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1.
J Vet Med Sci ; 84(5): 675-679, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35400672

RESUMO

A two-year-old male domestic cat showed lethargy, tonic-clonic convulsion, and mucosal jaundice. Upon admission, blood examination indicated severe neutropenia and thrombocytopenia, and ultrasonography revealed diffuse splenomegaly with a honeycomb appearance and abdominal lymph nodes enlargement in addition to a decrease in cardiac blood flow indicating a shock condition. Cytology of the spleen showed a cell population composed of immature large lymphoid cells with distinct nucleoli, suggesting lymphoma. The cat received symptomatic treatments but died four hours later. Reverse transcriptase polymerase chain reaction assay of the spleen sample indicated the presence of severe fever with thrombocytopenia syndrome (SFTS) virus S gene segment. Clinical features of this case that was diagnose as SFTS were similar to lymphoma. Therefore, pet owners and veterinary workers should be protected against infection of SFTS.


Assuntos
Doenças do Gato , Linfoma , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Doenças do Gato/diagnóstico , Gatos , Linfoma/veterinária , Masculino , Phlebovirus/genética , Febre Grave com Síndrome de Trombocitopenia/veterinária
2.
J Vet Med Sci ; 84(3): 439-444, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35110461

RESUMO

An 11-year-old neutered male Domestic Shorthair cat presented with a 3-month history of hypoglycemia, two episodes of seizure, and intermittent tick-like signs. Serum biochemistry revealed severe hypoglycemia associated with high insulin concentrations. Dynamic abdominal computed tomography (CT) indicated two pancreatic masses, which were enhanced most during the late arterial phase but had different degrees and variations of attenuation. Partial pancreatectomy was performed. Histopathology and immunohistochemistry confirmed that one mass was an insulinoma and the other was an ectopic splenic tissue, consistent with the differences in imaging findings. When an intrapancreatic lesion with hyper-attenuation on dynamic abdominal CT is detected, not only insulinoma or metastasis of malignancies but also intrapancreatic accessory spleen (IPAS) should be considered as differential diagnoses.


Assuntos
Doenças do Gato , Coristoma , Insulinoma , Pancreatopatias , Neoplasias Pancreáticas , Animais , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/cirurgia , Gatos , Coristoma/diagnóstico , Coristoma/cirurgia , Coristoma/veterinária , Diagnóstico Diferencial , Insulinoma/diagnóstico , Insulinoma/cirurgia , Insulinoma/veterinária , Masculino , Pancreatectomia/veterinária , Pancreatopatias/diagnóstico , Pancreatopatias/cirurgia , Pancreatopatias/veterinária , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/veterinária , Baço/patologia
3.
Behav Processes ; 193: 104526, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601053

RESUMO

Ungulates visually and olfactorily discriminating between vegetation patches in grasslands often encounter restriction of target visibility due to light intensity changes; however, little is known about their performance in such a context. We developed and tested an apparatus for evaluating the visual and olfactory discrimination ability of cattle under controlled target visibility, focusing on the discrimination at a short distance. The apparatus was designed to contain a discrimination target under a sliding cover of variable light transmission levels and behind a vent of a fixed size and aperture so as to control the visibility of the target (14-100% restrictions) while ensuring a constant level of odor. Twelve Japanese Black cows were allowed to choose between two apparatuses presenting a pair of targets: green forage versus empty, green forage versus dead forage, or green forage versus green-dead mixture. Cows rapidly learned to slide open the cover to reach the selected target, consistently chose the green forage against the alternative except against the green-dead mixture under 100% visual restriction, and remembered the reaching procedure for at least 16 days. The results indicate the usefulness of the apparatus for assessing close visual and olfactory discrimination ability of cattle in detail.


