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1.
Med Mol Morphol ; 57(1): 76-81, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38071257

RESUMO

In this study, we investigated specific and characteristic findings of the surface layer of surgical resected disc specimens in human temporomandibular joint osteoarthritis cases by transmission electron microscopy (TEM).Specimens were surgically removed from the TMJ of 5 cases (4 female patients: 5 cases) clinically osteoarthritis. Following findings were observed by TEM. Images were photographed on a JEM1400-Flash Electron microscope (JEOL, Japan) equipped with an EM-14661FLASH high-sensitivity digital complementary metal-oxide-semiconductor camera.Following findings were observed by TEM. 1) The surface is covered with plump fibroblastic and histiocytoid cells. 2) Collagen fiber bundles and collagenous matrix are exposed onto the eroded disc surface. 3) Fibrinous dense material is observed on the eroded disc surface. 4) Bundles of collagen fibers are densely observed. 5) Collagen bundles are rich around capillary vessels. 6) Synovial surface cells reveal features of activated macrophages with vacuole formation. Especially, plump fibroblastic and histiocytoid cells, and activated macrophages with vacuole, which were significant findings of the surface layer. These findings might have a significant effect on the regulation of synovial fluid.


Assuntos
Osteoartrite , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Elétrons , Membrana Sinovial/ultraestrutura , Articulação Temporomandibular/cirurgia , Microscopia Eletrônica de Transmissão , Colágeno/ultraestrutura
2.
Pharmaceuticals (Basel) ; 16(11)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-38004392

RESUMO

Auger electrons can cause nanoscale physiochemical damage to specific DNA sites that play a key role in cancer cell survival. Radio-Pt is a promising Auger-electron source for damaging DNA efficiently because of its ability to bind to DNA. Considering that the cancer genome is maintained under abnormal gene amplification and expression, here, we developed a novel 191Pt-labeled agent based on pyrrole-imidazole polyamide (PIP), targeting the oncogene MYCN amplified in human neuroblastoma, and investigated its targeting ability and damaging effects. A conjugate of MYCN-targeting PIP and Cys-(Arg)3-coumarin was labeled with 191Pt via Cys (191Pt-MYCN-PIP) with a radiochemical purity of >99%. The binding potential of 191Pt-MYCN-PIP was evaluated via the gel electrophoretic mobility shift assay, suggesting that the radioagent bound to the DNA including the target sequence of the MYCN gene. In vitro assays using human neuroblastoma cells showed that 191Pt-MYCN-PIP bound to DNA efficiently and caused DNA damage, decreasing MYCN gene expression and MYCN signals in in situ hybridization analysis, as well as cell viability, especially in MYCN-amplified Kelly cells. 191Pt-MYCN-PIP also induced a substantial increase in cytosolic dsDNA granules and generated proinflammatory cytokines, IFN-α/ß, in Kelly cells. Tumor uptake of intravenously injected 191Pt-MYCN-PIP was low and its delivery to tumors should be improved for therapeutic application. The present results provided a potential strategy, targeting the key oncogenes for cancer survival for Auger electron therapy.

3.
J Med Chem ; 66(13): 9023-9039, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37314161

RESUMO

This study provides the first example of a strategy to design a practical ligand toward lysosomal acid α-glucosidase (GAA) focusing on N-alkyl derivatives of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB). The optimized N-4'-(p-trifluoromethylphenyl)butyl-DAB (5g) showed a Ki value of 0.73 µM, which was 353-fold higher affinity than N-butyl-DAB (3f) without a terminal phenyl group. Docking analysis showed that the phenyl part of 5g was accommodated in a lipophilic pocket. Furthermore, the p-trifluoromethyl group effectively suppresses the fluctuation of the phenyl group, allowing it to produce a stable bonding form with GAA. 5g increased the midpoint of the protein's protein denaturation temperature (Tm) by 6.6 °C above that in the absence of the ligand and acted as a "thermodynamic stabilizer" to improve the thermal stability of rhGAA. 5g dose-dependently increased intracellular GAA activities in Pompe patient's fibroblasts with the M519V mutation; its effect was comparable to that of DNJ, which is under clinical trials.


