Biomedical subjects

Gianfranco Guarnieri

Publications and source records attributed to Gianfranco Guarnieri.

At least 19 recordsLinked to original sources

PubMed2007

Advances in carnitine in chronic uremia.

Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology. Carnitine is necessary for fatty acid transport to sites of beta-oxidation in the mitochondria, where it helps to prevent organic acid accumulation. Because of these key regulatory functions, carnitine represents a crucial determinant of mitochondrial energy metabolism, whose deficiency may lead to metabolic and clinical disturbances. Loss of carnitine through dialytic membranes occurs in maintenance hemodialysis, resulting in potential carnitine depletion and relative increments of esterified carnitine forms. Carnitine supplementation has been shown to counteract such alterations and may be associated with clinical benefit. In particular, carnitine supplementation in patients on hemodialysis may enhance response to erythropoietin, resulting in improved hematologic status. Carnitine was also reported to improve exercise tolerance and intradialytic symptoms. Carnitine supplementation may enhance insulin resistance, inflammatory and antioxidant status, protein balance, lipid profile, and cardiac function. Carnitine administration can be useful for selected patients on dialysis who do not adequately respond to standard therapy.

Carnitine↗

PubMed2007

Vascular sources of oxidative stress: implications for uremia-related cardiovascular disease.

Chronic oxidative stress that characterizes uremia has potentially devastating effects on the vasculature and has been advocated in the pathogenesis of accelerated atherosclerosis in this disease. Recent advances have been made in our understanding of the molecular mechanisms that regulate expression and activity of key enzymes of vascular oxidative stress (eg, nicotinamide adenine dinucleotide phosphate [NAD{P}H] oxidase) and that dissect their interactions with signalling pathways of inflammation. The finding that NAD(P)H oxidase is upregulated in experimental uremia has important consequences from a physiologic and a therapeutic standpoint. In addition, identification of novel proteins involved in systemic oxidative stress has shed some new light on the pathogenesis of vascular disease. p66(shc) is a cytoplasmic protein that is expressed in a wide range of cell types. Initially believed to be involved in signalling pathways that regulate cell growth and oxidative stress, it has now been shown to play a pivotal role in promoting endothelial dysfunction and atherosclerosis. Although a specific role in uremia-related vascular disease has not yet been shown, available data in humans suggest involvement of p66(shc) in clinical conditions associated with increased oxidative stress.

Adaptor Proteins, Signal Transducing↗

PubMed2006

MMP-9 microsatellite polymorphism and susceptibility to carotid arteries atherosclerosis.

OBJECTIVE: The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure. METHODS AND RESULTS: One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (chi2 test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries. CONCLUSIONS: The number of repeats (> or =22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

Carotid Artery Diseases↗

PubMed2006

Response of muscle protein and glutamine kinetics to branched-chain-enriched amino acids in intensive care patients after radical cancer surgery.

OBJECTIVE: Patients with cancer are characterized by decreased muscle protein synthesis and glutamine availability that contribute to an impaired immune response. These abnormalities worsen after surgical stress. We tested the hypothesis that pharmacologic doses of branched-chain amino acids would improve the early metabolic response after major cancer surgery. METHODS: By using a crossover experimental design, we compared the metabolic effects of isonitrogenous solutions of balanced and branched-chain-enriched amino acid mixtures infused at the rate of 82 mg x h(-1) x kg(-1) for 3 h in patients with colorectal or cervical cancer on the first and second days after radical surgery combined with intraoperative radiation therapy. The ratios of leucine to total amino acid (grams) in the two mixtures were 0.09 and 0.22, respectively. Muscle protein and glutamine kinetics were determined by using stable isotope of amino acids and the leg arteriovenous balance technique. Glucose and insulin were continuously infused throughout the 2-d study to maintain near euglycemia. RESULTS: Rates of muscle protein synthesis and degradation were not significantly affected by the balanced amino acid infusion. In contrast, the isonitrogenous, branched-chain-enriched amino acid mixture accelerated muscle protein turnover by stimulating (P <or= 0.05) protein synthesis. The rate of muscle glutamine de novo synthesis did not significantly change after infusion of the balanced amino acid mixture but increased (P <or= 0.05) by 263 +/- 69% during infusion of the branched-chain-enriched amino acid mixture. CONCLUSIONS: An excess of branched-chain amino acids in the presence of an optimal profile of other essential amino acids acutely increased muscle protein synthesis and glutamine flux from skeletal muscle in cancer patients after surgery.

