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1.
J Anim Sci ; 95(1): 485-498, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28177363

RESUMO

Two experiments were conducted to evaluate the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of finishing steers. In Exp. 1, 336 crossbred steers (initial BW of RAC feeding = 539 kg [SD 22]) were used in a 2 × 2 factorial arrangement of treatments with one factor being RAC dose (0 or 200 mg/steer daily) and the other factor being RAC duration (28 or 42 d prior to harvest). There were no RAC dose × duration interactions ( ≥ 0.08) for growth performance or carcass characteristics. Feeding 200 mg RAC/steer daily increased ( < 0.01) live final BW by 9.0 kg compared with steers not fed RAC. Carcass-adjusted final BW, ADG, and G:F were greater ( < 0.01) for steers fed 200 mg RAC/d compared with steers not fed RAC. Hot carcass weight was 4.7 kg heavier ( < 0.01) for steers fed 200 mg RAC/d compared with steers not fed RAC. In Exp. 2, crossbred steers ( = 576; experiment initial BW = 408 kg [SD 29]) were used in a randomized block design with a 3 × 3 factorial arrangement of treatments. Factors included RAC dose (0, 300, and 400 mg/steer daily) and RAC duration (14, 28, or 42 d prior to harvest). There was a tendency ( ≤ 0.08) for an interaction of RAC dose × duration for final live BW, DMI, and live G:F; therefore, simple effects are presented. At 28 d, live final BW for steers fed 400 mg RAC/d were heavier ( < 0.01) than for steers fed 0 mg RAC/d. There was a tendency at 28 d for increased live final BW for steers fed RAC at 300 mg/d ( = 0.08) compared with steers fed RAC at 0 mg and for steers fed 400 mg RAC/d compared with steers fed 300 mg RAC/d ( = 0.06). Live final BW was greater ( < 0.01) for steers fed RAC for 42 d at 300 and 400 mg/d compared with steers fed 0 mg; however, live final BW was similar ( = 0.48) between steers fed 300 and 400 mg RAC/d. Despite no RAC dose × duration interaction ( = 0.30) for HCW, simple effects will be presented for consistency. Hot carcass weight was greater for steers fed 300 and 400 mg RAC/d for 28 and 42 d compared with steers fed 0 mg at 28 ( ≤ 0.02) and 42 d ( < 0.01). Feeding 300 mg RAC/d for 28 or 42 d increased HCW by 5.1 and 7.6 kg, respectively, compared with steers fed 0 mg RAC. Additionally, feeding 400 mg RAC/d for 28 or 42 d resulted in increases of 8.9 and 9.4 kg, respectively, in HCW compared with steers fed 0 mg RAC. In conclusion, our results confirm that feeding RAC improves growth performance and carcass weight, with an optimal duration of feeding RAC being 28 d.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Composição Corporal/efeitos dos fármacos , Bovinos/crescimento & desenvolvimento , Fenetilaminas/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Esquema de Medicação , Masculino , Aumento de Peso/efeitos dos fármacos
2.
J Anim Sci ; 94(9): 3933-3946, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27898887

