Is there any relationship between cytokine spectrum of breast milk and occurence of eosinophilic colitis?

Aim: The aim of our study was to analyse cytokine composition of human milk and its relationship to the development of eosinophilic colitis (EC). Methods: Cytokines were measured by ELISA method in breast milk of 20 mothers of infants who developed EC and 20 controls. Results: We found significantly higher concentrations of interferon‐gamma (IFN‐gamma) (Th1 cytokine) in breast milk received by EC infants compared to controls (p = 0.0004). In contrary, IL‐18 (Th1‐inducing cytokine) was significantly higher in breast milk received by healthy infants comparing to EC infants (p = 0.001). Regulatory cytokine transforming growth factor beta1 (TGF‐beta1) showed higher concentrations in breast milk received by healthy infants, although the difference from EC group was not significant (p = 0.072). Conclusion: The results of our study showed that infants with EC were receiving breast milk with a possibly risky cytokine pattern indicating cytokine imbalance, impaired immunoregulation and the early Th1 shift.     

Induction effects of polychlorinated biphenyls,polycyclic aromatic hydrocarbons and other widespread aromatic environmental pollutants on microsomal monooxygenase activities in chick embryo liver

 Cytochrome P450-dependent 7-ethoxyresorufin O-deethylase (EROD), 7-pentoxyresorufin O-dealkylase (PROD) and 7-ethoxycoumarin O-deethylase (ECOD) activities in 14-day-old chick embryo livers were determined 24 h after pretreatment with selected widespread aromatic environmental contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), hexachlorobenzene, and dialkylesters of phthalic acid, and compared with the inducing potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the coplanar and mono-o-chlorinated PCBs. The effects of other model inducers, i.e. phenobarbital and pyrazole, were also examined. Specificity of EROD induction was estimated with regard to contaminants frequently present in environmental samples and dose-response curves for EROD induction were determined. A strong induction (comparable with that by mono-o-chlorinated biphenyl treatment) by dibenzo[a,h]anthracene, benzo[k]fluoranthene or benzo[b]fluoranthene was found, but the maximal level of EROD activity inducible by TCDD was not achieved, partly due to the high toxicity of the tested PAHs. 3-Methylcholanthrene showed moderate inducing potencies; benz[a]anthracene, benzo[a]pyrene, chrysene and 2,2′,3,4,4′,5′-hexachlorobiphenyl appeared to be weak inducers. Other PAHs and PCBs tested, as well as hexachlorobenzene, dialkyl phthalates, phenobarbital and pyrazole had no marked effects on the EROD level. ECOD activities were increased non-specifically by TCDD, 3-methylcholanthrene, hexachlorobenzene and phenobarbital. A significant enhancement of PROD activity by TCDD and related inducers was observed, while phenobarbital induced the PROD activity only weakly; SDS-PAGE analysis showed that the chicken phenobarbital-inducible cytochromes P4502H with apparent molecular weights 50 kDa were not markedly induced by the TCDD- or 3-methylcholanthrene treatments. Inhibition of EROD and PROD by 9-hydroxyellipticine, a specific inhibitor of rat hepatic cytochrome P4501A1, revealed that PROD induction by TCDD and other P4501A-inducers was probably a result of a broader substrate specificity of chick embryo P4501A. Measurement of EROD activities in chick embryo liver is highly sensitive, specific and suitable for the determination of TCDD-type toxicity of new drugs, agrochemicals, and industrial pollutants. Received: 4 January 1995 / Accepted: 28 September 1995     

