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1.
J Card Surg ; 32(1): 38-44, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27896834

RESUMEN

BACKGROUND: This study was performed to investigate the pre-existing histologic alterations at the time of complete repair in patients with tetralogy of Fallot (TOF) and evaluate their effects on the early postoperative outcomes. METHODS: Fourteen patients, seven with acyanotic TOF (SO2 > 90, group I) and seven with cyanotic TOF (SO2 < 90, group II), undergoing complete repair, were enrolled. Right ventricular biopsies were examined for cardiomyocyte injury and fibrosis by light microscopy and mitochondrial injury by electron microscopy. The association of the severity of histologic alterations and postoperative inotrope use, intensive care unit, and in-hospital stays were evaluated. RESULTS: Compared with group I, patients in group II had a higher inotrope score (p = 0.03) and longer intensive care unit (p = 0.01) and in-hospital stays (p = 0.04). Cardiomyocyte injury and mitochondrial damage scores were higher in group II (p = 0.01 and p = 0.02, respectively). Fibrosis was detected in all specimens but was more severe in group II (p < 0.001). However, we could not demonstrate any correlation between histologic alterations and early surgical outcomes. The history of spell was significantly associated with worse early surgical outcomes (p < 0.05). CONCLUSIONS: Pre-existing cardiomyocyte injury accompanied by mitochondrial damage and fibrosis were more pronounced in cyanotic TOF patients. Early repair may prevent the development of histopathologic alterations in these patients.


Asunto(s)
Ventrículos Cardíacos/patología , Miocardio/ultraestructura , Tetralogía de Fallot/patología , Procedimientos Quirúrgicos Cardíacos , Femenino , Fibrosis/patología , Ventrículos Cardíacos/cirugía , Humanos , Lactante , Masculino , Microscopía Electrónica de Transmisión , Tetralogía de Fallot/cirugía
2.
Toxicol Ind Health ; 33(7): 555-563, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28196456

RESUMEN

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles (NPs) in medicine, industry and cosmetics. They are generally considered as biocompatible. However, contradictory reports on their biosafety render them difficult to accept as 'safe'. In this study, we evaluated the neurotoxicity of direct AgNP treatment in rat hippocampal slices. We produced pure uncoated AgNPs by a pulsed laser ablation method. NP characterization was performed by Ultraviolet (UV) visible spectrophotometer, scanning electron microscope, transmission electron microscope (TEM) and energy-dispersive X-ray spectroscopy. Rat hippocampal slices were treated with AgNPs for an hour. AgNP exposure of hippocampal tissue resulted in a significant decrease in cell survival in a dose-dependent manner. Our TEM results showed that AgNPs were distributed in the extracellular matrix and were taken into the cytoplasm of the neurons. Moreover, we found that only larger AgNPs were taken into the neurons via phagocytosis. This study showed that the pure AgNPs produced by laser ablation are toxic to the neural tissue. We also found that neurons internalized only the large NPs by phagocytosis which seems to be the major mechanism in AgNP neurotoxicity.


Asunto(s)
Hipocampo/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Neuronas/efectos de los fármacos , Plata/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hipocampo/citología , Masculino , Fagocitosis , Ratas , Ratas Wistar , Espectrometría por Rayos X
3.
Am J Otolaryngol ; 37(5): 393-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27465503

RESUMEN

HYPOTHESIS: Tacrolimus helps healing of facial nerve injury. BACKGROUND: Positive effects of tacrolimus on axon regeneration and healing of injured peripheral nerves (eg. sciatic nerve) have been reported in the literature. Tacrolimus may be an additional treatment method that could improve the nerve healing after surgical treatment of cut injury of facial nerve. METHODS: 20 New Zealand rabbits were randomly separated into control and study groups of 10. In control group, no medical treatment was given after facial nerve anastomosis, and the animals were followed up for 2months. In the study group rabbits were given 1mg/kg/day tacrolimus subcutaneously for 2months after the facial nerve anastomosis. The histopathologic findings of axon regeneration like axon myelination were analyzed in both groups under electron and light microscopy. The data obtained in the groups were compared. RESULTS: Greater axon diameters, thicker myelin sheaths, and higher total number of myelinated axons were found in the tacrolimus group, suggesting better regeneration in this group when compared to the control group. There was less vacuolar degeneration in the study group. All these findings suggest that tacrolimus positively affects healing after facial nerve anastomosis. CONCLUSION: The results of this study indicate that tacrolimus has favorable effects on the healing process of the facial nerve after end-to-end anastomosis. Tacrolimus may be a promising agent in the future for nerve regeneration following traumatic facial paralysis surgery.


