Soccer and Risk of Cardiovascular Events.

Background: Physical and emotional stress have been associated with an increased incidence of acute coronary syndrome (ACS). Sporting events such as soccer matches can cause spectators to experience cardiovascular events. The objective of the present study was to determine whether an association of this type existed during a Spanish league competition. Methods: We recorded data from patients who were admitted with ACS during 2018 - 2020. Patients were divided into two groups: those who were admitted on the day the local team played and those who were admitted on nonmatch days. We determined various cardiovascular risk factors, including the degree of hostility and anxiety. Results: Away wins reduced the number of admissions with ACS by 30%, whereas a local loss increased hospitalizations by more than 30%. The profile of patient admitted on match days was a > 65 years old man, smoker (current or past), obese, with worse control of his hypertension, diabetes, and dyslipidemia, poor pharmacological adherence and high anxiety and hostility scores. Conclusions: A loss by the local team increases the number of admissions with ACS in males with a high burden of cardiovascular risk factors. Primary prevention measures should be taken to reduce the frequency of these events.

Mechanisms Underlying Testicular Damage and Dysfunction in Mice With Partial IGF-1 Deficiency and the Effectiveness of IGF-1 Replacement Therapy.

OBJECTIVE: To determine whether insulin-like growth factor (IGF-1) deficiency can cause testicular damage and to examine changes of the testicular morphology and testicular function-related gene expression caused by IGF-1 deficiency. Therefore, this study aims to determine the benefits of low doses of IGF-1 and to explore the mechanisms underlying the IGF-1 replacement therapy. MATERIALS AND METHODS: A murine model of IGF-1 deficiency was used to avoid any factor that could contribute to testicular damage. Testicular weight, score of histopathological damage, and gene expressions were studied in 3 experimental groups of mice: controls (wild-type Igf1(+/+)), heterozygous Igf1(+/-) with partial IGF-1 deficiency, and heterozygous Igf1(+/-) treated with IGF-1. RESULTS: Results show that the partial IGF-1 deficiency induced testicular damage and altered expression of genes involved in IGF-1 and growth hormone signaling and regulation, testicular hormonal function, extracellular matrix establishment and its regulation, angiogenesis, fibrogenesis, inflammation, and cytoprotection. In addition, proteins involved in tight junction expression were found to be reduced. However, low doses of IGF-1 restored the testicular damage and most of these parameters. CONCLUSION: IGF-1 deficiency caused the damage of the blood-testis barrier and testicular structure and induced the abnormal testicular function-related gene expressions. However, low doses of IGF-1 constitute an effective replacement therapy that restores the described testicular damage. Data herein show that (1) cytoprotective activities of IGF-1 seem to be mediated by heat shock proteins and that (2) connective tissue growth factor could play a relevant role together with IGF-1 in the extracellular matrix establishment.

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

BACKGROUND: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. AIMS: The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. METHODS: The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. RESULTS: Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. CONCLUSION: The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidative damage in aging rats.

GH and IGF-I concentrations decline with age. Age-related changes appear to be linked to decreases in the anabolic hormones, GH and IGF-I. The aim of this study was to investigate the antioxidant, anabolic, and metabolic effects of the IGF-I replacement therapy, at low doses, in aging rats. Three experimental groups were included in this protocol: young healthy controls (17 wk old); untreated old (O) rats (103 wk old); and aging rats (103 wk old) treated with IGF-I during 1 month (2.25 microg IGF-I/100 g body weight(-1).d(-1)). Compared with young controls, untreated aging rats showed a reduction of IGF-I and testosterone levels, and a decrease of serum total antioxidant status, which were corrected by IGF-I therapy. In addition, untreated O presented increased levels of serum glucose with hyperinsulinemia, cholesterol, and triglycerides, and a reduction of free fatty acid concentrations. IGF-I therapy was able to revert insulin resistance, and to reduce cholesterol and triglycerides levels increasing significantly free fatty acid concentrations. The O group showed higher oxidative damage in brain and liver tissues associated with alterations in antioxidant enzyme activities. IGF-I therapy reduced oxidative damage in brain and liver, normalizing antioxidant enzyme activities and mitochondrial dysfunction. In conclusion, low doses of IGF-I restore circulating IGF-I, improve glucose and lipid metabolism, increase testosterone levels and serum total antioxidant capability, and reduce oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities and mitochondrial function.

Little effects of insulin-like Growth Factor-I on testicular atrophy induced by hypoxia.

BACKGROUND: Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. METHODS: Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Then, rats with testicular atrophy (AT) were divided into two groups (n = 10 each): untreated rats (AT) receiving saline sc, and AT+IGF, which were treated with IGF-I (2 microg.100 g b.w.(-1).day(-1), sc.) for 28 d. Healthy controls (CO, n = 10) were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx) were assessed. RESULTS: Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased significantly steroidogenesis and PHGPx activity (p < 0.05). Interestingly, plasma IGF-I did not augment in rats with testicular atrophy treated with IGF-I, while IGFBP3 levels, that reduces IGF-I availability, was increased in this group (p < 0.05). CONCLUSION: In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrome or liver cirrhosis).

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis.

BACKGROUND: The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 microg x 100 g(-1) x day(-1)). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage. METHODS: Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry. RESULTS: Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05). CONCLUSION: the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.

Hematotesticular barrier is altered from early stages of liver cirrhosis: effect of insulin-like growth factor 1.

AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophyso-gonadal axis in rats with no ascitic cirrhosis. METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk, were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 microg/100 g.d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12). RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<0.01 vs untreated cirrhotic group). CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.

Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I.

BACKGROUND: Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis. METHODS: Advanced cirrhosis was induced by CCl4 inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using 14C or 35S-labelled subtracts in the three experimental groups. RESULTS: Intestinal active Na+-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased Vmax and a reduced affinity for sugar and four amino acids transporters (expressed as an increased Kt) in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy. CONCLUSIONS: The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids) are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I.