Assuntos
Odorantes , Olfato , Ração Animal , Animais , Bovinos , Feminino , Lactação
4.
Ann Nucl Med ; 35(12): 1293-1304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34410619

RESUMO

OBJECTIVE: p38α, a member of the mitogen-activated protein kinase superfamily, is ubiquitously expressed in a variety of mammalian cells. Activated p38α induces inflammatory responses to external stimuli, suggesting that non-invasive detection of activated p38α would be valuable for diagnosing inflammatory diseases. For this purpose, we designed radiolabeled compounds [123I]2-IR and [123I]4-IR based on a potent p38α selective inhibitor R1487 for use with single photon emission computed tomography (SPECT). In this study, we used 125I instead of 123I due to its more usable radiochemical properties, synthesized [125I]2-IR and [125I]4-IR, and evaluated their effectiveness as activated p38α imaging probes. METHODS: [123I]2-IR and [123I]4-IR were designed by introduction of a 123I atom at the 2- or 4-ositions of the phenoxy ring, preserving the pyrimidinopyridone structure of R1487. We synthesized 2-IR and 4-IR via a 7-step process. The inhibitory potencies of 2-IR, 4-IR, and p38α inhibitors were measured using an ADP-Glo™ kinase assay system. Radioiodination of 2-IR and 4-IR was performed via an organotin-radioiodine exchange reaction using the corresponding tributyltin precursors. Biodistributions were evaluated by determining radioactivity in tissues of interest after intravenous administration of [125I]2-IR and [125I]4-IR in normal ddY mice and turpentine oil-induced inflammation model mice. In vivo inhibition study was also performed in inflammation model mice after intravenous administration of [125I]4-IR with pretreatment of p38α inhibitors. RESULTS: We synthesized 2-IR and 4-IR at total yields of 17.5% and 19.2%, respectively. 4-IR had higher p38α inhibitory potency than 2-IR; both compounds were significantly less potent than R1487. [125I]2-IR and [125I]4-IR were successfully obtained from tributyltin precursors with high radiochemical yield (> 65%), purity (> 97%), and molar activity (~ 81 GBq/µmol). [125I]4-IR showed high radioactivity accumulation in the inflamed tissue (7.0 ± 1.2%D/g), rapid delivery throughout the body, and rapid blood clearance, resulting in a high inflammation-to-blood ratio (6.2 ± 0.4) and a high inflammation-to-muscle ratio (5.2 ± 1.3) at 30 min, while [125I]2-IR showed low radioactivity accumulation in inflamed tissue over the experimental period. Further, radioactivity accumulation in inflamed tissue after [125I]4-IR administration was significantly decreased by pretreatment with selective inhibitors. CONCLUSIONS: [123I]4-IR would be a promising imaging agent for detection of activated p38α.


Assuntos
Tomografia Computadorizada de Emissão de Fóton Único
5.
Anim Cogn ; 24(1): 99-106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32779060

RESUMO

The ability of ungulates to discriminate among vegetation patches depends largely on the senses of vision, olfaction, tactility, and gustation. However, little is known about how ungulates rely on the respective senses in response to varying patch characteristics. This study aimed to evaluate how relative importance of senses in patch discrimination by cattle is affected by the sensory contrast between the discrimination targets. Five Japanese Black cows were allowed to choose between two forage patches from a distance of about 1 m. Two combinations of forage patches were used: one was a pair of green and dead forages of bahiagrass (BG) with clear mutual contrast in appearance and odor, and the other was a pair of green forages of BG and cogongrass (CG) with visual and olfactory resemblance. Cows preferably located and ate the green BG as the first choice (Type 1), or as the second choice after touching (Type 2) or further biting (Type 3) the alternative in error. Overall, Type 1 accounted for a high above-chance proportion of 0.94 in the green BG vs. dead BG discrimination, indicating the primary importance of vision and olfaction. By contrast, in the green BG vs. green CG discrimination, Type 1 remained at the chance level of 0.55 with proportions of 0.17 for Type 2 and 0.28 for Type 3, indicating the primary importance of tactility on the muzzle and in the mouth. The context-specific importance of the four senses in patch discrimination represents an adaptive mechanism of animals foraging in grasslands.


