Early in vivo detection of denervation-induced atrophy by luminescence transient nanothermometry.

Denervation induces skeletal muscle atrophy due to the loss of control and feedback with the nervous system. Unfortunately, muscle atrophy only becomes evident days after the denervation event when it could be irreversible. Alternative diagnosis tools for early detection of denervation-induced muscle atrophy are, thus, required. In this work, we demonstrate how the combination of transient thermometry, a technique already used for early diagnosis of tumors, and infrared-emitting nanothermometers makes possible the in vivo detection of the onset of muscle atrophy at short (<1 day) times after a denervation event. The physiological reasons behind these experimental results have been explored by performing three dimensional numerical simulations based on the Pennes' bioheat equation. It is concluded that the alterations in muscle thermal dynamics at the onset of muscle atrophy are consequence of the skin perfusion increment caused by the alteration of peripheral nervous autonomous system. This work demonstrates the potential of infrared luminescence thermometry for early detection of diseases of the nervous system opening the venue toward the development of new diagnosis tools.

Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation.

Denervation-induced muscle atrophy is a frequent cause of skeletal muscle diseases. However, the role of the most important muscle growth factor, insulin-like growth factor (IGF-1), in this process is poorly understood. IGF-1 activity is controlled by six IGF-1 binding proteins (IGFBPs). In skeletal muscle, IGFBP-5 seems to have an important role in atrophic processes. Furthermore, pappalysins (PAPP-A) modulate muscle growth by increasing IGF-1 bioavailability through IGFBP cleavage. We aimed to study the time-dependent changes in the IGF1-IGFBP5-PAPP system and its regulators in gastrocnemius muscle after sciatic denervation. Gastrocnemius atrophy and overexpression of IGF-1 was observed from day 3 post-denervation. The proteolytic factors measured were elevated from day 1 post-denervation onwards. Expression of both IGFBP-5 and pappalysins were increased on days 1 and 3. Subsequently, on days 7 to 14 pappalysins returned to control levels while IGFBP-5 remained elevated. The ratio IGFBP-5/PAPP-A was correlated with the main proteolytic markers. All data suggest that the initial increase of pappalysins could facilitate the IGF-1 action on muscle growth, whereas their subsequent decrease could lead to further muscle wasting.

Fortasyn Connect Improves Neuropsychiatric Symptoms in Patients with Mild Cognitive Impairment and Dementia: Results from a Retrospective Real-World Study.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) manifest in the early stages of the disease and impair patients' and caregivers' quality of life. OBJECTIVE: To assess the effectiveness of the nutritional supplement Fortasyn Connect on BPSD for 12 months in people with mild cognitive impairment (MCI) and dementia in clinical practice. METHODS: Retrospective, national, single-center study of 236 patients (158 MCI and 78 dementia; 55.1% of AD etiology). BPSD were assessed with the Neuropsychiatric Inventory (NPI) at month 3, 6, and 12. Cognition (Mini-Mental State Examination, MMSE), depression (Geriatric Depression Scale, GDS), and everyday functioning (Blessed Dementia Scale, BLS-D; Rapid Disability Rating Scale 2, RDRS2) were also evaluated. RESULTS: Total NPI score, caregiver impact, and symptoms of depression, anxiety, apathy, and irritability improved after 3, 6, and 12 months from Fortasyn Connect initiation (p < 0.001). NPI decreases were more pronounced when baseline NPI score was higher than > 20 points (p < 0.001). The benefit was independent of gender, age, diagnosis, etiology, or concomitant treatment (p < 0.0001), although larger decreases in NPI total score were observed in MCI patients (p < 0.0001). After 12 months, GDS scores decreased (p = 0.042), and MMSE, BLS-D, and RDRS 2 scores remained stable. CONCLUSION: Fortasyn Connect improved BPSD over at least a year in patients with MCI and dementia. Depression, anxiety, apathy, and irritability were the symptoms that improved the most. The benefit was independent of patients' characteristics and treatment but was greater if prescribed early and when baseline NPI scores were higher.

