Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

Consolidated bioprocessing of raw starch with Saccharomyces cerevisiae strains expressing fungal alpha-amylase and glucoamylase combinations.

Cost-effective consolidated bioprocessing (CBP) of raw starch for biofuel production requires recombinant Saccharomyces cerevisiae strains expressing α-amylases and glucoamylases. Native Aureobasidium pullulans apuA, Aspergillus terreus ateA, Cryptococcus sp. S-2 cryA and Saccharomycopsis fibuligera sfiA genes encoding raw-starch α-amylases were cloned and expressed in the S. cerevisiae Y294 laboratory strain. Recombinant S. cerevisiae Y294[ApuA] and Y294[AteA] strains produced the highest extracellular α-amylase activities (2.17 U mL-1 and 2.98 U mL-1, respectively). Both the ApuA and AteA α-amylases displayed a preference for pH 4 to 5 and retained more than 75% activity after 5 days at 30°C. When ateA was co-expressed with the previously reported Aspergillus. tubingensis glucoamylase gene (glaA), the amylolytic S. cerevisiae Y294[AteA-GlaA] strain produced 45.77 g L-1 ethanol after 6 days. Ethanol production by this strain was improved with the addition of either 2.83 µL STARGEN 002 (54.54 g L-1 ethanol and 70.44% carbon conversion) or 20 µL commercial glucoamylase from Sigma-Aldrich (73.80 g L-1 ethanol and 90.19% carbon conversion). This is the first report of an engineered yeast strain that can replace up to 90% of the enzymes required for raw starch hydrolysis, and thus contributes to the realisation of a CBP yeast for starch-based biofuel production.

Male birthweight, semen quality and birth outcomes.

STUDY QUESTION: What are the relations among birthweight (BW), semen parameters and birth outcomes in a population-based sample? SUMMARY ANSWER: BW is unrelated to semen parameters, which are in turn unrelated to birth outcomes. WHAT IS KNOWN ALREADY: In clinical settings, there has been suggestion that semen parameters are related to BW when comparing fertile and infertile men; however, findings have been less clear in more general populations. STUDY DESIGN, SIZE, DURATION: Questionnaire data and semen samples were collected at baseline from 427 male participants of the population-based Longitudinal Investigation of Fertility and the Environment (LIFE) prospective cohort study from 2005 to 2009, who were followed prospectively to assess pregnancy outcomes among 226 singleton births. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men of at least 18 years of age who were married or in a committed relationship and trying to conceive were eligible for participation; physician-diagnosed infertility was an exclusion criterion. Participants were recruited from two geographic areas and semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure using methods including computer-aided semen analysis integrated visual optical system and sperm chromatin structure assay. Linear and mixed models were used for statistical analysis of the relations between men's BW, semen parameters, and BW, gestational age at delivery, birth length, head circumference and ponderal index of singleton births. MAIN RESULTS AND THE ROLE OF CHANCE: No association was observed between male BW and semen parameters or birth outcomes. Few associations were observed between semen parameters and birth outcomes, and the observed statistically significant associations were isolated and without a consistent pattern that would suggest an association between BW and birth outcomes. LIMITATIONS, REASONS FOR CAUTION: Men's BW was self-reported and may be subject to some imprecision. Semen analysis was performed the day after collection, an approach that impacts the assessment of motility and that may limit inference from our analyses of motility measures. In addition, inclusion criteria for selection into the cohort limits generalizability to generally healthy couples trying to conceive and without known subfertility. WIDER IMPLICATIONS OF THE FINDINGS: Despite suggestions from prior studies of male in utero exposures impacting BW and male reproductive health, there appears to be little support for such relations in this generally healthy population. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). The authors report no competing interests, and a Memo of Understanding with the National Institute of Occupational Safety and Health (NIOSH) for semen analysis. TRIAL REGISTRATION NUMBER: Not applicable.

Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients.

