Cardiac indexes, cardiac damage biomarkers and energy expenditure in professional cyclists during the Giro d'Italia 3-weeks stage race.

INTRODUCTION: The study of cardiac response to strenuous and continuous exercise is crucial to understanding the physiology of endurance. N-terminal proB-type natriuretic peptide (NT-proBNP) is a potential marker for monitoring myocardial wall stress, and troponins (TnT and TnI) are widely used in the diagnosis of cardiac ischemia and infarction. Strenuous exercise may generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, inducing the increased production of both these biomarkers. We measured changes in NT-proBNP and TnT in elite cyclists during a 3-week stage race, a model of strenuous exercise. MATERIALS AND METHODS: The study population was 9 professional cyclists participating in the 2011 Giro d'Italia. Pre-analytical and analytical phases scrupulously followed official recommendations. Anthropometric data, net energy expenditure and cardiac indexes (rate, diastolic and systolic blood pressure) were recorded. Blood samples were drawn pre-race (day - 1) and at days 12 and 22; NT-proBNP and highly sensitive-troponin (Hs-TnT) concentrations were assayed and corrected for plasma volume changes. RESULTS: Body-mass index decreased and energy expenditure increased by 52% during the race. NT-proBNP concentrations increased [day -1:23.52 ng/L (9.67-34.33); day 12:63.46 ng/L (22.15-93.31); P = 0.039; day 22:89.26 ng/L (34.66-129.78) vs.day -1; P < 0.001] and correlated with heart rate (r = -0.51; P = 0.006), systolic pressure (r = 0.39; P = 0.046) and energy expenditure (r = 0.70; P < 0.001). TnT concentrations did not vary, but a widened TnT amplitude distribution was observed. CONCLUSIONS: Increases in NT-proBNP correlated with higher energy expenditure over a 3-week cycling stage race, possibly indicating myocardial stress.

The role of inflammation in patients with intraductal mucinous neoplasm of the pancreas and in those with pancreatic adenocarcinoma.

BACKGROUND: There are very few data regarding inflammation in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. AIM: To evaluate the circulating concentrations of placental growth factor (PlGF), transforming growth factor-alpha (TGF-α), transforming growth factor-beta1 (TGF-ß1), tumour necrosis factor receptor 1 (TNF-R1) and matrix metalloproteinase-2 (MMP-2) in patients with IPMNs and in those with pancreatic adenocarcinomas. PATIENTS AND METHODS: Sixty-nine patients were enrolled: 23 (33.3%) had IPMNs and 46 (66.7%) had histologically confirmed pancreatic adenocarcinomas. Thirteen healthy subjects were also studied. PlGF, TGF-α, TGF-ß1, TNF-R1 and MMP-2 were determined using commercially available kits. RESULTS: TNF-R1 (p=0.003) was the only protein significantly different among the three groups. CONCLUSION: Serum TNF-R1 was elevated in patients with IPMNs and in those with pancreatic adenocarcinomas, suggesting a high apoptotic activity in both groups of patients studied.

NT-proBNP concentrations in mountain marathoners.

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

Serum leptin, but not adiponectin and receptor for advanced glycation end products, is able to distinguish autoimmune pancreatitis from both chronic pancreatitis and pancreatic neoplasms.

