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Due to their very poor proliferative capacity, the dysfunction of corneal endothelial cells can sometimes lead to incurable eye diseases that require corneal transplantation. Although many studies have been performed to reconstruct corneal endothelial cells, corneal transplantation is still considered to be the established approach. In this study, we developed bio-engineered Descemet stripping endothelial (DSE) layers, using porcine cornea and induced pluripotent stem cell (iPSC)-derived corneal endothelial cells (iCECs). First, we optimized a protocol to prepare an ultra-thin and decellularized Descemet stripping (DS) scaffold from porcine cornea. Our DS layers show over 90% transparency compared to the control. Porcine-derived cells and xenogenic antigens disappeared, whereas the collagen matrix remained in the graft. Next, corneal endothelial cell lines or iCECs were seeded on the decellularized DS graft and cultured for 7 days. The drying method reduced graft rolling and edema, and increased transparency during culture. The reseeded cells were evenly distributed over the graft, and most of the cells survived. Although future clinical studies are warranted, engineered DSE tissues using xenogenic tissues and stem cells will be useful tools for the treatment of incurable corneal diseases.
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Córnea/citología , Enfermedades de la Córnea/cirugía , Queratoplastia Endotelial de la Lámina Limitante Posterior/métodos , Células Madre/citología , Ingeniería de Tejidos/métodos , Animales , Células Cultivadas , Enfermedades de la Córnea/patología , Modelos Animales de Enfermedad , Endotelio Corneal/citología , Humanos , PorcinosRESUMEN
The present study was conducted to find the cytotoxicity in vitro of nimbolide, limonoids derivative of flowers and leaves from Azadirachta indica (neem tree) on the selected cell lines of cancer (Du-145, PC-3, A-549) and normal fibroblast cell lines (NIH3T3, CCD-18Co) using MTT assay. The cells were seeded in 96 multi-well tissue plate using different concentrations of nimbolide for 24hrs and 48hrs. The percentage of viability of cell lines was calculated by optical density obtained by micro plate reader and cytotoxic effect in term of IC50 value was determined by using linear regression analysis. The percentages of viability of cells treated with different concentrations of nimbolide were significantly lower (P<0.05) than the untreated cancer cell lines while in normal cell lines no significant difference (P>0.05) between treated and the non-treated cells was observed. Nimbolide exerted time and dose dependent cytotoxic effect on the cancer lines and mild effect on the normal cell lines. It was further confirmed through PKH 26. Results of the present study suggested nimbolide as a potent chemotherapeutic and chemopreventive agent as it exerted a more cytotoxic effect on cancer cell lines as compared with the normal cell lines. Nimbolide may be a new hope as an anticancer drug in future.
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Antineoplásicos Fitogénicos/farmacología , Azadirachta/química , Fibroblastos/efectos de los fármacos , Limoninas/farmacología , Células A549 , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Relación Dosis-Respuesta a Droga , Fibroblastos/patología , Humanos , Concentración 50 Inhibidora , Limoninas/aislamiento & purificación , Ratones , Microscopía de Contraste de Fase , Células 3T3 NIH , Células PC-3 , Factores de TiempoRESUMEN
The ultrastructure of porcine putative embryonic stem cells and porcine fetal fibroblasts (PFFs) was analyzed by transmission electron microscopy. The aim of this study was to compare the features of organelles in in vitro fertilization (IVF) derived porcine embryonic stem cells (IVF-pESCs) and somatic cell nuclear transfer (SCNT) derived pESCs (SCNT-pESCs). Also, the features of organelles in high-passage IVF-pESCs were compared with those in low-passage cells. The ultrastructure of PFFs showed rare microvilli on the cell surfaces, polygonal or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, elongated mitochondria, rich lysosomes and rich phagocytic vacuoles. IVF-pESCs showed rare microvilli on the cell surfaces, round or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rich ribosomes, long stacks of rough endoplasmic reticulum, elongated mitochondria, rare lysosomes and rare autophagic vacuoles. By contrast, SCNT-pESCs showed rich microvilli with various lengths and frequencies on the cell surfaces, polygonal nuclei with one reticular shaped nucleoli and heterochromatin, high cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, round mitochondria, rich lysosomes and rich phagocytic vacuoles with clear intercellular junctions. Furthermore, high-passage IVF-pESCs showed irregularly shaped colonies, pyknosis and numerous lysosomes associated with autophagic vacuoles showing signs of apoptosis. In conclusion, this study confirms that the ultrastructural characteristics of pESCs differ depending on their origin. These ultrastructural characteristics might be useful in biomedical research using pESCs, leading to new insights regarding regenerative medicine and tissue repair.
