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1.
Eur Spine J ; 29(10): 2470-2476, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783082

RESUMO

PURPOSE: To test the vertical posterior vertebral angles (VPVA) of the most caudal lumbar segments measured on EOS to identify and classify the lumbosacral transitional vertebra (LSTV). METHODS: We reviewed the EOS examinations of 906 patients to measure the VPVA at the most caudal lumbar segment (cVPVA) and at the immediately proximal segment (pVPVA), with dVPVA being the result of their difference. Mann-Whitney, Chi-square, and ROC curve statistics were used. RESULTS: 172/906 patients (19%) had LSTV (112 females, mean age: 43 ± 21 years), and 89/172 had type I LSTV (52%), 42/172 type II (24%), 33/172 type III (19%), and 8/172 type IV (5%). The cVPVA and dVPVA in non-articulated patients were significantly higher than those of patients with LSTV, patients with only accessory articulations, and patients with only bony fusion (all p < .001). The cVPVA and dVPVA in L5 sacralization were significantly higher than in S1 lumbarization (p < .001). The following optimal cutoff was found: cVPVA of 28.2° (AUC = 0.797) and dVPVA of 11.1° (AUC = 0.782) to identify LSTV; cVPVA of 28.2° (AUC = 0.665) and dVPVA of 8° (AUC = 0.718) to identify type II LSTV; cVPVA of 25.5° (AUC = 0.797) and dVPVA of - 7.5° (AUC = 0.831) to identify type III-IV LSTV; cVPVA of 20.4° (AUC = 0.693) and dVPVA of - 1.8° (AUC = 0.665) to differentiate type II from III-IV LSTV; cVPVA of 17.9° (AUC = 0.741) and dVPVA of - 4.5° (AUC = 0.774) to differentiate L5 sacralization from S1 lumbarization. CONCLUSION: The cVPVA and dVPVA measured on EOS showed good diagnostic performance to identify LSTV, to correctly classify it, and to differentiate L5 sacralization from S1 lumbarization.


Assuntos
Lordose , Anormalidades Musculoesqueléticas , Adulto , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sacro/diagnóstico por imagem , Adulto Jovem
2.
Radiol Med ; 123(6): 441-448, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29455423

RESUMO

PURPOSE: Cerebral microbleeds (CMBs) are small rounded lesions representing cerebral hemosiderin deposits surrounded by macrophages that results from previous microhemorrhages. The aim of this study was to review the distribution of cerebral microbleeds in patients with end-stage organ failure and their association with specific end-stage organ failure risk factors. MATERIALS AND METHODS: Between August 2015 and June 2017, we evaluated 15 patients, 9 males, and 6 females, (mean age 65.5 years). Patients population was subdivided into three groups according to the organ failure: (a) chronic kidney failure (n = 8), (b) restrictive cardiomyopathy undergoing heart transplantation (n = 1), and (c) end-stage liver failure undergoing liver transplantation (n = 6). The MR exams were performed on a 3T MR unit and the SWI sequence was used for the detection of CMBs. CMBs were subdivided in supratentorial lobar distributed, supratentorial non-lobar distributed, and infratentorial distributed. RESULTS: A total of 91 microbleeds were observed in 15 patients. Fifty-nine CMBs lesions (64.8%) had supratentorial lobar distribution, 17 CMBs lesions (18.8%) had supratentorial non-lobar distribution and the remaining 15 CMBs lesions (16.4%) were infratentorial distributed. An overall predominance of supratentorial multiple lobar localizations was found in all types of end-stage organ failure. The presence of CMBs was significantly correlated with age, hypertension, and specific end-stage organ failure risk factors (p < 0.001). CONCLUSIONS: CMBs are mostly founded in supratentorial lobar localization in end-stage organ failure. The improved detection of CMBs with SWI sequences may contribute to a more accurate identification of patients with cerebral risk factors to prevent complications during or after the organ transplantation.


