Performance and health of broiler chickens fed low erucic acid, lower fiber pennycress (CoverCressTM) grain.

CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to planting soybeans. Two experiments were conducted to evaluate 2 lines of the whole grain (CCWG-1: natural mutation and mutation breeding; CCWG-2: gene edited) and the whole grain pretreated with the potential palatability agent copper sulfate (CCWG-1-CuSO4; CCWG-2-CuSO4) as an ingredient for broilers. In Experiment 1, CCWG-1-CuSO4 was included in the diet at 0, 4, and 6% for 41 d. Feed intake, body weight gain, feed conversion, processing characteristics, organ weights, serum thyroid, macropathology and histology data were collected. In Experiment 2, broilers were fed diets containing Control, 2% CCWG-1, 4% CCWG-1, 4% CCWG-2, and 4.35% CCWG-1-CuSO4 for 42 d. Feed intake, body weight gain, feed conversion, organ weights, serum thyroid, blood chemistries, macropathology, and histology data were collected. In Experiment 1, feed intake and body weight were diminished with no effect on feed conversion for the birds consuming diets containing CCWG-1-CuSO4. In Experiment 2, feed intake and body weight were lower with no difference in feed conversion in birds fed diets containing greater than 2% CoverCress grain during d 0 to 28. During d 28 to 42 no difference in feed intake, body weight and an improvement in feed conversion was observed in birds fed all of the CoverCress grain products. In both experiments no significant negative effects were observed in processing, liver, kidney, and thyroid weights, T3, T4, blood chemistries, macropathology, and histopathology between the control and any of the CoverCress grain treatments. No difference in performance was observed in birds fed the mutant (4% CCWG-1) and gene-edited (4% CCWG-2) products. Pretreating CoverCress grain with copper sulfate did not have a significant effect on improving palatability. In conclusion, CoverCress grain can be safely fed to broilers when included at a target rate of 4% in diets and with total glucosinolate levels not to exceed 4.9 µmoles g-1.

Parental expectations before and after 12-month experience with video consultations combined with regular outpatient care for children with type 1 diabetes: a qualitative study.

AIM: To explore parents' expectations of the perceived barriers to and benefits of 1 year of monthly video consultations combined with regular outpatient care of children with type 1 diabetes. METHODS: The Virtual Diabetes Outpatient Clinic for Children and Youth (VIDIKI) study was a controlled, multicentre, perennial study with 240 participants from northern Germany. Fifty-four qualitative interviews with parents were analysed using qualitative content analysis. Before the intervention, 30 interviews were conducted to assess parents' expectations, and after 1 year, 24 interviews evaluated the experienced benefits and barriers to video consultations. RESULTS: Four main topics were identified from parents' responses to the video consultation. The main advantages of the video consultation compared with standard care were a higher frequency of contact for optimized insulin dosing and saving time; difficulties with internet connections were identified as the main barrier. A feeling of increased confidence with respect to insulin dosing was directly associated with telemedicine. Digital prescriptions and meeting the same diabetologist in both outpatient and telemedical care were mentioned as important improvements. The majority of interviewees preferred intervals of 4-6 weeks between video consultations. CONCLUSION: The higher frequency of contact with the diabetes team was considered a great relief by parents of children with type 1 diabetes. Apart from the time savings and flexibility in appointments, the most important advantages were the higher frequency of contact leading to short-term therapy adjustments and an increase in the ability to adjust therapy independently. (German Clinical Trials Registry No: DRKS00012645).

Highly efficient blazed grating with multilayer coating for tender X-ray energies.

For photon energies of 1 - 5 keV, blazed gratings with multilayer coating are ideally suited for the suppression of stray and higher orders light in grating monochromators. We developed and characterized a blazed 2000 lines/mm grating coated with a 20 period Cr/C- multilayer. The multilayer d-spacing of 7.3 nm has been adapted to the line distance of 500 nm and the blaze angle of 0.84° in order to provide highest efficiency in the photon energy range between 1.5 keV and 3 keV. Efficiency of the multilayer grating as well as the reflectance of a witness multilayer which were coated simultaneously have been measured. An efficiency of 35% was measured at 2 keV while a maximum efficiency of 55% was achieved at 4 keV. In addition, a strong suppression of higher orders was observed which makes blazed multilayer gratings a favorable dispersing element also for the low X-ray energy range.

Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content.

OBJECTIVE: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. METHODS: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. RESULTS: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43 g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. CONCLUSIONS: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d.

Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944).

PURPOSE: To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy. PATIENTS AND METHODS: Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy. RESULTS: Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001). CONCLUSIONS: After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.

