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The viral variability of 5 hepatitis C virus (HCV)-infected immunocompromised patients was analyzed and compared with that in isolates from immunocompetent subjects. The patients were followed longitudinally with regard to changes in hypervariable region 1 (HVR1) of HCV using a direct DNA sequencing approach. For the immunocompromised patients, viral nucleotide sequence variability was markedly lower than in immunocompetent HCV-positive patients. For 1 agammaglobulinemic patient and 1 AIDS patient, no variation in the major amino acid sequence of HCV HVR1 could be observed, while another agammaglobulinemic patient exhibited transient variations and amino acid substitutions despite the lack of functioning humoral immune response. The study supports the general hypothesis of humoral immune selection as the main force of sequence variation in the HVR1 region but suggests that other selection mechanisms may contribute to modulation of the composition of the viral population.

The influence of phenazone on the production of prostacyclin and thromboxane in human umbilical arteries was investigated by in vitro perfusion. With perfusate concentrations ranging from 10(-7) to 10(-4) M a decrease in the formation of both prostanoids was observed. The inhibitory effect of phenazone on prostanoid formation was found to be equal to that of indomethacin.

A. Mangia1, O. Dalgard2, N. Minerva3, H. Verbaan4, G. Scotto5, D. Bacca6, E. Agostinacchio7, K. Bjoro8, V. Carretta9, V. Piazzolla1, R. Cozzolongo10, M. Romano11, L. Mottola1, A. Andriulli12. 1Liver Unit, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy; 2Medical Department, Aker University Hospital, Oslo, Norway; 3Medical Department, Hospital, Canosa, Italy; 4Department of Surgery, Division of Gastroenterology and Hepatology, University Hospital, Malmoe, Sweden; 5Infectious Diseases Department, University Hospital, Foggia, 6Medical Department, Hospital, Casarano, 7Medical Department, ‘Santa Rita’ Hospital, Bari, Italy; 8Medical Department, RiksHospital, Oslo, Norway; 9Medical Department, Hospital, Venosa, 10Gastroenterology Department, IRCCS ‘S. De Bellis’, Castellana Grotte, 11Medical Department, ‘S. Pertini’ Hospital, Roma, 12Gastroenterology Department, IRCCS ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy E-mail: a.mangia@tin.it

Background/Aim: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. Methods: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21–70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. Results: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 µg/L vs. 75 µg/L P

Vascular effects of a thromboxane A2 mimetic, U46619, and prostacyclin on human umbilical arteries have been investigated by in vitro perfusions. Administration of U46619 invariably induced vasoconstrictory responses which were found to be dose-dependent and consistently stronger than those observed with other prostaglandins (e.g. PGF2 alpha and PGE2). Infusion of prostacyclin alone did not lead to significant alterations in the arterial perfusion pressure. However, when prostacyclin was introduced after a constriction with U46619 had been established, a transient pressure decrease was observed. When both drugs were introduced simultaneously, the U46619 response was suppressed. This suppression was partial and dependent on the PGI2 concentration.

Four major prostanoids (6-keto-PGF1 alpha, PGE2, PGF2 alpha and TXB2) were measured by specific radioimmunoassays in the outputs from human umbilical vessels perfused in vitro. As evaluated by scanning electron microscopy (SEM) only few blood platelets were attached to the vessel wall. After an initial flush with decreasing concentrations of all four prostanoids, a stable stage was reached, lasting for 4-5 hours. During this stage the production could be inhibited by indomethacin and only slightly stimulated with arachidonic acid. The TXA2 synthetase inhibitor UK 38485 depressed the TXB2 production, while only slightly affecting the other three prostanoids at very high concentrations. The arteries produced relatively more 6-keto-PGF1 alpha than did the vein.

The nutritional status of 33 consecutively admitted patients with anorexia nervosa (AN), was evaluated by anthropometric and biochemical methods. Mean weight loss was 30%, i.e., 17 kg body mass. Both mean triceps skin fold (TSF) and arm muscle circumference (AMC) were below the 5th percentile which is an indication of severe malnutrition. Mean creatinine height index (CHI) was 55% of the reference value which is also below the lower limit of the normal range. Serum transferrin was significantly reduced (p

Prostanoid formation in human umbilical vessels perfused in vitro was assessed at different oxygen tensions. At an atmosphere of 5% oxygen the production rate of prostacyclin (measured as 6-keto-PGF1α) was higher, while those of thromboxane A2 (measured as TXB2), PGE2 and PGF2α were lower than with 20%, 50% and 95% oxygen. The stimulatory effect of angiotensin II on prostanoid production was found to be independent on the prevailing oxygen tension. Vascular formation of prostanoids thus seems to be at least partially affected by the ambient oxygen tension. Though altered oxygen tension does not seen to affect angiotensin induced prostanoid formation, the action of other vasoactive agents influencing vascular formation of prostanoids may respond differently to hypoxia or hyperoxia.

A method was developed for the assessment of in vitro perfusion of the umbilical cord arteries. A perfusion pressure of 60-80 mmHg gave flow rates ranging from 30 to 40 ml/min per artery. Serotonin, PGF2 alpha and PGE2 were added to the perfusate and tested for vasoactivity. All substances induced a dose-dependent vasoconstriction. Serotonin proved to be the most potent vasoconstrictor. The minimum dose required to induce visible pressure responses was 10(-9) - 10(-8) M of serotonin and 10(-7) M of PGF2 alpha and PGE2. When adding methysergide to the perfusate, the serotonin response was abolished, while the effects of the prostanoids remained unaltered.

Effects of serotonin, prostaglandin E2, prostaglandin F2 alpha, U 46619 (a thromboxane A2 mimetic) and angiotensin I and II on the perfusion pressure were studied on vessel segments from human umbilical arteries, placental arteries and the umbilical vein during in vitro perfusions. All drugs were found to induce vasoconstriction. Serotonin displayed strong vasoconstrictor potencies in all vessel segments, whereas the responsiveness to the other autacoids differed greatly in the various segments. In the umbilical artery prostanoids were most potent in the juxtafetal segment, whereas angiotensin I and II displayed greatest effects in the juxtaplacental segment. The results lend additional support to the concept that angiotensins and prostanoids are of importance in the regulation of fetal extracorporeal blood flow.

Pseudomonas aeruginosa bacteria adhere to human epitheloid (HEp-2) cells in culture. Under normal atmospheric conditions (1 ATA), this adhesion increased significantly when the temperature rose from 22 to 37 degrees C. Under hyperbaric atmosphere (= air, 7 ATA) conditions, a similar, significant enhancement of bacterial adhesion to the cells was noted when the temperature rose. If the temperature was kept stable at 22 or 37 degrees C and the pressure was increased from 1 to 7 ATA, a pressure-induced enhancement was observed. This was statistically significant, at both temperature levels. Temperature-induced or -stimulated adhesion may help to explain some outbreaks of P. aeruginosa infections, for instance in whirlpools. The enhancement of this phenomenon under hyperbaric atmosphere conditions could have some relevance to recurrent P. aeruginosa otitis externa, a most common nuisance among professional divers.