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1.
BMC Vet Res ; 20(1): 181, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715073

RESUMO

BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.


Assuntos
Doenças das Cabras , Cabras , Leiomioma , Receptores de Progesterona , Neoplasias Vaginais , Animais , Feminino , Leiomioma/veterinária , Leiomioma/patologia , Leiomioma/cirurgia , Neoplasias Vaginais/veterinária , Neoplasias Vaginais/patologia , Receptores de Progesterona/metabolismo , Doenças das Cabras/patologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-37956668

RESUMO

A 50-year-old female Hermann's tortoise (Testudo hermannii boettgeri) was presented with anorexia and lethargy. Clinical examination revealed multiple, visually inconspicuous but indentable areas in the shell corresponding to osteolysis radiographically. Soft tissue nodules and osteolytic lesions were also noted in the limbs. Laboratory results revealed elevated aspartate aminotransferase activity and uric acid concentrations, hypoglycemia, and hyperphosphatemia. Klebsiella oxytoca was isolated from a biopsied scutal area, and the biopsy suggested neoplasia. After a short period of clinical improvement, the animal's condition deteriorated, and it died. Post mortem computed tomography revealed polyostotic lytic lesions of multiple bones and the shell with associated soft tissue nodules protruding into the coelom, and nodular lung lesions. Necropsy, histopathology, and immunohistochemistry secured a diagnosis of a poorly differentiated, pan-cytokeratin-positive squamous cell carcinoma with widespread soft tissue and bone metastases, osteolysis and desmoplasia.


Assuntos
Carcinoma de Células Escamosas , Osteólise , Tartarugas , Feminino , Animais , Osteólise/veterinária , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/veterinária
3.
J Behav Med ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017252

RESUMO

Individuals with cancer are recommended to engage in regular physical activity (PA) even during cancer therapy. The aim of this study was to explore how patient-reported physician PA counseling influences their PA intention and behavior in addition to psycho-cognitive determinants derived from the theory of planned behavior (TPB). A longitudinal study during cancer treatment was conducted among N = 115 patients with breast, prostate, or colorectal cancer (Mage = 58.0, SD = 11.5; 55.7% female). The median time since diagnosis was 2 months, and 19.1% were diagnosed with metastases. Participants provided information on PA counseling by their physicians and on psycho-cognitive variables of the TPB at three measurement points. Additionally, they wore accelerometers for seven days at baseline and three months later. Nearly half of participants (48%) reported basic PA counseling and 30% reported in-depth PA counseling. Patients in poorer health and with lower education reported significantly less in-depth counseling. In addition to patient self-efficacy in performing PA, only in-depth physician PA counseling, but not basic physician counseling, predicted intention for PA four weeks later. Patients' PA three months after baseline was predicted by patients' PA at baseline and their intention for PA. Overall, the PA level at baseline was identified as the most important predictor of PA three months later. Nevertheless, physicians seem to have the ability to increase their cancer patients' intention for PA by in-depth counseling.

4.
Qual Res Med Healthc ; 7(1): 10902, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37441128

RESUMO

Medicine in South Africa (SA), as in other parts of the world, is becoming an increasingly gender diverse profession, yet orthopaedic surgery continues to be dominated by men, with women constituting approximately 5% of the profession in SA. The aim of this descriptive qualitative study was to explore women's experiences of training and working as orthopaedic surgeons in SA and identify structures, practices, attitudes, and ideologies that may promote or impede the inclusion of women. Data were collected via focus group discussions with women orthopaedic surgeons (n=16). Grounded in phenomenology, data were analysed using thematic analysis following a data-driven inductive approach to making sense of participants' experiences. Five main themes emerged: i) dynamic working environments and the work of transformation; ii) negotiating competing roles of mother and surgeon; iii) belonging, exclusion and internalised sexism; iv) gaslighting and silencing; and v) acts of resistance - agency and pushing back. The findings highlight the dynamic process in which both men and women contribute to co-creating, re-producing, and challenging practices that make medicine more inclusive.