Amino Acids, Branched-Chain↗

PubMed2006

Association of interferon-gamma +874A polymorphism with reduced long-term inflammatory response in haemodialysis patients.

BACKGROUND: We have studied the effects of interferon (IFN)-gamma allelic variations on expression levels of pro- and anti-inflammatory cytokines and on long-term inflammatory status in haemodialysis patients. METHODS: Genotyping was performed in 123 patients for single nucleotide polymorphisms in the first intron of the IFN-gamma gene (+874 T/A). They were prospectively followed for 2 years. Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR technique) and serum C-reactive protein (CRP) concentrations were compared in patient groups with different IFN-gamma genotypes. Serum CRP was evaluated every month and inflammatory state was defined as percent of abnormal values (above 5 mg/l) over total determinations. Of the total, 102 patients survived and completed 24+/-1 monthly CRP determinations. The IFN-gamma +/-874 A/A, 'low-producer' genotype was associated with decreased (P<0.05) mRNA levels of IFN-gamma and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation (37+/-6%) than the +/-874 A/T and T/T, 'intermediate and high-producer' genotypes (59+/-6%, and 60+/-5%, respectively). The mRNA levels of tumor necrosis factor-alpha, IL-10 and of transforming growth factor-beta1 were not different in the three groups of patients. Pooled analysis in deceased (10+/-3 monthly CRP determinations) and survived patients confirmed the results obtained in the patients who completed the follow-up period. CONCLUSIONS: The 'low-producer' IFN-gamma +874 A/A genotype was associated with a preventive effect on long-term CRP elevation in haemodialysis patients possibly mediated by decreased gene expression of IFN-gamma and IL-6.

Aged↗

PubMed2006

Inflammation and adipose tissue in uremia.

Enhanced chronic systemic inflammation and reduced insulin sensitivity are often associated in patients with chronic renal failure, contributing to cardiovascular morbidity and mortality in these patients. Adipose tissue produces several hormones (adipocytokines including leptin, resistin, tumor necrosis factor-alpha, and adiponectin) that modulate both systemic inflammatory response and insulin action. High leptin, resistin, and tumor necrosis factor-alpha and low adiponectin are associated with proinflammatory conditions, whereas opposite patterns are commonly observed in the presence of increased insulin sensitivity, low inflammation, and reduced cardiovascular risk. Oxidative stress has also been shown recently to modulate adipocytokine production, resulting in a proinflammatory profile. Increments of plasma concentrations of both proinflammatory and anti-inflammatory adipocytokines have been reported in chronic renal failure, possibly caused by both passive accumulation from reduced renal excretion and metabolic abnormalities induced by uremia. The potential role of altered adipose tissue adipocytokine production in the onset of renal failure-associated inflammatory and metabolic derangements remains largely to be elucidated and is discussed in the current report.

Adiponectin↗

PubMed2005

MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques.

Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.

Aged↗

PubMed2005

Dysregulation of the endothelial nitric oxide synthase-soluble guanylate cyclase pathway is normalized by insulin in the aorta of diabetic rat.

Antiatherogenic effects of nitric oxide (NO) are mediated by activation of soluble guanylate cyclase (sGC) and are impaired by diabetes in animals and humans. We investigated whether uncontrolled diabetes and insulin therapy effect expression and function of the main enzymes of the endothelial nitric oxide (eNOS)-sGC signaling pathway in vivo. Expression and function of eNOS, sGC and protein kinase G (PKG) were studied by Western blot analysis and vasorelaxation to NO-donor in thoracic aortas from control (CON) and streptozotocin (SZT)-induced diabetic rats during uncontrolled diabetes (DM) and insulin treatment (INS) for 8 weeks. Protein level of eNOS was increased (+300%, P < 0.05), while sGC (-50%) and PKG (-65%) proteins were reduced (P < 0.03) in aortas of DM. Insulin treatment normalized these defects resulting in eNOS, sGC and PKG aortic protein content comparable to control. In aortic rings, diethylamine NONOate (DEA-NONOate)-induced vasorelaxation was attenuated (P< or =0.05) in DM compared to control and returned to normal in INS. Thus, experimental diabetes decreases sGC and PKG expression and their NO-dependent activation in aorta despite overexpression of eNOS. These abnormalities are normalized by insulin treatment and improved metabolic control.

