Biomedical subjects

Manuel Dujovny

Publications and source records attributed to Manuel Dujovny.

At least 19 recordsLinked to original sources

PubMed2005

Bone-like polyethelyne burr-hole cover.

OBJECTIVE: Several materials are available for covering burr holes but none of them are ideal with respect to biocompatibility, strength and morbidity. With these properties in mind, our objective was to design a porous polyethylene device, which looked like bone and provides protection and cosmesis while being quick and easy to apply. METHODS AND MATERIALS/RESULTS: A burr-hole cover was created to cover small cranial defects and craniostomies. Using high-density polyethylene, this cover was designed to resemble the bony structure of the skull. Its porous architecture allows for tissue ingrowth and bony integration. It consists of a cylinder which fits into the burr hole and a cap which can be sutured or anchored with titanium screws. CONCLUSIONS: The "bone-like" burr-hole cover provides adequate protection, biocompatibility and cosmesis and is simple to use. Alternative implants can be toxic to surrounding tissues, costly and time consuming to apply. This high-density polyethylene cover is compatible with surrounding tissue as well as being of a porous nature and the material it is made from offers high tensile strength for adequate protection.

Absorbable Implants↗

PubMed2005

Attenuation of pain perception after transposition of the greater omentum to the cauda equina region of rats--a preliminary observation.

BACKGROUND: This paper addresses a specific experimental design to suggest the possible role of the greater omentum in the modulation of pain in rats. METHODS: Fifteen male Sprague-Dawley rats weighing between 275 and 325 g were selected. The animals were randomized and then anesthetized with pentobarbital (35 mg/kg) and divided into three groups: (1) sham: laparotomy followed by laminectomy with exposure of the spinal epidural space (n=5); (2) transposition of pedicled omentum (n=5) to the cauda equina epidural space; and (3) transposition of pedicled omentum (n=5) to the cauda equina intradural space. The animals were operated upon and once more randomized by an independent investigator, so that the groups were thought to be similar during post-operative testing. The latency of paw withdrawal to noxious heat stimulation was tested and the values (seconds) plotted for 1, 3, 6, 11, 14 and 30 days after surgery. Randomization codes were open after the animals were euthanized. The analysis of variance (ANOVA) without replication was applied for each of the dataset and comparisons established among the different study groups involved. The omenta were removed and standard immunohistochemistry was performed for gamma-amino-butyric acid (GABA), serotonin, calcitonin-gene related protein (CGRP), vascular intestinal peptide (VIP) and Met-enkephalin. RESULTS: The response to high heating rates of stimulation favored intradural versus sham and epidural omental transpositions. High and low noxious heat stimulation suggested an increased threshold to noxious stimulation after the 3 and 30 days of omental transposition. In the low heat stimulation series, responses were comparatively higher than in the sham animals. CONCLUSIONS: The suggested increased threshold of response to noxious stimulation after transposition of the greater omentum onto the spinal cord of rats suggested a novel role of the omentum and a potential future application in the clinical arena.

Analysis of Variance↗

PubMed2004

Current concepts on the expression of neurotrophins in the greater omentum.

The omentum has been utilized in Neurosurgery since the late 1960s. Its overwhelming effects on fibroblast and peripheral nerve growths were soon noticed. However, there was no direct evidence of production of any of the growth factors by the omentum, although substances were shown to be present in the omentum. Three animals were used in the study. After removal of the omentum in one, the tissue was submitted to PCR for BDNF, NT3/4 and NT5. Water was the negative control utilized. There was marked expression of all neurotrophins in the omentum, indicating local production of all those substances. The omentum has, for the first time, demonstrated to produce and not only accumulate neurotrophins. Utilization of this concept may permit transplant or transposition of parts of the omentum into the central nervous system for the management of multiple diseases, including vascular dementia, strokes, Alzheimer's disease or Moya-Moya disease.

Animals↗

PubMed2004

Bone marrow stromal cell implantation for peripheral nerve repair.

Cell therapy using bone marrow stromal cells is a new promising therapy for regenerative medicine. Previous studies demonstrated that local bone marrow stromal cells implantation in the distal stump of transected sciatic nerve of rats promotes early functional recovery. The purpose of this study was to expand on the preliminary research by investigating the long-term efficacy of bone marrow stromal cells using the same experimental setting. Functional test and histological studies demonstrate that bone marrow stromal cell-treated rats exhibit significant improvement on a walking tract test at day 180 after surgery compared with control rats. Taken together, these data suggest that bone marrow stromal cell therapy is a safe and effective strategy for peripheral nerve injuries.

Animals↗

PubMed2004

Neomycin inhibits glioma cell migration.

Blocking migration is an attractive strategy to inhibit glioma tumorigenesis. Previous studies have indicated that neomycin inhibits glioma cells proliferation. The purpose of this study was to expand on the preliminary research by investigating the antimigratory effect of neomycin. We used glioma C6 cells to investigate the role of neomycin in cell migration in vitro. Cell wounding assay showed that neomycin inhibits in a dose-dependent manner glioma cells migration into the wound. Taken together, these results suggest that neomycin is an attractive candidate for the development of novel antimigratory molecules useful for the treatment of gliomas.

Animals↗

PubMed2004

Differentiation-inducing activity of neomycin in cultured rat glioma cells.

Induction of cellular differentiation is an attractive therapeutic strategy against glioma cell proliferation and tumorigenicity. Preliminary in vitro studies have indicated that neomycin inhibits the proliferation of cultured glioma cells and induces changes in cellular morphology, making it potentially useful as a therapeutic agent for gliomas. The purpose of this work was to expand on the preliminary research by investigating the differentiation effect of neomycin in rat C6 glioma cells, using glial fibrillary acidic protein (GFAP) staining as a reliable marker of differentiation for normal astrocytes and for tumors of astrocytic lineage. Cell cultures were grown in the absence or presence of 10 mM neomycin sulfate for 48 hours. Neomycin treatment produced changes in cell morphology and GFAP expression indicative of cellular differentiation. These results suggest that neomycin is an attractive differentiation agent for the treatment of gliomas.

Animals↗

PubMed2004

Perivascular delivery of neomycin inhibits the activation of NF-kappaB and MAPK pathways, and prevents neointimal hyperplasia and stenosis after arterial injury.

The nuclear transcription factor kappaB (NF-kappaB) is a cytoplasmic dimer that, as the family of mitogen-activated protein kinase (MAPK), can directly regulate the expression of early genes and genes involved in the stress response, following a variety of physiological or pathological stimuli. Both of them stimulate the transcription of many proteins, which are considered important during inflammation. A crucial role has been assigned to these factors in cellular proliferation and in neointimal hyperplasia secondary to the endothelial lesion of arterial vessels. On the other hand, it has been described that neomycin can have an inhibitory function on tumor cell proliferation, through the inhibition of different intracellular pathways of signaling, among them the NF-kappaB and MAPK pathways. Rat common carotid artery was subjected to balloon angioplasty. Neomycin sulfate (18 mg) was applied using pluronic acid gel on the adventitial surface of the injured vessel. MAPK and NF-kappaB activation was quantified after 24 hours with immunohistochemical staining. Neointimal formation was quantified after 14 days with morphometry. Immunohistochemistry results demonstrating MAPK and NF-kappaB activation reveal that both transcription factors are activated in the media of the control vessel wall. In contrast, the immunoreactivity for MAPK and NF-kappaB in the sections obtained from arteries treated with neomycin over 24 hours was insufficient or nonexistent. Treatment with neomycin on adventitia over 14 days in arteries on which angioplasty was performed shows a neointimal index (intimal area/medial area) decrease of 71% in comparison with arteries that were not treated. The adventitial neomycin treatment over 14 days produces a very significant increase (287.5%; p<0.0001) in the arterial luminal circumference in comparison with arteries treated with vehicle. These results support the theory that neomycin plays an important role against neointimal hyperplasia through the inhibition of MAPK and NF-kappaB activation.

Animals↗

PubMed2003

Dual blockade of mitogen-activated protein kinases ERK-1 (p42) and ERK-2 (p44) and cyclic AMP response element binding protein (CREB) by neomycin inhibits glioma cell proliferation.

Several growth factors and their receptors are expressed in inappropriately high abundance in gliomas and are further upregulated during the transition from low- to high-grade malignancy. In glioma cells growth factors induce expression of mitogen-activated protein kinase (MAPK) pathways. Here we report that neomycin restrained glioma cell proliferation in vitro by inhibition of p42/44 MAPK and the cyclic AMP element binding protein (CREB)-directed transcription pathways. Since alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential, neomycin offers great promise for treating cancer and other diseases associated with a sustained MAPK activity.