Carbohydrate epitopes are immunodominant at the surface of infectious Neoparamoeba spp.

Amoebic gill disease, the main disease of concern to the salmon industry in Tasmania, is caused by the amoeba, Neoparamoeba spp. Experimental infection can only be induced by exposure to wild-type (WT) parasites isolated from the gills of infected fish, as cultured amoebae are non-infective. To characterize the surface antigens of WT parasites, we produced monoclonal antibodies (mAbs) using subtractive immunization. Mice inoculated with non-infective parasites were treated with cyclophosphamide, to deplete reactive lymphocytes, and then immunized with different antigen preparations from infective parasites. When whole parasites were used for boosting, the percentage of WT unique mAbs was very high (86%) as was the percentage of mAbs specific for carbohydrate epitopes (89%). When deglycosylated membranes were used, the numbers of mAbs specific for non-carbohydrate epitopes did not increase, but the total number of WT unique mAbs was reduced (86-40%). Using an untreated membrane preparation, the total number of mAbs to surface molecules was very high, but all recognized carbohydrate epitopes. The total number of mAbs recognizing carbohydrate epitopes on the surface of the WT parasites was 97%, suggesting that the dominant epitopes on the surface molecules unique to WT parasites are carbohydrate in nature.

[A historical medical study of post-traumatic stress disorders in World War I soldiers]. / Die posttraumatischen Belastungsstörungen bei deutschen Soldaten des 1. Weltkrieges. Eine medizinhistorische Studie.

The concept of post-traumatic stress disorder (PTSD) was to be verified considering World War I soldiers suffering from psychiatric and neurologic diseases. According to hypotheses, relevant circumstances of the case history and significance of the direct military action had to be examined. In 2002, medical histories dating from 1914 to 1921 of male soldiers in Jena, Germany, were analyzed. Statistical examination carried out by means of the chi2 test revealed mental illness more frequently in soldiers with relevant family anamnesis, previous psychiatric treatment, or degree of voluntariness than in soldiers not so characterized. The accumulation of mental illnesses was lower in soldiers involved in military actions or directly with firing weapons than in soldiers never involved in battles. These results are in accord with historical but not current literature on PTSD. The author is of the opinion that psychiatric anamnesis is not given enough consideration in the concept of PTSD.

Poverty and household food security of black South African farm workers: the legacy of social inequalities.

OBJECTIVE: To assess socio-economic indicators, nutritional status and living conditions of farm workers and their families, with the purpose to develop research and intervention programmes aimed at enhancing nutritional status and quality of life. DESIGN AND SETTING: Three farm schools in two districts of the North-West Province and farming communities were selected. Anthropometrical measurements, structured face-to-face questionnaires and focus group discussions were carried out in 2002 and 2003 by a multidisciplinary research team. RESULTS: Access to electricity, water and sanitation, as well as monthly food rations or subsidies, vary and depend on farm owners. The majority of adults have education below or up to grade four, farm schools provide only up to grade seven. Distance to farm schools and intra-household issues hamper children's attendance and performance at school. Household food security is compromised due to a lack of financial resources, infrastructure and also household resource allocation. This impacts negatively especially on children, with half of them being underweight, stunted or wasted. Employment is usually linked to men, while most women have access to casual jobs only. Insecurity of residence and the perceived disempowered position towards farm owners add to feelings of hopelessness and stress. CONCLUSIONS AND RECOMMENDATIONS: This study highlights destitute living conditions of farm worker families. Apart from structural and financial constraints, paternalistic structures of the past might also hamper development. Based on these findings, follow-up research projects and in-depth investigations into underlying social issues with regard to nutrition insecurity and livelihoods of farm workers were initiated.

Nutrition security, livelihoods and HIV/AIDS: implications for research among farm worker households in South Africa.

OBJECTIVE: Previous research on the health transition and nutrition security in black South African households revealed the need for further research among farm workers who belong to the poorest population categories. This article gives an overview of the link between nutrition security, livelihoods and HIV/AIDS in South Africa, drawing conclusions for research among farm worker households. DESIGN AND SETTING: A literature review, observations on farms and interviews with farmers and key informants were carried out in 2003 and 2004. Peer examination was done with South African and German researchers from the natural and social sciences. RESULTS: Farm workers face poverty and nutrition insecurity and continue to be a tragically underserved population group, also in terms of research. There is furthermore a lack of in-depth research on underlying causes for nutrition security in South Africa and on the link with livelihoods, poverty and HIV/AIDS. Micro-social qualitative research from the household and gender perspective is required, as valid data on households, their internal dynamics and therefore the reflection of social realities are missing. A multidisciplinary research approach based on a new conceptual framework was developed to address the situation of farm worker households. CONCLUSION: The outlined research contributes to existing programmes on farms in the North West Province, with the findings being valid also for other parts of southern Africa facing poverty, nutrition insecurity and HIV/AIDS.