PURPOSE: Follicular redox balance is likely to be important for embryo quality during in vitro fertilization (IVF), and the anti-oxidative high desity lipoprotein (HDL) particle is the sole lipoprotein measured in follicular fluid (FF). Therefore, we investigated FF HDL particle components as predictors of embryo quality during IVF. METHODS: Two research follicles collected from each participant were individually tracked, and 103 women having at least one developed embryo were included in the analysis. Concentrations of 15 non-cholesterol HDL particle components and 26 HDL-cholesterol (HDL-C) particle size subfractions were determined. Embryo quality was assessed for embryo cell number, embryo fragmentation, and embryo symmetry. Multivariable Poisson regression with a sandwich variance estimator was used to evaluate associations between HDL particle components and embryo quality, adjusted for covariates. RESULTS: Higher γ-tocopherol concentration was associated with less embryo fragmentation (relative risk [RR] = 4.43; 95 % confidence interval [CI] 1.78, 11.06), and higher apolipoprotein A-1 concentration was associated with full embryo symmetry (RR = 3.92; 95 % CI 1.56, 9.90). Higher concentrations of HDL-C subfractions in the large and medium particle size ranges were associated with poorer embryo quality. CONCLUSIONS: FF HDL lipophilic micronutrients and protein components, as well as HDL-C particle size, may be important predictors of embryo quality during IVF.

Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10.

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and -rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB.

Associations between urinary phthalate concentrations and semen quality parameters in a general population.

STUDY QUESTION: Are urinary phthalate concentrations associated with altered semen quality parameters among males recruited from the general population? SUMMARY ANSWER: Urinary levels of metabolites of phthalate diesters are associated with lower total sperm counts, larger sperm head sizes, and higher percentages of morphologically abnormal sperm. WHAT IS KNOWN ALREADY: High dose experiments in rats implicate phthalates as anti-androgens. Studies involving infertile men seeking care suggest that phthalates influence measures of semen quality raising concern about the implications for men in the general population. STUDY DESIGN, SIZE, DURATION: This prospective cohort study comprised 501 male partners in couples discontinuing contraception to become pregnant, who were recruited from 16 US counties using population-based sampling frameworks from 2005 to 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: Urine and semen samples were obtained at baseline from 473 (94%) men, of whom 378 (80%) men provided a second sample the following month. Urine was analyzed for 14 monoester metabolites of phthalate diesters by high-performance liquid chromatography coupled to tandem mass spectrometry. Semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure. MAIN RESULTS AND THE ROLE OF CHANCE: Urinary mono-[2-(carboxymethyl) hexyl] phthalate (MCMHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), and mono-isononyl phthalate (MNP) were significantly associated with lower total sperm counts and concentrations, larger sperm head sizes, higher proportions of megalo head sperm morphology, and/or other morphological changes. Urinary mono-methyl phthalate (MMP) and mono-cyclohexyl phthalate (MCPP) were significantly associated with lower sperm motility, and urine mono-2-ethylhexyl phthalate (MEHP) was significantly associated with higher sperm motility. LIMITATIONS, REASONS FOR CAUTION: While adverse associations were observed, the implications of the findings for couple fecundity and fertility remain to be established. Cautious interpretation is needed in light of reliance on a single measurement of phthalate measure and no correction for multiple comparisons.

Expression and evaluation of enzymes required for the hydrolysis of galactomannan.

The cost-effective production of bioethanol from lignocellulose requires the complete conversion of plant biomass, which contains up to 30 % mannan. To ensure utilisation of galactomannan during consolidated bioprocessing, heterologous production of mannan-degrading enzymes in fungal hosts was explored. The Aspergillus aculeatus endo-ß-mannanase (Man1) and Talaromyces emersonii α-galactosidase (Agal) genes were expressed in Saccharomyces cerevisiae Y294, and the Aspergillus niger ß-mannosidase (cMndA) and synthetic Cellvibrio mixtus ß-mannosidase (Man5A) genes in A. niger. Maximum enzyme activity for Man1 (374 nkat ml(-1), pH 5.47), Agal (135 nkat ml(-1), pH 2.37), cMndA (12 nkat ml(-1), pH 3.40) and Man5A (8 nkat ml(-1), pH 3.40) was observed between 60 and 70 °C. Co-expression of the Man1 and Agal genes in S. cerevisiae Y294[Agal-Man1] reduced the extracellular activity relative to individual expression of the respective genes. However, the combined action of crude Man1, Agal and Man5A enzyme preparations significantly decreased the viscosity of galactomannan in locust bean gum, confirming hydrolysis thereof. Furthermore, when complemented with exogenous Man5A, S. cerevisiae Y294[Agal-Man1] produced 56 % of the theoretical ethanol yield, corresponding to a 66 % carbohydrate conversion, on 5 g l(-1) mannose and 10 g l(-1) locust bean gum.

