C → N and N → C solution phase peptide synthesis using the N-acyl 4-nitrobenzenesulfonamide as protection of the carboxylic function.

In this paper we describe a solution phase peptide synthesis strategy using the 4-nitrobenzenesulfonamido/N-methyl-4-nitrobenzenesulfonamido group as a protecting/activating system of the carboxyl function. The 4-nitrobenzenesulfonamido group is stable during peptide chain elongation (Fmoc chemistry). The N-aminoacyl or N-dipeptidyl-4-nitrobenzensulfonamides, when activated by methylation, can be easily coupled with another amino acid or reconverted into the free-carboxyl function amino acids or peptides. This activatable protecting group allows both the C → N and the N → C direction solution phase peptide synthesis. We also verified that the absolute configuration at the chiral centers does not change during the coupling reactions.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

AIMS: To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. METHODS: Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. RESULTS: At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). CONCLUSIONS: Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available. OBJECTIVE: Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women. DESIGN AND SETTING: A prospective baseline-randomized clinical study was conducted at the University "Federico II" of Naples, School of Medicine (Italy). PATIENTS: Ninety young overweight PCOS women were enrolled. MEAN OUTCOME MEASURES: Ninety young PCOS women were randomly subdivided into two groups, each composed of 45 subjects. The PCOS-T (trained) group underwent a 3-month structured ET program, whereas the PCOS-UnT (untrained) group did not. Hormonal and metabolic profiles and cardiopulmonary and exercise parameters were evaluated. RESULTS: After 3-month ET, PCOS-T showed a significant improvement in peak oxygen consumption (+35.4%; P<0.001) and in maximal workload (+37.2%; P<0.001). In PCOS-T we also observed a significant reduction in body mass index (-4.5%; P<0.001) and in C-reactive protein (-10%; P<0.001), and a significant (P<0.001) improvement in insulin sensitivity indexes. After 3 months, no changes were observed in PCOS-UnT. CONCLUSIONS: A 3-month structured ET program improves cardiopulmonary functional capacity in young PCOS women.

Efficacy of telecardiology in improving the results of cardiac rehabilitation after acute myocardial infarction.

BACKGROUND: This study was addressed to verify if Telecardiology (TC) improves the results of Cardiac Rehabilitation in patients following a home-based Cardiac Rehabilitation Program (CRP) after acute myocardial infarction (AMI). MATERIALS AND METHODS: We studied three groups of patients after AMI: Group A (control group): 15 patients, who followed a standard in-hospital CRP of 3 weekly sessions of 2 months duration; Group B (study group): 15 patients, who were enrolled in a home-based CRP of similar duration and were monitored by TC with the aid of an ecg-device (Sorin Life Watch CG 6106); Group C (second control group): 15 patients, who followed a home-based CRP without ecg-monitoring by TC. All patients performed a symptom-limited exercise testing at the beginning of the CRP. Psychometric data (STAI-Y1, STAI-Y2, BDI) were also evaluated. At the end of the CRP all patients underwent repeated exercise testing and psychometric evaluation. RESULTS: TC applied to the home-based CRP was associated with a good compliance to the program. Compared to Group C, in Group B we observed an increase of maximal heart rate, exercise duration, maximal work-load, and an improvement of anxiety, a trend to reduction of depression, and an improvement of quality of life. These results were very similar to Group A patients following a hospital-based CRP. CONCLUSIONS: TC improves compliance, functional capacity and psychological profile of patients undergoing a home-based CRP, compared to patients enrolled in a home-based CRP without ecg-monitoring by Telecardiology.

[Polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women]. / La sindrome dell'ovaio policistico: un esempio di complicanza cardiovascolare correlata all'obesità che colpisce giovani donne.

Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.

Favourable effects of exercise training on N-terminal pro-brain natriuretic peptide plasma levels in elderly patients after acute myocardial infarction.