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Células Madre Embrionarias/ultraestructura , Fertilización In Vitro/métodos , Técnicas de Transferencia Nuclear , Animales , Apoptosis , Blastocisto/citología , Línea Celular , Núcleo Celular/ultraestructura , Técnicas de Cocultivo , Citoplasma/ultraestructura , Células Madre Embrionarias/citología , Retículo Endoplásmico Rugoso/ultraestructura , Fibroblastos/ultraestructura , Ratones , Ratones Endogámicos ICR , Microscopía Electrónica de Transmisión , Microvellosidades/ultraestructura , Mitocondrias/ultraestructura , Fagocitosis , PorcinosRESUMEN
Increasing evidence indicates that the secretome of mesenchymal stem cells (MSCs) has therapeutic potential for the treatment of various diseases, including cartilage disorders. However, the paracrine mechanisms underlying cartilage repair by MSCs are poorly understood. Here, we show that human umbilical cord blood-derived MSCs (hUCB-MSCs) promoted differentiation of chondroprogenitor cells by paracrine action. This paracrine effect of hUCB-MSCs on chondroprogenitor cells was increased by treatment with synovial fluid (SF) obtained from osteoarthritis (OA) patients but was decreased by SF of fracture patients, compared to that of an untreated group. To identify paracrine factors underlying the chondrogenic effect of hUCB-MSCs, the secretomes of hUCB-MSCs stimulated by OA SF or fracture SF were analyzed using a biotin label-based antibody array. Among the proteins increased in response to these two kinds of SF, thrombospondin-2 (TSP-2) was specifically increased in only OA SF-treated hUCB-MSCs. In order to determine the role of TSP-2, exogenous TSP-2 was added to a micromass culture of chondroprogenitor cells. We found that TSP-2 had chondrogenic effects on chondroprogenitor cells via PKCα, ERK, p38/MAPK, and Notch signaling pathways. Knockdown of TSP-2 expression on hUCB-MSCs using small interfering RNA abolished the chondrogenic effects of hUCB-MSCs on chondroprogenitor cells. In parallel with in vitro analysis, the cartilage regenerating effect of hUCB-MSCs and TSP-2 was also demonstrated using a rabbit full-thickness osteochondral-defect model. Our findings suggested that hUCB-MSCs can stimulate the differentiation of locally presented endogenous chondroprogenitor cells by TSP-2, which finally leads to cartilage regeneration.
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Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Trombospondinas/metabolismo , Adulto , Anciano , Animales , Cartílago Articular/patología , Cartílago Articular/fisiopatología , Células Cultivadas , Técnicas de Cocultivo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Persona de Mediana Edad , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/patología , Conejos , Regeneración , Medicina Regenerativa , Líquido Sinovial/fisiología , Trombospondinas/fisiología , Trombospondinas/uso terapéuticoRESUMEN
BACKGROUND/AIM: Atlantoaxial subluxation (AAS) is a congenital or traumatic condition that often requires surgical stabilization. Surgery is performed via a ventral or dorsal approach. A ventral approach is challenging in toy breed dogs due to their small-sized bones. Reducing AAS by orthopedic wire via a dorsal approach can cause iatrogenic spinal cord damage. Due to these limitations, a Kishigami atlantoaxial tension band (Kishigami AATB) that remains in the epidural space has been devised. Similar to the Kishigami AATB, the present study developed a modified dorsal wiring method and evaluated it in toy breed dogs with AAS. MATERIALS AND METHODS: Medical data of toy breed dogs with AAS that underwent surgical stabilization using the modified dorsal wiring method from 2017 to 2020 were retrospectively reviewed. RESULTS: A total of 10 dogs were analyzed. Regarding the history of these dogs, six dogs had congenital AAS, and the remaining four dogs had traumatic AAS. Evaluation via computed tomography was available for five dogs, of which two dogs were identified as having incomplete ossification of their atlas. Although four dogs required a revision surgery because of recurrence of clinical signs or fracture of the atlas, final functional improvement was achieved in nine dogs. One dog showed worsened neurological status that led to death. CONCLUSION: Clinical results with the modified dorsal wiring method were similar to those with the Kishigami AATB. The modified dorsal wiring method is versatile as it could be applied to various shapes of dogs' atlas. Considering the shape of the atlas, it is recommended to apply the implant as far from the midline of the dorsal arch as possible to avoid fractures. With selection of suitable patients, this modified dorsal wiring method can be applied to dorsal stabilization of AAS in toy breed dogs.