The influence of sporadic anovulation on hormone levels in ovulatory cycles.

STUDY QUESTION: Do ovulatory hormone profiles among healthy premenopausal women differ between women with and without sporadic anovulation? SUMMARY ANSWER: Women with one anovulatory cycle tended to have lower estradiol, progesterone and LH peak levels during their ovulatory cycle. WHAT IS KNOWN ALREADY: Anovulation occurs sporadically in healthy premenopausal women, but the influence of hormones in a preceding cycle and the impact on a subsequent cycle's hormone levels is unknown. STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective cohort including 250 healthy regularly menstruating women, 18-44 years of age, from Western New York with no history of menstrual or ovulation disorders. The women were followed with up to eight study visits per cycle for two cycles, most of which were consecutive. PARTICIPANTS/MATERIALS, SETTING AND METHODS: All study visits were timed to menstrual cycle phase using fertility monitors and located at the University at Buffalo women's health research center from 2005 to 2007. The main outcomes measured were estradiol, progesterone, LH and follicle-stimulating hormone levels in serum at up to 16 visits over two cycles. Anovulation was defined as peak serum progesterone concentrations ≤5 ng/ml and no serum LH peak detected during the mid- or late-luteal phase visit. MAIN RESULTS AND THE ROLE OF CHANCE: Reproductive hormone concentrations were lower during anovulatory cycles, but significant reductions were also observed in estradiol (-25%, P = 0.003) and progesterone (-22%, P = 0.001) during the ovulatory cycles of women with one anovulatory cycle compared with women with two ovulatory cycles. LH peak concentrations were decreased in the ovulatory cycle of women with an anovulatory cycle (significant amplitude effect, P = 0.004; geometric mean levels 38% lower, P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Follow-up was limited to two menstrual cycles, and no ultrasound assessment of ovulation was available. Data were missing for a total of 168 of a possible 4072 cycle visits (4.1%), though all women had at least five visits per cycle (94% had seven or more per cycle). WIDER IMPLICATIONS OF THE FINDINGS: These results suggest a possible underlying cause of anovulation, such as a longer-term subclinical follicular, ovarian or hypothalamic/pituitary dysfunction, even among healthy, regularly menstruating women.

Impact of endocrine disruptors from mother's diet on immuno-hormonal orchestration of brain development and introduction of the virtual human twin tool.

Diet has long been known to modify physiology during development and adulthood. However, due to a growing number of manufactured contaminants and additives over the last few decades, diet has increasingly become a source of exposure to chemicals that has been associated with adverse health risks. Sources of food contaminants include the environment, crops treated with agrochemicals, inappropriate storage (e.g., mycotoxins) and migration of xenobiotics from food packaging and food production equipment. Hence, consumers are exposed to a mixture of xenobiotics, some of which are endocrine disruptors (EDs). The complex interactions between immune function and brain development and their orchestration by steroid hormones are insufficiently understood in human populations, and little is known about the impact on immune-brain interactions by transplacental fetal exposure to EDs via maternal diet. To help to identify the key data gaps, this paper aims to present (a) how transplacental EDs modify immune system and brain development, and (b) how these mechanisms may correlate with diseases such as autism and disturbances of lateral brain development. Attention is given to disturbances of the subplate, a transient structure of crucial significance in brain development. Additionally, we describe cutting edge approaches to investigate the developmental neurotoxicity of EDs, such as the application of artificial intelligence and comprehensive modelling. In the future, highly complex investigations will be performed using virtual brain models constructed using sophisticated multi-physics/multi-scale modelling strategies based on patient and synthetic data, which will enable a greater understanding of healthy or disturbed brain development.

