Dexrazoxane-a promising antidote in the treatment of accidental extravasation of anthracyclines.

Accidental extravasation of chemotherapy containing anthracycline often causes mutilating complications as a result of extensive tissue necrosis. Treatment therefore consists of extensive surgical debridement. We present the case of a 41-year-old woman with breast cancer who experienced extravasation of epirubicin. She was treated with an intravenous infusion of dexrazoxane for three successive days and recovered without surgical treatment and only slightly dysaesthesia in the surrounding tissue. Although infusion of dexrazoxane for this indication is still experimental we consider it a promising treatment for patients who have accidental extravasation of anthracyclines.     

Extracellular and intracellular factors influencing gene transfection mediated by 1,4-dihydropyridine amphiphiles

Double-charged 1,4-dihydropyridine (1,4-DHP) amphiphiles have been shown to condense DNA and efficiently transfect it into cells in vitro [Hyvönen et al., Biochim. Biophys. Acta 1509 (2000) 451]. Alkyl chain length and buffering capacity at endosomal pH range (5.0–7.4) affected complexation and transfection activity. In this study we examined how those chemical modifications of amphiphile–DNA complexes (amphiplexes) affect their interactions with extracellular polyanions (glycosaminoglycans, albumin) and lipid bilayers, their cellular uptake and intracellular distribution. To evaluate cellular uptake, CV1-P cells were incubated with labeled DNA–amphiphile complexes and analyzed by flow cytometry. Confocal laser fluorescence microscopy was used to investigate the intracellular distribution of amphiplexes. The results showed that biophysical properties of compounds can be changed by slight structural modifications. These factors determine the intracellular kinetics and transfection efficacy of the compounds. Some extracellular glycosaminoglycans and serum interfere with 1,4-DHP-amphiphile-mediated transfection by destabilizing the amphiplexes. Neither high cellular uptake, membrane destabilizing activity nor buffering capacity alone is adequate for high transfection efficacy. The activity results from complex interplay of various factors that determine intracellular kinetics and, consequently, transfection.     

Lack of immune response to methyl methacrylate in lymphocyte cultures

To analyze whether or not methyl methacrylate is immunologically inert, peripheral blood mononuclear cells were cultured with finely pulverized methyl methacrylate. Phytohemagglutinin (PHA) lectin, purified protein derivate of tuberculin (PPD) antigen, and culture medium alone were used as positive and negative controls. Lymphocyte kinetics on culture Days 0, 1, 3, and 5 were studied. Major histocompatibility complex locus II antigen (MHC locus II antigen; la) and interleukin-2 receptor (IL-2R; Tac) expression were analyzed using the avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis using ³H-thymidine incorporation and beta-scintillation counting. On culture Days 1 and 3, lymphocytes and monocytes were seen under the light microscope to be attached to methyl methacrylate particles. However, the results disclosed no methyl methacrylateinduced DNA synthesis, although methyl methacrylate-induced MHC locus II antigen and IL-2R activation marker expression were recorded; notably, this expression was less pronounced than that seen in PHA or PPD antigen driven lymphocyte response. The results suggest that methyl methacrylate is essentially an immunologically inert implant material. However, it seems to induce inflammatory mononuclear cell migration and adhesions leading to slightly nonspecific lymphocyte reaction.     

Metastasizing malignant pleomorphic adenoma in a young man

We present the case of a younger man with metastasizing carcinoma of unknown primary site, where autopsy revealed a malignant pleomorphic adenoma (MPA) of the submandibular gland. MPA is very rare in young persons.     