RESUMO

Two studies evaluated effects of replacing corn with a pellet containing alkaline treated corn stover, dried distillers' grains plus solubles (DDGS), and distillers' solubles on total tract digestion and performance of finishing cattle. Experiment 1 used 4 ruminally fistulated steers in a 4 × 6 Latin rectangle to evaluate total tract digestion. Treatments consisted of a control (CON) containing 50.3% dry-rolled corn (DRC), 40% modified distillers' grains plus solubles (MDGS), and 5% untreated corn stover. The next 2 treatments replaced 25% DRC (DM basis) with either a CaO-treated stover pellet (STOVPEL) or a pellet consisting of 64% CaO-treated corn stover, 18% DDGS, and 18% corn distillers' solubles (COMBPEL). The last treatment replaced 25% DRC with a mixture of feeds: 10% treated stover pellet, 10% DDGS, and 5% distillers' solubles (COMB). Experiment 2 used 336 crossbred steer calves (301 ± 25 kg initial BW) in a 2 × 3 + 1 factorial to evaluate effects of replacing corn with a pellet containing 64% CaO-treated corn stover, 18% DDGS, and 18% corn distillers' solubles on finishing performance. Factors included level of MDGS (20 or 40%) and pellet inclusion (10, 20, or 30%). The CON diet contained a 50:50 blend of DRC and high-moisture corn and 40% MDGS. All diets contained 5% wheat straw and 4% dry meal supplement. In Exp. 1, no differences ( ≥ 0.50) were observed between the CON, STOVPEL, COMB, or COMBPEL treatments for DM (76.5, 75.4, 72.5, and 78.0%, respectively; SEM 2.5) or OM (79.1, 79.7, 75.7, and 80.5%, respectively; SEM 2.4) digestibility. In Exp. 2, a linear increase ( = 0.03) in DMI was observed as pellet inclusion increased from 0% in the CON (10.6 kg/d [SE 0.13]) to 30% (11.0 kg/d [SE 0.13]) in treatments containing 40% MDGS. A quadratic response ( = 0.03) in DMI was observed as pellet inclusion increased in diets containing 20% MDGS due to greater DMI of the 20% pellet treatment. A linear decrease ( = 0.03) in G:F was observed as the level of pellet inclusion increased from 0 (0.182 [SE 0.02]) to 30% (0.175 [SE 0.02]) in diets containing 40% MDGS. In diets containing 20% MDGS, no differences ( ≥ 0.22) in G:F were observed as pellet inclusion increased from 10 to 30%. In conclusion, replacing up to 20% of corn (DM basis) in diets containing 20% MDGS had minimal impact on performance. Conversely, up to 30% of corn could be replaced in diets containing 40% MDGS with little impact on performance.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Digestão/fisiologia , Grão Comestível/química , Manipulação de Alimentos/métodos , Zea mays , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Dieta/veterinária , Suplementos Nutricionais , Grão Comestível/metabolismo , Trato Gastrointestinal/fisiologia , Masculino
3.
Adv Exp Med Biol ; 2016 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-27469013

RESUMO

The use of natural rubber latex (NRL) gloves in many occupations may lead to latex sensitization, allergic asthma, and skin reactions. Due to their good properties and environmental safety NRL gloves are still being used in the healthcare setting, but also in the food industry, by hairdressers, cleaners, etc. The aim of our study was to assess the protein and NRL allergen content in commercial gloves by different methods, including a new assay. Twenty commercially available NRL gloves were analyzed. Protein extraction was performed according to the international standard ASTM D-5712. Total protein content was measured with a modified Lowry method, NRL content with the CAP Inhibition Assay, the Beezhold ELISA Inhibition Assay, and an innovative ELISA with IgY-antibodies extracted from eggs of NRL-immunized hens (IgY Inhibition Assay). We found a high protein content in a range of 215.0-1304.7 µg/g in 8 out of the 20 NRL gloves. Seven of the 20 gloves were powdered, four of them with a high protein content. In gloves with high protein content, the immunological tests detected congruently high levels of NRL allergen. We conclude that a high percentage of commercially available NRL gloves still represent a risk for NRL allergy, including asthma. The modified Lowry Method allows to infer on the latex allergen content.

