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1.
Mater Sci Eng C Mater Biol Appl ; 109: 110573, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228937

RESUMO

Implant associated infections can result in devastating consequences for patients. One major cause is the formation of bacterial biofilms, which result in increased resistance against antimicrobial therapeutics. A reduction of implant associated infections can be achieved by functionalization of implant surfaces. The generation of three dimensional surface structures by femtosecond laser ablation is one method to fabricate bacterial repellent large scaled surfaces without altering the material chemical composition. The challenge is to reduce bacterial growth while improving cellular ongrowth. For this purpose, spike structures were created as small as possible by used fabrication method on cubic Ti90/Al6/V4-rods and their effectiveness against bacterial colonization was compared to unstructured Ti90/Al6/V4-rods. Rods were implanted in the rat tibia and infected intraoperatively with 103 CFU of Staphylococcus aureus. Besides clinical behaviour and lameness, the vital bacterial biomass, morphological appearance and the volume of eukaryotic cells were determined on the implant surface after 21 days. Bone alterations were examined by radiological and histological techniques. Unexpectedly, the laser-structured implants did not show a lower bacterial load on the implant surface and less severe infection related bone and tissue alterations compared to the group without structuring. Simultaneously, a better bony integration and a higher cellular colonization with eukaryotic cells was detected on the laser-structured implants. These findings don't support the previous in vitro results. Nevertheless, the strong integration into the bone is a powerful argument for further surface modifications focussing on the improvement of the antibacterial effect. Additionally, our results underline the need for in vivo testing of new materials prior to clinical use.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Implantes Experimentais/microbiologia , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Staphylococcus aureus/fisiologia , Animais , Aderência Bacteriana/efeitos dos fármacos , Lasers , Masculino , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/metabolismo , Infecções Relacionadas à Prótese/patologia , Ratos , Ratos Endogâmicos Lew , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia , Uracila/análogos & derivados
2.
Neuroscience ; 314: 134-44, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26642808

RESUMO

Fibroblast growth factors (FGFs) regulate development and maintenance, and reduce vulnerability of neurons. FGF-2 is essential for survival of midbrain dopaminergic (DA) neurons and is responsible for their dysplasia and disease-related degeneration. We previously reported that FGF-2 is involved in adequate forebrain (FB) target innervation by these neurons in an organotypic co-culture model. It remains unclear, how this ex-vivo phenotype relates to the in vivo situation, and which FGF-related signaling pathway is involved in this process. Here, we demonstrate that lack of FGF-2 results in an increased volume of the striatal target area in mice. We further add evidence that the low molecular weight (LMW) FGF-2 isoform is responsible for this phenotype, as this isoform is predominantly expressed in the embryonic ventral midbrain (VM) as well as in postnatal striatum (STR) and known to act via canonical transmembrane FGF receptor (FGFR) activation. Additionally, we confirm that the phenotype with an enlarged FB-target area by DA neurons can be mimicked in an ex-vivo explant model by inhibiting the canonical FGFR signaling, which resulted in decreased extracellular signal-regulated kinase (ERK) activation, while AKT activation remained unchanged.


Assuntos
Corpo Estriado/citologia , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/citologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Substância Negra/citologia , Substância Negra/metabolismo , Animais , Corpo Estriado/embriologia , Neurônios Dopaminérgicos/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vias Neurais/citologia , Vias Neurais/embriologia , Vias Neurais/metabolismo , Prosencéfalo , Isoformas de Proteínas/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Substância Negra/embriologia , Tirosina 3-Mono-Oxigenase/metabolismo
3.
J Neurooncol ; 90(3): 335-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18704268