Asunto(s)
Traumatismos del Nervio Facial/tratamiento farmacológico , Traumatismos del Nervio Facial/cirugía , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Animales , Modelos Animales de Enfermedad , Traumatismos del Nervio Facial/patología , Masculino , Regeneración Nerviosa , Conejos
4.
J Nanosci Nanotechnol ; 15(12): 10156-64, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26682462

RESUMEN

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapy after surgical transurethral resection. Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium of the same family as tuberculosis, that is capable of inducing a local inflammatory response upon instillation into the bladder. Intravesical therapy with BCG has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors than most chemotherapeutic agents used for the same indication. However, compared to intravesical chemotherapy, BCG immunotherapy provokes more pronounced local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, life-threatening or fatal sepsis. Nanoparticles with positive surface charge and mucoadhesive properties were developed to overcome these side effects. Hence, the aim of this study was to optimize and evaluate cationic chitosan (CS) nanoparticles encapsulating BCG in terms of antitumor efficacy after intravesical administration in bladder tumor, induced in rat model. It was found that nanoparticle formulations of 269-375 nm in size can be produced with 42% encapsulation efficiency. The zeta potential was positive and was suitable for intravesical administration. Antitumor efficacy was determined over the parameters of histopathological evaluation, survival rate and mean bladder weight in comparison to treatment with commercial BCG solution. Concerning survival rates, BCG-loaded chitosan nanoparticles resulted in significantly longer survival than BCG commercial product (up to 86 days of survival with no systemic side effects). When compared to healthy bladder weight averages, all groups (especially BCG commercial solution) showed higher bladder weights confirming tumor formation. Histopathological findings confirmed antitumor activity in all treatment groups and optimum findings were observed in groups treated with CS nanoparticles encapsulating BCG. At the same time, significant nanoparticle accumulation in bladder tissues was observed especially for BCG-loaded CS group. In this study, it was clearly observed that cationic CS nanoparticles provide a significantly improved perspective in intravesical immunotherapy of bladder tumors.


Asunto(s)
Administración Intravesical , Inmunoterapia/métodos , Mycobacterium bovis , Nanopartículas/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Quitosano/química , Ratas
5.
Ann Plast Surg ; 74(6): 684-92, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24317243

RESUMEN

BACKGROUND: Propolis and curcumin have antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective features. The goal of this study was to determine the effects of propolis and curcumin on nerve healing in rat sciatic nerve crush injuries and to compare these effects with results obtained using steroid treatment. METHODS: In the sham group, the right sciatic nerves of rats were dissected and exposed, and the skin was closed without any additional manipulation. In the control group (group C), after the right sciatic nerves of rats were exposed, crush damage was inflicted using a surgical clamp. In the control-methylprednisolone group, crush injuries were inflicted on sciatic nerves as in group C. After injury, 1-mg/kg methylprednisolone was administered daily for 6 days and was then tapered for 4 days. In the curcumin group, crush injuries were inflicted on sciatic nerves as in group C. Then, 100-mg/kg curcumin was given every day. In the propolis group, crush injuries were inflicted on sciatic nerves as in group C. Then, 200-mg/kg propolis was given every day. Rats were evaluated after 28 days using functional (walking track analysis and electrophysiological measurements), histomorphometric, electron microscopic, and muscle weight measurements. RESULTS: Compared to the control groups, the curcumin and propolis groups had better functional (walking track analysis and electrophysiological) results after experimental peripheral nerve crush injury. CONCLUSIONS: Curcumin and propolis, 2 traditional drugs, had a positive effect on nerve crush injuries. We are convinced that they can be used to support routine treatment in such nerve injuries.


Asunto(s)
Antiinflamatorios/uso terapéutico , Curcumina/uso terapéutico , Metilprednisolona/uso terapéutico , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Própolis/uso terapéutico , Nervio Ciático/lesiones , Animales , Antiinflamatorios/farmacología , Curcumina/farmacología , Esquema de Medicación , Femenino , Metilprednisolona/farmacología , Própolis/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
6.
Acta Neurochir (Wien) ; 154(6): 1045-54, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22354719