4.
Adv Exp Med Biol ; 921: 37-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27241513

RESUMO

The use of natural rubber latex (NRL) gloves in many occupations may lead to latex sensitization, allergic asthma, and skin reactions. Due to their good properties and environmental safety NRL gloves are still being used in the healthcare setting, but also in the food industry, by hairdressers, cleaners, etc. The aim of our study was to assess the protein and NRL allergen content in commercial gloves by different methods, including a new assay. Twenty commercially available NRL gloves were analyzed. Protein extraction was performed according to the international standard ASTM D-5712. Total protein content was measured with a modified Lowry method, NRL content with the CAP Inhibition Assay, the Beezhold ELISA Inhibition Assay, and an innovative ELISA with IgY-antibodies extracted from eggs of NRL-immunized hens (IgY Inhibition Assay). We found a high protein content in a range of 215.0-1304.7 µg/g in 8 out of the 20 NRL gloves. Seven of the 20 gloves were powdered, four of them with a high protein content. In gloves with high protein content, the immunological tests detected congruently high levels of NRL allergen. We conclude that a high percentage of commercially available NRL gloves still represent a risk for NRL allergy, including asthma. The modified Lowry Method allows to infer on the latex allergen content.


Assuntos
Alérgenos/análise , Asma/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Luvas Protetoras/efeitos adversos , Látex/efeitos adversos , Proteínas/análise , Borracha/efeitos adversos , Alérgenos/imunologia , Asma/imunologia , Humanos , Hipersensibilidade ao Látex/diagnóstico , Hipersensibilidade ao Látex/imunologia
5.
Adv Exp Med Biol ; 921: 51-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27161107

RESUMO

In Germany, bakers with occupational asthma willing to stay in their job are included in an interdisciplinary program of the Social Accident Insurance for Foodstuff and Catering Industry (BGN). The primary aim is to reduce flour dust exposure, and to provide adequate medical treatment. Our aim was to evaluate the program's effect on the disease's course using routinely collected data. Forty three bakers with allergic occupational asthma and with the available baseline level of IgE (f4, f5) were investigated. Changes in IgE related to wheat and rye flour exposure were measured by ImmunoCAP test during follow-up visits. A questionnaire on work-related allergic complaints (WRAC), the Asthma Control Test (ACT), a 10-point scale of asthma severity grade, and quality of life instruments (EQ-5D-5L, Mini-AQLQ) were administered. We found an improvement of asthma severity in 88.4 % of the bakers. WRAC were reported by 65 %; 77 % had good asthma control (ACT ≥ 20); and 81 % had regular asthma medication. A relevant reduction of ≥2 CAP-classes for both allergens was seen in 12 % of the subjects. Health-related and asthma-specific quality of life was high. We conclude that satisfactory asthma control is probably the result of adequate medical management. In a subgroup of bakers with decreased specific IgE, it may also be attributed to reduced allergen exposure.


Assuntos
Alérgenos/efeitos adversos , Asma Ocupacional/etiologia , Hipersensibilidade/etiologia , Imunoglobulina E/imunologia , Exposição Ocupacional/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Asma Ocupacional/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Anim Sci ; 94(12): 5382-5392, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28046162

RESUMO

Three experiments evaluated the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of feedlot steers. In total, 1,509 crossbred steers (530 kg initial BW [SD 22]) were used in a randomized complete block design using a 3 × 3 factorial treatment structure. Treatments consisted of RAC dose (0, 100, or 200 mg/steer daily) and duration (28, 35, or 42 d) of RAC feeding prior to harvest. Initiation of RAC dose was staggered (7 d apart) based on RAC duration, which resulted in common days on feed among treatments. Data from the 3 experiments were combined for statistical analyses. There were no RAC dose × duration interactions ( ≥ 0.85) for growth performance. Live final BW was not different ( ≥ 0.24) as RAC dose increased. Dry matter intake linearly decreased ( < 0.01) as RAC dose increased. Live ADG and G:F linearly increased ( ≤ 0.01) as RAC dose increased. Carcass-adjusted ADG and G:F linearly increased ( ≤ 0.02) as RAC dose increased. Compared with steers fed 0 mg RAC/steer daily, G:F was improved by 5.0 and 13.0% when steers were fed 100 ( = 0.31) and 200 ( = 0.01) mg RAC/steer daily, respectively. Hot carcass weight tended ( = 0.10) to linearly increase as RAC dose increased, with carcasses from steers fed 100 ( = 0.38) and 200 ( = 0.10) mg RAC/steer daily being 2.2 and 4.1 kg heavier, respectively, than carcasses from steers fed 0 mg RAC/steer daily. Increasing RAC dose linearly ( < 0.01) increased LM area and linearly ( = 0.02) decreased marbling score. Live final BW was not different ( ≥ 0.60) among RAC durations. Carcass-adjusted final BW, ADG, and G:F were not different ( ≥ 0.41) as RAC duration increased. Carcass traits did not differ ( ≥ 0.18) among RAC duration. Feeding 200 mg RAC/steer daily improved ADG, feed efficiency, and HCW. Increasing the feeding duration of RAC had no effect of growth performance or carcass characteristics. These data indicate that feeding 200 mg RAC/steer daily for 28 d improves steer growth performance.