Engineering yeasts for raw starch conversion.

Next to cellulose, starch is the most abundant hexose polymer in plants, an import food and feed source and a preferred substrate for the production of many industrial products. Efficient starch hydrolysis requires the activities of both α-1,4 and α-1,6-debranching hydrolases, such as endo-amylases, exo-amylases, debranching enzymes, and transferases. Although amylases are widely distributed in nature, only about 10 % of amylolytic enzymes are able to hydrolyse raw or unmodified starch, with a combination of α-amylases and glucoamylases as minimum requirement for the complete hydrolysis of raw starch. The cost-effective conversion of raw starch for the production of biofuels and other important by-products requires the expression of starch-hydrolysing enzymes in a fermenting yeast strain to achieve liquefaction, hydrolysis, and fermentation (Consolidated Bioprocessing, CBP) by a single organism. The status of engineering amylolytic activities into Saccharomyces cerevisiae as fermentative host is highlighted and progress as well as challenges towards a true CBP organism for raw starch is discussed. Conversion of raw starch by yeast secreting or displaying α-amylases and glucoamylases on their surface has been demonstrated, although not at high starch loading or conversion rates that will be economically viable on industrial scale. Once efficient conversion of raw starch can be demonstrated at commercial level, engineering of yeast to utilize alternative substrates and produce alternative chemicals as part of a sustainable biorefinery can be pursued to ensure the rightful place of starch converting yeasts in the envisaged bio-economy of the future.

Residency time, migration route and survival of Atlantic salmon Salmo salar smolts in a Canadian fjord.

Atlantic salmon Salmo salar smolts (n = 181) from two rivers were surgically implanted with acoustic transmitters and released to determine migration route, residency time and survival in a 50 km long estuarine fjord located on the south coast of Newfoundland, Canada. Data obtained from automated receivers placed throughout the Bay d'Espoir fjord indicated that migrating smolts used different routes to reach the outer areas of the fjord. The duration of time that smolts spent in the immediate estuary zone also differed between the two localities (7 and 17 days) although the total time smolts were resident in the fjord was similar and extensive (40 days). Many smolts were resident for periods of 4-8 weeks moving back and forth in the outer part of the fjord where maximum water depths range from 300 to 700 m. Survival in the estuary zone was greater for smolts with prolonged residency in estuarine habitat. Overall smolt survival to the fjord exit was moderately high (54-85%), indicating that the initial phase of migration did not coincide with a period of unusually high mortality.

Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma.

Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.

Synergistic codon optimization and bioreactor cultivation toward enhanced secretion of fungal lignin peroxidase in Pichia pastoris: Enzymatic valorization of technical (industrial) lignins.

Lignin peroxidase (LiP) is a well-recognized enzyme for its ability to oxidize lignins, but its commercial availability is limited, which hinders the biotechnological application of LiP-based bioprocesses in lignocellulose biorefineries. This study evaluated a combination strategy to improve the expression of LiP to promote its practical use. The strategy included optimization of the lipH8 gene of Phanerochaete chrysosporium according to the codon usage of Pichia pastoris, followed by fed-batch fermentation using a 14 L bioreactor (10 L working volume). The combination strategy achieved a maximum volumetric LiPH8 activity of 4480 U L-1, protein concentration of 417 mg L-1 and a specific activity of 10.7 U mg-1, which was higher than previous reports. Biochemical characterization showed that the recombinant LiPH8 (rLiPH8) was optimum at pH 3.0, 25 ℃ and 0.4 mM H2O2. Using the optimized conditions, rLiPH8 was used to treat isolated technical lignins namely soda-anthraquinone (SAQ) lignin and steam explosion (S-E) lignin. High-performance gel permeation chromatography (HP-GPC) analysis showed that the molecular weight (Mw) of SAQ and S-E lignins were increased by 1.43-and 1.14-fold, respectively, after the enzymatic treatment. Thermogravimetric analysis (TGA) also showed that the thermal stability of the lignins was improved, indicating that the enzyme treatment of lignins with rLiPH8 resulted in lignin re-polymerization. As the first report on rLiPH8 production using P. pastoris, this study has shed light on the possible route for the enhancement of rLiPH8 production and its potential application for upgrading technical lignins.

