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1.
Mediators Inflamm ; 2019: 8071619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148947

RESUMO

BACKGROUND: It is not predictable which patients will develop a severe inflammatory response after successful cardiopulmonary resuscitation (CPR), also known as "postcardiac arrest syndrome." This pathology affects only a subgroup of cardiac arrest victims. Whole body ischemia/reperfusion and prolonged shock states after return of spontaneous circulation (ROSC) may both contribute to this devastating condition. The vascular endothelium with its glycocalyx is especially susceptible to initial ischemic damage and may play a detrimental role in the initiation of postischemic inflammatory reactions. It is not known to date if an immediate early damage to the endothelial glycocalyx, detected by on-the-scene blood sampling and measurement of soluble components (hyaluronan and syndecan-1), precedes and predicts multiple organ failure (MOF) and survival after ROSC. METHODS: 15 patients after prehospital resuscitation were included in the study. Serum samples were collected on the scene immediately after ROSC and after 6 h, 12 h, 24 h, and 48 h. Hyaluronan and syndecan-1 were measured by ELISA. We associated the development of multiple organ failure and 30-day survival rates with these serum markers of early glycocalyx damage. RESULTS: Immediate serum hyaluronan concentrations show significant differences depending on 30-day survival. Further, the hyaluronan level is significantly higher in patients developing MOF during the initial and intermediate resuscitation period. Also, the syndecan-1 levels are significantly different according to MOF occurrence. CONCLUSION: Serum markers of glycocalyx shedding taken immediately on the scene after ROSC can predict the occurrence of multiple organ failure and adverse clinical outcome in patients after cardiac arrest.


Assuntos
Parada Cardíaca/sangue , Ácido Hialurônico/sangue , Sindecana-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Feminino , Parada Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Insuficiência de Múltiplos Órgãos/sangue , Estudos Prospectivos
2.
Unfallchirurg ; 122(12): 967-976, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30806727

RESUMO

BACKGROUND: The morbidity and mortality of polytrauma patients are substantially influenced by the extent of the posttraumatic inflammatory reaction. Studies have shown that TIMP­1 and MMP­9 play a major role in posttraumatic immune disorder in genome-wide mRNA microarray analyses. Furthermore, both showed differential gene expression profiles depending on the clinical parameters massive blood transfusion and traumatic brain injury. OBJECTIVE: The aim of this study was to evaluate TIMP­1 and MMP­9 serum concentrations in polytraumatized patients depending on the clinical parameters massive blood transfusion and traumatic brain injury in the early posttraumatic phase. MATERIAL AND METHODS: Polytrauma patients (≥18 years) with an "Injury Severity Score" (ISS) ≥ 16 points were enrolled in this prospective study. Serum levels of TIMP­1 and MMP­9 were quantified (at 0 h, 6 h, 12 h, 24 h, 48 h and 72 h) using an enzyme-linked immunosorbent assay (ELISA). Groups were divided according to the clinical parameter massive blood transfusion (≥10 red blood cell units [RBC units] in the first 24-hour posttrauma) and traumatic brain injury (CCT postive [cranial computed tomography]). RESULTS: Following massive blood transfusion (n = 21; 50 ± 15.7 years; ISS 39 ± 12.8 points) patients showed overall significantly increased TIMP­1 levels (p = 0.003) and significantly higher TIMP­1 values after 12-72 h. Traumatic brain injury patients (n = 28; 44 ± 19 years; ISS 42 ± 10 points) showed significantly higher MMP­9 levels (p = 0.049) in the posttraumatic period. CONCLUSION: Polytraumatized patients who received massive blood transfusions following major trauma showed significantly higher TIMP­1 levels than patients who did not receive massive transfusions. This seems to be an expression of a massively excessive inflammatory reaction and therefore represents a substantial factor in the pathogenesis of severe posttraumatic immune dysfunction in this collective. Furthermore, the significant increase in MMP­9 with accompanying traumatic brain injury reflects the pivotal role of matrix metalloproteinases in the pathophysiology of traumatic brain injury.