Assuntos
Composição Corporal/efeitos dos fármacos , Bovinos/crescimento & desenvolvimento , Fenetilaminas/farmacologia , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Relação Dose-Resposta a Droga , Masculino , Fenetilaminas/administração & dosagem , Aumento de Peso/efeitos dos fármacos
7.
Adv Exp Med Biol ; 840: 51-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25256339

RESUMO

Standard exercise testing (ET) comprises progressive exercise provocation with cardiovascular monitoring. Exercise tolerance is estimated by workload. Cardiopulmonary exercise testing (CPX) is a non-invasive measurement of ventilatory gas exchange which provides more accurate quantifications of cardiorespiratory fitness (CRF). Workload is usually increased stepwise in ET and continuously (ramp) in CPX. Our aim was to examine the comparability of the results. Thirty two healthy volunteers (17 females/15 males, age 26.8±6.1 years, BMI 24.5±3.0) underwent exercise testing on a bicycle ergometer up to maximum physical exhaustion; under ramp protocol (CPX) and 2-7 days later with a stepwise increase of workload (ET). We compared the physical work capacity under both methods at maximum workload, at heart rate of 150 and 170 beats/min (PWC150 and PWC170), and the exercise duration. We found that there were no statistically significant differences in the maximum heart rate (CPX: 177.1±11.7/min vs. ET: 178.5±11.2/min) or maximal workload (CPX: 219.8±50.6 vs. ET: 209.4±42.5). PWC150 and PWC150/kg were higher with CPX than those with ET (156.6±51 vs. 146.4±42.3, p<0.001 and 2.1±0.5 vs. 1.9±0.4, respectively, p<0.001). Exercise duration was almost equal (12.1 vs. 11.3 min). We conclude that overall physical performance was higher with CPX. Since the results are similar, we recommend the CPX: wattage and other parameters in performance assessment are to be determined directly, interpolations are obsolete.


Assuntos
Limiar Anaeróbio/fisiologia , Teste de Esforço/métodos , Teste de Esforço/normas , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Adulto , Feminino , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Resistência Física/fisiologia , Aptidão Física/fisiologia , Fatores Sexuais , Suporte de Carga/fisiologia , Adulto Jovem
8.
Am J Ind Med ; 52(12): 982-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19852017

RESUMO

BACKGROUND: Tetrahydrothiophene (THT) is frequently used to odorize natural (city) gas. Only sparse data on adverse health effects of THT on humans are available. METHODS: We performed a literature search and clinical investigations including case history and cardiopulmonary diagnostic tests in two symptomatic THT-exposed outpatients. RESULTS: The two THT-exposed city workers developed transient neurologic symptoms such as nausea, vomiting, headaches, as well as skin and mucosa irritation, chronic rhinitis, chronic obstructive pulmonary disease, arterial hypertension, and cardiac arrhythmia. The neurological symptoms and respiratory disorders were found to be caused by intermittently high THT exposures. In favor of a causal relationship were severe work-related neurological and respiratory symptoms in previously healthy workers, results of animal experiments, and another report with very similar findings in the literature. The etiology of arterial hypertension and cardiac arrhythmia, however, remains unclear. CONCLUSIONS: Our two case reports demonstrate that repeated high THT-exposures can--in addition to neurotoxic symptoms--elicit chronic obstructive pulmonary disease. We recommend improved primary and secondary preventive measures, including the establishment of a TLV.