RESUMEN

BACKGROUND: The goal of most acute therapies for spinal cord injury (SCI) in humans include attenuation of the early inflammatory response and may limit the extent of tissue injury and the consequent disability. OBJECTIVE: The purpose of this study was to investigate the early effects of methothrexate (MTX) treatment on myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also compared with methylprednisolone sodium succinate (MPSS) treatment. METHODS: Wistar rats were divided into seven groups: control; trauma alone (50 g/cm weight drop trauma); SCI + MPSS (30 mg/kg); SCI + low-dose (0.5 mg/kg) MTX (LDMTX); SCI + higher-dose (1 mg/kg) MTX (HDMTX); non-trauma + LDMTX; non-trauma + HDMTX. RESULTS: Administration of MTX and MPSS treatments significantly decreased MPO activity (p < 0.05) and MDA level (p < 0.05) in the first 24 h. The MTX treatments, particularly HDMTX, were more effective than MPSS in reducing MPO activity, and MTX treatments were also more effective than MPSS in reducing MDA level (p < 0.05). The MTX treatment was more protective on large- and medium-diameter myelinated axons in minimizing ultrastructural changes in the spinal-cord-injured rats, but did not induce neurotoxicity in normal spinal cord. CONCLUSION: The results of this study indicate that MTX treatment has a beneficial effect by reducing early neutrophil infiltration and the associated lipid peroxidation, and has significantly protective effects on the injured spinal cord tissue in the first 24 h after SCI. Given the anti-inflammatory properties of MTX, a single dose of MTX a week is used for non-neoplastic disease in humans, and MTX may have a beneficial role in the immediate management of acute SCI.


Asunto(s)
Peroxidación de Lípido/efectos de los fármacos , Metotrexato/farmacología , Infiltración Neutrófila/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/toxicidad , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/fisiología , Modelos Animales de Enfermedad , Femenino , Inmunosupresores/farmacología , Inmunosupresores/toxicidad , Peroxidación de Lípido/fisiología , Metotrexato/toxicidad , Infiltración Neutrófila/inmunología , Ratas , Ratas Wistar , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología
7.
Turk Neurosurg ; 31(1): 93-98, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33491171

RESUMEN

AIM: To examine the effect of propolis on the healing process in terms of both electrophysiological and ultrastructural parameters in a rat model of experimental spinal cord injury. MATERIAL AND METHODS: Thirty rats were divided into control, spinal cord trauma, and treated trauma groups with 10 rats per group. The rats were sacrificed after 10 days. Before sacrifice, all rats were neurologically assessed by electrophysiological monitoring, and immediately after sacrifice, the spinal cord was examined ultrastructurally by transmission electron microscopy (TEM). RESULTS: According to the electrophysiological examination, the treatment group was statistically significantly different from the trauma group. However, no statistically significant difference was found between the control and treatment groups. In terms of the TEM examination, the treatment group was significantly different from the trauma group. CONCLUSION: In this study, propolis was administered just before the induction of trauma, and the findings suggest that the use of propolis has a positive effect on the healing process. This implies that in order to prevent postoperative deficits, this treatment may be preferably applied before spinal cord surgery for trauma.


Asunto(s)
Própolis/uso terapéutico , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Animales , Masculino , Própolis/farmacología , Ratas , Ratas Wistar , Recuperación de la Función/fisiología , Médula Espinal/patología , Médula Espinal/ultraestructura , Traumatismos de la Médula Espinal/patología , Resultado del Tratamiento
8.
Ann Plast Surg ; 64(3): 342-50, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20179488

RESUMEN

Bone grafts, used for providing structural integrity of cranial vault remodeling, could not always integrate with the remaining bone structures. All efforts are focused on increasing incorporation of the applied bone grafts. Allografts were covered by chitosan so that slow release of bone morphogenetic protein-2 (BMP-2) and Transforming growth factor-beta-2 (TGF-beta-2) was achieved. Two hundred forty Wistar-Albino rats were distributed equally in 8 study groups. Study groups were designed as; defect group, autograft group, allograft group, chitosan group, allograft + chitosan, TGF-beta-2 group, BMP-2 group, and TGF-Beta-2 +BMP-2 group. Bone biopsies were obtained at second, eight, and 14th weeks. Bone regeneration was evaluated by morphologic studies detecting histologic bone healing and radiologic studies detecting bone density. Histologic findings were evaluated in 2 categories; tissue response to the implant and defect healing. Additionally, scanning electron microscopy for detailed morphologic evaluation was done. Bone density of the applied scaffold and the parietal bone at the same computed tomography section were measured in Hounsfield scale and this ratio was used for densitometry evaluations. Kruskal-Wallis test was used to analyze difference among groups according to the histologic and radiologic data. Pairwise comparisons were done using Mann-Whitney U test with Bonferroni correction. P < 0.05 was considered significant. In the morphologic studies, bone regeneration in BMP-2 group was found to be compatible with bone regeneration in gold standard autograft group and even better than it within 15 days. Chitosan is a biocompatible material. TGF-Beta-2 alone is not effective enough in bone regeneration; BMP-2 alone has a positive effect in every step of bone regeneration. Combining TGF-Beta-2 with BMP-2 does not lead to a better bone regeneration than using BMP-2 alone. A synergistic effect is not obtained by using these 2 factors together.


Asunto(s)
Matriz Ósea/efectos de los fármacos , Matriz Ósea/metabolismo , Proteína Morfogenética Ósea 2/efectos de los fármacos , Quitosano/farmacología , Supervivencia de Injerto , Periostio , Cráneo/efectos de los fármacos , Cráneo/metabolismo , Factor de Crecimiento Transformador beta2/efectos de los fármacos , Animales , Materiales Biocompatibles , Femenino , Periostio/efectos de los fármacos , Periostio/patología , Periostio/cirugía , Ratas , Ratas Wistar , Regeneración/efectos de los fármacos
9.
Br J Neurosurg ; 24(5): 578-83, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20868245

RESUMEN

The major aim of this study was to evaluate the efficiency of chitosan microspheres containing cyclosporine-A (Cs-A) on mitochondrial damage in traumatic brain injury (TBI) animal model. Trauma was introduced to male Sprague-Dawley (SD) rats similar to that of modified Feeney Method. Briefly, after craniectomy in the left parietal region (5 mm). Trauma was performed by dropping 24 g metal sterile rods through a teflon guide tube (9.3 cm) on a foot plate placed over the duramater. Just after the trauma, 20 mg/kg Cs-A (Sandimmune) has been administered to the traumatised SD rats intraperitoneally (i.p.). On the other hand, only chitosan microspheres containing 10 mg/kg was implanted at the craniectomy area locally after trauma in Group E. A small piece of surgicell was placed over the craniectomy hole and the scalp incision was sutured. 24 h after injury and the brain tissues were removed intact. The results were evaluated through lipid peroxidation ratio and ultrastructural grading system. The statistical comparisons were evaluated by using Mann Whitney- U test at the significance level p = 0.05. The lipid peroxidation ratios of sham (78.4 +/- 6.0 nmol/g tissue) and vehicle (80.2 +/- 10.6 nmol/g tissue) were significantly increased 24 h after TBI. However, for treatment groups (i.p. Cs-A; 20 mg/kg) and (10 mg/kg Cs-A in microspheres), statistically significant lower lipid peroxidation ratios were determined as 53.5 +/- 9.7 and 47.9 +/- 8.1 nmol/g tissue, respectively (p < 0.05). The mitochondrial damage scores of the treatment groups were recorded as 21.7 +/-2.6 and 19.4 +/- 3.9 for Group D and Group E, respectively. Both of these scores of the treatment groups were found as significantly different from the sham and vehicle groups' scores individually. The implantation of microsphere formulation has provided a better efficiency in keeping the uniformity of mitochondrial structure in this complex cascade of events after TBI.


Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Quitosano/administración & dosificación , Ciclosporina/administración & dosificación , Microesferas , Mitocondrias/efectos de los fármacos , Animales , Lesiones Encefálicas/patología , Modelos Animales de Enfermedad , Masculino , Mitocondrias/patología , Ratas , Ratas Sprague-Dawley
10.
J Clin Neurosci ; 16(4): 549-53, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19200733

RESUMEN

Immunomodulation of acute spinal cord injury may inhibit the activity of specific inflammatory cascades and result in recovery of motor function. In this study, evaluation of the protective effect of a well-known anti-inflammatory immunomodulator, immunoglobulin G (IgG), was conducted in rats after a 50 g/cm contusion spinal cord injury. Following injury, 400 mg/kg of IgG was administered to the treatment group. Twenty-four hours later, animals were assessed functionally via an inclined plane and the Basso-Beattie-Bresnahan motor scale and compared to controls. Tissue was reviewed for myeloperoxidase activiy (MPO) and lipid peroxidation (LPO), and electron microscopy was conducted to assess tissue ultrastructure. Significant functional preservation was observed in the IgG treatment group. In addition, biochemical assays revealed decreased MPO activity, and electron microscopic views of tissue showed preserved ultrastructure. IgG treatment following acute contusion injury to the rat spinal cord confers functional and structural neuroprotection.