BACKGROUND: regional or global impairment of left ventricular (LV) systolic or diastolic function leading to increased LV wall stress results in increased circulating levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP). OBJECTIVE: this study aims at evaluating the effect of exercise training (ET) on NT-pro-BNP plasma levels in older patients recovering from acute myocardial infarction (AMI). DESIGN: prospective randomised study. SETTING: Academic Medical Centre. SUBJECTS: forty older patients (33 males and 7 females) who experienced AMI. METHODS: patients were randomised into two groups, each composed of 20 patients: Group A were enrolled in a 3-month exercise-based cardiac rehabilitation (CR) programme and Group B were discharged home with generic instructions to continue physical activity. NT-pro-BNP, cardiopulmonary and Doppler-echocardiographic parameters were measured at baseline and at 3-month follow-up. RESULTS: in Group A, ET reduced NT-pro-BNP levels (from 1446 +/- 475 to 435 +/- 251 pg/ml, P<0.001) and increased maximal exercise parameters; there was also an inverse correlation between changes in NT-pro-BNP levels and in VO(2peak) (r = -0.67, P<0.01), E-wave (r = -0.42, P<0.01) and E/A ratio (r = -0.60, P<0.01). In Group B, after 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. LV volumes and left ventricular ejection fraction (LVEF) were unchanged after 3 months in both groups. CONCLUSIONS: three months ET in older patients after AMI was associated with a reduction in NT-pro-BNP levels and an overall improvement of exercise capacity, without negative LV remodelling and with improvement in early LV filling. Further investigation is required to evaluate whether in these patients the reduction of NT-pro-BNP levels at 3 months could be useful as a surrogate marker of favourable LV remodelling at a later follow-up.

Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone that is a powerful predictor of mortality in patients with coronary artery disease. DESIGN: This study aims at evaluating the effects of long-term exercise training on HRR after acute myocardial infarction (AMI), in order to clarify whether prolonged exercise training could maintain a long-term improvement of HRR. METHODS: Forty-four patients after AMI were enrolled in a 3-month hospital-based exercise training programme. At the end, patients were subdivided into two groups: group A (n=22), patients discharged with a specific home-based exercise training programme and instructions for improving leisure-time physical activity; group B (n=22), patients discharged with generic instructions to maintain physical activity. All patients underwent a cardiopulmonary exercise test before, at the end of 3 months exercise training and at 6 months follow-up. RESULTS: At the end of the hospital-based exercise training programme we observed an increase in peak oxygen consumption [VO2peak; from 13.9+/-3.6 to 18+/-2.7 ml/kg per min (A) and from 14.1+/-3.9 to 17.9+/-2.1 ml/kg per min (B), P<0.001] and in HRR [from 17.1+/-1.8 to 23.4+/-1.4 beats/min (A), and from 18.8+/-2.1 to 24.3+/-1.9 beats/min (B), P<0.001]. At 6 months' follow-up we observed a further improvement in VO2peak (from 18.0+/-2.7 to 20.3+/-2.7 ml/kg per min, P<0.001) and in HRR (from 23.4+/-1.4 to 27.8+/-2.1 beats/min, P<0.001) in group A, but a significant decrease in VO2peak and in HRR in group B (P<0.001). CONCLUSION: Long-term exercise training is useful for maintaining or improving the beneficial results of the standard 3-month exercise training programme on cardiovascular capacity and HRR. This observation may bear beneficial prognostic effects on patients after AMI.

Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction.

INTRODUCTION: N-terminal-pro-brain (B-type) natriuretic peptide (NT-pro-BNP) is a peptide hormone released from ventricles in response to myocyte stretch. The aim of the study was to investigate the influence of exercise training on plasma NT-pro-BNP to verify if this parameter could be used as a biological marker of left ventricular remodelling in myocardial infarction patients undergoing an exercise training programme. METHODS: Forty-four patients after myocardial infarction were enrolled into a cardiac rehabilitation programme, and were randomized in two groups of 22 patients each. Group A patients followed a 3-month exercise training programme, while group B patients received only routine recommendations. All patients underwent NT-pro-BNP assay, and cardiopulmonary exercise test before hospital discharge and after 3 months. RESULTS: In Group A, exercise training reduced NT-pro-BNP levels (from 1498+/-438 to 470+/-375 pg/ml, P=0.0026), increased maximal (VO2peak+4.3+/-2.9 ml/kg per min, P<0.001; Powermax+38+/-7, P<0.001) exercise parameters and work efficiency (Powermax/VO2peak+1.3+/-0.4 Power/ml per kg per min, P<0.001); there was also an inverse correlation between changes in NT-pro-BNP levels and in VO2peak (r=-0.72, P<0.001), E-wave (r=-0.51, P<0.001) and E/A ratio (r=0.59, P<0.001). In group B, at 3 months, no changes were observed in NT-pro-BNP levels, exercise and echocardiographic parameters. CONCLUSION: Three months exercise training in patients with moderate left ventricular systolic dysfunction after myocardial infarction induced a reduction in NT-pro-BNP levels, an improvement of exercise capacity and early left ventricular diastolic filling, without negative left ventricular remodelling. Whether the reduction of NT-pro-BNP levels could be useful as a surrogate marker of favourable left ventricular remodelling at a later follow-up remains to be further explored.

