1 The effects of selective inhibitors of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and guanosine 3': 5'-cyclic monophosphate (cyclic GMP) phosphodiesterases (PDEs) were investigated on PDEs isolated from the rat aorta and on relaxation of noradrenaline (1 pM) precontracted rat aortic rings, with and without functional endothelium. 2 Four PDE forms were isolated by DEAE-sephacel chromatography from endothelium-denuded rat aorta: a calmodulin-activated PDE (PDE I) which hydrolyzed preferentially cyclic GMP, two cyclic AMP PDEs (PDE III and PDE IV) and one cyclic GMP-specific PDE (PDE V). The latter was selectively and potently inhibited by zaprinast. The two cyclic AMP PDEs were discriminated by specific inhibitors: one was inhibited by cyclic GMP (PDE III) and by new cardiotonic agents (milrinone, CI 930, LY 195115 and SK&F 94120); the other was inhibited by denbufylline and rolipram (PDE IV). None of these drugs significantly inhibited PDE I. 3 The PDE III inhibitors caused endothelium-independent relaxations of rat aortic rings with the following EC50 values (aM concentration producing 50% relaxation) : LY 195115: 3.4, milrinone: 5.7, CI 930; 7.8, SK&F 94120: 14.7. Neither N0-monomethyl-L-arginine (L-NMMA, 300pM), an inhibitor of the Larginine-NO pathway, nor L-arginine (1 mM) modified the effect of PDE III inhibitors. However, methylene blue (1OpM) an inhibitor of soluble guanylate cyclase abolished relaxation induced by PDE III inhibitors except in the case of compound CI 930. 4 The specific PDE IV and PDE V inhibitors both produced endothelium-dependent relaxations which were inhibited by L-NMMA and by methylene blue (10piM). In the presence of L-NMMA, relaxation was restored by subsequent addition of L-arginine. 5 The relaxant effects of denbufylline and rolipram were studied in the presence of drugs stimulating either adenylate cyclase (forskolin and isoprenaline) or soluble guanylate cyclase (sodium nitroprusside, SNP), or inhibiting PDE III (milrinone). In endothelium-denuded rings, a relaxing effect of both denbufylline and rolipram was found in the presence of milrinone (EC5o values 1.7 and 12puM, respectively) or SNP (EC50 values 12.3 and 124pM, respectively), but not in the presence of forskolin or isoprenaline. However in the presence of functional endothelium, relaxations produced by PDE IV inhibitors were significantly potentiated by forskolin, isoprenaline, milrinone and SNP (respective EC50 values for denbufylline: 2, 2, 0.4 and 0.7 JM and for rolipram: 7, 13, 7 and 1.2 pM). 6 These results indicate that the relaxant effects of inhibitors of the cyclic AMP-specific PDE IV are markedly enhanced by cyclic GMP elevating agents and by the PDE III inhibitor milrinone. They support the hypothesis that cyclic GMP enhances cyclic AMP-mediated relaxation, possibly through the inhibition of the cyclic GMP-inhibited PDE III.

Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n ‫؍‬ 1,131), Nigeria (n ‫؍‬ 974), Chad (n ‫؍‬ 50), and the Central African Republic (n ‫؍‬ 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa.

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BackgroundHepatitis B virus (HBV) is the major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The global epidemiological scenario of HBV infection has been changing rapidly over the last two decades due to an effective immunization programme initiated by the World Health Organization. The objective of this study is to estimate the prevalence of HBV in apparently healthy young people and to identify the risk factors of transmission of the HBV among this population in Bangui.MethodsDried blood Spots from 801 adolescent high school and young adult university students were prepared by spotting a drop of whole blood (4 spots) from the same fingerprick onto Whatman filter paper. A blood sample aliquot eluted from DBS was then processed with commercial ELISA tests (Abbott Murex, Dartfort, UK) to detect HBsAg antigen, Anti-HBc and Anti-HBs antibodies).ResultsThe overall prevalence was 42.3% for antibody to hepatitis B core antigen, 15.5% for HBsAg of which 1.3% of HBsAg alone. HBV familial antecedents, sexual activity and socioeconomic conditions were the main risk factors of HBV infection encountered in the adolescents and young adults.ConclusionThese results show for the first time the high prevalence of HBV in apparently healthy young people in Bangui. This high prevalence is age- and sex-independent. Transmission risk factors were a familial antecedent of HBV, no utilisation of condoms and public scholarship. To lower HBV prevalence, an adequate program of active screening and vaccination for adolescents and young adults should be implemented, along with a universal immunization program.