Empowered women, social networks and the contribution of qualitative research: broadening our understanding of underlying causes for food and nutrition insecurity.

OBJECTIVE: To investigate underlying causes for food and nutrition insecurity in black South African households and to gain understanding of the factors contributing to better nutrition security, with emphasis on household organisation, gender and intra-household dynamics and social networks. DESIGN, SETTING AND SUBJECTS: Within a larger cross-sectional survey that investigated the impact of urbanisation on the health of black South Africans, 166 people, mostly women, were interviewed on household food security. Methods used were structured face-to-face interviews, in-depth interviews, observation, interviews with key informants and a sociodemographic questionnaire. Information was collected from 1998 to 2000 in 15 rural and urban areas of the North West Province, South Africa. RESULTS: Three-quarters of households in this sample are chronically food-insecure. Families are disrupted, due to migrant work, poverty and increasing societal violence, and half of households are female-headed. Certain categories of female-headed households and households based on partnership relationships, despite more limited resources, achieve a better or an equal economic status and better nutrition security than those households led by men, with the latter often being considered an economic liability. The reliance on and fostering of social ties and networks appear to be of central significance. CONCLUSION: Gender and intra-household relations, as well as social networks and income from informal sector activities, are often not uncovered by conventional statistical methods. Qualitative research can reveal the unexpected and furthermore empowers people, as their voices are heard.

Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating.

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned B (hStnB). Human stoned B is a brain-specific protein which co-enriches with other endocytic proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve terminals. A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu 2 homology domain of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle recycling by facilitating vesicle uncoating.

Evaluation of methods for predicting the toxicity of polycyclic aromatic hydrocarbon mixtures.

Risk assessments of polycyclic aromatic hydrocarbon mixtures are hindered by a lack of reliable information on the potency of both mixtures and their individual components. This paper examines methods for approximating the toxicity of polycyclic aromatic hydrocarbon (PAH) mixtures. PAHs were isolated from a coal tar and then separated by ring number using HPLC. Five fractions (A-E) were generated, each possessing a unique composition and expected potency. The toxicity of each fraction was measured in the Salmonella/mutagenicity assay and the Chick Embryo Screening Test (CHEST). Their abilities to induce ethoxyresorufin-O-deethylase and to inhibit gap junction intercellular communication in rat liver Clone 9 cells were also measured. In the Salmonella/mutagenicity assay, fractions were predicted to have potencies in the order C > D > E > B > A. Toxic equivalency factors (TEFs) for fractions A-E were in the order E > or = D > C > B > A. TEF values were 20,652, 20,929, 441, 306, and 74.1 micrograms of BaP equiv/g, respectively. A lack of agreement between assay-predicted potencies and chemical analysis-predicted potencies was observed with other assays and other methods of calculation. The results demonstrate the limitations of using a single method to predict the toxicity of a complex PAH mixture.

Investigation of organophilic montmorillonite clay inclusion in zearalenone-contaminated diets using the mouse uterine weight bioassay.

Previous studies with low-pH montmorillonite (LPHM) clay exchanged with alkylammonium compounds showed that these organo clays were quite effective in sorbing the estrogenic mycotoxin zearalenone (ZEN) from aqueous solution. The potential toxicity of these types of clays, in particular hexadecyltrimethylammonium (HDTMA) LPHM, led to the investigation of the sorption efficacy of clay exchanged with a less toxic primary amine analog, hexadecylamine (HDA). Isothermal analysis studies showed that HDA LPHM was able to bind ZEN, but less effectively than HDTMA LPHM as evidenced by a significantly lower Freundlich K (63,900 vs. 845). The in vivo effectiveness of these two clays to bind ZEN was tested utilizing the mouse uterine weight bioassay. At a dietary inclusion level of 0.25%, the clays did not have a negative impact on overall animal health as measured by final body weight; however, they did not protect the animals from the estrogenic effects induced by 35 mg ZEN/kg in the feed (i.e., the uterine weights were not reduced in comparison to ZEN alone). In fact, the HDTMA LPHM group showed an increase in uterine weight that was more than the ZEN treatment group. When the animals were fed 0.5% clay, both exchanged clays (i.e., HDTMA LPHM and HDA LPHM) resulted in decreased body weight gain. The uterine weights of ZEN-fed animals (either alone or in combination with clays) were not significantly different from each other. In contrast, the uterine:body weight ratio showed a dramatic increase in the groups fed exchanged clay + ZEN compared to ZEN alone. These results suggest that alkylamine groups may assist the transport or uptake of ZEN and result in an enhanced toxicity from contaminated feed. The findings from this study clearly demonstrate the need for careful testing of all mycotoxin-binding agents before their inclusion in the diet.