Studies on the assembly of large subunits of ribulose bisphosphate carboxylase in isolated pea chloroplasts.

Ribulose bisphosphate carboxylase consists of cytoplasmically synthesized "small" subunits and chloroplast-synthesized "large" subunits. Large subunits of ribulose bisphosphate carboxylase synthesized in vivo or in organello can be recovered from intact chloroplasts in the form of two different complexes with sedimentation coefficients of 7S and 29S. About one-third to one-half of the large subunits synthesized in isolated chloroplasts are found in the 7S complex, the remainder being found in the 29S complex. Upon prolonged illumination of the chloroplasts, newly synthesized large subunits accumulate in the 18S ribulose bisphosphate carboxylase molecule and disappear from both the 7S and the 29S large subunit complexes. The 29S complex undergoes an in vitro dissociation reaction and is not as stable as ribulose bisphosphate carboxylase. The data indicate that (a) the 7S large subunit complex is a chloroplast product, the (b) the 29S large subunit complex is labeled in vivo, that (c) each of these two complexes can account quantitatively for all the large subunits assembled into RuBPCase in organello, and that (d) excess large subunits are degraded in chloroplasts.

Coordination polymers of osmium: the nature of osmium black.

The design of cytochemical reagents that yield osmiophilic products from which an osmium black may be derived on exposure to osmium tetroxide has resulted in new methods described previously for the ultrastructural demonstration of enzyme activity and functional groups of macromolecules with the electron microscope. Attempts to determine the nature of the osmium black end products have been frustrated by their insolubility. The preparation of watersoluble analogs and their characterization as polymers suggest that the insoluble osmium blacks are coordination polymers. This is consonant with the unusually favorable properties of osmium black in electron microscopy. Although polymers of osmium have frequently been postulated as the end products of reaction of osmium tetroxide with tissue conistituents or with other organic compounds, this is the first example of their characterization.

The analysis of oral air using selected ion flow tube mass spectrometry in persons with and without a history of oral malodour.

OBJECTIVES: Oral malodour is a common disorder predominantly caused by bacterial metabolism of food stuffs in the mouth. It is routinely diagnosed and monitored by either the subjective rating or the measurement of oral volatile sulphur compound (VSC) levels. Non-sulphur compounds are also believed to contribute significantly to the condition although there is currently no direct means to assess their levels. In this study, we utilized selective flow tube mass spectrometry (SIFT-MS) to measure, in real time, a range of sulphur and non-sulphur containing compounds in oral air to determine whether the technique can be used to objectively monitor oral malodour. METHODS: Oral malodour was assessed using organoleptic scores in subjects with and without a history of oral malodour (n = 18) by a trained rater, while the chemical composition of oral air was analysed by both VSC sensor and SIFT-MS. RESULTS: Total VSC levels were significantly correlated with levels of hydrogen sulphide and methylmercaptan measured by SIFT-MS, but not with organoleptic scores. In subjects with elevated organoleptic score, only levels of methylmercaptan were significantly elevated. In three subjects with elevated tongue organoleptic scores but normal total VSC levels, SIFT-MS suggested that one subject possessed high levels of oral acetone while another had high oral levels of acetic acid. CONCLUSIONS: Our data suggest that SIFT-MS can be used to assess a wide range of compounds in oral air in addition to VSC to provide a clearer picture of the chemical nature of malodour. This may assist in the diagnosis and monitoring of the condition.

Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF.

