23 results on '"Nuss C"'
Search Results
2. An environmental management information system for closing knowledge gaps in corporate sustainable decision-making
- Author
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Stindt, D., Nuss, C., Bensch, S., Martin Dirr, and Tuma, A.
- Subjects
ddc:330 - Published
- 2018
3. On the attractiveness of product recovery: the forces that shape reverse markets
- Author
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Stindt, D., Quariguasi Frota Neto, Joao, Nuss, C., Dirr, M., Jakowczyk, Marta, Gibson, Andrew, and Tuma , A.
- Subjects
ddc:330 - Published
- 2016
4. Brincidofovir treatment of acyclovir-resistant disseminated varicella zoster virus infection in an immunocompromised host
- Author
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Mullane, K.M., primary, Nuss, C., additional, Ridgeway, J., additional, Prichard, M.N., additional, Hartline, C.B., additional, Theusch, J., additional, Mommeja-Marin, H., additional, and Larson, R.A., additional
- Published
- 2016
- Full Text
- View/download PDF
5. Herança da resistência à mancha-foliar de feosféria em milho
- Author
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PEGORARO, D. G., BARBOSA NETO, J. F., DAL SOGLIO, F. K., VACARO, E., NUSS, C. N., CONCEIÇÃO, L. D. H., Elton Vacaro, Empresa Agroeste Sementes Ltda., Claudio Natalino Nuss, Empresa Agroeste Sementes Ltda., Fábio Kessler Dal Soglio, Universidade Federal do Rio Grande do Sul - UFRGS/Faculdade de Agronomia, Diego Girardi Pegoraro, Fundação Pró-Sementes de Apoio à Pesquisa, José Fernandes Barbosa Neto, Universidade Federal do Rio Grande do Sul - UFRGS/Faculdade de Agronomia, and Léo Duc Haa Conceição, Universidade Federal do Rio Grande do Sul - UFRGS/Faculdade de Agronomia. Bolsista do PIBIC/CNPq.
- Subjects
Teste de Progênie ,Melhoramento Vegetal ,Variação Genética ,Phaeosphaeria Maydis ,genetic variation ,plant breeding ,progeny testing - Abstract
A mancha-foliar de feosféria tem causado expressiva redução no rendimento de grãos de milho, no Brasil, principalmente, em decorrência da crescente amplitude da data de semeadura, conjugada com o uso de áreas irrigadas e de plantio direto. É importante o desenvolvimento de genótipos resistentes a essa moléstia; porém a realização de uma seleção eficiente depende do entendimento da va-riabilidade genética e da herança da resistência. Com o objetivo de determinar a capacidade combinatória e o modo de herança do caráter, foram cruzadas sete linhagens de milho, para a realização das análises dialélica e média de gerações. Os experimentos foram conduzidos no Município de Xanxerê, SC, sendo avaliada a porcentagem de tecido foliar afetado pela moléstia 30 dias após o florescimento. Os genótipos apresentaram amplitude de 4,3% a 67,0% de área foliar afetada pela moléstia, na qual a linhagem LA06 e seus híbridos demonstraram elevada resistência. Os resultados indicaram que a seleção de genótipos resistentes à feosféria pode ser realizada com sucesso em programas de melhoramento do milho, visto que a manifestação do caráter é controlada por, pelo menos, dois genes independentes e com uma efetiva participação de efeitos aditivos. Made available in DSpace on 2011-04-09T12:23:10Z (GMT). No. of bitstreams: 1 pab20152.pdf: 218088 bytes, checksum: 3a41e276d069280c20ac237e3392525a (MD5) Previous issue date: 2002-04-11 Título em inglês: Inheritance of the resistance to phaeosphaeria leaf spot in maize.
- Published
- 2002
6. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion.
- Author
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Buerke, M, primary, Murohara, T, additional, Skurk, C, additional, Nuss, C, additional, Tomaselli, K, additional, and Lefer, A M, additional
- Published
- 1995
- Full Text
- View/download PDF
7. Kinetics of decarburization in the RH degasser at Sollac Dunkerque
- Author
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Nuss, C., primary, Gaggioli, A., additional, Ritt, J. P., additional, Gaye, H., additional, Zbaczyniak, Y., additional, Vromen, C., additional, and Butaye, J., additional
- Published
- 1995
- Full Text
- View/download PDF
8. Covalent Binding of Sulfamethoxazole Reactive Metabolites to Human and Rat Liver Subcellular Fractions Assessed by Immunochemical Detection
- Author
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Cribb, A. E., Nuss, C. E., Alberts, D. W., Lamphere, D. B., Grant, D. M., Grossman, S. J., and Spielberg, S. P.
