Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 270
Filter
1.
Cancer Genet ; 264-265: 29-32, 2022 06.
Article in English | MEDLINE | ID: mdl-35306447

ABSTRACT

Li-Fraumeni syndrome, caused by germline pathogenic variants in TP53, results in susceptibility to multiple cancers. Variants of uncertain significance (VUS) and reclassification of variants over time pose management concerns given improved survival with cancer surveillance for LFS patients. We describe the experience of TP53 variant reclassification at a pediatric cancer center. METHODS: We reviewed medical records (2010-2019) of 756 patients seen in Texas Children's Cancer Genetics Clinic. We noted initial TP53 classification and any reclassifications. We then classified TP53 variants following ClinGen TP53 variant curation expert panel recommendations using data from ClinVar, medical literature and IARC database. RESULTS: Of 234 patients tested for TP53, 27 (11.5%) reports contained pathogenic/likely pathogenic (P/LP) variants and 7 (3)% contained VUS. By January 2022, 4 of 6 unique VUS and 2 of 16 unique P/LP variants changed interpretations in ClinVar. Reinterpretation of these 4 VUS in ClinVar matched clinical decision at the time of initial report. Applying TP53 VCEP specifications classified 3 VUS to P/LP/benign, and one pathogenic variant to likely benign. CONCLUSIONS: Planned review of variant significance is essential, especially for patients with high probability of LFS.


Subject(s)
Genetic Predisposition to Disease , Li-Fraumeni Syndrome , Child , Genetic Testing , Germ Cells , Germ-Line Mutation/genetics , Humans , Li-Fraumeni Syndrome/epidemiology , Li-Fraumeni Syndrome/genetics , Tumor Suppressor Protein p53/genetics
2.
Vet J ; 273: 105676, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34148599

ABSTRACT

Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.


Subject(s)
Antigens, Bacterial/immunology , Antigens, Surface/immunology , Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines/immunology , Lipoproteins/immunology , Lyme Disease Vaccines/immunology , Animals , Antibodies, Bacterial/immunology , Antibody Formation , Borrelia burgdorferi/immunology , Dog Diseases/immunology , Dog Diseases/prevention & control , Dogs , Female , Lyme Disease/prevention & control , Lyme Disease/veterinary , Male , Vaccination/veterinary
3.
Poult Sci ; 98(8): 3176-3180, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-30953077

ABSTRACT

The purpose of this study was to determine if Eimeria oocysts recovered from litter at the time of chick placement in commercial broiler houses contained oocysts that were infectious for chickens. Over 100 litter samples were collected from 30 poultry farms representing a total of 60 different broiler houses with 9 houses sampled more than once over 1.5 yr. The samples were collected just before the placement of newly hatched chicks and after an anticoccidial drug (ACD) or Eimeria vaccine (VAC) program, and processed for counting oocysts followed by Eimeria species determination using ITS1 PCR. Broiler chicks were inoculated with recovered Eimeria oocysts to determine if the litter oocysts were viable and capable of causing patent infection. At placement, E. maxima (Emax) oocysts were detected in 70 of 75 houses after ACD program and 46 of 47 houses after VAC program. Eimeria acervulina, E. praecox, and/or E. tenella (Eapt) were detected in 75 of 75 houses after ACD program and 47 of 47 houses after VAC program. Viability testing revealed that 33.0% of broiler houses contained viable Emax oocysts, while 46.9% contained viable Eapt oocysts. During VAC programs, the concentration of Emax oocysts at placement and the total number of Emax oocysts shed by chickens in viability studies showed a very strong correlation (r = 0.83). Likewise, during ACD programs, the concentration of Eapt oocysts at placement and the total number of Eapt oocysts shed by chickens in the viability study showed a strong correlation (r = 0.62). In general, Eimeria oocyst levels at placement and number of viable oocysts shed by chickens in the viability study were similar among houses on the same farm. However, the number of Eimeria oocysts shed in the viability studies was considerably less than expected based on the number of oocysts given. These data suggest that nearly 100% of all poultry houses contain Emax and Eapt oocysts at placement with 30 to 50% of the houses containing viable Eimeria oocysts, thus possibly representing a source of the protozoa to newly hatched chicks.


