In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.

No abstract

alpha-Human atrial natriuretic peptide, a 28-amino-acid-residue peptide, was rapidly hydrolysed by pig kidney microvillar membranes in vitro, with a t1/2 of 8 min, comparable with the rate observed with angiotensins II and III. The products of hydrolysis were analysed by h.p.l.c., the pattern obtained with membranes being similar to that with purified endopeptidase-24.11 (EC 3.4.24.11). No hydrolysis by peptidyl dipeptidase A (angiotensin I converting enzyme, EC 3.4.15.1) was observed. The contribution of the various microvillar membrane peptidases was assessed by including specific inhibitors. Phosphoramidon, an inhibitor of endopeptidase-24.11, caused 80-100% suppression of the products. Captopril and amastatin (inhibitors of peptidyl dipeptidase A and aminopeptidases respectively) had no significant effect. Hydrolysis at an undefined site within the disulphide-linked ring occurred rapidly, followed by hydrolysis at other sites, including the Ser25--Phe26 bond.

The circulating form of atria1 natriuretic factor is a 28-residue peptide containing a 17-residue disulphide-linked ring. It has important actions on the kidney, largely on its haemodynamics, and at other sites including the adrenal cortex and CNS. It has a short half-life in vivo and is rapidly inactivated when incubated with kidney microvillar membranes. Of the battery of peptidases present in that membrane, only one, endopeptidase-24.11, is responsible for initiating the attack, and this commences with hydrolysis of the Cys'-PheS bond within the ring. Hydrolysis at this and other points has been shown to inactivate the peptide and this information has pointed the way to the synthesis of resistant analogues.Atria1 natriuretic peptide; Membrane peptidase; Neuropeptide; Endopeptidase-24.11 DISCOVERY OF ATRIAL NATRIURETIC FACTORAtria1 natriuretic factor (ANF) comprises a family of peptides with powerful natriuretic, diuretic and hypotensive activities which are present in storage granules of atrial muscle. The existence of these granules and their resemblance to secretory granules of other cells were reported more than 20 years ago [1,2] Abbreviations: ANF, atria1 natriuretic factor; ANP, atrial natriuretic peptide (l-28) the prefixes h and r indicating human and rat; could be affected by changes in the intake of water and sodium [3] and that injections of extracts of atria or granules promoted diuresis and natriuresis [4] and by 1983 it was becoming clear that these activities resided in a group of related peptides (for review and nomenclature see [S]). Several low-M, peptides have been isolated from rat atria, e.g. atriopeptins I, II and III and cu-rat atria1 natriuretic peptide (cu-rANP), all of which possess a disulphide-linked loop of 17 amino acid residues, with short N-and C-terminal extensions. However, the major circulating form of ANF in the rat appears to be the 28-residue peptide [6,7] which is derived from a high-M,, 152-residue precursor, rat pre-pro ANP (see [5]). Human atria also release a 28-amino acid peptide @-human atrial natriuretic peptide, a-hANP; [8]; fig.1) which differs from a-rANP by only one residue, Met" for Ilei* [9]. REGULATION OF RELEASE OF ANPSeveral factors have been found to stimulate