Enzymic control of irreversible binding of metabolically activated benzo(a)pyrene in perfused rat liver by monooxygenase activity

Addition of [³H]-benzo(a)pyrene to the perfusion medium of isolated rat livers results in irreversible binding of radioactivity to DNA, RNA and protein. Binding to DNA accounted for about 0.1% of the total radioactivity which was bound in livers from animals treated with oil or saline and was increased by a factor of 3–5 after pretreatment of the animals with -naphthoflavone or with phenobarbital. When the inhibitiors of monooygenase activity, -naphthoflavone or metyrapone, were present in the perfusion medium, irreversible binding was reduced in livers from both -naphthoflavone- and phenobarbital-pretreated animals, irrespective of the inhibitor used.In livers from animals treated with oil or saline protein and a RNA fraction containing tightly associated protein were able to bind [³H]-benzo(a)pyrene metabolites to about the same extent but after induction by pretreatment with -naphthoflavone binding to the RNA fraction was enhanced to a much higher extent than binding to the protein fraction. Pretreatment with phenobarbital did not result in an increased irreversible binding to RNA and protein.A considerable amount of 15–25% of the total radioactivity added to the perfusion medium was excreted into the bile after treatment of the animals with the tested inducers of monooxygenase activity compared to an excretion of 3% in animals treated with oil or saline.The results indicate that nucleic acid and protein adduct formation in the liver is controlled by the action of the cytochrome P-450-dependent monooxygenases.In part subject of the doctoral thesis of Erik Klaus, Fachbereich Biologie, University of Mainz     

Mutagenicity studies with praziquantel,a new anthelmintic drug: Tissue-, host-, and urine-mediated mutagenicity assays

Praziquantel, a new anthelmintic drug with activity against all species of schistosomes pathogenic to man, and against a wide range of Cestodes, was tested for mutagenic potential. For the detection of both base substitutions and frameshift mutations, Salmonella typhimurium TA 100 and TA 98 were used as tester strains. Using the plate assay with and without added S-9, host-mediated assay and urine-mediated assay without and after incubation with -glucuronidase/arylsulfatase, no mutagenic activity could be detected.     

Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites

Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide hydratase and monooxygenases are reflected in very dramatic differences in mutagenicity of benzo(a)pyrene which varied from extremely potent to a degree which could easily be overlooked. In order to investigate whether the differences in enzyme activities were causally linked to the observed differences in mutagenicity, the enzyme activities were modulated by inhibition and induction. These manipulations were always accompanied by the corresponding changes in mutagenicity.It is concluded that species such as mice which possess high monooxygenase activity but very low epoxide hydratase activity are much more susceptible than man to those toxic effects which are mediated by metabolically formed epoxides which are substrates of epoxide hydratase. In this regard, it is especially noteworthy that mice possess a much lower hepatic epoxide hydratase activity than man.Presented at the Symposium Influence of Metabolic Activations and Inactivations on Toxic Effects held at the 18th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section Toxicology, D-6500 Mainz, March 15, 1977     

A chimeric opioid peptide with mixed μ agonist/δ antagonist properties

Abstract: There is evidence to indicate that opioid compounds with mixed μ agonist/δ antagonist properties are analgesics with low propensity to produce tolerance and physical dependence. A chimeric peptide containing the potent and selective μ agonist H‐Dmt‐D‐Arg‐Phe‐Lys‐NH₂ ([Dmt¹]DALDA) (Dmt = 2′,6′‐dimethyltyrosine) and the potent and selective δ antagonist H‐Tyr‐TicΨ[CH₂‐NH]Cha‐Phe‐OH (TICP[Ψ]) (Cha = cyclohexylalanine), connected ‘tail‐to‐tail’ via a short linker, was synthesized using a combination of solid‐phase and solution techniques. The resulting peptide, H‐Dmt→D‐Arg→Phe→Lys‐NH‐CH₂‐CH₂‐NH‐Phe←Cha[NH‐CH₂]ΨTic←Tyr‐H, showed the expected μ agonist/δ antagonist profile in the guinea‐pig ileum and mouse vas deferens assays. Its μ and δ receptor binding affinities were in the low nanomolar range, as determined in rat brain membrane binding assays.     

B(a)P诱导小鼠前胃癌过程中组织病理学变化

目的：探讨B(a)P诱导小鼠前胃癌过程中胃组织形态学的动态改变。方法：小鼠用5mg／ml的B(a)P灌胃，每周两次，共4周。以后每隔4周处死一部分小鼠，对胃组织进行病理组织学观察。结果：从第17周开始小鼠前胃开始出现肉眼可见的肿瘤，前胃组织由局部腺体增生、排列紊乱逐步发展为腺体普遍异常增生，形成早期胃癌，进一步发展出现进展期胃癌。结论：B(a)P诱导的小鼠前胃癌的潜伏期大约3个月左右，前胃组织病理学动态变化过程是萎缩性胃炎、不典型增生、胃癌。     

Tratamiento del cáncer de esófago localizado y localmente avanzado: ¿algo ha cambiado?

Esophageal cancer has a dismal prognosis and the surgical treatment only cures a small percentage of patients. The survival achieved by traditional surgical procedures is being improved with extended resections, but at the cost of greater morbidity. Concurrent radiochemotherapy can obtain results similar to those of surgery. Nowadays, locally advanced esophageal cancer should have a multimodal approach, because neoadjuvant chemotherapy, with or without radiotherapy, has demonstrated to improve the survival of chemosensitive patients. Recently, the role of hyperfractionated radiotherapy and new drugs such as paclitaxel, docetaxel and irinotecan in neoadjuvant treatment is being evaluated.     

Molecular and functional characterization of porcine LFA-1 using monoclonal antibodies to CD11a and CD18

Abstract: We describe in this report the production and characterization of monoclonal antibodies (mAb) to the swine homologues of CD11a and CD18 antigens, and their use for phenotypic and functional analysis of porcine leukocytes. Monoclonal antibodies BL1H8 and BL2F1 precipitated two bands of approximately 170 and 95 kDa, whereas mAb BA3H2 brought down three bands of 170, 155 and 95 kDa, from alveolar macrophage lysates. Clearance of macrophage lysates with mAbs BL1H8 and BL2F1 resulted in complete removal of the 170-kDa band. The cell distribution of the molecules recognized by these mAbs was similar to that of human LFA-1. It was found on all leukocytes, although its expression varied among the different leukocyte subpopulations, with monocytes, granulocytes and a subset of CD8⁺ cells expressing the highest levels. Cross-blocking studies showed that these antibodies recognize different epitopes on porcine LFA-1. Both anti-LFA-1 mAbs strongly inhibited the mitogenic response of PBMC to ConA, whereas the anti-CD18 mAb had no effect. These anti-LFA-1 mAbs also inhibited the mixed lymphocyte reaction (MLR) and the NK cell-mediated lysis of K-562 cells.     

经上颌窦前壁钻孔行鼻窦内窥镜术30例报告

报告经上颌窦前壁钻孔行鼻窦内窥镜手术３０例，疗效较好。与鼻腔、鼻窦内窥镜手术比较，该术式具有观察方便，出血少，反应轻，操作方便，并发症少，术后复发率低等优点。     

Should children with infection be tested for lipid,lipoprotein and apolipoprotein?

The lipid profile is known to alter in patients with infection, but there has not been a study of the apolipoprotein levels in serum of otherwise healthy children during infection. Lipids, lipoproteins, apolipoproteins A-l and B and lipoprotein (a) were evaluated prospectively in 31 consecutive children, aged4–15 years, who were admitted to the hospital with bacterial pharyngitis. The degree of dyslipidemia associated with bacterial pharyngitis was assessed using each child as his/her own control and by comparison with 79 healthy children who had not had an infection during the past 3 months. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-l and apolipoprotein B levels were significantly decreased during the symptomatic phase of the disease, whereas the serum triglyceride level was slightly elevated. Serum lipoprotein (a) concentration did not change significantly. In conclusion, it is suggested that serum lipids, lipoproteins and apolipoproteins should not be assessed during infection because of the possible transient changes of these parameters during infection or inflammation.     

Prosopo-Thoracopagus Conjoined Twins and Other Cephalopagus-Thoracopagus Intermediates: Case Report and Review of the Literature

Prosopo-thoracopagus twins are united from the face down to the umbilicus, none with union in the brain but all with visceral anomalies intermediate between those of cephalopagus and thoracopagus. In a review of over 1200 cases of conjoined twins reported during the past 100 years, there were 14 that illustrate the continuum between cephalopagus and thoracopagus, including three that were united only from the cervical region to the umbilicus. Classic cephalopagus twins are joined from the top of the head to the umbilicus, sharing a single foregut as well as two relatively normal hearts, the “posterior” one often diminished. Typical thoracopagus, however, are conjoined only from the upper thorax to the umbilicus, each twin with a normal foregut but both sharing a single complex multiventricular heart. The intermediate cases shared either a single very abnormal heart or two hearts united by double aortic arches, and all except one had a single foregut. It is these cases intermediate between cephalopagus and thoracopagus which are the subject of this report. Received September 11, 1996; accepted December 16, 1996