Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity

Lauzon, Anne-Marie, Ann R. Elliott, Manuel Paiva, John B. West, and G. Kim Prisk. Cardiogenic oscillation phaserelationships during single-breath tests performed inmicrogravity. J. Appl. Physiol. 84(2):661-668, 1998.We studied the phase relationships of thecardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (µG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balanceO₂, preceded at residual volume bya 150-ml Ar bolus. Pairs of gas signals, all of which still showedcardiogenic oscillations, were cross-correlated, and their phasedifference was expressed as an angle. Phase relationships betweeninspired gases (e.g., He) and resident gas(N₂) showed no change from 1 G(211 ± 9°) to µG (163 ± 7°). Ar bolus and He wereunaltered between 1 G (173 ± 15°) and µG (211 ± 25°),showing that airway closure in µG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast,CO₂ reversed phase with He between1 G (332 ± 6°) and µG (263 ± 27°), stronglysuggesting that, in µG, areas of high ventilation are associated withhigh ventilation-perfusion ratio (A/).This widening of the range ofA/in µG may explain previous measurements (G. K. Prisk, A. R. Elliott,H. J. B. Guy, J. M. Kosonen, and J. B. West. J. Appl.Physiol. 79: 1290-1298, 1995) of an overallunaltered range ofA/in µG, despite more homogeneous distributions of both ventilation andperfusion.

     

Review of the in vivo genotoxicity tests performed with styrene

Results from new genotoxicity tests in laboratory animals have necessitated a comprehensive re-evaluation of the mutagenic potential of styrene in vivo. Available data suggest that styrene, after being metabolized to styrene oxide, is weakly positive in indicator tests detecting DNA adducts, DNA strand breaks and sister chromatid exchanges (SCEs). There is no convincing evidence of styrene clastogenicity in experimental animals when the quality of the studies and the plausibility of the test results are considered. Equivocal results were obtained after exposure to high doses causing lethality. A recently published in vivo micronucleus test (MNT) in bone marrow cells of mice conforming to the current OECD guideline was clearly negative. Consequently, our evaluation of the published genotoxicity data comes to the conclusion that styrene at high doses can induce genotoxic effects in indicator tests. These DNA effects depend upon the exposure levels of the target cells, the metabolic activation to styrene oxide and the efficiency of detoxification. Mutagenic effects of styrene can only be expected under extreme exposure conditions if styrene oxide is not efficiently detoxified and primary DNA lesions are not completely repaired. However, there is no clear evidence that styrene induces mutagenic/clastogenic effects in vivo when tested under appropriate test conditions.     

Ciclosporin administration during pregnancy induces ultrastructural changes on pancreatic beta-cells of newborn rats

Ciclosporin (CS) is an immunosuppressive agent used in the prevention of graft rejections and in the management of type 1 diabetes. However, the drug is not without side effects. The aim of this study was to evaluate eventual cytotoxic phenomena in the pancreas of newborn rats whose mothers had been treated with therapeutic doses of CS. For this purpose, 25 female Wistar rats were used, 20 of which were subjected to daily injections of 10 mg/kg BW/day i.p. of CS dissolved in Intralipid, administered during the whole gestational period. The results obtained indicated that CS did not arrest fetal development, even though the number of newborns per mother was reduced when compared to controls. Moreover, mothers and newborn rats were subjected to vacuolation of kidney proximal tubular cells and of the insulin-secreting pancreatic beta-cells. This alteration was more evident in the islet beta-cells of newborn rats. Therefore, CS is not only toxic to the mothers' endocrine beta-cells but also to those of any eventual offspring.     

A case of congenital warfarin syndrome due to maternal drug administration during the pregnancy

Warfarin, which is used for anticoagulant therapy, rarely produces congenital warfarin syndrome characterized with hypoplastic nose, stippled epiphyses, and skeletal abnormalities when ingested during pregnancy. Here, we present a male infant, whose mother was treated with warfarin because of a prosthetic heart valve replacement after rheumatic heart disease, with signs of warfarin embryopathy. The mother's first pregnancy at 12 weeks gestation resulted in abortus due to warfarin toxicity. Subsequently, she delivered two healthy girls after her treatment had changed to low molecular heparin during pregnancy periods. We want to emphasize that risk-benefit ratio should be well weighed by both obstetricians and cardiologists when considering warfarin therapy for a woman at childbearing age.     

