Effects of melatonin administration to rats with glycerol-induced acute renal failure

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.     

Decrease of carbohydrate in membrane glycoproteins during human erythrocyte ageing in vivo

Membrane glycoproteins from young human erythrocytes and erythrocytes aged in vivo were fractionated by gel filtraton. Three major groups of glycoproteins were obtained.The neutral hexoses and sialic acid contents of each group of glycoproteins from the old cells were found to be significantly reduced by comparison to the values found in the glycoproteins of the young cells. Thus, the previously observed decrease in neutral hexoses and in sialic acid contents of the full erythrocyte membrane during in vivo ageing does not affect only one particular group of glycoproteins but each of the groups of glycoproteins tested, including the major glycoproteins of the erythrocyte membrane, that is to say glycophorins.It is shown in addition, that the previously observed decrease per cell of the surface galactose and N-acetylgalactosamine residues of the ageing erythrocyte affect several groups of membrne glycoproteins including band 3, PAS-1, PAS-4 and PAS-3.The physiological significance of these experimental data is discussed.     

Prevalence of hepatitis C virus antibodies and hepatitis C virus-RNA in an urban population.

Several studies had been carried out on anti-hepatitis C virus (HCV) prevalence in populations with blood exposure risks and in blood donors. New tests are now available which allow the investigation to extend to other parameters such as antibody type and HCV-RNA. In this study the prevalence of anti-HCV c100-3 and the associated epidemiological, clinical, and virological markers were evaluated in subjects from an urban population located in central Italy. In positive cases the time persistence of HCV-RNA and anti-HCV antibody pattern was studied. For this purpose, sera from 1,484 randomly sampled individuals, aged 30-69 years, collected in 1985 and stored at -80 degrees C were retrospectively tested. The prevalence was 0.87% (i.e., 13 anti-HCV c100-3 positive cases). A significant association was observed with raised alanine transaminase (ALT) levels (P less than 0.001). Paired serum samples from 11 out of the 13 subjects collected in 1985 and 1991 were tested by nested polymerase chain reaction (PCR) using primers from the 5' non-coding region and by 4-RIBA. Concordant RIBA patterns between 1985 and 1991 were observed in the majority of positive paired sera (7/9) as well as for HCV-RNA (6/9). HCV-RNA was present in sera simultaneously positive to both types of antibody or to anti-c100-3 or anti-c22 alone. A wide spectrum of viral and antibody patterns in anti-HCV c100-3 positive sera was observed in this urban population and persisted for at least 6 years.     

Helicobacter pylori infection, plasma ammonia levels, and psychometric testing in cirrhotic patients

OBJECTIVE: The role of Helicobacter pylori (H. pylori) infection as a cause of hepatic encephalopathy is still debated. This study focused on the relationship between H. pylori, plasma ammonia levels, and intellectual function in cirrhotic patients. METHODS: Forty-seven cirrhotics with latent or mild hepatic encephalopathy were enrolled in the study, upon H. pylori assessment at endoscopy. Plasma ammonia level determinations and psychometric testing were performed at entry in all patients. Patients with H. pylori infection received a 2-wk standard dual therapy and bacterial eradication was assessed at endoscopy 6-8 wk later. On this occasion, plasma ammonia levels and psychometric assessments were repeated. Patients without H. pylori infection at entry were also studied after 6-8 wk for ammonia level assessment and psychometric testing, as a control group. Patients receiving lactulose therapy and those without therapy were grouped separately for statistical analysis. RESULTS: Among 21 patients without lactulose therapy (group A), basal plasma ammonia levels and psychometric testing scores did not significantly differ between 13 infected and eight uninfected patients. Similarly, among 26 patients undergoing lactulose therapy (group B), basal plasma ammonia concentration and psychometric testing scores did not significantly differ between 13 infected and 13 uninfected patients. Moreover, in group B, both the prevalence of previous overt hepatic encephalopathy episodes and the mean daily dose of lactulose therapy were similar between infected and uninfected patients. In addition, no significant reduction in the plasma ammonia concentrations and in psychometric testing scores emerged in both groups A and B after bacterial eradication. CONCLUSIONS: This study failed to find a relationship between H. pylori, plasma ammonia levels, and psychometric testing scores in cirrhotic patients with latent or mild hepatic encephalopathy.     

Increased energy expenditure in cirrhotic patients with hepatocellular carcinoma.

