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1.
Int J Obes (Lond) ; 41(3): 390-401, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27916986

RESUMO

Bakground/Objectives:Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug. SUBJECTS/METHODS: Small molecules modulating SR protein activity and splicing were tested for their abilities to interact with SRSF1 and to modulate LMNA (AS). Using an LMNA luciferase reporter we selected molecules that were tested in diet-induced obese (DIO) mice. Transcriptomic analyses were performed in the white adipose tissues from untreated and treated DIO mice and mice fed a chow diet. RESULTS: We identified a small molecule that specifically interacted with the RS domain of SRSF1. ABX300 abolished DIO in mice, leading to restoration of adipose tissue homeostasis. In contrast, ABX300 had no effect on mice fed a standard chow diet. A global transcriptomic analysis revealed similar profiles of white adipose tissue from DIO mice treated with ABX300 and from untreated mice fed a chow diet. Mice treated with ABX300 exhibited an increase in O2 consumption and a switch in fuel preference toward lipids. CONCLUSIONS: Targeting SRSF1 with ABX300 compensates for changes in RNA biogenesis induced by fat accumulation and consequently represents a novel unexplored approach for the treatment of obesity.


Assuntos
Processamento Alternativo/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Obesidade/patologia , Animais , Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Imunofluorescência , Lamina Tipo A/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Fatores de Processamento de Serina-Arginina/metabolismo
2.
Vet Pathol ; 54(4): 605-610, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28129095

RESUMO

Flat-Coated Retriever dogs are predisposed to the development of histiocytic sarcoma (HS), a poorly differentiated, highly malignant neoplasm. The authors have previously documented a significant lymphocytic infiltrate in such tumors. The objective of this study was to examine the presence and expression of regulatory T cells in HS tumor samples. Forty tumors were included in this study. All tumors were immunolabeled for CD3, CD79a, CD25, CD45RA, and FOXP3. The proportion of positive cells was compared between tumors presenting as a localized primary soft tissue mass (soft tissue origin HS) and disseminated HS affecting viscera, especially the spleen (splenic origin HS). By immunohistochemistry, 95% of infiltrating T cells were positive for Foxp3 in all sections, suggesting the presence of regulatory T cells. The proportion of cells positive for FOXP3 was higher in the tumors arising in soft tissues, whereas the proportion of CD45RA-positive cells was higher in the splenic origin HS. Canine HS has an aggressive clinical behavior and is uniformly fatal. The difference in the proportion of tumor-infiltrating lymphocytes positive for these 2 markers in the 2 locations may represent differences in tumor microenvironment between the 2 sites.


Assuntos
Doenças do Cão/patologia , Sarcoma Histiocítico/veterinária , Linfócitos T Reguladores/patologia , Animais , Complexo CD3/imunologia , Antígenos CD79/imunologia , Doenças do Cão/imunologia , Cães , Feminino , Fatores de Transcrição Forkhead/imunologia , Sarcoma Histiocítico/imunologia , Sarcoma Histiocítico/patologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Antígenos Comuns de Leucócito/imunologia , Masculino , Microambiente Tumoral/imunologia
3.
Vet Pathol ; 50(6): 1063-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23628694

RESUMO

Tumor hypoxia has been associated with increased malignancy, likelihood of metastasis, and increased resistance to radiotherapy and chemotherapy in human medicine. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that is induced by tumor hypoxia and regulates the pathways involved in cellular response and adaptation to the hostile tumor microenvironment. HIF-1 induces transcription of different proteins, including Ca-IX and Glut-1, which are considered endogenous markers of chronic hypoxia in solid tumors in humans. In this study, sections from 40 canine sarcomas (20 histiocytic sarcomas and 20 low-grade soft-tissue sarcomas) were immunostained for these markers. Expression of Glut-1 was scored based on percentage of positive staining cells (0 = <1%; 1 = 1%-50%; 2 = >50%) and intensity of cellular staining (1 = weak; 2 = strong); Ca-IX was scored based on percentage of positive cells (0 = <1%; 1 = 1%-30%; 2 = >30%). Intratumoral microvessel density was measured using CD31 to assess intratumoral neoangiogenesis. Histiocytic sarcomas showed statistically significant higher Glut-1 immunoreactivity and angiogenesis than did low-grade soft-tissue sarcomas. Intratumoral microvessel density in histiocytic sarcomas was positively associated with Glut-1 immunoreactivity score. These findings suggest a potential role of hypoxia in the biology of these tumors and may provide a base for investigation of the potential prognostic use of these markers in naturally occurring canine tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Doenças do Cão/metabolismo , Proteínas de Neoplasias/metabolismo , Sarcoma/veterinária , Animais , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Transportador de Glucose Tipo 1/metabolismo , Glicoproteínas/metabolismo , Hipóxia/veterinária , Imuno-Histoquímica/veterinária , Microvasos , Neovascularização Patológica/veterinária , Prognóstico , Estudos Retrospectivos , Sarcoma/metabolismo , Sarcoma/patologia , Sarcoma/cirurgia , Resultado do Tratamento
4.
Front Public Health ; 11: 1304572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249406