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats.

Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.

IGF-1 and IGFBP-3 in Inflammatory Cachexia.

Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic-growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic-GH-IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.

Addition of Olive Leaf Extract to a Mixture of Algae and Extra Virgin Olive Oils Decreases Fatty Acid Oxidation and Synergically Attenuates Age-Induced Hypertension, Sarcopenia and Insulin Resistance in Rats.

Olive-derived products, such as virgin olive oil (EVOO) and/or olive leaf extracts (OLE), exert anti-inflammatory, insulin-sensitizing and antihypertensive properties and may be useful for stabilizing omega 3 fatty acids (n-3 PUFA) due to their high content in antioxidant compounds. In this study, the addition of OLE 4:0.15 (w/w) to a mixture of algae oil (AO) rich in n-3 PUFA and EVOO (25:75, w/w) prevents peroxides formation after 12 months of storage at 30 °C. Furthermore, the treatment with the oil mixture (2.5 mL/Kg) and OLE (100 mg/Kg) to 24 month old Wistar rats for 21 days improved the lipid profile, increased the HOMA-IR and decreased the serum levels of miRNAs 21 and 146a. Treatment with this new nutraceutical also prevented age-induced insulin resistance in the liver, gastrocnemius and visceral adipose tissue by decreasing the mRNA levels of inflammatory and oxidative stress markers. Oil mixture + OLE also attenuated the age-induced alterations in vascular function and prevented muscle loss by decreasing the expression of sarcopenia-related markers. In conclusion, treatment with a new nutraceutical based on a mixture of EVOO, AO and OLE is a useful strategy for improving the stability of n-3 PUFA in the final product and to attenuate the cardiometabolic and muscular disorders associated with aging.

Olive Leaf Extract Supplementation to Old Wistar Rats Attenuates Aging-Induced Sarcopenia and Increases Insulin Sensitivity in Adipose Tissue and Skeletal Muscle.

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle.

Olive leaf extract supplementation improves the vascular and metabolic alterations associated with aging in Wistar rats.

Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3ß and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging.

Beneficial Effects of a Mixture of Algae and Extra Virgin Olive Oils on the Age-Induced Alterations of Rodent Skeletal Muscle: Role of HDAC-4.

Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle; it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.

A Mixture of Algae and Extra Virgin Olive Oils Attenuates the Cardiometabolic Alterations Associated with Aging in Male Wistar Rats.

Aging is one of the major risk factors for suffering cardiovascular and metabolic diseases. Due to the increase in life expectancy, there is a strong interest in the search for anti-aging strategies to treat and prevent these aging-induced disorders. Both omega 3 polyunsaturated fatty acids (ω-3 PUFA) and extra virgin olive oil (EVOO) exert numerous metabolic and cardiovascular benefits in the elderly. In addition, EVOO constitutes an interesting ingredient to stabilize ω-3 PUFA and decrease their oxidation process due to its high content in antioxidant compounds. ω-3 PUFA are commonly obtained from fish. However, more ecological and sustainable sources, such as algae oil (AO) can also be used. In this study, we aimed to study the possible beneficial effect of an oil mixture composed by EVOO (75%) and AO (25%) rich in ω-3 PUFA (35% docosahexaenoic acid (DHA) and 20% eicosapentaenoic acid (EPA)) on the cardiometabolic alterations associated with aging. For this purpose; young (three months old) and old (24 months old) male Wistar rats were treated with vehicle or with the oil mixture (2.5 mL/kg) for 21 days. Treatment with the oil mixture prevented the aging-induced increase in the serum levels of saturated fatty acids (SFA) and the aging-induced decrease in the serum concentrations of mono-unsaturated fatty acids (MUFA). Old treated rats showed increased serum concentrations of EPA and DHA and decreased HOMA-IR index and circulating levels of total cholesterol, insulin and IL-6. Treatment with the oil mixture increased the mRNA levels of antioxidant and insulin sensitivity-related enzymes, as well as reduced the gene expression of pro-inflammatory markers in the liver and in cardiac and aortic tissues. In addition, the treatment also prevented the aging-induced endothelial dysfunction and vascular insulin resistance through activation of the PI3K/Akt pathway. Moreover, aortic rings from old rats treated with the oil mixture showed a decreased response to the vasoconstrictor AngII. In conclusion, treatment with a mixture of EVOO and AO improves the lipid profile, insulin sensitivity and vascular function in aged rats and decreases aging-induced inflammation and oxidative stress in the liver, and in the cardiovascular system. Thus, it could be an interesting strategy to deal with cardiometabolic alterations associated with aging.

