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Biomedical subjects

M Dujovny

Publications and source records attributed to M Dujovny.

At least 19 recordsLinked to original sources
PubMed2006

Dobesilate inhibits the activation of signal transducer and activator of transcription 3, and the expression of cyclin D1 and bcl-XL in glioma cells.

OBJECTIVES: Because fibroblast growth factor (FGF) causes the intracellular accumulation of activated signal transducer and activator of transcription 3 (STAT3), we assessed whether dobesilate, a synthetic FGF inhibitor that has been reported to show antiproliferative and proapoptotic activities in glioma cell cultures, down-regulates the STAT3 signaling pathway in growing cultures of those cells. Because STAT3 signaling pathway plays pleiotropic roles in tumor proliferation, maintenance of STAT3 in its inactive state may prevent glioma growth and spreading. METHODS: Rat glioma C6 cells were treated with dobesilate and cultures were evaluated immunocytochemically for STAT3 activation and enhancement of the expression rate of cyclin D1 and bcl-XL. RESULTS: Dobesilate abrogates the accumulation of activated STAT3 in glioma cells. The decrease in the intracellular levels of activated STAT3 by the dobesilate treatment runs parallel with a significant attenuation of cyclin D1 and bcl-XL expression. CONCLUSION: Treatment with inhibitors of FGF down-regulates the STAT3 signaling pathway. These alterations could be correlated to the already observed inhibition of cell proliferation and promotion of apoptosis in glioma cell cultures by dobesilate. The reported results may open new avenues for developing new treatments against these tumors.

Animals↗
PubMed2005

Dihydroxy-2,5 benzenesulphonate (dobesilate) elicits growth arrest and apoptosis in glioma cells.

OBJECTIVES: Dihydroxy-2,5 benzenesulphonate (dobesilate) is used as an oral agent for treatment of vascular complications of diabetic retinopathy. We previously showed that blockade of fibroblast growth factor (FGF) driving angiogenesis with dobesilate inhibited new blood vessel formation in a mouse gelatine plug assay. In the present study we assessed the effects of dobesilate in rat glioma cells. METHODS: Rat C6 cells line were grown as adherent cells in Dulbecco modified Eagle medium supplemented with 1% (v/v) fetal bovine serum and antibiotics. Calcium dobesilate was added in independent experiments at the following concentrations: 10, 25, 50, 75 and 100 microM, and cells were incubated for 24 hours. Effects of dobesilate in glioma cell proliferation and survival were assessed using crystal violet staining and TUNEL assay, respectively. RESULTS: Incubation of glioma cells with dobesilate for 24 hours concentration-dependently decreased cell proliferation with an apparent IC50 of 25 microM, and this antiproliferative effect was related to a significant increase in glioma cell apoptosis. CONCLUSIONS: The results suggest that dobesilate is a promising candidate leading to the development of a new adjuvant therapeutic strategy for gliomas.

Animals↗
PubMed2005

Angiogenic capacity of human omental stem cells.

OBJECTIVES: The goals of the present study are to obtain, expand and characterize a stem cell population from human omentum and to evaluate its in vivo angiogenic capacities. METHODS: Human omental CD34+ cells were obtained from samples of human omentum by density gradient centrifugation in Ficoll. Proliferative pattern, marker expression (by flow cytometry) and angiogenic growth factor synthesis by omental cell cultures were determined. In vivo angiogenic capacity of the cells was evaluated in rats. RESULTS: Omental stem cells showed a high rate of proliferation (Ki67 staining), expressed CD34 marker and synthesized bFGF and VEGF. When implanted in rats, omental cells promoted neovascularization. Human omental cells were localized in rat tissue, mainly forming the endothelium of neo-vessels. Implantation of omental cells also facilitated angiogenesis of rat origin. CONCLUSION: CD34+ cell population of human omentum could be responsible for the clinical benefit of omental transplantation by promoting angiogenesis and synthesizing angiogenic growth factors to facilitate revascularization of injured tissue.

Animals↗
PubMed2003

Delayed minimally invasive cranioplasty.

Minimally invasive cranioplasty is presented. Stereolithography is a new technology applied for the manufacture of custom-made cranial prosthesis that can provide an accurate reproduction of difficult anatomical contours of large cranial defects. The pre-operative development of perfect-fit prostheses permits a significant decrease in the operative time, in the overall costs of surgery, as well as on the rate of complications observed in patients with large cranial defects. At the end, this paper reviews the current concepts of application of engineering into medicine.

Brain Diseases↗
PubMed2002

Neurocognitive assessment before and after cranioplasty.

OBJECTIVE: This paper addresses the possible value of neurocognitive tests on the evaluation of patients before and after cranioplasty for large cranial defects. METHODS: In a single patient with a large corrected cranial defect a detailed neurocognitive analysis was performed utilizing the EXIT interview and Cognistat before and after surgery. Planning and development of the surgical prosthesis were based on the pre-operative reconstruction of the head CT and on pre-operative pictures of the patient. Xenon-CT anatomical and quantitative cerebral blood flow (CBF) analysis was performed before and periodically after cranioplasty. FINDINGS: A significant improvement in major cognitive functions was observed after surgery. INTERPRETATION: Cognistat is a detailed neuropsychological battery that permits a better assessment of patients in diverse neurological conditions. The EXIT interview gives a better rapid assessment of cognition not provided by other methods, such as the mini-mental status examination (MMSE). The utilization of these techniques permits a better understanding of long-term outcomes for patients with diverse neurological conditions, including post-cranioplasty patients.

Adult↗
PubMed2002

Burr hole cover for ventriculoperitoneal shunts and ventriculostomy: technical note.

In patients who have undergone intracranial procedures, bone gaps or burr holes often result in small but undesirable scalp or skin depressions. The authors designed a burr hole cover for hydrocephalus shunt system or external ventricular drainage, which is shaped to alleviate the deformity of the burr hole by filling the bone defect and allowing the passage of the ventricular catheter. The specifications of this device and its clinical application are described.

Craniotomy↗
PubMed2001

Intervertebral foraminal ligaments of the lumbar spine: anatomy and biomechanics.

The anatomical existence of the transforaminal ligaments has been studied extensively. However, there are very few studies examining how the transforaminal ligaments could be involved in the causation of nerve root compression and the low back pain syndrome. In this article, the authors review earlier studies in an attempt to find anatomical and biomechanical correspondence between the intervertebral foraminal ligaments of the lumbar spine and the low back pain syndrome.

Aged↗
PubMed2001

Application of finite element analysis in neurosurgery.

With the rapid development of computer equipment, approximation by analytical solutions has become popular in mathematical modeling. Finite element (FE) analysis uses numerical methods to solve problems with physical phenomena, and these can be applied to various geometrically complex materials, such as brain. The FE formulation can provide such diverse domains as heat conduction, torsion of elastic material, diffusion and fluid flow, and it can view different objects of study in the neurosurgical field. In this article, the various applications of FE methods are introduced to illustrate the usefulness of the technique and the link between the external biomechanical aspect and internal phenomena in brain research.

Biomechanical Phenomena↗
PubMed2001

The neurochemical basis for the applications of the greater omentum in neurosurgery.

The omentum has been utilized in neurosurgery for over 30 years. However, the anatomical and physiological bases for its applications have not been described in great detail. In this paper, we will review the current status of the omentum applications for the management of central nervous system disorders.

Central Nervous System Diseases↗
PubMed2001

Endoscopic technique: a new model of subarachnoid hemorrhage in rats.

It has become increasingly evident that the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage (SAH) which described the ischemic consequences of cerebral arterial constriction is complex and multifactorial. In an attempt to study cerebral vasospasm, numerous investigators have used experimental animal models that resemble cerebral vasospasm in humans. No ideal model for SAH has been found as yet, and hence the quest for such a model continues. We developed an endoscopic technique that permits a direct vision of internal carotid artery and puncturing the artery to provoke SAH. This model will closely reflect the clinical setting of an aneurysm rupture. The onset of SAH was characterized by a sudden decrease of cerebral blood flow (CBF) and cerebral blood volume (CBV) by at least 40% in the first 20 min. Following this initial drop, there was an increase in the CBF and the CBV, however, they remained significantly below the base line values, at the end of 1 h. This study describes a new model of SAH in rat that simulates the clinical phenomenon of ruptured intracranial aneurysm that also produces cerebral vasospasm.

Animals↗
PubMed2000

Impact simulation on pre-formed prosthesis for large cranial defect.

Cranioplasty greater than 10 cm2 in size is challenging task for neurosurgeon. There are many successful trials to fill the small defect with various materials. Proper cranioplasty can provide subsequently restoration of cerebral protection, cosmetic aspect and neuronal function. However, larger defect may not provide adequate protection from the auto, industrial or sport accident even with cranioplasty. In this study, patch design using two popular materials was evaluated and compared with bone material. Then impact-releasing holes were implemented to the patch. The movement of the large patch and its effect on the underlying brain tissue upon simulated impact was evaluated by using finite element analysis.

Biomechanical Phenomena↗
PubMed1999

Syndrome of the trephined: theory and facts.

The pathophysiology behind "the syndrome of the trephined" has been under investigation over the past 50 years. Research related to barometric pressure, cellular metabolism, cerebrospinal fluid (CSF) dynamics, and the vasculature have attempted to decipher the mechanism of disease. These subjects are discussed in five papers along with specific topics related to the syndrome. The symptoms experienced after craniectomy, the resolution of symptoms with cranioplasty as well as CSF, cerebral blood flow, and metabolic studies are presented, respectively, with a review of the theories.

Journal Article↗
PubMed1999

A review of dural substitutes used in neurosurgery.

Numerous natural and synthetic substitutes have been proposed for dural grafting. Autografts, allografts, xenografts and nonabsorbable or absorbable polymer sheets have been used in experimental models and clinical practice. This article reviews the literature regarding the features, advantages, and related complications of different dural substitutes.

Journal Article↗
PubMed1999

Experimental animal models of traumatic brain injury: medical and biomechanical mechanism.

The numerous traumatic brain injury models were designed to study the nature of the human brain injury. The properties of six experimental injury models were reviewed in this article. Weight-drop models with or without skull protection were compared in terms of experimental setup, possible error source, and biomechanical prospect. The modified percussion models with or without rigid cortical impact were contrasted with regard to reliability, histopathological production, and deformation. The focal contusion model by mechanical suction force represented isolated cortical injury without compression brain injury. As a class of traumatic brain injury, brain retraction damage was reviewed in this article.

Journal Article↗
PubMed1999

Evaluation of expanded polytetrafluoroethylene (ePTFE) versus polydioxanone (PDS) for the repair of dura mater defects.

A comparative animal experimental study was performed to test the potential application of expanded polytetrafluoroethylene (ePTFE) vs. polydioxanone (PDS) as dural substitutes. Sixty male Sprague-Dawley rats underwent a right frontoparietal craniotomy, opening of the dura mater, and a small cortical lesion. The dural defect was covered with a piece of ePTFE or PDS. Animals were sacrificed at 30 days or 90 days. Following decalcification, heads including scalp, skull, and underlying brain were sectioned, stained with hematoxylin-eosin, and histologically analyzed. Dural defects repaired with ePTFE, showed minimal reactive changes and no adhesions to the brain surface. No foreign body type giant cell reaction was seen, and the graft became enclosed in a thin sheet of connective tissue. Dural defects repaired with PDS, showed some giant cell infiltration and ingrowth of collagen fibers. Both substitutes provided satisfactory biological function and biocompatibility. Expanded PTFE advantages included relative suppression of tissue ingrowth, ensheathment by connective tissue, and a high tearing strength. Although both materials show promise for use in dural grafting, further clinical studies are necessary to determine their potential applications as a human dural substitute.

Animals↗
PubMed1999

Computer-aided manufacturing of implants for the repair of large cranial defects: an improvement of the stereolithography technique.

The objective of this study is to demonstrate the utility of geometric modeling in cranioplasty; in other words, to use geometric modeling to generate a prototype that will be used as the base structure of a composite prosthesis for covering cranial defects. This geometric model is easy to manipulate and can be modified. To achieve this goal, the top surface of a cranial bone flap is digitized using a portable coordinate measurement machine. Intentionally, a sub-surface of the bone flap, representing the skull defect, was not digitized. A geometric model of the bone flap is generated that includes the undigitized region. With the technique described in this paper the authors generated the geometric model of the undigitized region (the skull defect). The geometric model of the bone flap is further manipulated and a series of conical cavities are introduced. Prototypes of the geometric models are manufactured using stereolithography. The clinical implications of this technique are discussed.

Antimutagenic Agents↗