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1.
BMC Vet Res ; 14(1): 195, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921290

RESUMO

BACKGROUND: Although mustelids occur worldwide and include a wide range of species, little is known about the diseases affecting them. Mustelids have regularly been submitted for post mortem investigation in the framework of the program for general wildlife health surveillance in Switzerland, which has been in place for nearly 60 years. We performed a retrospective analysis of the necropsy reports on mustelids submitted to the diagnostic service of the University of Bern. The aims of this study were to present an overview of the causes of mortality and morbidity observed in these carnivores, to assess differences among species, to assess changes in disease detection over the study period, and to describe the pathology of selected diseases. RESULTS: Five hundred and sixty-six reports from 1958 to 2015 were analyzed. Most animals were stone martens (Martes foina, 46%) and badgers (Meles meles, 44%); the remaining species were polecats (Mustela putorius, 4.7%), pine martens (Martes martes, 2%), stoats (Mustela erminea, 1.4%), weasels (Mustela nivalis, 0.8%) and otters (Lutra lutra, 0.3%). Infectious diseases (n = 262) were frequent and were mostly bacterial or viral; non-infectious conditions (n = 169) were less common and were mostly traumatic or due to metabolic disorders. The most frequent diagnoses included distemper (75% were badgers), amyloidosis (96% were martens), bacterial respiratory infections (all mustelids), biting lice (badgers only) and pulmonary and gastro-intestinal helminths (all species). Less frequent diseases included histoplasmosis (badgers only), aspergillosis, toxoplasmosis, hepatozoonosis, and sarcoptic mange. Lesions due to infection with distemper virus were primarily appreciated in the respiratory tract and central nervous system; they presented species-specific characteristics such as necrosis in the ependyma in badgers and absence of syncytia in stone martens. Amyloidosis in martens was multisystemic in most cases and included both AA and AL amyloidosis; the main macroscopic change was severe splenomegaly. CONCLUSION: Infectious diseases were the most frequent causes of morbidity and mortality of mustelids, with marked species-specific differences. Lung and skin were the most commonly affected organs. Contagious diseases such as canine distemper, sarcoptic mange and rabies in mustelids showed a similar temporal pattern as in red foxes (Vulpes vulpes), suggesting pathogen spillovers from foxes to mustelids.


Assuntos
Mustelidae , Animais , Animais Selvagens , Infecções Bacterianas/mortalidade , Infecções Bacterianas/veterinária , Causas de Morte , Feminino , Furões , Masculino , Vison , Mortalidade , Micoses/mortalidade , Micoses/veterinária , Lontras , Doenças Parasitárias em Animais/mortalidade , Estudos Retrospectivos , Suíça/epidemiologia , Viroses/mortalidade , Viroses/veterinária
2.
Parasit Vectors ; 10(1): 422, 2017 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-28915832

RESUMO

BACKGROUND: Besides acting as definitive hosts for Echinococcus multilocularis, dogs can become infected by the larval form of this parasite and thereby develop life-threatening alveolar echinococcosis (AE). Although AE is a zoonotic disease, most therapeutic and diagnostic approaches have been developed for human patients. In dogs, AE is typically diagnosed in the advanced stage of the disease when the parasitic mass has already caused abdominal distension. At that stage, complete resection of the parasitic mass is often impossible, leaving a guarded prognosis for the affected dogs. For humans, sensitive and specific diagnostic protocols relying on serology have been validated and are now widely used. In contrast, sensitive and specific laboratory diagnostic tools that would enable early diagnosis of canine AE are still lacking. The aim of the current study was to establish a serological protocol specifically adapted to dogs. METHODS: We tested several native and recombinant antigens (EmVF, Em2, recEm95, recEm18) in in-house ELISA, an in-house Western blot (WB), as well as a commercially available WB developed for serodiagnosing human AE (Anti-Echinococcus EUROLINE-WB®), using a panel of known status dog sera. RESULTS: RecEm95-antigen was revealed to be the most promising antigen for use in ELISA, demonstrating 100% (95% CI: 72-100%) sensitivity and 100% (95% CI: 93-100%) specificity in our study. The in-house WB using EmVF antigen performed as well as the recEm95-ELISA. The commercial WB also correctly identified all infected dogs, coupled with a specificity of 98% (95% CI: 91-100%). CONCLUSION: The recEm95-ELISA alone or in combination with either the in-house WB or the Anti-Echinococcus EUROLINE-WB® (IgG) with a minor modification should be considered as the best current approach for the serological diagnosis of dogs infected with the larval stage of E. multilocularis. However, larger studies with a focus on potentially cross-reacting sera should be undertaken to verify these findings.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Western Blotting/veterinária , Doenças do Cão/diagnóstico , Equinococose/veterinária , Echinococcus multilocularis/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Animais , Antígenos de Helmintos/genética , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Equinococose/diagnóstico , Equinococose/imunologia , Echinococcus multilocularis/química , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Masculino , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/veterinária
3.
Vet Rec ; 177(22): 569, 2015 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-26537856

RESUMO

Alveolar echinococcosis (AE), a parasitic disease primarily of the liver caused by the larval stage of Echinococcus multilocularis, is highly endemic in Switzerland. In contrast to well-established management protocols in people, little is known with regard to optimal treatment strategies in dogs. The objective of this study was to describe the clinical signs and diagnostic procedures in dogs with AE and to evaluate outcome following medical treatment alone or surgery and medical treatment. Of 23 putative AE cases between 2004 and 2014, 20 were classified as confirmed (n=18) or probable (n=2) AE, based on abdominal ultrasound, serology, cytology, histology and/or PCR. Most dogs presented with abdominal distension in an advanced stage of disease. Dogs receiving specific treatment (radical or debulking surgery together with medical treatment, or medical treatment alone) survived longer than dogs left untreated, but no difference was found between treatment types. Survival at one year was associated with absence of free abdominal fluid, absence of abdominal distension and treatment of any type. However, dogs treated with debulking surgery all faced relapse. Findings of this study suggest that in AE-affected dogs for which a therapeutic approach is regarded appropriate by owners and veterinarians, radical surgical resection and medical treatment or, if total resection is not possible, medical treatment alone should be considered. However, studies on larger numbers of dogs are necessary before definitive treatment recommendations can be made.


Assuntos
Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Equinococose Hepática/veterinária , Animais , Cães , Equinococose , Equinococose Hepática/diagnóstico , Equinococose Hepática/terapia , Feminino , Masculino , Estudos Retrospectivos , Resultado do Tratamento
4.
Vet Parasitol ; 205(1-2): 113-8, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24986466

RESUMO

A novel species-specific anti-beaver-IgG-alkaline-phosphatase conjugate was synthesized for the development of a new serological test for echinococcosis in beavers. Two different ELISAs conventionally used for human Echinococcus multilocularis serology (Em18-ELISA and Em2-ELISA) yielded diagnostic sensitivities of 0% and 46%, respectively. In contrast, the subsequently developed immunoblotting assay gave an 85% diagnostic sensitivity (11 out of 13 beavers with alveolar echinococcosis were immunoblotting-positive, i.e. showed reactivity with a specific 21 Mr band), and maximal specificity. In conclusion, this immunoblotting assay should be the method of choice for use in serological studies on E. multilocularis in Eurasian beavers, and the test proved suitable to investigate both animals alive and post-mortem.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Equinococose Hepática/veterinária , Immunoblotting/veterinária , Roedores/parasitologia , Animais , Equinococose , Equinococose Hepática/diagnóstico , Echinococcus/imunologia , Sensibilidade e Especificidade
5.
Vet Parasitol ; 197(1-2): 95-103, 2013 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-23680543

RESUMO

Bovine besnoitiosis caused by Besnoitia besnoiti is a chronic and debilitating disease. The most characteristic clinical signs of chronic besnoitiosis are visible tissue cysts in the scleral conjunctiva and the vagina, thickened skin and a generally poor body condition. However, many seropositive animals remain subclinically infected, and the role that these animals may play in spreading the disease is not known. The aim of the present study was to assess the intra-organ parasite distribution, the parasite load and the parasite-associated lesions in seropositive but subclinically infected animals. These animals were seropositive at the time of several consecutive samplings, had visible tissue cysts in the past and, at time of slaughter, had detectable specific anti-Besnoitia spp. antibody levels, but they did not show evident clinical signs at culling. Thus, histopathological, immunohistochemical and molecular analyses of several samples from the respiratory tract, reproductive tract, other internal organs and skin from six cows were performed. The tissue cysts were located primarily in the upper respiratory tract, i.e., in the rhinarium and larynx/pharynx (four cows), followed by the distal genital tract (vulva/vagina) and the skin of the neck (three and two cows, respectively, out of the four cows with cysts in the respiratory tract). We were unable to detect any parasites in the two remaining cows. Cysts were associated with a significant non-purulent inflammatory infiltrate consisting predominantly of T lymphocytes and activated monocytes/macrophages in two cows. The parasite burden, estimated by quantitative real-time PCR, was very low. It is noteworthy that the only animal that showed a recent increase in the antibody titre had the highest parasite burden and the most conspicuous inflammatory reaction against the cysts. In conclusion, although these cows no longer displayed any visible signs of besnoitiosis, they remained infected. Therefore, cows without visible signs of disease may still be able to transmit the parasite.


Assuntos
Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Animais , Bovinos , Doenças dos Bovinos/patologia , Doença Crônica , Coccidiose/parasitologia , Coccidiose/patologia , Feminino
6.
Neuroscience ; 233: 157-65, 2013 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-23270858

RESUMO

Parkinson's disease (PD) is an asymmetric neurodegenerative disorder, and secondary adaptive mechanisms of the less-affected side could potentially compensate for parkinsonian symptoms. Here, we analyzed gene expression changes on the healthy side of a unilateral PD rat model and correlated these changes with locomotor velocity, which is known to be decreased in PD. Four weeks after a unilateral 6-hydroxydopamine lesion, the spontaneous locomotor velocity of rats was recorded just prior to brain extraction. We then analyzed the gene expression levels of markers of the direct (dynorphin and D1-class dopamine receptors) and indirect (enkephalin and D2-class dopamine receptors) pathways in the contralateral healthy striatum by in situ hybridization histochemistry. In addition, we analyzed the expression of several striatal and cortical glutamatergic markers, as well as nigral tyrosine hydroxylase (TH) and nigral dopamine transporter (DAT). We found a significant positive correlation between the mRNA expression levels of contralateral D1-class dopamine receptors and the mean locomotor velocity, at 4 weeks after surgery in parkinsonian rats but not in controls. Moreover, we observed a significant increase in the level of dynorphin mRNA in the lateral part of the contralateral striatum of parkinsonian rats compared to the controls. In contrast, no contralateral changes were observed in the striatal indirect pathway. We also did not find any significant contralateral modifications of TH, DAT or glutamatergic markers in PD animals, indicating that changes in direct pathway genes are not due to nigrostriatal dopaminergic or corticostriatal glutamatergic innervation. In conclusion, our results suggest a role of the healthy striatal direct pathway in counteracting dopaminergic denervation effects on motor symptoms.


Assuntos
Córtex Cerebral/metabolismo , Dinorfinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transtornos Parkinsonianos/metabolismo , Receptores de Dopamina D1/metabolismo , Adaptação Fisiológica , Adrenérgicos , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Dinorfinas/genética , Encefalinas/genética , Encefalinas/metabolismo , Feminino , Lateralidade Funcional , Perfilação da Expressão Gênica , Locomoção/fisiologia , Neostriado/metabolismo , Neostriado/patologia , Proteínas do Tecido Nervoso/genética , Vias Neurais/fisiologia , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , RNA Mensageiro/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
7.
Transbound Emerg Dis ; 60(1): 59-68, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22429475

RESUMO

Bovine besnoitiosis is considered an emerging chronic and debilitating disease in Europe. Many infections remain subclinical, and the only sign of disease is the presence of parasitic cysts in the sclera and conjunctiva. Serological tests are useful for detecting asymptomatic cattle/sub-clinical infections for control purposes, as there are no effective drugs or vaccines. For this purpose, diagnostic tools need to be further standardized. Thus, the aim of this study was to compare the serological tests available in Europe in a multi-centred study. A coded panel of 241 well-characterized sera from infected and non-infected bovines was provided by all participants (SALUVET-Madrid, FLI-Wusterhausen, ENV-Toulouse, IPB-Berne). The tests evaluated were as follows: an in-house ELISA, three commercial ELISAs (INGEZIM BES 12.BES.K1 INGENASA, PrioCHECK Besnoitia Ab V2.0, ID Screen Besnoitia indirect IDVET), two IFATs and seven Western blot tests (tachyzoite and bradyzoite extracts under reducing and non-reducing conditions). Two different definitions of a gold standard were used: (i) the result of the majority of tests ('Majority of tests') and (ii) the majority of test results plus pre-test information based on clinical signs ('Majority of tests plus pre-test info'). Relative to the gold standard 'Majority of tests', almost 100% sensitivity (Se) and specificity (Sp) were obtained with SALUVET-Madrid and FLI-Wusterhausen tachyzoite- and bradyzoite-based Western blot tests under non-reducing conditions. On the ELISAs, PrioCHECK Besnoitia Ab V2.0 showed 100% Se and 98.8% Sp, whereas ID Screen Besnoitia indirect IDVET showed 97.2% Se and 100% Sp. The in-house ELISA and INGEZIM BES 12.BES.K1 INGENASA showed 97.3% and 97.2% Se; and 94.6% and 93.0% Sp, respectively. IFAT FLI-Wusterhausen performed better than IFAT SALUVET-Madrid, with 100% Se and 95.4% Sp. Relative to the gold standard 'Majority of test plus pre-test info', Sp significantly decreased; this result was expected because of the existence of seronegative animals with clinical signs. All ELISAs performed very well and could be used in epidemiological studies; however, Western blot tests performed better and could be employed as a posteriori tests for control purposes in the case of uncertain results from valuable samples.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças dos Bovinos/diagnóstico , Coccidiose/diagnóstico , Coccidiose/veterinária , Ensaio de Proficiência Laboratorial/métodos , Sarcocystidae/imunologia , Animais , Western Blotting , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Coccidiose/parasitologia , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Feminino , Ensaio de Proficiência Laboratorial/normas , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes Sorológicos
8.
Schweiz Arch Tierheilkd ; 154(5): 199-207, 2012 May.
Artigo em Alemão | MEDLINE | ID: mdl-22547335

RESUMO

The purpose of the present study was based upon the first diagnosed bovine cutaneous leishmaniasis in a cow in Switzerland in April 2009. We continued descriptively the search for other bovine cases in Switzerland. We carried out similar investigations in the original farm where the case had occurred, and in parallel also in the neighboring farm. Additionally, veterinary practitioners sent us an overall of 12 suspected cases of bovine leishmaniasis. Following diagnostic investigations, all cases were negative for Leishmania. The occurrence of this infection appears therefore to be a very rare event. Finally some differential diagnoses are discussed.