Assuntos
Doença de Depósito de Glicogênio Tipo II , alfa-Glucosidases , Humanos , alfa-Glucosidases/metabolismo , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/metabolismo , Ligantes , Lisossomos/metabolismo , Fibroblastos
4.
Sci Adv ; 9(22): eadg5495, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37267352

RESUMO

Salinity stress can greatly reduce seed production because plants are especially sensitive to salt during their reproductive stage. Here, we show that the sodium ion transporter AtHKT1;1 is specifically expressed around the phloem and xylem of the stamen in Arabidopsis thaliana to prevent a marked decrease in seed production caused by salt stress. The stamens of AtHKT1;1 mutant under salt stress overaccumulate Na+, limiting their elongation and resulting in male sterility. Specifically restricting AtHKT1;1 expression to the phloem leads to a 1.5-fold increase in the seed yield upon sodium ion stress. Expanding phloem expression of AtHKT1;1 throughout the entire plant is a promising strategy for increasing plant productivity under salinity stress.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Simportadores , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Simportadores/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Sódio/metabolismo , Regulação da Expressão Gênica de Plantas
5.
Dent Mater J ; 42(3): 319-326, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36858627

RESUMO

Bone regeneration requires cells, growth factors, and scaffolds that should have biocompatibility, porosity, and physical strength. Therefore, coral granules (CG) with diameters of 600-1,000 µm were prepared as a potential graft material from cultured edaphic thermostable corals. X-ray and electron microscopy characterization revealed that CGs were porous and permeable with lumen diameters of approximately 200 µm. Human periodontal ligament fibroblasts showed significantly increased mitochondrial activity in culture seven days after adding CG. After CG filling into an experimentally created one-wall infrabony defect in a beagle dog jawbone, the defect almost completely disappeared within approximately 8 weeks, and bone tissue growth was observed in the replacement area. This could indicate extremely rapid healing of a bone defect previously considered incapable of self-healing. Based on stable supply of cultured coral (Montipora digitata), CG is potentially an ideal replacement material for alveolar and jawbone defects.


Assuntos
Perda do Osso Alveolar , Substitutos Ósseos , Exoesqueleto Energizado , Cães , Humanos , Animais , Substitutos Ósseos/farmacologia , Regeneração Tecidual Guiada Periodontal , Perda do Osso Alveolar/cirurgia , Regeneração Óssea , Osso e Ossos
6.
Ultrasonics ; 129: 106907, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36495767

RESUMO

Observing alterations in cutaneous vasculature in response to any disease or pathology is considered as a potential diagnostic marker in the progression and cure of a disease. To observe skin morphologies and tissue conditions, high-frequency ultrasound (HFUS) has been used in dermatology, although its ability to selectively visualize micro-vessels is limited due to insufficient Doppler sensitivity to peripheral slow-speed blood flow. In recent studies, this issue has been improved by increasing the sensitivity of Doppler imaging to slow flow, leveraging advanced cutter filtering approaches based on singular value decomposition (SVD) techniques that aid to effectively extract flow signals overlapped with tissue echo signals. Nevertheless, in skin imaging, variations in flow speed, diameter, and depth of the blood vessels at different skin layers can make clutter filtering challenging because these variations are problematic in selecting the optimal cut-off value for the SVD filtering. In this study, we aimed to devise a novel region-based SVD filtering approach for ultrafast HFUS data to visualize cutaneous vascular networks. The proposed method divides the acquired high-framerate data into two regions based on B-mode cutaneous morphological identification (dermis layer and subcutaneous tissue). Singular value decomposition processing was performed on each region to effectively extract the desired flow signal, and the processed regions were merged to generate a single power Doppler image, thereby highlighting the appearance of a complete cutaneous vascular network. Finally, top-hat transform was applied to the power Doppler image to further suppress the background noises and enhances the visibility of the micro-vessels. Experimental observations of the human cutaneous circulation showed that the image quality (contrast-to-noise ratio) through the region-based SVD filtering was measured to be 4.1 dB (before top-hat filtering) and 5.2 dB (after top-hat filtering), which were improved from 3.4 dB and 4.0 dB obtained using the global SVD approach with and without top-hat filtering, respectively. We envisioned that this approach would provide diverse applications in the diagnosis of cutaneous disorders.