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Articulación Atlantoaxoidea , Enfermedades de los Perros , Fracturas Óseas , Luxaciones Articulares , Perros , Animales , Estudios Retrospectivos , Articulación Atlantoaxoidea/cirugía , Enfermedades de los Perros/cirugía , Luxaciones Articulares/cirugía , Luxaciones Articulares/veterinaria , Hilos OrtopédicosRESUMEN
BACKGROUND/AIM: Congenital portosystemic shunt (PSS) is a vascular anomaly forming a direct communication between portal and central venous systems, thus bypassing the liver. This condition is related to various clinical symptoms including those manifesting in the central nervous system, gastrointestinal tract, and urinary tract. Treatment of PSS includes medical management and surgery. When evaluating prognosis of dogs with PSS, serum biochemistry profiles including serum bile acid (SBA) and ammonia concentrations are routinely used as screening tests. However, the use of SBA concentration in Maltese is controversial because it can be measured above the reference range even in normal dogs of this breed. In addition, utilizing SBA levels to assess surgical prognosis of PSS is not widely understood in this breed. Thus, the present study evaluated whether SBA could be used as a screening test for PSS in Maltese dogs. MATERIALS AND METHODS: Medical records of dogs in the Veterinary Teaching Hospital from 2018 to 2020 were retrospectively reviewed. RESULTS: A total of 23 dogs with PSS and 30 Maltese dogs without PSS were analyzed. Although preoperative SBA levels were significantly higher in Maltese dogs (192 µmol/l) than in other dog breeds (137 µmol/l) with portocaval shunt, its concentrations were significantly decreased after surgery in both Maltese and other breeds of dogs. No significant difference was observed in postoperative SBA levels between Maltese and other dog breeds. The mean SBA levels for Maltese dogs without PSS (8 µmol/l) were within the reference interval (0-25 IU/l). CONCLUSION: Measuring pre- and post-operative SBA levels to evaluate prognosis of PSS might also be available for Maltese.
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Hospitales Veterinarios , Derivación Portosistémica Intrahepática Transyugular , Perros , Animales , Estudios Retrospectivos , Hospitales de Enseñanza , Ácidos y Sales BiliaresRESUMEN
The purpose of this study was to evaluate disease patterns among military working dogs (MWDs) at the Armed Forces Medical Research Institute (AFMRI) to provide basic medical data on Korean MWDs. The medical records of procedures performed at AFMRI between November 2017 and March 2021 were reviewed. Physical examination, diagnostic imaging, and laboratory tests were performed according to the status of each dog. A total of 353 MWDs (215 males and 138 females; mean age, 6 ± 3 years) were analyzed in this study. Among Korean MWDs, gastrointestinal (GI) disorders are the most frequently diagnosed, followed by dental and musculoskeletal disorders. Foreign body (FB) ingestion had the highest prevalence of GI disorders, with the most common FB being a leather collar or leash. General and dental surgeries, including removal of gastric FB and tooth extraction, were routinely performed at the AFMRI. Preventative care focusing on dental disease and FB ingestion may be helpful for effective performance and good quality of life in MWDs, with the regular assessment and prevention of environmental factors that may contribute to behavioral problems such as FB ingestion, coprophagy, and anorexia.