Effect of chronic ethanol consumption on the expression of complement components and acute-phase proteins in liver

The complement system can provoke but also participate in the repair of liver injury. Here we investigated by microarray analysis the effect of chronic ethanol consumption on hepatic mRNA expression of complement components and acute-phase proteins in complement C3-deficient (C3(-/-)) and wild-type (C3(+/+)) mice. Up-regulation by ethanol of factor B, C1qA-chain and clusterin but down-regulation of factor H, Masp-2, factor D and the terminal components C6, C8alpha and C9 was seen in both strains. Ethanol up-regulated C2 and down-regulated C4bp only in C3(+/+) mice, while in C3(-/-) mice up-regulation of C1qB-chain and vitronectin was observed. The expression of factor B, C6, C1qB and factor I was lower but that of factor D higher in C3(-/-) than in C3(+/+) mice. Ethanol induced mRNA synthesis of many acute-phase proteins including SPARC and lipocalin-2, but reduced the expression of SAP. The induction of early classical and alternative pathway components and suppression of terminal pathway components and soluble regulators may thus contribute to alcohol-induced liver injury. Lipocalin-2 and SPARC emerge as new candidate markers for early detection of liver damage.     

Non-participation and mortality in different socioeconomic groups: the FINRISK population surveys in 1972-92

BACKGROUND: Declining response rates pose a serious threat to the validity of estimates derived from epidemiological studies. If respondents and non-respondents differ systematically from each other, there can be a bias in the results of the study. A population-based cohort study was conducted to investigate disparities in socioeconomic structure between respondents and non-respondents and the contribution of these disparities to socioeconomic differences in total and cardiovascular mortality. DESIGN: Data comprised 32,354 male and female participants and 4890 non-participants aged 35-74 years who belonged to the sample in one of the five FINRISK surveys in 1972, 1977, 1982, 1987 or 1992 in Finland. They were followed up for 9 years and 6 months. RESULTS: It was found that the lower socioeconomic groups were over-represented among non-respondents both in men and women. When comparing the relative risk of death using the highest socioeconomic group of the participants as the reference group, it was found that although the socioeconomic gradient was similar for participants and non-participants-that is, lower groups had a higher risk of death-the risk was at a higher level among non-respondents. CONCLUSIONS: Basing analysis on participants does not distort the relative risk of death associated with socioeconomic position. However, it does underestimate the absolute risk.     

Early Alcoholic Liver Injury: Formation of Protein Adducts with Acetaldehyde and Lipid Peroxidation Products, and Expression of CYP2E1 AND CYP3A

The formation of protein adducts with reactive aldehydes resulting from ethanol metabolism and lipid peroxidation has been suggested to play a role in the pathogenesis of alcoholic liver injury. To gain further insight on the contribution of such aldehydes in alcoholic liver disease, we have compared the appearance of acetaldehyde, malondialdehyde, and 4-hydroxynonenal adducts with the expression of cytochrome P-450IIE1, and cytochrome P-4503A enzymes in the liver of rats fed alcohol with a high-fat diet for 2 to 4 weeks according to the Tsukamoto-French procedure and in control rats (high-fat liquid diet or no treatment). Urine alcohol and serum aminotransferase levels were recorded, and the liver pathology was scored from 0 to 10 according to the presence of steatosis, inflammation, necrosis, and fibrosis. The ethanol treatment resulted in the accumulation of fat, mild necrosis and inflammation, and a mean liver pathology score of 3 (range: 1 to 5). Liver specimens from the ethanol-fed animals with early alcohol-induced liver injury were found to contain perivenular, hepatocellular acetaldehyde adducts. Malondialdehyde and 4-hydroxynonenal adducts were also present showing a more diffuse staining pattern with occasional sinusoidal reactions. In the control animals, a faint positive reaction for the hydroxynonenal adduct occurred in some of the animals fed the high fat diet, whereas no specific staining was observed in the livers from the animals receiving no treatment Expression of both CYP2E1 and CYP3A correlated with the amount of protein adducts in the liver of alcohol-treated rats. Distinct CVP2E1 -positive immunohistochemistry was seen in 3 of 7 of the ethanol-fed animals. In 5 of 7 of the ethanol-fed animals, the staining intensities for CYP3A markedly exceeded those obtained from the controls. The present findings indicate that acetaldehyde and lipid peroxidatjon-derived adducts are generated in the early phase of alcohol-induced liver disease. The formation of protein adducts appears to be accompanied by induction of both CVP2E1 and CVP3A.