date literature review on the multifaceted anti-cachectic effects of ACVR2 blockade in preclinical models of cancer, as well as in combination with anticancer treatments.

Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

2008 ◽  
Vol 88 (2) ◽  
pp. 729-767 ◽  
Author(s):  
Gordon S. Lynch ◽  
James G. Ryall
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Therapeutic Potential ◽  
Muscle Growth ◽  
Neuromuscular Diseases ◽  
Cardiovascular Effects ◽  
Adrenergic System ◽  
Adrenergic Signaling ◽  
Beneficial Effects ◽  
Cardiovascular Side Effects

The importance of β-adrenergic signaling in the heart has been well documented, but it is only more recently that we have begun to understand the importance of this signaling pathway in skeletal muscle. There is considerable evidence regarding the stimulation of the β-adrenergic system with β-adrenoceptor agonists (β-agonists). Although traditionally used for treating bronchospasm, it became apparent that some β-agonists could increase skeletal muscle mass and decrease body fat. These so-called “repartitioning effects” proved desirable for the livestock industry trying to improve feed efficiency and meat quality. Studying β-agonist effects on skeletal muscle has identified potential therapeutic applications for muscle wasting conditions such as sarcopenia, cancer cachexia, denervation, and neuromuscular diseases, aiming to attenuate (or potentially reverse) the muscle wasting and associated muscle weakness, and to enhance muscle growth and repair after injury. Some undesirable cardiovascular side effects of β-agonists have so far limited their therapeutic potential. This review describes the physiological significance of β-adrenergic signaling in skeletal muscle and examines the effects of β-agonists on skeletal muscle structure and function. In addition, we examine the proposed beneficial effects of β-agonist administration on skeletal muscle along with some of the less desirable cardiovascular effects. Understanding β-adrenergic signaling in skeletal muscle is important for identifying new therapeutic targets and identifying novel approaches to attenuate the muscle wasting concomitant with many diseases.

Postischemic anti-inflammatory effects of bradykinin preconditioning

2001 ◽  
Vol 280 (1) ◽  
pp. H441-H454 ◽  
Author(s):  
Sakuji Shigematsu ◽  
Shuji Ishida ◽  
Dean C. Gute ◽  
Ronald J. Korthuis
Keyword(s):  
Microvascular Dysfunction ◽  
Concomitant Administration ◽  
No Synthase ◽  
Barrier Dysfunction ◽  
Subsequent Formation ◽  
Beneficial Effects ◽  
Rat Mesentery ◽  
Albumin Leakage ◽  
Anti Inflammatory ◽  
Adhesive Interactions

We sought to determine the mechanisms whereby brief administration of bradykinin (bradykinin preconditioning, BK-PC) before prolonged ischemia followed by reperfusion (I/R) prevents postischemic microvascular dysfunction. Intravital videomicroscopic approaches were used to quantify I/R-induced leukocyte/endothelial cell adhesive interactions and microvascular barrier disruption in single postcapillary venules of the rat mesentery. I/R increased the number of rolling, adherent, and emigrated leukocytes and enhanced venular albumin leakage, effects that were prevented by BK-PC. The anti-inflammatory effects of BK-PC were largely prevented by concomitant administration of a B2-receptor antagonist but not by coincident B1 receptor blockade, nitric oxide (NO) synthase inhibition, or cyclooxygenase blockade. However, NO synthase blockade during reperfusion after prolonged ischemia was effective in attenuating the anti-inflammatory effects of BK-PC. Pan protein kinase C (PKC) inhibition antagonized the beneficial effects of BK-PC but only when administered during prolonged ischemia. In contrast, specific inhibition of the conventional PKC isotypes failed to alter the effectiveness of BK-PC. These results indicate that bradykinin can be used to pharmacologically precondition single mesenteric postcapillary venules to resist I/R-induced leukocyte recruitment and microvascular barrier dysfunction by a mechanism that involves B2receptor-dependent activation of nonconventional PKC isotypes and subsequent formation of NO.

Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia

2009 ◽  
Vol 118 (5) ◽  
pp. 359-366 ◽  
Author(s):  
Paul K. Hamilton ◽  
Sinead M.T. Hughes ◽  
Richard D. Plumb ◽  
Adrian Devine ◽  
William Leahey ◽  
...  
Keyword(s):  
No Synthase ◽  
Superoxide Production ◽  
Membrane Association ◽  
Potential Mechanism ◽  
Post Translational Modification ◽  
Beneficial Effects ◽  
Atorvastatin Therapy ◽  
Enhancing Production ◽  
Free Radical Activity ◽  
Reduced Activity

In addition to lowering cholesterol, statins may alter endothelial release of the vasodilator NO and harmful superoxide free radicals. Statins also reduce cholesterol intermediates including isoprenoids. These are important for post-translational modification of substances including the GTPases Rho and Rac. By altering the membrane association of these molecules, statins affect intracellular positioning and hence activity of a multitude of substances. These include eNOS (endothelial NO synthase), which produces NO (inhibited by Rho), and NADPH oxidase, which produces superoxide (dependent on Rac). Statins may improve endothelial function by enhancing production of NO while decreasing superoxide production. A total of 40 hypercholesterolaemic patients were randomized to treatment with either atorvastatin or placebo; 20 normolipidaemic patients were also studied. Platelet nitrite, NO and superoxide were examined as was the cellular distribution of the GTPases Rho and Rac at baseline and after 8 weeks of treatment. Following atorvastatin therapy, platelet NO was increased (3.2 pmol/108 platelets) and superoxide output was attenuated [−3.4 pmol·min−1·(108 platelets)−1] when compared with placebo. The detection of both Rho and Rac was significantly reduced in the membranes of platelets, implying reduced activity. In conclusion, the results of the present study show altered NO/superoxide production following statin therapy. A potential mechanism for this is the change in the distribution of intracellular GTPases, which was considered to be secondary to decreases in isoprenoid intermediates, suggesting that the activity of the former had been affected by atorvastatin.

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