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1.
J Vet Med Sci ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32074518

RESUMO

A 9-year-old neutered male Wire Fox Terrier presented with an 1-month history of hindlimb paresis. Magnetic resonance imaging revealed a contrast-enhanced mass at the level of the L2 vertebral canal. The dog became paraplegic with no deep perception of the hindlimbs, and the mass was surgically removed. The histopathological diagnosis was of a malignant peripheral nerve sheath tumor (MPNST). The dog suffered a relapse of right hindlimb ataxia at 225 days after the surgery. The dog died 434 days after the surgery. Necropsy found a large mass in the abdominal cavity invading from the L2-nerve. This is the first report of MPNST invading the abdominal cavity through the nerve root.

2.
Bioorg Med Chem Lett ; 30(9): 126933, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32044185

RESUMO

In this paper, we present the phospholipidosis-inducing potential (PLIP) of forty fragment-sized diamines derived from N-benzyl-4-(methylamino)piperidine and discuss the relationship between their PLIP and the physicochemical properties. Our results demonstrate that the previously reported methods are not suitable for predicting the PLIP of fragment-sized diamines; the second basic pKa can distinguish PLIP-positive diamines from PLIP-negative diamines more accurately than ClogP or most basic pKa. To the best of our knowledge, this is the first report describing the relationship between PLIP and second basic pKa.

3.
Vet Comp Oncol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32072720

RESUMO

MicroRNA-214 (miR-214), a pivotal tumour-suppressive miRNA, is downregulated in canine hemangiosarcoma (HSA) cells. Although these tumour-suppressive miRNAs are potential therapeutic agents, their clinical efficacy may be limited because of their vulnerability to RNase-rich microenvironments and low in vivo transfection rates. We developed synthetic miR-214s with enhanced cytotoxicity, RNase resistance and quantity of miR-214 in/on cells. These synthetic miR-214s were synthesized by various chemical modifications (such as 4'-aminoethyl-2'-fluoro, 2'-fluoro, 2'-O-methyl, phosphorothioate and oligospermine modifications) of the wild-type mature miR-214 sequences. Transfection of HSA cells with synthetic miR-214 (miR-214 5AE) demonstrated significant growth suppressive effect and induced the strongest apoptotic response. Synthetic miR-214s (miR-214 5AE, miR-214 10AE and miR-214 OS) were much more stable than mature miR-214s in foetal bovine serum. Similar to mature miR-214, 5AE and OS suppressed the expression level of COP1 in HSA cells. The quantity of synthetic miR-214s in/on cells was higher than that of mature miR-214. In conclusion, we developed a clinically applicable, synthetic miR-214 5AE that regulates the COP1 protein expression similar to that mediated by mature miR-214. Additionally, miR-214 5AE confers better cytotoxicity, nuclease resistance and transfection rate than mature miR-214. Thus, miR-214 5AE could potentially be a novel miRNA-based chemotherapeutic agent that could improve the prognosis of HSA. Its in vivo effects on canine HSA need to be examined in future.

4.
Exp Cell Res ; 388(1): 111810, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891684

RESUMO

Canine hemangiosarcoma (HSA) is a commonly occurring aggressive tumor stemming from the vascular endothelial cells and is considered to be a good model for a similar disease in humans, called angiosarcoma. In this study, we reviewed drug libraries to identify new signal transduction inhibitors that can suppress the cell growth of canine HSA in vitro. We observed that tenovin-6, a sirtuin (SIRT) inhibitor, inhibited cell proliferation and induced cell death in three canine HSA cell lines (JuB4, Re12, and Ud6). These effects were induced through G1 cell cycle arrest and caspase-3 activation. Although tenovin-6 is known as an inhibitor of SIRT1 and SIRT2, knockout (KO) of genes encoding SIRT1 and/or SIRT2 had no apparent impact on cell proliferation in canine HSA. In addition, tenovin-6 showed cell growth inhibition in SIRT KO cells, as well as parental cells. These results indicated the cytotoxicity of tenovin-6 was a SIRT-independent event. Instead, we found that tenovin-6 inhibited autophagy flux in canine HSA cells, as evidenced by the suppression of lysosomal proteolysis. These results suggested that tenovin-6 induces cell growth suppression in canine HSA cells by impairing the lysosomal function. Therefore, tenovin-6 could be used in a new therapeutic strategy to treat canine HSA.

