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1.
N Z Vet J ; 70(6): 340-348, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35968551

RESUMO

CASE HISTORY: A 3-year-old, intact female mixed-breed dog, weighing 7 kg, was presented with generalised swelling of the tongue, leading to impaired deglutition and episodes of dyspnoea. From the age of 2 years, the dog had been under immunosuppressive therapy due to atopic dermatitis. CLINICAL FINDINGS AND TREATMENT: Multiple nodular lesions at the apex of the tongue were noted as well as mandibular and retropharyngeal lymph node enlargement. Serum biochemistry results showed inflammatory changes. The results of several biopsies taken over 7 months indicated persistent pyogranulomatous and necrotising glossitis despite ongoing antimicrobial treatment, first with amoxicillin/clavulanic acid and then pradofloxacin. No foreign material, acid-fast bacteria or fungal hyphae were detected throughout. The final diagnosis of Mycobacterium avium subsp. hominissuis (Mah) was reached after PCR and bacterial culture were carried out on the third biopsy sample. Therapy was initiated with rifampicin, clarithromycin and doxycycline, leading to complete remission of the lesions. DIAGNOSIS: Severe chronic pyogranulomatous and necrotising glossitis associated with infection by Mah. CLINICAL RELEVANCE: This report describes challenges in the diagnosis and therapy of a localised Mah infection in an iatrogenically immunocompromised dog. Successful treatment was only achieved with a specific combination of antibiotics administered long-term. ABBREVIATIONS: AF: Acid-fast; ALP: Alkaline phosphatase; CT: Computed tomography; MAC: Mycobacterium avium complex; Mah: Mycobacterium avium subsp. hominissuis.


Assuntos
Doenças do Cão , Glossite , Fosfatase Alcalina , Amoxicilina , Animais , Antibacterianos , Claritromicina , Ácido Clavulânico , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Cães , Doxiciclina , Feminino , Glossite/diagnóstico , Glossite/tratamento farmacológico , Glossite/veterinária , Imunomodulação , Mycobacterium , Mycobacterium avium , Rifampina
2.
Neuroscience ; 481: 111-122, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34856352

RESUMO

Fragmentation of the daily sleep-wake rhythm with increased nighttime awakenings and more daytime naps is correlated with the risk of development of Alzheimer's disease (AD). To explore whether a causal relationship underlies this correlation, the present study tested the hypothesis that chronic fragmentation of the daily sleep-wake rhythm stimulates brain amyloid-beta (Aß) levels and neuroinflammation in the 3xTg-AD mouse model of AD. Female 3xTg-AD mice were allowed to sleep undisturbed or were subjected to chronic sleep fragmentation consisting of four daily sessions of enforced wakefulness (one hour each) evenly distributed during the light phase, five days a week for four weeks. Piezoelectric sleep recording revealed that sleep fragmentation altered the daily sleep-wake rhythm to resemble the pattern observed in AD. Levels of amyloid-beta (Aß40 and Aß42) determined by ELISA were higher in hippocampal tissue collected from sleep-fragmented mice than from undisturbed controls. In contrast, hippocampal levels of tau and phospho-tau differed minimally between sleep fragmented and undisturbed control mice. Sleep fragmentation also stimulated neuroinflammation as shown by increased expression of markers of microglial activation and proinflammatory cytokines measured by q-RT-PCR analysis of hippocampal samples. No significant effects of sleep fragmentation on Aß, tau, or neuroinflammation were observed in the cerebral cortex. These studies support the concept that improving sleep consolidation in individuals at risk for AD may be beneficial for slowing the onset or progression of this devastating neurodegenerative disease.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Transgênicos , Doenças Neuroinflamatórias , Sono , Proteínas tau/metabolismo
3.
Internist (Berl) ; 60(4): 331-338, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30820589

RESUMO

Improved outpatient care of heart failure patients is considered crucial to avoiding unplanned cardiovascular hospitalizations and reducing mortality. Making up for regional and rural differences in heart failure care poses a further challenge. Telemedical care as a supplement to outpatient point-of-care medicine by the general practitioner and medical specialist is considered relevant to implementing this goal. This article presents the technical and organizational basics of telemedical methods in outpatient heart failure care. Current evidence on the efficacy of telemedical co-management is also explained based on the results from the nine most important randomized studies on telemedicine in heart failure. Particular attention is paid to the TIM-HF2 study published in 2018, which showed the superiority of telemedical co-management in terms of mortality and morbidity following recent hospitalization for heart failure. Pre-stratified subgroup analysis revealed no significant interactions in terms of the primary endpoint between urban and rural regions. Scalability is required in order to translate the telemedical study concept from TIM-HF2 to a nationwide care program for all patients in Germany. Telemed5000 is the first project to set its goal as the development of a telemedicine center for the telemedical co-management of up to 5000 patients using artificial intelligence. It is being funded by the Federal Ministry of Economics and Technology for the period 2019-2022.


Assuntos
Assistência Ambulatorial/métodos , Insuficiência Cardíaca/terapia , Monitorização Ambulatorial , Telemedicina , Alemanha , Humanos
4.
Vet J ; 236: 1-3, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29871741

RESUMO

Felid herpesvirus-1 (FeHV-1) and feline calicivirus (FCV) are the most important infectious causes of respiratory disease in cats. FeHV-1 and FCV co-infections are common in cats with upper respiratory tract disease, but it is unknown whether such co-infections also occur in cats with pneumonia. This study examined the lungs of naturally infected cats with FeHV-1 pneumonia for FCV co-infection by histopathology and immunohistochemistry. The frequency of FCV (13/21, 62%) in this group of cats suggests that co-infection is common in kittens with FeHV-1 pneumonia. FCV infected macrophages were often found in the lumen of FeHV-1 affected airways. In 8/13 (62%) cats, typical FCV lesions were distant from changes induced by FeHV-1. FCV infection of type II pneumocytes/alveolar macrophages was apparent in histologically unaltered areas. It is likely that damage to airways induced by FeHV-1 facilitates secondary infection with FCV due to reduced mucociliary clearance and impaired immune defences.


Assuntos
Infecções por Caliciviridae/veterinária , Doenças do Gato/virologia , Pneumonia Viral/veterinária , Animais , Animais Recém-Nascidos , Infecções por Caliciviridae/complicações , Infecções por Caliciviridae/patologia , Calicivirus Felino , Doenças do Gato/patologia , Gatos , Coinfecção , Feminino , Herpesviridae , Imuno-Histoquímica/veterinária , Pneumonia Viral/complicações , Pneumonia Viral/patologia
5.
Curr Protein Pept Sci ; 19(9): 900-908, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28745221

RESUMO

Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.


Assuntos
Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/prevenção & controle , Vacinas/uso terapêutico , Autoimunidade , Coreia/etiologia , Coreia/imunologia , Coreia/metabolismo , Coreia/prevenção & controle , Citocinas/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Mimetismo Molecular , Febre Reumática/etiologia , Febre Reumática/imunologia , Febre Reumática/metabolismo , Febre Reumática/prevenção & controle , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/imunologia , Streptococcus pyogenes
6.
Mol Genet Metab ; 120(3): 269-277, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28024876

RESUMO

Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form observed in both cases. The deletion follows recessive inheritance since the dam and a healthy male littermate of Case 1 were tested as heterozygous carriers. This is the first detailed description of CLN8 gene associated NCL in Alpenländische Dachsbracke dogs and thus provides a novel canine CLN8 model for this lysosomal storage disease. The presence of ceroid lipofuscin in extracerebral tissues may help to confirm the diagnosis of NCL in vivo, especially in new dog breeds where the underlying mutation is not known.


Assuntos
Doenças do Cão/diagnóstico por imagem , Doenças do Cão/genética , Deleção de Genes , Proteínas de Membrana/genética , Lipofuscinoses Ceroides Neuronais/veterinária , Animais , Autopsia , Doenças do Cão/patologia , Cães , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/veterinária , Imageamento por Ressonância Magnética , Masculino , Lipofuscinoses Ceroides Neuronais/diagnóstico por imagem , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/patologia , Análise de Sequência de DNA/métodos
7.
Artigo em Alemão | MEDLINE | ID: mdl-26830386

RESUMO

OBJECTIVE: The aim of this study was to investigate the role of the poultry red mite (Dermanyssus [D.] gallinae) in the horizontal transmission of avian influenza A virus (AIV) to chickens. This mite is the most common ectoparasite in poultry worldwide, and may play a role in the spread of infectious agents including AIV. Currently, the control of mites is difficult due to frequently developed resistance to many acaricides, their nocturnality and their ability to survive hidden without feeding for months. MATERIALS AND METHODS: D. gallinae were collected in a commercial layer farm and housed in self-made fibreboard boxes. SPF chickens were intravenously infected with AIV strain A/turkey/Ontario/7732/1966 (H5N9). The viraemia in chickens was monitored and at an appropriate time point about 1000 mites were allowed to suck on the AIV infected chickens. Re-isolation of the virus from blood-filled mites was tried daily for 14 days using chicken embryo fibroblast cultures and embryonated chicken eggs. Subsequently, the virus containing mites were placed into boxes that contained naïve SPF chickens to enable virus transmission from mites to chickens. Possible transmission to the chickens was examined using clinical signs, serology, gross lesions, histopathology and immunohistochemistry. RESULTS: Chickens developed a dose-dependent viraemia one day after infection, therefore this day was chosen for the bloodmeal of the mites. AIV was detected in mites after bloodsucking on AIV-infected chickens over a 10-day period. Naïve SPF chickens were infected during bloodsucking of AIV carrying mites. AIV isolates in mites and in chickens were undistinguishable from the original AIV inoculum by RT-PCR. CONCLUSIONS: D. gallinae ingested AIV during bloodmeals on AIV infected chickens and are able to transmit AIV to SPF chickens. Therefore, mites serve as mechanical vector of AIV and may play a major role in the circulation of AIV within a facility or area although the life span of infectious virus in the mite is limited. CLINICAL RELEVANCE: The proven transmission requires more than ever a systematic control of this ectoparasite in order to maintain poultry health and productivity. The demonstrated vector function of this mite is of great significance for poultry flocks all over the world.


Assuntos
Galinhas/parasitologia , Galinhas/virologia , Vírus da Influenza A , Influenza Aviária/transmissão , Ácaros/virologia , Doenças das Aves Domésticas/transmissão , Animais , Comportamento Alimentar , Influenza Aviária/parasitologia , Influenza Aviária/virologia , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/virologia , Viremia/veterinária
8.
Neuroscience ; 315: 162-74, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26701291

RESUMO

Obesity and type 2 diabetes mellitus (T2DM) convey an increased risk for developing dementia. The microtubule-associated protein tau is implicated in neurodegenerative disease by undergoing hyperphosphorylation and aggregation, leading to cytotoxicity and neurodegeneration. Enzymes involved in the regulation of tau phosphorylation, such as GSK3ß, are tightly associated with pathways found to be dysregulated in T2DM. We have shown previously that leptin-resistant mice, which develop obesity and a diabetic phenotype, display elevated levels of tau phosphorylation. Here we show cells cultured with leptin, an adipokine shown to have neuroprotective effects, reduces tau phosphorylation. To explore how this mechanism works in vivo we transduced an existing diabetic mouse line (Lepr(db/db)) with a tau mutant (tau(P301L)) via adeno-associated virus (AAV). The resulting phenotype included a striking increase in tau phosphorylation and the number of neurofibrillary tangles (NFTs) found within the hippocampus. We conclude that leptin resistance-induced obesity and diabetes accelerates the development of tau pathology. This model of metabolic dysfunction and tauopathy provides a new system in which to explore the mechanisms underlying the ways in which leptin resistance and diabetes influence development of tau pathology, and may ultimately be related to the development of NFTs.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Hipocampo/patologia , Leptina/metabolismo , Emaranhados Neurofibrilares/patologia , Obesidade/fisiopatologia , Proteínas tau/metabolismo , Animais , Cognição/fisiologia , Dependovirus/genética , Diabetes Mellitus Experimental/patologia , Feminino , Vetores Genéticos , Células HEK293 , Hipocampo/metabolismo , Humanos , Leptina/genética , Masculino , Camundongos Transgênicos , Emaranhados Neurofibrilares/metabolismo , Obesidade/patologia , Fosforilação , Proteínas tau/genética
9.
Eur J Cancer ; 51(1): 27-36, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25459392

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumours and is still associated with a poor prognosis in advanced disease. To improve the standard therapy with gemcitabine, we initiated a prospective randomised phase-II trial with gemcitabine (GEM) versus gemcitabine plus sunitinib (SUNGEM) based on data of in vitro trials and phase-I data for the combination treatment. The rational of adding sunitinib was its putative antiangiogenic mechanism of action. METHODS: A total of 106 eligible patients with locally advanced, unresectable or metastatic PDAC without previous system therapy were randomised to receive GEM at a dosage of 1.000mg/m(2) d1, 8, 15 q28 versus a combination of SUNGEM at a dosage of GEM 1.000mg/m(2) d1+8 and sunitinib 50mg p.o. d1-14, q21d. The primary end-point was progression free survival (PFS), secondary end-points were overall survival (OS), toxicity and overall response rate (ORR). RESULTS: The confirmatory analysis of PFS was based on the intend-to-treat (ITT) population (N=106). The median PFS was 13.3 weeks (95% confidence interval (95%-CI): 10.4-18.1 weeks) for GEM and 11.6 weeks for SUNGEM (95%-CI: 7.0-18.0 weeks; p=0.78 one-sided log-rank). The ORR was 6.1% (95%-CI: 0.7-20.2%) for GEM and for 7.1% (95%-CI: 0.9-23.5%) for SUNGEM (p=0.87). The median time to progression (TTP) was 14.0 weeks (95%-CI: 12.4-22.3 weeks) for GEM and 18.0 weeks (95%-CI: 11.3-19.3 weeks) for SUNGEM (p=0.60; two-sided log-rank). The median OS was 36.7 weeks (95%-CI: 20.6-49.0 weeks) for the GEM arm and 30.4 weeks (95%-CI: 18.1-37.6 weeks) for the SUNGEM (p=0.78, one-sided log-rank). In regard to toxicities, suspected SAEs were reported in 53.7% in the GEM arm and 71.2% in the SUNGEM arm. Grade 3 and 4 neutropenia was statistically significantly higher in the SUNGEM arm with 48.1% versus 27.8% in the GEM arm (p=0.045, two sided log-rank). CONCLUSIONS: The combination SUNGEM was not sufficient superior in locally advanced or metastatic PDAC compared to GEM alone in regard to efficacy but was associated with more toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Indóis/uso terapêutico , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Europa (Continente) , Feminino , Humanos , Indóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirróis/administração & dosagem , Sunitinibe , Resultado do Tratamento , Gencitabina
10.
Mycotoxin Res ; 30(4): 241-50, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25234267