Subject(s)
Coccidiosis/veterinary , Eimeria/isolation & purification , Oocysts/isolation & purification , Poultry Diseases/transmission , Animals , Animals, Newborn , Chickens , Coccidiosis/prevention & control , Coccidiosis/transmission , Coccidiostats/administration & dosage , Housing, Animal , Poultry Diseases/parasitology , Poultry Diseases/prevention & control , Protozoan Vaccines/administration & dosage , Vaccination/veterinary
4.
Nervenarzt ; 88(3): 222-233, 2017 Mar.
Article in German | MEDLINE | ID: mdl-27220643

ABSTRACT

In this article the guideline-adherent psychiatric psychotherapeutic treatment of patients with bipolar disorders is outlined and the required resources are estimated. Based on the core recommendations of the S3 guidelines for diagnostics and treatment of bipolar disorders published in 2012, inpatient treatment needs in hours per week and per patient are determined for both manic and bipolar depressive episodes. The resulting staffing requirements are estimated on this basis. In summary, for guideline-adherent inpatient psychiatric psychotherapeutic treatment the additional needs regarding the physician/psychotherapeutic domain add up to 44 min per patient and week during a manic episode and 88 min for patients with bipolar depression when compared to current psychiatry staffing regulations.


Subject(s)
Bipolar Disorder/therapy , Hospitalization/statistics & numerical data , Personnel Staffing and Scheduling/statistics & numerical data , Practice Guidelines as Topic , Psychotherapy/standards , Workload/statistics & numerical data , Bipolar Disorder/diagnosis , Bipolar Disorder/epidemiology , Germany/epidemiology , Guideline Adherence/standards , Guideline Adherence/statistics & numerical data , Humans , Inpatients/statistics & numerical data , Needs Assessment , Personnel Staffing and Scheduling/standards , Psychiatry/standards , Psychiatry/statistics & numerical data , Workload/standards
5.
Nervenarzt ; 87(5): 496-505, 2016 May.
Article in German | MEDLINE | ID: mdl-27126577

ABSTRACT

BACKGROUND: Although in recent years many efforts have been made in suicide prevention, suicidal ideation in prison is still a major problem. The present study is part of a project being carried out in Saxony, Germany on the investigation and prevention of suicide in prisons. OBJECTIVE: The aim of this study was to determine whether the duration of imprisonment, personality traits and personality disorders have an influence on the suicidal ideation of prisoners. MATERIAL AND METHODS: In this study 113 volunteers among prisoners from 6 prisons in Saxony participated in a structured interview and filled out several questionnaires on sociodemographic details, personality using the personality style and disorder inventory (PSSI) and the assessment of DSM-IV personality disorders (ADP-IV) questionnaire as well as attitudes towards suicide using the questionnaire on stressful social experiences (FBS) and the Viennese instrument for suicidality on correctional institutions (VISCI). RESULTS: Significant correlations were found between personality traits and personality disorders and suicidal ideation and suicide attempts. A positive correlation was also found between personality disorders and scores in the VISCI. High scores in the PSSI were correlated with all aspects of suicidal ideation; however, length of time spent in prison and total duration of imprisonment appeared to have little impact on suicide parameters and were only correlated with the self-declared current suicidal ideation. DISCUSSION: Although there were some limitations, this study could confirm data in the literature that personality disorders are associated with an increased risk of suicidal ideation in prisoners. The lack of association of suicidal thoughts as measured in this study with the total time spent in prison and duration of imprisonment is in contradiction to the results of other studies and warrants further investigation.


Subject(s)
Prisoners/psychology , Suicidal Ideation , Adolescent , Adult , Cross-Sectional Studies , Female , Germany , Humans , Interview, Psychological , Male , Middle Aged , Motivation , Personality Disorders/diagnosis , Personality Disorders/psychology , Statistics as Topic , Surveys and Questionnaires , Young Adult
6.
Nanoscale ; 7(37): 15434-41, 2015 Oct 07.
Article in English | MEDLINE | ID: mdl-26335720

ABSTRACT

Filament growth is a key aspect in the operation of bipolar resistive random access memory (RRAM) devices, yet there are conflicting reports in the literature on the direction of growth of conductive filaments in valence change RRAM devices. We report here that an insulating gap between the filament and the semiconductor electrode can be detected by the metal-insulator-semiconductor bipolar transistor structure, and thus provide information on the filament growth direction. Using this technique, we show how voltage polarity and electrode chemistry control the filament growth direction during electro-forming. The experimental results and the nature of a gap between the filament and an electrode are discussed in light of possible models of filament formation.