5.
Ann Clin Transl Neurol ; 8(8): 1680-1694, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34278743

RESUMO

OBJECTIVE: Traditional posturography measurements characterize postural instability in patients with chemotherapy-induced peripheral neuropathy (CIPN), while underlying postural control mechanisms remain unclear. Taking a model-based approach can yield insights into these mechanisms. This study's aim was to characterize the modifications in postural control of CIPN patients associated with exercise in relation to the postural behavior of healthy control participants (hCON) via an exploratory approach. METHODS: Thirty-one CIPN patients were randomly assigned to two interventions (balance plus moderate endurance training vs. moderate endurance training only) and exercised twice per week over 12 weeks. Baseline data were compared to 36 matched hCONs. We recorded spontaneous sway and postural reactions to platform tilts using Optotrak and a Kistler force platform pre- and post-intervention. Data interpretation relied on a model-based parameter identification procedure. RESULTS: Spontaneous sway amplitudes were larger and postural reactions smaller, with a relative phase advance, in our pre-intervention patients than the hCONs. Post-intervention, spontaneous sway, and postural reactions were reduced and the sensory-motor ratio larger in both groups, while the postural reaction timing differed between groups. INTERPRETATION: The abnormally small postural reactions in CIPN patients before the intervention can be interpreted as the consequence of abnormally strong velocity control-a strategy modification that may serve as a prediction mechanism to compensate for the lack of timely and accurate proprioceptive signals. While both groups reduced postural sway and showed an adapted sensory-motor ratio post-intervention, the interventions seemed to trigger different velocity control strategies. This study emphasizes the need for taking a more differentiated perspective on intervention effects. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00005419, prospectively registered on November 19, 2013.


Assuntos
Antineoplásicos/efeitos adversos , Terapia por Exercício , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/reabilitação , Equilíbrio Postural/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde
6.
Br J Cancer ; 125(7): 955-965, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34226683

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, unpleasant and usually long-lasting side effect of neurotoxic chemotherapeutic agents. This study aimed to investigate the preventive potential of sensorimotor- (SMT) and resistance training (RT) on CIPN. METHODS: Patients (N = 170) were randomised to SMT, RT or usual care (UC). Both exercise groups trained 3×/week for a total of 105 min/week during neurotoxic chemotherapy (mean length: 20 weeks). Before and 3 weeks after neurotoxic chemotherapy, CIPN signs/symptoms were assessed via Total Neuropathy Score (TNSr; primary endpoint) and EORTC QLQ-CIPN15 questionnaire. In addition, balance (centre of pressure), muscle strength (isokinetic), quality of life (QoL, EORTC QLQ-C30) and relative chemotherapy dose intensity (RDI) were investigated. The follow-up period covered 6 months after the end of chemotherapy. RESULTS: Intention-to-treat analyses (N = 159) revealed no differences regarding CIPN signs/symptoms. Exploratory per-protocol analyses (minimum training attendance rate 67%; N = 89) indicated that subjectively perceived sensory symptoms in the feet increased less during chemotherapy in the adherent exercisers (pooled group: SMT+RT) than in the UC group (-8.3 points (-16.1 to -0.4); P = 0.039, ES = 1.27). Furthermore, adherent exercisers received a higher RDI (96.6 ± 4.8 vs. 92.2 ± 9.4; P = 0.045), showed a better course of muscular strength (+20.8 Nm (11.2-30.4); P < 0.001, ES = 0.57) and QoL (+12.9 points (3.9-21.8); P = 0.005, ES = 0.64). During follow-up, CIPN signs/symptoms persisted in all groups. CONCLUSIONS: This study demonstrates that SMT and/or RT alleviate subjectively perceived sensory CIPN symptoms in the feet and other clinically relevant cancer therapy-related outcomes, if an appropriate training stimulus is achieved. CLINICAL TRIAL REGISTRATION: NCT02871284.


