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1.
Ann Burns Fire Disasters ; 36(2): 100-110, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681946

RESUMO

Firefighters are often exposed to high temperatures and by-products of combustion, which can affect their health. In this study, we assessed the impact of acute exposure of firefighters in fire simulators. Twenty male firefighters were exposed to fire simulators, and observed in four phases: pre-exposure (group 0, control) and after the end of the first (group 1), second (group 2), and fourth (group 3) weeks of training. Blood samples were collected and dosed to evaluate the response of the immune, inflammatory (C-reactive protein, IL6, and IL10), and endocrine systems (cortisone, total testosterone, free testosterone, SHBG, bioavailable testosterone, TSH, and free T4). In groups 0, 1, and 3, a thermographic evaluation was also carried out to study the temperature and body heat flow of the participants. Regarding the inflammatory process, an increase in C-reactive protein and a reduction in IL-10 were observed. With respect to hormonal markers, an increase in cortisol and reduced levels of free T4 and bioavailable testosterone were found after exposure, with recovery of testosterone levels in the final week of training. Thermoregulatory adaptation of the organism has been associated with changes in heat flow in the organism in people subjected to extreme temperatures, with emphasis on the performance of the lower limbs. Our findings demonstrate an inflammatory response with hormonal changes after exposure to fire and an adaptive response of thermal balance, which could aid understanding of the physiology of the human body in extreme situations.


Les sapeurs-pompiers (SP) sont régulièrement exposés à la chaleur et aux produits de combustion, qui peuvent avoir un retentissement sur leur santé. Nous avons évalué l'effet d'une exposition aiguë de 22 SP (tous des hommes) à incendie simulé grâce à la répétition à 4 reprises d'une même batterie d'examens (avant- T0, et à la fin des 1ère -T1 2ème - T2 et 3ème - T3 semaines d'entraînement). Des paramètres sanguins relatifs à l'inflammation et l'immunité (CRP, IL6, IL10) ainsi qu'au système endocrinien (cortisol, testostérones totale, libre et biodisponible, SHBG, TSH et T4 libre) étaient prélevés à chaque évaluation. Une étude thermographique, évaluant la température corporelle et le flux thermique corporel était réalisée à T0, T1 et T3. On constatait une augmentation de la CRP et une baisse de IL10. On observait une augmentation de la cortisolémie ainsi qu'une baisse de thyroxine libre et testostérone biodisponible, cette dernière se normalisant à T3. L'adaptation corporelle à la chaleur se traduit par une augmentation du flux thermique, en particulier aux membres inférieurs. Nous observons donc des réponses inflammatoire comme endocrinienne et une adaptation de la thermorégulation en cas d'exposition à un incendie, constatations pouvant contribuer à la compréhension de la physiologie humaine en situations extrêmes.

2.
Sci Rep ; 11(1): 7247, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790359

RESUMO

The correlation in type-II superconductors between the creep rate S and the Second Magnetization Peak (SMP) phenomenon which produces an increase in Jc, as a function of the field (H), has been investigated at different temperatures by starting from the minimum in S(H) and the onset of the SMP phenomenon detected on a FeSe0.5Te0.5 sample. Then the analysis has been extended by considering the entire S(H) curves and comparing our results with those of many other superconducting materials reported in literature. In this way, we find evidence that the flux dynamic mechanisms behind the appearance of the SMP phenomenon in Jc(H) are activated at fields well below those where the critical current starts effectively to increase. Moreover, the found universal relation between the minimum in the S(H) and the SMP phenomenon in Jc(H) shows that both can be attributed to a sequential crossover between a less effective pinning (losing its effectiveness at low fields) to a more effective pinning (still acting at high fields), regardless of the type-II superconductor taken into consideration.