Subject(s)
Computer Storage Devices , Electrodes , Models, Theoretical , Semiconductors , Electric Conductivity , Equipment Design , Nanotechnology
7.
Ann Oncol ; 26(6): 1194-1200, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25858497

ABSTRACT

BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Thiazoles/therapeutic use , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzamides , Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/enzymology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Europe , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Oxidoreductases/genetics , Pancreatic Neoplasms/enzymology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pharmacogenetics , Piperidines , Precision Medicine , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Pyridines , Risk Factors , Thiazoles/adverse effects , Time Factors , Treatment Outcome , United States , Gemcitabine
8.
Nanotechnology ; 26(8): 085303, 2015 Feb 27.
Article in English | MEDLINE | ID: mdl-25648852

ABSTRACT

We present experimental results showing how the growth rate, morphology and crystal structure of Au-catalyzed InP nanowires (NWs) fabricated by selective area metal organic molecular beam epitaxy can be tuned by the growth parameters: temperature and phosphine flux. The InP NWs with 20-65 nm diameters are grown at temperatures of 420 and 480 °C with the PH3 flow varying from 1 to 9 sccm. The NW tapering is suppressed at a higher temperature, while pure wurtzite crystal structure is preferred at higher phosphine flows. Therefore, by combining high temperature and high phosphine flux, we are able to fabricate non-tapered and stacking fault-free InP NWs with the quality that other methods rarely achieve. We also develop a model for NW growth and crystal structure which explains fairly well the observed experimental tendencies.

9.
RSC Adv ; 4(53): 28036-28040, 2014.
Article in English | MEDLINE | ID: mdl-26052433

ABSTRACT

We demonstrate an enzyme stabilization approach whereby a model enzyme is PEGylated, followed by controlled chemical modification with glutaraldehyde. Using this stabilization strategy, size increases and aggregation due to intermolecular crosslinking are avoided. Immediately following synthesis, the PEGylated enzyme with and without glutaraldehyde modification possessed specific activities of 372.9 ± 20.68 U/mg and 373.9 ± 15.14 U/mg, respectively (vs. 317.7 ± 19.31 U/mg for the native enzyme). The glutaraldehyde-modified PEGylated enzyme retains 73% original activity after 4 weeks at 37 °C (vs. 2% retention for control).

10.
Nanotechnology ; 24(47): 475302, 2013 Nov 29.
Article in English | MEDLINE | ID: mdl-24177750

ABSTRACT

Indium phosphide nanowires were grown by metalorganic molecular beam epitaxy using the selective-area vapor-liquid-solid method. We show experimentally and theoretically that the size of the annular opening around the nanowire has a major impact on nanowire growth rate. In addition, we observed a considerable reduction of the growth rate in dense two-dimensional arrays, in agreement with a calculation of the shadowing of the scattered precursors. Due to the impact of these effects on growth, they should be considered during selective-area vapor-liquid-solid nanowire epitaxy.

11.
Toxicol In Vitro ; 27(2): 798-803, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23274917

ABSTRACT

Precision-cut lung slices (PCLSs) are an organotypic lung model that is widely used in pharmacological, physiological, and toxicological studies. Genotoxicity testing, as a pivotal part of early risk assessment, is currently established in vivo in various organs including lung, brain, or liver, and in vitro in cell lines or primary cells. The aim of the present study was to provide the three-dimensional organ culture PCLS as a new ex vivo model for determination of genotoxicity using the Comet assay. Murine PCLS were exposed to increasing concentrations of ethyl methane sulfonate 'EMS' (0.03-0.4%) and formalin (0.5-5mM). Tissue was subsequently dissociated, and DNA single-strand breaks were quantified using the Comet assay. Number of viable dissociated lung cells was between 4×10(5) and 6.7×10(5)cells/slice. Even treatment with EMS did not induce toxicity compared to untreated tissue control. As expected, DNA single-strand breaks were increased dose-dependently and significantly after exposure to EMS. Here, tail length rose from 24µm to 75µm. In contrast, formalin resulted in a significant induction of DNA cross-links. The effects induced by EMS and formalin demonstrate the usefulness of PCLS as a new ex vivo lung model for genotoxicity testing in the early risk assessment of airborne substances in the future.