Strengths-Weaknesses-Opportunities-Threats Analysis for a Pediatric Anesthesia Program.

Risk management in healthcare institutions begins by first identifying the potential risks within a certain organization or specific area and then goes on to develop further strategies to reduce harm. The most common tool for this type of analysis is Strengths-Weaknesses-Opportunities-Threats (SWOT). METHODS: We conducted a SWOT analysis in our pediatric anesthesia program: key factors were identified in a matrix, prioritized in a score table, represented in a graph, and finally analyzed. RESULTS: Items obtained partial scores from 20 to 120. The item "lack of clinical protocols" was given greater weight (60) and received a lower value (1), resulting in the highest partial score (60) among the negative key factors and indicating a need for greater efforts to improve this specific aspect. CONCLUSION: The SWOT tool proved effective in identifying safety and quality key factors, and it provided information for initiating an improvement program.

Hormones and Muscle Atrophy.

The endocrine system is an essential regulator of muscle metabolism in both health and disease. Hormones such as growth hormone (GH), insulin-like growth factor-I (IGF-I) and androgens are the main regulators of muscle metabolism in both health and disease; have profound influences on muscle, acting as anabolic factors; and are important regulators of muscle mass. On the contrary, glucocorticoids have direct catabolic effects and induce muscle protein loss. Muscle wasting is a systemic response to fasting and several diseases like cancer, sepsis, renal and cardiac failure and trauma. Muscle atrophy also occurs in specific muscles with denervation, immobilization or inactivity. All of these conditions are characterized by significant changes in the endocrine environment. The aim of this review was to describe the role of endocrine system on the development of muscle atrophy. Understanding hormonal regulation of the skeletal muscle in these conditions might facilitate the development of hormone-mediated therapies for muscle atrophy.

Formoterol treatment prevents the effects of endotoxin on muscle TNF/NF-kB, Akt/mTOR, and proteolytic pathways in a rat model. Role of IGF-I and miRNA 29b.

Inflammatory diseases are associated with muscle wasting as a result of an increase in proteolysis. The purpose of this study was to elucidate whether administration of a ß2 adrenergic agonist, formoterol, was able to prevent the acute effects of sepsis induced by liposaccharide (LPS) injection on rat gastrocnemius muscle and to evaluate the possible roles of corticosterone, IGF-I, miR-23a, and miR-29b. For this purpose, male Wistar rats were injected with LPS and/or formoterol. Formoterol treatment decreased LPS-induced increase in serum corticosterone, TNFα upregulation, and NF-κB(p65) and Forkhead box protein O1 activation in the gastrocnemius. Atrogin-1, muscle RING-finger protein-1, microtubule-associated protein-1 light chain 3b (LC3b), and the lipidation of LC3b-I to LC3b-II were increased by LPS, and formoterol blocked these effects. Serum IGF-I and its mRNA levels in the gastrocnemius were decreased, whereas mecano growth factor and IGF binding protein 3 mRNA levels were increased in the rats injected with LPS but not in the rats that received LPS and formoterol. Similarly, LPS decreased Akt and mammalian target of rapamycin phosphorylation, and formoterol blocked these decreases. Finally, miR-29b expression in the gastrocnemius was upregulated by endotoxin injection, whereas miR-23a was not significantly different. Formoterol treatment did not significantly modify LPS-induced increase in muscle miR-29b. Furthermore, in control rats formoterol increased the expression of this miRNA. We conclude that formoterol decreases endotoxin-induced inflammation and proteolysis in rat skeletal muscle. Those responses can be a direct effect of ß2 adrenergic receptor stimulation or/and of blocking the effects of LPS on corticosterone and IGF-I. Muscle miR-23a and -29b do not seem to play an important role in those responses.

Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis.

Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. ß2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective ß2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 µg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.

D-TRP(8)-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway.

Sepsis induces anorexia and muscle wasting secondary to an increase in muscle proteolysis. Melanocyte stimulating hormones (MSH) is a family of peptides that have potent anti-inflammatory effects. Melanocortin receptor-3 (MC3-R) has been reported as the predominant anti-inflammatory receptor for melanocortins. The aim of this work was to analyse whether activation of MC3-R, by administration of its agonist D-Trp(8)-γMSH, is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS) or TNFα. Adult male rats were injected with 250 µg/kg LPS and/or 500 µg/kg D-Trp(8)-γMSH 17:00 h and at 8:00 h the following day, and euthanized 4 hours afterwards. D-Trp(8)-γMSH decreased LPS-induced anorexia and prevented the stimulatory effect of LPS on hypothalamic IL-1ß, COX-2 and CRH as well as on serum ACTH and corticosterone. Serum IGF-I and its expression in liver and gastrocnemius were decreased in rats injected with LPS, but not in those that also received D-Trp(8)-γMSH. However, D-Trp(8)-γMSH was unable to modify the effect of LPS on IGFBP-3. In the gastrocnemius D-Trp(8)-γMSH blocked LPS-induced decrease in pAkt, pmTOR, MHC I and MCH II, as well as the increase in pNF-κB(p65), FoxO1, FoxO3, LC3b, Bnip-3, Gabarap1, atrogin-1, MuRF1 and in LC3a/b lipidation. In L6 myotube cultures, D-Trp(8)-γMSH was able to prevent TNFα-induced increase of NF-κB(p65) phosphorylation and decrease of Akt phosphorylation as well as of IGF-I and MHC I expression. These data suggest that MC3-R activation prevents the effect of endotoxin on skeletal wasting by modifying inflammation, corticosterone and IGF-I responses and also by directly acting on muscle cells through the TNFα/NF-κB(p65) pathway.

The melanocortin receptor type 3 agonist d-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats.

BACKGROUND: Chronic inflammatory diseases induce cachexia that increases mortality and morbidity of the illness. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. Alpha-melanocyte stimulating hormone has an anti-inflammatory effect in arthritic rats and decreases muscle wasting. The aim of this work was to elucidate whether the anti-cachectic action of alpha-melanocyte stimulating hormone is mediated by the melanocortin receptor type 3 pathway. METHODS: Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant, and 6 days afterwards, arthritic rats were injected with the selective melanocortin receptor type 3 agonist d-Trp(8)-gammaMSH ( d-Trp(8)-γMSH) 500 µg/kg subcutaneously. or saline twice a day, for 10 days. RESULTS: d-Trp(8)-γMSH decreased the external signs of inflammation and body weight loss, but it was not able to modify the anorexigenic effect of arthritis or the increase in hypothalamic cyclooxygenase-2 (COX-2) expression. In contrast, d-Trp(8)-γMSH prevented arthritis-induced increase in hypothalamic IL-1ß and serum corticosterone levels and the decrease in serum IGF-I levels. d-Trp(8)-γMSH treatment also prevented arthritis-induced NF-kB(p65) phosphorylation and tumour necrosis factor-α mRNA increase in the gastrocnemius. d-Trp(8)-γMSH administration to arthritic rats increased gastrocnemius mass, its cross-sectional area, and mean fast fibre area. Those effects of d-Trp(8)-γMSH were associated with a decreased expression of atrogin-1 and muscle ring-finger protein-1 in the gastrocnemius. In rats treated with saline, arthritis increased the expression of autophagy marker genes LC3b, Bnip-3, and Gabarap1 as well as the conversion of LC3b I to LC3b II by lipidation in the gastrocnemius. d-Trp(8)-γMSH decreased gastrocnemius LC3b, Bnip-3, and Gabarap1 mRNA expression and prevented the increase in LC3b II in arthritic rats. CONCLUSION: These data suggest that d-Trp(8)-γMSH administration prevents the effect of arthritis on corticosterone and insulin-like growth factor-I serum levels and decreases muscle wasting, by down-regulating atrogenes and autophagy through modifying the NF-kB(p65)/tumour necrosis factor-α signalling transduction pathway.

