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The objective is to elucidate the effect of nitric oxide (NO)-renin-angiotensin system (RAS) interactions on renal hemodynamic function in uncomplicated, type 1 diabetes mellitus (DM). In 14 salt-replete, male healthy volunteers (C) and 9 male DM patients on euglycemia, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), and sodium excretion (UNaV) were measured at base-line and during a 90-min infusion of 3.0 μ.g-kg-1·min-1 NG-nitro-L-arginine-methyl-ester (L-NAME) after 3 days of pretreatment with either placebo (PL) or 50 mg losartan (LOS). Baseline GFR, RBF, and FF were higher in DM (P < 0.005). In the C group, PL + L-NAME caused declines in GFR (101 ± 3 to 90 ± 3 ml·min-1·1.73 m-2), RBF (931 ± 22 to 754 ± 31 ml·min-1·1.73 m-2), and UNaV (158 ± 12 to 82 ± 18 μmol/min) and an increase in FF (0.19 ± 0.02 to 0.21 ± 02; P < 0.001), which were not influenced by LOS pretreatment (P > 0.05 for LOS + L-NAME-C vs. PL + L-NAME-C). In DM, PL + L-NAME resulted in exaggerated renal effects, with changes in GFR (128 ± 3 to 104 ± 3 ml·min-1·1.73 m-2), RBF (1,019 ± 27 to 699 ± 34 ml·min-1·1.73 m-2), UNaV (150 ± 13 to 39 ± 14 μmol/min), and FF (0.22 ± 0.03 to 0.26 ± 0.02) that were significantly greater vs. PL + L-NAME-C (P < 0.005). LOS pretreatment blunted GFR, RBF, FF, and UNaV responses to L-NAME in DM (P < 0.005 vs. PL + L-NAME-DM), resulting in a response profile that was similar to PL + L-NAME and LOS + L-NAME in C (P > 0.05). Renal responses to L-NAME in uncomplicated, type 1 DM are exaggerated vs. C, consistent with an upregulation of NO bioactivity. LOS, without effects in C, prevents the accentuated actions of L-NAME in DM, thus indicating an augmented role for NO-RAS interactions in renal hemodynamic function in DM. [ABSTRACT FROM AUTHOR]

According to the "tubulocentric" hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute "distal" sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg-1·min-1 L-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (-0.26 ± 0.07 mmol/min C vs. -0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min-1·1.73 m-2) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min-1.1.73 m-2). In contrast, with ARG.HCl, DDNa rose in both groups (P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased (P = 0.001, +219 ± 20 ml·min-1·1.73 m-2 C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups (P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C (P = 0.001) and GFR, unchanged in C, declined in DM (-7.4 ± 0.9 ml·min-1·1.73 m-2, P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We describe a case of non-obstructive apical hypertrophic cardiomyopathy with atrial septal defect, in a 48-year-old caucasian female patient with chronic renal failure, hypothyroidism and primary amenorrhea, referred to our hospital for syncope, palpitation and shortness of breath. Methods and results: Electrocardiogram, transthoracic echocardiogram and cardiac magnetic resonance showed classical features of apical hypertrophic cardiomyopathy. Apical hypertrophic cardiomyopathy is morphologically characterized by apical ventricular hypertrophy, and is reported to be a relatively benign prognosis compared with the other type of hypertrophic cardiomyopathy. Conclusion: Apical hypertrophic cardiomyopathy is very rare in the West, is occasionally encountered in Japanese persons, but there have been only a few reports of its coexistence with atrial septal defect. Our present report is the first case of apical hypertrophic cardiomyopathy with atrial septal defect associated with renal failure, hypothyroidism and primary amenorrhea that could represent a multi-organ syndrome. This hypothesis was supported by the finding of the same characteristics in a sister of the patient. [Copyright &y& Elsevier]

Abstract: Aims: Multiple sclerosis is the most common cause of neurological disability in young adults. Mitoxantrone is a synthetic anthracenedione, recently approved for the treatment of worsening multiple sclerosis, which is known to induce cardiotoxicity. This study was designed to evaluate the early alterations in left ventricular function in patients with multiple sclerosis receiving mitoxantrone, by the use of the myocardial performance index, a new parameter of global (systolic and diastolic) ventricular function. Methods and results: The study included 29 Caucasian patients with multiple sclerosis (mean age 41.8±9.3years, 12 males and 17 females) treated with mitoxantrone (mean cumulative dose 30.8±18.2mg/m2) who were compared with 28 healthy subjects (mean age 37.8±11.8years, 13 males and 15 females). Both groups underwent a complete two-dimensional and Doppler echocardiography including assessment of the mitral inflow and left ventricular outflow patterns for estimation of the Doppler-derived myocardial performance index. This parameter is defined as the sum of isovolumic contraction time and isovolumic relaxation time, divided by ventricular ejection time. No differences were observed in blood pressure, heart rate, left ventricular diameters, mass and ejection fraction in multiple sclerosis patients compared to the controls. The mitral flow pattern showed a significant decrease of E wave calculated as peak velocity (E pv) (63.3±13.4 vs. 77.2±17.2, P <0.002) and time velocity integral (E tvi) (8.8±1.9 vs. 10.3±2.4, P <0.02), with a significant decrease of E pv/A pv ratio and a non-significant decrease of E tvi/A tvi ratio in the patients. In addition, E-wave deceleration time was significantly increased in multiple sclerosis patients compared to controls (178.2±30.2 vs. 137.9±14.7, P <0.0001). The mean value of myocardial performance index was 0.55±0.1 in patients compared to 0.37±0.06 in the controls (P <0.0001). A significant correlation between the given cumulative dose of mitoxantrone and myocardial performance index (r =0.67, P <0.001) and E-wave deceleration time (r =0.45, P <0.001) respectively were demonstrated. Conclusion: The myocardial performance index represents a parameter of combined systolic and diastolic myocardial performance strongly correlated with the given cumulative dose of mitoxantrone. The myocardial performance index may be an adjunctive parameter to conventional echocardiography for detecting sub-clinical cardiotoxicity of mitoxantrone in the clinical management of the multiple sclerosis patients. [Copyright &y& Elsevier]