- Abstract
Potentially serious idiosyncratic reactions associated with sulfamethoxazole (SMX) include systemic hypersensitivity reactions and hepatotoxicity. Covalent binding of SMX to proteins subsequent to its N-hydroxylation to form N
4 -hydroxysulfamethoxazole (SMX-HA) is thought to be involved in the pathogenesis of these reactions. A polyclonal antibody was elicited in rabbits against a SMX−keyhole limpet hemocyanin conjugate that recognized covalent protein adducts of SMX in microsomal protein and was used to characterize the covalent binding of SMX and its putative reactive metabolites to hepatic protein in vivo and in vitro. In vitro covalent binding of SMX to rat and human liver microsomal protein was NADPH-dependent, while binding of SMX-HA was not dependent on NADPH. SMX and SMX-HA produced similar patterns of covalent binding, with major protein targets in the region of 150, 100 (two bands), 70 (two bands), and 45−55 kDa. The pattern of covalent binding to human and rat liver microsomal protein was similar. Binding of SMX-HA was completely eliminated by GSH or by addition of cytosolic fractions and acetylcoenzyme A. The acetoxy metabolite of SMX also led to covalent binding, but it was primarily attributable to the formation of SMX-HA from acetoxySMX. In vivo exposure of rats to SMX did not result in detectable covalent binding by the methods employed. When rat liver slices were incubated with 2 mM SMX or 500 μM SMX-HA, no toxicity was observed and yet covalent binding of SMX-HA to 130, 100, 70, and 55 kDa proteins could be detected. These results confirm that covalent binding of SMX occurs via the formation of SMX-HA and that covalent binding of SMX-HA in vitro results from its conversion to the more reactive nitroso metabolite. Acetylation of SMX-HA protected against its covalent binding. Further studies are required to determine how this in vitro covalent binding relates to in vivo covalent binding in humans and to either direct or immune-mediated cytotoxicity in SMX idiosyncratic drug reactions.- Published
- 1996
9. Potencial discriminatório de três testadores em 'topcrosses' de milho
- Author
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Duarte Iran de Azevedo, Ferreira Josué Maldonado, and Nuss Cláudio Natalino
- Subjects
Zea mays ,progênie ,híbrido ,capacidade combinatória ,germoplasma ,Agriculture (General) ,S1-972 - Abstract
O objetivo deste trabalho foi determinar o potencial de três testadores endogâmicos elites a fim de avaliar e classificar 15 materiais genéticos para a síntese de híbridos. Quarenta e cinco híbridos mais quatro testemunhas foram avaliados em cinco ambientes, no ano agrícola 2000/2001, utilizando delineamento em blocos ao acaso, com três repetições. Foram avaliados os caracteres peso de grãos corrigido, altura de planta e altura de espiga. As estimativas de capacidade geral e específica de combinação foram obtidas pelo modelo de Griffing, adaptado por Vencovsky e Barriga, para análise em delineamento genético fatorial. O rendimento médio obtido entre os cinco ambientes variou de 8,97 t ha-1 a 12,21 t ha-1. Vinte e sete tratamentos superaram a média geral absoluta da melhor testemunha. A análise de variância conjunta revelou efeitos significativos de ambientes, capacidade geral de combinação dos parentais e testadores, capacidade específica de combinação e das interações ambiente x capacidade geral de combinação dos parentais e testadores. Os testadores promoveram uma classificação diferenciada para a base genética avaliada, com destaque para os cruzamentos entre parentais HS1, HS2, HS5 e HT4 com o testador LF e parentais L10 e HS5 com o testador L05.
