Leucoisoprenochrome-o-semiquinone formation in freshly isolated adult rat cardiomyocytes

Sustained high levels of circulating catecholamines can lead to cardiotoxicity. There is increasing evidence that this process may result from metal-catalyzed catecholamine oxidation into semiquinones, quinones, and aminochromes. We have previously shown that Cu2+-induced oxidation of isoproterenol into isoprenochrome induces toxic effects in isolated cardiomyocytes. The aim of this study was to characterize the isoproterenol oxidation process and to locate the formation of semiquinone radicals in cardiomyocyte suspensions. Freshly isolated rat cardiomyocytes were incubated with 1 or 10 mM isoproterenol and 20 microM Cu2+ for 4 h. The formation of an isoproterenol oxidation radical was detected in the extracellular medium, cells, membranes, and heavy organelles by electron spin resonance spectroscopy. An electron spin resonance signal assigned to leucoisoprenochrome-o-semiquinone increased in a time-dependent manner in the extracellular medium. A second electron spin resonance signal, characteristic of an immobilized radical, was also found in the cardiomyocytes. The latter was attributed to leucoisoprenochrome-o-semiquinone immobilized on cellular components such as membranes, cytoskeleton, nucleus, and heavy organelles. In addition, the levels of leucoisoprenochrome-o-semiquinone decreased in the presence of glutathione. Computer simulations of the experimental spectra indicate the formation of two distinct isomeric leucoisoprenochrome-o-semiquinone radicals during isoproterenol oxidation. The present study shows that the isoproterenol oxidation in isolated rat cardiomyocytes correlates with the formation of leucoisoprenochrome-o-semiquinone in the cells and in the extracellular medium, suggesting that it might be involved in cardiotoxicity induced by the oxidation of catecholamines.     

Fetal heart rate and survival of the very premature newborn

OBJECTIVE: Our purpose was to study the likelihood of survival of infants who are born before 28 weeks of gestation and to examine the influence of fetal heart rate findings on neonatal death. STUDY DESIGN: In this retrospective study, we analyzed the mortality rate of infants at 2 months of age as a function of various obstetric and prenatal indicators. RESULTS: At 2 months, 207 of 325 children were still alive. The survival rate was also a function of gestational age, birth weight, the administration of corticosteroids, multiple pregnancies, and fetal heart rate. Fetal heart rate had the greatest effect on the mortality rate. Children with a reactive rate were 4 times more likely to survive than children with a flat tracing (P =.003; odd ratio, 4; 95% CI, 12.1; 39.8). CONCLUSION: The results in our study lead us to think that recording the fetal heart rate before and during labor may be useful in the prediction of perinatal death and may help obstetric decision-making.     

Natural host relationships and genetic diversity of Whitewater Arroyo virus in southern Texas

The purpose of this study was to refine our knowledge of the natural host relationships of Whitewater Arroyo (WWA) virus. Two hundred eight rodents, representing nine species, were captured in July 1999 on the Chaparral Wildlife Management Area in southern Texas and tested for evidence of arenavirus infection. Antibody to an arenavirus was found in seven (21.9%) of 32 southern plains woodrats (Neotoma micropus) and none of 168 other rodents. Infectious WWA virus was isolated from four antibody-positive southern plains woodrats, one of 25 antibody-negative southern plains woodrats, and none of 176 other rodents. Collectively, the results indicate that the southern plains woodrat is a principal host of WWA virus in southern Texas. Analyses of viral gene sequence data revealed substantial genetic diversity among WWA virus strains isolated from the woodrats, suggesting that multiple variants of the virus can coexist in a single woodrat species in a small geographic area.     

General anaesthesia for Caesarean section in a patient with pulmonary atresia and an intact intraventricular septum

We report the case of a 22-year-old primigravida patient presenting pulmonary atresia with intact ventricular septum, a rare congenital heart disease. Caesarean delivery was performed at 32 weeks of gestation because of moderate maternal function deterioration and foetal growth restriction. General anaesthesia was used because of the presence of lumbar Harrington rods. The administration of etomidate, celocurine and a continuous perfusion of remifentanil right from induction ensured haemodynamic stability and a rapid emergence and recovery.     