3.
Nanotechnology ; 30(25): 254001, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-30831561

RESUMO

The measurements of DC magnetization M as a function of magnetic field (H) and time (t) have been performed in order to study the superconducting and pinning properties of a Fe(Se, Te) iron based superconductor fabricated by means of the Bridgman technique. By performing the superconducting hysteresis loops M(H) at different temperatures in the case of perpendicular and parallel field, the critical current density Jc (H) has been extracted in the framework of the Bean critical state model for both configurations. The Jc (H) curves have shown the presence of the second magnetization peak effect that causes an anomalous increase in the field dependence of the critical current density. In order to obtain the Jc anisotropy of the sample, we have performed the ratio between perpendicular and parallel critical current density values [Formula: see text] and compared its values with the literature ones. The information regarding the pinning energy U have been extracted by means of the relaxation of the irreversible magnetization M(t) in the case H∣∣c. In particular, performing relaxation measurements at different temperatures and magnetic fields, the temperature dependence of the pinning energy U(T) at different magnetic fields has been obtained showing an anomalous temperature scaling of the curves. The presence of a maximum in the U(T) curves suggests a pinning crossover at a given field and temperature H cr(T). The H cr(T) values have been fitted with the equation H cr(T) = H cr(0) (1 - T/T*) n whose results confirm the correlation between the elastic/plastic crossover and the end of the peak effect phenomenon.

4.
J Oral Microbiol ; 9(1): 1403843, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29805776

RESUMO

Background: Non-human primates appear to represent the most faithful model of human disease, but to date the oral microbiome in macaques has not been fully characterized using next-generation sequencing. Objective: In the present study, we characterized the clinical and microbiological features of naturally occurring periodontitis in non-human primates (Macaca mulatta). Design: Clinical parameters of periodontitis including probing pocket depth (PD) and bleeding on probing (BOP) were measured in 40 adult macaques (7-22 yrs), at six sites per tooth. Subgingival plaque was collected from diseased and healthy sites, and subjected to 16S rDNA sequencing and identification at the species or higher taxon level. Results: All macaques had mild periodontitis at minimum, with numerous sites of PD ≥ 4 mm and BOP. A subset (14/40) had moderate-severe disease, with >2 sites with PD ≥ 5mm, deeper mean PD, and more BOP. Animals with mild vs moderate-severe disease were identical in age, suggesting genetic heterogeneity. 16S rDNA sequencing revealed that all macaques had species that were identical to those in humans or closely related to human counterparts, including Porphyromonas gingivalis which was present in all animals. Diseased and healthy sites harboured distinct microbiomes; however there were no significant differences in the microbiomes in moderate-severe vs. mild periodontitis. Conclusions: Naturally occurring periodontitis in older macaques closely resembles human adult periodontitis, thus validating a useful model to evaluate novel anti-microbial therapies.

5.
G Chir ; 38(6): 285-290, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29442059

RESUMO

AIM: The incidence of rectal cancer continues to rise. The functional results after complete Total Mesorectal Excision (TME) depend on the segment of colon used for reconstruction of colonic continuity and the form, the volume and the functional proprieties of the "neorectum". The aim of our study is evaluate the efficacy of our Modified Transverse Coloplasty Pouch (MTCP) after the treatment of low rectal cancer in terms of functional outcomes and quality of life. PATIENTS AND METHODS: The study included 136 patients, underwent TME from January 2007 to December 2016 with diagnosis of extraperitoneal carcinoma of the rectum. The average distance of the tumor from the dentate line was 5.6 cm. Our follow-up protocol included functional outcome evaluation at 7th post-operative day (POD), 2nd month, and 6th month after the surgery. RESULTS: All patients (M/F 84/52) underwent anterior rectal resection (TME) with MTCP. Frequency of bowel movements per 24 hours in the studied patients compared at 7th POD, 2 months, and 6 months. Since the first post-operative weeks there is an encouraging reduction of the frequency of bowel movements. CONCLUSION: Modified Transverse Coloplasty Pouch (MTCP) had better functional results and quality of life compared to patients with a Colonic J Pouch (CJP) and traditional Transverse Coloplasty Pouch (TCP).