Assuntos
Combustíveis Fósseis/toxicidade , Irritantes/toxicidade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Odorantes , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Tiofenos/toxicidade , Idoso , Arritmias Cardíacas/induzido quimicamente , Dor no Peito/induzido quimicamente , Tosse/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Náusea/induzido quimicamente , Síndromes Neurotóxicas/diagnóstico , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/prevenção & controle , Roupa de Proteção , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Vômito/induzido quimicamente
9.
Cytogenet Genome Res ; 114(3-4): 292-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16954669

RESUMO

Anaplastic large cell lymphoma (ALCL) is an entity of non-Hodgkin lymphomas (NHL) that often occurs in young children and adolescents. In the majority of cases, ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK fusion or variant ALK translocations. In addition, there is an ALK-negative subtype of ALCL. The anaplastic lymphoid cell line TS1G6 established by interleukin (IL)-9 transfection of T-helper cells represents a murine model of this subtype. Here, we describe the cytogenetic features of this cell line using spectral karyotyping (SKY) and single-color fluorescence in situ hybridization (FISH). We show that TS1G6 cells exhibit a hypotetraploid karyotype with complex structural alterations. Several unbalanced translocations involved the chromosomal region 14E5, and different translocation partners, i.e. X?A6, 3A3 and 8A1. FISH analysis using a BAC clone containing c-myc confirmed the presence of six copies, but also demonstrated that two loci were irregularly located, indicating that additional intrachromosomal rearrangements had occurred. Moreover, a duplication of the region XF2 approximately 3 was identified. Furthermore, six chromosomes 15 were found, representing a trisomy 15 in a tetraploid chromosome complement, indicating an altered gene dosage of the oncogene c-myc located in region 15D3.


Assuntos
Aberrações Cromossômicas , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Animais , Mapeamento Cromossômico , Modelos Animais de Doenças , Humanos , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Camundongos , Células Tumorais Cultivadas
11.
Cell Death Differ ; 11(4): 468-78, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14726961

RESUMO

Oxidative stress releases intracellular calcium, which plays a pathogenic role in mammalian cell death. Here we report a search for the source of oxidative calcium in HeLa cells based on confocal epifluorescence microscopy. H(2)O(2) caused a rapid increase in cytosolic calcium, which was followed by mitochondrial Ca(2+) loading. Combined mitochondrial uncoupling with full depletion of thapsigargin-sensitive stores abrogated inositol 1,4,5-trisphosphate-mediated calcium release but failed to inhibit H(2)O(2)-induced calcium release, observation that was confirmed in MDCK cells. Prevention of peroxide-induced acidification with a pH clamp was also ineffective, discarding a role for endosomal/lysosomal Ca(2+)/H(+) exchange. Lysosomal integrity was not affected by H(2)O(2). Mature human erythrocytes also reacted to peroxide by releasing intracellular calcium, thus directly demonstrating the cytosolic source. Glutathione depletion markedly sensitized cells to H(2)O(2), an effect opposite to that achieved by DTT. Iron chelation was ineffective. In summary, our results show the existence of a previously unrecognized sulfhydryl-sensitive source of pathogenic calcium in the cytosol of mammalian cells.