- Published
- 2003
10. Combining ability of twelve maize populations
- Author
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Vacaro Elton, Barbosa Neto José Fernandes, Pegoraro Diego Girardi, Nuss Claudio Natalino, and Conceição Leo Duc Haa
- Subjects
Zea mays ,germplasm ,heterosis ,genetic variation ,Agriculture (General) ,S1-972 - Abstract
Genetic progress depends on germplasm quality and breeding methods. Twelve maize populations and their crosses were evaluated to estimate combining ability and potential to be included as source populations in breeding programs. Plant height, point of insertion of the first ear, number of ears per plant, number of grains per ear, root and stalk lodging and grain yield were studied in two locations in Brazil, during the 1997/98 season. Genotype sum of squares was divided into general (GCA) and specific (SCA) combining ability. Results indicated the existence of genetic divergence for all traits analyzed, where additive effects were predominant. The high heterosis levels observed, mainly in Xanxerê, suggested the environmental influence on the manifestation of this genetic phenomenon. Populations revealed potential to be used in breeding programs; however, those more intensively submitted to selection could provide larger genetic progress, showing the importance of population improvement for the increment of the heterosis in maize.
- Published
- 2002
11. Efeito de época de semeadura e adubação na mancha-foliar de Phaeosphaeria em milho
- Author
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Pegoraro Diego Girardi, Vacaro Elton, Nuss Claudio Natalino, dal Soglio Fábio Kessler, Sereno Maria Jane Cruz de Melo, and Barbosa Neto José Fernandes
- Subjects
Zea mays ,Phaeosphaeria maydis ,fatores ambientais ,doenças das plantas ,Agriculture (General) ,S1-972 - Abstract
O aumento da área de cultivo de milho, aliado a algumas práticas culturais, tem favorecido o surgimento da mancha-foliar causada pelo fungo Phaeosphaeria maydis. Como conseqüência, o rendimento de grãos tem decrescido, especialmente em áreas com plantio direto e maior amplitude da época de semeadura. O trabalho teve como objetivo avaliar a severidade de P. maydis em seis híbridos de milho, em cinco épocas de semeadura e em dois níveis de adubação. O experimento foi conduzido em Xanxerê, SC, na safra 1997/98, em blocos casualizados, com parcelas subdivididas, em duas repetições. As plantas foram avaliadas 30 dias após o florescimento, e a porcentagem da área foliar afetada foi registrada. Na medida em que a semeadura do milho foi retardada, houve um aumento na severidade da moléstia e uma redução no rendimento de grãos. As doses de adubação não apresentaram diferença quanto à severidade da moléstia. O mês de setembro apresentou menor severidade da mancha-foliar e maior rendimento de grãos. Houve uma correlação significativa entre o rendimento de grãos e a severidade da moléstia.
- Published
- 2001
12. Automobile acceleration control for fuel economy
- Author
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Nuss, C
- Published
- 1977
13. Flow Rate and Wall Shear Stress Characterization of a Biomimetic Aerosol Exposure System.
- Author
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Emma Sarles S, Hensel EC, Terry J, Nuss C, and Robinson RJ
- Subjects
- Humans, Biomimetics, Aerosols, Electronic Nicotine Delivery Systems
- Abstract
Current in vitro emissions and exposure systems lack biomimicry, use unrealistic flow conditions, produce unrealistic dose, and provide inaccurate biomechanical cues to cell cultures, limiting ability to correlate in vitro outcomes with in vivo health effects. A biomimetic in vitro system capable of puffing aerosol and clean air inhalation may empower researchers to investigate complex questions related to lung injury and disease. A biomimetic aerosol exposure system (BAES), including an electronic cigarette adapter, oral cavity module (OCM), and bifurcated exposure chamber (BEC) was designed and manufactured. The fraction of aerosol deposited in transit to a filter pad or lost as volatiles was 0.116±0.021 in a traditional emissions setup versus 0.098 ± 0.015 with the adapter. The observed flowrate was within 5% of programed flowrate for puffing (25 mL/s), puff-associated respiration (450 mL/s), and tidal inhalation (350 mL/s). The maximum flowrate observed in the fabricated BAES was 450 mL/s, exceeding the lower target nominal wall shear stress of 0.025 Pa upstream of the bifurcation and fell below the target of 0.02 Pa downstream. This in vitro system addresses several gaps observed in commercially available systems and may be used to study many inhaled aerosols. The current work illustrates how in silico models may be used to correlate results of an in vitro study to in vivo conditions, rather than attempting to design an in vitro system that performs exactly as the human respiratory tract., (Copyright © 2024 by ASME.)
