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1.
Gene Ther ; 19(8): 852-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21918551

RESUMO

Adeno-associated viral vector 9 (AAV9) has recently been shown to penetrate the blood-brain barrier via intravascular administration, making it a good candidate for diffuse gene delivery. However, the potential side effects of systemic delivery are unknown. Intrathecal viral vector administration may be more invasive than intravenous injections, but it requires far less vector and it can be performed on an outpatient basis, making it an ideal route of delivery for clinical translation. A total of 12 domestic farm pigs (<20 kg) underwent a single-level lumbar laminectomy with intrathecal catheter placement for AAV9 delivery. Animals were perfused and the tissue was harvested 30 days after treatment. Gene expression was assessed by anti-green fluorescent protein immunohistochemistry. Although a single lumbar injection resulted in gene expression limited to the lumbar segment of the spinal cord, three consecutive boluses via a temporary catheter resulted in diffuse transduction of motor neurons (MNs) throughout the cervical, thoracic and lumbar spinal cords. We now present the first successful robust transduction of MNs in the spinal cord of a large animal via intrathecal gene delivery using a self-complementary AAV9. These promising results can be translated to many MN diseases requiring diffuse gene delivery.


Assuntos
Dependovirus/genética , Técnicas de Transferência de Genes , Neurônios Motores/metabolismo , Medula Espinal/citologia , Suínos , Transdução Genética , Animais , Vetores Genéticos
2.
Neurochem Res ; 35(6): 881-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20024673

RESUMO

The intermediate filament (IF) synemin gene encodes three IF proteins (H 180, M 150, L 41 kDa) with overlapping distributions. Synemin M was present early with vimentin and nestin. Synemin H was found later in the nervous system and mesodermic derivatives concomitantly with angiogenesis and the migration of neural crest cells. Synemin L appeared later in neurons. A series of in vitro cell cultures were done to identify the linkage between synemin isoforms and specific cell types of the central nervous system (CNS). The neurons and glia from the brains of humans and rats were cultured and double immunostaining done with antibodies against the H/M or L synemin isoforms and neural cell types (betaIII-tubulin or NeuN) or astrocyte intermediate filaments (GFAP or vimentin). In neurons of the CNS, synemin H/M were co-expressed with GFAP, vimentin or nestin in glial cells, whereas synemin L was found in neurons.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Proteínas de Filamentos Intermediários/biossíntese , Neurônios/metabolismo , Animais , Encéfalo/citologia , Células Cultivadas , Humanos , Imuno-Histoquímica , Isoformas de Proteínas/biossíntese , Ratos
3.
Dig Liver Dis ; 40 Suppl 2: S260-4, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18598998

RESUMO

BACKGROUND: Infliximab (IFX), the chimeric anti TNFalpha antibody, an established treatment for Crohn's disease in adults and in children, is used less frequently in ulcerative colitis (UC). AIM OF THE STUDY: To report the clinical course of pediatric patients with active UC receiving IFX. PATIENTS AND METHODS: Charts of 22 patients were reviewed (13 male, 9 female): 4 with a severe UC attack refractory to systemic corticosteroids (CS); 18 with a protracted course, of which 16 CS-dependent and 2 CS-resistant. The baseline therapeutic program consisted of 3 consecutive intravenous infusions (0, 2, 6 weeks) of IFX (5 mg/kg), followed by a retreatment schedule (infusion every 8 weeks); azathioprine (AZA) was administered chronically in all. Clinical evaluation was done with the Lichtiger Colitis Activity Index (LCAI). Follow-up was performed until week 54. LCAI >/= 9 was considered treatment failure; a LCAI 9: 12 had a full response and were on remission at week 54 and did not receive CS (8 on IFX re-treatment and AZA, 4 on AZA alone); 6 had a partial response; 4 were non responders. Colectomy was performed in 7 patients, beyond the period of the acute attack in all but one. CONCLUSIONS: In children with severe ulcerative colitis IFX is a valuable treatment for inducing remission, avoiding emergency colectomy; retreatment may be offered to maintain remission.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Adolescente , Azatioprina/uso terapêutico , Criança , Quimioterapia Combinada , Feminino , Humanos , Infliximab , Itália , Masculino , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação
4.
Glia ; 54(3): 204-13, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16817202

RESUMO

The synemin gene encodes proteins belonging to the intermediate filament family. These proteins confer resistance to mechanical stress and modulate cell shape. Three synemin isoforms, of 180 (H), 150 (M) and 41 (L) kDa, are produced by alternative splicing of the pre-mRNA and are regulated differently during development. The three isoforms differ in their C-terminal tail domains, while their IF rod domains are identical. Synemins H/M occurred together with nestin and vimentin in glial progenitors during the early differentiation of the developing mouse central nervous system. They are later found in GFAP-labeled cells. In contrast, the L isoform appeared only in neurons, together with neurofilaments and betaIII-tubulin in the brain after birth. However, synemin L appeared from E13 in the peripheral nervous system, where it was confined to the neurons of spinal ganglia. In the meantime, the synemin H/M isoforms were found in both the neurons and Schwann cells of the sensorial ganglia from E11. Tissue fractionation and purification of IFs from adult mouse spinal cord revealed that the synemin L isoform binds to neurofilaments associated with the membrane compartment. This report describes the synthesis of the three synemin isoforms by selective cell types, and their temporal and spatial distributions. Mechanisms specific to neurons and glia probably control the splicing of the common synemin mRNA and the synthesis of each synemin isoform.


Assuntos
Proteínas de Filamentos Intermediários/genética , Neuroglia/fisiologia , Neurônios/fisiologia , Processamento Alternativo , Animais , Encéfalo/embriologia , Encéfalo/fisiologia , Células Cultivadas , Imuno-Histoquímica , Camundongos , Proteínas Musculares/genética , Neuroglia/citologia , Neurônios/citologia , Isoformas de Proteínas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/embriologia , Medula Espinal/fisiologia , Estresse Mecânico
5.
Aliment Pharmacol Ther ; 16(10): 1715-22, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12269963

RESUMO

BACKGROUND: Anti-Helicobacter pylori therapy has been reported to cause regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma in a high percentage of patients. However, in some patients, these lesions persist despite antibiotic treatment. AIM: To determine the various endosonographic findings that may predict the regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma post-antibiotics. METHODS: Seventy-six patients with Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma were studied. Follow-up data were available on 51 patients. All patients were treated with antibiotics. Participants underwent pre- and post-anti-Helicobacter pylori therapy endoscopy with gastric biopsies, followed by endoscopic ultrasonography examination of the stomach. RESULTS: Helicobacter pylori was eradicated in 45 of 51 (88%) patients. At the 2-year follow-up, complete regression of mucosa-associated lymphoid tissue lymphoma was seen in 28 of 51 (55%) patients: 12 of 16 (75%) patients in stage T1m N0, 11 of 19 (58%) patients in stage T1sm N0, four of eight (50%) patients in stages T1m N1 and T1sm N1, and one of four (25%) patients in stage T2 N0. None of the stage T2 N1 patients achieved clinical regression. CONCLUSIONS: Endoscopic ultrasonography evaluation of gastric mucosa-associated lymphoid tissue lymphoma plays a pivotal role in the initial staging and post-treatment follow-up evaluation of these lesions. Accurate staging is essential in the determination of the optimal treatment modality.


Assuntos
Endossonografia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Intervalo Livre de Doença , Quimioterapia Combinada/uso terapêutico , Feminino , Seguimentos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
6.
Ophthalmology ; 106(9): 1705-12, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10485538