Assuntos
Cálcio/metabolismo , Citosol/metabolismo , Ácido Egtázico/análogos & derivados , Células Epiteliais/metabolismo , Peróxido de Hidrogênio/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Cães , Ácido Egtázico/farmacologia , Retículo Endoplasmático/fisiologia , Células Epiteliais/efeitos dos fármacos , Espaço Extracelular/fisiologia , Células HeLa , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Concentração de Íons de Hidrogênio , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Fatores de Tempo
12.
Cell Death Differ ; 10(6): 687-97, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12761577

RESUMO

Apoptotic and necrotic blebs elicited by H(2)O(2) were compared in terms of dynamics, structure and underlying biochemistry in HeLa cells and Clone 9 cells. Apoptotic blebs appeared in a few minutes and required micromolar peroxide concentrations. Necrotic blebs appeared much later, prior to cell permeabilization, and required millimolar peroxide concentrations. Strikingly, necrotic blebs grew at a constant rate, which was unaffected throughout successive cycles of budding and detachment. At 1 microm diameter, the necks of necrotic and apoptotic blebs were almost identical. ATP depletion was discarded as a major factor for both types of bleb. Inhibition of ROCK-I, MLCK and p38MAPK strongly decreased apoptotic blebbing but had no effect on necrotic blebbing. Taken together, these data suggest the existence of a novel structure of fixed dimensions at the neck of both types of plasma membrane blebs in epithelial cells. However, necrotic blebs can be distinguished from apoptotic blebs in their susceptibility to actomyosin kinase inhibition.


Assuntos
Apoptose/fisiologia , Extensões da Superfície Celular/enzimologia , Células Epiteliais/enzimologia , Fosfotransferases/metabolismo , Actomiosina/metabolismo , Trifosfato de Adenosina/metabolismo , Extensões da Superfície Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células HeLa , Humanos , Peróxido de Hidrogênio/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Necrose , Peptídeos/antagonistas & inibidores , Peptídeos/metabolismo , Fosfotransferases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno , Quinases Associadas a rho
13.
Int J Oncol ; 18(6): 1145-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11351243

RESUMO

We developed a mouse model in a representative human derived head and neck cancer cell line for preclinical studies to evaluate antitumor response, tumor-free survival and host toxicity of alkylating agents, antimetabolites, platinum analogs and taxanes alone or in combination. Ninety athymic NMRI mice were inoculated with human derived oral squamous cell carcinoma cells growing on the hind paw to an average volume of 180 +/- 80 mm3. Animals were stratified according to tumor volume into 10 groups (n=6-10) and treated with ifosfamide (65 mg/kg b.w.), docetaxel (24 mg/kg b.w.), cisplatin (2 mg/kg b.w.), carboplatin (6 or 10 mg/kg b.w.), methotrexate (1 mg/kg b.w.), and fluorouracil (15 mg/kg b.w.) intravenously in single agent or combination (ifosfamide plus docetaxel or ifosfamide plus carboplatin) treatment schedules or controls. Tumor volume was measured 3 times per week for 60 days. The average tumor volume, the overall survival time and the response rates (CR, PR) of the treated animals were compared with the data obtained from untreated controls and statistically evaluated. Untreated tumors showed rapid and exponential tumor growth. Single agent therapies with ifosfamide, cisplatinum, and docetaxel lead to significant tumor regression and improved overall survival. Low dose carboplatin monotherapy induced significant tumor growth delay, but not significant tumor regression. Most impressive tumor-free survival was achieved by combination treatment with ifosfamide and docetaxel. This preclinical study demonstrates an animal model capable of differentiating various chemotherapy regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Modelos Animais de Doenças , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Animais , Plaquetas/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Camundongos , Camundongos Nus , Paclitaxel/administração & dosagem , Taxa de Sobrevida
14.
Chemistry ; 7(6): 1304-8, 2001 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-11322558

RESUMO

The asymmetric synthesis of enantiomerically pure a-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la) with gamma-substituted allylsilanes 9a-h is described. The allylsilanes were obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)-(3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the allylsilanes with la in the presence of the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic ethers 4a, 11 and 12a-c with two new stereogenic centres, with a selectivity of 1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The facial selectivity does not depend on the configuration of the allylsilane, and in all reactions the anti product is preferentially formed. Interestingly, a pronounced switch of facial selectivity takes place with increasing length of the alkyl group of the allylsilane.