Asunto(s)
Inmunoglobulina G/uso terapéutico , Factores Inmunológicos/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Conducta Animal , Modelos Animales de Enfermedad , Peroxidación de Lípido/fisiología , Masculino , Microscopía Electrónica de Rastreo/métodos , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , Examen Neurológico/métodos , Neuronas/patología , Neuronas/ultraestructura , Peroxidasa/metabolismo , Desempeño Psicomotor , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Factores de Tiempo
11.
Eur Arch Otorhinolaryngol ; 266(2): 231-5, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18542979

RESUMEN

Radiofrequency reduction has become one of the most popular methods in the treatment of inferior nasal concha hypertrophy. During surgical treatment of inferior nasal concha hypertrophy, it is important to cause minimal injury to the overlying ciliated epithelium, since if the ciliated structure of this epithelium is permanently disrupted, it is hard to carry out one of the important functions of lining of the nasal cavity, mucociliary clearance. In this study, the ultrastructure of inferior nasal concha epithelium was examined by transmission and scanning electron microscopy in 40 patients with inferior nasal concha hypertrophy. The biopsy specimens were taken before the radiofrequency treatment and 8 weeks after the radiofrequency treatment. Then, the effects of radiofrequency treatment on concha epithelium and morphology of ciliae were examined ultrastructurally. In the scanning and transmission electron microscopic examination of the tissue samples taken before radiofrequency treatment, no ultrastructural pathology was observed in the number and morphology of the ciliae and the inferior nasal concha epithelium. The biopsy specimens obtained 8 weeks after radiofrequency treatment also did not show any ultrastructural pathology in these parameters. However, in the transmission electron microscopic examination of the subepithelial tissue, fibrosis was observed in local areas in the biopsy specimens obtained 8 weeks after radiofrequency treatment. In conclusion, the results obtained from this study suggest that ciliated epithelium of the inferior nasal concha is not destroyed by radiofrequency reduction.


Asunto(s)
Ablación por Catéter/métodos , Mucosa Nasal/patología , Obstrucción Nasal/cirugía , Cornetes Nasales/patología , Biopsia con Aguja , Endoscopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Hipertrofia/complicaciones , Hipertrofia/patología , Hipertrofia/cirugía , Inmunohistoquímica , Masculino , Microscopía Electrónica de Transmisión , Mucosa Nasal/ultraestructura , Obstrucción Nasal/etiología , Obstrucción Nasal/patología , Estudios Prospectivos , Insuficiencia del Tratamiento , Cornetes Nasales/cirugía
12.
J Clin Neurosci ; 15(1): 60-5, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18061457

RESUMEN

Treatments for brain edema are important and one of the major options is corticosteroids. Cell membrane stabilization and prevention of formation of free radicals are the main mechanisms of action of steroids in edema treatment. As an alternative therapeutic agent, magnesium sulphate has been used for its neuroprotective effect in various injury models. In our animal model of brain injury, cold has been used in Sprague-Dawley rats. After brain injury, magnesium sulphate (600 mg/kg) or dexamethasone sodium phosphate (0.2 mg/kg) were administered to experimental groups. The degree of brain edema and lipid peroxidation was evaluated using the wet-dry weight method, the determination of malondialdehyde (MDA) levels and an ultrastructural grading system. Magnesium sulphate treatment was found to be the most effective choice due to the absence of side effects and comparable efficacy to corticosteroids.


Asunto(s)
Edema Encefálico/prevención & control , Dexametasona/análogos & derivados , Sulfato de Magnesio/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/ultraestructura , Edema Encefálico/etiología , Lesiones Encefálicas/complicaciones , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Peroxidación de Lípido/efectos de los fármacos , Microscopía Electrónica de Transmisión/métodos , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/fisiología , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas
13.
J Drug Target ; 26(1): 66-74, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28581827

RESUMEN

PURPOSE: The aim of this study is to test folate-conjugated cyclodextrin nanoparticles (FCD-1 and FCD-2) as a vehicle for reducing toxicity and increasing the antitumor efficacy of paclitaxel especially for metastatic breast cancer. METHODS: For the evaluation of PCX-loaded FCD nanoparticles, animal studies were realised in terms of survival rate, tumour size, weight change, metastazis and histopathological examination. RESULTS: FCD-1 displayed significant advantages such as efficient targeting of folate receptor positive breast cancer cells and having considerably lower toxicity compared to that of Cremophor®. When loaded with paclitaxel, FCD-1 nanoparticles, which have smaller particle size, neutral zeta potential, high encapsulation efficiency and better loading capacity for controlled release, emerged as an effective formulation in terms of cytotoxicity and high cellular uptake. In an experimental breast cancer model, anticancer activity of these nanoparticles were compatible with that of paclitaxel in Cremophor® however repeated administrations of FCD-1 nanoparticles were better tolerated by the animals. These nanoparticles were able to localise in tumour site. Both paclitaxel-loaded FCD-1 and FCD-2 significantly reduced tumour burden while FCD-1 significantly improved the survival. CONCLUSIONS: Folate-conjugated amphiphilic cyclodextrin nanoparticles can be considered as promising Cremophor®-free, low-toxicity and efficient active drug delivery systems for paclitaxel.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Ciclodextrinas/química , Sistemas de Liberación de Medicamentos/métodos , Ácido Fólico/química , Nanopartículas/química , Paclitaxel/uso terapéutico , Animales , Línea Celular Tumoral , Femenino , Transportadores de Ácido Fólico/química , Transportadores de Ácido Fólico/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Paclitaxel/administración & dosificación
14.
Surg Neurol ; 68(5): 547-55; discussion 555, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17586022