Assuntos
Cardiomiopatia Restritiva/complicações , Hemorragia Cerebral/diagnóstico por imagem , Falência Renal Crônica/complicações , Falência Hepática/complicações , Imageamento por Ressonância Magnética/métodos , Idoso , Cardiomiopatia Restritiva/cirurgia , Feminino , Transplante de Coração , Humanos , Falência Hepática/cirurgia , Transplante de Fígado , Masculino , Fatores de Risco
3.
J Ultrason ; 21(85): e162-e168, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34258042

RESUMO

Ultrasound is a fast, accessible, reliable, and radiation-free imaging modality routinely used to assess the soft tissues around the shoulder. It enables to identify a wide range of pathological conditions. Furthermore, most ultrasound-guided musculoskeletal interventional procedures around the shoulder produce better results in terms of accuracy and clinical efficacy than those performed in a blinded fashion. Indeed, intra-articular and peri-articular interventional procedures can be easily performed under continuous ultrasound monitoring to ensure the correct position of the needle and to deliver the medication to a specific target. Several technical approaches and medications can be used to treat different causes of painful shoulder. Intra-articular injections are applied to treat acromioclavicular osteoarthritis as well as glenohumeral joint osteoarthritis and adhesive capsulitis. Subacromial-subdeltoid bursitis, either presenting as a primary inflammatory condition or secondary to rotator cuff disorders, can be easily approached using ultrasound guidance to aspirate synovial effusion and to inject medications. Ultrasound-guided percutaneous irrigation is a well-established technique increasingly applied to treat patients with rotator cuff calcific tendinopathy. Also, degenerative rotator cuff tendinopathy can be conservatively treated by image-guided interventions, specifically with needling under ultrasound guidance that can be associated with injections of platelet-rich plasma. Lastly, periarticular peripheral nerve block can be quickly and safely performed under ultrasound guidance, particularly in conditions involving the suprascapular nerve in the setting of pre-operative analgesia or pain treatment in glenohumeral osteoarthritis and adhesive capsulitis. In this article, the most common ultrasound-guided procedures around the shoulder have been reviewed to discuss indications and techniques.

4.
Biomed Res Int ; 2020: 3086395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32596294

RESUMO

PURPOSE: To assess patients' experience of ultrasound-guided percutaneous irrigation of rotator cuff calcific tendinopathy (US-PICT). METHODS: Ninety-one patients (58 females; mean age: 50.5 ± 8.3 years) treated by US-PICT (local anesthesia, single-needle lavage, and intrabursal steroid injection) answered to a list of questions regarding their experience of the procedure before treatment, immediately after treatment, and three months later. The Borg CR10 scale was used to evaluate perceived pain, discomfort during anesthetic injection, and anxiety. The Wilcoxon, Spearman's rho, linear regression, and chi-square statistics were used. RESULTS: 81/91 patients complained mild discomfort during the injection of anesthetics (2, 1-2). Pain scores during US-PICT were very low (0, 0-1), with 70% patients having not experienced pain. After treatment, we found a significant reduction of pain (before: 8, 7-8; 3-month: 3, 1-6; p < .001) and anxiety (before: 5, 2-7; during treatment: 2, 1-7; p = 0.010), with high overall satisfaction (immediately after: 10, 9-10; 3-month: 9, 7-10) and confidence in the possibility of recovery (immediately after: 9, 8-10; 3-month: 10, 8-10), respectively. Treatments performed before US-PICT were not statistically associated with pain relief (p = 0.389) and clinical improvement (p = 0.937). We found a correlation between satisfaction immediately postprocedure and confidence in the possibility of recovery (p = 0.002) and between satisfaction three months after treatment and clinical improvement (p < 0.001) and patients' reminds about the description of the procedure (p = 0.005) and of the potential complications (p = 0.035). CONCLUSIONS: US-PICT is a mildly painful, comfortable, and well-tolerated procedure, regardless of any previous treatments. Patients' satisfaction is correlated with clinical benefit and full explanation of the procedure and its complications.