5.
Anticancer Drugs ; 31(2): 177-182, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31725045

RESUMO

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB-IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II-IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

6.
World J Surg Oncol ; 17(1): 229, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878937

RESUMO

BACKGROUND: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response. CASE PRESENTATION: A 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence. CONCLUSIONS: HAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.

7.
J Vet Med Sci ; 81(12): 1791-1803, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31597817

RESUMO

We evaluated the cytotoxic effect of isoleucine-zipper tumor necrosis factor-related apoptosis inducing ligand (izTRAIL) against cell lines, B101592, Cha, and C090115, derived from canine mammary gland tumors. These cells were derived from three dogs diagnosed with mammary adenoma or carcinoma. All three cells were positive for vimentin, while B101592 and C090115 were positive for cytokeratin (CK) AE1/AE3 and CK CAM5.2. Treatment with izTRAIL decreased the viability of the three cell lines. The proportion of annexin V+/propidium iodide- cells increased in all three cell lines after treatment with izTRAIL. Additionally, cell cycle analysis revealed that izTRAIL treatment increased the number of cells in sub-G1 phase. Moreover, izTRAIL treatment activated caspase-8 and caspase-3 and enhanced the levels of cleaved poly (ADP-ribose) polymerase. The cytotoxic effect of izTRAIL was mitigated upon co-treatment with caspase-8 or caspase-3 inhibitor. These results indicated that izTRAIL induces apoptosis in cell lines derived from canine mammary tumor, which was also previously reported in canine hemangiosarcoma cell lines. This suggested that canine tumor cells have conserved TRAIL receptors. This study will provide the basis for further studies on TRAIL receptors and TRAIL-related molecules.

8.
Am J Physiol Gastrointest Liver Physiol ; 317(4): G545-G555, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31460791

RESUMO

We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles of the noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the defecation reflex. Colorectal motility was measured with a balloon in anesthetized rats. Electrical stimulation of the LC and A11 region increased colorectal pressure only when a GABAA receptor antagonist was injected into the lumbosacral spinal cord. The effects of the LC stimulation and A11 region stimulation on colorectal motility were inhibited by antagonists of α1-adrenoceptors and D2-like dopamine receptors injected into the lumbosacral spinal cord, respectively. Spinal injection of a norepinephrine-dopamine reuptake inhibitor augmented the colokinetic effect of LC stimulation. The effect of stimulation of each nucleus was abolished by surgical severing of the parasympathetic pelvic nerves. Our findings demonstrate that activation of descending noradrenergic neurons from the LC and descending dopaminergic neurons from the A11 region causes enhancement of colorectal motility via the lumbosacral defecation center. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.NEW & NOTEWORTHY The present study demonstrates that electrical and chemical stimulations of the locus coeruleus or A11 region augment contractions of the colorectum. The effects of locus coeruleus and A11 stimulations on colorectal motility are due to activation of α1-adrenoceptors and D2-like dopamine receptors in the lumbosacral defecation center, respectively. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.

9.
Bioorg Med Chem Lett ; 29(16): 2332-2337, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31255484

RESUMO

To avoid production of a phospholipidosis-inducing metabolite, we replaced the amide structure of SUN13837 (1) with a 1,2,3-triazole. The resulting 1,2,3-triazole analog of 1 (compound 2) displayed greater neuroprotective activity than 1. Structural modification of 2 yielded compound 10, which showed improved neuroprotective activity and negligible mechanism-based inactivation against CYP3A4. In addition, installation of a methyl group at the 5-position of 1,2,3-triazole of 10 significantly boosted the neuroprotective activity. These 1,2,3-triazole derivatives displayed reduced phospholipidosis risk, sufficient systemic exposure, and high central nervous system penetration, and therefore may be potentially useful agents for the treatment of neurodegenerative diseases.