Assuntos
Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/prevenção & controle , Treinamento Resistido/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Modalidades de Fisioterapia/psicologia , Qualidade de Vida/psicologia , Resultado do Tratamento
7.
Materials (Basel) ; 14(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430323

RESUMO

Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.

8.
Sci Rep ; 11(1): 2398, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504885

RESUMO

Impaired postural control is often observed in response to neurotoxic chemotherapy. However, potential explanatory factors other than chemotherapy-induced peripheral neuropathy (CIPN) have not been adequately considered to date due to primarily cross-sectional study designs. Our objective was to comprehensively analyze postural control during and after neurotoxic chemotherapy, and to identify potential CIPN-independent predictors for its impairment. Postural control and CIPN symptoms (EORTC QLQ-CIPN20) were longitudinally assessed before, during and three weeks after neurotoxic chemotherapy, and in three and six months follow-up examinations (N = 54). The influence of peripheral nerve function as determined by nerve conduction studies (NCS: compound motor action potentials (CMAP) and sensory action potentials (SNAP)), physical activity, and muscle strength on the change in postural control during and after chemotherapy was analyzed by multiple linear regression adjusted for age and body mass index. Postural control, CIPN signs/symptoms, and CMAP/SNAP amplitudes significantly deteriorated during chemotherapy (p < .01). During follow-up, patients recovered from postural instabilities (p < .01), whereas CIPN signs/symptoms and pathologic NCS findings persisted compared to baseline (p < .001). The regression model showed that low CMAP and high SNAP amplitudes at baseline predicted impairment of postural control during but not after chemotherapy. Hence, pre-therapeutically disturbed somatosensory inputs may induce adaptive processes that have compensatory effects and allow recovery of postural control while CIPN signs/symptoms and pathologic peripheral nerve function persist. Baseline NCS findings in cancer patients who receive neurotoxic chemotherapy thus might assist in delineating individual CIPN risk profiles more precisely to which specific exercise intervention programs could be tailor-made.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Suscetibilidade a Doenças , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Equilíbrio Postural , Fatores de Risco , Avaliação de Sintomas
9.
Support Care Cancer ; 29(2): 1015-1023, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32556623

RESUMO

PURPOSE: To characterize sleep problems and to compare subjective and objective assessments in breast cancer patients starting neoadjuvant chemotherapy. METHODS: Sleep characteristics of 54 breast cancer patients starting neoadjuvant chemotherapy were analyzed. Subjective sleep characteristics were assessed with the Pittsburgh Sleep Quality Index (PSQI) and objective sleep measurements with an accelerometer (ActiGraph wGT3X-BT) worn on the wrist for 7 consecutive days. RESULTS: According to the common PSQI cut-off of 8, 10 (18.87%) of the patients were poor sleepers. ActiGraph measures did not mirror this classification as values for poor, and good sleepers did not differ significantly. Overall, Bland-Altman plots illustrated higher ActiGraph values for sleep efficiency and effective sleep time and lower values for sleep latency, compared with PSQI. For total sleep time, less disagreement between both measures was observed. Actigraphy was limited in precise identification of sleep begin and sleep latency but provided supplementary information about number and minutes of awakenings during the night. CONCLUSION: Subjective and objective measurement methods differed substantially in various parameters, with limitations in both methods. A combination of both methods might be most promising. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02999074.