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BACKGROUND/AIM: Atlantoaxial subluxation (AAS) is generally a congenital condition that mainly affects toy breed dogs. Previous studies in several toy breed dogs revealed that dogs with AAS had a relatively high proportion of incomplete ossification (IO) of the atlas and dens anomalies compared to dogs without AAS. These anatomical characteristics may be important in surgical decision-making. Thus, the present study evaluated morphological differences in the atlas and axis between Maltese dogs with and without AAS. MATERIALS AND METHODS: The medical records of Maltese dogs with and without AAS from 2015 to 2020 were analyzed. Abnormalities of the atlas and axis were evaluated using computed tomography (CT). RESULTS: A total of 45 dogs were reviewed. Maltese dogs with AAS revealed a higher ratio of IO of the atlas (56%) than non-affected dogs (19%). Dens anomalies were identified in 78% of the dogs with AAS and in 26% of non-affected dogs. The shape of the atlas has been identified as thin, solid compact bone in Maltese dogs. Dogs that revealed IO of the dorsal arch of the atlas showed significantly lower CT values (in Hounsfield units) than dogs without IO. The CT values of the midline of the dorsal arch were significantly lower than those of the outer surrounding region. Dens hypoplasia was defined by measuring the dens-to-axis length ratio according to a previous study. A significantly lower ratio was identified in dogs with AAS than in non-affected dogs. CONCLUSION: The incidence ratio of abnormalities of the atlas and axis in Maltese dogs with AAS was similar to that of previous studies. The dorsal arch of the atlas is composed of thin cortical bone with a vulnerable midline region. As dogs with AAS are more likely to be afflicted with abnormalities in the atlas and axis, considering these morphological features is important when planning the surgical stabilization of AAS.
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Articulación Atlantoaxoidea , Enfermedades de los Perros , Luxaciones Articulares , Perros , Animales , Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/cirugía , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Fitomejoramiento , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/veterinaria , Luxaciones Articulares/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To compare the chondrotoxicity of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes in vitro. STUDY DESIGN: Prospective, experimental study. STUDY MATERIAL: Equine articular chondrocytes. METHODS: Primary cultured equine chondrocytes were exposed to 0.5% bupivacaine, 2% lidocaine, or 2% mepivacaine for 30 or 60 minutes. After treatment, cell viability was evaluated by trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay in a dose dependent manner. Apoptosis and necrosis of chondrocytes were analyzed with the double staining of Hoechst 33258 and propidium iodide using fluorescence microscopy, and the results were confirmed using flow cytometry. RESULTS: After 30-minute exposure, trypan blue exclusion assay revealed that cell viability of 0.5% bupivacaine group was 28.73±8.44%, and those of 2% lidocaine and 2% mepivacaine were 66.85±6.03% and 86.27±2.00%, respectively. The viability of chondrocytes after saline treatment was 95.95±2.75%. The results of MTT assay and fluorescence microscopy had similar tendency with trypan blue assay. Each result showed that bupivacaine was the most toxic of the three local anaesthetics. Mepivacaine was less toxic than lidocaine. The results of the viability test suggest that bupivacaine and lidocaine exhibit a marked chondrotoxicity, and that this is mainly due to necrosis rather than apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE: Bupivacaine may induce detrimental chondrotoxicity when administered intra-articularly, especially in patients with joint disease, and we suggest that it should be used cautiously in equine practice. Mepivacaine may be an alternative to both bupivacaine and lidocaine.
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Anestésicos Locales/farmacología , Bupivacaína/farmacología , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Lidocaína/farmacología , Mepivacaína/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citometría de Flujo/veterinaria , Caballos , Microscopía Fluorescente/veterinariaRESUMEN
Basosquamous carcinoma (BSCC) is a rare malignancy, primarily composed of basal cells with foci of squamous differentiation. It is considered to be histologically an intermediate type between basal cell carcinoma and squamous cell carcinoma, and is known to have aggressive behaviors. BSCC occurred in a 17-year-old female minipin with a history of surgical excision for a mammary tumor. The right upper hindlimb was severely enlarged to 8 x 5 cm. Cross-section showed a homogenous white to yellow-white mass compressing the surrounding muscular tissues. The tumor metastasized also to the lungs, heart, abdominal cavity, liver and salivary gland. Microscopically, basaloid cells were crowded into solid nests or lobules separated by well-developed fibrous tissues with occasional keratinizations. Since there was no skin lesions, the tumor is assumed to be originated from the formerly present tumor in mammary gland. To our literature review, this case is the first BSCC with systemic metastasis in a dog.