15.
Toxicol Sci ; 60(1): 177-83, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11222884

RESUMO

The toxicity of a single hepatic intra-arterial administration of doxorubicin (DOX) coupled to a magnetically targeted drug carrier (MTC) was evaluated in a swine model. MTC is a microparticle composite of elemental iron and activated carbon. MTC-DOX is a new formulation of doxorubicin absorbed to the MTC and is designed for site-specific delivery to a solid tumor in the presence of an externally applied magnetic field. The magnetic field induces extravasation of MTCs through the vascular wall, leading to localization and retention in the tissue at the targeted site. Eighteen swine were assigned to 6 treatment groups, including 3 control groups (vehicle control, doxorubicin, MTC), and 3 experimental groups that received the MTC-DOX preparation. Animals were given a single administration of test article, evaluated over 28 days, and then sacrificed. Signs of toxicity were monitored via clinical status, total body weight, gross and microscopic pathology, and serum chemistries. Angiography was used to determine the extent of any embolization present. There were no adverse effects observed in the DOX-alone group. Biologically significant, treatment-related gross and microscopic lesions were limited to the targeted area of the liver only in groups receiving > or =75 mg of MTC (with or without doxorubicin). The severity of liver necrosis correlated to the severity of embolization following treatment. Doxorubicin was not freely circulating in any of the MTC-DOX groups, suggesting successful localization to the targeted site. The no-adverse-effect level (NOAEL) was determined to be the MTC-DOX low-dose group.


Assuntos
Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Sistemas de Liberação de Medicamentos/efeitos adversos , Angiografia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Peso Corporal/efeitos dos fármacos , Testes de Química Clínica , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Embolia/etiologia , Embolia/patologia , Feminino , Testes Hematológicos , Artéria Hepática/diagnóstico por imagem , Injeções Intra-Arteriais , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Magnetismo , Modelos Animais , Necrose , Nível de Efeito Adverso não Observado , Sistema Porta/diagnóstico por imagem , Sistema Porta/efeitos dos fármacos , Sistema Porta/patologia , Suínos
16.
Chemistry ; 7(1): 161-8, 2001 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-11205007

RESUMO

The stereoselective allylation of chiral methyl ketones to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols, is described. Reaction of the enantiopure ketones 8a-d and the racemic ketones 26a-d with the norpseudoephedrine derivative 2 or ent-2 and allylsilane in the presence of a catalytic amount of trifluoromethanesulfonic acid, led to a series of homoallylic ethers with good to excellent diastereoselectivity (85:15 to > 97:3). The allylation is reagent controlled and nearly independent from the stereogenic centers in the substrates. A partial kinetic resolution was observed using the racemic ketones 26a-d. In the reaction of the chiral ketones 8a-d with the achiral reagents ethoxytrimethylsilane and allylsilane only a low diastereoselectivity was observed.

17.
Lab Invest ; 80(10): 1523-31, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11045569

RESUMO

We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10(4) lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host.


Assuntos
Modelos Animais de Doenças , Linfoma Difuso de Grandes Células B/patologia , Quinase do Linfoma Anaplásico , Animais , Ciclofosfamida/uso terapêutico , Citocinas/genética , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-1/análise , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Tirosina Quinases/análise , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
J Vasc Interv Radiol ; 11(7): 823-36, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10928517