Assuntos
Dieta , Sensação , Animais , Bovinos , Cor , Feminino
6.
Ann Nucl Med ; 35(1): 83-91, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33067731

RESUMO

OBJECTIVE: Glucagon-like peptide-1 receptor agonist (GLP-1RA) has been reported to have therapeutic effects on diabetes and various diseases. Precise detection of GLP-1 receptor (GLP-1R) can be useful to diagnose and elucidate the mechanism of such diseases. Here we aimed to develop an imaging probe based on GLP-1RA that has high molar activity and sensitivity for detection of low-level GLP-1R expression in non-pancreatic diseases. METHODS: We selected the agonist exenatide (Ex4) as the parent peptide of a GLP-1R targeting probe and prepared Cys-Ex4 by addition of an N-terminal Cys residue and labeling with the prosthetic agent N-(3-[125I]iodophenyl)maleimide ([125I]IPM) to generate [125I]Ex4ipm. We evaluated the affinity of [125I]Ex4ipm for GLP-1R, as well as cellular binding profiles in insulinoma and prostate cancer cell lines, and in vivo biodistributions in normal and tumor-bearing mice to assess GLP-1R-dependent accumulation of radioactivity in tissues. RESULTS: [125I]Ex4ipm was easily synthesized with high radiochemical yield (73%), radiochemical purity (> 99%), and molar activity (81 GBq/µmol) via a thiol/maleimide reaction. Following administration to mice, [125I]Ex4ipm accumulated to high levels in the pancreas (23.3% ID/g), with radioactivity co-localizing in areas having insulin-positive ß cells. High amounts of radioactivity also accumulated in insulinomas that overexpressed GLP-1R (27.5% ID/g). In contrast, low amounts of [125I]Ex4ipm accumulation, corresponding to low expression levels of GLP-1R, were observed in prostate cancer cells and xenografts used as a model of non-pancreatic applications. CONCLUSION: Our results suggested that [123I]Ex4ipm could be valuable for GLP-1R imaging in diabetes, insulinomas, and various diseases related to GLP-1R.


Assuntos
Doença , Exenatida/química , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Radioisótopos do Iodo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos
7.
Ann Nucl Med ; 34(7): 486-495, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32385783

RESUMO

OBJECTIVE: Angiogenesis facilitates tumor survival and promotes malignancy. The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) tyrosine kinase (TK) signaling pathway is a key factor mediating angiogenesis, suggesting that this pathway may be a target for diagnosis and therapy. In this study, we aimed to develop small molecule radioiodinated probes applicable for in vivo VEGFR imaging considering the versatility and usefulness of single-photon emission computed tomography (SPECT). METHODS: We designed and synthesized four radioiodinated anthranilate compounds (6a-d) based on the structure of an anticancer drug targeting VEGFR-TK. The inhibitory potencies of corresponding cold compounds 4a-d and in vitro stability of compounds 6a-d were assessed by cellular proliferation inhibition assays and radio thin-layer chromatography after incubation in neutral solution. In vivo biodistributions were evaluated by determining radioactivity in tissues of interest after intravenous injection of test compounds in tumor-bearing mice. In vitro and in vivo blocking experiments using a selective VEGFR-TK inhibitor and SPECT/computed tomography (CT) imaging were performed in tumor-bearing mice. RESULTS: The radioiodinated compounds 6a-d were obtained with more than 68.0% radiochemical yield and more than 95% radiochemical purity. Because compounds 4a-d showed high inhibitory potencies and compounds 6c and 6d showed high in vitro stability, 6c ([125I]m-NPAM) and 6d ([125I]p-NPAM) were further evaluated. Analysis of the in vivo biodistribution revealed a tumor to blood radioactivity ratio of greater than 4 at 24 h after [125I]p-NPAM administration. Accumulation of radioactivity in cultured tumor cells and tumor xenografts after [125I]p-NPAM administration was significantly blocked by inhibitor pretreatment. Tumors were clearly imaged at 24 h after [125I]p-NPAM injection with SPECT/CT in comparison to that in inhibitor-pretreated tumor-bearing mice. CONCLUSION: [125I]p-NPAM may have potential applications as a lead compound for future development of a clinically usable VEGFR imaging probe for SPECT.