Assuntos
Processamento de Imagem Assistida por Computador , Processamento de Sinais Assistido por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Velocidade do Fluxo Sanguíneo/fisiologia , Imagens de Fantasmas , Ultrassonografia/métodos , Ultrassonografia Doppler/métodos
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 190-193, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086264

RESUMO

Visualization of cutaneous micro-vasculatures is a determined approach in the diagnosis of skin vascular disorders. Clinically, high frequency ultrasound (HFUS) modalities have been used for cutaneous morphological and structural imaging, but visualization of micro-vessels has always been remained a daunting task. These tiny structures might be visualized by devising a highly sensitive Doppler technique for HFUS systems. In this study, we proposed an imaging framework using HFUS (30 MHz) ultrafast Doppler imaging along with SVD clutter filtering that is proficient in detection of micro-scale circulation. The performance of the devised framework was examined on a 200-micron flow phantom made of poly-vinyl alcohol under four different flow rates (56 - 18 ul/min) and visualized the micro-structure with averaged detected diameter of 93 - 170 µm. The results indicated that the devised framework has sufficient sensitivity and resolvability to visualize the micro-vasculatures in dermis layer of skin (depth ≤ 4 mm). Clinical Relevance - This study brings an insight to visualize in-vivo cutaneous micro-vasculatures with ultrafast Doppler imaging in clinical applications for better assessment of cutaneous disorders.


Assuntos
Ultrassonografia Doppler , Imagens de Fantasmas , Ultrassonografia , Ultrassonografia Doppler/métodos
9.
J Med Chem ; 65(6): 4878-4892, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35244402

RESUMO

Autophagy inhibition is an attractive target for cancer therapy. In this study, we discovered inhibitors of Atg4B essential for autophagosome formation and evaluated their potential as therapeutics for prostate cancer. Seventeen compounds were identified as candidates after in silico screening and a thermal shift assay. Among them, compound 17 showed the most potent Atg4B inhibitory activity, inhibited autophagy induced by anti-castration-resistant prostate cancer (CRPC) drugs, and significantly enhanced apoptosis. Although 17 has been known as a phospholipase A2 (PLA2) inhibitor, other PLA2 inhibitors had no effect on Atg4B and autophagy. We then performed structural optimization based on molecular modeling and succeeded in developing 21f (by shortening the alkyl chain of 17), which was a potent competitive inhibitor for Atg4B (Ki = 3.1 µM) with declining PLA2 inhibitory potency. Compound 21f enhanced the anticancer activity of anti-CRPC drugs via autophagy inhibition. These findings suggest that 21f can be used as an adjuvant drug for therapy with anti-CRPC drugs.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Apoptose , Autofagia , Proteínas Relacionadas à Autofagia/química , Proteínas Relacionadas à Autofagia/farmacologia , Linhagem Celular Tumoral , Cisteína Endopeptidases/química , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
10.
Stress Biol ; 2(1): 52, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37676337

RESUMO

Potassium (K) is a major essential element in plant cells, and KUP/HAK/KT-type K+ transporters participate in the absorption of K+ into roots and in the long-distance transport to above-ground parts. In Arabidopsis thaliana, KUP9 is involved in the transport of K+ and Cs+ in roots. In this study, we investigated KUP9 function in relation to the K+ status of the plant. The expression of KUP9 was upregulated in older leaves on K+-depleted medium, compared to the expression of the other 12 KUP genes in the KUP/HAK/KT family in Arabidopsis. When grown on low K+ medium, the kup9 mutant had reduced chlorophyll content in seedlings and chlorosis in older rosette leaves. Tissue-specific expression of KUP9 determined by KUP9 promoter:GUS assay depended on the K+ status of the plants: In K+ sufficient medium, KUP9 was expressed in the leaf blade towards the leaf tip, whereas in K+ depleted medium expression was mainly found in the petioles. In accordance with this, K+ accumulated in the roots of kup9 plants. The short-term 43K+ tracer measurement showed that 43K was transferred at a lower rate in roots and shoots of kup9, compared to the wild type. These data show that KUP9 participates in the distribution of K+ in leaves and K+ absorption in roots under low K+ conditions.