Assuntos
Bolsas Cólicas , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
G Chir ; 38(6): 313-317, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29442064

RESUMO

AIM: Anal fistula is a common disease originated from abscess according the cryptoglandular theory. A rare etiology is the pilonidal disease. In our case we observed a pilonidal disease mimicking an anterior perianal fistula, associated with another posterior anal fistula. CASE PRESENTATION: A 36-year old man was referred to our department with an anal fistula with an anterior opening. Despite the clinical examination and the endoanal ultrasound, only during the surgery we discovered the origin of the anterior fistula from a misdiagnosed pilonidal sinus. There was also a posterior anal fistula in communication with the same abscess of the anterior one. We performed a two-step surgery with a first fistulectomy of the anterior tract, a drainage of abscess and the positioning of a seton for the posterior fistula. After about one month and the fall of the seton we evaluate the good healing of posterior anal fistula and excised the residual pilonidal sinus. CONCLUSION: This misdiagnosed pilonidal disease created in our clinical report a true challenge. Our goal was to eliminate as much disease as possible, but also to avoid major complications or recurrences. We refused an aggressive approach and chose a two-step surgery, with in the first approach not only a demolitive time but also a reconstruction to facilitate healing, and in the second time the complete eradication of the pathology.


Assuntos
Seio Pilonidal/diagnóstico , Fístula Retal/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Seio Pilonidal/complicações , Seio Pilonidal/cirurgia , Fístula Retal/complicações , Fístula Retal/cirurgia , Procedimentos Cirúrgicos Operatórios
7.
Unfallchirurg ; 119(7): 604-8, 2016 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-27286982

RESUMO

We report the case of a 24-year-old female after sustaining a shotgun wound in the left upper extremity and chest. Initial emergency diagnostics revealed numerous shotgun pellets scattered throughout the left-side soft tissue, chest and upper lung lobe with one pellet having migrated into the left ventricle of the heart.Due to the devastating injury pattern, gunshot wounds are interdisciplinarily challenging and should include extended initial diagnostics, such as contrast agent CT. The potential toxicity of elevated lead blood levels have to be taken into further account.


Assuntos
Corpos Estranhos/diagnóstico , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/cirurgia , Ventrículos do Coração/lesões , Ventrículos do Coração/cirurgia , Ferimentos por Arma de Fogo/diagnóstico , Acidentes , Adulto , Feminino , Corpos Estranhos/etiologia , Corpos Estranhos/cirurgia , Traumatismos Cardíacos/etiologia , Humanos , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/cirurgia
8.
Sci Rep ; 5: 10705, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26024506

RESUMO

Two-dimensional materials, such as graphene, topological insulators, and two-dimensional electron gases, represent a technological playground to develop coherent electronics. In these systems, quantum interference effects, and in particular weak localization, are likely to occur. These coherence effects are usually characterized by well-defined features in dc electrical transport, such as a resistivity increase and negative magnetoresistance below a crossover temperature. Recently, it has been shown that in magnetic and superconducting compounds, undergoing a weak-localization transition, a specific low-frequency 1/f noise occurs. An interpretation in terms of nonequilibrium universal conductance fluctuations has been given. The universality of this unusual electric noise mechanism has been here verified by detailed voltage-spectral density investigations on ultrathin copper films. The reported experimental results validate the proposed theoretical framework, and also provide an alternative methodology to detect weak-localization effects by using electric noise spectroscopy.

9.
Cerebellum ; 13(1): 121-38, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23943521

RESUMO

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.


Assuntos
Cerebelo/fisiopatologia , Terapia por Estimulação Elétrica , Estimulação Magnética Transcraniana , Animais , Ataxia Cerebelar/fisiopatologia , Ataxia Cerebelar/terapia , Terapia por Estimulação Elétrica/métodos , Humanos , Processos Mentais/fisiologia , Córtex Motor/fisiopatologia , Desempenho Psicomotor/fisiologia , Estimulação Magnética Transcraniana/métodos
10.
Acta Neurol Scand ; 123(3): 211-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20726842