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Carcinoma Basoescamoso/veterinaria , Enfermedades de los Perros/diagnóstico , Neoplasias Mamarias Animales/patología , Neoplasias de los Tejidos Blandos/veterinaria , Animales , Carcinoma Basoescamoso/patología , Carcinoma Basoescamoso/secundario , Enfermedades de los Perros/patología , Perros , Femenino , Neoplasias de los Tejidos Blandos/secundarioRESUMEN
BACKGROUND: Portosystemic shunt and atrial septal defect (ASD) are generally congenital diseases in dogs. Rarely, dogs with congenital vascular anomalies could be related to other vascular anomalies. CASE DESCRIPTION: A 1-year-old male Maltese dog, neutered and weighing 1.7 kg, was brought in for an additional assessment of a congenital portosystemic shunt (CPSS). CPSS was diagnosed as portocaval shunt by computed tomography. Surgical attenuation was performed. Although prognosis after CPSS attenuation was good, the dog was presented with exercise intolerance 1 year after the operation. Thoracic radiographs observed generalized cardiomegaly. Echocardiography revealed pulmonary hypertension and right-to-left shunting ASD. CONCLUSION: The present study reports a rare case of CPSS concurrent with ASD in a dog. As dogs with CPSS might have been associated with other vascular anomalies; therefore, echocardiography is recommended for early diagnosis of other cardiovascular anomalies.
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Enfermedades de los Perros , Defectos del Tabique Interatrial , Hipertensión Pulmonar , Derivación Portosistémica Intrahepática Transyugular , Animales , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Perros , Ecocardiografía/veterinaria , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/veterinaria , Hipertensión Pulmonar/veterinaria , Masculino , Derivación Portosistémica Intrahepática Transyugular/veterinariaRESUMEN
A 5-month-old male Maltese with right-sided circling, deafness, and blindness was presented. A diagnosis of communicating hydrocephalus was made. A ventriculoperitoneal shunt was implanted and the cerebrospinal fluid was drained by using an adjustable valve type (Medtronic Strata). The valve was set at 2.5 (135-155 mmH2O). This was done to prevent the possibility of an overdrainage-induced collapse of the brain parenchyma, which can occur rarely when canine hydrocephalus is treated by using a low-pressure valve. Computed tomography performed 6 weeks and 1 year after surgery revealed the ventricles had decreased in size. Thus, a high-pressure valve used during the treatment of hydrocephalus was able to maintain normal intracranial pressure.
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Enfermedades de los Perros/cirugía , Hidrocefalia/veterinaria , Derivación Ventriculoperitoneal/veterinaria , Animales , Ceguera/etiología , Ceguera/veterinaria , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ventrículos Cerebrales/patología , Sordera/etiología , Sordera/veterinaria , Perros , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/patología , Hidrocefalia/cirugía , Presión Intracraneal , Imagen por Resonancia Magnética , Masculino , Paresia/etiología , Paresia/veterinaria , Prótesis e Implantes , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Derivación Ventriculoperitoneal/métodosRESUMEN
CASE SUMMARY: Osteogenesis imperfecta (OI) is an inherited disorder related to the synthesis of type 1 collagen. Clinical signs of pain from the fracture of fragile bones are common. A 3-month-old male Chinchilla cat was presented for lameness and pain from a right femoral fracture. After surgical repair using intramedullary pins, and since repeated fractures occurred and there is little information about genes causing OI in cats, various examinations were performed to discriminate other diseases that could cause the pathological fracture. Primary hyperparathyroidism and nutritional or renal secondary hyperparathyroidism were ruled out through blood tests and ultrasonography. Quantitative CT confirmed low trabecular bone mineral density compared with normal cats. Radiography and histopathological examination revealed thin cortical bone. OI was tentatively diagnosed and long-term follow-up of the surgical repair was reviewed. Fractures were treated using intramedullary Kirschner wires. The same method of intramedullary pinning was then applied preventively to protect several other long bones by improving stress distribution and bending resistance. Follow-up was performed for 3 years until the patient's death due to undetermined reasons. RELEVANCE AND NOVEL INFORMATION: Although the patient underwent repeated fractures and bone unions, and needed medication for pain management sometimes, it was generally able to live as a companion cat. Therefore, palliative preventive intramedullary pinning could be used for long-term management of patients suspected of OI.
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The purposes of this study were to determine the optimal dose and delay time for lymphography by injection of Iohexol into popliteal lymph nodes and to assess images of computed tomography by the established protocol. Three different doses (30, 60 and 90 mgI/kg) of water-soluble iodinated contrast medium were injected into 15 popliteal lymph nodes of 10 adult beagles, and fluoroscopy was performed. Filling and duration of contrast media and the number of visible ducts from popliteal lymph nodes to the thoracic duct and its branches were recorded. CT lymphography was performed, and the number of visible thoracic ducts was compared with that found by radiographic lymphography. Radiographs obtained between 130 and 800 seconds after injection of contrast medium provided a detailed view of the thoracic duct. The dose of 60 mgI/kg was determined to enable quality diagnostic imaging without extranodal leakage in radiographic lymphography. There was no significant difference in the number of thoracic ducts between the two modalities at each anatomic location. However, CT lymphography provided images of the thoracic duct with better spatial resolution and without superimposition of surrounding tissue. The present study provides an adequate delay time and injection for identification of the canine thoracic duct, and therefore, this technique could be applied to diagnosis of disease associated with chest lymphatic drainage.