Assuntos
Radioisótopos do Iodo/química , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , ortoaminobenzoatos/química , ortoaminobenzoatos/síntese química , Animais , Técnicas de Química Sintética , Humanos , Masculino , Camundongos , Células PC-3 , Radioquímica , Distribuição Tecidual , ortoaminobenzoatos/farmacocinética
8.
Biochem Biophys Res Commun ; 528(1): 168-173, 2020 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-32451087

RESUMO

Integrin αvß3 is an effective marker of angiogenesis in cancer, and αvß3-specific imaging can yield important details about this complex physiological process. We utilized the recently reported and highly αvß3-specific peptide, bicyclic RGD (bcRGD), as the basic structure of an in vivo αvß3 imaging probe, and synthesized a radioiodinated form of bcRGD, namely [125I]bcRGD, with high radiochemical purity (>99%) and high molar activity (81 GBq/µmol). As expected, [125I]bcRGD exhibited high selectivity for αvß3 compared with αvß5 and α5ß1in vitro. [125I]bcRGD showed significantly higher accumulation in U-87MG cells (1.6% dose/mg) with high expression of αvß3 compared to A549 cells (0.3% dose/mg) with only moderate expression. Furthermore, 30 min after administration to tumor-bearing mice, [125I]bcRGD showed significantly higher accumulation in U-87MG tumors (3.8% ID/g) than in A549 tumors (2.1% ID/g), and the radioactivity accumulation ratios of U-87MG tumor/blood and U-87MG tumor/muscle were 4.0 and 6.0, respectively. These results highlight the promising properties of [123/125I]bcRGD for use as an in vivo αvß3 imaging probe, as well as the utility of bcRGD as a basic structure of molecular probes for both imaging and therapeutic applications. bcRGD may exhibit broad use in future theranostics applications targeting integrin αvß3-related diseases.


Assuntos
Integrina alfaVbeta3/metabolismo , Radioisótopos do Iodo/metabolismo , Neoplasias/metabolismo , Peptídeos Cíclicos/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Peptídeos Cíclicos/química , Distribuição Tecidual
9.
Anim Cogn ; 23(2): 405-414, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31915949

RESUMO

The ability of ungulates to discriminate among vegetation patches depends largely on the senses of vision, olfaction, tactility, and gustation. However, little is known about how ungulates rely on the respective senses in response to varying distances to discrimination targets. This study aimed to assess how cattle discriminate between patches of green and dead forages by means of senses, with a particular attention to the role of vision in relation to the distance to the forages. Thirteen Japanese Black cows were allowed to choose between the two forages from a distance of about 1 m without (- BF) or with (+ BF) a blindfold. The green forage differed from the dead forage in color, texture, odor, quality, and animals' preference. Cows located and ate the green forage as the first choice (Type 1), or as the second choice after touching (Type 2) or further biting (Type 3) the dead forage in error. Overall, the proportion of [Type 1]/[Types 1 + 2 + 3] was above the chance for both - BF and + BF with a decrease by blindfolding. The proportion of [Type 2]/[Types 2 + 3] was above the chance for both - BF and + BF with no effect of blindfolding. The results indicate that cattle discriminating green forage against dead forage rely greatly on vision and to a lesser degree on olfaction when away from the forages, but rely no longer on vision and at least on tactility on the muzzle or in the mouth when in contact with a wrong choice.


Assuntos
Ração Animal , Percepção de Cores , Comportamento Alimentar , Animais , Bovinos , Cor , Feminino , Cabeça , Movimento , Sensação
10.
J Labelled Comp Radiopharm ; 62(9): 580-587, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31215665