RESUMO

OBJECTIVE: The aim of this study was to investigate the long-term functional outcome and health status of patients with critical illness polyneuromyopathy (CIPNM). METHOD AND SUBJECTS: One hundred and twenty-four consecutive survival intensive care unit patients admitted to a neuro-rehabilitation Unit from January 2003 to December 2007 were identified. Patients with proven CIPNM by the electromyography were prospectively followed. The Barthel and modified Rankin Scales (mRS) were administered to all patients at baseline, discharge and follow-up. The SF-36 questionnaire was administered to ascertain health status. Each patient underwent an individually tailored rehabilitation therapy. RESULTS: Forty-two subjects (23M, 19F, mean age 58.4 ± 13.9) were enrolled. Of these, 30 patients were diagnosed electrophysiologically with CIP, six with critical illness myopathy (CIM) and six with a finding combination of CIP and CIM (CIP/CIM) subtype. The mean Barthel scores at baseline, discharge and follow-up were 16.7 ± 8.6, 81.7 ± 16.4 and 86.7 ± 15.9 (P < 0.001) and the median mRS scores were 5 (IQR: 5-5), 3 (IQR: 0-5) and 1 (IQR: 0-5). The mean length of neuro-rehabilitation stay was 76.2 ± 28.1 days. The SF-36 questionnaire administered at follow-up (mean 31.7 ± 15.8 months), showed significantly lower values compared to Italian normative. CONCLUSION: ICU patients with CIPNM treated in a neuro-rehabilitation setting resulted in a good functional outcome. Despite complete recovery, patients with CIPNM experienced difficulties in health status.


Assuntos
Nível de Saúde , Polineuropatias/diagnóstico , Polineuropatias/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/fisiopatologia , Estudos Prospectivos , Tempo , Fatores de Tempo
11.
Artigo em Inglês | MEDLINE | ID: mdl-21097230

RESUMO

Tremor constitutes the most common movement disorder; in fact 14.5% of population between 50 to 89 years old suffers from it. Moreover, 65% of patients with upper limb tremor report disability when performing their activities of daily living (ADL). Unfortunately, 25% of patients do not respond to drugs or neurosurgery. In this regard, TREMOR project proposes functional compensation of upper limb tremors with a soft wearable robot that applies biomechanical loads through functional electrical stimulation (FES) of muscles. This wearable robot is driven by a Brain Neural Computer Interface (BNCI). This paper presents a multimodal BCI to assess generation, transmission and execution of both volitional and tremorous movements based on electroencephalography (EEG), electromyography (EMG) and inertial sensors (IMUs). These signals are combined to obtain: 1) the intention to perform a voluntary movement from cortical activity (EEG), 2) tremor onset, and an estimation of tremor frequency from muscle activation (EMG), and 3) instantaneous tremor amplitude and frequency from kinematic measurements (IMUs). Integration of this information will provide control signals to drive the FES-based wearable robot.


Assuntos
Biorretroalimentação Psicológica/métodos , Terapia por Estimulação Elétrica/métodos , Eletroencefalografia/métodos , Potencial Evocado Motor , Movimento , Tremor/diagnóstico , Tremor/reabilitação , Interface Usuário-Computador , Algoritmos , Humanos , Sistemas Homem-Máquina , Terapia Assistida por Computador/métodos , Tremor/fisiopatologia
12.
Vet Immunol Immunopathol ; 137(1-2): 149-54, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20546932

RESUMO

We have recently introduced a macaque (Macaca mulatta) model of Leishmania braziliensis-induced chronic granulomatous cutaneous lesions affecting the nasal mucosa. Using an L. braziliensis strain that produces self-healing dermal lesions in macaques, here we characterises the systemic and local cell-mediated immune responses that led to controlled growth of granulomas in the infected host. As detected using flow cytometry, more cytokine-producing T-cell subsets were observed in granuloma-derived leukocytes that were analysed directly ex vivo than in the in vitro-restimulated cells from the peripheral blood and skin-draining lymph nodes (dLNs). We demonstrate that antigen-specific interferon-gamma (IFN-gamma)- or tumour necrosis factor alpha (TNF-alpha)-producing CD4(+) and CD8(+) cells are likely important for the immunological effectiveness of granulomas. However, their resolution can be ascribed to the concomitant recruitment of interleukin (IL)-10-producing CD4(+)CD25(+) regulatory T (Treg) cells that suppress the effector T-cell-mediated inflammatory response. The findings confirm that the macaque model can be used to fully elucidate the regulatory mechanisms that may render granulomas inadequate for fighting intracellular pathogens, which will need to be considered in the development of any therapeutic strategy designed to prevent immune pathology.