OBJECTIVE: Serum leptin and adiponectin determinations have been proposed as markers for distinguishing pancreatic cancer and chronic pancreatitis from autoimmune pancreatitis; however, no studies exist in patients with autoimmune pancreatitis and in those with intraductal papillary mucinous tumors of the pancreas. The aim of this paper was to evaluate the circulating concentrations of receptor for advanced glycation end products (RAGE), leptin and adiponectin in patients with chronic pancreatic diseases. MATERIAL AND METHODS: Seventy-five consecutive patients with chronic pancreatic diseases (47 males, 28 females; mean age 67.0 +/- 13.2 years; range 37-97 years) were studied: six (8.0%) had autoimmune pancreatitis, 23 (30.7%) had chronic pancreatitis, 34 (45.3%) had pancreatic cancer and the remaining 12 (16.0%) had intraductal papillary mutinous tumors of the pancreas. Leptin, adiponectin and RAGE were determined in serum using commercially available kits. The leptin concentrations were normalized to the lower and upper reference limits because of the different gender reference ranges. RESULTS: Normalized leptin concentrations were significantly lower in chronic pancreatitis patients (0.53 +/- 1.28; p = 0.008) and in those with pancreatic cancer (0.12 +/- 0.33; p < 0.001) compared to the overall population (0.58 +/- 1.23), whereas autoimmune pancreatitis patients had significantly higher concentrations of this protein (2.18 +/- 2.56; p = 0.004) compared to the overall population. RAGE and adiponectin concentrations were similar among the four groups of patients studied. Among the clinical variables considered, only pain was significantly related to leptin concentrations (patients with pain 0.18 +/- 0.54, patients without pain 1.07 +/- 1.64; p = 0.001). CONCLUSION: Serum leptin seems to be a good serum marker for differentiating autoimmune pancreatitis patients from those with chronic pancreatitis and pancreatic cancer.

Evaluation of microalbuminuria in patients with erectile dysfunction.

INTRODUCTION: The recent sophisticated diagnostic procedures aimed at identifying the exact cause of erectile dysfunction (ED) are often complicated in clinical application, invasive, or highly expensive. Microalbuminuria, a test easy to perform and of low cost, is a marker of extensive endothelial dysfunction, and it has been suggested to be linked to ED. AIM: The aim of this study was to investigate the eventual role of microalbuminuria in differentiating patients with arteriogenic and non arteriogenic ED. METHODS: The diagnosis of ED was based on the International Index of Erectile Function 5-questionnaire, and patients were classified as arteriogenic (N = 29) and non-arteriogenic (N = 49) in relation to the results of echo-color-doppler examination of cavernosal arteries in basal conditions and after intracavernous injection of 10 microg prostaglandin E(1). MAIN OUTCOME MEASURES: The microalbuminuria of 78 males without the most common atheriosclerotic risks and with ED was measured. RESULTS: Microalbuminuria, defined as urinary albumin/creatinine ratio, was not significantly (P > 0.05) different between patients of the two groups. CONCLUSIONS: Our data show that in ED patients the cavernosal arteries damage, as assessed by dynamic echo-color-doppler, may be independent on or precede extensive endothelial dysfunction, and that microalbuminuria cannot be predictive of penile arteriogenic etiology.

Prognostic role of clinical and laboratory criteria to identify early ventilator-associated pneumonia in brain injury.

BACKGROUND: We investigated the role of the clinical pulmonary infection score (CPIS), serum levels of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in the detection of patients with early ventilator-associated pneumonia (VAP). METHODS: Observational study in a university hospital. In 58 patients with severe brain injury receiving mechanical ventilation, CPIS, PCT, CRP and SAA were evaluated at ICU entry and at days 3 to 4 of hospital stay for VAP diagnosis (confirmed by endotracheal aspirate or BAL cultures). RESULTS: We found the following: (1) PCT at entry was increased in patients who later had early VAP develop (25 patients) compared to no VAP (median, 1.4 ng/mL; 25-75 percentiles, 0.14-0.78; vs median, 0.2 ng/mL; 25-75 percentiles, 0.76-2.4, p<0.001; sensitivity, 76%; and specificity, 75%); (2) CPIS increased at the day of VAP diagnosis, compared to entry (median, 6.6+/-1.1 vs 1.5+/-1.1, p<0.001; sensitivity, 97%; specificity, 100%), while other serum inflammatory markers did not change; and (3) deterioration in oxygenation and changes in tracheal secretions were the main determinants of CPIS changes. CONCLUSIONS: PCT may be a useful marker to predict which patients subsequently have early VAP. The CPIS could help as an early way to detect the patients with early VAP and who need further diagnostic testing.