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Perros/anatomía & histología , Yohexol/administración & dosificación , Yohexol/farmacología , Ganglios Linfáticos/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria , Animales , Medios de Contraste/administración & dosificación , Medios de Contraste/farmacología , Relación Dosis-Respuesta a DrogaRESUMEN
The present study was designed to investigate the in-vitro morphological assessment of apoptotic effect caused by nimbolide on the selected cancer cell lines (DU-145, PC-3, A-549) and normal cell lines (NIH3T3, CCD-18Co). The cells were grown in 6 well tissue culture plates after treatment with different concentrations of nimbolide and untreated control cells. Apoptotic and necrotic cells were measured using Hoechst 33342 and propidium iodide dual staining through a fluorescent microscope and also by staining with annexin V and propidium iodide through flow cytometric analysis. The activity of caspase 3, 8, and 9 was measured by caspases colorimetric assay kits. The number of apoptotic and necrotic cells were significantly higher in all selected cancer cell lines treated with nimbolide as compared with untreated control cells, whereas in normal cell lines no significant difference was observed between nimbolide treated and untreated cells. The activity of caspase 3, 8, and 9 was also significantly higher in all cancer cell lines treated with nimbolide as compared with untreated control cells while it did not change significantly in normal cell lines as compared with untreated control. The results of the present study suggested that nimbolide induced apoptosis only in cancer cells without affecting the normal cells and one of the apoptosis inducing mechanism is through the activation of caspases signaling pathways. Therefore, nimbolide may be a novel promising candidate as an anticancer drug in future.
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Nimbolide, an active chemical constituent of Azadirachta indica, reportedly has several physiological effects. Here, we assessed novel anticancer effects of nimbolide against bladder cancer EJ and 5637 cells. Nimbolide treatment inhibited the proliferation of both bladder cancer cell lines with an IC50 value of 3 µM. Treatment of cells with nimbolide induced G2/M phase cell cycle arrest via both Chk2-Cdc25C-Cdc2/cyclin B1-Wee1 pathway and Chk2-p21WAF1-Cdc2/cyclin B1-Wee1 pathway. Nimbolide increased JNK phosphorylation and decreased p38MAPK and AKT phosphorylation. Additionally, nimbolide impeded both wound healing migration and invasion abilities by suppressing matrix metalloproteinase-9 (MMP-9) activity. Finally, nimbolide repressed the binding activity of NF-κB, Sp-1, and AP-1 motifs, which are key transcription factors for MMP-9 activity regulation. Overall, our study indicates that nimbolide is a potential chemotherapeutic agent for bladder cancer.
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The role of hypertriglyceridemia (HTG) secondary to endocrine diseases in the occurrence of pancreatitis in dogs has not been fully investigated. The objective of the present study was to evaluate HTG as a mediator between endocrine diseases and pancreatitis in dogs. The study design was a retrospective case-control study. Medical records of dogs newly diagnosed with acutely presenting pancreatitis between 2012 and 2014 were reviewed for the presence or absence of hyperadrenocorticism (HAC), diabetes mellitus (DM), and hypothyroidism. A matched case-control analysis was performed, and the association between endocrine diseases and pancreatitis was evaluated using multiple logistic regression analysis. In dogs with pancreatitis, the odds of HAC (P < .001) and DM (P < .001) were 4.5 and 12.4 times that of dogs without pancreatitis, respectively. HTG significantly mediated the association between DM and pancreatitis but not between HAC and pancreatitis. Additional studies will be necessary to confirm these findings and to further elucidate the associations between endocrine diseases and pancreatitis.