Assuntos
Transfusão de Sangue , Lesões Encefálicas Traumáticas , Metaloproteinase 9 da Matriz , Inibidor Tecidual de Metaloproteinase-1 , Lesões Encefálicas Traumáticas/metabolismo , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-1/metabolismo
3.
Unfallchirurg ; 121(9): 723-729, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-29777283

RESUMO

Fractures of the base of the fifth metatarsal bone are one of the most frequent fractures to the foot and ankle. Despite the high frequency and although a number of studies are now available, treatment frequently does not follow the available evidence. Among the reasons is the inconsistent terminology used and that the studies available are neglected. The aim of this review is to present the current classifications, the available treatment studies and to derive evidence-based treatment recommendations. The term "Jones fracture" has been used inconsistently for different fracture entities and should, therefore, not be used anymore. Fractures are mostly classified according to Lawrence and Botte into three zones. However, the available studies demonstrate that type I and type II fractures according to Lawrence and Botte do not differ with respect to the prognosis. Both fractures can be successfully healed by functional treatment with weightbearing as tolerated. Consequently, a differentiation between these two zones does not seem to be meaningful. Therefore, they should be summarized as epi-metaphyseal fractures. Even dislocated, intra-articular, and multifragmentary fractures in this region can be functionally treated with good results. Fractures in the meta-diaphyseal region (Lawrence and Botte type III, distal to the IV and V intermetatarsal articulation) demonstrate a high rate of symptomatic non-unions after conservative treatment. Therefore, these fractures should be primarily treated operatively by closed reduction and intramedullary screw fixation.


Assuntos
Fraturas Ósseas/classificação , Fraturas Ósseas/terapia , Ossos do Metatarso/lesões , Fraturas Ósseas/diagnóstico , Humanos
4.
Unfallchirurg ; 120(12): 1007-1014, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-29038897

RESUMO

The most favorable treatment for acute Achilles tendon ruptures remains controversial. In particular, three key questions are intensively debated: is operative or non-operative treatment superior? If surgery is performed, should open or minimally invasive percutaneous techniques be used? How should the follow-up treatment be carried out? The aim of this article is to answer these essential questions based on the currently available evidence. Non-operative treatment leads to a higher rate of re-ruptures and inferior functional results when compared to operative treatment. The major disadvantage of open surgery is the increased risk of wound healing problems and wound infections. Due to the development of minimally invasive percutaneous techniques, complication rates could be significantly reduced and patient satisfaction could be significantly improved, without increasing the risk of re-ruptures. The functional outcome is still partially unsatisfactory independent of the type of treatment. This is particularly expressed in weakness of the gastrocnemius-soleus muscle complex; therefore, the follow-up treatment is of fundamental importance. The available evidence clearly underlines the importance of early weight bearing and mobilization of the ankle joint, as it is safe and leads to better function, patient satisfaction and faster return to work or sport, compared with partial weight bearing and immobilization. Nevertheless, treatment protocols vary greatly with the majority still carrying out open suture and immobilizing follow-up treatment with fixed plantar flexion. Based on the available data the authors recommend minimally invasive percutaneous suture of the tendon followed by progressive functional rehabilitation. Implementation of the available evidence into routine practice is the next important step for successful treatment of this challenging injury.


Assuntos
Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Traumatismos dos Tendões/cirurgia , Doença Aguda , Humanos , Imobilização/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Cuidados Pós-Operatórios/métodos , Recidiva , Técnicas de Sutura
5.
Unfallchirurg ; 120(12): 1044-1053, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-28980027

RESUMO

Achilles tendinopathy at the calcaneal insertion is classified into insertional tendinopathy, retrocalcaneal and superficial bursitis. The aim of this study was to present the current evidence on conservative and surgical treatment of insertional tendinopathy of the Achilles tendon. Conservative first-line therapy includes reduction of activity levels, administration of non-steroidal anti-inflammatory drugs (NSAID), adaptation of footwear, heel wedges and orthoses or immobilization. In addition, further conservative therapy options are also available. Eccentric stretching exercises should be integral components of physiotherapy and can achieve a 40% reduction in pain. Extracorporeal shock wave therapy has been shown to reduce pain by 60% with a patient satisfaction of 80%. Due to the limited evidence, injections with platelet-rich plasma (PRP), dextrose (prolotherapy) or polidocanol (sclerotherapy) cannot currently be recommended. Operative therapy is indicated after 6 months of unsuccessful conservative therapy. Open debridement allows all pathologies to be addressed, including osseous abnormalities and intratendinous necrosis. The success rate of over 70% is contrasted by complication rates of up to 40%. The Achilles tendon should be reattached, if detached by >50%. No valid data are available for the transfer of the tendon of the flexor hallucis longus (FHL) muscle but it is frequently applied in cases of more than 50% debridement of the diameter of the Achilles tendon. Lengthening of the gastrocnemius muscle cannot be recommended because insufficient data are available. Tendoscopy is a promising treatment option for isolated retrocalcaneal bursitis and has shown similar success rates to open debridement with significantly lower complication rates.