10.
BMC Vet Res ; 15(1): 192, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182094

RESUMO

BACKGROUND: Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Most DM-affected PWCs are homozygous for the mutant superoxide dismutase 1 (SOD1) allele; however, the genetic examination for the SOD1 mutation does not exclusively detect symptomatic dogs. In order to identify novel biomarkers, the plasma microRNA (miRNA) profiles of PWCs with DM were investigated. RESULTS: Quantification of the plasma levels of 277 miRNAs by an RT-qPCR array identified 11 up-regulated miRNAs and 7 down-regulated miRNAs in DM-affected PWCs from those in wild-type SOD1 PWCs. A pathway analysis identified 3 miRNAs: miR-26b, miR-181a, and miR-196a, which potentially regulate several genes associated with SOD1. In order to validate the diagnostic accuracy of the candidate miRNAs in the aged PWC population, candidate miRNAs in plasma were measured by RT-qPCR and a receiver operating characteristic (ROC) curve analysis was performed. miR-26b had the largest area under the ROC curve for distinguishing DM PWCs from healthy PWCs (sensitivity, 66.7%; specificity, 87.0%). The plasma level of miR-26b was significantly higher in the DM group than in the healthy control group. A positive correlation was observed between increases in the plasma level of miR-26b and disease progression. CONCLUSIONS: These results suggest that plasma miR-26b is a potential novel diagnostic biomarker of DM.


Assuntos
Doenças do Cão/genética , MicroRNAs/sangue , Doenças Neurodegenerativas/veterinária , Animais , Biomarcadores/sangue , Progressão da Doença , Doenças do Cão/diagnóstico , Cães , Feminino , Masculino , Mutação , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Superóxido Dismutase-1/genética
11.
PLoS One ; 14(6): e0217105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166966

RESUMO

Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.


Assuntos
Carcinoma de Células Grandes/genética , Carcinoma Neuroendócrino/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Proteômica , Carcinoma de Pequenas Células do Pulmão/genética , Idoso , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia
12.
Forensic Sci Med Pathol ; 15(3): 399-403, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250258

RESUMO

Rapid identification of pathogenic agents is important in response to the emergence of biocrime and bioterrorism, to facilitate appropriate confinement and treatment. As the rapid determination system of viral genome sequences (RDV method) using exhaustive gene amplification is useful for rapid identification, we examined whether this method could be applied to forensic samples. To detect pathogenic virus in a cat with suspected viral infections, fluid swab samples were applied to the RDV method. The following steps were performed: viral propagation, extraction of the viral genome, amplification of the first library, fragmentation of the library, amplification of the second library using non-specific primer sets, and direct sequencing of the amplicon. To confirm the viruses detected by this method, we performed conventional PCR using virus-specific primers. We detected pathogenic virus genome sequences from the swab samples and confirmed infection with these viruses. In addition, we directly detected a viral genome sequence from the nasal swab sample without the viral propagation step. The RDV method is infrequently used in forensic analysis. This method is practicable with equipment existing in a normal laboratory and is useful for rapid detection and identification of pathogenic viruses in forensic samples. This method would also be applicable to the detection of bacteria and fungi.


Assuntos
Genoma Viral/genética , Cavidade Nasal/virologia , Faringe/virologia , Animais , Caliciviridae/genética , Gatos , DNA Viral , Herpesviridae/genética , Reação em Cadeia da Polimerase , RNA Viral , Manejo de Espécimes
13.
Toxicol Appl Pharmacol ; 377: 114610, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195007

RESUMO

An endocrine-disrupting chemical Bisphenol A (BPA) binds specifically to a nuclear receptor (NR) named ERRγ. Although the importance of receptor-binding evaluation for human NRs is often stressed, the binding characteristics of so-called next-generation (NextGen) bisphenol compounds are still poorly understood. The ultimate objective of this investigation was to evaluate BPA and its NextGen analogs for their abilities to bind to 21 human NRs, the greatest members of NRs for which tritium-labeled specific ligands were available. After establishing the detailed assay conditions for each NR, the receptor binding affinities of total 11 bisphenols were evaluated in competitive binding assays. The results clearly revealed that BPA and the NextGen bisphenols of BPAF, BPAP, BPB, BPC, BPE, and BPZ were highly potent against one or more of NRs such as CAR, ERα, ERß, ERRγ, and GR, with IC50 values of 3.3-73 nM. These bisphenols were suggested strongly to be disruptive to these NRs. BPM and BPP also appeared to be disruptive, but less potently. BPF exhibited only weak effects and only against estrogen-related NRs. Surprisingly, most doubtful bisphenol BPS was supposed not to be disruptive. The NRs to which BPA and NextGen bisphenols did not bind were RARα, RARß, RARγ, and VDR. PPARγ, RORα, RORß, RORγ, RXRα, RXRß, and RXRγ, exhibited very weak interaction with these bisphenols. The ten remaining NRs, namely, ERRγ, ERß, ERα, CAR, GR, PXR, PR, AR, LXRß, and LXRα, showed distinctly strong binding to some bisphenols in this order, being likely to have consequential endocrine-disruption effects.

