PubMed Health⌕ Search

Biomedical subjects

Gianfranco Guarnieri

Publications and source records attributed to Gianfranco Guarnieri.

26 records · Page 2Linked to original sources
PubMed2004

Chronic systemic inflammation in uremia: potential therapeutic approaches.

Systemic inflammation characterizes several chronic diseases including uremia. Inflammation may contribute to morbidity and mortality by enhancing protein-calorie malnutrition, infectious complications, and atherosclerosis and cardiovascular disease. Although inflammation in renal disease can be caused, at least in part, by reduced renal clearance of proinflammatory mediators (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6), several pathogenetic mechanisms are likely to contribute to direct activation of the inflammatory process under these conditions. These mechanisms include accumulation of advance glycoxidation end products, production of reactive oxygen species and oxidative damage, and chronic infection. Support for direct activation of systemic inflammation provides a strong rationale for use of anti-inflammatory treatments in uremia. The current article describes the association between uremia and inflammation, provides evidence for activation of inflammatory process, and provides potential therapeutic approaches.

Chronic Disease↗
PubMed2003

Hyperleptinemia prevents increased plasma ghrelin concentration during short-term moderate caloric restriction in rats.

BACKGROUND & AIMS: Ghrelin is an orexigenic hormone secreted by the stomach. Increased plasma ghrelin concentration was reported during diet-induced weight loss in obese humans, suggesting that ghrelin contributes to adaptive increment in appetite associated with caloric restriction. Leptin reduces spontaneous food intake and body weight in rodents. The current study tested the hypothesis that increased plasma leptin prevents the potential increase in plasma ghrelin concentration during moderate caloric restriction in lean rats. METHODS: Six-month-old male rats (body weight, 367 +/- 9 grams) were randomly assigned to one of the following treatments (8 rats each) for 1 week: (1) leptin subcutaneous infusion to induce moderate hyperleptinemia and moderate caloric restriction (-26% of ad libitum), (2) vehicle infusion and pair feeding, and (3) vehicle infusion and ad libitum feeding. RESULTS: Leptin-treated (-19 +/- 5 grams) and pair-fed (-19 +/- 2) rats lost weight compared with ad libitum-fed rats (-3 +/- 1, P < 0.05). Compared with control (6.8 +/- 0.7 ng/mL), plasma leptin was higher in leptin-treated (18.6 +/- 0.9 ng/mL, P < 0.01) rats and lower in pair-fed rats (4.3 +/- 0.4 ng/mL, P < 0.05). Plasma ghrelin was substantially higher in calorie-restricted than control rats (2505 +/- 132 pg/mL vs. 1790 +/- 134 pg/mL, P < 0.01), and leptin treatment (1625 +/- 117 pg/mL) completely prevented this change. Plasma ghrelin concentration was negatively correlated with body weight changes in calorie-restricted and control (r = -0.75, P < 0.01) but not in leptin-treated rats (P > 0.8). CONCLUSIONS: Moderate hyperleptinemia prevents an increase of plasma ghrelin during moderate short-term caloric restriction. Satiety-inducing effects of leptin include suppression of gastric orexigenic signals and disruption of a potential feedback mechanism between body weight changes and plasma ghrelin in lean adult rats.

Animals↗
PubMed2003

Mechanisms of malnutrition in uremia.

Loss of lean body mass is common in chronic renal failure and may adversely affect morbidity and mortality of patients. The pathogenesis of protein wasting in chronic renal failure is multifactorial and is reviewed by the authors. When protein kinetics are determined in patients with uncomplicated uremic on conservative treatment by isotopically labeled amino acids, the results indicate that the rates of both protein synthesis and degradation are decreased both at whole body and skeletal muscle levels. On the other hand, if a complication is superimposed (ie, acidosis or infection), protein turnover accelerates, primarily because of proteolysis increase. Therapeutical implications are analyzed in this article. Recently, a cytokine-induced chronic inflammatory response has been proposed to explain the progressive protein loss often observed in these patients even in the absence of complications. Cytokine concentrations often have been found to be increased in both dialyzed and undialyzed chronically uremic patients. Tumor necrosis factor (TNF)-alpha clearance is reduced in uremia because this cytokine is catabolized and excreted mainly by the kidneys. In addition, we found that gene expression for TNF-alpha in circulating blood cells is enhanced in chronically uremic patients, suggesting that an activation of the systemic inflammatory response may contribute to the metabolic, vascular, and immune complications of this disease.

Cytokines↗
PubMed2003

Mechanisms of altered protein turnover in chronic diseases: a review of human kinetic studies.

