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1.
J Laryngol Otol ; 136(7): 639-644, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34991747

RESUMO

BACKGROUND: Congenital midnasal stenosis has previously been described as a cause of nasal obstruction in infants, and conservative and interventional treatments have been suggested. However, midnasal stenosis in adults has not been reported and related normative measurements have not been studied. METHODS: Three adult patients presented with nasal obstruction and, based on examination and radiological findings, were diagnosed with midnasal stenosis. Anatomical measurements were studied in axial and coronal computed tomography scans, and compared with findings for 161 healthy individuals. RESULTS: Anatomical measurements showed that the endonasal cavity was larger in males than females. The midnasal region was found to be constricted in patients compared to healthy controls. CONCLUSION: This is the first study to report on midnasal stenosis in adults and to define normative anatomical measurements in adults. In patients presenting with nasal obstruction, midnasal stenosis should be suspected during endoscopic visualisation of medially located middle turbinates and uncinate processes in nasal cavities. A definitive diagnosis of midnasal stenosis can be made by examining paranasal sinus computed tomography scans. Endoscopic middle turbinectomy, complete uncinectomy, mega maxillary antrostomy and partial anterior ethmoidectomy have been suggested to relieve midnasal stenosis.


Assuntos
Obstrução Nasal , Doenças Nasais , Adulto , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/cirurgia , Feminino , Humanos , Lactente , Masculino , Cavidade Nasal/anormalidades , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Obstrução Nasal/diagnóstico por imagem , Obstrução Nasal/etiologia , Obstrução Nasal/cirurgia , Doenças Nasais/complicações , Valores de Referência , Conchas Nasais
3.
J Laryngol Otol ; 134(4): 332-337, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32238199

RESUMO

OBJECTIVE: To evaluate the colour values of nasal mucosa for the purpose of presenting an objective parameter of allergic rhinitis. METHODS: Seventy-three patients with allergic rhinitis (allergy group) and 73 normal healthy individuals (control group) were included in the study. Endoscopic examinations were conducted, and endoscopic photographs of the septum and both inferior turbinates were taken. The Adobe Photoshop Elements 7.0 software program was used to measure the numerical values of red-green-blue (RGB) colour components in the endoscopic photographs of nasal mucosa. RESULTS: The G and B values were significantly higher in the allergy group compared to the control group (both p < 0.05). Cumulative R, G and B values of all measurement points were significantly higher in the allergy group compared to the control group (p < 0.05). CONCLUSION: Nasal mucosa discolouration can be measured objectively with RGB analysis to aid the diagnosis of allergic rhinitis.


Assuntos
Cor/normas , Endoscopia/métodos , Mucosa Nasal/anatomia & histologia , Fotografação/instrumentação , Rinite Alérgica/diagnóstico , Adulto , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Septo Nasal/diagnóstico por imagem , Rinite Alérgica/epidemiologia , Rinite Alérgica/patologia , Sensibilidade e Especificidade , Software , Conchas Nasais/diagnóstico por imagem
4.
J Laryngol Otol ; 133(7): 600-603, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31232258

RESUMO

OBJECTIVE: The aim of this study was to examine whether melatonin is involved in the pathogenesis of nasal polyposis. METHOD: This study included 29 patients with nasal polyposis and undergoing functional endoscopic sinus surgery. As a control group, 26 patients who had been operated on for a deviated nasal septum and concha bullosa were enrolled. Samples were taken from the nasal polyp tissue and from the resected middle concha bullosa mucosa of the control group. Serum samples were taken from all patients. RESULTS: It was found that the tissue and serum melatonin levels in the nasal polyp group were significantly lower compared with the tissue and serum melatonin levels in the control group. CONCLUSION: In nasal polyposis, the melatonin level in the serum and tissue is lower than in individuals without polyposis. This deficiency may play a role in the pathogenesis of nasal polyposis.