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Hiperfunción de las Glándulas Suprarrenales/veterinaria , Diabetes Mellitus/veterinaria , Enfermedades de los Perros/etiología , Hipertrigliceridemia/veterinaria , Hipotiroidismo/veterinaria , Pancreatitis/veterinaria , Hiperfunción de las Glándulas Suprarrenales/complicaciones , Animales , Estudios de Casos y Controles , Diabetes Mellitus/etiología , Perros , Femenino , Hipertrigliceridemia/complicaciones , Hipotiroidismo/complicaciones , Masculino , Pancreatitis/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this investigation was to evaluate the regenerative response to deproteinized porous bovine bone mineral (BM) when used alone or in combination with a bioresorbable porcine-derived bilayer collagen membrane (CM) for alveolar ridge augmentation in dogs. MATERIALS AND METHODS: The mandibular premolars were extracted unilaterally and three ridge defects were induced in six mongrel dogs. Each defect site was randomly assigned to one of the following treatment groups: BM alone (group A), BM in combination with CM (group B), or neither membrane nor bone graft, which served as a control (group C). No adverse events occurred during the experimental period. Dental computed tomography (CT) scans were taken after postoperative periods of 8 and 16 weeks. RESULTS: The percentage of CT-derived bone density in groups A and B was significantly different from that of group C (p < 0.01) at 8 and 16 weeks. The percentage of CT-derived bone density of the dogs in Group B was significantly higher than that of those in group A at 8 and 16 weeks (p < 0.01). Gross evaluation of the 3-dimensional CT reconstruction image of the canine mandibles after 16 weeks of implantation showed that group B had the greatest amount of bone augmentation and excellent thickness of the buccal aspect of the alveolar ridge. CONCLUSION: These results suggest that BM leads to more successful bone regeneration for guided bone regeneration procedures, especially in conjunction with the use of a CM as a barrier in order to promote the regeneration of canine alveolar ridge defects.
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Pérdida de Hueso Alveolar/cirugía , Aumento de la Cresta Alveolar/métodos , Diente Premolar/cirugía , Sustitutos de Huesos/uso terapéutico , Colágeno/uso terapéutico , Implantes Absorbibles , Animales , Densidad Ósea/fisiología , Regeneración Ósea/fisiología , Sustitutos de Huesos/farmacología , Bovinos , Colágeno/farmacología , Perros , Estudios de Seguimiento , Regeneración Tisular Guiada Periodontal/métodos , Masculino , Membranas Artificiales , Estadística como Asunto , Porcinos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
A variety of dental implant systems are now available that optimize bone-to-implant contact. The present study was performed to compare the outcomes, by measuring peri-implant osseointegration, following immediate and delayed insertion of square-threaded and resorbable-blasted-media (RBM)-treated surface implants in the dog's mandible. Three dogs were used and four implants were inserted in each dog. All implants were used for histological and histomorphometrical evaluations. The contact lengths and osseointegrated areas following immediate implantation were 74.99% and 56.08%, and those following delayed implantation were 78.22% and 66.08%, respectively. The implantation method in dogs using the square-threaded and RBM treated surface implant system achieved higher percentages of osseointegration than previously reported and the two implantation techniques did not differentially influence osseointegration. Thus, immediate implantation of this implant system, which minimizes the number of surgical procedures, is an optimal clinical method to replace extracted teeth in dogs.
Asunto(s)
Implantes Dentales , Oseointegración , Animales , Implantes Dentales/efectos adversos , Perros , Encía/patología , Masculino , MandíbulaRESUMEN
The objective of this study was to evaluate the bone uptake of the bone-seeking radionuclide (99m)technetium-methylene diphosphonate ((99m)Tc-MDP) in order to examine and compare the clinical efficacies of tibial plateau leveling osteotomy (TPLO) and cranial tibial wedge osteotomy (CTWO) for the correction of experimentally induced cranial cruciate ligament (CrCL) transected stifle. Fifteen healthy adult beagle dogs, weighing between 10 and 15 kg, were used for this study. Dogs were assigned to TPLO (n=5), CTWO (n=5) or a control sham group (n =5) and screened with both physical and complete orthopedic examinations. Left CrCLs were transected and two of the three groups were stabilized using TPLO and CTWO. Scintigraphic evaluation of the stifle was performed before TPLO or CTWO surgical repair of the left limb and again at 4, 8 and 12 weeks after surgery. Bone uptake values at 8 and 12 weeks for the TPLO and CTWO groups were not significantly different from their preoperative values, but these differed significantly from the control group at 4, 8 and 12 weeks (p<0.01). No significant differences were found between TPLO and CTWO values. In summary, the relative efficacy of CTWO approximately equals that of TPLO. Moreover, the results of this study confirmed that TPLO and CTWO inhibited the progression of osteoarthritis in CrCL-deficient dogs.