Deamination of fumonisin B(1) and biological assessment of reaction product toxicity.

Fumonisin B(1), a potent mycotoxin found in grain, has been resistant to degradation and detoxification by a variety of methods, including milling, fermentation, ammoniation, and ozonation. The primary amine of this compound contributes significantly to its toxicity; therefore, the major aim of this research was to remove this moiety via diazotization. In this study, fumonisin B(1) was deaminated in aqueous solution under conditions of acidic pH and low temperature (pH 1.0 and 5 degrees C) with the addition of NaNO(2). The concentration of fumonisin B(1) in the solution was analyzed by HPLC using o-phthaldialdehyde to derivatize the primary amine. Progress of the reaction was monitored as a loss of the derivatized peak as observed by HPLC with fluorescence detection. TLC analysis showed the disappearance of fumonisin B(1) following diazotization. Further, TLC displayed at least four reaction products that were not primary amines. Matrix-assisted laser desorption/ionization mass spectrometry coupled with time-of-flight analysis of the diazotization products also showed a diminished amount of authentic fumonisin B(1) and allowed identification of a product formed by the replacement of the primary amine with a hydroxyl group. The adult Hydra attenuata bioassay indicated a marked decrease in the toxicity of the products in comparison to parent fumonisin B(1). Optimization of this reaction could result in a rapid and practical method for the reclamation of fumonisin B(1)-contaminated feeds.

Development and characterization of a carbon-based composite material for reducing patulin levels in apple juice.

Patulin, a heterocyclic lactone produced by various species of Penicillium and Aspergillus fungi, is often detected in apple juices and ciders. Previous research has shown the effectiveness of granular activated carbon for reducing patulin levels in aqueous solutions, apple juices, and ciders. In this study, ultrafine activated carbon was bonded onto granular quartz to produce a composite carbon adsorbent (CCA) with a high carbonaceous surface area, good bed porosity, and increased bulk density. CCA in fixed-bed adsorption columns was evaluated for efficacy in reducing patulin levels from aqueous solutions and apple juice. Columns containing 1.0, 0.5, and 0.25 g of CCA were continuously loaded with a patulin solution (10 microg/ml) and eluted at a flow rate of 1 ml/min. Results indicated that 50% breakthrough capacities for patulin on 1.0-, 0.5-, and 0.25-g CCA columns were 137.5, 38.5, and 19.9 microg, respectively. The effectiveness of CCA to adsorb patulin and prevent toxic effects was confirmed in vitro using adult hydra in culture. Hydra were sensitive to the effects of patulin, with a minimal affective concentration equal to 0.7 microg/ml; CCA adsorption prevented patulin toxicity until 76% breakthrough capacity was achieved. Fixed-bed adsorption with 1.0 g of CCA was also effective in reducing patulin concentrations (20 microg/liter) in a naturally contaminated apple juice, and breakthrough capacities were shown to increase with temperature. Additionally, CCA offered a higher initial breakthrough capacity than pelleted activated carbon when compared in parallel experiments. This study suggests that CCA used in fixed-bed adsorption systems effectively reduced patulin levels in both aqueous solutions and naturally contaminated apple juice; however, the appearance and taste of apple juice may be affected by the treatment process.

Conditional transformation of rat embryo fibroblast cells by a cyclin D1-cdk4 fusion gene.

Cyclin D1 gene overexpression is a frequent event in a number of human cancers. These observations have led to the suggestion that cyclin D1 alterations might play a role in the etiology of cancer. This possibility is supported by the finding that transfection of mammalian cells with cyclin D1 can accelerate progression through the G1 phase of the cell cycle. Moreover, cyclin D1 can function as an oncogene by cooperating with activated Ha-ras to transform primary rat embryo fibroblasts (REFs). In addition, cyclin D1 transgenics develop hyperplasia and neoplasia of the thymus and mammary gland. We have constructed a novel fusion gene consisting of full-length human cyclin D1 and cdk4 genes. This fusion gene was expressed in insect cells and the fusion protein was shown to be enzymatically active. The fusion gene was expressed in mammalian cells under the control of tet-repressor. This fusion gene immortalized primary REFs, and cooperated with activated Ha-ras to transform primary REFs, in terms of anchorage-independent growth in vitro and formation of tumors in vivo. Utilizing a tet-regulated gene expression system, we have shown that proliferation of stably transfected primary REFs in vitro and in vivo is dependent on the continued expression of the cyclin D1-cdk4 fusion gene. These cell lines could be useful in the discovery of novel cancer therapeutics to modulate cyclin D1.cdk4 activity.