Assuntos
Actigrafia/métodos , Neoplasias da Mama/complicações , Terapia Neoadjuvante/métodos , Polissonografia/métodos , Transtornos do Sono-Vigília/etiologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Autorrelato
10.
Gait Posture ; 77: 156-163, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32036320

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect deriving from neurotoxic chemotherapeutic agents. The underlying nerve injury can affect proprioception causing impaired postural control, gait difficulties and a higher risk of falling. Overall, the symptoms and functional limitations negatively affect patients' independence and quality of life. RESEARCH QUESTION: Our objective was to analyze postural control in cancer patients before and after neurotoxic chemotherapy and to compare these data to healthy controls. METHODS: Participants were 35 cancer patients (PAT) and 35 healthy, one-to-one gender, age, height, and weight matched controls (HMC). Postural control of HMC was tested once, whereas PAT were tested prior to (PATpre) and three weeks after completion of neurotoxic chemotherapy (PATpost). Temporal, spatial and frequency domain measures of the center of pressure (COP) were calculated using a force plate. The following balance conditions were analyzed: bipedal stance with open (BPEO) and closed eyes (BPEC), semi-tandem (STEO, STEC) and monopedal stance (MPEO). CIPN was assessed clinically (Total Neuropathy Score) and via questionnaire. Time and group differences were determined by using Wilcoxon-signed-rank tests. Spearman correlation was applied to analyze associations between severity of CIPN and postural control. RESULTS: PATpost showed significantly increased temporal and spatial measures of the COP (p < .05) - both after neurotoxic chemotherapy (PATpre-PATpost) and in comparison to HMC. Withdrawal of visual control resulted in greater temporal and spatial COP displacements in PATpost than in the comparative groups (PATpre, HMC). Correlation analyzes revealed moderate associations of COP measures with clinical CIPN measures and low to none for the questionnaires. SIGNIFICANCE: Three weeks after completion of neurotoxic chemotherapy, PATpost showed significant balance deficits compared to PATpre and HMC. Especially the deficits in the standing conditions with closed eyes may indicate an impaired proprioception. This hypothesis is supported by the finding that stronger CIPN symptoms were associated with poorer postural control. However, future studies need to take further influencing factors on postural control into account (e.g. strength) in order to generate efficacious rehabilitation measures.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Equilíbrio Postural/efeitos dos fármacos , Acidentes por Quedas , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/fisiopatologia , Equilíbrio Postural/fisiologia , Propriocepção/efeitos dos fármacos , Estudos Prospectivos , Qualidade de Vida
11.
BMC Public Health ; 17(1): 843, 2017 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29065873

RESUMO

BACKGROUND: In Germany, medical care of prisoners is completely separated from extramural health care. The extent and quality of medical care among prisoners in Germany are therefore largely unknown. We performed a secondary data analysis of pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid substitution treatment (OST) delivered to prisons in 11 federal states (FS) in Germany between 01/2012 and 03/2013. The aims of this study were to assess (i) the treatment availability for the selected diseases and OST in German prisons, (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and OST during the study period. METHODS: Substances unique to or typically used for the treatment of each disease were defined as marker substances with defined daily doses (DDD). For each marker substance we assessed the cumulative number of DDD, the average daily number of DDD (DDDd) and average treatment prevalence per day in percent (adTP). Accordingly, the DDDd represents one person treated per day and the adTP means the proportion of prisoners treated per day. We compared the adTP of the diseases with previously measured prevalences. RESULTS: We obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58% for HCV and OST. Twice as many delivered marker substances for TB were indicated for the continuation phase and chemoprevention than the intensive phase. The HIV adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39% for HIV, 0.12% for HCV and 2.18% for OST. CONCLUSIONS: According to our findings treatment rates for TB were consistent with the expected TB prevalence, at least in Berlin. HIV treatment seems to be offered to an adequate proportion of estimated infected prisoners. In contrast, the HCV treatment prevalence was low. High variation among FS in provision of all treatments, particularly of OST, point to inconsistent treatment practices, although nationwide extramural treatment guidelines for Germany exist.