11.
Sci Rep ; 11(1): 12149, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34234174

RESUMO

Pteris vittata is an arsenic (As) hyperaccumulator plant that accumulates a large amount of As into fronds and rhizomes (around 16,000 mg/kg in both after 16 weeks hydroponic cultivation with 30 mg/L arsenate). However, the sequence of long-distance transport of As in this hyperaccumulator plant is unclear. In this study, we used a positron-emitting tracer imaging system (PETIS) for the first time to obtain noninvasive serial images of As behavior in living plants with positron-emitting 74As-labeled tracer. We found that As kept accumulating in rhizomes as in fronds of P. vittata, whereas As was retained in roots of a non-accumulator plant Arabidopsis thaliana. Autoradiograph results of As distribution in P. vittata showed that with low As exposure, As was predominantly accumulated in young fronds and the midrib and rachis of mature fronds. Under high As exposure, As accumulation shifted from young fronds to mature fronds, especially in the margin of pinna, which resulted in necrotic symptoms, turning the marginal color to gray and then brown. Our results indicated that the function of rhizomes in P. vittata was As accumulation and the regulation of As translocation to the mature fronds to protect the young fronds under high As exposure.


Assuntos
Arsênio/metabolismo , Flores/metabolismo , Raízes de Plantas/metabolismo , Pteris/metabolismo , Poluentes do Solo/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Arabidopsis/ultraestrutura , Autorradiografia , Biodegradação Ambiental , Transporte Biológico , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Hidroponia/métodos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/ultraestrutura , Tomografia por Emissão de Pósitrons , Pteris/crescimento & desenvolvimento , Pteris/ultraestrutura
12.
Oncol Lett ; 21(3): 207, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33574946

RESUMO

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application.

13.
J Exerc Sci Fit ; 19(2): 91-97, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33343670

RESUMO

BACKGROUND/OBJECTIVE: To elucidate the effects of walking exercise using a wearable device and functional wear on spinal alignment and jump performance. METHODS: In total, 27 female college soccer players were randomly divided into two groups: trunk solution (TS) and compression garments (CGs). Spinal alignment, jump performance, and electromyography activity during the jump performance of the two groups were measured after a 20-min walking exercise. The values for each group were compared t pre- and post-intervention. RESULTS: The flexibility of the lower thoracic vertebrae in spinal alignment was increased during extension in the TS group. However, the post-value of the abdominal external oblique muscle during a countermovement jump (CMJ) was significantly lower than its pre-value (p < 0.05). In addition, even though spinal alignment was not affected in the CG group, post-values of the jump height during squat jump and CMJ were significantly higher than their pre-values (p < 0.05). Furthermore, the post-value of the biceps femoris during the countermovement jump with arm was significantly lower than its pre-value (p < 0.05). CONCLUSION: Our study suggested that walking exercise using TS may increase the range of motion of the lower thoracic vertebrae in athletes and reduce the muscular activity of the vastus lateralis during CMJ. Additionally, although spinal aliment is not affected, the jump height may increase using CGs.

14.
J Sports Sci ; 38(21): 2423-2429, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32614675

RESUMO

ACE I/D polymorphism has been recently associated with the susceptibility to inflammation and muscle damage after exercise. The aim of this study was to understand the association between the ACE I/D polymorphism and muscle injuries in a large cohort of elite football players from two different countries. Seven hundred and ten male elite football players from Italy (n = 341) and Japan (n = 369) were recruited for the study. Genomic DNA was extracted from either the buccal epithelium or saliva using a standard protocol. Structural-mechanical injuries and functional muscle disorders were recorded from 2009 to 2018. A meta-analysis was performed using Review Manager 5.3.5. In the Japanese cohort, the ACE I/D polymorphism was significantly associated with muscle injury using the D-dominant model (OR: 0.48, 95% CI: 0.24-0.97, P = 0.040). The meta-analysis showed that in the pooled model (Italian and Japanese populations), the frequencies of the DD+ID genotypes were significantly lower in the injured groups than in non-injured groups (OR: 0.61, 95% CI: 0.38-0.98, P = 0.04) with a low degree of heterogeneity (I2  = 0%). Our findings suggest that the ACE I/D polymorphism could influence the susceptibility to developing muscle injuries among football players.