RESUMO

This study describes the association between tail necrosis in rabbits and mycotoxins in rabbit feed. Clinical cases of tail necrosis were observed in 14 out of 103 rabbits kept in an outdoor group housing, fed with hay and a commercial pelleted feed. The observed clinical symptoms, alopecia, erosions, crusts and necrosis were restricted to the tail area and exclusively occurred in young rabbits aged 113 ± 20 days. Dermatological examination suggested that ischemia had caused necrosis. Analysis of blood samples showed an elevated level of creatine kinase. No weight loss occurred in affected rabbits. Trauma caused by injuries or technopathic lesions was also excluded. Histopathologically, the lesions were characterized by acute muscle fibre degeneration and chronic active dermatitis with granulation tissue formation. Necropsy of one rabbit revealed hepatocellular degeneration and necrosis as remarkable findings. Feed analysis for ergot alkaloids by enzyme immunoassays yielded a mean and maximum ergot alkaloid content of 410 ± 250 µg/kg and 1,700 µg/kg, respectively. Faeces of affected rabbits contained ergot alkaloids at levels up to 200 µg/kg. The mean and maximum dietary intake of total ergot alkaloids were 17 and 71 µg/kg bodyweight, respectively. Fusarium toxins (trichothecenes, zearalenone, fumonisins) were also found in the feed, but at levels which did not explain the observed effects. The results indicate that ergot alkaloids may have been the cause of tail necrosis, which is supported by literature data showing that rabbits are especially sensitive towards these toxins.


Assuntos
Dieta/métodos , Alcaloides de Claviceps/toxicidade , Necrose/patologia , Cauda/patologia , Ração Animal , Animais , Alcaloides de Claviceps/análise , Fezes/química , Feminino , Análise de Alimentos , Histocitoquímica , Fígado/patologia , Masculino , Músculos/patologia , Necrose/etiologia , Coelhos , Pele/patologia
11.
Vet J ; 201(2): 156-65, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24857252

RESUMO

Feline calicivirus (FCV) is a pathogen of felids and one of the most common causative agents of feline upper respiratory disease (URD). Reports of natural FCV pneumonia in the course of respiratory tract infections are sparse. Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only from experimental studies. The aim of the present study was to assess the type and extent of pulmonary involvement in natural respiratory FCV infections of domestic cats and to identify the viral target cells in the lung. For this purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV and relevant cell markers were performed on diagnostic post-mortem specimens collected after fatal URD, virulent systemic FCV or other conditions. All groups of cats exhibited similar acute pathological changes, dominated by multifocal desquamation of activated alveolar macrophages (AM) and occasional type II pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD). In fatal cases, this was generally seen without evidence of epithelial regeneration. In cats without clinical respiratory signs, type II pneumocyte hyperplasia was present alongside the other changes, consistent with the post-damage proliferative phase of DAD. FCV infected and replicated in AM and, to a lesser extent, type II pneumocytes. This study shows that lung involvement is an infrequent but important feature of FCV-induced URD. AM are the main viral target cell and pulmonary replication site, and their infection is associated with desquamation and activation, as well as death via apoptosis.


Assuntos
Infecções por Caliciviridae/veterinária , Calicivirus Felino/fisiologia , Doenças do Gato/virologia , Macrófagos Alveolares/virologia , Infecções Respiratórias/veterinária , Animais , Infecções por Caliciviridae/virologia , Calicivirus Felino/isolamento & purificação , Gatos , Feminino , Imuno-Histoquímica/veterinária , Hibridização In Situ/veterinária , Masculino , Reação em Cadeia da Polimerase/veterinária , RNA Viral/análise , Infecções Respiratórias/virologia , Virulência
13.
Artigo em Alemão | MEDLINE | ID: mdl-23990013

RESUMO

Against the background of considerable population ageing processes in rural areas, it is expected that access to the health care system in these regions will deteriorate. Within this context, the question arises as to whether elderly people have the ability to overcome increasing distances in order to receive adequate medical care. Hence the objective of this study is an in-depth analysis of the everyday mobility of elderly people living in rural areas. The empirical analysis is based on the German National Travel Survey "Mobilität in Deutschland 2008". Findings show that older women in particular experience limitations in their mobility options. Only 63% of mobility-impaired women (aged > 75 years) were mobile outside their homes, and only 37% had access to a car, which can be regarded as the crucial factor for being mobile. It follows that older and mobility-impaired women have to cope with everyday life under difficult conditions. In the context of the growing problem of access to the health care system in rural areas, the challenge is to ensure adequate primary health care for a large proportion of the immobile elderly.


Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/tendências , Limitação da Mobilidade , Saúde da População Rural/estatística & dados numéricos , Saúde da População Rural/tendências , População Rural/estatística & dados numéricos , População Rural/tendências , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Distribuição por Sexo , Viagem/estatística & dados numéricos , Viagem/tendências
14.
Horm Metab Res ; 45(11): 827-33, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23794400

RESUMO

In the last years, mainly 2 high-intensity-training (HIT) protocols became common: first, a Wingate-based "all-out" protocol and second, a 4×4 min protocol. However, no direct comparison between these protocols exists, and also a comparison with high-volume-training (HVT) is missing. Therefore, the aim of the present study was to compare these 3 endurance training protocols on metabolic, hormonal, and psychological responses. Twelve subjects performed: 1) HVT [130 min at 55% peak power output (PPO)]; 2) 4×4 min at 95% PPO; 3) 4×30 s all-out. Human growth hormone (hGH), testosterone, and cortisol were determined before (pre) and 0', 30', 60', 180' after each intervention. Metabolic stimuli and perturbations were characterized by lactate, blood gas (pH, BE, HCO3⁻, pO2, PCO2), and spirometric analysis. Furthermore, changes of the person's perceived physical state were determined. The 4×30 s training caused the highest increases in cortisol and hGH, followed by 4 × 4 min and HVT. Testosterone levels were significantly increased by all 3 exercise protocols. Metabolic stress was highest during and after 4×30 s, followed by 4×4 min and HVT. The 4×30 s training was also the most demanding intervention from an athlete's point of view. In conclusion, the results suggest that 4×30 s and 4×4 min promote anabolic processes more than HVT, due to higher increases of hGH, testosterone, and the T/C ratio. It can be speculated that the acute hormonal increase and the metabolic perturbations might play a positive role in optimizing training adaptation and in eliciting health benefits as it has been shown by previous long term training studies using similar exercise protocols.


Assuntos
Exercício Físico/fisiologia , Exercício Físico/psicologia , Hormônios/sangue , Metabolismo/fisiologia , Resistência Física/fisiologia , Adulto , Gasometria , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Lactatos/sangue , Motivação , Consumo de Oxigênio , Testosterona/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-23608891

RESUMO

Neurological cases, especially in foals, are rare in the daily practical work. The most common causes are traumata and infectious diseases of the central nervous system (CNS). This case report provides further insights into the wide spectrum of possible neuropathological lesions by detailing a complex malformation with unilateral neurological signs that occurred later post natum. Thus, clinicians should also be aware of malformations in case of respective neurological patients. A Hanoverian foal was presented with progressive ataxia. General and blood examination revealed no further alterations. By neurologic examination, a unilateral hypermetria was diagnosed and a cysternography of the head was performed. A cerebellar malformation was assumed and the foal was euthanized due to poor prognosis. At necropsy, a unilateral absence of a cerebellar hemisphere and vermis accompanied by contralateral malformation of the mesencephalon was diagnosed. The missing areas of the right cerebellar hemisphere were replaced by a cystic formation. The left part of the mesencephalic lamina quadrigemina was reduced in size and the corpus callosum was hypoplastic. Additional microscopical findings were most obvious near the cyst formation and included angiofibrosis in remaining cerebellar and mesencephalic parenchyma and leptomeninges, heterotopia of cerebellar neurons, sclerosis in cerebellar cortex, focal proliferation of meningeal cells and mild mononuclear perivascular infiltrates. Occassional irregular neuronal arrangement in the mesencephalon was also present. Infectious agents such as Borna disease virus, rabies virus, and equine herpesvirus were not detected. Therefore, the complex malformation in this foal might have been caused by a destructive, possibly ischemic event, or could represent a sequel of a primary retrocerebellar cyst with accompanying compression of adjacent parenchyma.


Assuntos
Ataxia Cerebelar/veterinária , Cerebelo/anormalidades , Doenças dos Cavalos/diagnóstico , Mesencéfalo/anormalidades , Malformações do Sistema Nervoso/veterinária , Animais , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/patologia , Cerebelo/patologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/patologia , Evolução Fatal , Doenças dos Cavalos/fisiopatologia , Cavalos , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/patologia
16.
J Cell Sci ; 126(Pt 12): 2571-6, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23591813

RESUMO

In Drosophila, Insulin-like peptide 2 (Dilp-2) is expressed by insulin-producing cells in the brain, and is secreted into the hemolymph to activate insulin signaling systemically. Within the brain, however, a more local activation of insulin signaling may be required to couple behavioral and physiological traits to nutritional inputs. We show that a small subset of neurons in the larval brain has high Dilp-2-mediated insulin signaling activity. This local insulin signaling activation is accompanied by selective Dilp-2 uptake and depends on the expression of the Imaginal morphogenesis protein-late 2 (Imp-L2) in the target neurons. We suggest that Imp-L2 acts as a licensing factor for neuronal IIS activation through Dilp-2 to further increase the precision of insulin activity in the brain.


Assuntos
Encéfalo/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Insulina/metabolismo , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Drosophila , Larva/metabolismo , Morfogênese/fisiologia , Ligação Proteica
17.
Perfusion ; 28(2): 114-24, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23257678

RESUMO

This paper reviews the basic fluid dynamics underlying extracorporeal membrane oxygenation (ECMO) cannula design. General cannula features and their effect on flow are discussed and the specific requirements of different ECMO circuits are explained. The current commercially available cannula options for veno-arterial and veno-venous circuits are reviewed and the main characteristics presented.


Assuntos
Catéteres , Oxigenação por Membrana Extracorpórea , Modelos Cardiovasculares , Humanos
18.
Vet Immunol Immunopathol ; 149(3-4): 208-15, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22871576

RESUMO

Although insulin resistance (IR) has been increasingly recognized in horses, a clear understanding of its pathophysiology is lacking. The purpose of the present study was to determine the early pathologic changes in IR horses by characterizing alterations in proteins that play key roles in innate immunological responses and inflammatory pathways, and by identifying potential links with glucose transport and insulin signaling. Visceral (VIS) and subcutaneous (SC) adipose tissue and skeletal muscle (SM) biopsies were collected from horses, which were classified as insulin-sensitive (IS) or IR based on the results of an insulin-modified frequently sampled intravenous glucose tolerance test. Protein expression of Toll-like receptor 4 (TLR-4), suppressor of cytokine signaling 3 (SOCS-3) and tumor necrosis factor alpha (TNF-α) were quantified by Western blotting in VIS and SC adipose depots and SM, as well as insulin receptor substrate 1 (IRS-1). To better characterize the potential relationship between inflammation, IR and impaired glucose transport, we correlated active cell surface glucose transporter 4 (GLUT-4) content (measured by a cell surface biotinylated assay) with individual- and tissue-specific data related to inflammation. IR was associated with a significantly increased expression of TLR-4 and SOCS-3 in SM and VIS tissue, without a significant change in SC site. We also observed a significant increase in TNF-α in VIS, but not in SC, tissue of IR vs. IS horses. There was no difference in total content or serine phosphorylation of IRS-1 for any sampling site in IR compared to IS horses. We further observed a significant positive correlation between TLR-4 content and SOCS-3, as well as a significant negative correlation between SOCS-3 content and GLUT-4 trafficking. Taken together, the data suggested a pro-inflammatory state in SM and VIS, but not SC, adipose depot during compensated IR. In addition, SOCS-3 appears to be a novel link between inflammation and dysregulated glucose metabolism and insulin sensitivity during the early pathogenesis of insulin resistance.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/metabolismo , Inflamação/metabolismo , Resistência à Insulina/imunologia , Animais , Transporte Biológico , Biópsia/veterinária , Feminino , Teste de Tolerância a Glucose/veterinária , Transportador de Glucose Tipo 4/imunologia , Cavalos , Inflamação/imunologia , Proteínas Substratos do Receptor de Insulina/sangue , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Modelos Lineares , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Gordura Subcutânea/imunologia , Gordura Subcutânea/metabolismo , Proteínas Supressoras da Sinalização de Citocina/sangue , Receptor 4 Toll-Like/sangue , Fator de Necrose Tumoral alfa/sangue
19.
J Dent Res ; 91(7 Suppl): 29S-37S, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22699664