Assuntos
Tendão do Calcâneo , Tendinopatia/diagnóstico , Tendinopatia/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Artroscopia/métodos , Desbridamento/métodos , Diagnóstico Diferencial , Terapia por Estimulação Elétrica , Tratamento por Ondas de Choque Extracorpóreas/métodos , Humanos , Exercícios de Alongamento Muscular/métodos , Modalidades de Fisioterapia , Transferência Tendinosa/métodos
6.
Unfallchirurg ; 119(2): 92-8, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-26796120

RESUMO

Acute ankle fractures are one of the most common fractures in adults with an incidence of 0.1-0.2 % per year. Operative treatment by open reduction and internal fixation (ORIF) is the standard method of treatment for unstable or dislocated fractures. The main goal of the operation is the anatomical realignment of the joint and restoration of ankle stability; nevertheless, anatomical reduction does not automatically lead to favorable clinical results. According to several studies the mid-term and in particular the long-term outcome following operative treatment is often poor with residual symptoms including chronic pain, stiffness, recurrent swelling and ankle instability. There is growing evidence that this poor outcome might be related to occult intra-articular injuries involving cartilage and soft tissues. In recent studies the frequency of fracture-related osteochondral lesions was reported to be approximately 64 %. By physical examination, standard radiography or even computed tomography (CT), these intra-articular pathologies cannot be reliably diagnosed; therefore, many authors emphasize the value of ankle arthroscopy in acute fracture treatment as it has become a safe and effective diagnostic and therapeutic procedure. Arthroscopically assisted open reduction and internal fixation (AORIF) allows control of the reduction as well examination of all intra-articular structures. If necessary, intra-articular pathologies can be addressed by removing ruptured ligaments and loose bodies, performing chondroplasty or microfracturing. So far there is no evidence that supplementary ankle arthroscopy increases the complication rate. On the other hand, the positive effect of AORIF has also not been clearly documented; nevertheless, there are clear indications that arthroscopically assisted fracture treatment is beneficial, especially in complex fractures.


Assuntos
Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/patologia , Articulação do Tornozelo/cirurgia , Artrodese/métodos , Artroscopia/métodos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Tornozelo/patologia , Artrodese/instrumentação , Artroscopia/instrumentação , Feminino , Fixação Intramedular de Fraturas/métodos , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Unfallchirurg ; 119(2): 86-91, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-26810229

RESUMO

Tibiotalocalcaneal arthrodesis (TTCA) is indicated for a variety of disorders, including end-stage osteoarthritis, severe deformities and complications after operative interventions on the upper and lower ankle joints. Due to the biomechanical advantages, TTCA is predominantly performed with curved retrograde intramedullary nails allowing compression before locking. Hindfoot arthrodesis is most commonly performed by extensive open surgical approaches. Despite a patient satisfaction rate greater than 80 %, current reviews have reported mean complication rates of more than 50 % with a pronounced variance in bone union rates. This is influenced by the sometimes severe preexisting diseases in this patient collective. A predictive risk assessment for complications following TTCA revealed a significantly increased risk in the presence of diabetes mellitus, revision surgery or preoperative ulceration. In these high-risk patients, a reduction of the invasiveness of the procedure could possibly reduce the complication rates. Arthroscopic TTCA therefore appears to be a promising alternative approach. Even though only few case reports and one case series have been published, in the total collective of 17 patients only one subtalar non-union and one minor complication were reported. Despite the limited evidence available, arthroscopic TTCA appears to be a promising therapy option in patients with an increased risk profile and comorbidities, such as critical soft tissue situations, plantar ulceration, peripheral arterial occlusive disease (PAOD) and diabetes mellitus.


Assuntos
Articulação do Tornozelo/cirurgia , Artrodese/métodos , Artroscopia/métodos , Fixação Intramedular de Fraturas/métodos , Osteoartrite/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Articulação do Tornozelo/diagnóstico por imagem , Artrodese/instrumentação , Artroscopia/instrumentação , Terapia Combinada/efeitos adversos , Terapia Combinada/instrumentação , Terapia Combinada/métodos , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Resultado do Tratamento
8.
Clin Exp Immunol ; 156(2): 278-84, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19250281

RESUMO

Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1(-/-) mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1(-/-) mice displayed similar organ burdens to wild-type mice. CX3CR1(-/-) mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.