Exercise-based cardiac rehabilitation improves heart rate recovery in elderly patients after acute myocardial infarction.

BACKGROUND: Heart rate recovery (HRR), defined as the fall in HR during the first minute after exercise, is a marker of vagal tone, which is a powerful predictor of mortality in patients with coronary artery disease and in older patients. Whether exercise training (ET) modifies HRR in elderly patients recovering from acute myocardial infarction (AMI) is still unknown. Therefore, this study aims at evaluating the effect of ET on HRR in elderly AMI patients. METHODS: This was a prospective observational study including 268 older patients after AMI (217 men, 51 women), subdivided in two groups: Group A (n = 104), enrolled in an ET program; Group B (n = 164), discharged with generic instructions to continue physical activity. At baseline and at 3-month follow-up, all Group A and 54/164 Group B patients underwent a cardiopulmonary exercise stress test, whereas 110/164 Group B patients underwent an exercise stress test. RESULTS: After completion of the ET program, in Group A we observed an improvement in oxygen consumption at peak exercise (VO2peak; from 14.7 +/- 1.3 to 17.6 +/- 1.9 mL/kg/min, p < .001), in the rate of increase of ventilation per unit of increase of carbon dioxide production (VE/VCO2slope; from 34.2 +/- 3.8 to 30.4 +/- 3.0, p < .001), and in HRR (from 13.5 +/- 3.7 to 18.7 +/- 3.5 beats/min, p < .001). The changes in VO2peak and in VE/VCO2slope after ET were correlated with the improvement of HRR (r = -0.865, p < .01; r = -0.594, p < .01, respectively). No changes in these parameters were observed in Group B patients. CONCLUSIONS: In older AMI patients, ET results in HRR improvement, which was correlated to the improvement in cardiopulmonary parameters. These findings may shed additional light on the possible mechanisms of the beneficial prognostic effects of ET in this patient population.

[Inflammatory syndrome after thoracic aortic endoprosthesis implantation associated with cortico-suprarenal adenoma]. / Sindrome infiammatoria post-impianto di endoprotesi aortica toracica associata ad adenoma surrenalico.

We report a case of a 68-year-old patient, admitted with diagnosis of aneurysm of the descending thoracic aorta to the Department of Cardiac Surgery, where he underwent percutaneous endovascular application of 4 endoprostheses in the descending thoracic aorta. After antibiotic prophylaxis and hemodynamic stabilization, the patient was admitted to the Cardiac Rehabilitation Unit for the management of the of postoperative course and undergo a program of cardiac rehabilitation. Five days following admission and before starting physical training, the patient developed fever associated with neutrophil leukocytosis, strong activation of inflammatory markers and sideropenic anemia, compatible with post-implantation inflammatory syndrome. Significant hypokalemia also occurred. Further investigations showed left cortical-suprarenal adenoma. The inflammatory state relapsed spontaneously and the patient was discharged with indication to undergo an endocrinologic consultation.

Role of smokers in the household and of cardiac rehabilitation in smoking behaviour after acute myocardial infarction.

OBJECTS: This study aims to evaluate the influence of household smokers and of a prolonged, comprehensive home-based Cardiac Rehabilitation Program (CRP) on patient's long term smoking behaviour after AMI. METHODS: 164 male post-AMI patients, all smokers until the day of AMI, were subdivided into three groups: Group A (n=54): patients with recent AMI, discharged from hospital without enrolment in CRP; Group B (n=55): similar to Group A but enrolled in an 8 weeks hospital-based CRP and then discharged home with routine care; Group C (n=55) enrolled in an 8 weeks hospital-based CRP followed by a further 10 months of formal home-based CRP, with scheduled hospital follow-up visits. RESULTS: Smoking resumption at 12 months was influenced by the presence of household smokers (HS): 38% of patients with HS resumed smoking compared to 27% of patients without HS (p <0.01). Adherence to a CRP was inversely correlated to smoking resumption: there were fewer smoking patients at 12 months from AMI in Group C than in Groups A or B (11% in C vs. 29% and 55% in B and A, respectively, p <0.001). CONCLUSIONS: Long term maintenance of CRP seems to be the best way to achieve a reduction of long term smoking habit and maintain adherence to prescription in patients after AMI. Counselling and behavioural intervention should also be extended to family members in order to maximize the benefit of secondary prevention.