RESUMO

Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.


Assuntos
Arteriosclerose/complicações , Síndromes de Imunodeficiência/complicações , Síndrome Nefrótica/complicações , Osteocondrodisplasias/complicações , Embolia Pulmonar/complicações , Anormalidades Dentárias/etiologia , Alelos , Anodontia/etiologia , Arteriosclerose/genética , Dente Pré-Molar/anormalidades , Proteína Morfogenética Óssea 4/análise , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , DNA Helicases/análise , DNA Helicases/genética , Fibroblastos/patologia , Humanos , Síndromes de Imunodeficiência/genética , Dente Molar/anormalidades , Mutação/genética , Síndrome Nefrótica/genética , Odontogênese/genética , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária , Embolia Pulmonar/genética , Pele/citologia , Germe de Dente/patologia , Raiz Dentária/anormalidades , Dente Decíduo/anormalidades , Transcrição Gênica/genética , Fator de Crescimento Transformador beta1/análise , Proteína Wnt3A/análise
20.
J Biomed Mater Res A ; 100(8): 2034-44, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22581657

RESUMO

The aim of our study was to generate a biofunctionalized, three-dimensional (3D) biomaterial to enhance jaw periosteal cell (JPC) adhesion and differentiation into osteogenic tissue. Therefore, open-cell polylactic acid (OPLA) scaffolds were coated covalently with different RGD peptides (a conserved recognition sequence of the most ECM proteins--arginine-glycine-asparagine) and different coating variants. The linear and cyclic RGD peptides were either applied directly or indirectly via a poly-L-lysine (PLL) spacer. JPCs were analyzed on coated constructs in 2D and 3D cultures and showed enhanced rates for indirectly coated scaffolds using the PLL spacer. By gene expression, we detected significantly increased levels of osteogenic marker genes, such as alkaline phosphatase, RUNX2, and AMELY in JPCs seeded onto PLL/linear RGD constructs compared to the otherwise-coated constructs. An analysis of the JPC mineralization capacity revealed the highest amounts of calcium-phosphate precipitates in cells growing within the PLL/linear scaffolds. Additionally, the JPC adhesion behavior on OPLA scaffolds seems to be mediated by ITGB3, ITGB1, and ITGAV, as shown by blocking assays. We concluded that coating of OPLA constructs with linear RGD peptides via PLL represents a suitable approach for functionalizing the polymer surface and enhancing adhesion, proliferation, and mineralization of JPCs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Arcada Osseodentária/citologia , Oligopeptídeos/farmacologia , Osteogênese/efeitos dos fármacos , Periósteo/citologia , Polilisina/farmacologia , Biomarcadores/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Calcificação Fisiológica/genética , Adesão Celular/efeitos dos fármacos , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Imobilizadas/farmacologia , Integrinas/metabolismo , Ácido Láctico/farmacologia , Osteogênese/genética , Poliésteres , Polímeros/farmacologia , Alicerces Teciduais/química
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