Assuntos
Músculo Esquelético/lesões , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Futebol/lesões , Predisposição Genética para Doença , Genótipo , Humanos , Itália , Japão , Masculino , Adulto Jovem
15.
Med Mol Morphol ; 53(2): 82-85, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31820106

RESUMO

The aim of this study is to reveal the morphological property about the loose bodies (LBs) of temporomandibular joint (TMJ) by scanning electron microscope (SEM). We obtained specimens from two female cases of released loose body by surgical operation. These specimens were fixed by soaking in a mixture of 5% glutaraldehyde or 4% formaldehyde for one week. They were cut into half pieces. These specimens were observed at an accelerating voltage of 3 kV under a SEM (JSM-5500, JEOL, Tokyo). In the electron microscopic findings, it seems to be separated into two different parts as inside part and outside part. On the inside part, collagen fibers were running very densely in the same direction in an orderly neatly manner. Whereas, we observed waved collagen fibers running irregularly with many spaces on the outside part. Outside part seems to be porous pattern compared with inside part. It might be that the surface and outside part included many active fibroblasts. As results, it seems that the LBs might develop in a multi-layer style, in which fibrous tissues were piled up loosely around the inside part. The proliferating activity of LBs grows from the inside to outside of SC in TMJ.


Assuntos
Condromatose Sinovial/patologia , Corpos Livres Articulares/patologia , Articulação Temporomandibular/ultraestrutura , Condromatose Sinovial/etiologia , Condromatose Sinovial/cirurgia , Colágeno/ultraestrutura , Feminino , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Humanos , Corpos Livres Articulares/complicações , Corpos Livres Articulares/cirurgia , Microscopia Eletrônica de Varredura , Articulação Temporomandibular/patologia , Articulação Temporomandibular/cirurgia
16.
ACS Omega ; 4(25): 21251-21259, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31867519

RESUMO

Novel tetracyanidonitridorhenium(V) complexes with five-membered N-heteroaromatic ligands, (PPh4)2[ReN(CN)4L] [L = imidazole (Him) (2), 1-methylimidazole (Mim) (3), and pyrazole (pyz) (4)] and (PPh4)2[ReN(CN)4L]·L [L = Him (5) and Mim (6)], were synthesized by the reactions of (PPh4)2[ReN(CN)4] (1) with Him, Mim, and pyz, and their structures were determined by single-crystal X-ray analysis. The complexes 2, 3, 4, and 6 showed intense photoluminescence, with the emission quantum yields (Φem) being 0.65-0.75 in the solid state at 296 K. In contrast, the Φem and τem values of 5 are significantly smaller and shorter, respectively, than the relevant values of 2. The interconversion reactions among 1, 2, and 5 accompanied by large photoluminescence-intensity changes were accomplished by solvent-free reactions and exposure of water. The mechanochemical reaction of 2 with 1 mol equiv of Him in the solid state gave 5. Complex 5 was also obtained by the mechanochemical reaction of 1 with 2 mol equivalents of Him in the solid state. By placing solid of 5 in water, the solid showed intense photoluminescence to give 2. Complex 1 was produced under vacuum at 185 °C from 2 or 5.