Genetic control of chemokines in severe human internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis. METHODS: Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5Delta32, CCR2 V64I, and SDF-1-801A polymorphisms. RESULTS: The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25-2.60; p=0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p=0.015). No significant differences were observed with the other polymorphisms. CONCLUSION: The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.

Fecal calprotectin and elastase 1 determinations in patients with pancreatic diseases: a possible link between pancreatic insufficiency and intestinal inflammation.

BACKGROUND: Fecal calprotectin determination has been demonstrated to be useful in diagnosing various inflammatory diseases of the gastrointestinal tract; however, data available for patients with pancreatic diseases are scarce. Our aim was to assess fecal calprotectin in order to evaluate the presence of intestinal inflammation in patients with pancreatic disease. METHODS: Eligible patients with suspected pancreatic illness were enrolled, and in all of them fecal calprotectin and elastase-1, as well as serum amylase and lipase activities, were assayed using commercially available kits. RESULTS: A total of 90 subjects (47 men, 43 women, mean age 58.6 +/- 14.9 years) were enrolled: 20 (22.2%) had chronic pancreatitis; 15 (16.7%) had pancreatic cancer; six (6.7%) had chronic nonpathological pancreatic hyperenzymemia; 16 (17.8%) had nonpancreatic diseases; and 23 (25.6%) had no detectable diseases. Diarrhea was present in 19 patients (21.1%). In univariate analyses, the presence of diarrhea and low fecal elastase-1 concentrations were significantly associated (P = 0.019 and P = 0.002, respectively) with abnormally high fecal calprotectin concentration, and the multivariate analysis demonstrated that low fecal elastase-1 concentration was the only variable independently associated with a high fecal calprotectin concentration. CONCLUSIONS: Pancreatic insufficiency may cause intestinal inflammation, probably because of a modification of the intestinal ecology.

Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL.

N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01). The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of 20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months. The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival. Patients in whom chemotherapy fails to induce such a decrease are at risk of early death. Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography.

Comparison of three strategies for myocardial protection during coronary artery bypass graft surgery based on markers of cardiac damage.

OBJECTIVES: To evaluate myocardial damage during coronary artery bypass grafting using three different intermittent cardioplegia and then measuring cTnI and CKMBm release. DESIGN AND METHODS: Forty-two patients belonging to the hypothermic crystalloid (n = 16), hypothermic (n = 13), and normothermic blood (n = 13) groups were collected when removing the aortic cross-clamp (t = 0) and after 4, 12, 24 and 48 h. For each patient, cumulative cTnI and CKMBm release was calculated as the five measurement mean. There were no significant preoperative and operative differences in the three groups. RESULTS: In the normothermic group, cTnI mean values at 4, 12, and 24 h were significantly lower than those in both hypothermic groups; moreover, CKMBm mean values were higher at 4, 12, and 24 h in the hypothermic crystalloid group and at 4 and 12 h in the hypothermic blood group than in the normothermic group. In the normothermic group, the area under the curve of the release of both markers was significantly lower than in the hypothermic groups. No significant difference was reported in the release of both markers in hypothermic groups. CONCLUSIONS: A strategy of normothermic cardioplegia seems to preserve myocardium better than hypothermic cardioplegia.

Does gabexate mesilate affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination?