Subject(s)
Comet Assay/methods , Lung/drug effects , Mutagens/toxicity , Animals , Antineoplastic Agents, Alkylating/toxicity , DNA Damage , Ethyl Methanesulfonate/toxicity , Female , Formaldehyde/toxicity , In Vitro Techniques , Lung/metabolism , Mice , Mice, Inbred BALB C
12.
Nanotechnology ; 23(46): 465201, 2012 Nov 23.
Article in English | MEDLINE | ID: mdl-23093285

ABSTRACT

The resistive switching effect in metal oxides and other dielectric materials is among the leading future non-volatile memory technologies. Resistive switching is widely ascribed to the formation and rupture of conductive filaments in the oxide, which are generated by temperature-enhanced nano-scale ion migration or other thermal effects. In spite of the central role of the local filament temperature on the switching effect, as well as on the conduction and reliability physics, no measurement methods of the filament temperature are yet available. In this work, we report on a method for evaluating the conducting filament temperature, using a metal-insulator-semiconductor bipolar transistor structure. The filament temperature is obtained by analyzing the thermal excitation rate of electrons from the filament Fermi level into the conduction band of a p-type semiconductor electrode. Measurements were carried out to obtain the conductive filament temperature in hafnia at varying ambient temperatures in the range of 3-300 K. Significant Joule heating of the filament was observed across the entire measured ambient temperature range. The extracted temperatures provide physical insight into the resistive switching effect.

13.
Pharmacopsychiatry ; 45(1): 1-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21989601

ABSTRACT

INTRODUCTION: The aim of this prospective study was to investigate the influence of lithium serum levels on subclinical psychopathological features during the euthymic interval in patients with an affective disorder. METHODS: The study included 54 patients with a recurrent affective disorder undergoing a continuous prophylactic lithium treatment (31 unipolar, 23 bipolar). The observation period lasted for 2 years and included 332 visits. Visits consisted of a detailed interview, a continuous measurement of lithium levels and the collection of validated scales including HAMD, YMRS, CGI, VAMS and the SCL-90R. Several correlations between lithium serum levels and different psychopathological features during the euthymic interval were calculated on an individual patient basis and on a group basis to reveal generally occurring correlations. RESULTS: No generally occurring significant correlations between lithium serum levels and specific psychopathological features were found. Only on a single patient level, 32 significant correlations between lithium level and specific psychopathological features were found, partly indicating a negative and partly indicating a positive influence of higher lithium levels on psychopathological symptoms. Nevertheless, in the group analyses no significant correlations were found. DISCUSSION: Higher lithium levels were not associated with an improved psychopathological status, but they were not associated with a worse status (due to a higher burden of side effects) either. According to the literature there is currently no strong evidence to treat patients with a higher lithium level. It is recommended to start with a lower level and to continue with individual adjustments in accordance to prophylactic efficacy and tolerability.


Subject(s)
Affective Disorders, Psychotic/blood , Affective Disorders, Psychotic/psychology , Antimanic Agents/therapeutic use , Drug Monitoring , Lithium Chloride/therapeutic use , Lithium/blood , Adult , Affect/drug effects , Affective Disorders, Psychotic/physiopathology , Affective Disorders, Psychotic/prevention & control , Aged , Antimanic Agents/adverse effects , Antimanic Agents/pharmacokinetics , Female , Germany , Hospitals, University , Humans , Lithium Chloride/adverse effects , Lithium Chloride/pharmacokinetics , Male , Medical Records , Middle Aged , Outpatient Clinics, Hospital , Prospective Studies , Psychiatric Status Rating Scales , Secondary Prevention , Young Adult
14.
Arq. bras. med. vet. zootec ; 63(6): 1541-1546, dez. 2011. tab
Article in Portuguese | LILACS | ID: lil-608980