17.
Brain Res ; 1719: 208-216, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31132338

RESUMO

This study was aimed at evaluating the regional changes in the cerebral metabolic rate of oxygen (CMRO2) in relation to the cerebral blood flow (CBF) in the bilateral common carotid artery occlusion (BCAO) rat model. Ligation of the bilateral common carotid arteries (or a sham operation in control animals) was performed in 10-week-old male Wistar rats. O-15 PET images were acquired in the subacute phase (1 week after the surgery) and chronic phase (6 weeks after the surgery) with the animals under anesthesia, using a small-animal PET system and the O-15 gas steady-state inhalation method with arterial blood sampling developed in our previous study. Histopathological staining by Klüver-Barrera method and immunocytochemistry staining by glial fibrillary acidic protein were performed. Cognitive function was tested by using the apparatus of Y-maze. Significantly lower CBF and higher oxygen extraction fraction were observed in broad areas of the cerebrum in the subacute phase in the BCAO rats, with recovery in the chronic phase. A stable decrease of the CMRO2 in the subacute phase of arterial occlusion and later was observed in the BCAO rat model, mainly in the anterior cerebral artery territory. Atrophy and rarefaction of corpus callosum were found in the BCAO in the chronic phase. Activity of astrocytes in the BCAO was prominent in the both phases. Working memory was impaired in the BCAO in the chronic phase. Regional changes in cerebral perfusion and oxygen metabolism in the subacute and chronic phases of arterial occlusion were clarified in a rat model of BCAO by quantitative O-15 PET based on the steady-state method.


Assuntos
Circulação Cerebrovascular/fisiologia , Oxigênio/metabolismo , Animais , Encéfalo/metabolismo , Isquemia Encefálica/patologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/fisiologia , Estenose das Carótidas/metabolismo , Cognição , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
18.
Int Heart J ; 60(3): 715-727, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105143

RESUMO

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.


Assuntos
Oclusão Coronária/patologia , Vasos Coronários/patologia , Microvasos/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Animais , Angiografia Coronária/métodos , Angiografia Coronária/tendências , Oclusão Coronária/complicações , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Microcirculação/fisiologia , Microvasos/ultraestrutura , Modelos Animais , Infarto do Miocárdio/etiologia , Miocárdio/patologia , Suínos
19.
Ann Nucl Med ; 33(6): 394-403, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30820863

RESUMO

OBJECTIVE: L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) and L-3-18F-alpha-methyl tyrosine (18F-FAMT), in relation to the tumor blood flow, using rat xenograft models. METHODS: Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of 18F-FAMT or 18F-FBPA (scan duration = 70 min) following 15O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K1, k2, and total distribution volume (Vt) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vt. Tumor blood flow (TBF) was represented by the K1 value in 15O-water PET. RESULTS: LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vt values of both 18F-FBPA and 18F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vt value of either 18F-FBPA or 18F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. CONCLUSIONS: This study revealed that total distribution volumes of the LAT1-targeting PET tracers 18F-FBPA and 18F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.


Assuntos
Circulação Sanguínea , Transformação Celular Neoplásica , Glioma/patologia , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Animais , Compostos de Boro/metabolismo , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Glioma/irrigação sanguínea , Glioma/diagnóstico por imagem , Glioma/metabolismo , Humanos , Masculino , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/metabolismo , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo , Fenilalanina/farmacocinética , Traçadores Radioativos , Compostos Radiofarmacêuticos/metabolismo , Ratos , Distribuição Tecidual , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/farmacocinética
20.
Appl Radiat Isot ; 139: 251-255, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29870920

RESUMO

We proposed use of astatine-210 in preclinical study. Astatine-210 has higher yield of production and is easier to quantify than astatine-211. We produced astatine-210 with Bi target and 40 MeV alpha beam accelerated by cyclotron, free astatine-210 was separated and injected to normal rats. Three male rats (blocking group) were injected non-radioactive iodide before injection of astatine-210. Compared with the control group, the astatine-210 accumulations in the blocking group decreased to 24% in the thyroid.


Assuntos
Astato/administração & dosagem , Astato/farmacocinética , Iodeto de Sódio/administração & dosagem , Partículas alfa/efeitos adversos , Partículas alfa/uso terapêutico , Animais , Astato/isolamento & purificação , Masculino , Proteção Radiológica , Ratos , Ratos Wistar , Glândula Tireoide/metabolismo , Glândula Tireoide/efeitos da radiação , Distribuição Tecidual
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