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Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV-related hepatitis and cirrhosis.
Full text linkAbstract: Aim: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-alpha and c-myc.
Methods: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-alpha, IL-1 beta, TGF-alpha and c-myc in liver specimens was detected by semiquantitative comparative RT-PCR.
Results: TNF-alpha levels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1 beta was higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-alpha and staging (P=0.05) and between IL-1 beta levels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-alpha expression and HCV genotype (P=0.02).
Conclusion: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-alpha levels. As HCV-related liver damage progresses, TNF-alpha levels drop while IL-1 beta and c-myc levels increase, which may be relevant to liver carcinogenesis
Proliferazione epatocellulare ed apoptosi in relazione al danno ossidativo nelle epatopatie alcol-correlate
No full textNelle patologie alcol-correlate, la produzione di radicali liberi può svolgere un ruolo importante nella patogenesi del danno epatico ed influenzare il turnover cellulare. Lo scopo di questo studio è stato di correlare i livelli di perossidazione lipidica, delle difese anti-ossidanti e del metabolismo del ferro con i processi di citoproliferazione ed apoptosi riscontrati in pazienti con epatopatia alcolica, e di paragonarli con quelli ottenuti in pazienti con epatopatie virali.
Nei 55 pazienti studiati, suddivisi in 10 con epatopatia alcolica (EC), 34 con epatite cronica HCV-correlata (HCV) ed 11 con epatite cronica HBV-correlata (HBV) sono stati studiati i livelli di: ferritina sierica, ferro tissutale (assorbimento atomico), cisteina, glutatione ridotto/ossidato (HPLC), malondialdeide (fluorimetria); e, parallelamente, l'istologia con la proliferazione epatocellulare (anticorpo monoclonale Ki67) e l'indice apoptotico (ISEL).
I livelli di ferritina e di ferro non differiscono tra i pazienti con EC ed HCV, anche se entrambi risultano significativamente più elevati rispetto ai pazienti con HBV (p<0,05). La malondialdeide, e quindi la perossidazione lipidica, è significativamente più elevata nei pazienti con EC e con HCV rispetto a quelli con epatite cronica HBV (p<0,0001 e p<0,05) e correla con il ferro tissutale (r=0,597, p<0,0001) e la ferritina sierica (r=0,437, p<0,05). I livelli di glutatione sono significativamente inferiori nei pazienti con EC rispetto a quelli riscontrati in pazienti con HCV ed HBV (p<0,05), mentre la cisteina risulta più elevata (p<0,05). L'indice apoptotico è leggermente più basso nei pazienti con EC, con apoptosi più frequentemente evidenziabile nell'area centrolobulare, e meno epatociti proliferanti, sia complessivamente (p<0,02) che nelle due differenti aree. In conclusione, quindi, questo studio conferma che il consumo cronico di alcol:
induce danno perossidativo più rilevante, correlato con l'accumulo di ferro tissutale;
riduce le difese anti-ossidanti, abbassando la disponibilità di glutatione epatico;
induce un accumulo di cisteina, precursore/metabolita del glutatione a livello epatico, probabilmente per induzione della gGT;
correla con una meno evidente e differente distribuzione della proliferazione ed apoptosi rispetto a quanto riscontrato nel danno virale.
Questi risultati possono spiegare il diverso tipo di cirrosi che deriva dal danno epatico alcolico ed il più basso rischio di sviluppo di cancro
mTOR and LC3 Gene and Protein Expression in Chronic Liver Disease and in Primary and Secondary Human Liver Cancer
No full textEstrogens receptors and oxidative damage in the liver
No full textThere is considerable evidence that reactive oxygen species (ROS) have a causative role in chronic hepatic injury and cancer development via direct and indirect mechanisms. Estrogens produce free oxygen radicals through redox cycling and affect cell proliferation, also in the liver. We are presently involved in evaluating the possible relationship between estrogens receptor expression, type of receptor, oxidative DNA damage and c-myc in chronic liver disease. The data on DNA adducts, c-myc mRNA and variant estrogen receptor in patients with HCV- or HBV-related chronic liver disease are suggesting that those positive for variant liver estrogen receptor present higher genomic oxidative damage, as reflected in 8-OHdG levels. We are also observing that patients with chronic hepatitis and cirrhosis, when positive for variant estrogen receptor, present higher c-myc m-RNA expression, a factor reportedly associated with increased genomic instability, augmented cytoproliferation and carcinogenesis. Our own and other author's data are shedding new light on estrogen pathophysiology, liver damage and hepatic cancer
Fine-needle biopsy in focal liver lesions: the usefulness of a screening programme and the role of cytology and microhistology.
No full textWe evaluated the diagnostic usefulness of 244 ultrasound-guided fine-needle biopsies (FNB) in 226 patients with suspected liver malignancies, A malignancy was detected in 166 cases (73%) -145 hepatocellular carcinomas (HCC), 21 metastases; benign lesions were aspirated in 60 cases (27%). The sensitivity of FNB was 93%, with 100% specificity, In the FNB false-negative cirrhotic nodules, a final diagnosis of HCC was reached on repeating the biopsy 1-8 months later. When both cytological and microhistological examinations were performed, the positive correlation between the two techniques was 80%, with a slightly higher sensitivity for microhistology (93%). The malignancies diagnosed were potentially resectable in 26% of cases. We experienced 1 acute complication of FNB and 1 case of needle tract tumour seeding. These results confirm that FNB is useful in diagnosing malignant liver tumours, We believe that US-guided FNB is the first-choice invasive technique for assessing focal benign lesions and malignant tumors in the liver
Effects of iron deprivation and oral iron supplementation on DNA damage in a model of colitis in rats.
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