Animals↗

PubMed2003

Stereolithography: neurosurgical and medical implications.

We present material to define and understand the concept of Stereolithography (STL) and its potential benefits to the field of neurosurgery and other medical specialties. A historical and scientific review of the literature on stereolithography, its evolution and uses in neurosurgery, forensic medicine, and other medical specialties are described. Considerations regarding different techniques used to obtain STL are discussed. The reproduction of cranial and vascular structures using this technique is evaluated. Data acquisition and model fabrication are the two basic steps required for stereolithography to create custom models for multiple applications in cranio-facial surgery, vascular studies, orthopedic surgery, urology and forensic medicine, among others. Stereolithography is a relatively new technique which continues to grow in many medical fields. Pre-operative education of patients, better understanding of patient anatomy, and the creation of custom-made prostheses are proven benefits of this technique.

Blood Vessels↗

PubMed2003

Glioma cell-associated sustained activation of the transcription factor, nuclear factor-kappa B, was inhibited by neomycin.

Experimental evidence suggests that the transcription factor nuclear factor-Kappa B (NF-kappa B) plays an important role in tumor cell invasion, apoptosis suppression and growth. Malignant glioma is one of the most intractable tumors because of its invasiveness to surrounding brain tissue. Our study investigated the role of neomycin on NF-kappa B activity in glioma cell cultures. We performed immunocytochemical analysis of cells with the antibody NF-kappa Bp65 which results show that neomycin decreases significantly the activation of NF-kappa B when added to glioma cultures for 30 min. This finding supports an important role for neomycin in glioma invasion, apoptosis and growth. Collectively, these data suggest a rationale for clinical trials with neomycin in the treatment of gliomas.

Animals↗

PubMed2003

Advances in ICP monitoring techniques.

With the advent of newer devices for measuring intracranial pressure (ICP) and cerebral metabolism, more alternatives continue to rise aiming to control ICP. This manuscript presents a proposed analysis of different ICP monitoring devices in order to make appropriate selection of them in our clinical setting including general and pediatric applications. A systematic review of the literature was made analyzing the technical advances in ICP monitoring. The recent in vitro and in vivo tests as well as mathematical/computer models were reviewed. Practical applications of principles were discussed and compared based on the mode of pressure transformation. A ventricular catheter connected to an external strain gauge transducer or catheter tip pressure transducer device is considered to be the most accurate method of monitoring ICP and enables therapeutic CSF drainage. The significant infections or hemorrhage associated with ICP devices causing patients morbidity are clinically rare and should not deter the decision to monitor ICP. Parenchymal catheter tip pressure transducer devices are advantageous when ventricular ICP cannot be obtained or if there is an obstruction in the fluid couple, though they have the potential for significant measurement differences and drift due to the inability to recalibrate. Subarachnoid or subdural fluid-coupled devices and epidural ICP devices are currently less accurate. With an increasing miniaturization of the transducers, fiberoptic systems have been developed, however, there is a problem of measurement accuracy during the period of patient monitoring and external calibration should be performed frequently to ensure constant accuracy. Ventriculostomies continue to have a pivotal role in ICP control. With a rational understanding of the applications and limitations of the different ICP monitoring devices, the outcome for critically ill neurological patients is optimized.

Animals↗

PubMed2003

Antiproliferative action of neomycin is associated with inhibition of cyclin D1 activation in glioma cells.

The progression of mammalian cells through G1 phase of the cell cycle is governed by the D-type cyclins (D1, D2, D3). These proteins are induced at the beginning of the G1 phase and associate with serine/threonine cyclin-dependent kinases to form holoenzymes. Overexpression of cyclin D1 in human cancers as well as in several cancer cell lines has been reported. Here, we employed mitotic selection to synchronize the C6 glioma cell cycle at the start of the G1 phase and assessed the effects of neomycin on cyclin D1 protein detection by immunocytochemical analysis. Cyclin D1 activation as well as cell proliferation were already significantly reduced after 3 h of incubation of the cells with neomycin. These findings suggested that the antiproliferative effects of neomycin in gliomas could be mediated by inhibition of the expression of cyclin D1 gene and support further consideration of therapeutic use of neomycin in a Phase I clinical study for patients with recurrent glioblastoma.