RESUMO

PURPOSE: To evaluate the feasibility of endovascular techniques in treating venous outflow obstruction resulting from compression of the iliac vein by the iliac artery of the left lower extremity (May-Thurner syndrome). MATERIALS AND METHODS: A retrospective analysis of 39 patients (29 women, 10 men; median age, 46 years) with iliac vein compression syndrome (IVCS) was performed. Nineteen patients presented with acute deep vein thrombosis (DVT) and 20 patients presented with chronic symptoms. All patients presented with leg edema or pain. In the acute group, patients were treated with catheter-directed thrombolysis (120,000-180,000 IU urokinase/h) and angioplasty followed by stent placement. In the chronic group, patients were treated with use of angioplasty and stent placement alone (n = 8), or in combination with thrombolysis (n = 12). Patients were then followed-up with duplex ultrasound and a quality-of-life assessment. RESULTS: Initial technical success was achieved in 34 of 39 patients (87%). The overall patency rate at 1 year was 79%. Symptomatically, 85% of patients were completely or partially improved compared with findings before treatment. Thirty-five of 39 patients received stents. The 1-year patency rate for patients with acute symptoms who received stents was 91.6%; for patients with chronic symptoms who received stents, the 1-year patency rate was 93.9%. Five technical failures occurred. Major complications included acute iliac vein rethrombosis (< 24 hours) requiring reintervention (n = 2). Minor complications included perisheath hematomas (n = 4) and minor bleeding (n = 1). There were no deaths, pulmonary embolus, cerebral hemorrhage, or major bleeding complications. CONCLUSION: Endovascular reconstruction of occluded iliac veins secondary to IVCS (May-Thurner) appears to be safe and effective.


Assuntos
Veia Ilíaca , Doenças Vasculares Periféricas/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia , Cateterismo Periférico/instrumentação , Doença Crônica , Terapia Combinada , Constrição Patológica/terapia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ativadores de Plasminogênio/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Stents , Síndrome , Terapia Trombolítica , Ultrassonografia Doppler Dupla , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Grau de Desobstrução Vascular , Trombose Venosa/terapia
19.
Verh Dtsch Ges Pathol ; 84: 187-98, 2000.
Artigo em Alemão | MEDLINE | ID: mdl-11217440

RESUMO

As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus.


Assuntos
Imunoterapia/métodos , Interleucina-9/imunologia , Linfoma Difuso de Grandes Células B/terapia , Linfócitos T/imunologia , Animais , Linhagem Celular , Feminino , Humanos , Interleucina-9/genética , Transfusão de Linfócitos , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante Isogênico
20.
J Vasc Interv Radiol ; 9(6): 986-90, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9840046

RESUMO

PURPOSE: The purpose of this work was to evaluate the incidence of bile peritonitis following T-tube removal in liver transplant patients as a function of the method of T-tube removal. Removal at the bedside was compared to removal in the interventional radiology department with subsequent placement of a temporary drainage catheter. MATERIALS AND METHODS: From June 1987 through July 1993, 1,105 patients underwent orthotopic liver transplantation at the UCLA Medical Center. Three hundred patients were randomly selected from this group and their charts were reviewed. Two hundred sixty-three patients who had choledocho-choledochostomies over a T tube, and adequate documentation of the method of T-tube removal and subsequent clinical course were included in the study. Forty-one patients had their drainage catheter removed at the bedside, and 222 patients had their T-tube removed over a wire in the interventional radiology department with subsequent placement of a temporary drainage catheter. RESULTS: Among all patients included in this study, 10.3% had bile peritonitis. Of the patients who had their T-tube removed at the bedside, 19.5% had bile peritonitis, whereas only 8.6% of the patients who had their T-tube removed in the interventional radiology department had bile peritonitis. This result is statistically significant (P < .05). CONCLUSION: Placing a temporary drain at the time of T-tube removal in the interventional radiology department results in a significant reduction in the incidence of bile peritonitis in liver transplant patients. The procedure is relatively simple, quickly mastered, and well tolerated by patients.


Assuntos
Bile , Intubação/instrumentação , Transplante de Fígado , Peritonite/prevenção & controle , Adolescente , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Cateterismo/instrumentação , Coledocostomia/efeitos adversos , Coledocostomia/instrumentação , Drenagem/instrumentação , Humanos , Incidência , Intubação/efeitos adversos , Pessoa de Meia-Idade , Quartos de Pacientes , Radiologia Intervencionista , Estudos Retrospectivos , Stents/efeitos adversos , Fatores de Tempo
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