Basal energy expenditure was measured by indirect calorimetry in 12 cirrhotic patients with hepatocellular carcinoma. Values were compared to those observed in 12 cirrhotic patients without hepatocellular carcinoma but with similar nutrition status. Energy expenditure was also predicted in each patient by the Harris-Benedict equation. Basal energy expenditure, whether expressed as kilocalorie per day or corrected for kilogram body weight or for kilogram fat-free mass, was found increased in cirrhotic patients with hepatocellular carcinoma. These patients expended an average of 250 kcal/day more than was expected given their body size. The highest values were observed in the patients who experienced a recent significant weight loss. Our study demonstrates that the presence of hepatocellular carcinoma on liver cirrhosis increases the metabolic rate of patients. This factor could contribute to progressive malnutrition in patients with hepatocellular carcinoma and should be taken into consideration when these patients are given nutritional support.     

Hyperthermic antiblastic perfusion in the treatment of cancer of the extremities

From February 1982 to December 1983, 42 patients affected by neoplasms of the limbs were treated at the Istituto Nazionale Tumori of Milan by hyperthermic antiblastic perfusion in extracorporeal circulation at the temperature of 40-41 degrees C for 1 h. Thirty-two were affected by melanoma, 4 by osteogenic sarcoma, 2 by squamous-cell carcinoma, 1 by liposarcoma, 1 by hemangiopericytoma, 1 by clear-cell sarcoma and 1 by Kaposis's sarcoma. As regards the immediate response, a complete plus partial remission rate of 88% without any major complication was obtained. The follow-up period is too short for any considerations about overall survival. However, because of these good clinical results we consider this method able to locally control the evolution of neoplasms of the extremities, allowing in many cases a limb salvage.     

Melanoma inhibits macrophage activation by suppressing toll-like receptor 4 signaling

BACKGROUND: Activated macrophages defend against tumors by secreting cytokines to recruit secondary immune cells, presenting antigen to T cells, and by direct tumor cytotoxicity. Peritoneal macrophages harvested from melanoma-bearing mice are less cytotoxic to melanoma cells, and produce less superoxide, nitric oxide, and tumor necrosis factor-alpha (TNF-alpha) than those from nontumor-bearing mice. Similar impairment of macrophage activation occurs in vitro using media harvested from cultured melanoma cells. Stimulation of Toll-like receptor 4 (TLR-4) activates macrophages and results in the release of TNF-alpha. We hypothesized that melanoma inhibits macrophage activation by suppressing TLR-4 signaling. STUDY DESIGN: Melanoma conditioned media (MCM) was generated from B16 melanoma cells. Peritoneal macrophages from TLR-4 competent or TLR-4 incompetent mice were exposed to control or MCM for 24 hours; then stimulated with lipopolysaccharide. TNF-alpha secretion, TNF-alpha mRNA production, nuclear factor-kappaB (NF-kappaB) activation, and TLR-4 surface expression were measured. RESULTS: Peritoneal macrophages exposed to MCM produced considerably less TNF-alpha in response to stimulus than controls (691 pg/mL versus 2,066 pg/mL, p < 0.001). TNF-alpha production by TLR-4 incompetent macrophages was not affected by MCM (454 pg/mL versus 480 pg/mL). Stimulated TNF-alpha mRNA and activated NF-kappaB were decreased in MCM treated C57BL/6 macrophages (by 38% and 33%, respectively). TLR-4 surface expression, however, was not decreased by exposure to MCM. CONCLUSIONS: Melanoma inhibits macrophage activation by suppressing TLR-4 signaling downstream of the TLR-4 receptor.     

Carotid endarterectomy: survival rates of 227 patients.

From March 1963 to March 1974, 227 patients with carotid stenosis underwent unilateral or bilateral carotid endarterectomy at l'H?pital de l'Enfant-Jésus in Québec. Survival during the first 7 years after operation was analysed by life-table methods based on full intervals. The observed probability of death in this group was significantly higher than the probability expected in the general population, by 6.8% in the 1st year and 3.9% in the 2nd year. In the next 3 years the differences were much smaller (0.5, 0.9 and 1.4%). The major causes of death were myocardial infarction and stroke. Women fared somewhat better than men after the 1st year of follow-up. Unexpectedly, patients who underwent unilateral endarterectomy had lower survival rates in each of the first 5 years after operation than patients who underwent staged bilateral operations, whether survival was measured from the date of the first or the second operation.