Maternal methamphetamine administration during pregnancy influences on fetal rat heart development. [corrected

Methamphetamine (MAP) is one of the most abused drugs in Japan. The rate of MAP abuse by young women has recently reached more than 50 percent in adolescents. A major health concern is that these women will continue to use MAP during pregnancy. The purpose of this study was to investigate whether MAP administered to the mother during pregnancy would change the expression of α- and β- myosin heavy chain (MHC) mRNA in rat neonatal hearts, as detected by quantitative RT-PCR. In addition, morphological changes in the rat neonatal ventricles were examined. Pregnant rats were injected intraperitoneally with MAP (1 mg/kg/day) starting at day 0 of gestation and ending at day 21. There was a significant increase in α-MHC mRNA expression in the neonatal ventricular muscle in the experimental group compared with the control at postnatal day (P) 0 and 5. α-MHC mRNA expression in both groups was similar after P9. β-MHC mRNA expression was similar in both groups at P0. Postnatal β-MHC mRNA expression decreased rapidly, but significant alteration was not detected. Neonatal rats at P0 exhibited some cardiac changes, including hypertrophy, degeneration, and disarrangement of myofibers, but these lesions disappeared by P14. We conclude that chronic maternal administration of MAP changes the α- and β-MHC mRNA expression pattern in fetal and neonatal hearts, correlating with abnormal development, plasma level of hormones, and myocardial damage. At the same time, it is indicated that neonatal cardiomyocytes have reversibility.     

Developmental programming in sheep: administration of testosterone during 60-90 days of pregnancy reduces breeding success and pregnancy outcome

Evidence suggests that exposure to excess steroids during critical periods of fetal development leads to reproductive disorders. Exposure of female lambs to excess testosterone (T) from Days 60 to 90 of gestation (T60-90; term, 147 days) delayed onset of the LH surge and resulted in to male-typical reproductive behavior. The objectives of this study were to test the ability of T60-90 ewes to mate, conceive and lamb during the first three breeding seasons (Years 1, 2 and 3). Pregnant Suffolk ewes were injected with T propionate in cottonseed oil (100mg, im twice weekly) or vehicle (control; C) from Days 60 to 90 of gestation. In Year 1, ewes (C=12, T60-90=12) were kept with a vasectomized ram for 3 months and markings/visual observation of copulations were recorded. Rams had paint applied to their chest to facilitate detection of estrus and mating. All C but only three T60-90 ewes were marked (P<0.001). All ewes were then estrus-synchronized with two injections of prostaglandin F2alpha (20mg, im) given 11 days apart and allowed to mate with a painted, fertile ram. Nine of 12 C and 4 of 12 T60-90 ewes (P=0.1) were mated. Based on estrus and long-term monitoring of progesterone, more C than T60-90 became pregnant (82 and 18%, respectively; P<0.01). In Year 2, to maximize ram exposure, two C and two T60-90 estrus-synchronized ewes were placed with a painted, fertile ram at a time and mated ewes were removed to a nearby pen to force mating with others. Twenty-four hour video monitoring revealed the rams mated more C than T60-90 ewes (83 and 25%, respectively; P=0.01). In both Years 1 and 2, the rams preferred C over T60-90 ewes; therefore in Year 3 rams were given access only to T60-90 ewes. Only four T60-90 estrus-synchronized ewes were placed with a painted ram at a time. Not given an option, 91% of the T60-90 ewes were marked resulting in 4 of 11 (36%; first-service pregnancy rate in the breeding herd was 91%) ewes becoming pregnant to the synchronized estrus. Collectively these studies showed that fertility in T60-90 females was severely compromised, even after overcoming ram preference for controls.     

Determination of biofilm mechanical properties from tensile tests performed using a micro-cantilever method

Recently, a micro-cantilever method was introduced for measuring the ultimate tensile strength of intact bacterial biofilms. Herein, is reported the analysis of the video files from the testing of a 4-day-old Staphylococcus epidermidis biofilm to determine the elastic modulus, toughness, and failure strain. Elastic modulus (1270±280 Pa) was within the range of previously reported values (17–6000 Pa). The high failure strains (240±16%) indicate the substantial ductility of bacterial biofilms. In addition, the toughness of the biofilm sample was determined from the area under the stress–strain plot (2.8±0.44 kJ m^?3). Thus, it was demonstrated that the micro-cantilever test video files can be used for the determination of other mechanical property parameters besides ultimate tensile strength.     

Malaria during pregnancy

Each year approximately 50 million women living in malaria endemic areas become pregnant and are at risk of the adverse health impact of malaria. Approximately half of them live in sub-Saharan Africa and most of them in areas of intense falciparum transmission. The increased susceptibility to malaria of pregnant women has long been recognized. Although some progress has been accomplished in recent years, resulting in the identification of intermittent preventive treatment (IPTp) and insecticide treated nets (ITNs) as key strategies to control malaria in pregnancy in Africa, much work needs to be done to control malaria effectively in this high at risk group. There are still many gaps in knowledge that need to be addressed: from the biological mechanism(s) that explains the increased susceptibility during pregnancy, the most effective control measures in different transmission areas and the best drugs for case management.