RESUMO

Objectives: This study investigates the association between cohort derived dementia and serologically confirmed SARS-CoV-2 infection, an underexplored phenomena in low-and middle-income countries. Examining this relationship in a rural South African community setting offers insights applicable to broader healthcare contexts. Methods: Data were collected from Black South Africans in the Mpumalanga province who participated in the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa. Cohort derived dementia was developed using a predictive model for consensus-based dementia diagnosis. Multinomial logistic regression models estimated the association between predicted dementia probability in 2018 and SARS-CoV-2 infection risk in 2021, controlling for demographics, socioeconomic status, and comorbidities. Results: Fifty-two percent of the tested participants had serologically confirmed SARS-CoV-2 infections. In the fully adjusted model, cohort derived dementia was significantly associated with over twice the risk of serological diagnosis of COVID-19 (RRR = 2.12, p = 0.045). Conclusion: Complying with COVID-19 prevention recommendations may be difficult for individuals with impaired cognitive functioning due to their symptoms. Results can inform community-based public health initiatives to reduce COVID-19 transmission among South Africa's rapidly aging population.


Assuntos
COVID-19 , Demência , Adulto , Humanos , Idoso , África do Sul/epidemiologia , Estudos Longitudinais , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Demência/diagnóstico , Demência/epidemiologia , Teste para COVID-19
5.
J Small Anim Pract ; 64(9): 590-594, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36990106

RESUMO

Canine transmissible venereal tumour (CTVT) is a contagious cancer spread by transfer of living cancer cells. Occasional cases are observed in the UK in dogs imported from endemic regions. Here, we report a case of imported canine transmissible venereal tumour that was transmitted to a second dog within the UK. Transmission of genital canine transmissible venereal tumour occurred despite neutered status of the second dog. The aggressive course of disease in both cases, which included metastasis, resistance to therapeutic interventions and ultimate euthanasia of both dogs, is described. The diagnosis of canine transmissible venereal tumour was made using a combination of cytology, histology, immunohistochemistry and PCR to detect the LINE-MYC rearrangement. Practitioners unfamiliar with canine transmissible venereal tumour are reminded of this disease of concern, particularly when imported dogs are placed in multi-dog households, irrespective of neuter status.


Assuntos
Doenças do Cão , Tumores Venéreos Veterinários , Cães , Animais , Tumores Venéreos Veterinários/diagnóstico , Tumores Venéreos Veterinários/tratamento farmacológico , Tumores Venéreos Veterinários/patologia , Doenças do Cão/diagnóstico , Reação em Cadeia da Polimerase/veterinária , Imuno-Histoquímica , Reino Unido
6.
Biol Lett ; 7(3): 364-7, 2011 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-21247939

RESUMO

In many species, females display brightly coloured and elaborate traits similar to those that males use in intra- and inter-sexual selection processes. These female characters are sometimes related to fitness, and might function as secondary sexual characteristics that have evolved through sexual selection. Here, we used descriptive data from 674 females in 10 populations and an experimental removal of Trichostrongylus tenuis parasites in four populations, to examine the effects of season, age, condition, and parasites on the size of supra-orbital combs displayed by female red grouse Lagopus lagopus scoticus. We found that comb size (i) was greater during the breeding than the non-breeding season, (ii) was greater in adult than in young females, (iii) was positively correlated with body condition, and (iv) negatively correlated with parasite abundance. Experimentally, we showed that comb size increased proportionally to the number of worms removed after parasite dosing. Our findings provide a better understanding of proximate mechanisms behind the expression of a male-like trait in females, and we discuss its possible function as a female ornament.


Assuntos
Crista e Barbelas/fisiologia , Galliformes/fisiologia , Interações Hospedeiro-Parasita , Estações do Ano , Trichostrongylus/fisiologia , Envelhecimento , Animais , Feminino , Galliformes/parasitologia , Masculino
7.
Vet Pathol ; 48(3): 764-71, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20930108

RESUMO

The Flat Coated Retriever is a breed at risk of development of histiocytic sarcoma (HS), but in contrast to the disseminated form of disease recognized in the Bernese Mountain Dog, most reports of HS in Flat Coated Retrievers describe a localized lesion affecting the musculature or fascia of limbs. The purpose of this study was to review data and material received though an ongoing Flat Coated Retriever tumor survey to better define the presentation of HS in the breed and to determine the utility of subclassification of tumors arising at different sites by histology and immunohistologic phenotyping. Data on 180 dogs bearing HS-like tumors were available for review, which showed that although the majority (101 lesions, 57%) were primary limb lesions, 47 dogs (26%) had visceral, mainly splenic lesions with no peripheral primary tumor. A detailed histologic and immunohistologic review of 20 limb tumors and 20 splenic tumors showed that 2 distinct phenotypic subtypes could be identified: a histiocytic subtype, most prevalent in the splenic tumors, and a histiocytic-spindle-pleomorphic subtype, mainly seen in the limb tumors. Despite their variable morphology, all tumors expressed major histocompatibility complex class II and the leukocyte antigen CD18, but only those tumors in the spleen consistently expressed CD11d. The majority of tumors also contained a mild to moderate infiltrate of T lymphocytes.


Assuntos
Doenças do Cão/patologia , Sarcoma Histiocítico/veterinária , Imuno-Histoquímica/veterinária , Animais , Cães , Feminino , Sarcoma Histiocítico/classificação , Sarcoma Histiocítico/patologia , Masculino , Estudos Retrospectivos
8.
Infect Immun ; 78(1): 326-36, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19884329

RESUMO

In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Inflamação/induzido quimicamente , Salmonelose Animal/prevenção & controle , Vacinas contra Salmonella/imunologia , Salmonella typhimurium/metabolismo , Animais , Proteínas de Bactérias/genética , Injeções Intravenosas , Lipopolissacarídeos , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Mutação , Salmonelose Animal/patologia , Vacinas contra Salmonella/administração & dosagem , Vacinas contra Salmonella/efeitos adversos , Salmonella typhimurium/genética , Salmonella typhimurium/imunologia , Baço/patologia , Fatores de Tempo , Receptor 4 Toll-Like/genética , Virulência
10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32467000

RESUMO

OBJECTIVE: To assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. MATERIAL AND METHODS: We included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT Choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2-2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. RESULTS: The location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p<0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). CONCLUSIONS: PET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients.


Assuntos
Adenocarcinoma/secundário , Neoplasias Ósseas/secundário , Colina/análogos & derivados , Radioisótopos de Flúor , Calicreínas/sangue , Neoplasias Pulmonares/secundário , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Gerenciamento Clínico , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Sensibilidade e Especificidade
11.
J Small Anim Pract ; 61(3): 202-205, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29761888

RESUMO

Pyogranulomatous inflammation has been extensively described in cats, in particular in cases of feline infectious peritonitis and also associated with Mycobacteria, Actinomyces, Nocardia, Rhodococcus and fungal infections. Idiopathic sterile pyogranulomatous dermatitis has also been described. In this case series we describe the clinical presentation, histopathology and outcome of three cases of feline idiopathic sterile steroid-responsive pyogranuloma with different presentation and different locations of the lesion, but with the common feature of having a mass with no superficial skin involvement.


Assuntos
Peritonite Infecciosa Felina , Animais , Doenças do Gato , Gatos , Granuloma/veterinária
12.
J Comp Pathol ; 177: 18-33, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32505237

RESUMO

Chronic pancreatitis (CP) is a common disease in the English cocker spaniel (ECS) and is characterized histologically by duct destruction, interlobular fibrosis and dense periductular and perivenous lymphocytic aggregates. These features are also found in human autoimmune pancreatitis type 1, part of a glucocorticoid-responsive, multiorgan syndrome, newly recognized as IgG4-related disease (IgG4-RD). Human IgG4-RD affects one or several organs, often showing a predominance of IgG4+ plasma cells histologically, with an IgG4+:total IgG+ plasma cell ratio of >40%. This study investigated whether ECSs with CP and/or inflammatory disease in several organs show an increase in IgG4+ plasma cells within affected tissues. Histological sections of pancreas, liver, kidney, salivary gland and conjunctiva were obtained from ECSs with idiopathic chronic inflammatory disease affecting those tissues. Tissue samples from age-matched dogs of other breeds with similar diseases were also sampled. Control diseased tissue samples, from dogs without a suspected immune-mediated disease, were included. A subset of ECSs and dogs of other breeds presented with disease in more than one organ. Immunohistochemistry was performed with primary reagents detecting total IgG and three of the four canine IgG subclasses (IgG2, IgG3 and IgG4). Normal sections of pancreas and liver showed an absence of labelled plasma cells of any subclass. Normal kidney and salivary gland sections showed the presence of a few labelled plasma cells (<10 plasma cells/high-power field). Fourteen tissue sections from 12 ECSs and seven sections from six dogs of other breeds showed elevated numbers of IgG4+ plasma cells and IgG4+:IgG+ ratios >40%. Individual dogs (ECSs and other breeds) showed marked increases in IgG4+ cells. There were no significant differences in the number of IgG4+ plasma cells between ECSs and dogs of other breeds for affected pancreas, liver, salivary glands and conjunctiva. Kidney sections had more IgG4+ cells, for both ECSs and dogs of other breeds, than did sections from other organs. Dogs of other breeds had significantly more IgG4+ plasma cells in affected kidneys than ECSs. In conclusion, several ECSs and dogs of other breeds fulfilled the histological criteria for the diagnosis of IgG4-RD, supporting the existence of a multiorgan immune-mediated disease in ECSs and some dogs of other breeds.


Assuntos
Doenças do Cão , Doença Relacionada a Imunoglobulina G4/veterinária , Animais , Túnica Conjuntiva/citologia , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/patologia , Cães , Humanos , Imunoglobulina G/metabolismo , Doença Relacionada a Imunoglobulina G4/patologia , Imuno-Histoquímica/veterinária , Inflamação , Rim/citologia , Rim/imunologia , Rim/patologia , Fígado/citologia , Fígado/imunologia , Fígado/patologia , Pâncreas/citologia , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite Crônica/imunologia , Pancreatite Crônica/patologia , Pancreatite Crônica/veterinária , Plasmócitos/metabolismo , Glândulas Salivares/citologia , Glândulas Salivares/imunologia , Glândulas Salivares/patologia
13.
Clin Transl Oncol ; 21(3): 355-362, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30128953

