Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Somatostatin modulates both cyclooxygenase-2 expression and proliferation in human colon cancer cells

introduction. Among cyclooxygenase isoforms, COX-1 and COX-2, the latter is sigmficantly implicated in colorectal tumongenesis and cell proliferation. By contrast, somatostatin (SST) may negatively modulate colon cancer growth. This study investigates the effects of SST on COX-2 expression and proliferation in colon cancer cells, either under basal conditions or upon stimulation with gastrin-17 (G-17). Methods. Experiments were performed on human colon adenocarcinoma cell line HT29. Reverse transcription-polymerase chain reaction (RTPCR) was used to assess mRNA expression of gastrin CCK-2 receptors, SST receptors (SSTR from 1 to 5), COX-1 and COX-2. Phosphorylation of MAP-kinase as well as COX-1 and COX-2 protein expression were determined by westem blot analysis. Cell proliferative activity was estimated by direct cell count. Results. RT-PCR revealed the expression of CCK-2 receptors, SSTR-3, SSTR-4, SSTR-5, COX-1 and COX-2 transcripts under basal conditions. COX-1 and COX-2 protein expression was confirmed by western blot. SST (0.1-100 nM) significantly decreased the basal growth rate in HT29 cells (-41.3% at 1 riM), and concentration-dependently inhibited the proliferative effects exerted by G-17 0.1 ~M (-55.2% at 1 nM). Western blot assay showed that COX-2, but not COX-l, expression was significantly enhanced by G-17. This stimulant action was prevented upon incubation of HT29 cells with PD-98059 (1-100 nM) or wortmannin (10-50 p,M), acting as inhihitors of MAP-kinase and PI3-kinase, respectively. SST reduced COX-2, but not COX-I, expression under basal conditions as well as after stimulation with G-17. Likewise, G-17 exerted a stimulant effect on MAP-kinase phosphorylation, which was fully counteracted by SST in a concentrationdependent manner. Conclusions. 1) SST can downregulate the expression of COX-2 in colon cancer cells, and such inhibitory effect may account for the antiproliferative action of this gastrointestinal peptide; 2) in colon cancer cells COX-2 expression is positively regulated by mitogenic transduction signals and this mechanism can be counteracted by inhibitory pathways induced by SST

DISTRIBUTION AND FATE OF ALPHA-NAPHTHYL-ISOTHIOCYANATE (ANIT) IN ORGANS AND BODY-FLUIDS OF RAT

alpha-Naphthyl-isothiocyanate (ANIT) is a well known toxic substance which induces characteristic hepatic lesions. Its distribution in some organs and body fluids was investigated by using spectrophotometry, gas-chromatography and thin-layer chromatography. The results indicate that ANIT concentrates in the liver, kidneys and blood but not in the brain, urine and bile. Another five ANIT-like substances have also been examined, but no trace of them has been found in these organs and body fluids. The authors suppose that ANIT is metabolized to an unknown metabolite which is responsible for the toxic action of ANIT. None of the ANIT-like substances examined by us can be indentified with this metabolite

Conformational effects on the activity of drugs. 10. Synthesis, conformation, and pharmacological properties of 1-(2,5-dimethoxyphenyl)-2-aminoethanols and their morpholine analogues

1-(2,5-Dimethoxyphenyl)-2-aminoethanols I (R = H, Me, or CHMe2) and their morpholine analogs II (R = H, Me, or CHMe2) were synthesized and tested for agonistic and antagonistic adrenergic activity. The preferred conformation of the amino alcs. and their cyclic analogs was studied by NMR and IR. I (R = H) oxalate salt [83436-86-6] and I (R = Me)-HCl [63991-17-3] had both α-stimulating and -blocking activity in the rat vas deferens, whereas I (R = CHMe2)-HCl [83436-85-5] and II oxalates had only α-blocking activity. The only β-adrenergic activity obsd. was shown by I (R = CHMe)-HCl salt, which had a moderate blocking effect in the isolated guinea pig atria. Apparently, the changes in the pharmacol. activity involved in the transformation of the adrenergic drugs into their morpholine analogs are influenced more by characteristics of the arom. moiety than by the ethanolamine or propanolamine structure of the drug