Assuntos
Francisella tularensis , Pulmão/imunologia , Receptores de Quimiocinas/deficiência , Tuberculose Pulmonar/metabolismo , Tularemia/metabolismo , Animais , Receptor 1 de Quimiocina CX3C , Células Dendríticas/imunologia , Suscetibilidade a Doenças , Feminino , Citometria de Fluxo , Imunofenotipagem , Macrófagos Alveolares/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Mycobacterium tuberculosis , Neutrófilos/imunologia , Receptores de Quimiocinas/genética , Tularemia/imunologia
9.
J Phys Chem A ; 113(40): 10795-802, 2009 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-19757785

RESUMO

The work of Noid et al. [ J. Chem. Phys. 1977 , 67 , 404 ] has shown that sharp molecular spectra can be obtained through a Fourier transform of the autocorrelation function of a classical trajectory. In the present work, we extend this idea to obtain a spectrum by Fourier transform of the dipole moment function of collision product trajectories. We show that this "classical collision spectrum" (CCS) is related to the cross section for creating the product times an Einstein A factor. As a test case, we analyze product CO trajectories obtained from O + CO collisions at 8 km/s and focus on the spectral resolution of the CCS. The CCS of these trajectories shows rich quantum-like features, including well-separated vibrational overtones and rotational band heads, which become more pronounced with particular trajectory weighting methods. For polyatomic cases, the hope is that the CCS can be deconvolved into ro-vibrational specific probabilities and cross sections for quasi-periodic trajectories, which would otherwise overlap in a conventional classical trajectory energy analysis. Chaotic trajectories are expected to broaden and decrease the achievable resolution of the CCS. Chaotic motion will therefore impact the ability to separate ro-vibrational specific cross sections, an issue that will be addressed in future work.

10.
Oper Orthop Traumatol ; 31(3): 201-210, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-30918997

RESUMO

OBJECTIVE: Repair of the lateral ligament complex of the ankle joint; identification and treatment of intra-articular pathologies. INDICATIONS: Symptomatic chronic lateral ankle instability. Treatment of osteochondral lesions associated with lateral ankle instability. CONTRAINDICATIONS: Osteoarthritis of the ankle joint, risk factors such as peripheral occlusive disease, diabetic foot syndrome, complex regional pain syndrome. SURGICAL TECHNIQUE: Diagnostic arthroscopy of the ankle joint utilizing anterolateral and -medial portals; identification and treatment of intra-articular pathologies; identification and preparation of the distal fibula; insertion of two suture anchors; the sutures are passed inside-out through the joint capsule, the scarred lateral ligaments, the extensor retinaculum using a suture lasso; by tying down the sutures the tissue grasped is then pulled against the distal fibula; this will stabilize the lateral ligament complex. POSTOPERATIVE MANAGEMENT: Partial weight-bearing and short leg cast for 2 weeks, then 4 weeks ankle brace and range of motion exercises, thereafter functional physical therapy, ankle brace only during exercises; no sports for at least 3 months. RESULTS: Currently, one randomized controlled trial is available comparing open to arthroscopic lateral ankle ligament repair. Open repair was always combined with arthroscopy to treat intra-articular pathologies. In all patients, surgery led to a significant increase of the American Orthopaedic Foot and Ankle Score (AOFAS), Karlsson Score and visual analog score (VAS), but no significant differences between the open and arthroscopic procedure after one year with similar complications (arthroscopy group: 3 temporary nerve irritations and 2 patients with pain over the knot; open treated group: 2 temporary nerve irritations and one abscess). Intra-articular pathologies were treated in 68% of the arthroscopically treated patients and 70% of the patients treated by open surgery. One out of two retrospective comparative studies reported a significantly shorter operation time and time to return to daily activity and significantly lower VAS three days postoperatively for arthroscopically treated patients, while the other parameters assessed were comparable.