Assuntos
Infecções por HIV/terapia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hepatite C/terapia , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Prisioneiros , Tuberculose/terapia , Feminino , Alemanha , Humanos , Masculino , Prisioneiros/estatística & dados numéricos
12.
Dev Cell ; 23(1): 193-201, 2012 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-22814607

RESUMO

Schwann cells produce myelin sheaths and thereby permit rapid saltatory conductance in the vertebrate peripheral nervous system. Their stepwise differentiation from neural crest cells is driven by a defined set of transcription factors. How this is linked to chromatin changes is not well understood. Here we show that the glial transcription factor Sox10 functions in Schwann cells by recruiting Brg1-containing chromatin-remodeling complexes via Baf60a to regulatory regions of Oct6 and Krox20 genes. It thereby stimulates expression of these transcriptional regulators that then cooperate with Sox10 to convert immature into myelinating Schwann cells. The functional interaction between Sox10 and Brg1 is evident from gain- and loss-of-function studies, similar neuropathies in the corresponding mouse mutants, and an aggravated neuropathy in compound mutants. Our results demonstrate that the transcription factor-mediated recruitment of the chromatin-remodeling machinery to specific genomic loci is an essential driving force for Schwann cell differentiation and myelination.


Assuntos
Diferenciação Celular/fisiologia , Montagem e Desmontagem da Cromatina/fisiologia , DNA Helicases/fisiologia , Bainha de Mielina/fisiologia , Proteínas Nucleares/fisiologia , Células de Schwann/citologia , Células de Schwann/metabolismo , Fatores de Transcrição/fisiologia , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Galinhas , DNA Helicases/genética , Células HEK293 , Humanos , Camundongos , Camundongos Transgênicos , Bainha de Mielina/ultraestrutura , Proteínas Nucleares/genética , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Fatores de Transcrição SOXE/fisiologia , Fatores de Transcrição/genética
13.
Cell Transplant ; 20(10): 1589-602, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21396167

RESUMO

Cell-based approaches using mesenchymal stromal precursor cells (MSCs) for the regeneration of intervertebral discs are attracting increased interest, even though the intervertebral disc is a very demanding environment. Implanted cells eventually face acidic pH, hypoxia, and a lack of nutrients. While the regenerative potential of MSCs for skeletal tissues has been well described, it is still questionable whether human MSCs can be prepared for prolonged survival and proper functioning and whether they can differentiate under the adverse conditions encountered in the disc. Here we examined the influence of hypoxia during expansion and differentiation on the chondrogenesis of MSCs. Chondrogenic differentiation was performed in in situ solidifying gelatin hydrogels, which represent a suitable matrix for delivering and anchoring cells within the disc tissue. To consider limitations in nutrition in the intervertebral disc, differentiation was performed at low cell concentrations in the gelatin hydrogels. Standard high-density micromass cultures served as reference controls. To determine the quality of chondrogenesis we analyzed typical marker molecules such as collagen types I, II, X, Sox-9, MIA, and aggrecan mRNA using RT-qPCR and determined protein deposition by histological stainings and biochemical methods. We could demonstrate that in gelatin-based hydrogels chondrogenic differentiation of human MSCs is possible at low cell concentrations. The quality of chondrogenic differentiation could be improved by hypoxia. Best results were obtained when the entire in vitro process, including MSC expansion and subsequent differentiation, was done under hypoxic conditions. MSCs that were expanded under reduced oxygen tension were primed for a chondrogenic differentiation.


Assuntos
Condrogênese/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Células Cultivadas , Condrogênese/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Colágeno Tipo X/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOX9/metabolismo
14.
Biotechniques ; 41(4): 445-50, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17068960