Aims: Previous studies using Doppler Tissue Echocardiography (DTE) have suggested that the early-diastolic myocardial velocity behaves as a relatively load-independent index of left ventricular relaxation in patients with cardiac diseases; it is not ascertained if this holds true also in normal human hearts.Methods and results: We assessed the influence of a progressive reduction of preload, obtained by Lower Body Negative Pressure (LBNP), on the diastolic and systolic myocardial waves compared to the inflow patterns estimated in left and right ventricles in nine healthy subjects. LBNP caused a significant decrease in end-diastolic volume, stroke volume and systolic arterial pressure, whilst heart rate increased only at maximum preload reduction; meridional end-systolic stress did not change significantly. The early (E′) and late (A′) myocardial velocities, at mitral and tricuspid annulus, decreased similarly during lower body suction, so that E′/A′ ratio did not change. However, due to reduced early (E) but unchanged late (A) diastolic velocities, the E/A ratio of inflow patterns decreased. Systolic (S′) myocardial velocities also decreased during LBNP. LBNP induced greater changes of myocardial diastolic and systolic velocities in the right than in the left ventricle.Conclusion: In this study, myocardial E′, A′ and S′ velocities, in both the left and the right ventricle, were significantly affected by preload in healthy subjects. Our results support the usefulness of the E′/A′ ratio as a relatively load-independent index of diastolic function. [ABSTRACT FROM AUTHOR]

Summary: Laboratory animal allergy (LAA) is caused by an immunological hypersensitivity reaction to highmolecular- weight antigens that are present in laboratory animals' urine, dander and saliva. All laboratory animal facility personnel who regularly come in contact with laboratory animals, such as technicians, researchers, cleaning staff, veterinarians and even administrative staff, are at risk of developing LAA. Generally, most epidemiological studies indicate a LAA prevalence ranging from 6% to 44% and an incidence ranging from 9% to 30%. Prevalence and incidence data vary widely because the diagnosis is not uniformly defined: some diagnoses are made solely on the basis of symptoms, whereas others also require a positive skin test or confirmation of the presence of laboratory animal allergen-specific IgE antibodies., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by Aracne Editrice, Roma, Italy.)

According to the 2018 European Union Ageing Report, the demographic profile of the European population is projected to be older. Aging cannot be considered a homogeneous process, and only in certain cases is "successful", with maintained functional ability, which is determined by intrinsic capacity, the environment, and their interaction. When intrinsic capacity is lost, elders with chronic diseases develop frailty, a condition with high-risk of disability. Old-age dependency-ratio is projected to increase from 29.6% to 51.2% in the EU in 2070: thus, the need of new approaches targeting the prevention of disability. Numerous studies are conducted in the European Innovation Partnership on Active and Healthy Ageing and addressing identification, treatment, coordination and integration of care in frail older subjects. SUNFRAIL is aimed at developing a model, good practices and tools to improve the identification, prevention and care of frailty and management of multimorbidity. SPRINTT is testing the effectiveness of a multi-component treatment able to treat frailty and sarcopenia. VIGOUR, a project aimed at strengthening integrated-care in different contexts of European Countries, verifies enablers and obstacles encountered in the real world by these good practices. Through the creation of Parma-Lab and Frailty-Team in the Academic-Hospital of Parma combined with the contribution of Parma Health-Trust in the "Community Health-Centers", the Projects were translated into Health Services Arena. This response bridging European Studies and clinical practice, aims to early detecting and caring 75-year older citizens with frailty and multimorbidity, living in the community, not institutionalized and at risk of hospitalization and mobility ADL-disability.

The Doppler echocardiographic examination is the most important and common method used for cardiac imaging due to its safety, its relatively low cost and the great amount of morphofunctional information it can provide. It also plays a relevant role in the assessment of cardiac involvement underlying systemic diseases, in most of which the complication rate is often subclinical and represents one of the main causes of mortality. Advances in technology have lead to an increase in diagnostic accuracy and the range of applications of echocardiography. Among the new techniques, tissue Doppler echocardiography has been shown to identify early ventricular changes in both diastolic and systolic phases and in the preclinical stage of systemic diseases such as amyloidosis, systemic lupus erythematosus, vasculitis, with possible cardiac involvement. The increased sensitivity derives from the possibility of assessing longitudinal mechanics, which seems affected earlier than the circumferential one by pathological processes. Tissue Doppler echocardiography analysis, associated with a complete clinical history, can make an early diagnosis or arise a diagnostic suspicion to the physician, allowing early detection and rapid implementation of diagnostic and therapeutic measures able to improve patient prognosis.