RESUMO

Monoamine oxidase B (MAO-B), predominantly expressed in glial cells, plays an important role in neurotransmitter regulation, and MAO-B activity relates to several neuronal diseases. Here, we aimed to develop a radiofluorinated MAO-B imaging probe based on the structure of a selective MAO-B inhibitor, MD-230254. We synthesized and evaluated a series of compounds in vitro and in vivo. A series of fluorinated analogs of MD-230254 were synthesized and evaluated for inhibitory potency and selectivity toward MAO-B. 5-[4-(2-[18 F]Fluorobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (2-[18 F]FBPO) was synthesized from a corresponding tributylstannyl precursor and [18 F]CH3 COOF. Biodistribution after intravenous injection of 2-[18 F]FBPO was evaluated in male ddY mice with or without pretreatment by inhibitors. Among the compounds synthesized and evaluated, 2-FBPO showed high inhibitory potency and selectivity toward MAO-B comparable with MD-230254. 2-[18 F]FBPO was successfully synthesized by an electrophilic reaction with a high radiochemical purity of more than 99%. 2-[18 F]FBPO was efficiently taken up by the brain and showed rapid blood clearance, which provided a brain/blood radioactivity ratio of 3.7 at 90 minutes postinjection. The brain radioactivity was significantly decreased by pretreatment with an MAO-B selective inhibitor. The great potential of 2-[18 F]FBPO as an MAO-B imaging probe, applicable to a variety of diseases, is indicated.


Assuntos
Radioisótopos de Flúor/química , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/síntese química , Monoaminoxidase/metabolismo , Oxidiazóis/química , Oxidiazóis/síntese química , Tomografia por Emissão de Pósitrons/métodos , Animais , Técnicas de Química Sintética , Marcação por Isótopo , Masculino , Camundongos , Inibidores da Monoaminoxidase/farmacocinética , Oxidiazóis/farmacocinética , Radioquímica , Ratos , Distribuição Tecidual
11.
Anim Cogn ; 22(5): 707-718, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31127432

RESUMO

Relatively little is known about the ability of ungulates to visually discriminate vegetation patches while foraging on grasslands despite extensive studies with man-made stimuli presented indoors. This study aimed to assess visual discrimination ability of cattle (Bos taurus) under conditions closer to the actual foraging situation. Twelve Japanese Black cows were afforded four successive opportunities to choose between green and dead forages presented as 25 × 25 cm patches 1, 2, or 3 m ahead while walking through a 25-m-long field area. Apparatuses for presenting the forages as visual stimuli were designed to minimize olfactory cues. The green forage differed from the dead forage in appearance (color and texture) and quality (digestible dry matter and crude protein). Cows preferred the green forage to the dead forage and were able to use the forages as visual cues to discriminate them. The proportion of green forage choices was 0.70-0.72 (different from the chance at P < 0.001), 0.57 (P < 0.05), and 0.53 (P ≥ 0.1) at the distances of 1, 2, and 3 m, respectively. The results indicate that the ability of ungulates to visually discriminate vegetation patches during foraging in grasslands would not be as high as that expected from the visual acuity reported in the previous indoor studies.


Assuntos
Percepção de Cores , Comportamento Alimentar , Percepção Visual , Animais , Bovinos , Feminino
12.
Ann Nucl Med ; 33(5): 333-343, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30953245

RESUMO

OBJECTIVE: p38 mitogen-activated protein (MAP) kinase (p38α) has drawn attention as a new target molecule for the treatment and diagnosis of cancer, and its overexpression and activation have been reported in various types of cancer. In this study, a single photon emission computed tomography (SPECT) imaging probe of p38α was developed to noninvasively image p38α activity for effective qualitative diagnosis of cancer. METHODS: Pyrrolepyridine derivatives, m-YTM and p-YTM, were designed and synthesized based on the structure of the p38α-selective inhibitor. Radioactive iodine-labeled m-YTM, [125I]m-YTM, was synthesized because m-YTM greatly inhibited the phosphorylation of p38α upon examining the inhibitory effects of the compounds. After investigating the binding affinity of [125I]m-YTM to the recombinant p38α, a saturation binding experiment using activated p38α and inactive p38α was performed to determine the binding site. Uptake of [125I]m-YTM into various cancer cell lines was investigated, and the pharmacokinetics was evaluated using tumor-bearing mice. RESULTS: The inhibitory activity of m-YTM was approximately 13 times higher than that of SB203580, a p38α-selective inhibitor. The binding site of [125I]m-YTM was estimated to be the p38α activating site, similar to that of SB203580, because the [125I]m-YTM bound strongly to both activated p38α and inactive p38α. Various different cancer cells incorporated [125I]m-YTM; however, its accumulation was significantly reduced by treatment with SB203580. Pharmacokinetics study of [125I]m-YTM in B-16 tumor-bearing mice was examined which revealed high accumulation of radioactivity in tumor tissues. The ratios of radioactivity in the B-16 tumor to that in blood were 3.1 and 50 after 1 and 24 h, respectively. The ratio of radioactivity in the tumor to that in blood in the tumor-bearing mice generated using other cancer cell lines was also ≥ 1 at 1 h after the administration of the probe. CONCLUSIONS: This study suggests that [123I]m-YTM has potential as a p38α imaging probe effective for various cancer types.