αMSH blunts endotoxin-induced MuRF1 and atrogin-1 upregulation in skeletal muscle by modulating NF-κB and Akt/FoxO1 pathway.

Alpha melanocyte stimulating hormone (αMSH) has been shown to have anti-inflammatory and anticachectic actions. We hypothesized that αMSH administration could attenuate the effect of lipopolysaccharide (LPS) on the skeletal muscle through modifications in IGF-Akt-FoxO1 pathway, or/and in serum corticosterone. Adult male Wistar rats were injected with LPS and/or αMSH. αMSH administration reduced LPS-induced increase in liver TNFα and serum nitrites as well as NF-κB activation in skeletal muscle. In contrast, αMSH was not able to prevent the stimulatory effect of LPS on serum concentration of ACTH and corticosterone. LPS decreased serum levels of IGF-I and IGFBP3 and their expression in the liver (P < 0.01). However IGFBP3 expression in the gastrocnemius was increased by LPS. Treatment with αMSH prevented the effects of LPS on IGFBP3 but not on IGF-I. In the gastrocnemius αMSH blocked LPS-induced decrease in pAkt as well as the increase in pNF-κB(p65), FoxO1, atrogin-1, and MuRF1 levels. These results suggest that αMSH blunts skeletal muscle response to endotoxin by downregulating atrogenes and FoxO1 at least in part by controlling NF-κB activation and Akt signalling, but not through modifications in the secretion of corticosterone or IGF-I.

Eficacia y seguridad de la quercetina como complemento alimenticio / Efficacy and safety of quercetin as dietary supplement

La quercetina es un antioxidante natural presente en gran variedad de alimentos que se ha asociado con la prevención de determinadas enfermedades. Sus propiedades beneficiosas han sido claramente demostradas en estudios preclínicos, sin embargo, las dosis utilizadas han sido superiores a las de una dieta rica en este flavonoide. Por este motivo, se han desarrollado procesos para la obtención y posterior comercialización de la misma como suplemento alimenticio. A pesar de que en los últimos años se ha incrementado el consumo de preparados de quercetina, no están bien definidos cuáles son los efectos tóxicos derivados de su administración. Además, no se han establecido dosis diarias admisibles que aseguren la seguridad de su uso. Mediante esta revisión pretendemos analizar la información presente en la bibliografía, tanto de las propiedades terapéuticas asociadas a la quercetina, como de los posibles riesgos debidos al aumento de su consumo (AU)

Quercetin is a natural antioxidant present in a variety of food that has been associated with the prevention of certain diseases. Its beneficial properties have been clearly demonstrated in preclinical studies, however, the doses used were higher than those of a diet rich with this flavonoid. For this reason, the production and commercialization processes of quercetin as a food supplement have been developed. Although in recent years the consumption of quercetin preparations has increased, toxic effects resulting from its administration have not been well defined. Furthermore, no acceptable daily intakes have been established to ensure the safety of its use. Through this review we attempt to analyze the information in the literature, both therapeutic properties of quercetin and the possible risks due to its increased consumption (AU)

Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting.

Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. α-Melanocyte-stimulating hormone (α-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic α-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with α-MSH (50 µg/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake (P < 0.01). In addition, α-MSH decreased hypothalamic expression of IL-1ß, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, α-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. α-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral α-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.