Assuntos
Artroscopia/métodos , Instabilidade Articular , Ligamentos Laterais do Tornozelo , Tornozelo , Articulação do Tornozelo/cirurgia , Humanos , Instabilidade Articular/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
J Int Med Res ; 47(3): 1185-1194, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30616490

RESUMO

OBJECTIVE: To determine free and total cortisol serum concentrations in the first 24 h after trauma and to evaluate the influence of traumatic brain injury (TBI) on their dynamics. METHODS: This prospective cohort study enrolled patients who had experienced multiple trauma and were admitted to a level 1 trauma centre. The patients were divided in two groups based on the presence of TBI according to clinical and radiological findings. Blood was collected initially as well as at 12 h and 24 h after the traumatic injury. Total cortisol, corticosteroid binding globulin (CBG) and free cortisol levels were determined. RESULTS: The study analysed data from 49 patients (36 males and 13 females) with a mean ± SD age of 45.0 ± 16.0 years. Of these, 36 presented with TBI and 13 had multiple injuries without TBI. Patients with TBI showed significantly lower concentrations of total cortisol and free cortisol compared with patients without TBI. Repeated measures analysis revealed different concentration dynamics in patients with TBI, with no increase in cortisol after trauma. CONCLUSION: Multiple trauma patients with TBI are at risk of acute impaired cortisol secretion and show an attenuated stress response as early as 12 h after injury.


Assuntos
Biomarcadores/sangue , Lesões Encefálicas Traumáticas/complicações , Hidrocortisona/sangue , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/diagnóstico , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/etiologia , Prognóstico , Estudos Prospectivos
12.
Mol Cell Biol ; 16(8): 4349-56, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8754835

RESUMO

Heterochromatin in metazoans induces transcriptional silencing, as exemplified by position effect variegation in Drosophila melanogaster and X-chromosome inactivation in mammals. Heterochromatic DNA is packaged in nucleosomes that are distinct in their acetylation pattern from those present in euchromatin, although the role these differences play in the structure of heterochromatin or in the effects of heterochromatin on transcriptional activity is unclear. Here we report that, as observed in the facultative heterochromatin of the inactive X chromosome in female mammalian cells, histones H3 and H4 in chromatin spanning the transcriptionally silenced mating-type cassettes of the yeast Saccharomyces cerevisiae are hypoacetylated relative to histones H3 and H4 of transcriptionally active regions of the genome. By immunoprecipitation of chromatin fragments with antibodies specific for H4 acetylated at particular lysine residues, we found that only three of the four lysine residues in the amino-terminal domain of histone H4 spanning the silent cassettes are hypoacetylated. Lysine 12 shows significant acetylation levels. This is identical to the pattern of histone H4 acetylation observed in centric heterochromatin of D. melanogaster. These two observations provide additional evidence that the silent cassettes are encompassed in the yeast equivalent of metazoan heterochromatin. Further, mutational analysis of the amino-terminal domain of histone H4 in S. cerevisiae demonstrated that this observed pattern of histone H4 acetylation is required for transcriptional silencing. This result, in conjunction with prior mutational analyses of yeast histones H3 and H4, indicates that the particular pattern of nucleosome acetylation found in heterochromatin is required for its effects on transcription and is not simply a side effect of heterochromatin formation.


Assuntos
Proteínas de Drosophila , Regulação Fúngica da Expressão Gênica , Heterocromatina/metabolismo , Histona Desacetilases , Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae , Transcrição Gênica , Acetilação , Acetiltransferases/metabolismo , Cromatina/metabolismo , Proteínas de Ligação a DNA/genética , Histona Acetiltransferases , Nucleossomos/ultraestrutura , RNA Mensageiro/genética , Sirtuína 2 , Sirtuínas , Transativadores/genética
13.
mBio ; 8(2)2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28442606

RESUMO

Exported proteins of bacterial pathogens function both in essential physiological processes and in virulence. Past efforts to identify exported proteins were limited by the use of bacteria growing under laboratory (in vitro) conditions. Thus, exported proteins that are exported only or preferentially in the context of infection may be overlooked. To solve this problem, we developed a genome-wide method, named EXIT (exported in vivotechnology), to identify proteins that are exported by bacteria during infection and applied it to Mycobacterium tuberculosis during murine infection. Our studies validate the power of EXIT to identify proteins exported during infection on an unprecedented scale (593 proteins) and to reveal in vivo induced exported proteins (i.e., proteins exported significantly more during in vivo infection than in vitro). Our EXIT data also provide an unmatched resource for mapping the topology of M. tuberculosis membrane proteins. As a new approach for identifying exported proteins, EXIT has potential applicability to other pathogens and experimental conditions.IMPORTANCE There is long-standing interest in identifying exported proteins of bacteria as they play critical roles in physiology and virulence and are commonly immunogenic antigens and targets of antibiotics. While significant effort has been made to identify the bacterial proteins that are exported beyond the cytoplasm to the membrane, cell wall, or host environment, current methods to identify exported proteins are limited by their use of bacteria growing under laboratory (in vitro) conditions. Because in vitro conditions do not mimic the complexity of the host environment, critical exported proteins that are preferentially exported in the context of infection may be overlooked. We developed a novel method to identify proteins that are exported by bacteria during host infection and applied it to identify Mycobacterium tuberculosis proteins exported in a mouse model of tuberculosis.