BACKGROUND: High-density lipoprotein (HDL) is the sole lipoprotein present in follicular fluid (FF). The objectives of this study were to examine HDL lipid composition and associated enzyme activities in FF and serum and to relate these levels to embryo morphology parameters in women undergoing in vitro fertilization (IVF). METHODS: Serum and FF were prospectively obtained from 60 women undergoing IVF. HDL lipids, apolipoprotein AI (ApoAI), paraoxonase 1 (PON1) and paraoxonase 3 (PON3) activities were determined. Bivariate analysis and ordinal logistic regression models were employed to examine the associations between biochemical measures and embryo morphology parameters [embryo cell number (ECN) and embryo fragmentation score (EFS)] as surrogate markers of oocyte health. RESULTS: All biochemical parameters were significantly (P < 0.05) lower in FF than serum except PON3 levels which were significantly higher. FF-HDL cholesterol (OR 0.66, 95%CI 0.46-0.96) and ApoAI (OR 0.13, 95%CI 0.03-0.97) levels were negative predictors for EFS; however, their effects were not independent and the level of one moderated the effect of the other. Limited to Day 3 embryo transfers, FF-PON1-arylesterase activity was a significant positive predictor for ECN (OR 1.09, 95%CI 1.01-1.17). CONCLUSIONS: In this pilot study, our data suggests that HDL and its component proteins within FF may play protective roles in the health of the human oocyte and subsequent early embryo development. We describe for the first time the activities of PON1 and PON3 in FF. We suspect that PON3 activity may be locally generated due to higher activities in FF compared with serum.

[Alveolar capillary dysplasia and persistent pulmonary hypertension of the newborn]. / La dysplasie alvéolo-capillaire: une cause exceptionnelle d'hypertension artérielle pulmonaire persistante du nouveau né. A propos d'un cas.

Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. The diagnosis of this condition is made by histological study of a pulmonary biopsy. Familial forms and associated genitor-urinary and gastrointestinal malformations have been reported. Despite optimal management, the prognosis remains poor. The authors report the case of a neonate who developed cyanosis and cardiogenic shock on the 10th day of life. There was no associated neonatal pathology. Echocardiography showed supra-systemic pulmonary hypertension with normal cardiac structure. Pulmonary vasodilator therapies (inhaled NO, prostacyclin, sildenafil, bosentan) were ineffective and the child died on the 25th day of life. Autopsy revealed alveolar capillary dysplasia.

[Fulminant myocarditis presenting like acute myocardial infarction in a 6-year-old girl]. / Myocardite aiguë fulminante mimant un infarctus du myocarde chez une enfant de 6 ans.

Acute myocarditis is a rare inflammatory cardiac disease in children with potentially fatal issue. Clinical findings are very variable from nausea and vomiting to acute cardiovascular collapse. The cardiac function can be reversible with circulatory support. We report the case of a 6-year-old girl with ECG changes like myocardial infarction and diagnosis of fulminant myocarditis. She developped rapidly a cardiogenic shock and died before treatment with mechanical circulatory support.

Use of phenobarbital and high doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in the treatment of brain tumor-bearing mice.

It has been shown that the nitrosoureas are substrates for hepatic microsomal enzymes in vitro and that phenobarbital (PB) administered in multiple doses prior to nitrosourea administration significantly reduces the activity of the nitrosoureas in murine brain tumor models. In the present study, the effect of PB on 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was assessed by determining the CCNU dose which would result in the long-term survival of 50% of the treated mice, and the CCNU dose which would result in the toxic death of 50% of the treated mice, with or without PB pretreatment in C56BL/6J mice. The therapeutic index, the CCNU dose which would result in the long-term survival of 50% of the treated mice, per the CCNU dose which would result in the toxic death of 50% of the treated mice, without PB pretreatment was 2.1; the therapeutic index of CCNU after PB pretreatment was 1.7. There is no significant difference between the therapeutic indices. Thus, the reduction in the tumoricidal activity of CCNU after PB pretreatment was restored by increasing the dose of CCNU without a significant change in its lethal toxicity.l