Lecithin: cholesterol-acyltransferase (LCAT) activity in alcoholic liver disease

The activity of LCAT (the controlling enzyme for cholesterol esterification in plasma) is known to be reduced in alcoholic cirrhosis, while little is known about early stage (liver steatosis) alcoholics. In this study, LCAT activity was assayed by Stokke and Norum's method, before and after a 15-day sobriety period, in liver steatosis and in cirrhosis alcoholics. Before alcohol withdrawal, LCAT activity was depressed in both groups. After the sobriety period, LCAT activity was significantly raised in liver steatosis patients, but was still lower than in controls; in cirrhosis patients, it was increased, but not significantly. According to our results, LCAT activity impairment in alcoholic liver disease is sustained by both the hypothesized mechanisms, alcohol-related metabolic disorders and lowered LCAT-enzyme production, but to different degrees, depending on the stage of the disease. In liver steatosis, metabolic disorders play a major role, as a liver-impairment-induced decrease in LCAT production seems rather unlikely, and increased LCAT activity is more likely to be sustained by metabolic normalisation than by any recovery of the damaged liver. However, the lack of improvement in about 20% of patients, and the fairly wide scattering of individual data, suggest a minor LCAT production impairment in liver steatosis too. In cirrhosis, the major role seems to be played by a permanent decrease in LCAT production, as no significant rise in LCAT activity was observed after alcohol withdrawal. However the restored LCAT activity observed in some patients could be related to improvement in the metabolic disorder, thus confirming the effectiveness of this mechnism in cirrhosis too.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistence of Mammary Artery Branches and Blood Supply to the Left Anterior Descending Artery

Background. Partial harvesting of the left internal mammary artery (LIMA) is a widespread technique used during minimally invasive coronary operations performed through a left anterior small thoracotomy. The influence of persisting LIMA branches was investigated to evaluate their effect on the blood flow of the left anterior descending artery.

Methods. Thirty patients, 15 with totally (group A) and 15 with partially (group B) harvested LIMAs, were evaluated. All the patients underwent postoperative angiography, during which a flow map of the LIMA was performed. The average peak velocity and the diastolic-to-systolic peak velocity ratio were recorded. The LIMA graft flow pattern was recorded in the proximal and distal thirds of the artery. Intramammary adenosine (12 to 14 μg) was injected and the average peak velocities before and after injection were calculated.

Results. The average peak velocity was similar in both groups in the proximal and distal thirds of the LIMA (25 ± 7 and 26 ± 5 cm/sec, respectively, in group A versus 27 ± 5 and 25 ± 5 cm/sec, respectively in group B; p = NS). The diastolic-to-systolic peak velocity ratio was similar proximally (0.78 ± 0.3 in group A versus 0.69 ± 0.3 cm/s in group B; p = NS), but not distally (1.72 ± 0.1 in group A versus 0.97 ± 0.3 in group B; p < 0.0005). The LIMA graft flow reserve was similar both proximally and distally (2.6 ± 0.6 and 2.5 ± 0.3 cm/s, respectively, in group A versus 2.6 ± 0.5 and 2.6 ± 0.3 cm/s, respectively, in group B; p = NS).

Conclusions. The persistence of LIMA branches does not influence the blood flow of the left anterior descending artery after acute adenosine-induced myocardial hyperemia. If a left anterior small thoracotomy is used in left anterior descending artery direct revascularization, complete LIMA harvesting is not mandatory and depends on the personal preference of the surgeon.     

Setting a maximum allowable concentration for urea in reclaimed potable water and evaluating the nature of its biological action

The purpose of the study was to identify maxim allowable concentrations of urea in reclaimed potable water. The urea concentration equal to 80 mg/l is the threshold dose influencing the taste and flavor of water. Urea is a low toxicity substance (LD50 = 14,300 mg/kg), the effect of which is not cumulative. However, when used in high doses it affects bioenergetic and cholinergic processes and causes changes in ECG, higher nervous activity and visceral structure. It has been shown that when applied to warm-blooded animals the acting dose of urea is 14.3 and 1.43 mg/kg (1/1000 and 1/10000 LD50), the threshold dose is 0.72 mg/kg (1/20000 LD50), and the ineffective dose is 0.36 mg/kg (1/40000 LD50) which amounts to the concentration of 10 mg/l. In terms of toxic effects the dose equal to 10 mg/l is taken to be the maximally allowable concentration of urea. It is recommended to use the Laham biotest for measuring urea in water.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Developmental regulation of lectin-binding patterns in Paracentrotus lividus gonads, gametes, and early embryos.

By use of several lectins (ConA, WGA, SBA, GS I, PNA), a study was carried on gametes and developing embryos of the sea urchin Paracentrotus lividus, to investigate developmental changes in cell surface, leading to changements in cell-environment interactions. ConA, WGA, and SBA, with high affinity, bind to the vitelline membrane of unfertilized eggs, while PNA labelling at the same site is weak; GS I-binding is only present in the cytoplasm and cortical region of the unfertilized eggs. Immediately after fertilization, no ConA-binding is present in the membrane, while WGA- and SBA-binding molecules are located in the fertilization layer. In zygotes, 40 min after fertilization, ConA affinity sites were again present in both cytoplasm and cortical region. During cleavages and gastrulation, ConA binds to the blastomere cytoplasm and cortical region, to the intercellular matrix, and to the cytoplasm of mesenchyme cells. WGA binds to the cortical region of cleaving blastomeres, including the hyaline layer, up to the unhatched blastula. Then it labels the gastrula inner and outer surfaces. SBA binds to the blastomere membranes; no GS I- and PNA-binding was detected during embryonic development. Sperms are bound by all the lectins, except GS I. Mannose and glucose conjugates are the most represented throughout the whole development of P. lividus, and their origin and locations are developmentally regulated. Galacto-residues are scarcely represented or are masked by other terminal sugars (e.g. sialic acid), and become functional during particular developmental events (cell movements).