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BACKGROUND: The current discourse within the thoracic surgical and pulmonological communities pertains to a contentious debate over the optimal selection criteria for thoracostomy tube diameters utilized in the management of pleural effusions. A comprehensive examination of the variables that inform the clinical decision-making paradigm for the determination of appropriate chest tube calibers is imperative to enhance patient management and elevate the prognostic results. OBJECTIVES: The objective of this inquiry is to elucidate the determinants that influence thoracic surgeons and pulmonologists in their selection of chest tube size for the management of pleural effusions. METHODS: This cross-sectional study was based on an electronic questionnaire that was sent to the targeted populations through e-mail or a professional WhatsApp. The survey assessed the considerations of chest tube size selection as well as the respective advantages, disadvantages, and potential complications related to each size. RESULTS: The conducted study encompassed participants, with a nearly even distribution between thoracic surgeons (49.1%) and pulmonologists (50.9%). Most of these practitioners are within tertiary-level medical institutions (82.1%). A preference for small-bore chest tubes (SBCT), defined as < 14 French (Fr), was indicated by 54.8% of participants. The drawbacks associated with SBCT, such as kinking (60%) and blockage (70%), influenced the decision-making process negatively, while pain was a significant factor in the selection against LBCT (64%). Ultrasound guidance was a positive influence for the selection of SBCT (55%). Complications associated with LBCT included visceral and vascular injuries (55.7%), wound infection (45.3%), re-expansion pulmonary edema (43.3%), and subcutaneous emphysema (57.5%). In contrast, malposition was a complication more commonly associated with SBCT (49.1%). CONCLUSION: The decision regarding chest tube size was influenced by several critical factors which included the nature of pleural effusion, the volume of pleural fluid, and potential complications specific to the size of the chest tube used.
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PURPOSE: Graphene-polymer nanocomposites significantly impact dental filler and antibacterial applications. The study aims to overcome some problems dental filers present and improve their properties and antibacterial activity. Synthesis graphene oxide (GO) and poly (methyl methacrylate) (PMMA) were used to reinforce two types of commercial hybrid/nano-dental fillings. METHODS: Developed acoustic-solution-sonication-casting methods were applied to fabricate the new graphene-polymer-dental filler nanocomposites. The structure, morphology, rheological and mechanical properties, and antibacterial of the newly fabricated filling-PMMA/ GO nanocomposites were investigated. RESULTS: Fourier transform infrared (FTIR) showed a significant interaction between the filling and the additional materials. The X-ray diffraction (XRD) analysis revealed a considerable change in crystalline behavior. Optical microscope (OM) with field emission scanning electron microscopy (FESEM) pictures demonstrated a substantial change in the morphology of the samples with a homogeneous and fine dispersion of the nanomaterials in the filler matrix. Multi-frequency ultrasound mechanical properties measured the ultrasonic velocity, absorption coefficient, compressibility, bulk modulus, and other mechanical properties that notably enhanced after GO contributed up to 325% of the ultrasonic absorption coefficient compared with hybrid/nano-fillers. Rheological properties were measured as viscosity, absorption coefficient, and specific viscosity, which significantly improved after adding PMMA and incorporating GO up to 57% of the viscosity, compared with hybrid/nano-fillers. The inhibition zone of moth bacteria, such as Enterococcus faecalis and E. staph bacteria, improved after the contribution of GO nanosheets up to 46%. CONCLUSION: Nanofillers nanocomposites presented better properties and inhabitances zone diameter of antibacterial.
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BACKGROUND: Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors' perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals. METHOD: A cross-sectional study was conducted from the 15th to the 30th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors' perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions. RESULTS: A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment. CONCLUSION: Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice.
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Aprendizaje , Rondas de Enseñanza , Femenino , Humanos , Estudios Transversales , Personal de Salud , HospitalesRESUMEN
An important goal in researching the biology of olfaction is to link the perception of smells to the chemistry of odorants. In other words, why do some odorants smell like fruits and others like flowers? While the so-called stimulus-percept issue was resolved in the field of color vision some time ago, the relationship between the chemistry and psycho-biology of odors remains unclear up to the present day. Although a series of investigations have demonstrated that this relationship exists, the descriptive and explicative aspects of the proposed models that are currently in use require greater sophistication. One reason for this is that the algorithms of current models do not consistently consider the possibility that multiple chemical rules can describe a single quality despite the fact that this is the case in reality, whereby two very different molecules can evoke a similar odor. Moreover, the available datasets are often large and heterogeneous, thus rendering the generation of multiple rules without any use of a computational approach overly complex. We considered these two issues in the present paper. First, we built a new database containing 1689 odorants characterized by physicochemical properties and olfactory qualities. Second, we developed a computational method based on a subgroup discovery algorithm that discriminated perceptual qualities of smells on the basis of physicochemical properties. Third, we ran a series of experiments on 74 distinct olfactory qualities and showed that the generation and validation of rules linking chemistry to odor perception was possible. Taken together, our findings provide significant new insights into the relationship between stimulus and percept in olfaction. In addition, by automatically extracting new knowledge linking chemistry of odorants and psychology of smells, our results provide a new computational framework of analysis enabling scientists in the field to test original hypotheses using descriptive or predictive modeling.
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Biología Computacional/métodos , Bases de Datos de Compuestos Químicos , Odorantes , Algoritmos , Fenómenos Químicos , Humanos , Modelos Moleculares , Percepción Olfatoria/fisiología , Relación Estructura-ActividadRESUMEN
Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke.
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Axones/metabolismo , Bilirrubina/metabolismo , Lesiones Encefálicas/metabolismo , Corteza Cerebral/metabolismo , Hemorragia Cerebral/metabolismo , Accidente Cerebrovascular/metabolismo , Animales , Axones/patología , Lesiones Encefálicas/patología , Corteza Cerebral/patología , Hemorragia Cerebral/patología , Masculino , Ratones , Oxidación-Reducción , Accidente Cerebrovascular/patologíaRESUMEN
Delayed complications of subarachnoid hemorrhage (SAH) such as angiographic vasospasm, cortical spreading ischemia, microcirculatory dysfunction, and microthrombosis are reported in both patients and animal models of SAH. We demonstrated previously that SAH is associated with increased oxidative stress in the brain parenchyma, and that this correlates with dysfunction of endothelial nitric oxide synthase (eNOS) (homodimeric uncoupling). Uncoupling of eNOS exacerbated oxidative stress and enhanced nitric oxide (NO) depletion, and was associated with multiple secondary complications such as microthrombosis, neuronal apoptosis, and release of reactive oxygen species. Thus, we hypothesized that genetic abbrogation of eNOS would confer a beneficial effect on the brain after SAH. Using a prechiasmatic injection model of SAH, we show here that eNOS knockout (KO) significantly alleviates vasospasm of the middle cerebral artery and reduces superoxide production. Endothelial nitric oxide synthase KO also affected other nitric oxide synthase isoforms. It significantly increases neuron nitric oxide synthase expression but has no effect on inducible nitric oxide synthase. Endothelial nitric oxide synthase KO decreases Zn(2+) release after SAH, reduces microthrombi formation, and prevent neuronal degeneration. This work is consistent with our findings where, after SAH, increased oxidative stress can uncouple eNOS via Zn(2+) thiolate oxidation, or theoretically by depletion or oxidation of tetrahydrobiopterin, resulting in a paradoxical release of superoxide anion radical, further exacerbating oxidative stress and microvascular damage.
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Trombosis Intracraneal/prevención & control , Óxido Nítrico Sintasa de Tipo III/genética , Hemorragia Subaracnoidea/complicaciones , Vasoespasmo Intracraneal/prevención & control , Animales , Western Blotting , Circulación Cerebrovascular/fisiología , Modelos Animales de Enfermedad , Fibrinógeno/metabolismo , Inmunohistoquímica , Trombosis Intracraneal/enzimología , Trombosis Intracraneal/etiología , Trombosis Intracraneal/patología , Ratones , Ratones Noqueados , Neuronas/enzimología , Neuronas/patología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/fisiología , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Hemorragia Subaracnoidea/enzimología , Superóxidos/metabolismo , Vasoespasmo Intracraneal/enzimología , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/patología , Zinc/metabolismoRESUMEN
Early brain injury (EBI) has become an area of extreme interest in the recent years and seems to be a common denominator in the pathophysiology of global transient ischemia and subarachnoid hemorrhage (SAH). In this paper, we highlight the importance of cerebral hypoperfusion and other mechanisms that occur in tandem in both pathologies and underline their possible roles in triggering brain injury after hemorrhagic or ischemic strokes.
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Microcirculatory dysfunction may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). This study investigated structural changes in microvessels and their relationship to brain injury after SAH. We used 15 mice (n = 5 for each group) to create sham, saline-injected (100 µl 0.9% NaCl) or SAH (100 µl autologous blood) model by injection into the prechiasmatic cistern. We sacrificed mice 2 days after surgery and examined the brains using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunohistochemical staining of fibrinogen. We assessed neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling (TUNEL). Nitric oxide (NO) was measured with 4,5-diaminofluorescein-2-diacetate. TEM and SEM demonstrated that mice with SAH had significantly more of them arterioles with lesion characteristics consistent with microthrombi. Microthrombi number correlated with the number of apoptotic neurons and decreased NO in the brain. In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal death and decreased NO. These data suggest NO depletion may contribute to the formation of microthrombosis and arteriolar constriction, which in turn results in neuronal cell death.
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Microvasos/patología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patología , Trombosis/etiología , Análisis de Varianza , Animales , Constricción Patológica/fisiopatología , Modelos Animales de Enfermedad , Fibrinógeno/metabolismo , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Microcirculación/fisiología , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Microvasos/metabolismo , Microvasos/ultraestructura , Neuronas/patología , Óxido Nítrico/metabolismo , Hemorragia Subaracnoidea/etiologíaRESUMEN
Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of -translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates, and humans. Animal studies were generally of poor methodologic quality, and there was evidence of publication bias. Fresh blood injection to simulate SAH (vs. clot placement) and evaluation of vasospasm more than 3 days after SAH were independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans, and that injection of fresh blood and evaluation of vasospasm more than 3 days after SAH may be preferable for preclinical models.
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Modelos Animales de Enfermedad , Hemorragia Subaracnoidea/complicaciones , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/etiología , Animales , Angiografía Cerebral , Humanos , PubMed/estadística & datos numéricos , Vasoconstricción/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of -1.74; 95% confidence interval -2.04 to -1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.
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Angiografía Cerebral , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasoespasmo Intracraneal/tratamiento farmacológico , Animales , Interpretación Estadística de Datos , Modelos Animales de Enfermedad , Perros , Femenino , Humanos , Macaca , Masculino , Ratones , Sesgo de Publicación , Conejos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ratas , Especificidad de la Especie , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patología , Resultado del Tratamiento , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/patologíaRESUMEN
One of the major complications after subarachnoid hemorrhage (SAH) is angiographic vasospasm in the large arteries at the base of the brain. However, a clinical trial of clazosentan demonstrated a 65% relative risk reduction in angiographic vasospasm but no effect on mortality or clinical outcome, raising questions about the role of angiographic vasospasm played in outcome after SAH. The purpose of this study was to determine if reducing or reversing angiographic vasospasm with clazosentan reduced other secondary complications such as microthromboembolism, loss of long-term potentiation (LTP) and neuronal cell death in a rat model of SAH. SAH in rats was created by injection of 300 µl non-heparinized autologous blood into the pre-chiasmatic cistern. Clazosentan, 10mg/kg bolus, or vehicle control was administered 1h after SAH intravenously, followed by a continuous infusion (1mg/kg/h) into the jugular vein using an osmotic pump. Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls. However, clazosentan did not prevent the formation of microthromboemboli, neuronal cell death and degeneration and loss of LTP, suggesting there is a dissociation between large-artery angiographic vasospasm and other secondary complications of SAH. This result suggests that alleviation of angiographic vasospasm alone may not be sufficient to prevent other secondary complications or that off-target drug effects after systemic administration of clazosentan counteract the beneficial effects on angiographic vasospasm.