Assuntos
Infecções Bacterianas/microbiologia , Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/metabolismo , Tuberculose/microbiologia , Fatores de Virulência/metabolismo , Animais , Modelos Animais de Doenças , Camundongos
14.
Int J Pharm ; 514(2): 384-391, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27130363

RESUMO

Combining the advantage of higher efficacy due to local pulmonary administration of pyrazinoic acid (POA) and potent effect of pyrazinoic acid ester (PAE) delivered as an aerosol would aid in tuberculosis therapy. A combination spray dried dry powder, composed of POA, PAE (n-propyl POA), maltodextrin and leucine, was prepared for aerosol delivery to animals. Solid-state characteristics of morphology (scanning electron microscopy) crystallinity (X-ray powder diffraction), thermal properties (thermogravimetric analysis and differential scanning calorimetry) and moisture content (Karl Fisher) were evaluated. Particle size distributions, by volume (laser diffraction) for the dispersed powder and by mass (inertial impaction) were determined. Efficient delivery of the powder to a nose only animal exposure chamber employed a novel rotating brush/micro-fan apparatus. Spherical, crystalline particles were prepared. The volume median diameter, ∼1.5µm, was smaller than the mass median aerodynamic diameter, ∼3.0µm, indicating modest aggregation. Drug content variations were observed across the particle size distribution and may be explained by PAE evaporative losses. Delivery to the nose-only exposure chamber indicated that boluses could be administered at approximately 3min intervals to avoid aerosol accumulation and effect uniform dose delivery with successive doses suitable for future pharmacokinetic and pharmacodynamic studies.


Assuntos
Administração Intranasal/instrumentação , Administração Intranasal/veterinária , Inaladores de Pó Seco/métodos , Inaladores de Pó Seco/veterinária , Pós/uso terapêutico , Pirazinamida/análogos & derivados , Administração por Inalação , Animais , Combinação de Medicamentos , Composição de Medicamentos/métodos , Composição de Medicamentos/veterinária , Tamanho da Partícula , Pós/administração & dosagem , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico
15.
J Exp Psychol Hum Percept Perform ; 16(1): 211-6, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2137519

RESUMO

Sperling, Landy, Dosher, and Perkins (1989) argued that all previous research on the kinetic depth effect has been contaminated by stimulus artifacts, and they developed a new task that they believe can successfully overcome this problem. The present discussion offers a counter-argument that artifacts are not as pervasive in previous research as Sperling et al. imply and that their proposed method is subject to precisely the same limitations as earlier studies. Also discussed are some general guidelines of experimental design in this type of research to minimize the possibility that subjects will adopt an inappropriate response strategy that does not truly reflect their visual perceptions of three-dimensional form.


Assuntos
Atenção , Percepção de Profundidade , Percepção de Forma , Percepção de Movimento , Aceleração , Aprendizagem por Discriminação , Humanos , Psicofísica
16.
J Exp Psychol Hum Percept Perform ; 14(4): 582-90, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2974869

RESUMO

Earlier studies of motion parallax found unambiguous relative depth perception when random dot patterns were systematically translated in accordance with either motion of the observer's head or motion of the display scope. The need for such relative motion between an observer and a flow field was examined by placing a flow field in a limited area (window) in a large scope and translating the window relative to the observer. Accuracy in judging surface orientation and quantitative depth estimates were determined by the velocity field relative to the observer and were not measurably affected by whether this field was produced with a stationary or a moving window. Accuracy was consistently higher for smaller ratios of maximum to minimum projected velocities, reaching 100% in one experiment with a 1.12:1 ratio. We conclude that fully effective motion parallax does not require relative motion between the observer's head and the contours of a flow field.