14.
Proc Natl Acad Sci U S A ; 116(21): 10412-10417, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31036645

RESUMO

Sex is determined by diverse mechanisms and master sex-determination genes are highly divergent, even among closely related species. Therefore, it is possible that homologs of master sex-determination genes might have alternative functions in different species. Herein, we focused on Sex-lethal (Sxl), which is the master sex-determination gene in Drosophila melanogaster and is necessary for female germline development. It has been widely shown that the sex-determination function of Sxl in Drosophilidae species is not conserved in other insects of different orders. We investigated the function of Sxl in the lepidopteran insect Bombyx mori In lepidopteran insects (moths and butterflies), spermatogenesis results in two different types of sperm: nucleated fertile eupyrene sperm and anucleate nonfertile parasperm, also known as apyrene sperm. Genetic analyses using Sxl mutants revealed that the gene is indispensable for proper morphogenesis of apyrene sperm. Similarly, our analyses using Sxl mutants clearly demonstrate that apyrene sperm are necessary for eupyrene sperm migration from the bursa copulatrix to the spermatheca. Therefore, apyrene sperm is necessary for successful fertilization of eupyrene sperm in B. mori Although Sxl is essential for oogenesis in D. melanogaster, it also plays important roles in spermatogenesis in B. mori Therefore, the ancestral function of Sxl might be related to germline development.

15.
Vet Radiol Ultrasound ; 60(4): 456-464, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099095

RESUMO

Although lung lobectomy is the most common treatment option for dogs with solitary lung tumors, surgery often cannot be performed at the time of diagnosis. In this retrospective, case series study, we described the effects of hypofractionated radiotherapy for tumor mass reduction in nine dogs with solitary lung adenocarcinoma that were later considered for surgical resection, and we assessed the tolerability of the radiation protocol. Tumors were deemed unresectable by the attending veterinarian. The dose prescription was 7.0-12.0 Gy/fraction in four to seven fractions, administered weekly for a total dose of 40-50 Gy. Treatment planning prioritized normal tissue dose constraints. The median interval between the last radiotherapy session and maximum tumor size reduction was 56 (range: 26-196) days, with six and three dogs exhibiting a partial response and stable disease, respectively. Although acute and late radiation-induced toxicity to the skin and/or lungs developed in all nine dogs, it was self-limiting or improved with short-term anti-inflammatory treatment. Tumor progression after initial size reduction was confirmed in three dogs at 62, 126, and 175 days, respectively, after the last radiotherapy session. Seven of the nine dogs underwent lobectomy a median of 68 days after radiotherapy when tumors were in partial response or stable disease or at the time of progression, and five received systemic chemotherapy concurrent with or after radiotherapy. These findings suggest that hypofractionated radiotherapy for canine solitary lung adenocarcinoma is useful when the tumor is large or when surgery cannot be performed immediately after diagnosis.


Assuntos
Adenocarcinoma de Pulmão/veterinária , Doenças do Cão/radioterapia , Neoplasias Pulmonares/veterinária , Hipofracionamento da Dose de Radiação , Radioterapia/veterinária , Adenocarcinoma de Pulmão/radioterapia , Animais , Cães , Feminino , Neoplasias Pulmonares/radioterapia , Masculino , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/veterinária , Radioterapia/métodos , Estudos Retrospectivos
16.
Vet Comp Oncol ; 17(3): 385-393, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31012230

RESUMO

This retrospective study aimed to evaluate factors associated with survival and to compare characteristics between tumour localizations in dogs with urinary transitional cell carcinoma (TCC) that underwent whole-body computed tomography (CT) at diagnosis. Dogs with histologically confirmed TCC that received medical therapy between 2010 and 2017 were included; dogs that underwent surgery or radiotherapy for the primary tumour were excluded. According to the CT findings, primary tumour localization (classified into the Bladder, Urethra and Bladder and Urethra groups), prostate involvement, iliosacral lymphadenomegaly, sternal lymphadenomegaly and metastasis to the bone and lung were evaluated for survival analysis. CT at diagnosis revealed iliosacral lymphadenomegaly, sternal lymphadenomegaly, bone metastasis and lung metastasis in 47.7%, 18.5%, 24.6% and 35.4% of the 65 included dogs, respectively. The overall median survival time was 196 days. On multivariable analysis, TCC localization (hazard ratio [HR], 1.90; P = .037), bone metastasis (HR, 2.76; P = .013) and sternal lymphadenomegaly (HR, 3.56; P = .004) were significantly associated with survival. Compared to the Bladder group (n = 16), the Urethra group (n = 26) had higher metastasis rates to the bone (6.3% vs 42.3%; P = .045) and lung (6.3% vs 46.2%; P = .022). The survival time was shorter in the Urethra group than in the Bladder group (121.5 vs 420 days; P < .001), and it was similar only in female dogs (247 vs 420 days; P = .031). These findings suggest that whole-body CT could be valuable for predicting the prognosis in urinary TCC.


Assuntos
Carcinoma de Células de Transição/veterinária , Doenças do Cão/patologia , Tomografia Computadorizada por Raios X/veterinária , Neoplasias Urológicas/veterinária , Imagem Corporal Total/veterinária , Animais , Carcinoma de Células de Transição/patologia , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Urológicas/diagnóstico por imagem , Neoplasias Urológicas/patologia
17.
Vet Comp Oncol ; 17(3): 285-297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30767429

RESUMO

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an apoptosis-inducing cytokine that shows potential therapeutic value for human neoplasms, and is effective in some canine tumours; however, its potential for killing canine hemangiosarcoma (HSA) cells is unknown. Thus, we evaluated the proapoptotic effect of TRAIL in nine canine HSA cell lines. Cells (JuA1, JuB2, JuB2-1, JuB4, Re11, Re12, Re21, Ud2 and Ud6) were cultured with three recombinant human TRAILs (rhTRAILs): TRAIL-TEC derived from Escherichia coli, TRAIL-TL derived from mammalian cells and isoleucine zipper recombinant human TRAIL (izTRAIL) containing an isoleucine-zippered structure that facilitates trimerization. TRAIL-TEC did not decrease the cell viability in any of the cell lines tested, whereas the other two rhTRAILs effectively decreased the viability of all cell lines as assessed by the WST-1 assay. In canine HSA cells, izTRAIL induced apoptosis more effectively than TRAIL-TL. In JuB4, Re12, and Ud6 cells, izTRAIL increased the activation of caspase-3 and caspase-8 and caused poly (ADP-ribose) polymerase degradation. Moreover, izTRAIL treatment increased the proportion of Annexin V+/ Propidium iodide (PI)- apoptotic cells and nuclear fragmentation in izTRAIL-sensitive cells. These results show that rhTRAIL can induce apoptosis in canine HSA cells, but the sensitivity of TRAIL was different depending on the cell lines. Therefore, TRAIL could be an effective therapeutic agent against canine HSA, but the specific mechanism of resistance should be determined to clarify under what conditions this treatment would be most effective.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Doenças do Cão , Hemangiossarcoma , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Cães , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/genética
18.
J Occup Health ; 61(1): 36-53, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30698334

RESUMO

OBJECTIVE: A systematic review was performed to study factors of occurrence and improvement methods of presenteeism attributed to diabetes. METHODS: We set 2 clinical questions; (a) how comorbidities and complications of diabetes induce presenteeism and (b) what interventions or conditions effectively improve presenteeism. Then, we conducted a comprehensive search with MEDLINE/PubMed and Scopus databases and extracted those that met the clinical questions. RESULTS: Eighteen papers studied occurrence of presenteeism by comorbidities and complications of diabetes. Most studies were cross-sectional and had a low quality of evidence. However, the associations of hypoglycemia, diabetic neuropathy, and mood disorders with presenteeism were relatively well studied. The papers that discussed effective interventions or conditions for improving presenteeism were very limited. CONCLUSIONS: Our review suggests that presenteeism attributed to diabetes is mainly caused by hypoglycemia, diabetic neuropathy, and mood disorders. There are very limited evidences, but available information suggests that improving glycemic control, adjusting treatment regimen by evaluating the impact on work, providing psychological support, and developing suitable work accommodations may effectively reduce presenteeism.