Animals↗

PubMed2003

Brain retraction injury.

This paper reviews the literature of the brain retraction injury during the last century. The review focused on the instrument characteristic as well as the physiopathological and histopathological damage of the brain induced by brain retraction. It was found that lesions were induced by cerebral ischemia. We conclude that a better monitoring system needs to be developed to avoid brain injury.

Animals↗

PubMed2002

Late outcome following central nervous system injury in child abuse.

OBJECTIVE: The object of this study was to increase our understanding of the social, clinical, radiographic and psychological consequences of child abuse after the initial insult and to describe the role of neurosurgery and other specialties in this context. METHODS: A review of the literature on child abuse (using scientific journals, textbooks, and internet reports) was conducted, with special attention given to child abuse in infants. The biomechanical patterns of injury, the long-term neurological, psychological, and social outcomes and methods of rehabilitation are reviewed. CONCLUSIONS: Head injury associated with physical abuse carries a significantly worse clinical outcome than accidental trauma. Late findings in CT scans and MRI show evidence of cerebral atrophy in 100% and cerebral ischemia in 50% of physical abuse cases. Abuse and neglect have a strong impact in developing children, producing emotional, cognitive, and social problems that may persist throughout the rest of their lives. Outcome cannot be improved without an integrated rehabilitation strategy encompassing early field management, hospital therapy, precise targeting of educational and cognitive needs, and finally return to the community. New ancillary tests have emerged that are aimed at improving rehabilitation and illuminating the long-term physiological and functional impact of abuse.

Central Nervous System Diseases↗

PubMed2002

CNS child abuse: epidemiology and prevention.

The problem of child abuse and the central nervous system implications are reviewed from a multidimensional approach. Statistics regarding prevalence, risk factors, epidemiological considerations, and physiological aspects are studied. The incidence is reviewed in the United States and in other countries where incidence and social services are also described. Implications for prevention efforts are considered.

Age Factors↗

PubMed2002

Antiproliferative effect of neomycin in glioma cells.

The angiogenic growth factor (AGF) family of signaling molecules has been implicated in normal development and in physiological process as well as in human malignancy. Since blockage of nuclear translocation of AGF in endothelial cells with neomycin resulted in inhibition of the growth factor capacity to induce angiogenesis, we treated glioma cells with neomycin and assessed its effects on cell proliferation. Administration of 10mM neomycin during two days resulted in a 56% inhibition of glioma cells proliferation. This result may provide the basis for the development of a novel adjuvant therapeutic strategy forgliomas.

Animals↗

PubMed2002

Inhibition of rat glioma growth by neomycin. Preliminary report.

Tumor development is known to largely depend on angiogenesis, and nuclear translocation of angiogenic factors is one of the crucial steps in tumor angiogenesis. This preliminary study was designed to investigate the suppression of tumor growth by neomycin, an inhibitor of nuclear translocation of several angiogenic factors overexpressed in gliomas. We found that intratumoral osmotic pump delivery of 10 mM neomycin caused significant inhibition of C6 glioma tumor development (85%) in rats. The data establish neomycin as a potential inhibitor of angiogenesis-dependent tumor growth and raise the possibility for its use as therapy in pathologies in which neovascularization is involved, including neoplasia.

Animals↗

PubMed2002

Peripheral nerve regeneration by bone marrow stromal cells.

Adult bone marrow contains stem cells that have attracted interest through their possible use for cell therapy in neurological diseases. Bone marrow stromal cells (MSCs) were harvested from donor adult rats, cultured and pre-labeled with bromodeoxyuridine (BrdU) previously to be injected in the distal stump of transected sciatic nerve of the rats. Distal nerve stump of control rats received culture medium solution. MSCs-treated rats exhibit significant improvement on walking track test at days 18 and 33 compared to controls. Dual immunofluorescence labeling shows that BrdU reactive cells survive in the injected area of transected sciatic nerve at least 33 days after implantation, and almost 5% of BrdU cells express Schwann cell-like phenotype (S100 immunoreactivity). Because MSCs injected in a lesioned peripheral nerve can survive, migrate, differentiate in Schwann cells, and promote functional recovery, they may be an important source for cellular therapy in several neurological diseases.

Animals↗