Assuntos
Calcinose , Manguito Rotador/diagnóstico por imagem , Tendinopatia , Irrigação Terapêutica , Ultrassonografia de Intervenção/métodos , Adulto , Ansiedade , Artralgia , Calcinose/diagnóstico por imagem , Calcinose/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Tendinopatia/diagnóstico por imagem , Tendinopatia/terapia , Irrigação Terapêutica/efeitos adversos , Irrigação Terapêutica/métodos , Resultado do Tratamento
5.
PLoS One ; 15(9): e0237984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881882

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) infected individuals may have osteoporosis. We aimed to evaluate the bone mineral density (BMD) in naïve antiretroviral (ARV) treated HIV positive patients comparing native Italian group (ItG) to a Migrants group (MiG) upon arrival in Italy. METHODS: We conducted a cross-sectional study on 83 HIV patients less than 50 years old. We used the dual-energy X-ray absorptiometry (DXA) within six months from the HIV diagnosis. Participants were categorized as having low BMD if the femoral neck or total lumbar spine Z-score was- 2 or less. RESULTS: MiG showed low BMD more often than ItG (37.5% vs.13.6%), especially for the female gender (16.7% vs. 0.0%). A low CD4 rate (<200 cells/µl) was most often detected in MiG than ItG. In particular, we found most often male Italians with abnormal CD4 than male migrants (67.8% vs. 33.3%) and vice versa for females (30.5% vs. 66.7%). We found an abnormal bone mineral density at the lumbar site. Low BMD at the lumbar site was more frequently observed in female migrants than female Italians. Both male and female migrants had a Z-score value significantly lower than male and female Italians, respectively. By logistic regression low vitamin-D level was positively correlated to low BMD in ItG only. All data were verified and validated using a triple code identifier. CONCLUSIONS: Both DXA and vitamin-D evaluation should be offered after the diagnosis of HIV infection. Lumbar site low BMD is an initial condition of bone loss in HIV young patients, especially in female migrants. Vitamin D levels and supplementation may be considered after HIV diagnosis independently of age to improve bone health. HIGHLIGHTS: This study evaluates the frequency of bone mineral density in HIV positive patients naive to antiretroviral therapy. It compares the density of the native Italian population with that of HIV Migrants upon arrival in Italy. The results show that HIV positive migrants, even if younger than 50 years of age, are at risk for osteoporosis, especially if they are female.


Assuntos
Densidade Óssea/fisiologia , Infecções por HIV/diagnóstico , Absorciometria de Fóton , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Osteoporose/etnologia , Osteoporose/etiologia , Osteoporose/patologia , Fatores Sexuais , Migrantes , Vitamina D/sangue
6.
Eur J Radiol ; 128: 109043, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32438261

RESUMO

PURPOSE: To evaluate the diagnostic performance of machine learning for discrimination between low-grade and high-grade cartilaginous bone tumors based on radiomic parameters extracted from unenhanced magnetic resonance imaging (MRI). METHODS: We retrospectively enrolled 58 patients with histologically-proven low-grade/atypical cartilaginous tumor of the appendicular skeleton (n = 26) or higher-grade chondrosarcoma (n = 32, including 16 appendicular and 16 axial lesions). They were randomly divided into training (n = 42) and test (n = 16) groups for model tuning and testing, respectively. All tumors were manually segmented on T1-weighted and T2-weighted images by drawing bidimensional regions of interest, which were used for first order and texture feature extraction. A Random Forest wrapper was employed for feature selection. The resulting dataset was used to train a locally weighted ensemble classifier (AdaboostM1). Its performance was assessed via 10-fold cross-validation on the training data and then on the previously unseen test set. Thereafter, an experienced musculoskeletal radiologist blinded to histological and radiomic data qualitatively evaluated the cartilaginous tumors in the test group. RESULTS: After feature selection, the dataset was reduced to 4 features extracted from T1-weighted images. AdaboostM1 correctly classified 85.7 % and 75 % of the lesions in the training and test groups, respectively. The corresponding areas under the receiver operating characteristic curve were 0.85 and 0.78. The radiologist correctly graded 81.3 % of the lesions. There was no significant difference in performance between the radiologist and machine learning classifier (P = 0.453). CONCLUSIONS: Our machine learning approach showed good diagnostic performance for classification of low-to-high grade cartilaginous bone tumors and could prove a valuable aid in preoperative tumor characterization.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/patologia , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Adulto , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos
7.
Neuroradiol J ; 31(4): 356-361, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29565219

RESUMO

Purpose The aim of this study was to determine the occurrence and distribution of the 'central vein' sign in white matter lesions on susceptibility-weighted magnetic resonance images in patients with multiple sclerosis (MS) and cerebral small vessel disease (CSVD). Materials and methods T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of 19 MS patients and 19 patients affected by CSVD were analysed for the presence and localisation of focal hyperintense white matter lesions. Lesions were subdivided into periventricular or non-periventricular (juxtacortical, subcortical, deep white matter and cerebellar) distributed. The number and localisation of lesions presenting with the central vein sign were recorded and compared between MS and CSVD lesions. Results A total of 313 MS patients and 75 CSVD lesions were identified on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. The central vein sign was found in 128 MS lesions (40.9%), and the majority of them (71/128, 55.5%) had a periventricular distribution. The central vein sign was found in 22 out of 75 (29.3%) CSVD lesions, and periventricular distribution was seen in six out of 22 (27.2%) CSVD lesions. The difference in the proportion of white matter hyperintense lesions that presented with the central vein sign on susceptibility-weighted images in patients with MS and CSVD was statistically different, and a significantly higher number of MS patients presented with lesions with the central vein sign compared to CSVD patients. Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.


Assuntos
Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Veias/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Prevalência , Estudos Retrospectivos , Veias/patologia , Substância Branca/irrigação sanguínea , Adulto Jovem
8.
Expert Rev Gastroenterol Hepatol ; 10(6): 671-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27027652

RESUMO

Focal steatosis and fatty sparing are a frequent finding in liver imaging, and can mimic solid lesions. Liver regional variations in the degree of fat accumulation can be related to vascular anomalies, metabolic disorders, use of certain drugs or coexistence of hepatic masses. CT and MRI are the modalities of choice for the noninvasive diagnosis of hepatic steatosis. Knowledge of CT and MRI appearance of focal steatosis and fatty sparing is crucial for an accurate diagnosis, and to rule-out other pathologic processes. This paper will review the CT and MRI techniques for the diagnosis of hepatic steatosis and the CT and MRI features of common and uncommon causes of focal steatosis and fatty sparing.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Fígado Gorduroso Alcoólico/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Adulto , Idoso , Fígado Gorduroso Alcoólico/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
9.
Brain Res Mol Brain Res ; 139(2): 361-6, 2005 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-16039006

RESUMO

The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK-) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK-) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK-). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.


Assuntos
Dopamina/metabolismo , Regulação da Expressão Gênica/fisiologia , Neurônios/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Substância Negra/citologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Masculino , Microinjeções/métodos , Mutagênese/fisiologia , Neurônios/virologia , Polietilenoimina/farmacologia , Proteínas Tirosina Quinases/deficiência , Ratos , Ratos Endogâmicos F344 , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Substância Negra/metabolismo , Substância Negra/virologia , Fatores de Tempo , Transfecção/métodos , beta-Galactosidase/metabolismo
10.
Folia Morphol (Warsz) ; 64(3): 130-44, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16228947

RESUMO

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson's disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ss-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson's disease.


Assuntos
Fosfatos de Cálcio/química , Vetores Genéticos , Herpesvirus Humano 1/genética , Doença de Parkinson/etiologia , Polietilenoimina/química , Receptores Proteína Tirosina Quinases , Receptores de Fatores de Crescimento de Fibroblastos , Substância Negra/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Cricetinae , Camundongos , Células NIH 3T3 , Nanotecnologia , Ratos , Receptores Proteína Tirosina Quinases/química , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/química , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Substância Negra/virologia , Transdução Genética/métodos
11.
Nat Commun ; 6: 7563, 2015 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-26102562

RESUMO

During a planetary transit, atoms with high atomic number absorb short-wavelength radiation in the upper atmosphere, and the planet should appear larger during a primary transit observed in high-energy bands than in the optical band. Here we measure the radius of Venus with subpixel accuracy during the transit in 2012 observed in the optical, ultraviolet and soft X-rays with Hinode and Solar Dynamics Observatory missions. We find that, while Venus's optical radius is about 80 km larger than the solid body radius (the top of clouds and haze), the radius increases further by >70 km in the extreme ultraviolet and soft X-rays. This measures the altitude of the densest ion layers of Venus's ionosphere (CO2 and CO), useful for planning missions in situ, and a benchmark case for detecting transits of exoplanets in high-energy bands with future missions, such as the ESA Athena.