Assuntos
Percepção de Profundidade , Percepção de Movimento , Campos Visuais , Cabeça/fisiologia , Humanos
17.
J Exp Psychol Hum Percept Perform ; 24(4): 1257-72, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9706715

RESUMO

Perceived shape, rotation, and rigidity were investigated in displays with linear velocity gradients in the vertical and horizontal directions. Different temporal relationships between these gradients simulated perspective projections of frontally oriented or rotated translating dihedral angles, orthographic projections of rotating dihedral angles, or nonrigid motion. Displays with nonzero horizontal gradients were judged to represent greater angle magnitudes (less relative depth) than displays with 0 horizontal gradients. The temporal relationship between the vertical and horizontal gradients did not influence judged shape but did affect rotation and rigidity judgments; rigid rotations were judged to rotate most, and nonrigid displays were rated as least rigid. These results indicate that the visual system integrates information from more than 1 velocity field. Possible integration methods based on first-order optic flow analysis are discussed.


Assuntos
Percepção de Forma/fisiologia , Percepção de Movimento/fisiologia , Rotação , Dimensão Vertical , Humanos , Modelos Psicológicos
18.
J Exp Psychol Hum Percept Perform ; 11(2): 122-32, 1985 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3159832

RESUMO

Previous research on visually induced self-motion found that stimulation of the central visual field (up to 30 degrees in diameter) results in perceived object motion while self-motion requires peripheral stimulation. In the present study, perceived self-motion was induced with a radially expanding pattern simulating observer motion through a space filled with dots, with visual angles of 7.5 degrees, 10.6 degrees, 15 degrees, and 21.2 degrees. Speed and texture density were also varied. The duration of reported self-motion (a) decreased with increased speed, (b) failed to increase with increased visual angle, and (c) decreased with visual angle at the highest speed level. In a second experiment, subjects rated the perceived depth of the displays. The speed and speed/area interaction effects on judged depth matched those found for induced self-motion. These results suggest an extension of the focal/ambient theory: In addition to a more primitive ambient processing mode that requires peripheral vision, there is a higher level system concerned with ambient processing that functions in the central visual field and uses more complex stimulus information, such as internal depth represented in a radially expanding pattern.


Assuntos
Percepção de Movimento , Campos Visuais , Percepção de Profundidade , Humanos , Enjoo devido ao Movimento/psicologia , Ilusões Ópticas , Fatores de Tempo
19.
J Exp Psychol Hum Percept Perform ; 10(6): 749-60, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6239904

RESUMO

Parallel projections of dots on the surface of a transparent sphere rotating about a vertical axis provide strong impressions of depth and spherical shape. The hypothesis was tested that these impressions are the result of three perceptual heuristics: (a) The sinusoidal projected velocity function of each dot in the horizontal dimension tends to be perceived as a rotary motion in depth; (b) the projected velocity gradient in the vertical dimension is perceived as curvature in depth; and (c) the simultaneously visible fields of dots moving in opposite directions are perceived as surfaces separated in depth. When each factor was varied independently, all three significantly affected judgments of spherical shape and depth. Similar results were obtained with cylinders. The first factor was more important for shape judgments; the second was generally more important for depth judgments. These results, together with those of earlier studies in which these factors led to similar effects for different stimuli and transformations, suggest that these are general principles applicable to the perception of structure from both rigid and nonrigid motion.


Assuntos
Percepção de Profundidade , Percepção de Forma , Ilusões , Percepção de Movimento , Ilusões Ópticas , Aprendizagem por Discriminação , Humanos
20.
J Exp Psychol Hum Percept Perform ; 19(3): 598-614, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8331315

RESUMO

Perceived orientation in depth and 3D shape was investigated for perspective projections of translations and orthographic projections of rotations of 3D dihedral angles. The principal findings were that (a) perceived orientation in depth depends on the sign of the velocity gradient, even in the case of orthographic projections; (b) the relationship between perceived orientation and the sign of the velocity gradient is greater for shallower gradients in orthographic projections of rotations, consistent with previous findings for perspective translations; (c) the magnitudes of simulated dihedral angles were underestimated (relative depth overestimated) for orthographic projections of rotations but were overestimated for perspective projections of translations; and (d) the judged magnitude of the dihedral angle depends on the velocity ratio and on image compression; it cannot be predicted from the velocity ratio or the velocity gradient alone.


Assuntos
Percepção de Profundidade , Rotação , Percepção Visual , Adulto , Feminino , Percepção de Forma , Humanos , Masculino , Modelos Teóricos , Movimento (Física)
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