RESUMO

For a feasible and cost-effective impedance measurement of cellular alterations in real-time, we combined commercially available microelectrode arrays (MEAs), consisting of 60 microelectrodes, with a conventional impedance analyzer. For proof of principle, a breast carcinoma cell line (MCF-7) was cultured on MEAs, and cellular alterations were measured by impedance spectroscopy at a frequency ranging from 10 Hz to 1 MHz. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) at different concentrations to activate protein kinase C (PKC)-mediated extra- and intracellular changes. By addition of 0.03 microM PMA, an increase of the relative impedance (Z(rel)) was observed after 10 min with a maximum at 1 kHz. Moreover a gradual elevation of the impedance was measured 60 min after stimulation with PMA. If 0.3 microM PMA was applied, the maximal amplitude of the relative impedance after 60 min shifted from 1 kHz (0.03 microM PMA) to 150 Hz. Subsequently, the impedance was further increased up to 90 min after PMA application, after which the impedance reduced after 240 min. Since we could use MEAs for at least 10 times without affecting the sensitivity, our study revealed that commercially available MEAs comprising nanocolumnar titanium nitrite electrodes are suitable microstructures for a highly reproducible and cost-effective multisite measurement of intracellular processes by impedance spectroscopy.


Assuntos
Análise Espectral/métodos , Acetato de Tetradecanoilforbol/farmacologia , Ligas/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Impedância Elétrica , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Estudos de Viabilidade , Feminino , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Imuno-Histoquímica , Microeletrodos , Microscopia de Fluorescência , Nanotecnologia/métodos , Níquel/química , Análise de Sequência com Séries de Oligonucleotídeos , Titânio/química
15.
BMC Neurosci ; 5: 55, 2004 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-15588278

RESUMO

BACKGROUND: The neuroprotective effect of xenon has been demonstrated for glutamatergic neurons. In the present study it is investigated if dopaminergic neurons, i.e. nerve-growth-factor differentiated PC-12 cells, are protected as well against hypoxia-induced cell damage in the presence of xenon. RESULTS: Pheochromocytoma cells differentiated by addition of nerve growth factor were placed in a N2-saturated atmosphere, a treatment that induced release of dopamine, reaching a maximum after 30 min. By determining extracellular lactate dehydrogenase concentration as marker for concomitant cellular damage, a substantial increase of enzymatic activity was found for N2-treated cells. Replacement of N2 by xenon in such a hypoxic atmosphere resulted in complete protection against cellular damage and prevention of hypoxia-induced dopamine release. Intracellular buffering of Ca2+ using the Ca-chelator 1, 2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester (BAPTA) reduced the neuroprotective effect of xenon indicating the essential participation of intracellular Ca2+-ions in the process of xenon-induced neuroprotection. CONCLUSIONS: The results presented demonstrate the outstanding property of xenon to protect neuron-like cells in a hypoxic situation.


Assuntos
Hipóxia/prevenção & controle , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Xenônio/uso terapêutico , Análise de Variância , Animais , Benzazepinas/farmacologia , Cálcio/metabolismo , Células Cultivadas , Quelantes/farmacologia , Dopamina/efeitos adversos , Dopamina/metabolismo , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Embrião de Mamíferos , Hipóxia/etiologia , L-Lactato Desidrogenase , Mesencéfalo/citologia , Fator de Crescimento Neural/farmacologia , Neurônios/metabolismo , Células PC12/efeitos dos fármacos , Piperazinas/farmacologia , Ratos , Sulpirida/farmacologia
16.
Exp Cell Res ; 297(2): 484-94, 2004 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15212950

RESUMO

The glial cell line-derived neurotrophic factor (GDNF) is involved in the development and maintenance of neural tissues. Mutations in components of its signaling pathway lead to severe migration deficits of neuronal crest stem cells, tumor formation, or ablation of the urinary system. In animal models of Parkinson's disease, GDNF has been recognized to be neuroprotective and to improve motor function when delivered into the cerebral ventricles or into the substantia nigra. Here, we characterize the network of 43 genes induced by GDNF overproduction of neuronal progenitor cells (ST14A), which mainly regulate migration and differentiation of neuronal progenitor cells. GDNF down-regulates doublecortin, Paf-ah1b (Lis1), dynamin, and alpha-tubulin, which are involved in neocortical lamination and cytoskeletal reorganization. Axonal guidance depends on cell-surface molecules and extracellular matrix proteins. Laminin, Mpl3, Alcam, Bin1, Id1, Id2, Id3, neuregulin1, the ephrinB2-receptor, neuritin, focal adhesion kinase (FAK), Tc10, Pdpk1, clusterin, GTP-cyclooxygenase1, and follistatin are genes up-regulated by GDNF overexpression. Moreover, we found four key enzymes of the cholesterol-synthesis pathway to be down-regulated leading to decreased farnesyl-pyrophospate production. Many proteins are anchored by farnesyl-derivates at the cell membrane. The identification of these GDNF-regulated genes may open new opportunities for directly influencing differentiation and developmental processes of neurons.