- Published
- 2024
- Full Text
- View/download PDF
14. Characterization of mass distribution in a biomimetic aerosol exposure system.
- Author
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Sarles SE, Hensel EC, Nuss C, Terry J, and Robinson R
- Subjects
- Biomimetics, Inhalation Exposure analysis, Humans, Aerosols, Electronic Nicotine Delivery Systems
- Abstract
Objective: Lack of biomimicry in geometry and flow conditions of emissions systems for analytical testing and biological exposure has led to fundamental limitations, including a poor understanding of dose delivered to specific airway locations. This work characterizes mass distribution of a JUUL® brand e-cigarette in a Biomimetic Aerosol Exposure System (BAES)., Materials and Methods: A combination of mass balance, direct measurements, and inferences based on direct measurements were used to characterize regional and local dose as a function of system flow path configuration and emissions topography profile., Results: Doses produced by the emissions topography profile with only puffing were significantly different from profiles with clean air inhalation following puffs. Mass characterization results support that dose can be manipulated using flow path geometry. Local and regional deposition was mapped throughout the system., Discussion and Conclusions: We estimate the fraction of yield to the mouth deposited at several locations throughout the system for a variety of puffing and respiration topographies and show that emissions topography profile and system flow path geometry affect dose. This work provides proof-of-concept for assessing mass distribution as a function of aerosol generator (e-cigarette product), user airway geometry, and inhalation and puffing topography.
- Published
- 2024
- Full Text
- View/download PDF
15. Achilles Tendon Ruptures in Middle-Aged Rats Heal Poorly Compared With Those in Young and Old Rats [Formula: see text].
- Author
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Leahy T, Nuss C, Evans MK, Fung A, Shetye S, and Soslowsky LJ
- Subjects
- Animals, Humans, Rats, Rats, Inbred F344, Rupture, Treatment Outcome, Wound Healing, Achilles Tendon diagnostic imaging, Tendon Injuries
- Abstract
Background: Achilles tendon ruptures are painful and debilitating injuries and are most common in middle-aged patients. There is a lack of understanding of the underlying causes for increased rupture rates in middle-aged patients and how healing outcomes after a rupture might be affected by patient age. Therefore, the objective of this study was to define age-specific Achilles tendon healing by assessing ankle functional outcomes and Achilles tendon mechanical and histological properties after a rupture using a rat model., Hypothesis: Rats representing the middle-aged patient population would demonstrate reduced healing capability after an Achilles tendon rupture, as demonstrated by a slower return to baseline ankle functional properties and inferior biomechanical and histological tendon properties., Study Design: Controlled laboratory study., Methods: Fischer 344 rats were categorized by age to represent young, middle-aged, and old patients, and Achilles tendon ruptures were induced in the right hindlimb. Animals were allowed to heal and were euthanized at 3 or 6 weeks after the injury. In vivo functional assays and ultrasound imaging were performed throughout the healing period, and ex vivo tendon mechanical and histological properties were assessed after euthanasia., Results: Rats representing middle-aged patients displayed reduced healing potential compared with the other age groups, as they demonstrated decreased recovery of in vivo functional and ultrasound assessment parameters and inferior mechanical and histological properties after an Achilles tendon rupture., Conclusion: These findings may help explain the increased rupture rate observed clinically in middle-aged patients by suggesting that there may be altered tendon responses to daily trauma., Clinical Relevance: The results provide novel data on age-specific healing outcomes after an Achilles tendon rupture, which underscores the importance of considering a patient's age during treatment and expectations for outcomes.