RESUMEN

BACKGROUND: The purpose of this study was to investigate the effect of EPO on LPO, on ultrastructural findings, and on antiapoptotic bcl-2 and survivin gene expressions after TBI. The authors also compared the activity of EPO with that of MPSS. METHODS: Wistar rats were divided into 6 groups: sham-operated, control, moderate TBI-alone (300 g/cm), TBI + EPO-treated (1000 IU/kg), TBI + MPSS-treated (30 mg/kg), and TBI + vehicle-treated (0.4 mL albumin solution) groups. RESULTS: Compared with the levels in control and sham-operated animals, LPO was significantly elevated in rats in the trauma-alone group. The administration of EPO and MPSS significantly decreased the LPO levels (P < .05). Trauma also increases the antiapoptotic bcl-2 gene expression significantly at 24 hours postinjury (P < .05), but it has no effect on survivin expression. The EPO and MPSS treatments caused significant elevation in both gene expressions (P < .05). It is also showed that MPSS has more protective effect than EPO on brain ultrastructure, especially on the structure of small- (P < .05) and medium-sized myelinated axons, after TBI. CONCLUSIONS: EPO has protective effects after moderate TBI, and this effect seems better than MPSS on antiapoptotic gene expression and LPO. The protection of cerebral subcellular organelles after traumatic injury is more prominent in MPSS-treated animals than EPO-treated animals quantitatively. This experimental study indicates that the benefits of EPO in the management of TBI have promising results and prompts further studies on the difference between EPO and MPSS in histopathological findings at the subcellular level.


Asunto(s)
Lesiones Encefálicas/patología , Encéfalo/efectos de los fármacos , Eritropoyetina/farmacología , Peroxidación de Lípido/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Eritropoyetina/uso terapéutico , Radicales Libres/metabolismo , Microscopía Electrónica de Transmisión , Proteínas Asociadas a Microtúbulos/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Proteínas Recombinantes , Survivin
15.
Urol J ; 14(6): 5064-5067, 2017 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-29101765

RESUMEN

PURPOSE: We aimed to investigate the exact localization of neural pathway and the frequency of nerve fibers, which are located in the pelvic facial layers in the prostate and periprostatic regions. MATERIALS AND METHODS: We used four fresh frozen cadavers in this trial. Anatomical layers of anterior rectus fascia and abdominal rectus muscle were dissected to reach the retropubic area. Prostate, visceral and parietal pelvic fascia, levator ani muscle and puboprostatic ligaments were identified. Nine tissue samples, each 1x1 cm in size, were obtained from each cadaver and grouped separately. The locations of these samples are as follows. Group G I from 12 o'clock (apical region), G II from right prostatic apex, G III from 2 o'clock, G IV from right far pelvic lateral, G V from 5 o'clock, G VI from 7 o'clock, GVII from left far pelvic lateral, G VIII from 10 o'clock and G IX from left prostatic apex. Nerve distribution, frequency and diameters of these 9 groups were compared to each other. RESULTS: 36 specimens were obtained from 4 cadavers. Mean number of nerve fibers was 14.1. The number of nerve fibers in each location were not statistically different from each other (P = .9). Mean nerve diameter was 89.1 µm. Mean diameter of nerves was statistically different between groups II, III IV and VI and VIII (P = .001). No difference was seen amongst others. CONCLUSION: The distributions of nerve fibers at prostate and peri-prostatic region were homogeneous while the nerve diameters varied amongst the different regions.


Asunto(s)
Fascia/anatomía & histología , Plexo Hipogástrico/anatomía & histología , Próstata/inervación , Puntos Anatómicos de Referencia , Cadáver , Disección , Humanos , Masculino
16.
J Neurosurg Sci ; 61(4): 380-387, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25366581

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the effect of the systemic administration of dipyrone in a triple subarachnoid hemorrhage (SAH) model of cerebral vasospasm in rabbits. METHODS: Experimental subarachnoid hemorrhage was induced in rabbits by injecting autologous arterial blood into the cisterna magna. Digital subtraction angiographies (DSA) were performed before and after the first experimental SAH, and at 30, 45, 60 minutes and 72 hours after the first drug administration to measure the diameter of basilar artery. Intracisternal blood injections were repeated 24 and 48 hours after the first injection. Dipyrone (N.=20) or 0.9% NaCl (N.=20) was administered intravenously after initial SAH induction and repeated at 8-hour intervals intramuscularly. After sacrificing by perfusion-fixation, basilar arteries were removed and sectioned for transmission electron microscopic (TEM) examination. RESULTS: The average basilar artery diameter measured by DSA was 724±19 µm in the control, and 686±29 µm in treatment group before SAH. After SAH, mean basilar artery diameters decreased to 71% and 68% of their basal values, respectively. Dipyrone significantly attenuated the basilar artery diameter at one and 72 hours after the first drug administration, in comparison to the control group. TEM studies showed more edema in the endothelial cells of the basilar arteries of the control group when compared to the treatment group. CONCLUSIONS: Dipyrone showed a beneficial effect in autologous blood-induced basilar artery vasospasm in rabbits. These data support the idea that dipyrone can be a potential candidate drug to be tested in patients suffering from cerebral vasospasm secondary to subarachnoid hemorrhage.


Asunto(s)
Dipirona/farmacología , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasodilatadores/farmacología , Vasoespasmo Intracraneal/tratamiento farmacológico , Angiografía de Substracción Digital , Animales , Dipirona/administración & dosificación , Modelos Animales de Enfermedad , Conejos , Hemorragia Subaracnoidea/diagnóstico por imagen , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/diagnóstico por imagen
17.
Neurol Res ; 28(8): 841-4, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17288742

RESUMEN

OBJECTIVE: Neurodestructive procedures have been used for treating intractable pain for a long time. Pulsed radiofrequency (RF) is a newly defined energy type. Pulsed RF may be used in the treatment of patients with some pain syndromes in whom the pain could not be controlled by the alternative techniques. The objective of the present study was to examine the histological and electron microscopical changes in rat brain after pulsed RF application. METHODS: Forty-five male rats were used in these experiments. Lesions were applied stereotactically to the target areas of the rat brains. Two different RF energy type were used as representative models of pulsed-RF and conventional-RF procedures. The rats were kept alive for 21 days and then killed. The effect of pulsed RF lesions on cerebral tissue ultrastructure was studied. RESULTS: In the pulsed RF group, intracytoplasmic edema, clarity of the mitochondrial cristas and opening in the cell membrane pores were observed on the electron microscopic examination. In the conventional RF group, these findings were more prominent. In the pulsed RF group, the ratio of the effected neurons was 5.5% on light microscopic examination. In the conventional RF group, the ratio of the effected neurons was 14.26% and central necrosis was observed additionally. DISCUSSION: Pulsed RF caused ultrastructural changes in the neurons. The pulsed RF may possibly cause a depression on the cell membrane potential by opening the cell membrane pores and resulting in the ion entrance into the cell cytoplasm and intracytoplasmic edema. However, it seems that all these changes were reversible.


Asunto(s)
Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Electrocoagulación/efectos adversos , Microscopía Electrónica de Transmisión , Ondas de Radio/efectos adversos , Técnicas Estereotáxicas , Animales , Encéfalo/patología , Encéfalo/ultraestructura , Electrodos , Masculino , Ratas
18.
Surg Neurol ; 64 Suppl 2: S28-32, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16256837

RESUMEN

BACKGROUND: Spinal cord injury (SCI) is a common and often irreversible lesion that can incapacitate patients. Precursor cells in the spinal cord proliferate in response to trauma, and this proliferation can be enhanced by exogenous stimuli such as specific growth factors. In the present study, we examined electron microscopic detection of the proliferation, distribution, and phenotypic fate of these precursor cells in the injured adult rat spinal cord. METHODS: Adult female Sprague-Dawley rats weighing 250 to 300 g were divided into 3 groups. The first group consisted of spinal cord-injured animals with application of a 2.4-g clip extradurally around the spinal cord at the T1 level. A 26-g clip was applied in the second group. The third group included normal uninjured animals. Rats were sacrificed at 3 days, 3 weeks, and 6 weeks after injury. A segment of the spinal cord, 0.4 cm in length, encompassing the injury site was removed and was prepared for electron microscopy. RESULTS: Three days after mild injury (2.4-g clip), ependymal cells had begun to proliferate and had migrated from the central canal. They had a tendency to surround perivascular spaces close to the axons. The central canal rostral to the lesion site was widely dilated at 6 weeks postoperative in the moderately injured groups (26-g clip). The layer of ependymal cells lining the dilated canal showed reduction in cell height. Traumatic syringomyelic cavities were observed in all of the animals. There was an active proliferative response of the ependymal cells to injury. Large clusters of displaced ependymal cells associated with the dilated central canal were observed. Rests of ependymal cells were observed remote from the central canal with a tendency to form rosettes and accessory lumina 6 weeks after trauma. Fascicles of 3 to 8 fibers enclosed within an ependymal cell were a common finding among the ependymal clusters. There were also debris and some ependymal cells in the lumen. CONCLUSION: Trauma induces active proliferation of precursor cells in the ependymal region. These cells may replace neural tissue lost to SCI and may assist in axonal regeneration.