Assuntos
Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Pirróis/química , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Transporte Biológico , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Pirróis/metabolismo , Pirróis/farmacocinética , Pirróis/farmacologia , Distribuição Tecidual
13.
Behav Processes ; 157: 315-319, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30071245

RESUMO

This study was conducted to investigate how cattle (Bos taurus) respond to objects presented for the first time and repeatedly in a stimulus-rich environment where they can freely graze and interact with conspecifics. Twenty-five Japanese Black cows were subjected to three repeats of a novel object test in which animals stocked on a pasture as a group were exposed to the same and different objects across the test repeats. Responses of cows towards the objects were quantified by both approach (entering within a 0.5-m distance of the object) and contact (physical touch with the object) measures as occurrence (1 or 0) and number of reactions and latency to the first reaction. Cows were consistent in the approach to the first-time objects (repeatability = 0.39-0.62, Kendall's W = 0.58, P < 0.05), but not in the approach to the repeatedly presented objects or in the contact with both types of objects (P > 0.05). Individuals which consistently approached the novel objects could be regarded as highly exploratory and/or bold in personality. Future work should consider novel object response in cattle across a range of contexts.


Assuntos
Bovinos/psicologia , Processos Grupais , Herbivoria/fisiologia , Personalidade , Animais , Feminino
14.
Bioorg Med Chem ; 26(8): 1609-1613, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29478801

RESUMO

Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR-TKIs) are used as molecular targeted therapy for non-small cell lung cancer (NSCLC) patients. The therapy is applied to the patients having EGFR-primary L858R mutation, but drug tolerance caused by EGFR-secondary mutation is occurred within one and half years. For the non-invasive detection of the EGFR-TKIs treatment positive patients by positron emission tomograpy (PET) imagaing, fluorine-18 labeled thienopyrimidine derivative, [18F]FTP2 was newly synthesized. EGFR inhibition assay, cell uptake study, and blocking study indicated [18F]FTP2 binds with high and selective affinity for EGFR with L858R mutation, and not with L858R/T790M dual mutations. On animal PET study using tumor bearing mice, H3255 cells expressing L858R mutated EGFR was more clearly visualized than H1975 cells expressing L858R/T790M dual mutated EGFR. [18F]FTP2 has potential for detecting NSCLC which is susceptible to EGFR-TKI treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/química , Compostos Radiofarmacêuticos/química , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Relação Dose-Resposta a Droga , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
15.
Anim Sci J ; 88(6): 909-917, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27723180

RESUMO

This study conducted four experiments to assess preference of cattle between centipedegrass (Eremochloa ophiuroides; CG) and bahiagrass (Paspalum notatum; BG) under manipulated vegetation conditions. In each experiment, three Japanese Black cows (Bos taurus) were individually allowed to graze four plots of conterminous monocultures of CG and BG (30 min for each 10 × 10 m plot). Vegetation of the plots was the combinations of two patch sizes (coarse and fine; 5 × 10 m and 5 × 5 m, respectively) × two relative availabilities of the grasses (CGtall /BGshort and CGshort /BGtall ). Tall and short patches were created by varying regrowth durations after cutting, and almost always offered a clear CG-BG contrast in availability (height and mass) and quality (digestibility and protein) with the trade-off relationship. Cows always preferred or equally selected CG to BG, with the preference being affected by the relative availability of grasses in three of the four experiments but not by the patch size at all. Test of intake rate maximization on both short-term and daily bases indicated that cows chose between the grasses to simultaneously enhance daily potential intake of dry matter, digestible energy and protein. The results strengthen the value of CG as a forage.


