Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks.

Monensin, a well known ionophore antibiotic, may cause severe damage in neuronal cells by altering Na+/K+-ATPase and Ca2+-ATPase. We investigated whether IRFI-042, a synthetic analogue of vitamin E, may block lipid peroxidation in neuronal cells and protect against monensin neurotoxicity in chicks. Monensin toxicity was induced in chicks by once-daily administration (150 mg/kg by oral gavages), for 8 days. Sham animals received a saline solution and were used as controls. All animals were randomized to receive either IRFI-042 (20 mg/kg) or its vehicle. Survival rate, brain lipid peroxidation, mRNA for neuronal and inducible nitric oxide synthases (nNOS and iNOS) and brain histological evaluations, including immunohistochemical expression of nNOS and iNOS were performed. Monensin administration decreased survival rate, induced behavioural changes, increased brain lipid peroxidation, reduced brain nNOS mRNA and immunostaining and enhanced iNOS mRNA and immunostaining in the brain in chicks. IRFI-042 significantly improved the survival rate and counteracted monensin-induced changes in chick brains. Our data suggest that monensin is responsible of neurotoxicity in chicks by inducing oxidative stress/lipid peroxidation and that IRFI-042 might represent a useful pharmacological approach to protect against the neuronal damage induced by this monovalent carboxylic ionophorous polyether antibiotic.

Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol.

BACKGROUND AND PURPOSE: Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis. EXPERIMENTAL APPROACH: Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. CONCLUSIONS AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

Ultrasonography in diagnosis and evaluation of fibrocystic liver diseases: two case reports.

This paper describes 2 cases of a rare biliary cystic disease. A patient with Caroli's disease and another with bile duct swelling that were initially diagnosed by ultrasound and power color Doppler. Diagnosis was later confirmed by additional instrumental examinations. The first case was totally asymptomatic and only identified by chance, while the second was symptomatic and determined severe pain and dyspepsia. In both pathologies US B mode imaging and power color Doppler examination revealed the characteristic lesions of the intrahepatic biliary tree diseases and ruled out their vascular nature and communication with the portal and arterial tree.

Perihepatic lymphadenopathy in chronic hepatitis C: a complementary diagnostic element?

BACKGROUND AND AIMS: The authors searched for perihepatic lymph nodes during ultrasonography performed for other symptoms in 1222 Sicilian outpatients in order to assess the incidence and possible significance of the association of perihepatic lymph nodes and chronic hepatitis C. METHOD: One or two lymph nodes were observed in 184/1222 patients, and 142 of these 184 were anti-hepatitis C virus (HCV) positive. RESULTS: Our results confirmed a very high incidence of perihepatic lymphadenopathy during chronic hepatitis. The concomitant presence of HCV virus and perihepatic lymph nodes may confirm the marked lymphotropism of this virus. CONCLUSION: As anti-HCV positivity is frequent in asymptomatic subjects with normal alanine aminotransferase concentrations, the authors believe that searching for sentinel perihepatic lymph nodes during abdominal ultrasonography could be recommended in routine diagnostic screening for HCV infection. Any perihepatic lymph nodes detected by this method could pinpoint subjects for whom more specific examinations are required, especially in areas where the virus is particularly endemic.

Association of alpha-interferon and acetyl cysteine in patients with chronic C hepatitis.

BACKGROUND: Numerous experimental findings have underlined the relationships between liver damage and production of oxygen-derived free radicals during inflammation. In chronic hepatitis C liver disease this damage may be attributed to altered oxide-reductive balance and glutathione (GSH) depletion. Moreover, it may be linked to chronic inflammation provoked by the replicative activity of the hepatitis C virus and its relationships with immune system cells. Our aim was to assess the effects of combined IFN + NAC treatment to compare the effects of interferon alpha-n1 associated with N-acetyl cysteine treatment with the results observed using interferon therapy alone. EXPERIMENTAL DESIGN: prospective randomised study. SETTING: Ambulatory and hospitalised care. PATIENTS: 77 selected patients affected by chronic C hepatitis. INTERVENTIONS: our patients were investigated by laboratory tests (ALT values, RIBA test, HCV-RNA, oxide-reductive balance), liver biopsy and liver US. The recruited subjects were treated with interferon and N-acetyl cysteine or with interferon alone. RESULTS: Our findings confirmed the presence of oxidative stress in patients with chronic hepatitis C and showed earlier relapse in patients treated with interferon alone. The difference between the results in patients treated with interferon and N-acetyl cysteine and those on interferon alone was significant. CONCLUSIONS: The good results and absence of side effects in patients treated with interferon + N-acetyl cysteine recommend wider use of this association.

[A case of deep vein thrombosis]. / Un caso di trombosi venosa profonda.

The case of a woman admitted to hospital various times because of the onset of a mantle-like oedematous syndrome is reported. Observations revealed a narrowing at the level of the internal jugular and right subclavian veins with total obliteration of the right anonymous vein caused by previous thrombosis induced by intravenous implantation of a pace-maker.