Animals↗

PubMed2005

Metabolic effects of ghrelin and its potential implications in uremia.

Ghrelin is a recently described hormone secreted by the stomach. Ghrelin administration in ad-libitum-fed rodents was shown to increase appetite as well as body weight and body fat content, showing metabolic effects of ghrelin in vivo and suggesting its involvement in the pathogenesis of obesity. However, plasma ghrelin concentration was shown to be inversely correlated with body weight and body fat in people and rodents. Increased plasma ghrelin concentration was also reported during diet-induced weight loss and in malnourished states. These findings suggest that circulating ghrelin is regulated by nutritional state and body fat with a feedback mechanism opposing changes in body composition, with a potential key adaptive role during calorie restriction. Plasma ghrelin concentration was shown to be increased in advanced renal failure and hemodialysis patients. The known metabolic effects of ghrelin and the potential implications of hyperghrelinemia in kidney disease will be discussed in this article.

Adipose Tissue↗

PubMed2005

Metabolic consequences of physical inactivity.

Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.

Amino Acids↗

PubMed2005

The impact of inflammation on metabolic regulation in chronic kidney disease: a review.

Chronically uremic patients are characterized by a low-grade systemic inflammation that reflects the consequences of an unbalanced production of proinflammatory and anti-inflammatory cytokines and contributes to the progression of atherosclerotic vascular disease and malnutrition. The causes of inflammation in end-stage kidney disease have been studied in details. Nonetheless, the degree of activation of the systemic inflammatory response shows great interindividual variability that cannot be explained by renal disease or dialysis. The amount of cytokine that is produced on a definite stimulus varies among individuals. Single nucleotide polymorphisms in the promoter or coding regions of cytokine genes lead to high or low productions of these mediators and may genetically explain this heterogeneity. The "low-producer" genotypes for the anti-inflammatory cytokine interleukin-10 are more permissive for a greater level of systemic inflammation and for increased cardiovascular morbidity and mortality in patients on hemodialysis. Potential pharmacologic and nutritional approaches for treatment of systemic inflammation have been identified in recent years. In addition, physical exercise training may reduce the systemic inflammatory response. Definition of the relationships between different cytokine gene polymorphisms and systemic inflammation in chronically uremic patients will improve efficacy of targeted anti-inflammatory treatments.

Anti-Inflammatory Agents↗

PubMed2005

MMP-9 microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration.

PURPOSE: To assess if a polymorphism (PM) of the microsatellite (CA(13-27)) in the promoter region of Matrix Metalloproteinase 9 (MMP-9) was associated with the exudative form of age-related macular degeneration (AMD) and to its risk factors. METHODS: In 107 patients with AMD (AMD Group) and 223 age- and gender-matched controls (Control Group) with cataract, demographic, clinical data, and MMP-9 PM have been compared. RESULTS: The comparison of allelic frequencies showed a different pattern of CA repeats between AMD and Control Group (P < 0.00005), in particular the prevalence of longer microsatellites (> or = 22 CA repeats) was higher in AMD than in Control Group (O.R. 2.49, 95% CI 1.71-3.37, P < 0.001). Analyses of genetic frequencies gave similar results. Logistic regression confirmed that 22 or more CA repeats are associated to AMD. The only association between MMP-9 PM and other risk factors for AMD was with BMI (Spearman's R = 0.298, P < 0.00005): all patients with both microsatellites > or = 22 CA repeats were overweight or obese (chi2 test P < 0.0005, compared to other genotypes). CONCLUSIONS: Longer microsatellites in the promoter of MMP-9 are associated to the exudative form of AMD and to body mass index, a well-known risk factor for the disease.

Aged↗

PubMed2004

Moderate caloric restriction, but not physiological hyperleptinemia per se, enhances mitochondrial oxidative capacity in rat liver and skeletal muscle--tissue-specific impact on tissue triglyceride content and AKT activation.

