Effects of azithromycin on the expression of ATP binding cassette transporters in epithelial cells from the airways of cystic fibrosis patients.

Induction of ATP Binding Cassette (ABC) proteins involved in chloride transport has been proposed as a possible mechanism of the beneficial effects of azithromycin (AZM) in cystic fibrosis (CF) patients. This study focused on the effects of AZM on mRNA and protein expression of Multidrug Resistance-associated Protein 1 (MRP1) and Multidrug Resistance Protein 1 (MDR1) by real-time quantitative PCR, flow cytometry and gene reporter assays in two CF and two isogenic non-CF airway epithelial cell lines. We detected higher levels of MRP1 and lower levels of MDR1 mRNA in CF versus non-CF cells while both proteins were not differentially expressed. After AZM treatment we found modest differences in MRP1 and MDR1 mRNA expression while protein levels were unaffected. The ability of AZM to regulate MRP1 promoter transcriptional activity was excluded by gene reporter assays. Our data do not support the hypothesis of induction of ABC transporters by AZM.

Plasma nitrite/nitrate and erythropoietin levels in cross-country skiers during altitude training.

BACKGROUND: The aim of this study was to evaluate the effects of training at altitude on plasma nitrite/nitrate and erythropoietin levels since previously it has been reported an interaction of the NO/cGMP system in erythropoietin production. METHODS: Nine physically trained cross-country male skiers, usually living at 800-1200 m altitude, underwent 6 days of intensive training at a moderate altitude of 3100 m preceeded by 2 days of acclimatisation. Six team-managers, selected as controls, did not undergo any regular physical activity in the last 5 years and during the altitude period. Haematological parameters, erythropoietin and nitrite/nitrate were measured prior to reach the place at altitude, at the end of the period at moderate altitude and 7 days after returning at home. RESULTS: Haematocrit significantly increased in controls after 8 days at altitude. Erythropoietin levels significantly increased after the intensive altitude training only in trained subjects (13.1+/-1.7 vs 6.7+/-1.7 mU x ml-1, p<0.001). Nitrite/nitrate baseline values were significantly higher in trained subjects compared to untrained (49.9+/-17.9 vs 25.4+/-2.8 micromol x l(-1), p<0.01); the altitude period significantly increased nitrite/nitrate levels, in untrained subjects, to the same values observed in trained subjects under control conditions (47.0+/-10.3 micromol x l(-1)). CONCLUSIONS: In our experimental conditions we demonstrated the influence of hypoxia on Epo levels in athletes sustaining a short-term training and the role of a regular physical activity (partly independent from altitude hypoxia) on NO production.

Alcohol, smoking and papillomavirus infection as risk factors for esophageal squamous-cell papilloma and esophageal squamous-cell carcinoma in Italy.

Esophageal papilloma, an infrequent benign tumor, and esophageal squamous-cell carcinoma sometimes appear to be associated with human papillomavirus (HPV) infection, HPV being implicated in anogenital carcinogenesis. Our aim was to assess whether there is any epidemiological difference in terms of risk factors for papilloma and cancer. From 1989 to 1996, a total of 12,011 patients (53% male, median age 52.7 years) were submitted to esophagogastroduodenoscopy by our Digestive Endoscopy Service. The genome of HPV was sought by PCR using 2 different primer sets. Of the total, 42 subjects (0.35%), 50% male with a mean age of 45.1 years, were suffering from esophageal squamous-cell papilloma and 45 (0.37%), 91% male with a mean age of 63.0 years, from esophageal squamous-cell carcinoma. Of these patients, only 2 with papilloma were HPV(+). Compared with the general endoscopic population, patients with papilloma do not present significantly different characteristics (even in terms of frequency of esophagitis and hiatal hernia). Those with carcinoma differ significantly both from the general endoscopic population and from those with papilloma in that they are more often male (p < 0. 0001), older (p < 0.0001) and drinkers (p < 0.0001); they differ significantly only from the general population, but not from the papilloma patients, in smoking habits. Papilloma appears to be neither a lesion involving a risk of development into a malignancy nor a marker for any such risk. Environmental factors, such as alcohol and smoking, appear to play a decisive role in esophageal carcinogenesis in northern Italy.

Early detection of pancreatic cancer following the diagnosis of chronic pancreatitis.

AIM: To assess whether patients with misdiagnoses of chronic pancreatitis (CP), followed at an early stage by a diagnosis of pancreatic cancer (PCr), present different epidemiological characteristics from patients suffering either from CP alone or from CP with late degeneration to PCr. METHODS: We arbitrarily subdivided our patient series into three groups: (1) 12 CP who developed PCr within 4 years after onset of symptoms; (2) 12 CP developing PCr after the 4th year, and (3) 701 CP with no subsequent development of PCr. The variables studied were age, sex, drinking and smoking habits, tumor localization, and presence of intraductal calcifications and diabetes mellitus at the time of diagnosis of CP. RESULTS: There were no significant differences between CP and 'late' PCr in any of the study variables considered. As compared with the CP group, the 'early' PCr cases were older (58.7 vs. 40.7 years; p < 0.0001), with a lower proportion of males (58 vs. 88%; p < 0.01), smaller proportions of both smokers (42 vs. 88%; p < 0.0001) and subjects drinking more than 40 g of alcohol/day (42 vs. 86%; p < 0. 0001), and a greater incidence of non-insulin-dependent diabetics at the time of diagnosis of CP (25 vs. 3.7%; p < 0.012). As compared with the 'late' PCr group, the malignancies in the 'early' PCr cases were more often located in the head of the pancreas (100 vs. 50%; p < 0.01). Multivariate logistic regression analysis selected age over 50 (odds ratio OR 13.5, 95% confidence interval CI 2.79-65.5; p < 0. 001), smoking habits (OR 0.14, 95% CI 0.04-0.49; p < 0.002), and non-insulin-dependent diabetes (OR 5.91, 95% CI 1.20-29.1; p < 0. 028) as variables identifying subjects with 'early' PCr. CONCLUSIONS: A high suspicion of a pancreatic tumor is necessary when CP is diagnosed in a patient with atypical epidemiological characteristics for this condition, possibly female, aged over 50, who is not a smoker or drinker, and suffers from non-insulin-dependent diabetes.

Some properties of cytochrome b5 from liver microsomes of man, monkey, pig and chicken.

1. Cytochrome b(5) was released from liver microsomes of man, monkey, pig and chicken by incubation with a crude lipase preparation. 2. By using DEAE-cellulose chromatography, ammonium sulphate fractionation, Sephadex-gel filtration and a final gradient elution on DEAE-Sephadex A-50, cytochromes b(5) were obtained from the four species studied, all possessing similar spectral properties. 3. Stokes radii of the cytochromes were measured by gel filtration. 4. N-Terminal amino acids for the different cytochromes were serine for man and monkey, alanine for pig and glycine for chicken. 5. Amino acid analyses of the cytochromes are presented. 6. Peptide ;fingerprint' patterns of tryptic digests of the different cytochromes are discussed and clearly show increasing similarity for more closely related species.