RESUMO

PURPOSE: Adjuvant radiotherapy (ART) for biochemical relapse (BR) after radical prostatectomy (RP) showed increased disease-free survival (DFS) in three previous randomized trials. Retrospective phase II trials evaluated if early salvage RT (ESRT) is equivalent to ART. Our study aims to compare ART and ESRT to salvage RT. MATERIALS AND METHODS: We compared RP plus ART and ESRT versus SRT. Indication for RT was made by PSA determination after RP: ART when PSA ≤ 0.2 ng/ml, ESRT when PSA ≤ 0.3 after PSA rise from 0.0 to SRT PSA ≥ 0.3. The cause of death of each patients was analyzed, DFS, cause-specific survival (CSS) overall survival (OS) and metastasis-free survival (MFS) in relation to RT intention. RESULTS: Between 1993 and 2008, 204 patients with a median age of 65 years (44-75) were treated. The median follow-up was 160 months (28.1-273.3). At diagnosis, 89.7% had localized clinical stages and 90.2% had Gleason (G) ≤ 7. The median PSA was 10 (range 4-101). The postoperative G was ≥ 7 in 66.2%; 56.4% had ≥ 2 positive margins; 29.4% received ART, 20% ESRT and 59.3% SRT. The DFS for ART, ESRT and SRT was 74, 56 and 39% with significant differences between the three groups (p < 0.001). ART + ESRT were combined versus SRT; for the DFS, the significant differences (p < 0.001) remained 67% versus 39%. Positive margins, pT3 and pre-RT PSA were significant factors on multivariate analysis. The CSS in the ART + ESRT group was 92 vs. 78% in the SRT group (p < 0.05). OS was 69% in ART + ESRT vs. 57% in SRT (p < 0.05). MFS was 82.7% in ART + ESRT vs. 67.4% in SRT. CONCLUSIONS: In this study the ART + ESRT presented benefits versus SRT in DFS, CSS, OS and MFS.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/mortalidade , Estudos Retrospectivos , Terapia de Salvação/mortalidade
14.
Res Vet Sci ; 84(2): 257-68, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17597173

RESUMO

Epizootic outbreaks of diarrhoeas have emerged and disseminated in different rabbit farms in Mexico causing great economical losses, during the past years. Seven, 5-weeks-old New Zealand White (NZW) rabbits chosen at random from 35 ill animals that were remitted for postmortem, histopathology, and ultrastructural examinations were studied. Bacteriological and parasitological studies were carried out in three additional ill rabbits of same age. In a field trail 45, 5-weeks-old apparently healthy NZW rabbits were observed daily for sanitary status for a 5-week period. Some of the rabbits did not response to the preventive drug treatment and were therefore, used to study the development of the disease. Clinical signs, gross lesions, and mortality throughout the fattening period were recorded. Eight, 8-weeks-old NZW rabbits who survived an outbreak were assessed for gamma-globulins in serum of the total protein fraction during a 3-week period. Gamma-globulins were also measured in eight free-disease healthy rabbits of same breed and age. Lesions of the small intestine consisted of mucoid enteropathy, lymphocytic plasmocytic enteritis with atrophy and fusion of villi, and hyperplasia of globet cells. Serosal edema was present. Ultrastructural examinations of jejunum and ileum from 3/7 diseased rabbits, revealed enterocytes in apoptosis, mixed with degenerative and/or necrotic changes together with infiltration of lymphocytes, macrophages, neutrophils, and loss of microvillus. There were electron dense structures suggestive of virus particles inside the nuclei and cytoplasm of some enterocytes. There was lymphoid spleen atrophy and proliferation of reticuloendothelial cells in 7/7 rabbits. Interstitial pneumonia in 4/7 rabbits was found. Encephalitozoon cuniculi was detected in the brain of 1/7 rabbits. Escherichia coli were detected in 3/3 cases and Eimeria spp. in 2/3 cases. Mortality rate in the field study was 51.1% and the spread of the disease occur in 9/9 cages. The proportion of gamma-globulins in rabbits who survive an outbreak was much lower (P=0.0001) than free-disease healthy rabbits (8.1+/-1.0 and 14.0+/-1.0, respectively). The disease was multifactorial and consisted of sub-acute mucoid enteropathy probably induced by viral infection and aggravated by the proliferation of opportunistic pathogens common to rabbits. This may explain the severe degenerative and necrotic changes observed in the small intestine of diarrhoeic rabbits.


Assuntos
Diarreia/veterinária , Surtos de Doenças/veterinária , Coelhos/imunologia , Coelhos/virologia , Animais , Diarreia/epidemiologia , Diarreia/imunologia , Diarreia/patologia , Mucosa Intestinal/patologia , México/epidemiologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/patologia , Infecções Oportunistas/veterinária , Viroses/complicações , Viroses/imunologia , Viroses/patologia , Viroses/veterinária
15.
Clin Transl Oncol ; 10(5): 281-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18490245

