Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure

Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis.A significant prevalence (85\%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA.We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis

Quality of life and treatment satisfaction in adults with Type 1 diabetes: A comparison between continuous subcutaneous insulin infusion and multiple daily injections

Aims: The aim of this case-control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Methods: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. Results: Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA1c were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (β = 5.96; P < 0.0001), daily hassles (β = 3.57; P = 0.01) and fears about hypoglycaemia (β = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (β = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. Conclusions: This large, non-randomized, case-control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens. © 2008 The Authors

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Tertulia

Tertulia intende offrire al lettore italiano alcuni tasselli fondamentali del variegato mosaico della modernità ispanica. Tra gli autori tradotti figurano Miguel de Unamuno, José Ortega y Gasset, María Zambrano, Pedro Laín Entralgo e Leopoldo Alas Clarín

TERTULIA

SALETTA DELL’UVA propone una collana d’ispanistica con cui intende offrire al pubblico italiano una cernita di alcuni fra i testi più rilevanti nella storia della letteratura e del pensiero spagnoli. L’ambito prescelto è, dunque, quel territorio di confine – frastagliato ed estremamente vasto nella tradizione ispanica – che collega la letteratura (filosofica) alla filosofia (letteraria); o meglio, quella frangia in cui si coniugano la plasticità e l’attenzione per le differenze concrete della scrittura letteraria con la riflessione ermeneutica e l’aspirazione cognitiva del discorso filosofico

TERTULIA

SALETTA DELL’UVA propone una collana d’ispanistica con cui intende offrire al pubblico italiano una cernita di alcuni fra i testi più rilevanti nella storia della letteratura e del pensiero spagnoli. L’ambito prescelto è, dunque, quel territorio di confine – frastagliato ed estremamente vasto nella tradizione ispanica – che collega la letteratura (filosofica) alla filosofia (letteraria); o meglio, quella frangia in cui si coniugano la plasticità e l’attenzione per le differenze concrete della scrittura letteraria con la riflessione ermeneutica e l’aspirazione cognitiva del discorso filosofico

TERTULIA

SALETTA DELL’UVA propone una collana d’ispanistica con cui intende offrire al pubblico italiano una cernita di alcuni fra i testi più rilevanti nella storia della letteratura e del pensiero spagnoli. L’ambito prescelto è, dunque, quel territorio di confine – frastagliato ed estremamente vasto nella tradizione ispanica – che collega la letteratura (filosofica) alla filosofia (letteraria); o meglio, quella frangia in cui si coniugano la plasticità e l’attenzione per le differenze concrete della scrittura letteraria con la riflessione ermeneutica e l’aspirazione cognitiva del discorso filosofico

Magnetic resonance imaging in the evaluation of the gastric emptying and antral motion: feasibility and reproducibility of a fast not invasive technique

PURPOSE:The aim of this study was to evaluate reproducibility of a fast MRI protocol to measure gastric emptying and motility of the gastric antrum. METHODS AND MATERIALS: Gastric emptying and antral speed were measured in 12 type 1 diabetic patients (mean age 43 years) and 9 healthy volunteers (mean age 31 years). Subjects, fasting from 6h, were evaluated in supine position using a 1.5T MR scanner and a eight-channels phased-array body coil after ingestion of 400 ml of a vanillas pudding mixed with 5 ml of Gd-DTPA. Axial 3D T1w sequence at 0 and 30 min for volume evaluation and cine-steady state acquisition every 5 min for a total time of 30 min for gastric wave speed assessing were acquired. Two blinded observers extrapolated T(1/2) from gastric volume assessment and speed of gastric waves. RESULTS: All the patients tolerated the examination. The T(1/2) cut-off was of 115 min with an accuracy in differentiate controls from diabetics of 96% (95% CI 0.766-0.992; p<0.001), while the antral speed cut-off was of 0.15 mm/s with an accuracy of 87% (95% CI 0.628-0.977; p<0.001). The inter-observer agreement for the volumes at time 0 and 30 min was respectively 0.983 (95% CI 0.9628-0.9929; p<0.001) and 0.9933 (95% CI 0.9847-0.9971; p<0.001) with an agreement of 0.9918 (95% CI 0.9853-0.9954; p<0.001), while for antral speed it was of 0.935 (95% CI 0.9097-0.9528; p<0.001). CONCLUSIONS: MRI is a reproducible technique for the evaluation of gastric emptying and antral motility. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved