Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Serenoa Repens, lycopene and selenium: a triple therapeutic approach to manage benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a major health concern that is likely to have an increasing impact in line with the gradual aging of the population. BPH is characterized by smooth muscle and epithelial proliferation primarily within the prostatic transition zone that can cause a variety of problems for patients, the most frequent are the lower urinary tract symptoms. BPH is thought to involve in disruption of dihydrotestosterone (DHT)-supported homeostasis between cell proliferation and cell death, and, as a result, proliferative processes predominate and apoptotic processes are inhibited. Phytotherapeutic supplements, mainly based on Saw Palmetto-derived Serenoa Repens (SeR), are numerous and used frequently. Serenoa Repens reduces inflammation and decreases in vivo the androgenic support to prostatic cell growth. Furthermore, SeR stimulates the apoptotic machinery; however, data supporting efficacy is limited, making treatment recommendations difficult. Besides SeR, selenium (Se), an essential trace element mainly functioning through selenoproteins and able to promote an optimal antioxidant/oxidant balance, and lycopene (Ly), a dietary carotenoid synthesized by plants, fruits, and microorganisms with a strong antioxidant activity, has been shown to exert beneficial effects in prostate disease. SeR is frequently associated with Ly and Se, in order to increase its therapeutic activity in benign prostatic hyperplasia (BPH). It has been shown that the Ly-Se-SeR association has a greater and enhanced antiinflammatory activity that might be of particular interest in the treatment of BPH. The Ly-Se-SeR association is also more effective than SeR alone in reducing prostate weight and hyperplasia, in augmenting the pro-apoptotic Bax and caspase-9 and blunting the anti-apoptotic Bcl-2 mRNA. In addition, Ly-Se-SeR more efficiently suppresses the EGF and Vascular Endothelial Growth Factor (VEGF) expressions in hyperplastic prostates. Therefore, SeR particularly when combined with Se and Ly may have a greater potential for the management of benign prostate hyperplasia.

Productive performance and histological features of intestinal mucosa of broiler chickens fed different dietary protein levels.

To evaluate the effect of decreasing dietary protein on growth performance, carcass traits, and intestinal mucosal morphometry, 180 female Hubbard strain broiler chickens were divided into 3 groups and fed 3 isoenergetic diets ad libitum from 14 d of age until slaughter age (49 d). The treatments varied according to 3 protein levels: high-protein diet (HiP, 22.5% CP, DM basis), medium-protein diet (MedP, 20.5% CP), and low-protein diet (LowP, 18.5%). Diets were obtained by replacing wheat middlings with soybean meal and were formulated to meet or exceed broiler amino acid requirements of the NRC. Morphometric indices of duodenum, jejunum, and ileum were measured at the end of the feeding period and included villus height, crypt depth, villus-to-crypt ratio, and apparent villus surface area. The dietary protein level had a significant effect on final BW of birds, whereas ADG, ADFI, and feed efficiency remained unaffected by dietary treatment. The muscle (breast and drumstick) yields were significantly higher in birds fed the HiP diet compared with those of the MedP and LowP diets. Meat quality traits were not affected by the protein level. The villus surface area of all intestinal segments did not change among groups. Instead, reducing the dietary protein level to 20.5% resulted in a higher villus height and villus height to crypt depth ratio in the duodenum and ileum. On the basis of our findings, even if the high-protein diet promoted meat yield, a medium-protein diet could positively support broiler growth performance, as confirmed by favorable morphometric features of the intestine.

Apoptosis of gut-associated lymphoid tissue in rainbow trout Oncorhynchus mykiss after incubation with Candida albicans and bacterial lipopolysaccharide.

Until now a few studies have been carried out on the gut lymphoid system in fish despite its protective role in the host. Here, we have evaluated the effects of Candida albicans (Ca) and lipopolysaccaride (LPS) on the pyloric and terminal segments of gut in the rainbow trout Oncorhynchus mykiss. In particular, data show that both Ca and LPS are able to cause apoptosis of intestinal lymphoid cells as detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) procedure. These findings suggest a further modality of gut response in fish to environmental antigens.

Canine leishmaniosis and euthanasia in Italy: a critical legal-ethical analysis.

The increasing awareness that control of zoonotic visceral leishmaniosis (ZVL) depends on effective control of canine leishmaniosis has promoted research into leishmanial infection in dogs, but has also encouraged the indiscriminate elimination of seropositive dogs. Public health campaigns in various parts of the world (e.g. in Brazil and China) are designed to reduce the incidence of human ZVL by targeting/killing dogs. However, not all situations are the same; in Italy, for example, there would be little support for this type of control measure because attitudes towards animals are different. Moreover, research has suggested that the destruction of seropositive dogs is a relatively ineffective control measure. In this context, the authors reflect on some epidemiological, ethical and juridical aspects, aiming to contribute to the discussion and to find more feasible solutions.