RESUMO

OBJECTIVE: To assess the effectiveness of a single dose of radio therapy (8 Gy vs. 6 Gy) plus zoledronic acid in cancer patients with bone metastases in treating pain; quality of life, time to onset of skeletal events and functional status. MATERIAL AND METHODS: A total of 139 patients from 22 Spanish hospitals were randomly assigned to: Group A, administered a single dose of 8 Gy+zoledronic acid (4 mg iv, in 15-min infusions), and Group B, administered a single dose of 6 Gy+zoledronic acid (4 mg iv, in 15-min infusions). The main variable was pain, which was assessed with the Visual Analogue Pain Scale (VAS) in supine, seated and standing positions. RESULTS: There was a total of 118 patients for intention to treat (n=67 in Group A and n=51 in Group B). The most frequent primary neoplasms were the lung (29.66%), prostate (22.03%) and breast (21.19%). Sixty patients were analysed per protocol, n=34 in group A and n=26 in group B. Improvements were observed in the VAS scores for pain in all three positions. The mean time to onset of the event was greater (p=0.0211) in Group A than in Group B (122 vs. 81.62 days). Functional status improved in Group A, and quality of life improved in both groups. CONCLUSION: The two groups achieved similar levels of pain control in supine, seated and standing positions. Quality of life also improved in both groups. However, the higher dose (8 Gy dose) in combination with zoledronic acid is associated with a longer period without skeletal events.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Manejo da Dor , Radioterapia , Idoso , Neoplasias Ósseas/complicações , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Qualidade de Vida , Ácido Zoledrônico
16.
Mol Cell Biol ; 19(12): 7913-24, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10567517

RESUMO

In earlier research, we identified a 43-kDa c-ErbAalpha1 protein (p43) in the mitochondrial matrix of rat liver. In the present work, binding experiments indicate that p43 displays an affinity for triiodothyronine (T3) similar to that of the T3 nuclear receptor. Using in organello import experiments, we found that p43 is targeted to the organelle by an unusual process similar to that previously reported for MTF1, a yeast mitochondrial transcription factor. DNA-binding experiments demonstrated that p43 specifically binds to four mitochondrial DNA sequences with a high similarity to nuclear T3 response elements (mt-T3REs). Using in organello transcription experiments, we observed that p43 increases the levels of both precursor and mature mitochondrial transcripts and the ratio of mRNA to rRNA in a T3-dependent manner. These events lead to stimulation of mitochondrial protein synthesis. In transient-transfection assays with reporter genes driven by the mitochondrial D loop or two mt-T3REs located in the D loop, p43 stimulated reporter gene activity only in the presence of T3. All these effects were abolished by deletion of the DNA-binding domain of p43. Finally, p43 overexpression in QM7 cells increased the levels of mitochondrial mRNAs, thus indicating that the in organello influence of p43 was physiologically relevant. These data reveal a novel hormonal pathway functioning within the mitochondrion, involving a truncated form of a nuclear receptor acting as a potent mitochondrial T3-dependent transcription factor.


Assuntos
Mitocôndrias Hepáticas/metabolismo , RNA/biossíntese , Receptores dos Hormônios Tireóideos/fisiologia , Fatores de Transcrição/fisiologia , Animais , Sítios de Ligação , Linhagem Celular , Chlorocebus aethiops , Camundongos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiologia , RNA Mitocondrial , Ratos , Receptores Citoplasmáticos e Nucleares , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Transfecção , Tri-Iodotironina/metabolismo
17.
Clin Transl Oncol ; 9(3): 172-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17403628

RESUMO

Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Pequenas/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Medula Espinal/secundário , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/radioterapia , Vértebras Cervicais , Intervalo Livre de Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Paraplegia/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/radioterapia , Vértebras Torácicas , Resultado do Tratamento
18.
Clin Transl Oncol ; 19(3): 373-378, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27770397

RESUMO

PURPOSE: We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT). MATERIALS AND METHODS: Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA ≥4 ng/ml (BF) and/or metastases. RESULTS: Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40-68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups. CONCLUSIONS: No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Braquiterapia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Idoso , Terapia Combinada , Seguimentos , Humanos , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Fatores de Tempo
19.
J Comp Pathol ; 156(1): 14-20, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27889201