- Published
- 2022
- Full Text
- View/download PDF
16. Limited Scar Resection for Chronic Achilles Tendon Repair: Use of a Rat Model.
- Author
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Counihan M, Leahy T, Nuss C, Newton J, Mohanty S, Soslowsky LJ, and Farber D
- Subjects
- Animals, Rats, Cicatrix, Rats, Sprague-Dawley, Rupture surgery, Treatment Outcome, Achilles Tendon surgery, Plastic Surgery Procedures, Tendon Injuries surgery
- Abstract
Background: Achilles tendon rupture diagnosis is frequently missed, leading to the development of a chronic rupture that requires surgical intervention to remove scar tissue and return the elongated Achilles tendon to appropriate functional length. The limited scar resection (LSR) intervention strategy may provide an advantage over other techniques, as it is less invasive and nondestructive to other tissues, although there is little evidence comparing outcomes between intervention strategies., Hypothesis: The LSR technique would be a viable treatment option for chronic Achilles tendon ruptures and would perform comparably with a more clinically accepted procedure, the gastrocnemius fascial turndown (GFT), in postintervention functional outcome measures and tendon mechanical and histological properties., Study Design: Controlled laboratory study., Methods: Chronic Achilles tendon ruptures were induced in the right hindlimb of Sprague-Dawley rats by Achilles tendon transection without repair, immobilization in dorsiflexion, and 5 weeks of cage activity. Animals were randomly divided between the intervention strategy groups (LSR and GFT), received 1 week of immobilization in plantarflexion, and were sacrificed at 3 or 6 weeks postintervention. In vivo functional outcome measures (gait kinetics, passive joint function, tendon vascular perfusion) were quantified during healing, and tendon mechanical and histological properties were assessed postsacrifice., Results: When compared with the GFT, the LSR technique elicited a faster return to baseline in gait kinetics, although there were few differences between groups or with healing time in other functional outcome measures (passive joint function and vascular perfusion). Quasi-static mechanical properties were improved with healing in both surgical intervention groups, although only the LSR group showed an improvement in fatigue properties between 3 and 6 weeks postintervention. Histological properties were similar between intervention strategies, except for decreased cellularity in the LSR group at 6 weeks postintervention., Conclusion: The LSR technique is a viable surgical intervention strategy for a chronic Achilles tendon rupture in a rodent model, and it performs similarly, if not better, when directly compared with a more clinically accepted surgery, the GFT., Clinical Relevance: This study supports the increased clinical use of the LSR technique for treating chronic Achilles tendon rupture cases.
- Published
- 2021
- Full Text
- View/download PDF
17. Roadside drug testing: An evaluation of the Alere DDS ® 2 mobile test system.
- Author
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Rohrig TP, Moore CM, Stephens K, Cooper K, Coulter C, Baird T, Garnier M, Miller S, Tuyay J, Osawa K, Chou J, Nuss C, Collier J, and Wittman KC
- Subjects
- Adolescent, Adult, Aged, Humans, Middle Aged, Pharmaceutical Preparations blood, Substance Abuse Detection instrumentation, Young Adult, Driving Under the Influence, Pharmaceutical Preparations analysis, Saliva chemistry, Substance Abuse Detection methods
- Abstract
The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action., (Copyright © 2017 John Wiley & Sons, Ltd.)
- Published
- 2018
- Full Text
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18. Automated indexing of the Hazardous Substances Data Bank (HSDB).
- Author
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Nuss C, Chang HF, Moore D, and Fonger GC
- Subjects
- Medical Subject Headings, National Library of Medicine (U.S.), United States, Abstracting and Indexing methods, Databases, Factual, Electronic Data Processing, Hazardous Substances
- Abstract
The Hazardous Substances Data Bank (HSDB), produced and maintained by the National Library of Medicine (NLM), contains over 4600 records on potentially hazardous chemicals. To enhance information retrieval from HSDB, NLM has undertaken the development of an automated HSDB indexing protocol as part of its Indexing Initiative. The NLM Indexing Initiative investigates methods whereby automated indexing may partially or completely substitute for human indexing. The poster's purpose is to describe the HSDB Automated Indexing Project.
- Published
- 2003
19. Two new laws affect Arizona's dental community.
- Author
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Jones CA and Nuss C
- Subjects
- Arizona, Dental Hygienists legislation & jurisprudence, Dental Technicians legislation & jurisprudence, Dentists legislation & jurisprudence, Humans, Insurance, Dental legislation & jurisprudence, Certification legislation & jurisprudence, Legislation, Dental