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Dioxanos/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/fisiopatología , Sulfonamidas/uso terapéutico , Tetrazoles/uso terapéutico , Análisis de Varianza , Animales , Caspasa 3/metabolismo , Distribución de Chi-Cuadrado , Modelos Animales de Enfermedad , Estimulación Eléctrica , Fibrinógeno/metabolismo , Fluoresceínas , Hipocampo/fisiopatología , Etiquetado Corte-Fin in Situ , Técnicas In Vitro , Potenciación a Largo Plazo/fisiología , Masculino , Compuestos Orgánicos , Fosfopiruvato Hidratasa/metabolismo , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/patología , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/etiologíaRESUMEN
BACKGROUND AND PURPOSE: Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury. METHODS: Mice were subjected to subarachnoid hemorrhage by injection of blood into the chiasmatic cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed. RESULTS: Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not affect superoxide anion radical, peroxynitrite, or microthromboemboli in the brain. Endothelial nitric oxide synthase uncoupling and neuronal injury also were not reduced by clazosentan. CONCLUSIONS: This study shows large-artery vasospasm is pathophysiologically independent of some other effects of subarachnoid hemorrhage. The findings have implications for development of treatments for this disease.
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Dioxanos/uso terapéutico , Estrés Oxidativo/fisiología , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/fisiopatología , Sulfonamidas/uso terapéutico , Tetrazoles/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/fisiopatología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Dioxanos/farmacología , Modelos Animales de Enfermedad , Antagonistas de los Receptores de la Endotelina A , Ratones , Ratones Transgénicos , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/fisiología , Estrés Oxidativo/efectos de los fármacos , Piridinas/farmacología , Pirimidinas/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Hemorragia Subaracnoidea/complicaciones , Sulfonamidas/farmacología , Tetrazoles/farmacología , Tromboembolia/etiología , Tromboembolia/prevención & control , Vasoespasmo Intracraneal/complicacionesRESUMEN
Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembolism and neuronal apoptosis. Here we test the hypothesis that recoupling eNOS with simvastatin can prevent these complications. SAH was created in mice that were treated with vehicle or simvastatin starting 2 weeks before or 30 minutes after SAH. SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO. These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, microthromboemboli and neuronal injury.
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Óxido Nítrico Sintasa de Tipo III/metabolismo , Simvastatina/farmacología , Hemorragia Subaracnoidea/patología , Animales , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Operón Lac , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Fosforilación/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Simvastatina/uso terapéutico , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/metabolismoRESUMEN
Subarachnoid hemorrhage (SAH) comprises only about 7% of all strokes worldwide but is associated with severe mortality and morbidity. SAH is associated with a number of secondary pathologies, such as: transient cerebral vasospasm, delayed ischemic neuronal deficit (DIND), cortical spreading depression, microcirculatory modifications, microthrombosis and ischemic complications. Available data demonstrate that there are complex interactions among these secondary complications, and NO plays an important role among the interactions. NO has been implicated to be a crucial molecule in eliminating vasospasm, facilitating neuroprotection, anti-microthrombosis, cerebral ischemic tolerance and promoting endothelial cell function. Therefore, therapeutic agent targeting a key component in the pathopyhysiology of SAH such as NO and its related enzymes would be favorable for future development of SAH drugs. Alternatively, because of the complex nature of the secondary complications after SAH, agents with multiple efficacies on these complications, or the combination of several agents such as NO donors, oxide radical scavengers and neuroprotectants might be more desirable.
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Óxido Nítrico/metabolismo , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/metabolismo , Animales , Depuradores de Radicales Libres/uso terapéutico , Humanos , Enfermedades del Sistema Nervioso/etiología , Fármacos Neuroprotectores/uso terapéutico , Donantes de Óxido Nítrico/uso terapéutico , Estrés Oxidativo/fisiología , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/terapia , Vasoconstricción/efectos de los fármacos , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/metabolismoRESUMEN
We studied whether endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled in large cerebral arteries after subarachnoid hemorrhage (SAH) and also whether this causes cerebral vasospasm in a mouse model of anterior circulation SAH. Control animals underwent injection of saline instead of blood (n=16 SAH and n=16 controls). There was significant vasospasm of the middle cerebral artery 2 days after SAH (lumen radius/wall thickness ratio 4.3 ± 1.3 for SAH, 23.2 ± 2.1 for saline, P<0.001). Subarachnoid hemorrhage was associated with terminal deoxynucleotidyl transferase dUTP nick-end labeling, cleaved caspase-3, and Fluoro-Jade-positive neurons in the cortex and with CA1 and dentate regions in the hippocampus. There were multiple fibrinogen-positive microthromboemboli in the cortex and hippocampus after SAH. Transgenic mice expressing lacZ under control of the eNOS promoter had increased X-gal staining in large arteries after SAH, and this was confirmed by the increased eNOS protein on western blotting. Evidence that eNOS was uncoupled was found in that nitric oxide availability was decreased, and superoxide and peroxynitrite concentrations were increased in the brains of mice with SAH. This study suggests that artery constriction by SAH upregulates eNOS but that it is uncoupled and produces peroxynitrite that may generate microemboli that travel distally and contribute to brain injury.
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Óxido Nítrico Sintasa de Tipo III/metabolismo , Hemorragia Subaracnoidea/enzimología , Animales , Arteriolas/enzimología , Arteriolas/patología , Western Blotting , Caspasa 3/metabolismo , Arterias Cerebrales/enzimología , Arterias Cerebrales/patología , Fibrinógeno/metabolismo , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Trombosis Intracraneal/enzimología , Trombosis Intracraneal/patología , Operón Lac/genética , Ratones , Ratones Transgénicos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Ácido Peroxinitroso/metabolismo , Hemorragia Subaracnoidea/genética , Superóxidos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Vasoespasmo Intracraneal/enzimologíaRESUMEN
INTRODUCTION: Statins have been studied in patients with aneurysmal subarachnoid hemorrhage (SAH) but the history, pharmacology, and studies have not been reviewed recently. METHODS: The development of statins as well as their biological effects and pharmacology are reviewed. Recent clinical studies in patients with SAH are summarized. RESULTS: Statins lower serum cholesterol but they also have antioxidant, anti-inflammatory, vasodilatory, angiogenic, neuroprotective, vasoprotective, and endothelial preserving actions. In patients with SAH, they may decrease the incidence of symptomatic vasospasm, although the effects on overall outcome are less clear. They should be continued in patients who are taking them on admission and perhaps initiated in those who have indications for them. Side effects are rare. CONCLUSION: A large randomized, double-blind clinical trial is needed before it can be determined that statins are beneficial for patients with aneurysmal SAH.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/prevención & control , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/prevención & control , Animales , Ensayos Clínicos como Asunto/normas , Modelos Animales de Enfermedad , Humanos , Hemorragia Subaracnoidea/etiología , Vasoespasmo Intracraneal/etiologíaRESUMEN
Nigerian strain of Peste des Petit Ruminant (PPR) virus and Mannheimia haemolytica (MH) biotype A serotype 2, was used successfully to reproduce a concurrent disease in West African Dwarf goats. The development of the various pathological features were studied at regular intervals following infection. The acute inflammatory reaction which had developed by day 3 after initial infection was characterised by flooding of the alveoli by neutrophils, oedema, hemorrhage and syncytial cells together with a moderate bronchial and bronchiolar epithelial necrosis. This progressed to a milder acute broncho interstitial pneumonia with giant cells. At this stage, the mucosal immunity were well developed especially the aggregate form of NALT and more of nodular forms of BALT. The organisms were demonstrated with strong immunostaining in the necrotic center, necrotic alveolar wall, fibrin, serous exudate, and degenerated leukocyte in the alveoli and respiratory airways. The bacterial antigens were observed as a strong immunostaining in the blood vessels of the nasal septum, sinusoid in the liver and interstium of the kidney, cytoplasm of alveolar macrophages, pneumocytes, bronchial and bronchiolar epithelium, in the monocytes in the blood vessels. These findings confirmed the enhancement of MH tropism especially in the respiratory tract, liver and kidney. It also showed that West african dwarf goats are highly susceptible to the intratracheal combined infection of PPR virus and MH. The fact that the infection induces strong mucosal responses, this phenomenon can be explored in Africa with the use of combined PPR virus and MH intranasal vaccines to curtail the menace of pneumonia associated with the combined infection on field.
Asunto(s)
Antígenos Bacterianos/aislamiento & purificación , Enfermedades de las Cabras/microbiología , Mannheimia haemolytica/clasificación , Infecciones por Pasteurellaceae/veterinaria , Peste de los Pequeños Rumiantes/complicaciones , Células Epiteliales Alveolares/microbiología , Animales , Células Epiteliales/microbiología , Enfermedades de las Cabras/etiología , Cabras , Inmunohistoquímica/veterinaria , Riñón/microbiología , Hígado/microbiología , Macrófagos/microbiología , Mucosa Nasal/microbiología , Infecciones por Pasteurellaceae/complicacionesRESUMEN
In this report we present a case of a young lady with abdominal abscesses and septicemia caused by Mycobacterium chelonae complex. Identification of the organism and initiation of the appropriate antimicrobial therapy was delayed, resulting in significant morbidity and multiple hospital admissions. Gram staining of these organisms from blood culture can be easily overlooked or confused with either debris or diptheroids. We concluded that detection of Gram-positive rod colonies should prompt an acid-fast stain to distinguish diphtheroids from rapidly growing mycobacteria in immunosuppressed patients.
Asunto(s)
Bacteriemia/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium chelonae/aislamiento & purificación , Absceso Abdominal/diagnóstico , Absceso Abdominal/microbiología , Adulto , Antituberculosos/uso terapéutico , Bacteriemia/microbiología , Técnicas Bacteriológicas/métodos , Femenino , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón/efectos adversos , Microscopía , Infecciones por Mycobacterium no Tuberculosas/microbiología , Coloración y Etiquetado/métodos , Factores de TiempoRESUMEN
A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. A needle was inserted stereotactically into the prechiasmatic cistern and 100 microl autologous arterial blood injected over seconds (n=10). Effects were compared to injection of saline (n=10) or to sham operation (n=7). Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P<0.009, Student's t-test). In order to determine if SAH in this model was associated with neuronal injury, brains were examined for TUNEL and fluoro-jade-positive cells. 60% of SAH but not saline-injected mice exhibited TUNEL-positive cells in the cerebral cortex and 30% of the SAH but no saline-injected mice had fluoro-jade positive cells in the cortex, hippocampus and dentate gyrus. The model is simple to perform and may be useful for investigating the pathophysiology of SAH.
Asunto(s)
Corteza Cerebral/patología , Circulación Cerebrovascular , Modelos Animales de Enfermedad , Arteria Cerebral Media/patología , Hemorragia Subaracnoidea/patología , Análisis de Varianza , Animales , Apoptosis , Masculino , Ratones , Microscopía Confocal , Coloración y Etiquetado , Vasoespasmo Intracraneal/patologíaRESUMEN
Clinical evidence suggests that factors other than cerebral vasospasm, such as delayed neuronal and astrocytic cell death, may play a role in the poor prognosis of patients with subarachnoid hemorrhage (SAH). Here we examined this using immunohistochemistry and confocal microscopy in 3 different brain areas in a dog model of SAH. Using antibodies against neuronal marker neuronal nuclear protein (NeuN) and astrocyte marker glial fibrillary acidic protein (GFAP) in conjunction with apoptosis marker (cleaved caspase-3), we quantified neurons and astrocytes to monitor the degree of apoptosis in both groups. Experimental SAH group showed 44 +/- 1% caspase-3 positive neurons in comparison to the 2.0 +/- 0.1% in the control group (P < 0.001, 6 animals each group). For astrocytes, a total 25 +/- 1% were caspase-3 positive in day 7 SAH group, as compared to 0.40 +/- 0.01% for controls (P < 0.001). Regional analysis revealed that neuronal caspase-3 immunoreactivity in all 3 regions were significantly higher (P < 0.001) in SAH animals than that in the control animals. However, the analysis of total area, size and signal co-localization of GFAP with caspase-3 indicated that astrocytic reactivity and proliferation are seen primarily in the hippocampal area, with the least changes detectable in the brainstem. We conclude that in the dog model, there was a significant increase of neuronal and astrocytic cleaved caspase-3, possibly reflecting apoptosis, following SAH induction. These changes coupled with neurological deterioration seen in patients may present a possible reason for the poor outcome in SAH patients.