ABSTRACT

Verificou-se a ocorrência de bactérias do gênero Aeromonas e estimou-se o prazo de validade comercial de filés de pintado (Pseudoplatystoma coruscans) com pele, durante estocagem em refrigeração por meio da quantificação de microrganismos heterotróficos aeróbios psicrotróficos e análises físico-químicas para determinação do pH e detecção de amônia e gás sulfídrico. Foram utilizadas 45 amostras de filé de pintado, com aproximadamente 100 gramas cada, embaladas individualmente em polietileno de alta densidade e armazenadas em câmara frigorífica entre 0ºC e 3ºC. A cada dois a três dias de estocagem, três unidades de filés foram submetidas a análises microbiológicas e físico-químicas, totalizando 15 análises durante o período de estocagem. As contagens de Aeromonas sp. e microrganismos heterotróficos aeróbios psicrotróficos variaram de 1,89 a 9,47logUFC/g e 0 a 6,54logUFC/g, respectivamente. A variação do pH foi de 6,20 a 6,97, e as análises de amônia e gás sulfídrico foram negativas durante todo o período. O pH dos filés de pintado atingiu o limite máximo de 6,4 aos 23 dias de estocagem, e estimou-se o seu prazo de validade comercial.


This word studied the occurrence of bacteria from genus Aeromonas and estimate the shelf life of "pintado" fish fillets (Pseudoplatystoma coruscans), during cold storage, through the quantification of psychrotrophic aerobic microorganisms, physical and chemical analyses for presence of ammonia and gas sulphide (H2S) and pH as used in 45 samples of "pintado" fillets with approximately 100 grams each, individually packed in high density polyethylene and stored in cold storage (0ºC to 3ºC). Every 2-3 days of storage, 3 units of fillets were subjected to microbiological and physicochemical analysis for a total of 15 days during the storage period. The Aeromonas sp. and psychrotrophic microorganisms count varied from 1.89 to 9.47logCFU/g and 0 to 6.54logCFU/g, respectively. The pH variation was from 6.20 to 6.97 and ammonia and H2S analyses were negative during the whole period. According under Brazilian legislation (Brazil, 1981) estimated the commercial shelf life of "pintado" fillets being 23 days when the pH reached a value of 6.4. The pH of the "pintado" fillets reached the maximum limit of 6.4 at 23 days of storage, being its estimated commercial shelf life.

15.
Avian Dis ; 54(3): 1002-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20945780

ABSTRACT

The purpose of the present study was to evaluate the species composition and salinomycin sensitivity of Eimeria oocysts isolated from commercial broiler farms that differed by means of coccidiosis control (anticoccidial drugs [ACD] vs. live oocyst vaccines [VAC]). A comparison of Eimeria species composition and salinomycin sensitivity was also made before and after a producer switched from salinomycin to live oocyst vaccines. In general, no significant difference was observed in the concentration of Eimeria spp. oocysts in litter from VAC-utilizing farms compared to litter from ACD-utilizing farms. Application of PCR-based methods to detect coccidia found that Eimeria species distribution in litter from VAC operations more closely resembled the species composition in the live oocyst vaccines. Drug sensitivity testing found that Eimeria oocysts from VAC operations displayed greater salinomycin sensitivity as measured by weight gain and feed conversion efficiency compared to oocysts from ACD farms. These findings provide additional evidence for the usefulness of live oocyst vaccines to restore ionophore sensitivity in poultry operations that contain an ionophore-resistant population of Eimeria spp. oocysts.