Assuntos
Doenças dos Bovinos/epidemiologia , Leishmaniose/veterinária , Animais , Anticorpos Antiprotozoários/sangue , Autopsia/veterinária , Biópsia/veterinária , Bovinos , Doenças dos Bovinos/diagnóstico , Diagnóstico Diferencial , Cães , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Cabras , Cavalos , Leishmania/imunologia , Leishmaniose/diagnóstico , Leishmaniose/epidemiologia , Pele/patologia , Suíça/epidemiologia
9.
Int J Surg Case Rep ; 2(8): 269-71, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22096750

RESUMO

INTRODUCTION: Chylous ascites is defined by an accumulation of chylous fluid in the peritoneal cavity and it clinically appears as a milky fluid in which laboratory examination reveals triglycerides, cholesterol, and sometimes chylomicrons and lymphocytes. PRESENTATION OF CASE: We report the first case of primary chylous ascites observed during laparoscopy for unexplained secondary infertility. DISCUSSION: Chylous ascites has never been linked to fertility but bathes all internal reproductive organs surfaces and is considered a communication mean between ovaries. CONCLUSION: Despite a lack of evidence, the question of peritoneal fluid role remains in infertility.

10.
Gynecol Obstet Fertil ; 39(11): 640-3, 2011 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21996329

RESUMO

Ectopic pregnancy is a common problem usually diagnosed at an early stage and often in an emergency situation. Both medical and surgical treatments can be used for its management. In case of surgical treatment, laparoscopy rather than open surgery must be practiced. Concerning the choice between salpingostomy and salpingectomy, it depends of the controlateral tubal patency. In case of altered controlateral tube, if a sparing surgery is possible it should be preferred. However, this question is still debated if the controlateral tube seems patent.


Assuntos
Endoscopia/métodos , Gravidez Ectópica/cirurgia , Feminino , Humanos , Gravidez , Salpingectomia , Salpingostomia
11.
Zoonoses Public Health ; 58(7): 472-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21824348

RESUMO

Toxoplasmosis is one of the most important zoonotic diseases worldwide and is caused by the protozoan Toxoplasma gondii. Besides vertical infection during pregnancy, humans can get infected post-natally either by peroral uptake of sporulated Toxoplasma oocysts or by ingestion of tissue cysts upon consumption of raw or undercooked meat. The aim of this study was to approximate the risk of human infection via meat consumption by estimating the seroprevalence of T. gondii in slaughtered animals in Switzerland and to compare data with prevalences assessed 10 years ago. The study included pigs, cattle, sheep and wild boar of different age groups and housing conditions whenever possible and applicable. A P-30-ELISA was used to detect T. gondii-specific antibodies and to determine seroprevalences in meat juice of slaughtered animals. A total of 270 domestic pigs (120 adults, 50 finishing, 100 free-ranging animals), 150 wild boars, 250 sheep (150 adults, 100 lambs) and 406 cattle (47 calves, 129 heifers, 100 bulls, 130 adult cows) were tested. Seropositivity increased with the age of the assessed animals. Independent of the age-group, the overall seroprevalence was lowest in wild boars (6.7%), followed by pigs (23.3%), cattle (45.6%) and sheep (61.6%), respectively. Conventional fattening pigs and free-ranging pigs surprisingly had comparable seroprevalences (14.0% and 13.0%, respectively). Unlike in other European countries, where generally a decrease in the number of seropositive animals had been observed, we found that the prevalence of seropositive animals, when compared with that of 10 years ago, had increased for most species/age groups. Conclusively, the results demonstrated a high seroprevalence of T. gondii in animals slaughtered for meat production and revealed that increasing age of the animals is a more important risk factor than housing conditions in Switzerland.


Assuntos
Anticorpos Antiprotozoários/isolamento & purificação , Carne/parasitologia , Toxoplasmose Animal/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Feminino , Humanos , Masculino , Gravidez , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/parasitologia , Suíça/epidemiologia
12.
Vet Parasitol ; 177(3-4): 290-7, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21183278

RESUMO

The protozoan parasite Toxoplasma gondii infects almost all warm blooded animal species including humans, and is one of the most prevalent zoonotic parasites worldwide. Post-natal infection in humans is acquired through oral uptake of sporulated T. gondii oocysts or by ingestion of parasite tissue cysts upon consumption of raw or undercooked meat. This study was undertaken to determine the prevalence of oocyst-shedding by cats and to assess the level of infection with T. gondii in meat-producing animals in Switzerland via detection of genomic DNA (gDNA) in muscle samples. In total, 252 cats (44 stray cats, 171 pet cats, 37 cats with gastrointestinal disorders) were analysed coproscopically, and subsequently species-specific identification of T. gondii oocysts was achieved by Polymerase Chain Reaction (PCR). Furthermore, diaphragm samples of 270 domestic pigs (120 adults, 50 finishing, and 100 free-range animals), 150 wild boar, 250 sheep (150 adults and 100 lambs) and 406 cattle (47 calves, 129 heifers, 100 bulls, and 130 adult cows) were investigated by T. gondii-specific real-time PCR. For the first time in Switzerland, PCR-positive samples were subsequently genotyped using nine PCR-restriction fragment length polymorphism (PCR-RFLP) loci (SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) for analysis. Only one of the cats shed T. gondii oocysts, corresponding to a T. gondii prevalence of 0.4% (95% CI: 0.0-2.2%). In meat-producing animals, gDNA prevalence was lowest in wild boar (0.7%; 95% CI: 0.0-3.7%), followed by sheep (2.0%; 95% CI: 0.1-4.6%) and pigs (2.2%; 95% CI: 0.8-4.8%). The highest prevalence was found in cattle (4.7%; 95% CI: 2.8-7.2%), mainly due to the high prevalence of 29.8% in young calves. With regard to housing conditions, conventional fattening pigs and free-range pigs surprisingly exhibited the same prevalence (2.0%; 95% CI: 0.2-7.0%). Genotyping of oocysts shed by the cat showed T. gondii with clonal Type II alleles and the Apico I allele. T. gondii with clonal Type II alleles were also predominantly observed in sheep, while T. gondii with mixed or atypical allele combinations were very rare in sheep. In pigs and cattle however, genotyping of T. gondii was often incomplete. These findings suggested that cattle in Switzerland might be infected with Toxoplasma of the clonal Types I or III, atypical T. gondii or more than one clonal Type.


Assuntos
Doenças do Gato/parasitologia , Gastroenteropatias/veterinária , Carne/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/genética , Animais , Doenças do Gato/epidemiologia , Gatos , Bovinos , DNA de Protozoário/química , DNA de Protozoário/genética , Fezes/parasitologia , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/parasitologia , Masculino , Músculo Esquelético/parasitologia , Oocistos/parasitologia , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Prevalência , Ovinos , Suínos , Suíça/epidemiologia , Toxoplasma/genética , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia
13.
Oncogene ; 30(9): 1082-97, 2011 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-21057537

RESUMO

Fulvestrant is a selective estrogen receptor downregulator (SERD) and highly effective antagonist to hormone-sensitive breast cancers following failure of previous tamoxifen or aromatase inhibitor therapies. However, after prolonged fulvestrant therapy, acquired resistance eventually occurs in the majority of breast cancer patients, due to poorly understood mechanisms. To examine a possible role(s) of aberrantly expressed microRNAs (miRNAs) in acquired fulvestrant resistance, we compared antiestrogen-resistant and -sensitive breast cancer cells, revealing the overexpression of miR-221/222 in the SERD-resistant cell lines. Fulvestrant treatment of estradiol (E2)- and fulvestrant-sensitive MCF7 cells resulted in increased expression of endogenous miR-221/222. Ectopic upregulation of miR-221/222 in estrogen receptor-α (ERα)-positive cell lines counteracted the effects of E2 depletion or fulvestrant-induced cell death, thus also conferring hormone-independent growth and fulvestrant resistance. In cells with acquired resistance to fulvestrant, miR-221/222 expression was essential for cell growth and cell cycle progression. To identify possible miR-221/222 targets, miR-221- or miR-222- induced alterations in global gene expression profiles and target gene expression at distinct time points were determined, revealing that miR-221/222 overexpression resulted in deregulation of multiple oncogenic signaling pathways previously associated with drug resistance. Activation of ß-catenin by miR-221/222 contributed to estrogen-independent growth and fulvestrant resistance, whereas TGF-ß-mediated growth inhibition was repressed by the two miRNAs. This first in-depth investigation into the role of miR-221/222 in acquired fulvestrant resistance, a clinically important problem, demonstrates that these two 'oncomirs' may represent promising therapeutic targets for treating hormone-independent, SERD-resistant breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos , Estradiol/análogos & derivados , MicroRNAs/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Fulvestranto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima , beta Catenina/genética
14.
Gynecol Obstet Fertil ; 38(9): 550-2, 2010 Sep.
Artigo em Francês | MEDLINE | ID: mdl-20709587

RESUMO

Operative hysteroscopic surgery can lead to intra-uterine adhesions reducing procreation chances. Prevention of this kind of adhesions is necessary. Several pre-, per-, and post-operative means have been proposed against these adhesions. However data concerning their functional interest are lacking.


Assuntos
Histeroscopia/efeitos adversos , Infertilidade Feminina/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Doenças Uterinas/prevenção & controle , Feminino , Humanos , Infertilidade Feminina/etiologia , Aderências Teciduais/complicações
15.
J Neural Transm Suppl ; (72): 207-15, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17982897

RESUMO

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will increase with increased life expectancy. The AD brain is marked by severe neurodegeneration like the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems in the hippocampus and cerebral cortex. Recent findings suggest that these pathological changes are causally induced by mitochondrial dysfunction, increased oxidative stress and elevated apoptosis. Until now, AD cannot be diagnosed by a valid clinical method or a biomarker before the disease has progressed so far that dementia is present. Furthermore, no valid method is available to determine which patient with mild cognitive impairment (MCI) will progress to AD. Therefore, a correct diagnosis in the early stage of AD is not only of importance considering that early drug treatment is more effective but also that the psychological burden of the patients and relatives could be decreased. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and mitochondrial dysfunction as biomarker for AD in a peripheral cell model, the lymphocytes.


Assuntos
Doença de Alzheimer/diagnóstico , Apoptose/fisiologia , Biomarcadores , Linfócitos/fisiologia , Doenças Mitocondriais/diagnóstico , Estresse Oxidativo/fisiologia , Fatores Etários , Idoso , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/fisiopatologia , Análise Mutacional de DNA , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Entrevista Psiquiátrica Padronizada , Doenças Mitocondriais/fisiopatologia , Neurônios/fisiologia , Oligopeptídeos/genética , Células PC12 , Nexinas de Proteases , Ratos , Receptores de Superfície Celular/genética , Fatores de Risco , Sinapses/fisiologia
16.
Cell Death Differ ; 14(3): 568-75, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17024227

RESUMO

We studied monocytic differentiation of primary mouse progenitor cells to understand molecular mechanisms of differentiation. We found a tightly controlled non-apoptotic activation of caspase-3 that correlated with differentiation. Although caspase activity was already detected during monocytic differentiation, a caspase-3 target has not been identified yet. We show that hematopoietic progenitor kinase 1 (HPK1) is processed towards its N- and C-terminal fragments during monocytic differentiation. While HPK1 is an immunoreceptor-proximal kinase in T and B cells, its role in myeloid cells is elusive. Here, we show that the N-terminal cleavage product, HPK1-N, comprising the kinase domain, confers progenitor cell survival independent of the growth factor IL-3. Furthermore, HPK1-N causes differentiation of progenitor cells towards the monocytic lineage. In contrast to full-length kinase, HPK1-N is constitutively active causing sustained JNK activation, Bad phosphorylation and survival. Blocking of caspase activity during differentiation of primary mouse progenitor cells leads to reduced HPK1-N levels, suppressed JNK activity and attenuated monocytic differentiation. Our work explains growth factor-independent survival during monocytic differentiation by caspase-mediated processing of HPK1 towards HPK1-N.


Assuntos
Interleucina-3/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Monócitos/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Animais , Apoptose , Caspase 3/metabolismo , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Camundongos , Monócitos/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Células-Tronco/fisiologia , Transfecção , Proteína de Morte Celular Associada a bcl/metabolismo
17.
J Neural Transm (Vienna) ; 113(11): 1753-61, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16736246

RESUMO

The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo epsilon 4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD. In the present study, we investigated whether abnormalities in apoptosis and caspase-3 activity can be found at the level of lymphocytes and a T cell subtype, CD4 T cells, from AD patients compared to aged sex- and ApoE genotype-matched non-demented controls. Under different experimental conditions (at baseline or after in vitro incubation in the presence of proapoptotic stimuli) increased levels of apoptosis and enhanced caspase-3 activity were detected in lymphocytes from AD patients. This difference was most pronounced in the CD4(+) T cell subtype. Notably, we found a significant increase of apoptotic cells and caspase-3 activity in lymphocytes from AD patients bearing one or two alleles of the ApoE4 compared to non-E4 carriers. Again, these effects were strongest in CD4(+) T cells. Circulating amyloid-beta (A beta) levels did not differ between AD patients bearing ApoE4 and non-ApoE4 and age-matched controls. Therefore, it is likely that circulating A beta is not responsible for the observed effects, which might rather reflect an ongoing systemic response in AD, e.g. an increase in CD95 expression.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Apoptose/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Caspase 3/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/sangue , Linfócitos T CD4-Positivos/patologia , Ativação Enzimática/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Reação em Cadeia da Polimerase , Fatores de Risco , Receptor fas/metabolismo
18.
J Bone Joint Surg Br ; 88(5): 614-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16645106

RESUMO

The treatment of osteochondral lesions of the talus has evolved with the development of improved imaging and arthroscopic techniques. However, the outcome of treatment for large cystic type-V lesions is poor, using conventional grafting, debridement or microfracture techniques. This retrospective study examined the outcomes of 50 patients with a cystic talar defect who were treated with arthroscopically harvested, cored osteochondral graft taken from the ipsilateral knee. Of the 50 patients, 45 (90%) had a mean good to excellent score of 80.3 (52 to 90) in the Karlsson-Peterson Ankle Score, at a mean follow-up of 36 months (24 to 83). A malleolar osteotomy for exposure was needed in 26 patients and there were no malleolar mal- or nonunions. One patient had symptoms at the donor site three months after surgery; these resolved after arthroscopic release of scar tissue. This technique is demanding with or without a malleolar osteotomy, but if properly performed has a high likelihood of success.


Assuntos
Transplante Ósseo/métodos , Osteocondrite/cirurgia , Tálus/cirurgia , Adolescente , Adulto , Traumatismos do Tornozelo/complicações , Traumatismos do Tornozelo/fisiopatologia , Artroscopia/métodos , Cistos Ósseos/etiologia , Cistos Ósseos/fisiopatologia , Cistos Ósseos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocondrite/etiologia , Osteocondrite/fisiopatologia , Osteotomia/métodos , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
19.
Arch Surg ; 136(12): 1353-8, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11735858

RESUMO

Management of chronic pancreatitis is mainly palliative. Most patients with chronic pancreatitis require surgical evaluation and intervention when there is suspicion of pancreatic malignancy, evidence of intractable pain, or development of pancreatitis-related local complications. The ideal operation for chronic pancreatitis, therefore, should be designed to exclude the existence of malignancy, provide long-lasting pain relief, and correct the local complications. It should be as simple and safe as possible and should preserve the remaining endocrine and exocrine functions of the pancreas.


Assuntos
Cuidados Paliativos/métodos , Pâncreas/cirurgia , Pancreaticojejunostomia , Pancreatite/cirurgia , Anastomose em-Y de Roux , Doença Crônica , Humanos , Pancreatectomia , Ductos Pancreáticos/anatomia & histologia , Ductos Pancreáticos/cirurgia
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