RESUMO

Because of possible long-term toxicity, cranial radiotherapy (RT) was withheld as part of standard treatment for brain metastasis (BM) from non-seminomatous germ cell tumours (NSGCT). This study evaluates this change in management in our institute. Twenty-two consecutive patients with BM from NSGCT were analysed. Ten patients presented with BM at initial diagnosis (group 1), two patients developed BM at extra-cranial complete remission (CR) (group 2), and ten patients during treatment of the primary tumour without achieving CR (group 3). All patients received cisplatin-based induction chemotherapy. In group 1, three patients with a single metastasis and three patients with multiple BM underwent craniotomy. Five patients received chemotherapy and whole brain RT (WBRT), and five patients received chemotherapy without WBRT. In group 2, both patients underwent craniotomy for a relapse with multiple BM. One patient received additional high-dose (HD) chemotherapy with WBRT, and the other HD chemotherapy without WBRT. In group 3, one patient underwent craniotomy, seven patients received WBRT, and four patients additional HD chemotherapy. In group 1, five of ten patients (50%) achieved CR (follow-up 49-245 months), in four of those five without WBRT. In group 2, both patients achieved CR (follow-up 146 and 211 months). In group 3, one of ten patients (10%) achieved CR after HD chemotherapy and WBRT (follow-up 107 months). It is concluded that cure in patients with BM from NSGCT can be achieved with standard induction chemotherapy without WBRT.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Cisplatino/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Adulto , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/cirurgia , Craniotomia/métodos , Estudos de Avaliação como Assunto , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/classificação , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
4.
Acta Neurochir Suppl ; 71: 127-30, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9779164

RESUMO

Recent early cerebral blood flow (CBF) studies on severe head injury have revealed ischemia in a substantial number of patients with a variety of CT diagnoses. However, the underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathology. Therefore, acute CBF and CBV measurements were performed in 51 adult severely head injured patients within 24 hours after injury. For this purpose the stable Xenon-CT procedure was used for assessment of CBF, and a dynamic CT imaging technique was used for determining CBV. All ischemic patients were found among 35 subjects studied within 4 hours after injury (31%). Based on the occurrence of regional ischemia seven patients with varying anatomical lesions on CT were selected for comparison between CBF and CBV in ischemic and non-ischemic areas. Both CBF (p < 0.02) and CBV (p < 0.02) exhibited significantly lower values in the ischemic zones. Ten patients showing a subdural hematoma (SDH) were studied preceding surgery and seven were ischemic in at least one lobe or brainstem. Ipsilateral CBF was lower than CBF in the contralateral side (p < 0.1). CBV at the ipsilateral side was significantly reduced compared to the contralateral side (p < 0.05). Follow-up studies were performed in three ischemic patients and in one borderline ischemic patient immediately after removal of SDH showing a striking increase in both CBF and CBV. In the remaining 26 subjects follow-up studies were obtained between day 2 and day 8 and all patients showed CBF values within the normal range. These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels. This has implications for acute post-traumatic therapeutical strategies and management of the severely head injured patient and may lead to testing of new drugs that are effective in interfering with processes causing this ischemia.


Assuntos
Volume Sanguíneo/fisiologia , Isquemia Encefálica/fisiopatologia , Encéfalo/irrigação sanguínea , Traumatismos Cranianos Fechados/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Dominância Cerebral/fisiologia , Feminino , Traumatismos Cranianos Fechados/diagnóstico , Homeostase/fisiologia , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Tomografia Computadorizada por Raios X
5.
Neurosurgery ; 42(6): 1276-80; discussion 1280-1, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9632185

RESUMO

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.


Assuntos
Volume Sanguíneo/fisiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/fisiologia , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/fisiopatologia , Adolescente , Adulto , Criança , Traumatismos Craniocerebrais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X
6.
Stroke ; 28(10): 1998-2005, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9341710

RESUMO

BACKGROUND AND PURPOSE: Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements. METHODS: The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV = CBF x MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue. RESULTS: The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs. CONCLUSIONS: The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT x CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.


Assuntos
Volume Sanguíneo , Circulação Cerebrovascular , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/fisiopatologia , Feminino , Hemodinâmica , Humanos , Pressão Intracraniana , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Xenônio
8.
J Neurotrauma ; 13(1): 17-23, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8714859

RESUMO

Cerebral ischemic insults in at least 30% of severely head injured patients at a very early stage following trauma and are associated with early death. To date, the threshold for ischemia of 18 mL/100g/min used in human head injury studies has been adopted from animal studies (by temporary occlusion of the middle cerebral artery). Since the traumatized brain becomes more susceptible to irreversible damage if accompanied by ischemia one may question whether the threshold for ischemic vulnerability is higher than 18 mL/100 g/min. Cerebral ischemia can cause atrophy. Therefore, the authors obtained computerized tomography (CT) scans in 33 comatose head-injured patients (Glasgow Coma Score of 8 or less) at least 3 months following injury and compared ventricle sizes (as a reflection of atrophy) with cerebral blood flow (CBF) obtained within 4 h (average 2.3 +/- 0.8 h) after injury. Ventricular measurements were performed in three fashions: the third ventricular size (cm), the bicaudate cerebral ventricular index (BCVI), and the hemispheric ventricular index (HCVI). No significant correlation was found between early CBF and any of the ventricule sizes. Applying a multiple correlation analysis with four independent parameters [CBF, CBF/time postinjury, CBF/(time postinjury)2, age], only age emerged as a significant indicator for predicting ventricle size (p < 0.001). We also compared CBF data, obtained within 4 h after trauma, from survivors at 3 months after injury (mean CBF of 32 mL/100 g/min) with CBF data from non-survivors (CBF 20 mL/100 g/min). The difference in CBF between survivors and nonsurvivors was significant at p < 0.001 (Wilcoxon rank-sum test). The proportion of patients with CBF less than or equal to 20 mL/100 g/min was 56% in the nonsurvivors and only 5% in survivors. The difference in the proportions was significant at p < 0.001 (chi-square test). We conclude that a measure of atrophy does not correlate with ultra-early CBF. However, based on the clear distinction between survivors and nonsurvivors, we suggest the threshold for ischemia after head injury be redefined as a CBF of 20 mL/100 g/min.


Assuntos
Lesões Encefálicas/complicações , Isquemia Encefálica/etiologia , Traumatismos Craniocerebrais/complicações , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Fatores Etários , Idoso , Animais , Atrofia , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Ventrículos Cerebrais/irrigação sanguínea , Ventrículos Cerebrais/patologia , Circulação Cerebrovascular , Confusão , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/fisiopatologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Análise de Regressão , Fatores de Tempo
9.
J Neurosurg ; 82(6): 966-71, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7760199

RESUMO

A traumatic cerebral contusion causes a zone of perifocal neuronal necrosis, the cause of which is not known; the surgical management of these lesions remains controversial. To determine the pathophysiological mechanisms responsible for brain damage after contusions, the authors performed cerebral blood flow (CBF) mapping studies and related these to change in local cerebral blood volume (CBV) and ultrastructure. In 11 severely head injured patients with contusion, CBF and CBV were measured in pericontusional areas using stable xenon-computerized tomography (CT). These studies demonstrated a profound reduction in perilesional CBF (mean 17.5 +/- 4 ml/100 g/min), which was always accompanied by a zone of edema defined by CT density measurements. Mean CBV in these regions was 2.3 +/- 0.4 ml/100 g, a reduction to approximately one-half the value of 4.8 ml/100 g found in the nonedematous regions, and to approximately 35% of the value of 6.0 ml/100 g found in normal volunteers. Ultrastructural analysis of the pericontusional tissue, taken at surgery in four patients with high intracranial pressure showed glial swelling with narrowing of the microvascular lumina due to massive podocytic process swelling. Additionally, some suggestion of vascular occlusion due to erythrocyte and leukocyte stasis was seen. These data support the conclusion that microvascular compromise by compression and/or occlusion is a major event associated with profound perilesional hypoperfusion, which is a uniform finding within edematous pericontusional tissue.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/patologia , Isquemia Encefálica/etiologia , Traumatismos Craniocerebrais/complicações , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Vasos Sanguíneos/ultraestrutura , Volume Sanguíneo , Concussão Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Xenônio
10.
Can J Neurol Sci ; 21(2): S6-11, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8087732

RESUMO

The relationships between cerebral blood flow (CBF), cerebral metabolism (cerebral metabolic rate of oxygen, CMRO2) and cerebral oxygen extraction (arteriovenous difference of oxygen, AVDO2) are discussed, using the formula CMRO2 = CBF x AVDO2. Metabolic autoregulation, pressure autoregulation and viscosity autoregulation can all be explained by the strong tendency of the brain to keep AVDO2 constant. Monitoring of CBF, CMRO2 or AVDO2 very early after injury is impractical but the available data indicate that cerebral ischemia plays a considerable role at this stage. It can best be avoided by not "treating" arterial hypertension and not using too much hyperventilation, while generous use of mannitol is probably beneficial. Once in the ICU, treatment can most practically be guided by monitoring of jugular bulb venous oxygen saturation. If saturation drops below 50%, the reason for this must be found (high intracranial pressure, blood pressure not high enough, too vigorous hyperventilation, arterial hypoxia, anemia) and must be treated accordingly.


Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular , Traumatismos Craniocerebrais/fisiopatologia , Monitorização Fisiológica/métodos , Encéfalo/irrigação sanguínea , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Traumatismos Craniocerebrais/metabolismo , Humanos , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/fisiopatologia , Oxigênio/sangue , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Fatores de Tempo
11.
J Neurosurg ; 80(2): 324-7, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8283273

RESUMO

The authors report two cases of severe head injury with acute subdural hematoma, in which cerebral blood flow (CBF) and cerebral blood volume (CBV) measurements were obtained prior to evacuation of the subdural hematoma and again immediately after removal. The first patient, a 21-year-old man with a motor response localizing to pain, had a global CBF of 18.2 ml/100 gm/min and a decreased global CBV of 3.7 ml/100 gm at 2.3 hours after injury. Immediately after removal of the subdural hematoma (8.1 hours after injury), CBF and CBV measurements revealed increases to 35.5 ml/100 gm/min and 5.8 ml/100 gm, respectively. The second patient, a 49-year-old woman with a normal flexor motor response to pain, had preoperative global values of 15.8 ml/100 gm/min for CBF and 2.0 ml/100 gm for CBV at 3 hours after injury. Postoperatively (9.3 hours after injury), the CBF and CBV values increased to 41.6 ml/100 gm/min and 4.0 ml/100 gm, respectively. The first patient, with only borderline ischemia and removal of the subdural hematoma within 3 hours, made a good recovery, while the second patient, with prolonged lower levels of CBF, remained in a persistent vegetative state. The low values of preoperative CBV argue for compression of the microcirculation as the cause of ischemia.


Assuntos
Hematoma Subdural/cirurgia , Ataque Isquêmico Transitório/fisiopatologia , Adulto , Circulação Cerebrovascular , Feminino , Hematoma Subdural/complicações , Hematoma Subdural/diagnóstico por imagem , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Radiografia
12.
Artigo em Inglês | MEDLINE | ID: mdl-8310862

RESUMO

During the last few years continuous measurements of CBF by means of a thermal diffusion blood flow probe have been proposed as a possible means for monitoring the patient's CBF in a clinical setting. Also, it has been suggested that continuous CBF data from head injured patients can be correlated with other continuously recorded clinical parameters, such as ICP and blood pressure, in order to clarify pathophysiological mechanisms such as "plateau-waves". We measured regional cortical blood flow continuously with a thermal diffusion flow probe in 13 comatose head injured patients after undergoing craniotomy for evacuation of a traumatic intracranial mass lesion in order to assess the reliability and usefulness of the method. In seven patients stable Xenon-CT CBF studies were performed with the flow probe in place, in order to compare the two methods. The continuous blood flow values did not correlate with regional or global stable Xenon-CT values. These results indicate that continuous monitoring of CBF with the thermal diffusion method as currently used cannot be used in the clinical management of the patient. Further research will have to be directed to the question as to whether changes in CBF are reliably measured with this method. If this is true, the thermal diffusion flow probe with its high temporal resolution may still be useful in investigating pathophysiological mechanisms such as interaction between CBF, ICP, mean arterial blood pressure (MABP), and end-expiratory CO2 (etCO2).


Assuntos
Regulação da Temperatura Corporal/fisiologia , Dano Encefálico Crônico/fisiopatologia , Lesões Encefálicas/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Cuidados Críticos , Monitorização Fisiológica/instrumentação , Termômetros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Concussão Encefálica/fisiopatologia , Concussão Encefálica/cirurgia , Lesões Encefálicas/cirurgia , Meios de Contraste , Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Complicações Pós-Operatórias/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Processamento de Sinais Assistido por Computador/instrumentação , Tomografia Computadorizada por Raios X/métodos , Xenônio
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