- Published
- 2000
20. Hypotensive mechanisms of amifostine.
- Author
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Ryan SV, Carrithers SL, Parkinson SJ, Skurk C, Nuss C, Pooler PM, Owen CS, Lefer AM, and Waldman SA
- Subjects
- Adrenergic Agents pharmacology, Amifostine adverse effects, Amifostine metabolism, Animals, Aorta, Thoracic drug effects, Arginine analogs & derivatives, Arginine pharmacology, Blood Pressure drug effects, Calcium metabolism, Cyclic AMP metabolism, Cyclic GMP metabolism, Ephedrine pharmacology, In Vitro Techniques, Ligands, Male, Mercaptoethylamines pharmacology, Muscle, Smooth, Vascular drug effects, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase antagonists & inhibitors, Radiation-Protective Agents adverse effects, Radiation-Protective Agents metabolism, Random Allocation, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha metabolism, Amifostine pharmacology, Hypotension chemically induced, Radiation-Protective Agents pharmacology
- Abstract
Amifostine, a chemo- and radioprotective agent developed as adjunctive therapy for malignancies, induces hypotension after approximately 20% of patient administrations. This study examines the molecular mechanisms underlying hypotension induced by amifostine. Amifostine and its metabolite, WR-1065, induced dose-dependent hypotension in anesthetized rats that was not blocked by N(G)-methyl L arginine (L-NAME), an NO synthase inhibitor. WR-1065 but not amifostine induced concentration-dependent relaxation of isolated rat aortic rings in an endothelium-independent fashion. Relaxation was not associated with increases in cGMP or cAMP and could not be blocked by L-NAME or indomethacin. Similarly, neither amifostine or WR-1065 activated adenylyl, particulate guanylyl, or soluble guanylyl cyclases. WR-1065 relaxed rat aortic rings precontracted with norepinepherine, suggesting alpha-adrenergic blocking activity. However, neither amifostine nor WR-1065 altered the ability of prazosin or phentolamine to bind to alpha-adrenergic receptors. Further, WR-1065 had no effect on receptor-mediated increases in intracellular calcium in BAL 17 murine B lymphocytes in vitro. Thus, hypotension after administration of amifostine is mediated by WR-1065 and appears to result from direct relaxation of vascular smooth muscle. Smooth muscle relaxation induced by WR-1065 is not related to production of nitric oxide, prostaglandins, or cyclic nucleotides; alpha-adrenergic receptor antagonism; or interference with receptor-dependent increases in intracellular calcium. Administration of ephedrine, an efficacious adrenergic agonist, attenuated hypotension induced by amifostine in anesthetized rats and may be useful in alleviating hypotension associated with amifostine administration in patients.
- Published
- 1996
- Full Text
- View/download PDF
21. Further investigations of the role of acetylation in sulphonamide hypersensitivity reactions.
- Author
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Nuss CE, Grant DM, Spielberg SP, and Cribb AE
- Abstract
Abstract Sulphonamide hypersensitivity reactions are believed to be mediated through reactive intermediates derived from oxidation of the paraamino group to form sulphonamide hydroxylamines. Sulphamethoxazole hydroxylamine (SMX-HA) can be acetylated by N-acetyltransferase (NAT) enzymes to form an acetoxy metabolite (acetoxySMX). In the current studies, acetoxySMX was found to be not toxic over the concentration range of 0 to 500 μM towards a human lymphoblastoid cell line (RPMI 1788) or a human hepatoma cell line (HepG2). Further, transient expression of NAT1 in COS-1 cells or stable transfection of NAT1 andNAT2 in HepG2 cells did not alter the toxicity of SMX-HA in vitro. The activity of NAT1 in isolated mononuclear leucocytes (a reflection of systemic NAT1 activity) determined with paraaminobenzoic acid as a substrate was not different between controls (n = 11) or patients with a known hypersensitivity reaction (n = 5) (4.1 ±1.2 nmol min(-1)mg(-1) vs 5.7 ± 1.4 nmol min(-1) mg(-1)). Thus, acetoxy SMX is unlikely to play a significant role in mediating SMX hypersensitivity reactions anda constitutive deficiency in NAT1 activity is not a common finding in patients susceptible to SMX hypersensitivity reactions.