Subject(s)
Chickens , Coccidiosis/veterinary , Eimeria/drug effects , Eimeria/physiology , Poultry Diseases/parasitology , Pyrans/pharmacology , Animals , Coccidiosis/drug therapy , Coccidiosis/parasitology , Coccidiosis/prevention & control , Coccidiostats/administration & dosage , Coccidiostats/pharmacology , Drug Resistance , Poultry Diseases/drug therapy , Poultry Diseases/prevention & control , Protozoan Vaccines/administration & dosage , Protozoan Vaccines/immunology
16.
Toxicol Lett ; 196(2): 117-24, 2010 Jul 01.
Article in English | MEDLINE | ID: mdl-20394810

ABSTRACT

The aim of this study was to establish an air-liquid interface (ALI) culture of precision-cut lung slices (PCLS) for direct exposure of lung cells to gaseous contaminants. Nitrogen dioxide (NO(2)) and ozone (O(3)) were selected as model gas compounds. Acute pro-inflammatory and toxic effects of NO(2) and O(3) on live lung tissue were investigated. Murine PCLS were exposed to different flow rates (3-30mL/min) of synthetic air, O(3) (3.5-8.5ppm), or NO(2) (1-80ppm). Tissue survived ex vivo in ALI culture and resisted exposure to NO(2) (1-10ppm) and O(3) (3.5-8.5ppm) for 1h. Longer exposure to NO(2) resulted in a clear loss of viability, whereas exposure to O(3) was less effective. Exposure to NO(2) dose-dependently induced release of the pro-inflammatory IL-1alpha (40%), whereas RANTES, IL-12, and eotaxin remained unchanged. Early secretion of IL-1alpha (80%), RANTES (>800%), MIP-1beta (44%), and MCP-1 (60%) was already detected after 1h of exposure to O(3). The obtained data showed that direct exposure to O(3) and NO(2) induced cytotoxicity and pro-inflammatory responses in PCLS with ALI culture. This provides a model that more closely resembles in vivo exposure of airborne contaminants, and thus should be appropriate for toxicity testing.


Subject(s)
Lung/drug effects , Nitrogen Dioxide/toxicity , Ozone/toxicity , Animals , Chemokine CCL2/metabolism , Chemokine CCL4/metabolism , Chemokine CCL5/metabolism , Dose-Response Relationship, Drug , Female , Gases , Inflammation Mediators/metabolism , Interleukin-12/metabolism , Interleukin-1alpha/metabolism , Lipopolysaccharides/pharmacology , Lung/immunology , Lung/pathology , Mice , Mice, Inbred BALB C , Time Factors , Tissue Culture Techniques , Tissue Survival/drug effects
17.
Med Phys ; 34(9): 3649-64, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17926969

ABSTRACT

The continuing research and further development in flat panel detector technology have led to its integration into more and more medical x-ray systems for two-dimensional (2D) and three-dimensional (3D) imaging, such as fixed or mobile C arms. Besides the obvious advantages of flat panel detectors, like the slim design and the resulting optimum accessibility to the patient, their success is primarily a product of the image quality that can be achieved. The benefits in the physical and performance-related features as opposed to conventional image intensifier systems, (e.g., distortion-free reproduction of imaging information or almost linear signal response over a large dynamic range) can be fully exploited, however, only if the raw detector images are correctly calibrated and postprocessed. Previous procedures for processing raw data contain idealizations that, in the real world, lead to artifacts or losses in image quality. Thus, for example, temperature dependencies or changes in beam geometry, as can occur with mobile C arm systems, have not been taken into account up to this time. Additionally, adverse characteristics such as image lag or aging effects have to be compensated to attain the best possible image quality. In this article a procedure is presented that takes into account the important dependencies of the individual pixel sensitivity of flat panel detectors used in 2D or 3D imaging and simultaneously minimizes the work required for an extensive recalibration. It is suitable for conventional detectors with only one gain mode as well as for the detectors specially developed for 3D imaging with dual gain read-out technology.


Subject(s)
Models, Theoretical , Radiographic Image Interpretation, Computer-Assisted , Tomography, X-Ray Computed/methods , Calibration , Phantoms, Imaging , Tomography, X-Ray Computed/instrumentation
18.
Toxicol Lett ; 140-141: 205-11, 2003 Apr 11.
Article in English | MEDLINE | ID: mdl-12676467