Molecular characterization of high affinity, high capacity clays for the equilibrium sorption of ergotamine.

Ergot alkaloids (mycotoxins) produced by Claviceps and Neotyphodium species of fungi may contaminate animal feedstuffs and results in disease in livestock. In this study, diverse phyllosilicate clays and other adsorbent materials, differing in chemical and structural characteristics, were tested for their ability to sorb ergotamine, a prevalent ergot mycotoxin, from acidic solution. Results indicated minimal binding to those sorbents possessing low surface area, cation exchange capacity and inaccessible interlayer regions. Cetyl pyridinium-exchanged montmorillonite (organoclay) exhibited decreased propensity for ergotamine in acidic solution as compared with the unexchanged hydrophilic parent clay. The highest ergotamine sorption was observed with cation exchanged montmorillonite clays; whereas, when collapsed, these same clays sorbed very little ligand. Based on initial binding experiments, calcium and sodium montmorillonite clays were prioritized for further characterization, including: capacity, affinity, and heat (enthalpy) of adsorption. Computer models of energy-minimized ergotamine isomers and clay were used to illustrate possible mechanisms of ergot alkaloid sorption at interlayer sites. Additional studies are warranted to assess the stability of ergot alkaloid/clay complexes under alkaline conditions to further understand the mechanism of adsorption.

Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420.

PURPOSE: The Cancer and Leukemia Group B conducted parallel phase I trials of cytarabine, daunorubicin, and etoposide (ADE) with or without PSC-833 (P), a modulator of p-glycoprotein-mediated multidrug resistance. PATIENTS AND METHODS: One hundred ten newly diagnosed patients > or = 60 years of age with de novo acute myeloid leukemia (AML) were treated. All patients received cytarabine by continuous infusion for 7 days at 100 mg/m(2)/d. The starting dose of daunorubicin was 30 mg/m(2)/d for 3 days. Etoposide was administered at a dose of 100 mg/m(2)/d for 3 days, except in the last cohort administered ADEP, who received 60 mg/m(2). PSC-833 was given intravenously with a loading dose of 1.5 mg/kg over 2 hours and a simultaneous continuous infusion of 10 mg/kg/d continued until 24 hours after the last dose of daunorubicin or etoposide. RESULTS: There was no toxicity attributed to the PSC-833. Dose-limiting toxicity was primarily gastrointestinal (diarrhea, mucositis in the ADEP group). The estimated maximum-tolerated doses, calculated using a logistic regression model, were daunorubicin 40 mg/m(2)/d for 3 days with etoposide 60 mg/m(2) for 3 days in the ADEP group and daunorubicin 60 mg/m(2)/d for 3 days and etoposide 100 mg/m(2)/d for 3 days in the ADE group. Twenty-one (48%) of 44 patients achieved complete remission with ADE, compared with 29 (44%) of 66 patients treated with ADEP. CONCLUSION: It is necessary to decrease the doses of daunorubicin and etoposide when they are administered with PSC-833, presumably because of the effect of the modulator on the pharmacokinetics of these agents. A phase III trial comparing the regimens derived from this phase I trial has recently begun.

Utilization of electrochemically generated ozone in the degradation and detoxication of benzo[a]pyrene.

The ability of electrochemically generated ozone (O3) to degrade and detoxify the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) was assessed utilizing the chick embryotoxicity screening test (CHEST) and Hydra attenuata bioassays. Aqueous solutions containing 10 microg/ml BaP and 0.5% (v/v) acetonitrile were subjected to ozonolysis for 0 to 30 min. Rapid degradation of BaP was evident by both gas chromatography/mass spectroscopy (GC/MS) and high-performance liquid chromatography (HPLC) analysis. HPLC fluorescence detection revealed no BaP shortly after 5 min of ozonolysis, while HPLC with PDA detection demonstrated continued reactions with ozone over the 30-min time course. As little as 2 min of O3 treatment afforded protection from BaP-induced mortality and toxicity (embryolethality and liver discoloration) in the chicken embryos. In the hydra bioassay, no toxicity was observed in the adult hydra until the ozonolysis products were reconstituted 100-fold from their initial post-ozonolysis concentrations. The results obtained from this study clearly demonstrate the potential application of electrochemically generated O3 for the detoxication and prevention of toxicity of BaP. Both CHEST and hydra assays predict that the ozonolysis products of BaP are less toxic than the parent compound.