Asunto(s)
Epéndimo/ultraestructura , Traumatismos de la Médula Espinal/patología , Células Madre/fisiología , Células Madre/ultraestructura , Animales , Proliferación Celular , Epéndimo/fisiopatología , Femenino , Microscopía Electrónica , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/fisiopatología , Vértebras Torácicas , Factores de Tiempo
19.
Surg Neurol ; 64 Suppl 2: S11-6, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16256831

RESUMEN

OBJECTIVE: The aims of this study were to evaluate the efficiency of dexamethasone sodium phosphate (DSP) in the treatment of cold injury-induced brain edema and to compare systemic and topical application of DSP. METHODS: Sprague-Dawley rats weighing nearly 300 g were used in the experiments. Brain edema was formed by cold injury using metal sterile rods with a diameter of 4 mm that were previously cooled at -80 degrees C. Twenty-four hours after the injury, animals were decapitated and brain tissues were investigated by wet-dry weight method, lipid peroxidation ratio, and histological examination. RESULTS: The degree of edema was significantly lowered in groups in which DSP was administered using chitosan microspheres and by intraperitoneal route (P < .05). The statistical evaluation of the experimental results was performed using Mann-Whitney U test. Histological findings transmission electron microscopy (TEM) correlated with the quantitative results. CONCLUSION: Both intraperitoneal- and microsphere-administered DSP were found to be very effective in a cold injury brain edema model. The authors believe that future studies should lead to new applications of the microsphere formulations prepared by chitosan as the matrix material in many other therapies.


Asunto(s)
Edema Encefálico/prevención & control , Lesiones Encefálicas/complicaciones , Quitosano , Dexametasona/análogos & derivados , Sistemas de Liberación de Medicamentos , Microesferas , Animales , Edema Encefálico/etiología , Edema Encefálico/patología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Frío/efectos adversos , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Peroxidación de Lípido , Masculino , Ratas , Ratas Sprague-Dawley
20.
Saudi Med J ; 26(3): 425-8, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15806212

RESUMEN

OBJECTIVE: The ruptures of tendo calcaneus often occur between the age of 30-45 years as described by several textbooks. It is also described that some diseases and drugs are said to be responsible in the etiology; however, there are no studies related with the detailed histological structure of collagen fibrils found in the tendon in the age groups of humans. In view thereof, this study was aimed to obtain further information on the etiology and to find an answer regarding the frequency of the ruptures occurring between the age of 30-45 years in humans. METHODS: In the study, the biopsy specimens taken from 28 patients (ages 1-68 year) who had undergone surgery due to tendo calcaneus ruptures or achilloplasty operation were examined by transmission electron microscope. All the specimens were prepared according to routine electron microscopic tissue preparation technique. The patients were divided into 7 age groups (1-9, 10-19, 20-29, 30-39, 40-49, 50-59, >60 years) and there were 4 patients in each group. The transverse diameters of collagen fibers were measured from the ultra thin sections and statistical analysis of the results were performed. The study was carried out in the electron microscopy laboratory of the Anatomy Department of Hacettepe University, Ankara, Turkey between January 2004 and September 2004. RESULTS: The diameters of the collagen fibers were higher in the 20-29 year-old group compared to other groups and it showed a statistically significant difference. In patients who were in the 30-39 year-old group or older, the diameters of the collagen fibers were lesser than the 20-29 year-old group. However, an increase was observed in the collagen fibril concentration of these groups. In examination of the specimens of patients who were under 20-year-old, the diameter of the collagen fibers were less than the 20-29 year-old group. The electron microscopic appearance of the tissue sample of a one-year-old patient had a specific organization and in this patient, both the diameters and concentration of collagen fibers were less. CONCLUSION: We believe that the decrease in the diameters of collagen fibers of 30-45 year-old patients who are in the active period of their life, can play a role in the etiology of the frequency of tendo calcaneus ruptures similar to other etiologic factors.


Asunto(s)
Tendón Calcáneo/ultraestructura , Envejecimiento/patología , Colágeno/ultraestructura , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Lactante , Microscopía Electrónica , Persona de Mediana Edad
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