Protein synthesis in the atrioventricular node during acute experimental cardiac hypertrophy in the rat

The relative concentration of autoradiographic grains was measured over the atrioventricular node of the adult rat heart 2 h after the intravenous injection of [³H]-leucine and 20 h after the induction of left ventricular cardiac hypertrophy by constriction of the abdominal aorta. In comparison with control tissues, the grain counts in equal area samples show a 32% greater concentration in the hypertrophying hearts. The results indicate a significantly increased rate of incorporation of amino acid into the proteins of nodal tissues accompanying early hypertrophic changes.     

Hb Amsterdam [alpha32(B13)Met--Ile (alpha2)]: a new unstable variant associated with an alpha-thalassemia phenotype and a new African polymorphism

We have characterized a new abnormal hemoglobin (Hb) at position 32 of the alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of Prednisone treatment in Surinam. Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic hypochromic anemia was observed with high reticulocyte (40%) and ferritin (500 microg/L) levels, and hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal haptoglobin level (68 mg/100 mL). None of the common alpha-thalassemia (thal) deletion defects were present. The beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at codon 32, changing the methionine into an isoleucine residue. The mutation, called Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic hypochromic anemia. Both Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition, Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174). Hb Amsterdam is the first mutation ever described at codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.     

Lactic acidosis,diabetes mellitus and the biguanide compounds

Summary After a brief outline of the factors regulating plasma lactate levels in normal and diabetic subjects, the AA. summarize the history, the possible mechanism of action and the therapeutic applications of the guanidine derivatives. The possibility that these drugs may increase the danger of lactic acidosis is discussed.

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Zusammenfassung Nach einer kurzen Schematisierung der Faktoren, welche die Laktatspiegel im Plasma normaler Personen und Diabetiker regeln, fassen die AA. die Geschichte, den moeglichen Wirkungsmechanismus und die therapeutischen Anwendungen der Guanidin-Derivate zusammen. Es wird die Moeglichkeit der Steigerung der Azidose-Periode (Milchsaeure) durch diese Arzneimittel diskutiert.

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Resumen Al cabo de breve esquema de los factores que regulan los niveles de lactato en el plasma de sujetos normales y diabéticos, los AA. resumen la historia, el modo de acción posible y las aplicaciones terapéuticas de los derivados de la guanidina. Se discute la posibilidad que estos fármacos puedan aumentar el período de la acidosis láctica.

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Resume Après un bref schème des facteurs qui réglent les niveaux du lactate dans le plasma des sujets normaux et diabétiques, les AA. résument l'histoire, le possible mécanisme d'action et les applications thérapeutiques des dérivés de la guanidine. On discute sur la possibilité que ces médicaments puissent accroître la période de l'acidose lactique.

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Riassunto Dopo un breve schema dei fattori che regolano i livelli di lattato nel plasma dei soggetti normali e diabetici, gli AA. riassumono la storia, il possibile meccanismo di azione e le applicazioni terapeutiche dei derivati della guanidina. Viene discussa la possibilità che questi farmaci possano incrementare il pericolo dell'acidosi lattica.

     

The role of impaired esophageal and gastric motility in end-stage lung diseases and after lung transplantation

Today, many questions persist regarding the causal relationship of gastroesophageal reflux disease (GERD) to promote aspiration and its potential to induce both pulmonary and allograft failure. Current hypotheses, which have identified GERD as a nonimmune risk factor in inducing pulmonary and allograft failure, center on the role of GERD-induced aspiration of gastroduodenal contents. Risk factors of GERD, such as impaired esophageal and gastric motility, may indirectly play a role in the aspiration process. In fact, although impaired esophageal and gastric motility is not independently a cause of lung deterioration or allograft failure, they may cause and or exacerbate GERD. This report seeks to review present research on impaired esophageal and gastric motility in end-stage lung disease to characterize prevalence, etiology, pathophysiology, and current treatment options within this special patient population.     

A 20-year long term experience of the Italian Diamond-Blackfan Anaemia Registry: RPS and RPL genes,different faces of the same disease?

Diamond–Blackfan anaemia (DBA) is a rare and heterogeneous disease characterised by hypoplastic anaemia, congenital anomalies and a predisposition for malignancies. The aim of this paper is to report the findings from the Italian DBA Registry, and to discuss the Registry’s future challenges in tackling this disease. Our 20-year long work allowed the connection of 50 Italian Association of Paediatric Haematology and Oncology (AIEOP) centres and the recruitment of 283 cases. Almost all patients have been characterised at a molecular level (96%, 271/283), finding a causative mutation in 68% (184/271). We confirm the importance of determination of erythrocyte adenosine deaminase activity (eADA) and of ribosomal RNA assay in the diagnostic pipeline and characterisation of a remission state. Patients with mutations in large ribosomal subunit protein (RPL) genes had a significant correlation with the incidence of malformations, higher eADA levels and more severe outcomes, compared to patients with mutations in small ribosomal subunit protein (RPS) genes. Furthermore, as a consequence of our findings, particularly the incidence of malignancies and the high percentage of patients aged >18 years, we stress the importance of collaboration with adult clinicians to guarantee regular multi-specialist follow-up. In conclusion, this study highlights the importance of national registries to increase our understanding and improve management of this complex disease.     

Assessing inter- and intra-individual cognitive variability in patients at risk for cognitive impairment: the case of minimal hepatic encephalopathy

Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies.