Early DNase-I therapy delays secondary brain damage after traumatic brain injury in adult mice.

Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood-brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p < 0.0001) and to stabilize BBB integrity (p = 0.019) 1 day post-injury (dpi). At 6 h post injury LD-treated animals showed less cleavage of fibrin (p = 0.0014), and enhanced perfusion as assessed by micro-computer-tomography (p = 0.027). At 5 dpi the number of Iba1-positive cells (p = 0.037) were reduced, but the number of CD45-positive cells, motoric function and brain lesion volume was not different. Posttraumatic-treatment with DNase-I therefore stabilizes the BBB, reduces the formation of brain edema, immune response, and delays secondary brain damage. DNase-I might be a new approach to extend the treatment window after TBI.

Ribonuclease-1 treatment after traumatic brain injury preserves blood-brain barrier integrity and delays secondary brain damage in mice.

Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood-brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12 h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24 h and 120 h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (- 31% RNase 40 µg/kg vs. vehicle), brain water accumulation (- 5.5%), and loss of BBB integrity (- 21.6%) at 24 h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (- 53.3%) and microglial activation (- 18.3%) at 120 h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI.

Biofunctionalization of synthetic bone substitutes with angiogenic stem cells: Influence on regeneration of critical-size bone defects in an in vivo murine model.

PURPOSE: The aim of this study was to investigate the influence of human bone marrow-derived endothelial progenitor cells (EPC) on vascularization and bone regeneration in combination with a bone-substitute material (BSM) in a critical-size bone defect in a murine model. Critical-size bone defects were performed and the defects were filled according to the group membership. MATERIALS AND METHODS: Eighteen rats were randomized in two experimental groups: BSM (BoneCeramic) with/without EPC biofunctionalization, and a control group without BSM and EPC. Calvaria bone defects were performed and the defects were filled according to the group membership. After 8 weeks, qualitative tissue response of newly formed bone mass was analyzed by histology, cone beam CT (CBCT) and micro-CT (µCT) scans. Occurrence of tumor masses due to EPC vascularization in peripheral organs was investigated microscopically in histological slides of liver and kidney. RESULTS: The combination of EPC and BSM showed smaller bone defects in the CT scans and the histological evaluation as the single use of BSM without EPC by trend (p = 0.067). Further, a higher amount of blood vessels could be found in histological slices of BSM in combination with EPC. No inflammatory response or tumor formation could be found. CONCLUSION: These findings confirm the biocompatibility of the used BSM and provide evidence that the combination of BSM with EPC might be effective for bone vascularization and regeneration. Using EPC in augmentation sites might overall lead to faster and better bone regeneration and should be further investigated in future studies.

A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke. Cerebral vasospasm that occurs in the aftermath of the bleeding is an important factor determining patient outcome and is therefore frequently taken as a study endpoint. However, in small animal studies on SAH, quantification of cerebral vasospasm is a major challenge. Here, an ex vivo method is presented that allows quantification of volumes of entire vessel segments, which can be used as an objective measure to quantify cerebral vasospasm. In a first step, endovascular casting of the cerebral vasculature is performed using a radiopaque casting agent. Then, cross-sectional imaging data are acquired by micro computed tomography. The final step involves 3-dimensional reconstruction of the virtual vascular tree, followed by an algorithm to calculate center lines and volumes of the selected vessel segments. The method resulted in a highly accurate virtual reconstruction of the cerebrovascular tree shown by a diameter-based comparison of anatomical samples with their virtual reconstructions. Compared with vessel diameters alone, the vessel volumes highlight the differences between vasospastic and non-vasospastic vessels shown in a series of SAH and sham-operated mice.

Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage.

Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore. SAH animals developed large vessel vasospasm, as shown by significantly lower vessel volumes of a 2.5-mm segment of the left middle cerebral artery (MCA) (SAH 5.6 ± 0.6 nL, sham 8.3 ± 0.5 nL, p < 0.01). Induction of SAH significantly reduced cerebral perfusion of the corresponding left MCA territory compared to values before SAH, which only recovered partly (SAH vs. sham, 15 min 35.7 ± 3.1 vs. 101.4 ± 10.2%, p < 0.01; 3 h, 85.0 ± 8.6 vs. 121.9 ± 13.4, p < 0.05; 24 h, 75.3 ± 4.6 vs. 110.6 ± 11.4%, p < 0.01; 72 h, 81.8 ± 4.8 vs. 108.5 ± 14.5%, n.s.). MCA vessel volume did not correlate significantly with MCA perfusion after 72 h (r = 0.34, p = 0.25). Perfusion correlated moderately with neuroscore (24 h: r = - 0.58, p < 0.05; 72 h: r = - 0.44, p = 0.14). There was no significant correlation between vessel volume and neuroscore after 72 h (r = - 0.21, p = 0.50). In the murine SAH model, cerebral hypoperfusion occurs independently of large vessel vasospasm. Neurological outcome is associated with cortical hypoperfusion rather than large vessel vasospasm.

Response of chromoblastomycosis to voriconazole.

Chromoblastomycosis is a chronic fungal infection of the epidermis, dermis and subcutaneous tissue, in which the most common etiologic agent in Brazil is Fonsecaea pedrosoi. In more advanced cases we found many difficulties in their treatment, and therefore, we report a case of extensive and severe chromoblastomycosis, with therapeutical failure of first choice treatments, but good response to voriconazole.

Response of chromoblastomycosis to voriconazole

Abstract: Chromoblastomycosis is a chronic fungal infection of the epidermis, dermis and subcutaneous tissue, in which the most common etiologic agent in Brazil is Fonsecaea pedrosoi. In more advanced cases we found many difficulties in their treatment, and therefore, we report a case of extensive and severe chromoblastomycosis, with therapeutical failure of first choice treatments, but good response to voriconazole.

The role of muscular trauma in the development of heterotopic ossification after hip surgery: An animal-model study in rats.

BACKGROUND: Heterotopic ossification (HO), the formation of bone in soft tissues, is a frequent complication after surgery of the hip and the pelvis. Although the pathophysiological entities responsible for the formation of HO remain largely unclear, muscle trauma is alleged to play a central role in the pathogenic mechanisms underlying HO. However, for this observation, made by many surgeons for decades, no objective evidence has been provided yet. METHODS: Fifty male Wistar rats were subjected to surgery of the right hip. The femoral canal was reamed in three steps up to 2mm. Animals formed 2 groups: in group 1 (25 animals) every effort was taken not to injure the muscles. In contrast, in the rats of group 2 (25 animals), an additional muscle lesion was created. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography, and classified using a modified Brooker classification system. A chi-square test was used to assess the statistical hypothesis comparing both groups. RESULTS: A significant higher amount of heterotopic bone was observed in animals that underwent additional muscular trauma. CONCLUSION: According to our data, muscle trauma seems to play an important role in the development of HO after hip surgery. Hence, during surgery, particular care not to injure the surrounding muscular tissue should be taken.

Relação entre enfermeiros e médicos no Hospital das Clínicas da Universidade Federal de Goiás: a perspectiva do profissional de enfermagem / Profesional relaationhip between nurses and doctors at the clinical hospital of federal university of goiás: the view ofnuurses / Relacón profesioonal entre enfermeras y médicos en el hospital de la universidad federal de goiás: la visión de las enfermeras

El conflicto en la relación entre médicos y enfermeras es un tema tabú en los servicios de salud y poco discutido en la literatura. Se sabe que el conflicto entre estas dos profesiones, identificados como los principales responsables de la atención al paciente, se debe a la combinación de diversos factores que van desde la creación del equipo multidisciplinario hasta las cuestiones salariales. El estudio tiene por objeto determinar si desde el punto de vista de enfermeria, hay un conflicto en la relación con los médicos en el Hospital das Clínicas de la Universidad Federal de Goiás (HC / UFG) y los factores que intervienen. Con este fin, 82 enfermeras respondieron a un cuestionario con preguntas demográficas y sobre las variables que afectan a la relación (Escala Likert). El resultado muestra predominio del sexo femenino (89%), edad promedio 40,5 años, tiempo promedio de trabajo 11 años y horario semanal promedio de 30 horas. El análisis factorial identificó tres Fatores de Protección (División de tareas, Reconocimento y Reflex en el paciente) y tres Factores de generación de conflictos (Comunicación, Reconocimiento y Condiciones de trabajo), mientras que el conflicto esté subyacente a los procesos de trabajo y de la relación intersubjetiva. El paciente es el principal beneficiario cuando hay buena relación y las fallas en la comunicación, las condiciones de trabajo y remuneración no digna son factores de desestabilización de la relación multiprofesional.

The conflict in the relationship between doctors and nurses is a taboo subject in the health service and little discussed in the literature. It is known that the conflict between these classes, that are directly responsible for the care of the patient, is caused by the combination of diverse factors ranging from the establishment of the group of work until the salary. The research presented here aimed to verify if there is conflict in the relationship between doctors and nurses at the Clinical Hospital of the Federal University of Goiás (HC) and the factors that may promote or prevent it. An amount of 82 nurses were interviewed to study this population and the categories of variables that interfere in their relationship with other professionals. The result was a population with a prevalence of females (89%) with mean age of 40.5 years, average working time at the HC of 11 years and with weekly working hours average of 30. Factor analysis identified three protective factors (Division of tasks, Teaching hospital and Influences in the patient) and three other conflict generator factors (Communication, Recognition and working conditions), while the conflict underlies the processes related to work and personal relationship. The patient is the primary beneficiary when there is a good relation. Bad communication, non-appropriate working conditions and unworthy remuneration are destabilizing factors for the inter-professional relationship.

O conflito na relação entre médicos e enfermeiros é assunto tabu nos serviços de saúde e pouco discutido na literatura. Sabe-se que o conflito entre essas duas profissões, tidas como as principais responsáveis pelo cuidado do paciente, é causado pela associação de diversos fatores que vão desde a constituição da equipe multiprofissional até as questões salariais. O estudo pretende averiguar se, na visão da enfermagem, há conflito na relação com médicos, no Hospital das Clínicas da Universidade Federal de Goiás (HC/UFG) e os quais os fatores associados. Para tanto, 82 enfermeiros responderam a um questionário com dados demográficos e perguntas em escala Likert, sobre as variáveis que interferem na relação interprofissional. O resultado demonstra predomínio do gênero feminino (89%), idade média de 40,5 anos, tempo de trabalho médio no HC de 11 anos e carga horária semanal média de 30 horas. Da análise fatorial foram identificados três fatores de proteção (Divisão das tarefas, Influencia hospital escola e Reflexo no paciente) e três de geração de conflitos (Comunicação, Reconhecimento e Condições de trabalho), estando o conflito subjacente aos processos de trabalho e de relação intersubjetiva. O paciente é o principal beneficiado quando existe boa relação. Ruídos de comunicação, condições de trabalho inapropriadas e a remuneração indigna configuram-se como fatores desestabilizadores da relação interprofissional.

Pore characteristics of bone substitute materials assessed by microcomputed tomography.

OBJECTIVES: Pore configurations of alloplastic biomaterial scaffolds play a major role for new bone formation in vivo. Current studies on characteristics of pores in bone substitute materials focus on individual particles or single blocks. Thus, three-dimensional (3-D) architecture of particle aggregates, representing the clinical relevant in vivo situation is not adequately taken into account. The aim of this study was the visualization and quantification of pore properties, both of the scaffold structure of single particles as well as of the micro-morphology of complex 3-D aggregated particle-conglomerates. MATERIAL AND METHODS: In model experiments, standardized plexiglass cylinders were stuffed with commercial bone substitute material particles with diverse chemical composition (HA, beta-TCP, HA-SiO(2), HA-beta-TCP, bioactive glass), origin (phycogenic, bovine, synthetic) and granulation (50 mum-2000 mum). Analogue to establish procedures for native (human) bone samples, non-fixed bone substitute materials were scanned by high-resolution microcomputed tomography. In addition to computer animated two-dimensional and 3-D reconstruction of the samples, median pore thickness and pore size distribution were determined. Materials representative for their chemical constitution were documented by SEM imaging. RESULTS: Investigated specimens significantly were different in micro-morophology and pore properties, ranging from highly porous to rather solid. The most voluminous pores were localized interparticularly. Within one product line, the determined pore properties showed a significant correlation with single particle grain sizes. CONCLUSION: The generation and interpretation of micro-CT based 3-D pore models can provide further insight into the expected osteoconduction dynamics and therefore might serve as a basis for further modifications of scaffold size and geometry as well as for further invasive studies on the biological behaviour of the scaffolds.

Impact of Crest Night Effects bleaching gel on dental enamel, dentin and key restorative materials. In vitro studies.

PURPOSE: To examine the effects of a paint-on 19% sodium percarbonate 'overnight' bleaching gel on the structure and integrity of enamel, dentin and some common restorative materials, with a laboratory cycling model. METHODS: Enamel, root dentin and restorative materials (glass-ionomer, composite and amalgam) were prepared in methacrylate molds with surface polishing. A treatment regimen was carried out including diurnal incubation in pooled human saliva and including twice daily toothbrushing with standard fluoridated dentifrice. Test samples were treated daily with Crest Night Effects bleaching gel, which included drying of surfaces, painting of percarbonate bleaching gel, and then incubation throughout the day (8 hours) to simulate overnight wear. Treatments were carried out over 14 days, to simulate clinical exposure periods. Control and test specimens were evaluated for surface and subsurface structure and morphological integrity utilizing surface microhardness, surface profilometry, and confocal laser scanning microscopy. RESULTS: Percarbonate bleaching film treatments had no effects on enamel or root dentin surface microhardness, or on subsurface ultrastructural integrity of enamel and coronal dentin. Surface profilometry confirmed retention of small amounts of residual silicone polymers, which contributed to CLSM air objective appearance and surface roughness measures. Restoratives were generally passive to bleaching gel treatments, though composite showed a tendency to attract retained residual silicone film.