The study aimed at determining, in lean tissues from nonobese rats, whether physiological hyperleptinemia with leptin-induced reduced caloric intake and/or calorie restriction (CR) per se: 1) enhance mitochondrial-energy metabolism gene transcript levels and oxidative capacity; and 2) reduce triglyceride content. Liver and skeletal muscles were collected from 6-month-old Fischer 344 rats after 1-wk leptin sc infusion (0.4 mg/kg . d: leptin + approximately 3-fold leptinemia vs. ad libitum-fed control) or moderate CR (-26% of those fed ad libitum) in pair-fed animals (CR). After 1 wk: 1) leptin and CR comparably enhanced transcriptional expression of mixed muscle mitochondrial genes (P < 0.05 vs. control); 2) CR independently increased (P < 0.05 vs. leptin-control) hepatic mitochondrial-lipooxidative gene expression and oxidative capacity; 3) hepatic but not muscle mitochondrial effects of CR were associated (P < 0.01) with increased activated insulin signaling at AKT level (P < 0.05 vs. leptin-control); 4) liver and muscle triglyceride content were comparable in all groups. In additional experiments, assessing time course of posttranscriptional CR effects, 3-wk superimposable CR (P < 0.05): 1) increased both liver and muscle mitochondrial oxidative capacity; and 2) selectively reduced muscle triglyceride content. Thus, in nonobese adult rat: 1) moderate CR induces early increments of mitochondrial-lipooxidative gene expression and time-dependent increments of oxidative capacity in liver and mixed muscle; 2) sustained moderate CR alters tissue lipid distribution reducing muscle but not liver triglycerides; 3) mitochondrial-lipid metabolism changes are tissue-specifically associated with hepatic AKT activation; 4) short-term physiological hyperleptinemia has no independent stimulatory effects on muscle and liver mitochondrial-lipooxidative gene expression. Increased lean tissue oxidative capacity could favor substrate oxidation over storage during reduced nutrient availability.

Animals↗

PubMed2004

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle.

Ghrelin is a gastric hormone increased during caloric restriction and fat depletion. A role of ghrelin in the regulation of lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous ghrelin administration in rodents. We investigated the potential effects of peripheral ghrelin administration (two times daily 200-micrograms [DOSAGE ERROR CORRECTED] sc injection for 4 days) on triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle, ghrelin increased body weight but not food intake and circulating insulin. In liver, ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased triglyceride content while reducing activated (phosphorylated) stimulator of fatty acid oxidation, AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative enzyme activities. In contrast, triglyceride content was reduced (P < 0.05) after ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle, ghrelin increased (P < 0.05) mitochondrial oxidative enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of peroxisome proliferator-activated receptor-gamma, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities (P < 0.05). Thus ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors triglyceride deposition in liver over skeletal muscle. These novel effects of ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to caloric restriction and loss of body fat.

Adenylate Kinase↗

PubMed2004

Short-term bed rest impairs amino acid-induced protein anabolism in humans.

Diminished muscular activity is associated with alterations of protein metabolism. The aim of this study was to evaluate the effect of short-term muscle inactivity on regulation of whole-body protein deposition during amino acid infusion to simulate an experimental postprandial state. We studied nine healthy young volunteers at the end of 14 day periods of strict bed rest and of controlled ambulation using a cross-over design. Subjects received a weight-maintaining diet containing 1 g protein kg(-1) day(-1). l[1-(13)C]leucine was used as a marker of whole-body protein kinetics in the postabsorptive state and during a 3 h infusion of an amino acid mixture (0.13 g amino acid (kg lean body mass)(-1) h(-1)). In the postabsorptive state, bed rest decreased (P < 0.05) the rate of leucine disposal (R(d)) to protein synthesis and tended to decrease leucine rate of appearance (R(a)) from proteolysis, whereas the rate of leucine oxidation did not change significantly. Amino acid infusion increased leucine R(d) to protein synthesis and oxidation and decreased leucine R(a) from proteolysis in both the bed rest and ambulatory conditions. Changes from basal in leucine R(d) to protein synthesis were lower (P < 0.05) during bed rest than those in the ambulatory period, whereas changes in leucine R(a) from proteolysis and oxidation were not significantly different. During amino acid infusion, net leucine deposition into body protein was 8 +/- 3% lower during bed rest than during the ambulatory phase. In conclusion, short-term bed rest leads to reduced stimulation of whole-body protein synthesis by amino acid administration. Results of this study were, in part, presented at the meeting, Experimental Biology, 2004, Washington DC.