Pattern and permanence of phosphate-induced nephrocalcinosis in rabbits

Objective. The purpose of this study was to observe the pattern and permanence of phosphate-induced nephrocalcinosis (NC) in rabbits. Materials and methods. Thirty immature New Zealand white rabbits were divided into 10 controls and 20 test subjects who were given oral phosphate. Unilateral nephrectomy was performed at 3–6 weeks, and 10 of the test group were withdrawn from the substance. All surviving rabbits were terminated at 6–14 weeks post nephrectomy. Weekly US was performed, as well as US, CT and serum creatinine evaluation at the time of nephrectomy and prior to planned demise. Results. Of the 20 rabbits that received oral phosphate, 16 had NC by 3 weeks and the remainder by 6 weeks. The severity was proportional to intake. NC occurred in the cortex in 69 %, the corticomedullary junction (CMJ) in 81 % and the medulla in 27 % of cases. Only 5 of 10 rabbits that returned to oral water post nephrectomy were suitable for follow-up on pathology. NC improved in 3 of these animals. Conclusion. NC in rabbits occurs maximally at the CMJ but also frequently in the cortex. NC was not permanent or static but improved in 3 of 5 rabbits when phosphate was withdrawn. Received: 3 July 1997 Accepted: 12 August 1997     

Incidence of Australia antigen in leprosy

Ninety seven male patients attending the Leprosy clinic of the Dermatology Out-patients' Department were studied for the detection of Australia antigen. There was a 20% antigen positivity in patients suffering from Lepromatous Leprosy and 5.7% in the cases with Tuberculoid Leprosy. SGPT level was found to be significant in patients with Lepromatous Leprosy having Australia antigen as compared to other groups.     

Diversity and evolution of AbaR genomic resistance islands in Acinetobacter baumannii strains of European clone I

To assess the diversity of AbaR genomic resistance islands in Acinetobacter baumannii European clone I (MLST clonal complex 1), we investigated 26 multidrug-resistant strains of this major clone isolated from hospitals in 21 cities of 10 European countries between 1984 and 2005. Each strain harbored an AbaR structure integrated at the same position in the chromosomal ATPase gene. AbaR3, including four subtypes based on variations in class 1 integron cassettes, and AbaR10 were found in 15 and 2 strains, respectively, whereas a new, unique AbaR variant was discovered in each of the other 9 strains. These new variants, designated AbaR11 to AbaR19 (19.8 kb to 57.5 kb), seem to be truncated derivatives of AbaR3, likely resulting from the deletions of its internal parts mediated by either IS26 elements (AbaR12 to AbaR19) or homologous recombination (AbaR11). AbaR3 was detected in all 10 strains isolated in 1984 to 1991, while AbaR11 to AbaR19 were carried only by strains isolated since 1997. Our results and those from previous publications suggest that AbaR3 is the original form of AbaR in European clone I, which may have provided strains of the lineage with a selective advantage facilitating their spread in European hospitals in the 1980s or before.     

Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: The role of enhanced cytochrome P450 1B1 expression

Long-term deregulated inflammation represents one of the key factors contributing to lung cancer etiology. Previously, we have observed that tumor necrosis factor-α (TNF-α), a major pro-inflammatory cytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-α, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line. Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levels of both parent B[a]P and its metabolites. TNF-α altered production of the metabolites associated with dihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNA adducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-α also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 for B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together, the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions.     

A rare tumor and an ethical dilemma in a family with a germline TP53 mutation

We describe a family with a history of cancer suggestive of the Li-Fraumeni syndrome (LFS). A 27-year-old woman suffered at 17 years of age from phyllodes breast tumor and was shown to carry a germline mutation in the TP53 gene. Two years after testing, she became pregnant and was offered prenatal diagnosis by her gynecologist. The patient expressed her commitment to deliver the baby regardless of its mutation status, but with a strong interest in having the child tested soon after the birth. When she was informed that testing of children is usually postponed until after they reach 18 years of age, she consulted several geneticists, who repeatedly discouraged her from the intent to test the newborn. In the end, the patient decided for prenatal genetic testing only to learn the mutation status of the child. This scenario being unacceptable, she was offered early postnatal testing of the child, and this analysis showed that the newborn boy carried the mutation. Based on this finding, the family was enrolled into a preventive screening program for childhood cancer. The case illustrates ethical problems associated with early predisposition testing in LFS, and the lack of consensus on this issue in the literature.