- Published
- 1996
- Full Text
- View/download PDF
22. Antipeptide antibodies against overlapping sequences differentially inhibit human CYP2D6.
- Author
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Cribb A, Nuss C, and Wang R
- Subjects
- Amino Acid Sequence, Animals, Antibodies immunology, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System immunology, Enzyme Inhibitors immunology, Enzyme-Linked Immunosorbent Assay, Humans, Microsomes, Liver enzymology, Mixed Function Oxygenases immunology, Molecular Sequence Data, Rabbits, Antibodies pharmacology, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors pharmacology, Mixed Function Oxygenases antagonists & inhibitors
- Abstract
Two peptides that correspond to sequences within the major 33-amino acid sequence recognized by human liver-kidney microsomal-1 autoantibodies were used to elicit antibodies in rabbits (four per peptide) against CYP2D6. Peptide 1(DPAQPPRDLTEAFLA) corresponded to amino acids 263-277, and peptide 2 (LLTEHRMTWDPAQPPRDLTE) corresponded to amino acids 254-273 of CYP2D6. The peptide-keyhole limpet hemocyanin conjugates elicited good immune responses against their respective peptides as judged by enzyme-linked immunosorbent assay (titers of 1/10,000 to 1/30,000). The antisera recognized CYP2D6 on Western blots and, to varying extents, inhibited recombinant CYP2D6 and liver microsomal CYP2D6 activity. Immunization with peptide 2 produced antisera with the greatest inhibitory potency. Antiserum from a rabbit (#236) immunized with peptide 2 inhibited up to 95% of dextromethorphan O-demethylase activity in human liver microsomes at the highest concentration tested (40% v/v) but did not significantly inhibit CYP1A2, CYP2C9, CYP2E1, or CYP3A4 marker activities. On Western blot, only a single immunoreactive protein comigrating with recombinant CYP2D6 was recognized. In liver microsomes from a CYP2D6-deficient individual, no proteins were recognized, and the antisera did not cross-react with recombinant CYP1A2, CYP2C9, CYP2E1, or CYP3A4. There was a significant correlation between the quantity of immunoreactive CYP2D6 as determined by immunoblotting with anti-peptide 2 antiserum and dextromethorphan O-demethylation in a panel of 10 human liver microsomes (r = 0.95). These data identify a peptide sequence (peptide 2) that can be used to raise antisera that specifically recognize and inhibit CYP2D6.
- Published
- 1995
23. Beneficial effects of oligotide, a novel oligodeoxyribonucleotide, in murine traumatic shock.
- Author
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Skurk C, Nuss C, and Lefer AM
- Subjects
- Animals, Biomarkers, Blood Pressure drug effects, Cell Adhesion drug effects, Drug Evaluation, Preclinical, Endothelium, Vascular drug effects, Intestine, Small drug effects, Intestine, Small enzymology, Male, Mesenteric Arteries drug effects, Mesenteric Arteries physiopathology, Neutrophils drug effects, Nitrogen blood, P-Selectin, Peroxidase analysis, Platelet Membrane Glycoproteins analysis, Rats, Rats, Sprague-Dawley, Shock, Traumatic complications, Shock, Traumatic physiopathology, Thrombin pharmacology, Vasodilation drug effects, Vasodilator Agents pharmacology, Oligodeoxyribonucleotides therapeutic use, Shock, Traumatic drug therapy
- Abstract
The effects of oligotide, an oligodeoxyribonucleotide analog, were investigated in an experimental model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma and receiving only the vehicle (i.e., Krebs-Henseleit solution) developed a severe form of traumatic shock characterized by marked hypotension (61 +/- 6 mmHg), a survival time of 115 +/- 21 min, endothelial dysfunction, significant increases in plasma free amino-nitrogen concentration (p < .001) as well as elevated intestinal myeloperoxidase activity. In contrast, oligotide given intravenously (15 mg/kg bolus + 10 mg/kg/h infusion for 5 h) resulted in a significant prolongation of survival time to 209 +/- 31 min (p < .01), a significant and sustained increase in mean arterial blood pressure, a significant attenuation of plasma free amino-nitrogen concentration (p < .01), and intestinal myeloperoxidase activity (p < .05). Furthermore, oligotide significantly preserved superior mesenteric artery (SMA) endothelial function as seen by the relaxation response of isolated SMA rings to acetylcholine (71 +/- 5% vs. 36 +/- 5%, p < .01 compared to untreated trauma rats). Moreover, oligotide in a concentration-dependent manner attenuated unstimulated human neutrophil adherence to either thrombin or trauma-activated SMA endothelium in vitro (p < .001). Thus, our data suggest that the mechanism of the protective effect of oligotide in traumatic shock is improving endothelial function and diminishing neutrophil accumulation leading to reduced tissue injury.
- Published
- 1995
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