Assuntos
Leishmania braziliensis , Leishmaniose Cutânea/imunologia , Animais , Modelos Animais de Doenças , Interleucina-10/biossíntese , Macaca mulatta , Linfócitos T/imunologia
14.
J Neurosurg Sci ; 54(2): 49-54, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21313955

RESUMO

In geometrical terms, tumor vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic, together with the highly variable vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological features have now been well established, quantitative analyses of neovascularity in two-dimensional histological sections still fail to view tumor architecture in non-Euclidean terms, and this leads to errors in visually interpreting the same tumor, and discordant results from different laboratories. A review of the literature concerning the application of microvessel density (MVD) estimates, an Euclidean-based approach used to quantify vascularity in normal and neoplastic pituitary tissues, revealed some disagreements in the results and led us to discuss the limitations of the Euclidean quantification of vascularity. Consequently, we introduced fractal geometry as a better means of quantifying the microvasculature of normal pituitary glands and pituitary adenomas, and found that the use of the surface fractal dimension is more appropriate than MVD for analysing the vascular network of both. We propose extending the application of this model to the analysis of the angiogenesis and angioarchitecture of brain tumors.


Assuntos
Neoplasias Encefálicas/irrigação sanguínea , Fractais , Microvasos/anatomia & histologia , Modelos Anatômicos , Neovascularização Patológica/patologia , Hipófise/irrigação sanguínea , Adenoma/irrigação sanguínea , Humanos , Neoplasias Hipofisárias/irrigação sanguínea
15.
Antimicrob Agents Chemother ; 54(1): 502-5, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19822700

RESUMO

This study compared the efficacies of two N-methylglucomine antimoniate (MA) dose regimens for treating macaques with Leishmania braziliensis-induced chronic skin disease. Whereas all animals treated with the full dose (20 mg MA/kg/day) were cured, 50% of the monkeys receiving a low-dose regimen (5 mg MA/kg/day) relapsed. The antimony concentrations in macaque plasma and tissue samples were greater in the full-dose group than in that receiving a subtherapeutic MA regimen. Our data also suggest the presence of drug-induced hepatic pathology.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Animais , Antimônio/sangue , Antiprotozoários/administração & dosagem , Rim/parasitologia , Rim/patologia , Leishmania braziliensis , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Fígado/parasitologia , Fígado/patologia , Macaca mulatta , Meglumina/administração & dosagem , Antimoniato de Meglumina , Compostos Organometálicos/administração & dosagem , Baço/parasitologia , Baço/patologia
16.
J Phys Condens Matter ; 21(25): 254207, 2009 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-21828431

RESUMO

We study the vortex dynamics in the instability regime induced by high dissipative states well above the critical current in Nb superconducting strips. The magnetic field and temperature behavior of the critical vortex velocity corresponding to the observed dynamic instability is ascribed to intrinsic non-equilibrium phenomena. The Larkin-Ovchinnikov (LO) theory of electronic instability in high velocity vortex motion has been applied to interpret the temperature dependence of the critical vortex velocity. The magnetic field dependence of the vortex critical velocity shows new features in the low-field regime not predicted by LO.

17.
J Assist Reprod Genet ; 25(9-10): 461-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18925430

RESUMO

PURPOSE: To conduct a prospective randomized study in order to investigate the effect of recombinant HCG (rHCG) on oocyte nuclear and cytoplasm maturity compared to urinary HCG (uHCG), for inducing ovulation in women treated with ICSI for male factor infertility. MATERIALS AND METHODS: We compared 89 patients randomly assigned to one of the two study groups. Group A consisted of 42 women who received a subcutaneous (s.c.) injection of 250 microg rHCG and group B consisted of 47 patients receiving an intramuscular (i.m.) injection of 10,000 IU uHCG. RESULTS: Patients treated with rHCG showed a rate of metaphase II oocytes, a number of metaphase II oocytes with mature cytoplasm and a rate of metaphase II oocytes with mature cytoplasm calculated from total MII oocytes statistically higher than in patients treated with uHCG. However this differences were not associated with a significantly better clinical outcome. CONCLUSION: Our data show that in women treated with ICSI for male factor infertility, rHCG increases the rate of metaphase II oocytes, the number and the rate of MII oocytes with mature cytoplasm compared to uHCG. A larger study comparing transfer cycles of embryos all derived from oocytes with mature cytoplasm and transfer cycles of embryos all derived from oocytes with immature cytoplasm may be needed to clarify clinical correlations.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Oócitos/efeitos dos fármacos , Indução da Ovulação , Injeções de Esperma Intracitoplásmicas , Adulto , Feminino , Humanos , Infertilidade Masculina , Masculino , Metáfase , Oócitos/citologia , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem
18.
J Pathol ; 216(3): 375-86, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18702174

RESUMO

In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leishmania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long-term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1-mediated, immunity-induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1-cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections.


