[EASL clinical practice guidelines: prevention and treatment of hemorrhage and thrombosis in liver cirrhosis].

Hemorrhage and thrombosis prevention and treatment in patients with cirrhosis faces certain clinical difficulties. Therefore, this guideline is formulated to provide practical guidance on controversial topics, such as the current perspectives on hemostasis in liver disease, whether invasive procedures need to correct thrombocytopenia and coagulation abnormalities, and the necessity of thromboprophylaxis in hospitalized patients with abnormal coagulation. Many of the recommendations in the guidelines are not useful measures; however, they were stem under the oversight of an expert panel, and are widely used in clinical practice. Here, we compile and summarize the recommendations on the above topics in order to share them with readers.

[Baveno VII - Renewing consensus in portal hypertension: personalized care for portal hypertension].

The Baveno VII workshop held in October 2021 was featured by the subject of personalized care in portal hypertension. The workshop focused on the following 9 topics including: the relevance and indications for measuring the hepatic venous pressure gradient as a gold standard; the use of non-invasive tools for the diagnosis of compensated advanced chronic liver disease and clinically significant portal hypertension; the impact of etiological and of non-etiological therapies in the course of cirrhosis; the prevention of the first episode of decompensation; the management of the acute bleeding episode; the prevention of further decompensation; as well as the diagnosis and management of splanchnic vein thrombosis and other vascular disorders of the liver. This essay provides a compilation and summary of recommendations regarding the abovementioned topics, and presents the most recent research proceedings and the corresponding consensus to our readers.

alpha beta Spectrin coiled coil association at the tetramerization site.

On the basis of sequence homology studies, it has been suggested that the association of human erythrocytes alpha and beta spectrin at the tetramerization site involves interactions between helices. However, no empirical details are available, presumably due to the experimental difficulties in studying spectrin molecules because of its size and/or its structural flexibility. It has been speculated that erythrocyte tetramerization involves helical bundling rather than coiled coil association. We have used recombinant spectrin peptides to model alpha and beta spectrin to study their association at the tetramerization site. Two alpha peptides, Sp alpha 1-156 and Sp alpha 1-368, and one beta peptide, Sp beta 1898-2083, were used as model peptides to demonstrate the formation of the alpha beta complex. We also found that the replacement of R28 in Sp alpha 1-368 to give Sp alpha 1-368R28C abolished complex formation with the beta peptide. Circular dichroism techniques were used to monitor the secondary structures of the individual peptides and of the complex, and the results showed that both Sp alpha 1-156 and Sp beta 1898-2083 peptides in solution, separately, included helices that were not paired with other helices in the absence of their binding partners. However, in a mixture of Sp alpha 1-156 and Sp beta 1898-2083 and formation of the alpha beta complex, the unpaired helices associated to form coiled coils. Since the sequences of these two peptides that are involved in the coiled coil association are derived from a native protein, the information obtained from this study also provides insight toward a better understanding of naturally occurring coiled coil subunit-subunit association.

Studies of the erythrocyte spectrin tetramerization region.

Human erythrocyte spectrin dimers associate at the N-terminal region of alpha spectrin (alpha N) and the C-terminal region of beta-spectrin (beta C) to form tetramers. We have prepared model peptides to study the tetramerization region. Based on phasing information obtained from enzyme digests, we prepared spectrin fragments consisting of the first 156 amino-acid residues and the first 368 amino-acid residues of alpha-spectrin (Sp alpha 1-156 and Sp alpha 1-368, respectively), and found that both peptides associate with a beta-spectrin model peptide, with an affinity similar to that found in alpha beta dimer tetramerization. Spin label EPR studies show that the region consisting of residues 21-46 in alpha-spectrin is helical even in the absence of its beta-partner. Multi-dimensional nuclear magnetic resonance studies of samples with and without a spin label attached to residue 154 show that Sp alpha 1-156 consists of four helices, with the first helix unassociated with the remaining three helices, which bundle to form a triple helical coiled coil bundle. A comparison of the structures of erythrocyte spectrin with other published structures of Drosophila and chicken brain spectrin is discussed. Circular dichroism studies show that the lone helix in Sp alpha-156 associates with helices in the beta peptide to form a coiled coil bundle. Based on NMR and CD results, we suggest that the helices in Sp alpha 1-156 exhibit a looser (frayed) conformation, and that the helices convert to a tighter conformation upon association with its beta-partner. This suggestion does not rule out possible conversion of a non-structured conformation to a structured conformation in various parts of the molecule upon association. Spectrin mutations at residues 28 and 45 of alpha-spectrin have been found in patients with hereditary elliptocytosis. NMR studies were also carried out on Sp alpha 1-156R28S, Sp alpha 1-156R45S and Sp alpha 1-156R45T. A comparison of the structures of Sp alpha 1-156 and Sp alpha 1-156R28S, Sp alpha 1-156R45S and Sp alpha 1-156R45T is discussed.