Human albumin synthesis is increased by an ultra-endurance trial

PURPOSE: The purpose of this study was to determine whether an ultra-endurance event is a strong stimulus to increase albumin synthesis involved in the process of intravascular albumin mass increase associated with transient hypervolemia. METHODS: The albumin synthetic rate was measured in six young men, 3 d before (C) and on the 1st (R1) and 8th (R8) days of the recovery from an ultra-endurance trial (5 h daily for 4 d). Albumin fractional (FSR) and absolute (ASR) synthetic rate were determined using a primed-constant infusion of [1(-13) C] leucine. Plasma volume (PV) using Evans Blue dye dilution and total body water (TBW) using bioelectrical impedance analysis were measured on C, R1, and R8. RESULTS: On R1 as compared with C: 1). PV (+23.3 +/- 3.2%; P相似文献   

Characterization of Hodgkin's lymphoma-like undifferentiated carcinoma of the nasopharyngeal type as a particular UCNT subtype mimicking Hodgkin's lymphoma

Undifferentiated carcinoma of the nasopharyngeal type (UCNT) that histologically mimics Hodgkin's lymphoma (HL) ("Hodgkin's lymphoma-like UCNT"--HL-like UCNT) is known as a diagnostic pitfall. Using immunohistochemistry, Western blot and cDNA array technology, we wanted to document its phenotypical and molecular characteristics. We report herein 5 cases of UCNT that morphologically mimic HL and 3 classical UCNT cases. We compared the expression profiles of a thousand selected genes in HL-like UCNT and in classical UCNT cases. No difference in the profile of EBV infection was noted between the HL-like UCNT and control cases. Significant differences were detected in the expression of genes involved in the matrix modelling, angiogenesis, apoptosis and regulation of the Th-2 interleukins. The eosinophil chemoattractant eotaxin was expressed in the stroma of HL-like UCNT, but not in the control cases. The eotaxin receptor CCR3 was expressed in both stromal and carcinoma cell populations of HL-like UCNT, this pattern being similar to the one observed in HL. These results show that UCNT morphologically resembling HL share also some specific phenotypical and molecular features with HL, and might deserve to be isolated as a particular UCNT subtype.     

Organochlorines and risk of prostate cancer

This pilot study examined the relationships of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) with prostate cancer. Ninety-nine controls were frequency matched by age in 5-year increments to 58 prostate cancer patients. Thirty PCBs and 18 OCPs were measured in serum by gas chromatography. Multiple logistic regression was used to assess the magnitude of association. Seven organochlorines, dieldrin, p,p'-DDE, trans-nonachlor, oxychlordane, heptachlor epoxide, and PCBs 153 and 180 were detected in at least 20% of all study participants. Adjusting for age, body mass index, and a history of prostatitis, oxychlordane and PCB 180 were associated with an increased risk of prostate cancer. This study suggests that long-term, low-dose exposure to specific OCPs and PCBs in the general population may contribute to an increased risk of prostate cancer and supports further investigation in this area.     

Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens

4-Methylbenzylidene-camphor (4-MBC) is an organic sunscreen that protects against UV radiation and may therefore help in the prevention of skin cancer. Recent results on the estrogenicity of 4-MBC have raised concerns about a potential of 4-MBC to act as an endocrine disruptor. Here, we investigated the direct interaction of 4-MBC with estrogen receptor (ER) alpha and ERbeta in a series of studies including receptor binding, ER transactivation and functional tests in human and rat cells. 4-MBC induced alkaline phosphatase activity, a surrogate marker for estrogenic activity, in human endometrial Ishikawa cells. Interestingly, 4-MBC induced weakly ERalpha and with a higher potency ERbeta mediated transactivation in Ishikawa cells at doses more than 1 microM, but showed no distinct binding affinity to ERalpha or ERbeta. In addition, 4-MBC was an effective antagonist for ERalpha and ERbeta. In an attempt to put 4-MBC's estrogenic activity into perspective we compared binding affinity and potency to activate ER with phyto- and xenoestrogens. 4-MBC showed lower estrogenic potency than genistein, coumestrol, resveratrol, bisphenol A and also camphor. Analysis of a potential metabolic activation of 4-MBC that could account for 4-MBC's more distinct estrogenic effects observed in vivo revealed that no estrogenic metabolites of 4-MBC are formed in primary rat or human hepatocytes. In conclusion, we were able to show that 4-MBC is able to induce ERalpha and ERbeta activity. However, for a hazard assessment of 4-MBC's estrogenic effects, the very high doses of 4-MBC required to elicit the reported effects, its anti-estrogenic properties as well as its low estrogenic potency compared to phytoestrogens and camphor has to be taken into account.     

ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility

We describe two signaling events downstream of ERK-MAP kinase contributing to cell motility in colon carcinoma cells. The Fos family member Fra-1 is expressed in an ERK-dependent manner. Silencing of Fra-1 expression with short interfering RNAs leads to losses of cell polarization, motility, and invasiveness in vitro. These effects of ablating Fra-1 are a consequence of activation of a RhoA-ROCK pathway by beta1-integrin, leading to an increase in the amount of stress fibers and stabilization of focal adhesions. We propose that Fra-1 promotes cell motility by inactivating beta1-integrin and keeping RhoA activity low. This depression of RhoA activity is necessary to permit a second ERK-dependent signaling event via uPAR, the receptor for urokinase-type plasminogen activator, to activate Rac and to drive motility through polarized lamellipodia extension.