Vaccination of mice for research purpose: alum is as effective as and safer than complete Freund adjuvant.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. Glomerulonephritis (GLN) is one of the major causes of morbidity and mortality in SLE. It has recently been demonstrated that adjuvants of vaccines could cause the so called ASIA syndrome. The study aimed to assess the effects of Complete Freund's Adjuvant (CFA) vs alum injections in NZB/NZWF1 mice. Mice (n=10 each group) were injected with a total volume of 200 µL of: CFA in PBS (group 1), alum in PBS (group 2), PBS (group 3) as controls, PTX3/CFA (group 4), PTX3/alum (group 5), 3 times, 3 weeks apart /given in each injection, three weeks apart from ten weeks of age. Urine samples were collected weekly to evaluate proteinuria. Blood samples were collected before every injection, at 21 weeks of age, and at death to evaluate levels of anti-PTX3 and anti-dsDNA. Proteinuria free survival and survival rates were analyzed by the Kaplan-Meier method using Mantel-Cox's test for comparisons. CFA-treated mice developed both anti-dsDNA antibodies and proteinuria earlier and at higher levels than alumtreated and PBS-injected mice, starting from 13 weeks of age. Proteinuria free survival rates (proteinuria ≥ 300 mg/dL) and survival rates were lower in CFA-treated mice than those treated with alum or injected with PBS (P<0.001 for all). No difference was observed between the alum-treated group and PBS-injected mice. Notably, groups 4 and 5, immunized with PTX3, developed anti-PTX3 antibodies and no significant difference was observed. Alum seems to be as effective as and safer than CFA as adjuvant, since it did not affect disease progression in immunized NZB/NZWF1 mice.

Effects of glucocorticoids in ventilated piglets with severe pneumonia.

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown. The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia. In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (10(6) cfu x mL(-1)) was bronchoscopically inoculated. The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue. In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

Aprotinin efficacy on intraoperative bleeding and transfusion requirements in orthotopic liver transplantation.

BACKGROUND: Bleeding complications frequently occur during orthotopic liver transplantation (OLT), particularly in patients with liver cirrhosis. Enhanced fibrinolytic activity in plasma was seen to play a key role in the development of the hemostatic disorder and of hemorrhages. Aprotinin, a serine protease inhibitor, has been used in the prevention and/or treatment of hyperfibrinolytic states. STUDY DESIGN AND METHODS: In the present study, the effect of aprotinin on bleeding complications and transfusion requirements was investigated in OLT patients with liver cirrhosis. Seven consecutive cirrhotic patients undergoing OLT were infused with aprotinin following an original protocol (1,000,000-KIU intravenous loading dose plus 500,000 kallikrein-inhibitory units per hour until skin closure). Seven previous cirrhotic OLT patients not receiving aprotinin were used as controls. RESULTS: In the treated group, a significant decrease in the number of transfused units of packed red cells (48.7%, p < 0.01), fresh-frozen plasma (24.4%, p < 0.05), platelets (35.9%, p < 0.01), and autologous blood (55.2%, p < 0.01) was observed as compared with the control group. Moreover, the mean length of operation was significantly shorter in the aprotinin-infused patients than in untreated patients (8.3 +/- 1.2 vs. 10.1 +/- 1.8 hours, respectively; p < 0.01)). In the aprotinin-treated group, the antifibrinolytic efficacy was confirmed by the lack of increase in D-dimer levels and decrease of fibrinogen in plasma; on the contrary, these changes were always seen in the group not receiving aprotinin. CONCLUSION: Infusion of aprotinin during OLT in cirrhotic patients can be recommended for the prevention of hyperfibrinolysis-triggered bleeding, thus reducing transfusion requirements. A possible protective effect on the primary nonfunction of the grafted liver is suggested.

[The use of intra-arterial lipiodol in assessing hepatocarcinomas treated by percutaneous alcoholization. The initial experience]. / Uso del lipiodol intra-arterioso nella valutazione degli epatocarcinomi trattati con alcolizzazione percutanea. Prime esperienze.

Eight patients with inoperable hepatocellular carcinoma were treated by means of percutaneous alcoholization of the malignancy (11 nodular lesions less than 5 cm O). Upon treatment completion they were all given intraarterial injection of lipiodol, which was followed, a week later, by a CT scan. At angiography, during the parenchymal phase, 7 of 11 nodules appeared as avascular areas, whereas in the remaining 4 cases an intense parenchymal effect was seen within the previously treated areas. Lipiodol CT scans revealed intense uptake of oily material in the 4 hypervascular lesions as well as in 1 of those with avascular appearance. In 4 lesions, pathology of bioptic specimens obtained from the areas with contrast pooling was consistent with the persistence of viable neoplastic tissue. In these patients alcoholization had therefore to be continued. Lipiodol accumulation within previously treated nodules has proved to be related to the presence of residual neoplasm. Moreover, in 2 cases, focal retention of lipiodol was very helpful for biopsy under CT guidance. According to our experience, we believe lipiodol administration followed by CT to be very useful in evaluating and staging HCCs. We nevertheless believe that the procedure should be performed only after alcoholization has been completed: this would inform us of treatment effectiveness and subsequently enable us to decide whether treatment can be discontinued.