PURPOSE OF REVIEW: Changes in hormone secretion, tissue perfusion, oxygen availability, energy-protein intake, free amino acid pattern, hydration state, acid-base balance as well as activation of the systemic inflammatory response may affect protein synthesis and degradation. The overall purpose of this review is to describe how these factors may interact to change protein turnover in the different directions seen in kinetic studies in humans. RECENT FINDINGS: Evidence indicates that, in vivo, changes of protein synthesis and degradation are strictly related. When protein synthesis is primarily suppressed, protein degradation is found to be unchanged or even slightly decreased. When protein degradation is primarily accelerated, the rate of synthesis is unchanged or even increased. Chronic disease states can, therefore, be characterized either by decreased or accelerated protein turnover. Apparent discrepancies among various studies in chronic uraemia, liver cirrhosis, chronic obstructive pulmonary disease and cancer may stem from the fact that the pathogenesis of protein metabolism abnormalities is multifactorial. When the effects of inflammatory mediators and stress hormones start overwhelming factors that tend to decrease protein synthesis and turnover (decreased protein-energy intake, physical activity, tissue oxygen delivery, leucine levels, etc.), the rate of protein degradation and turnover may increase. SUMMARY: Low-protein turnover conditions are usually associated with the adequate sparing of body proteins, whereas in high-protein turnover conditions protein loss may proceed at a faster rate. Nonetheless, impaired recovery from acute complications and the reduced renewal of damaged and toxic proteins are potential undesired consequences of low-protein turnover.

Chronic Disease↗
PubMed2002

Interleukin-1 receptor antagonist: a sensitive marker of instability in patients with coronary artery disease.

BACKGROUND: Increased plasma levels of acute phase reactants are correlated with acute coronary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) modulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively investigated whether detection of increased levels of IL-1Ra in patients may be useful in the characterization of coronary syndromes. METHODS: Plasma levels of IL-1Ra were measured in 118 consecutive patients undergoing coronary angiography with a clinical diagnosis of recent unstable angina (N = 57), chronic stable angina (N = 49) or atypical chest pain (N = 12). RESULTS: Angiography showed significant coronary disease in the first two groups and was normal in the latter group. Patients with unstable angina had significantly higher levels of IL-1Ra than stable patients [158 (110-224) vs 108 (95-154) pg/ml, P = 0.002] and individuals with chest pain and normal coronary angiogram [110 (97-123) pg/ml, P: = 0.038]. In contrast, while C-reactive protein levels were significantly higher in patients with stable and unstable angina vs those without coronary disease (0.29 vs 0.06 mg/dl, P: = 0.022), they did not discriminate between stable and unstable angina patients (0.22 vs 0.32 mg/dl, P: = 0.66). CONCLUSIONS: These results indicate that IL-1Ra may be a sensitive marker of clinical instability in patients with coronary artery disease.

Aged↗
PubMed2002

Pentoxifylline acutely reduces protein catabolism in chronically uremic patients.

BACKGROUND: We investigated the ability of pentoxifylline, a drug with hemorheological actions known to block tumor necrosis factor-alpha (TNF-alpha) release, to modulate whole-body protein kinetics in undialyzed patients with chronic uremia. METHODS: Leucine rate of appearance (Ra) from proteolysis and leucine oxidation, a marker of net protein loss, were determined by infusing l-[1-13C]leucine and using the reciprocal pool model for calculations. RESULTS: Intravenous infusion of pentoxifylline in the postabsorptive state (1 mg/kg within 3 hours) decreased the intracellular leucine Ra from proteolysis by -16% +/- 4% versus -3% +/- 2% of saline (P = 0.02) and leucine oxidation by -16% +/- 4% versus +4% +/- 2% of saline (P = 0.003). Combined infusions of pentoxifylline and a balanced amino acid mixture (0.2 mg/kg/min) decreased whole-body proteolysis by -53% +/- 7% versus -26% +/- 6% of amino acid infusion alone (P = 0.02). Circulating levels of TNF-alpha and TNF-alpha soluble receptors (sTNF-Rs) were elevated (P < 0.001) in patients compared with healthy controls. Pentoxifylline infusion did not significantly affect TNF-alpha levels, but decreased sTNF-Rs both in the postabsorptive state and during hyperaminoacidemia. CONCLUSION: Pentoxifylline acutely decreased whole-body proteolysis in chronically uremic patients. Potential explanations for these pharmacological effects may include downregulation of the TNF-alpha system or other mechanisms related to the rheological action of the drug (eg, increased amino acid or insulin delivery to target cells).

Amino Acids↗
PubMed2002

Sensitivity of whole body protein synthesis to amino acid administration during short-term bed rest.

We tested the hypothesis that a reduced stimulation of whole-body protein synthesis by amino acid administration represents a major mechanism for the bed rest-induced loss of lean body mass. Healthy young subjects and matched controls were studied on the last day of a 14-day bed rest or ambulatory period, as part of the overall protocol "Short-term Bed Rest - Integrated Physiology" set up by the German Aerospace Centre (DLR) in co-operation with the European Space Agency. A balanced mixture of essential and non-essential amino acids was intravenously infused in the postabsorptive state for 3 hours at the rate of 0.1 g/kg/hour. The oxidative and non-oxidative (i.e., to protein synthesis) disposal of the infused leucine was determined by stable isotope and mass spectrometry techniques. The clearance of total infused amino acids tended to be greater (P=0.07) in the ambulatory group than in the bed rest group. When leucine clearance was partitioned between its oxidative and non-oxidative (i.e., to protein synthesis) components, the results indicated that the oxidative disposal was not statistically different in the bed rest and in the ambulatory groups. In contrast, the non-oxidative leucine disposal (i.e., to protein synthesis) was about 20% greater (P<0.01) in the ambulatory group than in the bed rest group. In conclusion, these preliminary data suggest that 14-day bed rest impairs the ability to utilise exogenous amino acids for protein synthesis.

Journal Article↗