Assuntos
Complicações do Diabetes , Promoção da Saúde/métodos , Saúde do Trabalhador , Presenteísmo/métodos , Absenteísmo , Comorbidade , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/psicologia , Diabetes Mellitus , Eficiência , Humanos , Cultura Organizacional
19.
J Vet Med Sci ; 81(3): 365-368, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30674745

RESUMO

A 4-year-old male Toy Poodle was presented with a history of status epilepticus. On presentation, neurological examination revealed a delay in postural reactions in the right pelvic limb. Magnetic resonance imaging showed a fluid-containing cystic lesion that compressed the mesencephalon, hippocampus, and amygdala. The cyst was surgically removed via left rostrotentorial craniotomy. The final diagnosis was an intracranial ectopic choroid plexus cyst. The patient has remained free of seizures for 18 months after surgery. This is the first case report of an intracranial ectopic choroid plexus cyst that was surgically removed in a dog.


Assuntos
Encefalopatias/veterinária , Plexo Corióideo , Cistos/veterinária , Doenças do Cão/patologia , Animais , Encefalopatias/patologia , Plexo Corióideo/patologia , Cistos/patologia , Cães , Imagem por Ressonância Magnética/veterinária , Masculino
20.
Knee Surg Sports Traumatol Arthrosc ; 27(2): 491-497, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30196436

RESUMO

PURPOSE: The purpose of this study was to evaluate the signal/noise quotient (SNQ) for graft maturation and the serial changes observed in the magnetic resonance imaging (MRI) findings after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction using a hamstring tendon autograft at a minimum of 5 years after surgery. METHODS: Forty-five patients who underwent DB ACL reconstruction between 2007 and 2010 were included in this prospective study. All participants underwent postoperative MRI at 3 weeks and 3, 6, 9 and 12, 18, 24, 36, 48 and 50 months. The signal intensity (SI) characteristics of the reconstructed graft were evaluated on oblique axial proton density-weighted MR imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was calculated to quantitatively determine the normalized SI. The SNQ of the AMB and PLB was evaluated separately. RESULTS: The mean SNQ of the AM bundle (AMB) continued to increase until 6 months after surgery (5.2 ± 1.2), and then gradually decreased and became well stabilized by 18 months (3.3 ± 0.5), after which it remained unchanged. On the other hand, the mean SNQ of the PL bundle (PLB) continued to increase until 9 months after surgery (6.2 ± 1.1), and then decreased incrementally and became well stabilized by 24 months (4.1 ± 0.5). The SI of PLB was significantly higher than that of AMB between 3 and 24 months (p = 0.04, 0.03, 0.01, 0.04, 0.02 and 0.03, respectively). CONCLUSIONS: These results indicate that at least 18 months is needed after ACL reconstruction to sufficiently restore the SI of the AMB, while at least 24 months are needed to for the PLB. The SI of the PLB was significantly higher than that of the AMB at 3-24 months after surgery, indicating that the PLB showed inferior graft maturity to the AMB until 24 months after surgery. For clinical relevance, the correct understanding of serial changes in graft maturation may potentially be used in decision-making regarding a return to sports. LEVEL OF EVIDENCE: Prospective case series, Level IV.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/reabilitação , Tendões dos Músculos Isquiotibiais/transplante , Articulação do Joelho/diagnóstico por imagem , Transplantes/diagnóstico por imagem , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Autoenxertos , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Imagem por Ressonância Magnética , Masculino , Período Pós-Operatório , Estudos Prospectivos , Transplante Autólogo , Transplantes/fisiopatologia , Adulto Jovem
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