Importation of mycobacteriosis with ornamental fish: Medico-legal implications.

Mycobacterium fortuitum, as well as Mycobacterium marinum and Mycobacterium chelonae, are the etiological agents of fish Mycobacterioses. Mycobacteriosis has been reported to affect a wide range of freshwater and marine fish species, suggesting an ubiquitous distribution, and can cause zoonotic infections (known as "fish tank granuloma" or "swimming pool granuloma") in humans exposed to fish and contaminated water. Infection in human consists of nodular cutaneous lesions that can progress to tenosynovitis, arthritis, and osteomyelitis, depending on the immunological status. Authors describe some cases observed during routinary diagnostic activity in aquarium fish. Fish were sampled and histopathological, microbiological, and biomolecular exams were carried out. Histopathology showed systemic granulomatosis. Microbiological and biomolecular exams allowed us to identify the M. fortuitum as a main species. Finally, some considerations on the legal aspects of such disease are discussed.

Isolation of Enterobacter sakazakii from ass' milk in Sicily: case report, safety and legal issues.

Enterobacter sakazakii (Es) infections are likely to involve newborns and infants, causing meningitis and necrotizing enterocolitis and sepsis. Contamination of infant formulae milk during factory production or bottle preparation is implicated. Es has been isolated from environmental sources and from food other than infant formula and milk powder, but why it is associated only with the consumption of infant formulae, is unclear. According to Regulation (EC) No. 2073/2005 on the microbiological criteria for foodstuffs, Es is considered a microorganisms of greatest concern in infant formulae and follow-on formulae. Es is included between "safety criteria". The isolation of two strains of Es from 50 samples of ass' milk in Sicily is described. The antibiotic resistance profile of the isolates revealed a multiple resistance profile, including fluoroquinolones, commonly used to treat the infections. The authors underline the importance of survey because in Italy ass' milk is considered one of the solutions for infants suffering from hypersensitivity to milk protein of some animal species. There is scarce information about the ecology and the uncertainty concerning the source of infection in the children and adults; the authors are concerned that ass' milk could become a high-risk food.

Histological, histochemical and morphometric changes of splenic melanomacrophage centers (SMMCs) in Sparicotyle-infected cultured sea breams (Sparus aurata).

Diseases caused by parasites are much more frequently described in cultured fish, which suffer from artificial conditions and numerous stress factors. This study investigates the histological, histochemical and morphometric modifications of splenic melanomacrophage centers (SMMCs) infected by Sparicotyle chrisophrii (Monogenea, ectoparasite of the gills) in sea breams (Sparus aurata), cultured in floating cages in the Gulf of Gaeta (Italy). Infected fish swam near the water surface, showing severe signs of anemia. Several spleens were collected from both healthy and dead fish (70-100 gr. body weight). A spleen histopathology was evaluated by using traditional stainings, such as Haematoxylin and Eosin (HE), Periodic Acid-Schiff reaction (PAS), Perl's reaction for haemosiderin and Schmorl's reaction for lipofuscins. Furthermore, SMMCs morphometry was performed on PAS-stained sections to study 7 morphometric parameters [Mean SMMCs profile area (MPA), Mean SMMCs maximum diameter (Media), Mean SMMCs minimum diameter (media), Mean SMMCs diameter (Dia), Mean SMMCs Perimeter (P), Mean SMMCs Form Factor (FF) and Mean SMMCs number per square millimeter of spleen tissue (MN)]. A light microscope of HE stained sections of spleen revealed a dramatic increase in the size and number of SMMCs in parasitized animals. Morphometric data illustrated statistically significant differences (p < 0.01) of all studied parameters between healthy and diseased fish. This study emphasizes the importance of using histopathological investigations to unravel the complex biological host/parasite interaction, which results in systemic lesions affecting reared marine species.

Medico-legal considerations of canine leishmaniosis in Italy: an overview of an emerging disease with reference to the buying and selling of dogs.

Leishmaniosis is a common infection in the canine population. Domestic dogs are the main reservoir hosts for zoonotic human visceral leishmaniosis in both the Old and New Worlds. In fact, canine leishmaniosis is not just a veterinary problem. In the light of some recent advances in the field of diagnosis, the author evaluated the medico-legal aspects of buying and selling dogs that are potentially affected by leishmaniosis. This paper clarifies why it is impossible to attribute redhibitory vice (an essential defect in a product which renders it useless or so diminishes its usefulness or value that it must be presumed that, if he had been aware of it, the buyer would not have bought it, or would have paid a lesser price) to this disease and highlights the necessity to improve Sicilian regional law no. 15 of 3 July 2000 concerning the creation of a dog register by giving every animal a health book. With this aim in mind, the author suggests that leishmaniosis be included in the list of notifiable diseases that appears in article 1 of the Italian Veterinary Police Regulations so as to reduce the possibilities of fraudulent trade in dogs known to be infected before purchase.