RESUMO

Fibroblast activating protein (FAP) is a membrane serine protease expressed by activated fibroblasts, particularly tumour associated fibroblasts (TAFs). FAP expression has not been reported in canine mast cell tumours (MCTs). The objective of this study was to evaluate the expression of FAP in TAFs and its correlation with histological grade, mitotic index and Ki67 expression in canine MCTs. FAP expression was evaluated by immunohistochemistry (IHC) in 30 canine MCTs. Twenty-eight (90%) of the MCTs expressed FAP in the stroma, 16 cases showed low to intermediate FAP score and 14 cases had a high FAP score. FAP was correlated positively with both Patnaik (P = 0.007) and Kiupel (P = 0.008) grading systems, mitotic index (P = 0.0008) and Ki67 expression (P = 0.009). High stromal FAP expression could be a potential negative prognostic factor in canine MCTs.


Assuntos
Doenças do Cão/patologia , Fibroblastos/patologia , Gelatinases/biossíntese , Sarcoma de Mastócitos/veterinária , Mastocitoma/veterinária , Proteínas de Membrana/biossíntese , Serina Endopeptidases/biossíntese , Animais , Doenças do Cão/metabolismo , Cães , Endopeptidases , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Índice Mitótico , Gradação de Tumores
20.
Rev. enferm. neurol ; 21(3): 220-225, sep.-dic. 2022. ilus, tab, graf
Artigo em Espanhol | LILACS, BDENF | ID: biblio-1428382

RESUMO

Introducción. La pandemia por COVID-19 ha evidenciado la importancia de la metodología epidemiológica, por lo que es significativo fortalecer su aprendizaje en todos los niveles formativos del área de ciencias de la salud. Objetivo. Aplicar metodología epidemiológica de carácter descriptivo y analítico para el estudio de una base de datos de casos COVID-19 en la República Mexicana. Material y métodos. Se realizó una búsqueda de bases de datos en sitios web oficiales sobre los casos de COVID-19, y se recuperó un archivo en formato Excel con la información de 65,536 casos al día 10 de abril del 2021 a las 01:14hrs. Posteriormente, se realizó análisis estadístico de las diferentes variables mediante el programa SPSS, versión 21 en español, consistente en cálculo de prevalencias, razón de productos cruzados (RPC) y medidas de asociación, en lo cual participaron alumnos del cuarto semestre de enfermería. Resultados. La prevalencia para el género masculino fue de 53 %, y para el femenino de 47 %, con una media aritmética de edad de 35 años. La Chi cuadrada entre género y resultado de laboratorio positivo fue de 6527.9, con un 99 % de probabilidad de que haya asociación entre las variables. Asimismo, para la relación hipertensión y resultado de laboratorio positivo la Chi cuadrada fue de 51.97. La RPC para diabetes y resultado de laboratorio positivo fue de 1.4. Conclusiones. La aplicación de indicadores epidemiológicos básicos representa una herramienta importante para el fenómeno epidemiológico COVID-19, pues establece una caracterización de la epidemia en nuestro país.


Introduction: The COVID-19 pandemic has evidenced the importance of epidemiological methodology, so it is significant to strengthen its learning at all educational levels in the area of health sciences. Objetive. Apply descriptive and analytical epidemiological methodology for the study of a database of COVID-19 cases in the Mexican Republic. Material and methods: A search of databases on official websites on COVID-19 cases was carried out, and an Excel format file was recovered with the information of 65,536 cases as of April 10, 2021 at 01:14 a.m. Subsequently, a statistical analysis of the different variables was carried out using the SPSS program, version 21 in Spanish, consisting of calculation of prevalence, ratio of cross products (RPC) and measures of association, in which fourth semester nursing students participated. Results: The prevalence for the male gender was 53%, and for the female 47%, with an arithmetic mean age of 35 years. The Chi square between gender and positive laboratory result was 6527.9, with a 99% probability of an association between the variables. Likewise, for the relationship between hypertension and a positive laboratory result, the Chi square was 51.97. The RPC for diabetes and positive laboratory result was 1.4. Conclusions: The application of basic epidemiological indicators represents an important tool for the epidemiological phenomenon COVID-19, since it establishes a characterization of the epidemic in our country.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Indicadores de Morbimortalidade , Base de Dados , COVID-19
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