BACKGROUND/AIMS: To explore the possibility that the preventive effect of gabexate mesilate on endoscopic retrograde cholangiopancreatography-related acute pancreatitis may be mediated by its modulation of acute phase proteins. METHODOLOGY: Thirty consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomly assigned to receive 1g of gabexate mesilate (13 patients) or a placebo (17 patients) by continuous i.v. infusion starting 30 minutes before the endoscopy session and continuing for 12 hours afterward. In all patients, C-reactive protein, serum amyloid A and interleukin 6 serum concentrations were determined before endoscopy and 4, 8, 12 and 24 hours afterward. RESULTS: Interleukin 6 basal serum concentrations were not statistically different between patients who had been treated with gabexate mesilate and those who had received the placebo (P = 0.279), whereas C-reactive protein (P = 0.033) and serum amyloid A (P = 0.022) basal values were significantly lower in the gabexate mesilate group than in the placebo group. Compared to basal values, serum interleukin 6 concentrations significantly increased at 4 (P = 0.048) and at 8 (P = 0.025) hours; the increase of serum interleukin 6 concentrations was not significant at 12 (P = 0.092), but became significant at 24 (P = 0.025) hours. C-reactive protein and serum amyloid A serum concentrations increased significantly only at 12 (P = 0.001, P = 0.012, respectively) and 24 (P < 0.001, P = 0.013, respectively) hours. The modifications of serum concentrations of interleukin 6, C-reactive protein and serum amyloid A were not significantly different between the gabexate mesilate and the placebo groups. CONCLUSIONS: Gabexate mesilate does not affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination and it is able to prevent acute pancreatitis related to endoscopic retrograde cholangiopancreatography via a different mechanism than that explored in this study.

Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.

Glucose accelerates copper- and ceruloplasmin-induced oxidation of low-density lipoprotein and whole serum.

Glucose at pathophysiological concentrations was able to accelerate copper-induced oxidation of isolated low-density lipoprotein (LDL) and whole serum. The efficiency of glucose was favored under the following circumstances: (a) when LDL oxidation was induced by low copper concentration, (b) when LDL was partly oxidized, i.e. enriched with lipid peroxides. The glucose derivative methyl-alpha-D-glucoside was ineffective on Cu2+-induced LDL oxidation, pointing out the essential role of the reactivity of the aldehydic carbon for the pro-oxidative effect. When LDL oxidation was induced by a peroxyl radical generator, as a model of transition metal independent oxidation, glucose was ineffective. Glucose was found to stimulate oxidation of LDL induced by ceruloplasmin, the major copper-containing protein of human plasma. Thus, glucose accelerated oxidation of LDL induced by both free and protein bound copper. Considering the requirement for catalytically active copper and for the aldehydic carbon, the pro-oxidative effect of glucose is likely to depend on the increased availability of Cu+; this is more efficient in decomposing lipid peroxide than Cu2+, accounting for acceleration of LDL oxidation. The possible biological relevance of our work is supported by the finding that glucose was able to accelerate oxidation of whole serum, which was assessed by monitoring low-level chemiluminescence associated with lipid peroxidation.

Circadian temporal organization of lipidic fractions in elderly people. Entrainment to the dietary schedule.

BACKGROUND AND AIMS: Changes in some rhythmometric parameters have been reported in the elderly as a consequence of both structural and neurochemical changes occurring in the central nervous system. Since alterations of lipid and lipoprotein metabolism are directly involved in several age-related disorders, the aim of this study was to investigate the circadian temporal organization of some important lipidic fractions (total cholesterol, triacylglycerol, apolipoprotein A1 and B) in physiological aging. METHODS: Thirty old hospitalized subjects were synchronized for daily activities, sleeping/waking habits, and time/quality of meals. Twenty-four healthy young individuals served as controls. After an overnight fast, samples were taken beginning at 08:00 every 4 hours until 20:00, and every 2 hours from 20:00 to 04:00. Rhythmometric data were analyzed by single and population mean Cosinor analysis, and by ANOVA; the comparison of the rhythm's parameters between elderly and young subjects was carried out by the Mesor test and the amplitude-acrophase using Hotelling's test. RESULTS: Elderly subjects exhibited statistically significant circadian rhythms for total cholesterol (p<0.00002), triacylglycerol (p<0.000001), apo A-1 (p<0.0013), and apo B (p