Adult↗

PubMed2004

Lack of direct effect of moderate hyperleptinemia to improve endothelial function in lean rat aorta: role of calorie restriction.

Leptin stimulates vascular sympathetic activity and NO release. The resulting effect of hyperleptinemia on endothelial function is unknown. Reduction of food intake associated with hyperleptinemia may mediate some of the vascular effects of leptin. This study was designed to assess the relative effects of short-term moderate caloric restriction and hyperleptinemia on vascular function in lean rat. Endothelium-dependent and -independent vasorelaxation, nitric oxide synthase (eNOS) expression and nitrite production were measured in lean rats receiving leptin subcutaneous infusion (-26% caloric intake, -4% body weight versus control) or moderate caloric restriction (pair-feeding) for one week. Plasma leptin was increased (P < = 0.05) by approximately 300% in the leptin-infused group, while it decreased (P < or = 0.05) by approximately 40% in calorie-restricted animals. Both leptin infusion and calorie restriction resulted in improved (P < 0.05) endothelium-dependent vasorelaxation to acetylcholine (EC50: -6.1 +/- 0.2 and -6.2 +/- 0.2 versus -5.4 +/- 0.2 in control) and unaltered endothelium-independent vasodilation to DEA-NONOate. Furthermore, in aortas from leptin-infused and calorie-restricted rats, expression of eNOS and nitrite production were increased (P < = 0.05) to similar extent compared to control animals. These findings suggest that moderate short-term calorie restriction with adaptive hypoleptinemia has independent beneficial effects on endothelial function in lean animals by enhancing eNOS expression and function. In addition, physiological hyperleptinemia does not independently contribute to improved vascular function above and beyond the effect of calorie restriction.

Animals↗

PubMed2004

Myostatin expression is not altered by insulin deficiency and replacement in streptozotocin-diabetic rat skeletal muscles.

BACKGROUND AND AIMS: Insulin is a major post-prandial muscle-anabolic hormone. A substantial loss of skeletal muscle mass occurs in insulin-deprived diabetes and is reversed by insulin treatment. Myostatin is a negative regulator of muscle mass upregulated in several chronic catabolic conditions. Whether myostatin expression is altered in insulin-deprived diabetes is unknown. In spite of opposite effects on muscle mass the potential role of basal circulating insulin in the regulation of myostatin expression is also undetermined. METHODS: We measured (Northern Blot) myostatin transcript levels in muscle groups with different fiber composition in streptozotocin-diabetic male rats receiving one of the following treatments for eight weeks: (1) control (C); (2) diabetes without treatment (DM); (3) diabetes with once-daily slow-acting insulin treatment (INS). RESULTS: INS normalized plasma insulin and prevented weight reduction observed in DM. In fast-twitch gastrocnemius muscle myostatin transcript levels were unchanged (P>0.4) in both DM and INS compared to C. Myostatin transcripts were not measurable in any group in slow-twitch soleus muscle. CONCLUSIONS: Muscle-specific myostatin expression is not increased under catabolic conditions in insulin-deprived diabetes. Insulin treatment also does not change myostatin transcript levels. The data provide the first assessment of potential interplay between insulin and myostatin and they do not support a major role of circulating insulin in the in vivo regulation of myostatin gene expression. A role of myostatin in muscle catabolism in chronic insulin-deprived diabetes is also not indicated by the current results.

Animals↗

PubMed2004

MMP-9 microsatellite polymorphism and multiple sclerosis.

A polymorphism (PM) in the microsatellite of the promoter region of matrix metalloproteinase 9 (MMP-9), modulating its expression, could play a role in susceptibility to multiple sclerosis (MS). MMP-9 PM was determined in 95 patients with MS (MS Group) and 95 age- and sex-matched controls (Control Group). Comparison of allelic frequencies showed that a higher number of CA repeats characterized the MS group (P<0.0001) and prevalence of carriers of > or =22 CA repeats was higher in the MS than in the Control Group (OR 3.4, 95% CI: 1.7-6.8, P<0.0001). An earlier age at disease onset was a characteristic of patients with >22 CA repeats (33+/-10 vs. 28+/-10, P=0.027). No differences were found in the main MRI parameters.

Adolescent↗