Assuntos
Bovinos/fisiologia , Bovinos/psicologia , Dieta/veterinária , Preferências Alimentares , Herbivoria/fisiologia , Paspalum/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimento , Animais , Digestão , Ingestão de Alimentos , Feminino , Qualidade dos Alimentos
16.
Anim Sci J ; 87(11): 1443-1452, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26931311

RESUMO

This study investigated responsiveness of beef cattle to various environmental stimuli by subjecting 15-16 Japanese Black cows to five tests repeated twice. Within individual behavioral measures, cows were moderately (repeatability = 0.54-0.70) or highly (repeatability = 0.74-0.89) consistent in flight distance during grazing and resting in the human approach tests, maximum distance from the group pen and the number of total and different feed tub visits in the feeding-sociability trade-off test, and unwillingness to enter the restraint, movement under restraint and flight speed after release from restraint in the social isolation and restraint test. By contrast, cows were not consistent in the latency to make the first contact and the number of contacts with novel object(s) in the novelty test (repeatability = 0.24-0.39). Across behavioral measures in different tests, cows showed no consistency (P ≥ 0.05) in any combinations of measures from the two human approach tests, the trade-off test and the social isolation and restraint test. In conclusion, human approach (particularly during resting), feeding-sociability trade-off and social isolation and restraint situations can be used for evaluating personality in Japanese Black cows, while the value of the novelty test needs to be reexamined.


Assuntos
Comportamento Animal/fisiologia , Bovinos/fisiologia , Bovinos/psicologia , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Vínculo Humano-Animal , Comportamento Social , Animais , Feminino , Herbivoria/fisiologia , Humanos , Personalidade/fisiologia , Descanso/fisiologia , Descanso/psicologia , Isolamento Social/psicologia
17.
Nucl Med Biol ; 43(1): 101-107, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26602328

RESUMO

Phosphatidylinositol 3-kinase (PI3K) activity and protein expression levels are often increased in tumor regions. Since PI3K plays a crucial role in regulating cell growth and proliferation, inhibiting PI3K-dependent pathways could be a promising approach for cancer treatment. In clinical practice, however, evaluation of PI3K expression levels is limited to immunohistochemistry of patient samples, which requires invasive biopsies. Here we report the synthesis of three candidate compounds, FMTA-1, 2 and 3, and evaluate their capacity to detect PI3K expression levels with positron emission tomography (PET). Among the three candidates, FMTA-2 showed a lower IC50 value for PI3K. (18)F Radiolabeling of FMTA-2 to produce [(18)F]FMTA-2 was accomplished and its capacity for detecting PI3K expression levels was evaluated in vitro and in vivo. Cell uptake of [(18)F]FMTA-2 correlated well with cellular PI3K expression levels, and was suppressed by the ATP-competitive PI3K inhibitor ZSTK474. In an in vivo experiment using tumor-transplanted model mice, a higher signal-to-noise ratio (S/N) was seen with [(18)F]FMTA-2 in animals transplanted with DMS114 cells (expressing high PI3K levels) relative to DU145 cells (expressing low PI3K levels). However, in vivo pharmacokinetics of [(18)F]FMTA-2 was undesirable and the absolute amount of this compound that accumulated at the tumor region was low. To the best of our knowledge, this study represents the first trial of a PET tracer for detecting PI3K. Although further improvement of the probe is required prior to clinical application, these results should encourage future work.