Assuntos
Diferenciação Celular/genética , Movimento Celular/genética , Genes Reguladores , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Células-Tronco/metabolismo , Animais , Western Blotting , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Transformação Celular Viral , Proteína Duplacortina , Regulação para Baixo , Técnica Direta de Fluorescência para Anticorpo , Regulação da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Modelos Biológicos , Fatores de Crescimento Neural/genética , Neurônios/citologia , RNA Mensageiro/análise , Ratos , Retroviridae/genética , Células-Tronco/citologia , Temperatura , Regulação para Cima
17.
Life Sci ; 72(17): 1909-18, 2003 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-12597990

RESUMO

Hypoxia-induced neuronal damage and glutamate release were investigated in a N(2)- or in xenon-atmosphere for embryonic rat cortical neurons; cellular damage and glutamate over-release were observed in N(2)-treated cells whereas xenon protected the cells from the hypoxic insult. The protective effect of xenon was strongly reduced by pre-incubating neurons with the calcium-chelator BAPTA-AM indicating a role for calcium in this process. The results demonstrate (a) the neuroprotective properties of xenon, suggest (b) a relationship between the prevention of neurotransmitter release in a hypoxic situation and neuroprotection and present (c) evidence that such neuroprotection may be based on yet other xenon-dependent mechanisms.


Assuntos
Anestésicos Inalatórios/toxicidade , Córtex Cerebral/citologia , Ácido Egtázico/análogos & derivados , Hipóxia Encefálica/patologia , Neurônios/patologia , Síndromes Neurotóxicas/prevenção & controle , Xenônio/toxicidade , Animais , Benzilaminas/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Quelantes/farmacologia , Maleato de Dizocilpina/farmacologia , Ácido Egtázico/farmacologia , Ácido Glutâmico/metabolismo , Hélio/farmacologia , L-Lactato Desidrogenase/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Nitrogênio/farmacologia , Ratos , Sulfonamidas/farmacologia
18.
Artif Organs ; 26(2): 140-4, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11879242

RESUMO

The success of apheresis treatment is often measured as a decrease in the detected antibodies and an improvement in different disease-related scores. Sometimes, however, the seriousness of the disease does not correlate with the antibody level. During a period of 8 years, 15 patients (3 myasthenia gravis, 1 multiple sclerosis, 2 systemic lupus erythematosus, 3 alloimmunized kidney transplant, 6 rheumatoid arthritis) were treated by protein A immunoadsorption. Lymphocyte subpopulations (activated T cells, cytolytic T cells, B cells, natural killer cells) and inflammatory proteins (ferritin, C-reactive protein, alpha1-antitrypsin, alpha2-macroglobulin) were analyzed. After observing clinical outcomes, the patients could be divided into 2 groups, respectively: Group 1, responding patients with remission of disease; and Group 2, delayed-responding patients, who required chronic treatment. Group 1 patients characteristically showed a greater increase in activated T and cytolytic T cells which correlated with a greater decrease of B cells. It might be possible that protein A immunoadsorption induced immunomodulation. Further immunological investigation is required to verify these findings.


Assuntos
Remoção de Componentes Sanguíneos , Técnicas de Imunoadsorção , Linfócitos , Adulto , Artrite Reumatoide/terapia , Feminino , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/terapia
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