Assuntos
Melatonina/deficiência , Pólipos Nasais/etiologia , Deformidades Adquiridas Nasais/cirurgia , Seios Paranasais/cirurgia , Adulto , Endoscopia , Feminino , Humanos , Masculino , Melatonina/sangue , Pólipos Nasais/metabolismo , Pólipos Nasais/cirurgia , Deformidades Adquiridas Nasais/metabolismo , Seios Paranasais/metabolismo
5.
Eur Arch Otorhinolaryngol ; 274(10): 3667-3672, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28795232

RESUMO

Patients perceive the pulling of a nasal splints as the most feared and stressful part of nasal surgery. Even the incisions made for alar base surgery can partly or entirely dehisce. So, we have been using modified Doyle silicone splints. We compared the modified Doyle silicone splints with conventional Doyle silicone splint. Included in the study were 64 patients undergoing alar base surgery together with open septorhinoplasty. Group 1 (n = 32) patients received a conventional Doyle intranasal silicone splint and group 2 (n = 32) received modified splint that we call a hemi-split Doyle splint. The pain felt by the patients during the removal of the splints was recorded according to the visual analogue scale (VAS). On days two and four postoperatively, the nasal stuffiness score (NOSE) was recorded. On day four postoperatively an intranasal examination was conducted to establish if dehiscence had occurred on the alar base incision line. In group 2, the pain scores during splints removal were significantly lower than those in group 1. Whereas no dehiscence on the alar base incision line was observed after tampon removal in group 2, the incision dehisced in eight patients in group 1. The NOSE scores on postoperative days two and four showed no difference between the groups. The hemi-split Doyle splint causes less pain during removal and particularly does not lead to dehiscence of incisions made during alar base surgery in rhinoplasty patients.


Assuntos
Remoção de Dispositivo , Obstrução Nasal/cirurgia , Septo Nasal/cirurgia , Dor Processual , Rinoplastia , Silicones/farmacologia , Contenções , Administração Intranasal , Adulto , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/instrumentação , Remoção de Dispositivo/métodos , Feminino , Humanos , Masculino , Medição da Dor , Dor Processual/diagnóstico , Dor Processual/etiologia , Dor Processual/prevenção & controle , Estudos Prospectivos , Rinoplastia/efeitos adversos , Rinoplastia/instrumentação , Rinoplastia/métodos , Resultado do Tratamento
6.
Int J Pediatr Otorhinolaryngol ; 100: 247-253, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28802382

RESUMO

OBJECTIVES: The purpose of this study is to evaluate the possible protective role of naringenin in gentamicin-induced ototoxicity through an audiological, biochemical and histopathological evaluation. METHODS: This study was conducted on 32 adult male rats that were randomized into 4 groups(control, gentamicin, naringenin + gentamicin, and naringenin). Naringenin was given to the rats via oral gavage in a dose of 50 mg/kg/day during the 14 day study period. Gentamicin was given by the intraperitoneal route in a dose of 120 mg/kg/day. Audiological assessment was performed by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) measurements, applied to all rats at the beginning of the study, and also on day 14. Biochemical parameters were calculated on day 14 to evaluate the oxidative and antioxidative status. Their cochleae were removed and examined histopathologically, also on day 14. The cochlea of animals were evaluated with the terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end labeling (TUNEL) method for apoptosis. RESULTS: On days 14, DPOAE values and ABR thresholds were preserved in group 3(naringenin + gentamicin) when compared with group 2(gentamicin)(p < 0.008). The total oxidant status values and oxidative stress index values were significantly higher in group 2(gentamicin) than in other groups (p < 0.008). The total antioxidant status value was significantly higher in group 3(naringenin + gentamicin) and group 4(naringenin) than in group 2(gentamicin)(p < 0.008). The number of TUNEL positive cells in both the organ of Corti and the stria vascularis were found to be statistically lower in group 3(naringenin + gentamicin) than in group 2(gentamicin)(p < 0.05). CONCLUSION: Our study has demonstrated that the ototoxic effect generated by gentamicin could be ameliorated with the concurrent use of naringenin.


Assuntos
Antibacterianos/efeitos adversos , Otopatias/induzido quimicamente , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Flavanonas/farmacologia , Gentamicinas/efeitos adversos , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cóclea/efeitos dos fármacos , Orelha Interna/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos
7.
J Laryngol Otol ; 130(1): 95-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26515526

RESUMO

OBJECTIVE: Azelastine nasal spray is a topical antihistaminic drug for the symptomatic treatment of allergic rhinitis. This study aimed to investigate the effects of azelastine on nasal and nasopharyngeal microflora. METHODS: Swab samples from 25 patients prescribed azelastine nasal spray monotherapy were collected just before treatment and after 1 month of treatment. After incubation of inoculates, the number of bacteria present in cultures was measured (in colony-forming units per millilitre). RESULTS: Evaluation of the number of microflora revealed increased bacterial reproduction after treatment, but this difference was not statistically significant. The use of azelastine nasal spray decreased the reproduction of three potentially pathogenic bacteria; however, it did not affect the reproduction of other potentially pathogenic bacteria. CONCLUSION: The use of azelastine nasal spray for one month did not have a statistically significant effect on the numbers of nasal and nasopharyngeal microflora; it is therefore safe from a microbiological viewpoint.


Assuntos
Antialérgicos/farmacologia , Nasofaringe/microbiologia , Ftalazinas/farmacologia , Administração Intranasal , Adolescente , Adulto , Estudos Transversais , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/microbiologia , Sprays Nasais , Estudos Prospectivos , Adulto Jovem
8.
Minerva Anestesiol ; 78(9): 1005-12, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22475807

RESUMO

BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary hypertension is associated with a poor prognosis. Prone position is effective to improve oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However, combination of these interventions has not been examined before. The hypothesis was that this combination had additive effects on oxygenation and pulmonary hemodynamics as compared with each intervention alone. METHODS: In a prospective, randomized cross-over study, ten pigs were anesthetized, intubated and ventilated with volume controlled ventilation. Carotid, jugular venous and pulmonary artery catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg). Measurements were repeated in randomized different sequences of prone or supine positions with or without iloprost inhalation (220 ng/kg/min) (four combinations). Systemic and pulmonary arterial pressures; arterial and mixed venous blood gases; and Qs/Qt and the resistances were recorded. RESULTS: Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine (37±10 vs. 31±8 mmHg; P<0.05) and prone positions (38±9 vs. 29±8 mmHg; P<0.05); but did not obtain a significant improvement in oxygenation in both positions. Prone position improved the oxygenation (p<0.0001) compared to supine position in both with (361±140 vs. 183±158 mmHg, P<0.05) or without iloprost application (331±112 vs. 167±117 mmHg, P<0.05); but did not achieve a significant decrease in MPAP. CONCLUSION: Although iloprost reduced pulmonary arterial pressures, and prone positioning improved oxygenation; there are no additive effects of the combination of both interventions on both parameters. To treat both pulmonary hypertension and hypoxemia, application of iloprost in prone position is suggested.


Assuntos
Hipertensão Pulmonar/terapia , Iloprosta/uso terapêutico , Oxigênio/sangue , Decúbito Ventral , Síndrome do Desconforto Respiratório/terapia , Administração por Inalação , Animais , Pressão Sanguínea , Artérias Carótidas , Estudos Cross-Over , Avaliação Pré-Clínica de Medicamentos , Hipertensão Pulmonar/etiologia , Hipóxia/etiologia , Hipóxia/terapia , Iloprosta/administração & dosagem , Iloprosta/farmacologia , Veias Jugulares , Masculino , Ácido Oleico/toxicidade , Prognóstico , Estudos Prospectivos , Artéria Pulmonar , Distribuição Aleatória , Respiração Artificial , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/complicações , Sus scrofa , Suínos
9.
Minerva Anestesiol ; 77(6): 598-603, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21617623

RESUMO

BACKGROUND: Apneic oxygenation (AO) is applied during surgery and in intensive care units. Even with AO, apnea is associated with progressive hypoxemia, limiting the tolerable amount of time in AO. This experimental study evaluates the effects of a recruitment maneuver (RM) on oxygenation, CO2 retention, and survival times during prolonged apnea, supported or not supported with intratracheal apneic oxygenation. METHODS: Following Ethic Committee approval, 15 male Sprague-Dawley rats were anesthetized and ventilated with PCV and FiO2:1 for 15 minutes. After obtaining a basal arterial blood-gas sample, the rats were randomized into 3 groups and disconnected from the ventilator: group (G) 1 (N.=6): AO with a cannula inserted into the carina; G2 (N=6): RM (40 cm H2O CPAP applied for 30 seconds) before AO; and G3 (N.=3): no application after disconnection (G3 was stopped after the first 3 subjects died within 3 minutes). Further arterial blood-gas samples were taken after 1, 3, and 6 minutes (T1, T3, and T6). Survival times after the start of AO were recorded. RESULTS: G2 was associated with significantly higher values of PaO2 at T3 and T6 when compared to G1 (345±56 vs. 233±65 mm Hg at T3 and 258±31 vs. 180±31 mm Hg at T6, respectively, P<0.05). There were significant changes in PaO2, pH, and PaCO2 over time in all subjects, but no differences were observed between G1 and G2 in pH or PaCO2. Survival time in G2 was significantly longer as opposed to G1 (G1: 10.3±2.3 min; G2: 14.3±3.6 min; P<0.05). CONCLUSION: RM prior to AO prolongs tolerance to apnea, probably by increasing the time before intolerable hypoxemia occurs, without a significant difference in PaCO2 levels.


Assuntos
Oxigênio/metabolismo , Alvéolos Pulmonares/metabolismo , Animais , Apneia , Cuidados Intraoperatórios/métodos , Masculino , Ratos , Ratos Sprague-Dawley
10.
Bioresour Technol ; 101(11): 3970-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20138508

RESUMO

High rate mesophilic anaerobic contact reactors (MACR) represent a proven sustainable technology for a wide range of different industrial effluents. These reactors demonstrate quite similar features to their aerobic counterparts, activated sludge systems. A lab-scale high rate mesophilic anaerobic contact reactor was operated with wastewater originated from a potato-processing plant, at six different loading rates of 1.1-5g COD/L per day. The operational performance of MACR was monitored from start-up by assessing COD removal efficiency, total volatile fatty acid production and biogas composition. Furthermore, various kinetic models have been successfully applied to the experimental data to determine substrate balance, maximum utilization rate and volumetric methane production. The COD removal efficiencies were found to be 78-92% and the methane percentage of the biogas produced was 80-89%. Additionally, the methane yield coefficient was found to be 0.394 L CH(4)/gTCOD(rem).


Assuntos
Reatores Biológicos , Indústria Alimentícia , Resíduos Industriais , Poluentes da Água/metabolismo , Anaerobiose , Biocombustíveis , Ácidos Graxos Voláteis/biossíntese , Cinética , Solanum tuberosum
11.
J Hazard Mater ; 176(1-3): 843-8, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20022175

RESUMO

The objective of this study was to examine the effects of organic loading rate and hydraulic retention time on volatile fatty acid composition and treatment efficiency of high rate thermophilic anaerobic contact reactor (TACR) treating potato-chips wastewaters. The operational performance of TACR was monitored from start-up by assessing chemical oxygen demand (COD) removal efficiencies, volatile fatty acid (VFA) production and biogas composition. The reactor was studied at different organic loading rates (OLRs) ranging from 0.6 to 8 kg COD/m(3) d. The COD removal efficiencies were found to be 86-97% and the methane percentage of the biogas produced was 68-89% during the OLRs studied. The approximate methane yield was found to be 0.42 m(3) CH(4)/kg COD(removed). The major intermediate products of anaerobic digestion were acetate, propionate, iso-butyrate, butyrate, iso-valerate, valerate, iso-caproate and caproate. The use of thermophilic anaerobic contact reactor offers a sustainable technology for the treatment of potato-chips wastewaters since high COD removal efficiencies and high methane percentage in the biogas produced can be attained even at high OLRs.


Assuntos
Biodegradação Ambiental , Indústria Alimentícia , Resíduos Industriais/prevenção & controle , Purificação da Água/métodos , Anaerobiose , Reatores Biológicos , Ácidos Carboxílicos/análise , Ácidos Graxos Voláteis/análise , Solanum tuberosum/metabolismo , Poluentes Químicos da Água/metabolismo
12.
Thorac Cardiovasc Surg ; 55(3): 177-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17410504

RESUMO

BACKGROUND: This study was designed to compare the early effects of docetaxel and paclitaxel on pulmonary physiology after isolated lung perfusion. METHODS: Rats underwent isolated left lung perfusion with docetaxel in group 1 (n = 5), paclitaxel in group 2 (n = 5), and 0.9 %NaCl in the control group (n = 5). Ventilation pressures, compliance of the lungs, blood gas analysis and histopathological results were compared between the groups. RESULTS: In group 1 and group 2, the decrease in PaO (2) (p = 0.008) and increase in ventilation pressures were significantly higher than in the control group ( P = 0.016). In group 2, pCO (2) retention was higher compared to the docetaxel perfusion group ( P = 0.016). In the histochemical assessment, intra-alveolar hemorrhage and mononuclear cell infiltration were dense and perivascular edema was not present in group 1. In group 2, perivascular and intraalveolar edema were found to be dense. CONCLUSION: Perfusion by either of the chemotherapeutics resulted in an alteration of lung physiology in rat lungs. If isolated lung perfusion is administered using chemotherapeutics from the taxanes group, it is suggested that docetaxel could be the first choice for isolated lung perfusion.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Docetaxel , Pulmão/patologia , Neoplasias Pulmonares/secundário , Masculino , Paclitaxel/administração & dosagem , Ratos , Ratos Sprague-Dawley , Taxoides/administração & dosagem
13.
Br J Anaesth ; 96(5): 645-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16531442

RESUMO

BACKGROUND: In this prospective, clinical study we tested the hypothesis whether two different doses of spinal administered bupivacaine and accordingly, two different levels of spinal anaesthesia can affect the dose requirement of propofol during BIS guided sedation. METHODS: Fifty women undergoing vaginal hysterectomy (high spinal group, HS) or transvaginal tape (TVT) procedure for urinary incontinence (low spinal group, LS) under spinal anaesthesia were enrolled to the study. In group HS, 17.5 mg and in group LS, 7.5 mg of hyperbaric bupivacaine were given intrathecally. After 15 min to obtain the appropriate level of spinal anaesthesia, propofol infusion was started at a rate of 100 microg kg(-1) min(-1) to reach a BIS level of less than 75 (onset time), and titrated to maintain the BIS value between 65 and 75. Propofol infusion was stopped 45 min after placing the spinal to measure the time to reach a BIS level of 90 (recovery time). RESULTS: Median anaesthetic level was T3 (T1-4) in the HS group and T10 (T9-11) in the LS group. In both the HS and the LS groups, onset time was 226 (47) vs 273 (48) s (P=0.001), recovery time was 234 (47) vs 202 (56) s (P=0.03), total dose of propofol was 2.17 (0.43) vs 3.14 (0.56) mg kg(-1) (P<0.001), respectively. CONCLUSION: A high spinal block obtained with hyperbaric bupivacaine 17.5 mg was associated with a faster onset, delayed recovery and lower doses of propofol sedation compared with a low spinal block with 7.5 mg of the same drug.


Assuntos
Raquianestesia/métodos , Anestésicos Locais/administração & dosagem , Sedação Consciente/métodos , Hipnóticos e Sedativos/administração & dosagem , Propofol/administração & dosagem , Adulto , Bupivacaína/administração & dosagem , Esquema de Medicação , Eletroencefalografia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Estudos Prospectivos , Incontinência Urinária/cirurgia
14.
Bioresour Technol ; 96(13): 1518-21, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15939281

RESUMO

Apricot stones were carbonised and activated after treatment with sulphuric acid (1:1) at 200 degrees C for 24 h. The ability of the activated carbon to remove Ni(II), Co(II), Cd(II), Cu(II), Pb(II), Cr(III) and Cr(VI) ions from aqueous solutions by adsorption was investigated. Batch adsorption experiments were conducted to observe the effect of pH (1-6) on the activated carbon. The adsorptions of these metals were found to be dependent on solution pH. Highest adsorption occurred at 1-2 for Cr(VI) and 3-6 for the rest of the metal ions, respectively. Adsorption capacities for the metal ions were obtained in the descending order of Cr(VI) > Cd(II) > Co(II) > Cr(III) > Ni(II) > Cu(II) > Pb(II) for the activated carbon prepared from apricot stone (ASAC).


Assuntos
Carvão Vegetal/química , Metais Pesados/química , Prunus , Sementes/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água , Adsorção , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Sementes/ultraestrutura , Espectrofotometria Atômica , Ácidos Sulfúricos
15.
Neuroscience ; 127(4): 881-91, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15312900

RESUMO

Hippocampal neurogenesis in adult mammals is influenced by many factors. Lesioning of the entorhinal cortex is a standard model used to study injury and repair in the hippocampus. Here we use bromodeoxyuridine (BrdU) labeling combined with immunohistochemical identification using cell type specific markers to follow the fate of neural progenitors in the hippocampus following entorhinal cortex lesioning in mice. We show that unilateral entorhinal cortex lesioning does not alter the rate of neural progenitor proliferation in the ipsilateral dentate gyrus during the first 3 days after lesioning. However it enhances cell survival at 42 days post-lesioning leading to an increased number of beta-III tubulin and calbindin-immunoreactive neurons being produced. By contrast, when BrdU was administered 21 days post-lesioning, the number of surviving cells 21 days later was similar on the lesioned and non-lesioned sides. Thus, acutely entorhinal cortex lesioning promotes neurogenesis by enhancing survival of either neural progenitors or their progeny. However, this stimulus to neurogenesis is not sustained into the recovery period.


Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Animais , Diferenciação Celular/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Células-Tronco/citologia , Células-Tronco/fisiologia
16.
Gene Ther ; 11(15): 1188-94, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15164096

RESUMO

The twitcher mouse is a natural model of Krabbe disease caused by galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis were only partially successful. Here, we report the transgenic (tg) rescue of the twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg mice exhibited growth, motor function, and fertility similar to those of nonaffected animals. These animals had normal levels of GALC activity in brain and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was only partially cleared. Nonetheless, these mice have been maintained for over 1 year without any sign of disease. Since pathological damage associated with GALC deficiency is confined to the nervous system, our work represents the first successful rescue of the twitcher mouse and opens the possibility of developing novel therapeutic approaches.


Assuntos
Cromossomos Artificiais Bacterianos , DNA/administração & dosagem , Galactosilceramidase/genética , Terapia Genética/métodos , Leucodistrofia de Células Globoides/terapia , Zigoto/enzimologia , Animais , Sequência de Bases , Clonagem de Organismos , Galactosilceramidase/análise , Galactosilceramidase/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Camundongos , Camundongos Mutantes Neurológicos , Camundongos Transgênicos , Dados de Sequência Molecular , Fenótipo , Transgenes
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