ABSTRACT

The in vitro study of adverse cellular effects induced by inhaled pollutants poses a special problem due to the difficulties of exposing cultured cells of the respiratory tract directly to test atmospheres that can include complex gaseous and particulate mixtures. In general, there is no widely accepted in vitro exposure system. However, in vitro methods offer the unique possibility for use of human cells, developed and validated cell culture and exposure device (CULTEX(1)) using the principle of the air/liquid exposure technique. Cells of the respiratory tract are grown on porous membranes in transwell inserts. After removal of the medium, the cells can be treated on their superficial surfaces with the test atmosphere, and at the same time they are supplied with nutrients through the membrane below. In comparison with other experimental approaches, the goal of our studies is to analyze the biological effects of test atmospheres under environmental conditions, i.e. without humidifying the atmosphere or adding additional CO(2). The system used is small and flexible enough independent of a cultivation chamber and thus offers the opportunity for onsite study of indoor and outdoor atmospheres in the field. The efficacy of the exposure device has already been demonstrated in the analysis of dose-dependent cytotoxic and genotoxic effects of exposure of epithelial lung cells to complex mixtures such as native diesel exhaust and side-stream smoke.


Subject(s)
Air Pollutants/toxicity , Bronchi/drug effects , Toxicity Tests , Cells, Cultured , Equipment Design , Humans , Nitrogen Dioxide/toxicity , Ozone/toxicity , Toxicity Tests/instrumentation , Toxicity Tests/methods
19.
Toxicol In Vitro ; 16(2): 185-92, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11869881

ABSTRACT

To investigate the effects of native diesel motor exhaust on human lung cells in vitro, a new experimental concept was developed using an exposure device on the base of the cell cultivation system CULTEX (Patent No. DE19801763.PCT/EP99/00295) to handle the cells during a 1-h exposure period independent of an incubator and next to an engine test rig. The final experimental set-up allows the investigation of native (chemically and physically unmodified) diesel exhaust using short distances for the transportation of the gas to the target cells. The analysis of several atmospheric compounds as well as the particle concentration of the exhaust was performed by online monitoring in parallel. To validate the complete system we concentrated on the measurement of two distinct viability parameters after exposure to air and undiluted, diluted and filtered diesel motor exhaust generated under different engine operating conditions. Cell viability was not influenced by the exposure to clean air, whereas dose-dependent cytotoxicity was found contingent on the dosage of exhaust. Additionally, the quality of exhaust, represented by two engine operating conditions (idling, higher load), also showed well-distinguishable cytotoxicity. In summary, the experimental set-up allows research on biological effects of native engine emissions using short exposure times.


Subject(s)
Bronchi/drug effects , Cell Culture Techniques/instrumentation , Cell Culture Techniques/methods , Epithelial Cells/drug effects , Vehicle Emissions/toxicity , Air Pollutants/toxicity , Bronchi/cytology , Cell Count , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Epithelial Cells/cytology , Humans
20.
J Neurosci ; 21(22): 8956-65, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11698606

ABSTRACT

Most studies of spinal interneurons in vertebrate motor circuits have focused on the activity of interneurons in a single motor behavior. As a result, relatively little is known about the extent to which particular classes of spinal interneurons participate in different behaviors. Similarities between the morphology and connections of interneurons activated in swimming and escape movements in different fish and amphibians led to the hypothesis that spinal interneurons might be shared by these behaviors. To test this hypothesis, we took advantage of the optical transparency of zebrafish larvae and developed a new preparation in which we could use confocal calcium imaging to monitor the activity of individual identified interneurons noninvasively, while we simultaneously filmed the movements of the fish with a high-speed digital camera. With this approach, we could directly examine the involvement of individual interneurons in different motor behaviors. Our work revealed unexpected differences in the interneurons activated in swimming and escape behaviors. The observations lead to predictions of different behavioral roles for particular classes of spinal interneurons that can eventually be tested directly in zebrafish by using laser ablations or mutant lines with interneuronal deficits.


Subject(s)
Escape Reaction/physiology , Interneurons/physiology , Nerve Net/physiology , Spinal Cord/physiology , Swimming/physiology , Agar , Animals , Calcium/metabolism , Fluorescent Dyes , Larva , Microscopy, Video , Nerve Net/cytology , Restraint, Physical/methods , Spinal Cord/cytology , Zebrafish
SELECTION OF CITATIONS
SEARCH DETAIL
...