Assuntos
Leishmania braziliensis/fisiologia , Leishmaniose Cutânea/imunologia , Macaca mulatta/imunologia , Doenças dos Macacos/parasitologia , Pele/imunologia , Pele/parasitologia , Animais , Antígenos de Protozoários/análise , Quimiotaxia de Leucócito , Citometria de Fluxo , Granuloma/imunologia , Granuloma/parasitologia , Imunofenotipagem , Leishmania braziliensis/ultraestrutura , Contagem de Leucócitos , Macaca mulatta/parasitologia , Masculino , Microscopia Eletrônica , Modelos Animais , Doenças dos Macacos/imunologia , Linfócitos T/imunologia
19.
Cell Death Differ ; 15(5): 867-78, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18259192

RESUMO

Proper attachment to the extracellular matrix (ECM) is essential for cell survival. The loss of integrin-mediated cell-ECM contact results in an apoptotic process termed anoikis. However, mechanisms involved in regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we demonstrate that reactive oxygen species (ROS) produced through the involvement of the small GTPase Rac-1 upon integrin engagement exert a mandatory role in transducing a pro-survival signal that ensures that cells escape from anoikis. In particular, we show that ROS are responsible for the redox-mediated activation of Src that trans-phosphorylates epidermal growth factor receptor (EGFR) in a ligand-independent manner. The redox-dependent phosphorylation of EGFR activates both extracellular signal-regulated protein kinase and Akt downstream signalling pathways, culminating in degradation of the pro-apoptotic protein Bim. Hence, our results shed new light on the mechanism granting the adhesion-dependent antiapoptotic effect, highlighting a fundamental role of ROS-mediated Src regulation in ensuring anoikis protection.


Assuntos
Anoikis/fisiologia , Sobrevivência Celular/fisiologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 11 Semelhante a Bcl-2 , Adesão Celular/fisiologia , Linhagem Celular , Ativação Enzimática , Receptores ErbB/metabolismo , Matriz Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Integrinas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Ativação Transcricional , Proteínas rac1 de Ligação ao GTP/metabolismo , Quinases da Família src/metabolismo
20.
IEEE Trans Biomed Circuits Syst ; 2(4): 269-79, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23853130

RESUMO

Upper limb postural tremor consists of mechanical-reflex and central-neurogenic oscillations, superimposed upon a background of irregular fluctuations in muscle force. Muscle spindles play key-roles in the information flow to supra-spinal and spinal generators. Oscillations were delivered using a new generation portable myohaptic device, called ldquowristalyzer,rdquo taking into account the ergonomy of upper limbs and allowing a fine adjustment to each configuration of upper limb segments. The nominal torque of the first generation device is 4 Nm, with a maximal rotation velocity of 300 degrees/s and a range of motion of plusmn45 degrees. Reliability was assessed in basal condition and during loading conditions. We assessed the effects of the addition of inertia on postural tremor of the finger in a group of 26 neurological patients and the effects of wrist oscillations upon contralateral postural tremor in 6 control subjects and in 7 neurological patients exhibiting a postural tremor. Patients showed two different behaviors in response to inertia and exhibited an increased variability of postural tremor during fast oscillations (13.3 Hz). One patient with overactivity of the olivocerebellar pathways exhibited a drop in the peak frequency of more than 20%. The relative power of the 8-12 Hz subband was significantly higher in controls both in basal condition and during oscillations (p = 0.028 and p = 0.015, respectively). The second generation wristalyzer allows to investigate the effects of mechanical oscillations up to frequency of 50 Hz. This mechatronic device can assess the responsiveness of tremor generators to stimulation of muscle spindles and biomechanical loading. Potential applications are the monitoring of dysmetria under various inertial or damping conditions, the assessment of rigidity in Parkinson's disease and the characterization of voluntary muscle force.

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