Assuntos
Descoberta de Drogas , Radioisótopos de Flúor , Fosfatidilinositol 3-Quinases/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Triazinas/metabolismo , Animais , Transporte Biológico , Linhagem Celular Tumoral , Masculino , Camundongos , Radioquímica , Triazinas/síntese química , Triazinas/química
18.
Anim Sci J ; 87(5): 674-80, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26355386

RESUMO

In south-western Japan, centipedegrass (Eremochloa ophiuroides; CG) offers a novel option for a warm-season perennial for grazing use in areas where bahiagrass (Paspalum notatum; BG) can be grown. However, the potential of CG as a forage has not been fully explored because of the short history as a forage crop. We conducted four experiments to evaluate CG (cv. TifBlair) in comparison with BG (cv. Pensacola) in terms of sward characteristics, nutritive value and choice by animals. In each experiment, four Japanese Black cows (Bos taurus) were individually allowed to graze conterminous monocultures of CG and BG (5 × 10 m each) for 30 min. Irrespective of regrowth durations and fertilizer rates, CG was consistently shorter, leafier and denser, contained lower acid detergent fiber and cellulose, and was preferred or equally selected by cows, as compared with BG. Furthermore, CG maintained sufficient levels of crude protein (80-89 g/kg DM) to ensure voluntary intake of ruminant animals under extended regrowth(‡) and without fertilizer, whereas BG failed to do so (65 g/kg DM). CG provided higher digestible dry matter than BG when crude protein concentration exceeded 86 g/kg DM. The results indicate advantages of CG as a forage.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Bovinos/fisiologia , Bovinos/psicologia , Comportamento de Escolha/fisiologia , Herbivoria , Valor Nutritivo , Paspalum , Poaceae , Animais , Celulose/análise , Digestão , Ingestão de Alimentos , Feminino , Paspalum/química , Paspalum/crescimento & desenvolvimento , Proteínas de Plantas/análise , Poaceae/química , Poaceae/crescimento & desenvolvimento
19.
Am J Nucl Med Mol Imaging ; 4(4): 293-302, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24982815

RESUMO

The aim of this study was to determine whether the uptake of radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy) quinazoline ([(125)I]PYK) could predict the response of non-small cell lung cancer (NSCLC) cells to radiotherapy in vitro. Four NSCLC cell lines, PC9, HCC827, A549, and H1975 were used. Cells were irradiated with doses ranging from 2 Gy to 8 Gy and/or exposed to 1 µM gefitinib. The effects of radiation and gefitinib were assessed by the CCK-8 assay and confirmed by reverse transcription-polymerase chain reaction and immunoflorescence microscopy. The uptake of [(125)I]PYK was determined by incubating cells with a tracer. The cell cycle was assessed by flow cytometry. The expression of EGFR was measured by western blotting. The results obtained revealed that the uptake of [(125)I]PYK was higher in PC9 and HCC827 cells than in A549 and H1975 cells. PC9 cells and HCC827 cells were also more radiosensitive than A549 and H1975 cells. The gefitinib pretreatment reduced the S phase fraction and enhanced radiation effects in PC9 and HCC827 cells. These results indicate that the uptake of [(125)I]PYK is related to the effects of radiation in NSCLC cells. Radioiodinated PYK may be useful in predicting the response of NSCLC in patients to radiotherapy.

20.
Anim Sci J ; 85(6): 729-34, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24798642

RESUMO

Use of visual cues to locate specific food resources from a distance is a critical ability of animals foraging in a spatially heterogeneous environment. However, relatively little is known about how long animals can retain the learned cue-reward association without reinforcement. We compared feeding behavior of experienced and naive Japanese Black cows (Bos taurus) in discovering food locations in a pasture. Experienced animals had been trained to respond to a visual cue (plastic washtub) for a preferred food (grain-based concentrate) 1 year prior to the experiment, while naive animals had no exposure to the cue. Cows were tested individually in a test arena including tubs filled with the concentrate on three successive days (Days 1-3). Experienced cows located the first tub more quickly and visited more tubs than naive cows on Day 1 (usually P < 0.05), but these differences disappeared on Days 2 and 3. The performance of experienced cows tended to increase from Day 1 to Day 2 and level off thereafter. Our results suggest that Japanese Black cows can associate a visual cue with a food reward within a day and retain the association for 1 year despite a slight decay.


Assuntos
Comportamento Animal/fisiologia , Bovinos/fisiologia , Bovinos/psicologia , Sinais (Psicologia) , Comportamento Alimentar/psicologia , Alimentos , Recompensa , Percepção Visual/fisiologia , Animais , Feminino , Fatores de Tempo
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