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1.
Aust Vet J ; 102(7): 331-338, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38351862

RESUMO

Phalaris aquatica is pasture species introduced into Australia during early European settlement. Consumption of the plant can cause the neurological condition chronic phalaris toxicity (CPT) in sheep and cattle. In recent years, there has been an increase in reports of CPT in macropods, which has raised concerns regarding its impacts on their welfare. Currently, little is known about the distribution or seasonal patterns of this disease in wildlife, information pivotal in assessing its potential risks. Between 2021 and 2022, we conducted a survey targeting government bodies, veterinary businesses and wildlife organisations to investigate the locations and time of occurrence of CPT in macropods in the state of Victoria, Australia. We received 13 survey responses, 12 verbal reports, a full record of investigated cases from a university veterinary school and cases from a wildlife rescue organisation. Over the period of 11 years, Victoria had 918 cases of CPT recorded in macropods from 36 local government areas, with cases concentrated centrally just north of the state capital of Melbourne and July (midwinter) being the month with the highest case count (n = 220). There was a significant positive correlation between case count and both the abundance of kangaroos (Macropus giganteus and Macropus fuliginosus) (P < 0.01) and the abundance of P. aquatica (P = 0.009), and a significant negative correlation between annual case count and average rainfall of March (P = 0.016) and April (P = 0.02). Understanding these relationships will assist land and wildlife managers in predicting the risk and magnitude of disease outbreaks of CPT each in Victoria.


Assuntos
Macropodidae , Estações do Ano , Animais , Vitória/epidemiologia , Animais Selvagens , Intoxicação por Plantas/veterinária , Intoxicação por Plantas/epidemiologia , Inquéritos e Questionários
3.
Vet J ; 296-297: 105995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207985

RESUMO

Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood samples were collected 6 months apart, around the autumn equinox and spring equinox, and plasma concentrations of ACTH were measured by chemiluminescent immunoassay. Pairwise breed comparisons within each season were performed on log transformed data using the Tukey test. Estimated mean differences in ACTH concentrations were expressed as fold difference with 95 % confidence intervals (CI). Reference intervals for each breed group per season were calculated using non-parametric methods. In autumn, higher ACTH concentrations were found among non-Shetland pony breeds compared with Thoroughbreds (1.55 fold higher; 95 % CI, 1.35-1.77; P < 0.001), and in Shetland ponies compared with Thoroughbreds (2.67 fold higher; 95 % CI, 2.33-3.08; P < 0.001) and non-Shetland pony breeds (1.73 fold higher; 95 % CI, 1.51-1.98; P < 0.001). In spring, no differences were identified among breed groups (all P > 0.05). Reference intervals were similar among breed groups in spring, but upper limits for ACTH concentrations were markedly different between Thoroughbred horses and pony breeds in autumn. These findings emphasise that breed should be accounted for when determining and interpreting reference intervals for ACTH concentrations among healthy horses and ponies in autumn.


Assuntos
Doenças dos Cavalos , Doenças da Hipófise , Cavalos/genética , Animais , Doenças dos Cavalos/genética , Doenças da Hipófise/genética , Doenças da Hipófise/veterinária , Hormônio Adrenocorticotrópico , Estações do Ano , Marcha
4.
Int J Cardiol ; 379: 82-88, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36931398

RESUMO

BACKGROUND: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. METHODS: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. RESULTS: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF physiology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 µg/L). Analysing the correlation between various iron parameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes. CONCLUSIONS: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT03671122.


Assuntos
Insuficiência Cardíaca , Deficiências de Ferro , Masculino , Humanos , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Volume Sistólico/fisiologia , Ferro/metabolismo , Ferritinas , Transferrina , Miocárdio/metabolismo , Músculo Esquelético
5.
Aust Vet J ; 100(4): 181-186, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35122431

RESUMO

OBJECTIVE: Identify veterinarians' practices, recommendations and perceptions when preventing tetanus in horses in Australia. METHODS: Graduated members of Equine Veterinarians Australia participated in an online survey about the prevention of tetanus in horses in Australia. RESULTS: Of 77 respondents (response rate ~ 8%), 50 (65%) reported that they had attended collectively 145-152 cases of tetanus in horses in Australia (1.1 cases of tetanus observed/10 veterinarian-years since qualification). The estimated case fatality rate (CFR) was at least 79%. Puncture wounds were most frequently suspected as the entry point (32%; n = 47). Five respondents (7%) reported cases of localised tetanus. Three respondents reported generalised tetanus within 2 weeks of tetanus antitoxin (TAT) administration. Respondents did not report any cases of tetanus in horses which had been vaccinated according to manufacturer's recommendations. All respondents recommended vaccination, but over 50% (N = 45) stated 'lack of veterinary recommendation' as often or sometimes a reason why clients did not vaccinate horses. Opinions varied on the use of TAT for peri-exposure prophylaxis; 67% of respondents dosed TAT independent of body weight, with the rest dosing according to body weight. Cases of Theiler's disease related to the use of TAT were not reported in Australia by respondents. DISCUSSION: The caseload of equine tetanus appears relatively low among equine veterinarians in Australia. Consistent with the literature, estimated CFR was high. Respondents' recommendations and perceptions about tetanus vaccination were generally consistent but varied regarding TAT usage. Evidence for TAT usage is limited and we recommend studies of TAT efficacy in horses.


Assuntos
Doenças dos Cavalos , Tétano , Médicos Veterinários , Animais , Austrália , Doenças dos Cavalos/prevenção & controle , Cavalos , Humanos , Inquéritos e Questionários , Tétano/prevenção & controle , Tétano/veterinária
6.
J Intern Med ; 289(3): 369-384, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32776357

RESUMO

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Valsartana/uso terapêutico , Idoso , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Sistema de Registros , Volume Sistólico , Suécia
7.
Aust Vet J ; 98(11): 570-573, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32830314

RESUMO

Chlamydia psittaci was detected by PCR in the lung and equine foetal membranes of two aborted equine foetuses and one weak foal from two different studs in Victoria, Australia. The abortions occurred in September 2019 in two mares sharing a paddock northeast of Melbourne. The weak foal was born in October 2019 in a similar geographical region and died soon after birth despite receiving veterinary care. The detection of C. psittaci DNA in the lung and equine foetal membranes of the aborted or weak foals and the absence of any other factors that are commonly associated with abortion or neonatal death suggest that this pathogen may be the cause of the reproductive loss. The detection of C. psittaci in these cases is consistent with the recent detection of C. psittaci in association with equine abortion in New South Wales. These cases in Victoria show that C. psittaci, and the zoonotic risk it poses, should be considered in association with equine reproductive loss in other areas of Australia.


Assuntos
Chlamydophila psittaci , Doenças dos Cavalos , Aborto Animal/epidemiologia , Animais , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , New South Wales , Gravidez , Vitória/epidemiologia
8.
Pituitary ; 23(2): 167-170, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858400

RESUMO

PURPOSE: Tatton-Brown-Rahman syndrome (TBRS) is a newly defined genetic entity characterized by overgrowth and intellectual disability, resulting from germline mutations in the gene encoding DNA methyltransferase 3 alpha (DNMT3A). Affected individuals with benign and malignant tumors have been reported; to our knowledge pituitary adenomas (and other tumors identified in our patient) have not yet been described in this syndrome. CASE: We report the case of a 34-year-old woman with TBRS who developed a GH-secreting pituitary macroadenoma and other benign tumors and cystic lesions involving diverse organ systems. Whole-exome sequencing revealed a heterozygous, likely pathogenic variant (c.700_709 del10, p. Gly234ArgfsX79) in exon7 of DNMT3A, and a heterozygous variant of uncertain significance (c.25 C>T, p.Arg9Trp) in exon 1 of the gene encoding aryl hydrocarbon receptor-interacting protein (AIP). The patient failed somatostatin analog treatment, and underwent surgery. The tumor retained AIP expression, and analysis of tumor DNA indicated the presence of both AIP alleles, consistent with no loss of heterozygosity. These findings suggest that the AIP variant was not the primary driver of pituitary adenoma development. CONCLUSION: Our case suggests that TBRS might be associated with pituitary adenoma and a broader spectrum of tumors than previously thought, making long-term follow up of these patients crucial to identify tumors early, and to elucidate the clinical spectrum of the disorder for optimization of management.


Assuntos
Acromegalia/genética , Adulto , Alelos , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Feminino , Hormônio do Crescimento/metabolismo , Heterozigoto , Humanos , Deficiência Intelectual/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação/genética , Neoplasias Hipofisárias/genética , Sequenciamento do Exoma
9.
Osteoporos Int ; 31(2): 379-389, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31664476

RESUMO

Our study aimed at constructing and validating the Lebanese Osteoporosis Knowledge Scale adapted for use among Lebanese women and to assess factors associated with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures. This scale showed adequate psychometric properties; higher knowledge scores were reached in women who already heard about the disease and had a formal education. As a result, the LOKS-19 can be used to measure knowledge of osteoporosis and help assess osteoporosis-related interventions. INTRODUCTION: The primary objective of this study was to describe the construction of the Lebanese Osteoporosis Knowledge Scale (LOKS) and assess its psychometric properties in a representative sample of Lebanese women aged 40 years and above. Secondary objectives were to explore factors associated with this knowledge score. METHODS: A cross-sectional study carried out between March and June 2018, enrolled 560 women over the age of 40 years living in the community. This proportionate sample was randomly selected from all Lebanese governorates to cover the entire Lebanese area. A survey was developed and adapted to the Lebanese population based on preexisting scales. Personal interviews were conducted to collect data. RESULTS: The items of the LOKS were distributed across seven factors with an Eigenvalue over 1 solution, outlining an overall value of 55.89% of the variance. A high Cronbach's alpha was found for the full scale (0.725). Individuals having a university level of education (beta = 1.62; compared to illiteracy), having heard of osteoporosis (beta = 2.62), taking supplements of calcium and vitamin D compared to none (beta = 0.77), and having had Crohn's disease (beta = 1.71) had significantly higher knowledge scores of osteoporosis; oppositely, having diabetes (beta = - 1.17), currently taking chemotherapy (beta = - 2.25), and ever having had a fracture (beta = - 0.74) were significantly correlated with lower awareness of osteoporosis. CONCLUSIONS: Our findings suggest that the LOKS-19 can be used to measure knowledge of osteoporosis and help assess osteoporosis-related interventions. A better knowledge seems to be associated with more preventive measures and less risk of fracture.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Osteoporose , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Psicometria , Fatores de Risco , Inquéritos e Questionários
10.
Aust Vet J ; 97(7): 220-224, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31236928

RESUMO

OBJECTIVE: To determine the nature of serological responses in Australian horses using a commercial duplex indirect ELISA (iELISA) following vaccination against strangles. DESIGN: A group (n = 19) of client-owned horses from five properties were recruited to receive a primary course of a Streptococcus equi subsp. equi (S. equi) extract vaccine. Serological responses were determined by duplex iELISA incorporating S. equi-specific fragments of two cell wall proteins, SEQ2190 and SeM (antigens (Ag) A and C, respectively). METHODS: The horses were administered a primary strangles vaccination course. Blood was collected immediately prior to each of the three vaccinations at 2-week intervals and additionally at 28 and 56 days following the 3rd vaccination (V3). RESULTS: Significant increases in mean antibody levels of horses following vaccination were limited only to AgC, which was significantly increased at T2/V3, 14 days following V2 (ratio of geometric means = 3.7; 95% confidence interval (CI): 1.6, 8.4; P = 0.003). There was no increase in mean antibody to Ag A (ratio of geometric means = 1.4; 95% CI: 0.6, 3.2; P = 0.39). Four horses (22%) exceeded the test cut-off for AgC following vaccination. CONCLUSION: Vaccination of Australian horses is unlikely to interfere greatly with detection of strangles using the duplex iELISA. No responses would be anticipated to AgA following vaccination with Equivac© S/Equivac© 2in1 and only a minority are likely to respond to AgC. We conclude that the results of this study validate the usefulness of the duplex iELISA to assist control measures for strangles outbreaks in Australian horse populations.


Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Doenças dos Cavalos/prevenção & controle , Infecções Estreptocócicas/veterinária , Streptococcus equi , Animais , Anticorpos Antibacterianos/sangue , Austrália , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Doenças dos Cavalos/sangue , Cavalos , Masculino , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/prevenção & controle , Vacinação/veterinária
11.
Osteoporos Int ; 30(4): 771-786, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30840113

RESUMO

Our study investigated the characteristics of Lebanese women population groups with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures in order to identify categories that should be targeted in future campaigns and educational programs. Higher knowledge scores were reached in women who already heard about the disease and had a formal education. As a result, osteoporosis awareness campaigns and educational programs are mostly needed in populations with lower educational levels. INTRODUCTION: Our study investigated the characteristics of Lebanese women population groups with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures. METHODS: A cross-sectional study, conducted between March and June 2018, enrolled 560 community dwelling women aged 40 years and above. A questionnaire was used to collect data. A proportionate random sample from all Lebanese Mohafazat was used. Data collection was performed through personal interviews. The median was used as a cutoff point for both the Knowledge and Health Belief scales. RESULTS: The study results showed that 47.3% of participants had a poor knowledge score. Women who received no education, compared to a higher education and have not previously heard about the disease, had lower knowledge scores. In addition, women not taking calcium and vitamin D supplements and not exercising or exercising less than 20 min per day compared to those having these characteristics had lower osteoporosis knowledge levels. A lower knowledge score was associated with less recognized benefits of adequate calcium intake and regular physical activity, more perceived barriers towards their practice, and a less important health motivation. A lower level of education correlated to the same results. CONCLUSION: Lower knowledge scores were reached in women who have never heard of osteoporosis and had a lower level of education. As a result, osteoporosis awareness campaigns and educational programs need to target population categories with lower educational levels.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Osteoporose/etiologia , Adulto , Fatores Etários , Estudos Transversais , Escolaridade , Feminino , Humanos , Líbano , Pessoa de Meia-Idade , Osteoporose/prevenção & controle , Osteoporose/psicologia , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/prevenção & controle , Osteoporose Pós-Menopausa/psicologia , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários
12.
Opt Lett ; 43(20): 5098-5101, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30320829

RESUMO

We introduce a fiber-based laser system providing 130 fs pulses with 3.5 nJ energy at 920 nm at a 43 MHz repetition rate and illustrate the potential of the source for two-photon excited fluorescence microscopy of living mouse brain. The laser source is based on frequency-doubling high-energy solitons generated and frequency-shifted to 1840 nm in large mode area fibers. This simple laser system could unleash the potential of two-photon microscopy techniques in the biology laboratory where green fluorescent proteins with two-photon absorption spectrum peaking around 920 nm are routinely used.

13.
J Intern Med ; 283(4): 380-391, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29430747

RESUMO

AIMS: Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. METHODS AND RESULTS: In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r = -0.30, P = 0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P > 0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P = 0.023). CONCLUSIONS: Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Função do Átrio Esquerdo/fisiologia , Biomarcadores/metabolismo , Fenômenos Biomecânicos/fisiologia , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Estudos Prospectivos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/sangue
14.
Biomed Opt Express ; 9(1): 142-156, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29359093

RESUMO

In situ fluorescence lifetime imaging microscopy (FLIM) in an endoscopic configuration of the endogenous biomarker nicotinamide adenine dinucleotide (NADH) has a great potential for malignant tissue diagnosis. Moreover, two-photon nonlinear excitation provides intrinsic optical sectioning along with enhanced imaging depth. We demonstrate, for the first time to our knowledge, nonlinear endogenous FLIM in a fibered microscope with proximal detection, applied to NADH in cultured cells, as a first step to a nonlinear endomicroscope, using a double-clad microstructured fiber with convenient fiber length (> 3 m) and excitation pulse duration (≈50 fs). Fluorescence photons are collected by the fiber inner cladding and we show that its contribution to the impulse response function (IRF), which originates from its intermodal and chromatic dispersions, is small (< 600 ps) and stable for lengths up to 8 m and allows for short lifetime measurements. We use the phasor representation as a quick visualization tool adapted to the endoscopy speed requirements.

16.
Aust Vet J ; 92(12): 504-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25424766

RESUMO

CASE REPORT: Seven eastern grey kangaroos (Macropus giganteus) grazing pastures including Phalaris spp. in Victoria showed neurological deficits characterised by ataxia, head tremors and collapse. Gross examination of the brains and spinal cords of affected kangaroos showed a greenish discolouration in several regions of the grey matter. Histologically, intracytoplasmic accumulation of pigment granules was detected in the neurons, most prominently in the thalamus, brainstem and ventral horns of the spinal cord. Pigment granules were positive to stains used for identification of melanin, including Fontana-Masson stain and Schmorl's reaction. CONCLUSION: The combination of clinical signs and obvious neuronal pigmentation is consistent with chronic Phalaris spp. toxicity, a condition well documented in domestic ruminants.


Assuntos
Macropodidae , Doenças do Sistema Nervoso/veterinária , Phalaris/intoxicação , Animais , Autopsia/veterinária , Encéfalo/patologia , Eutanásia Animal , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/patologia , Vitória
17.
Cell Death Dis ; 4: e627, 2013 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-23661005

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies. Cancer stem cells (CSCs), which are not targeted by current therapies, may be the reason for pronounced therapy resistance. A new treatment option in phase II trials is cabozantinib that inhibits the pancreatic CSC surface marker and tyrosine kinase receptor c-Met. The purpose of this study was to evaluate the effect of cabozantinib to stem-like features and therapy resistance. Established PDA cell lines, a gemcitabine-resistant subclone, non-malignant pancreatic ductal cells and primary spheroidal cultures from patient tumors were analyzed by MTT-assay, flow cytometry, colony and spheroid formation assays, western blotting, qRT-PCR, antibody protein array, immunohistochemistry and morphological features. Cabozantinib inhibited viability and spheroid formation and induced apoptosis in malignant cells with minor effects in non-malignant cells. After long-term cabozantinib treatment, PDA cells had altered anti- and pro-apoptotic signaling, but still responded to cabozantinib, as apoptosis only slightly decreased and viability only slightly increased suggesting a low resistance-inducing potential of cabozantinib. In parallel, c-Met expression and the pluripotency transcription factor SOX2 were downregulated, which might counteract development of full therapy resistance in long-term treated subclones. In single-treatment studies, cabozantinib increased efficacy of gemcitabine. Most importantly, cabozantinib strongly induced apoptosis and reduced viability in PDA cell lines, which are completely resistant toward gemcitabine. In primary, CSC-enriched spheroidal cultures cabozantinib downregulated CSC markers SOX2, c-Met and CD133 and induced apoptosis. These findings suggest that the clinical use of cabozantinib may be more effective than current chemotherapeutics.


Assuntos
Anilidas/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Piridinas/farmacologia , Células-Tronco/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Gencitabina
18.
J Intern Med ; 273(4): 410-21, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23331339

RESUMO

BACKGROUND: Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta-cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function. METHODS: Acute coronary syndrome ACS patients with IGT or T2DM (n = 71), screened by oral glucose tolerance test (OGTT) 4-23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg (n = 34) or placebo (n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose-lowering agents other than the study drug. The study end-point was beta-cell function assessed using the insulinogenic index (IGI = ΔInsulin30 /ΔGlucose30 ), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test. RESULTS: The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol(-1) and 1394 vs. 1106 pmol L(-1) min(-1) respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group (P = 0.013) and AIRg was 1909 and 1043 pmol L(-1) min(-1) (P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L(-1) in sitagliptin-treated patients and 6.0 mmol L(-1) in those who received placebo compared with 5.8 and 5.9 mmol L(-1) respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group (P = 0.003). Sitagliptin was well tolerated. CONCLUSION: Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.


Assuntos
Síndrome Coronariana Aguda/complicações , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Intolerância à Glucose/diagnóstico , Células Secretoras de Insulina/metabolismo , Pirazinas/administração & dosagem , Triazóis/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Seguimentos , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Intolerância à Glucose/complicações , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Células Secretoras de Insulina/efeitos dos fármacos , Estudos Prospectivos , Fosfato de Sitagliptina , Resultado do Tratamento
19.
Equine Vet J ; 45(2): 235-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22943193

RESUMO

REASONS FOR PERFORMING STUDY: During the 2007 Australian equine influenza (EI) outbreak, an accelerated primary course 14 day intervaccination schedule was proposed, but not widely implemented. Expert opinion was divided as to the efficacy of such a schedule given the lack of published data. This study determined the level and duration of humoral immunity following administration of a recombinant canarypox-vectored vaccine (ALVAC-EIV) with a primary intervaccination interval of 14 days and booster at 105 days. OBJECTIVES: To examine whether protective levels of immunity of adequate duration were achieved following a primary course reduced from a minimum interval of 28 to 14 days. Antibody responses to 2 H3N8 American lineage virus strains (including A/equine/Sydney/6085/2007) were assessed and compared to previous challenge studies using ALVAC-EIV at conventional intervaccination intervals. METHODS: Fourteen Thoroughbred horses and 2 ponies from a rural racehorse training property in Victoria, Australia, were vaccinated with ALVAC-EIV on Days 0, 14 and 105. Serial blood samples were collected over the next 32 weeks and tested with haemagglutination inhibition and single radial haemolysis (SRH) in full assays to evaluate the serological response. RESULTS: All horses and ponies responded to the accelerated ALVAC-EIV vaccination schedule. Mean SRH antibodies remained above those consistent with clinical protection for the duration of the study period. All vaccinates demonstrated high SRH antibodies 14 days following V2, thereby achieving 100% herd immunity to homologous viral challenge. CONCLUSIONS: An accelerated vaccination schedule conferred long-lasting protective antibody levels despite a >50% reduction in the recommended V1-V2 interval. POTENTIAL RELEVANCE: High levels of rapidly acquired herd immunity are critical in containing an outbreak of such a highly contagious pathogen as EIV. In a strategic vaccination programme, it is important that horses remain protected for sufficient time to allow control programmes to succeed. An accelerated 14 day primary course intervaccination interval and booster at 105 days achieves both of these objectives.


Assuntos
Anticorpos Antivirais/sangue , Doenças dos Cavalos/prevenção & controle , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Animais , Cavalos , Esquemas de Imunização , Vacinas contra Influenza/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Vacinação
20.
Aust Vet J ; 90(7): 252-4, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22731944

RESUMO

A 5-year-old Thoroughbred mare presented with signs of severe pain and was taken to exploratory laparotomy based on suspicion of an acute abdominal lesion. A mild gastrointestinal lesion was discovered, but was considered disproportional to the severity of signs displayed. The mare was later euthanased because of intractable pain. Comprehensive postmortem examination, including polymerase chain reaction testing of central nervous system tissue samples, allowed a definitive diagnosis of Murray Valley encephalomyelitis to be made. This case demonstrates the variability of clinical presentations in horses infected with Murray Valley encephalitis virus.


Assuntos
Vírus da Encefalite do Vale de Murray/isolamento & purificação , Encefalite por Arbovirus/veterinária , Doenças dos Cavalos/diagnóstico , Animais , Encefalite por Arbovirus/diagnóstico , Evolução Fatal , Feminino , Cavalos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária
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