12.
J Med Case Rep ; 8: 282, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25146384

RESUMO

INTRODUCTION: To date intracranial complication caused by tooth extractions are extremely rare. In particular parietal subdural empyema of odontogenic origin has not been described. A literature review is presented here to emphasize the extreme rarity of this clinical entity. CASE PRESENTATION: An 18-year-old Caucasian man with a history of dental extraction developed dysarthria, lethargy, purulent rhinorrhea, and fever. A computed tomography scan demonstrated extensive sinusitis involving maxillary sinus, anterior ethmoid and frontal sinus on the left side and a subdural fluid collection in the temporal-parietal site on the same side. He underwent vancomycin, metronidazole and meropenem therapy, and subsequently left maxillary antrostomy, and frontal and maxillary sinuses toilette by an open approach. The last clinical control done after 3 months showed a regression of all symptoms. CONCLUSIONS: The occurrence of subdural empyema is an uncommon but possible sequela of a complicated tooth extraction. A multidisciplinary approach involving otolaryngologist, neurosurgeons, clinical microbiologist, and neuroradiologist is essential. Antibiotic therapy with surgical approach is the gold standard treatment.


Assuntos
Empiema Subdural/etiologia , Lobo Parietal/diagnóstico por imagem , Sinusite/complicações , Sinusite/diagnóstico por imagem , Extração Dentária/efeitos adversos , Doença Aguda , Adolescente , Antibacterianos/uso terapêutico , Craniotomia/métodos , Diagnóstico Diferencial , Empiema Subdural/tratamento farmacológico , Empiema Subdural/cirurgia , Seguimentos , Humanos , Masculino , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Meropeném , Metronidazol/uso terapêutico , Sinusite/tratamento farmacológico , Espaço Subdural/diagnóstico por imagem , Tienamicinas/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vancomicina/uso terapêutico
13.
J Neurochem ; 97(5): 1243-58, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16524369

RESUMO

Developing and mature midbrain dopamine (DA) neurons express fibroblast growth factor (FGF) receptor-1 (FGFR1). To determine the role of FGFR1 signaling in the development of DA neurons, we generated transgenic mice expressing a dominant negative mutant [FGFR1(TK-)] from the catecholaminergic, neuron-specific tyrosine hydroxylase (TH) gene promoter. In homozygous th(tk-)/th(tk-) mice, significant reductions in the size of TH-immunoreactive neurons were found in the substantia nigra compacta (SNc) and the ventral tegmental area (VTA) at postnatal days 0 and 360. Newborn th(tk-)/th(tk-) mice had a reduced density of DA neurons in both SNc and VTA, and the changes in SNc were maintained into adulthood. The reduced density of DA transporter in the striatum further demonstrated an impaired development of the nigro-striatal DA system. Paradoxically, the th(tk-)/th(tk-) mice had increased levels of DA, homovanilic acid and 3-methoxytyramine in the striatum, indicative of excessive DA transmission. These structural and biochemical changes in DA neurons are similar to those reported in human patients with schizophrenia and, furthermore, these th(tk-)/th(tk-) mice displayed an impaired prepulse inhibition that was reversed by a DA receptor antagonist. Thus, this study establishes a new developmental model for a schizophrenia-like disorder in which the inhibition of FGF signaling leads to alterations in DA neurons and DA-mediated behavior.


Assuntos
Diferenciação Celular/genética , Dopamina/metabolismo , Mesencéfalo/metabolismo , Neurônios/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Esquizofrenia/genética , Animais , Crescimento Celular , Modelos Animais de Doenças , Dopamina/análogos & derivados , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Predisposição Genética para Doença/genética , Ácido Homovanílico/metabolismo , Masculino , Mesencéfalo/crescimento & desenvolvimento , Mesencéfalo/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibição Neural/genética , Regiões Promotoras Genéticas/genética , Reflexo de Sobressalto/genética , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Transdução de Sinais/genética , Substância Negra/crescimento & desenvolvimento , Substância Negra/metabolismo , Substância Negra/fisiopatologia , Tirosina 3-Mono-Oxigenase/genética , Área Tegmentar Ventral/crescimento & desenvolvimento , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/fisiopatologia
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