The veterinary surgeon in natural disasters: Italian legislation in force.

Law No. 225/1992 established a National Service of Civil Protection, with the important role of 'safeguarding life, goods, settlements and the environment from damage deriving from natural disasters, catastrophes and calamities' (art. 1). This law arranges civil protection as a co-ordinated system of responsibilities administrated by the state, local and public authorities, the world of science, charitable organisations, the professional orders and other institutions, and the private sector (art. 6). The President of the Republic's Decree No. 66/1981 'Regulation for the application of Law No. 996/1970, containing norms for relief and assistance to populations hit by natural disasters--Civil Protection' mentions veterinary surgeons among the people that are called upon to intervene. In fact, in natural disasters the intervention of the veterinary surgeon is of great importance. The authors examine these laws and other legislation relating to the National Service of Civil Protection.

Low-dose dobutamine responsiveness in idiopathic dilated cardiomyopathy: relation to exercise capacity and clinical outcome.

AIMS: To evaluate myocardial contractile reserve using low-dose dobutamine echocardiography in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy stratified by peak exercise oxygen consumption (VO(2)). METHODS AND RESULTS: Sixty clinically stable patients (56+/-11 years; 45 males) with idiopathic cardiomyopathy and NYHA class I to III symptoms of heart failure were studied and followed-up for 13+/-3 months. All patients underwent cardiopulmonary exercise testing and low-dose dobutamine. The dobutamine infusion protocol consisted of an initial dose of 2.5 micro. kg(-1)per 3 min, increasing by 2.5 micro. kg(-1)per min every 3 min; the maximal dose was 10 micro. kg(-1)per min. The end-systolic volume index, left ventricular ejection fraction and cardiac output were measured at baseline and peak dobutamine dose and their change calculated as ((peak dose value-baseline value)/baseline value]x100. Ten normal subjects with normal left ventricular function and no coronary artery lesions served as a control group to compare low-dose dobutamine results. All analysed echocardiographic variables either at baseline or following dobutamine infusion were significantly lower in patients with chronic heart failure as a whole compared to the control group. When the patients were grouped according to Weber's classification, a statistically significant decrease in percentange changes in end-systolic volume index (rho=-0.77;P<0.0001), left ventricular ejection fraction (rho=-0.72;P<0.0001) and cardiac output (rho=-0. 82;P<0.0001) from class A to class C was observed. The mean percentage decrease in end-systolic volume index following the dobutamine infusion was 28.7+/-9% in class A (peak VO(2)>20 ml. kg(-1). min(-1)), 18.6+/-8% in class B (peak VO(2)between 16 and 20 ml. kg. min(-1)), and only 6.4+/-6% in class C (peak VO(2)between 10 and 16 ml. kg(-1). min(-1)) patient groups. At multivariate analysis, only the percentage change in end-systolic volume index was significantly associated with a peak VO(2)<15 ml. kg(-1). min(-1)(P=0.006). During the follow-up, 17 patients had events (15 readmissions for worsening heart failure and two deaths). At multivariate analysis, only the percentage change in end-systolic volume index was significantly associated with the occurrence of events (P=0.003). The area under the receiver operating characteristic curve for percentage change in end-systolic volume index was not significantly different from that for peak VO(2)(0. 86+/-0.04 vs 0.80+/-0.06;P:ns). CONCLUSION: This study indicates that in patients with chronic heart failure secondary to idiopathic cardiomyopathy, the cardiac response to low-dose dobutamine, as assessed by echocardiography, is correlated with peak VO(2), an objective and accurate measure of the severity of the disease and clinical outcome.

Diastolic dysfunction and baroreflex sensitivity in hypertension.

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P

Percent achieved of predicted peak exercise oxygen uptake and kinetics of recovery of oxygen uptake after exercise for risk stratification in chronic heart failure.

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P<0.0001). Other independent predictors of death were EF, T1/2VO2max, NSVT and inability to take ACE-inhibitors. The discriminatory accuracy of VO2max for cardiac death was not significantly greater than that of %VO2max. In conclusion, the determination of %VO2max does not enhance risk stratification in CHF whereas the kinetics of oxygen consumption after exercise can provide prognostic information.

Assessment of cardiac vagal activity in patients with hyperthyroidism.

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon.

OBJECTIVE: The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS: Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS: Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS: The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.