RESUMO

OBJECTIVE: To assess the effect of blepharoptosis on patients' visual function and health-related quality of life and to determine what measures are associated with postsurgical change in functional status. DESIGN: Prospective, observational case series. PARTICIPANTS: One hundred patients with unilateral or bilateral blepharoptosis. INTERVENTION/MAIN OUTCOME MEASURES: Preoperative and postoperative upper eyelid position (i.e., margin reflex distance [MRD]) and superior visual field (SVF) height, as well as subjective visual function and health-related quality-of-life functional status before and after ptosis surgery. RESULTS: There was a mean 30-point increase in functional index score after ptosis repair (P < 0.001). Lower (more ptotic) preoperative upper eyelid position and SVF (combined eye) were associated with greater change in functional index after surgery (r = -0.290, P = 0.007 and r = -0.39, P = 0.003, respectively). Preoperative visual field testing with manual lid elevation was not significantly correlated to the postoperative change in functional index (P > 0.100). The strongest correlation of postoperative functional index change was with the preoperative functional status (r = -0.79, P < 0.001). CONCLUSIONS: Patients' functional status is reduced by blepharoptosis, and surgical repair results in measurable increase in health-related quality of life. Patients' self-reported preoperative functional impairment is most strongly associated with the degree of postsurgical functional improvement.


Assuntos
Blefaroptose/fisiopatologia , Blefaroptose/cirurgia , Pálpebras/fisiopatologia , Qualidade de Vida , Visão Ocular/fisiologia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pálpebras/cirurgia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos da Visão/fisiopatologia , Campos Visuais/fisiologia
8.
Toxicology ; 81(2): 103-12, 1993 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-8378936

RESUMO

Two-year skin carcinogenicity studies were conducted in C3H mice to assess the effects of irritation and selected compositional parameters on the carcinogenic potential of four petroleum liquids. Three samples (lightly refined paraffinic oil, LRPO; lightly hydrodesulfurized specialty oil, LHSO; jet fuel, JF) can be generically classified as middle distillates, i.e. distillation occurs between 350 and 700 degrees F (175-370 degrees C). The fourth sample was a Steam Cracked Gas Oil (SCGO) that distilled within the same range. In studies that assess the effects of irritation on tumorigenicity, LRPO was tested undiluted or was diluted to 50% and 25% in either mineral oil (which eliminated irritation of the skin) or toluene (which did not). Undiluted LRPO elicited tumors in 8% of the mice. Both dilution procedures eliminated tumorigenic potential. Thus, it was possible to maintain a visible level of skin irritation equivalent to that elicited by undiluted LRPO without inducing tumors. SCGO elicited a chronic irritant state grossly equivalent to LRPO but was not tumorigenic. Jet Fuel A (JF) was tested undiluted using both a standard skin painting protocol and an intermittent dosing schedule in which treatment was suspended periodically to allow skin irritation to resolve. The standard treatment protocol of JF resulted in both marked skin irritation and tumors in 44% of the mice. However, using the intermittent schedule, the tumor yield was reduced to 2%. Collectively these data demonstrate that tumor formation is not a necessary sequelae to chronic skin irritation. Conversely, prevention of a marked chronic irritant state was accompanied by decreased tumor yield. These data suggest that the chronic irritant state may be a necessary but not sufficient condition for tumor formation. In studies to assess the effects of compositional parameters, a lightly hydrodesulfurized specialty oil (LHSO) similar to LRPO but refined to have negligible levels of sulfur compounds (3 ppm), elicited chronic irritant and tumor responses (10%) similar to LRPO. Thus, the level of sulfur compounds does not appear to affect the tumorigenic activity for products in this boiling range. The SCGO which did not produce tumors contained only aromatic hydrocarbons, a finding consistent with previous reports that aromatics may not be the source of tumorigenic potential in petroleum fractions boiling between 350 and 700 degrees F (175-370 degrees C).


Assuntos
Petróleo/toxicidade , Neoplasias Cutâneas/induzido quimicamente , Animais , Masculino , Camundongos , Camundongos Endogâmicos C3H , Neoplasias Cutâneas/patologia
9.
Dig Dis Sci ; 36(8): 1116-20, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1864206

RESUMO

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4% +/- 30.4 vs 80.3 +/- 8.3 of controls, mean +/- SD, P = 0.007) and a slower than normal ejection phase (9.1%/min +/- 6.6 vs 18.1 +/- 4.5, P = 0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min +/- 15.4 vs 74.7 min +/- 11.5 in the controls (P = 0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative charges of extraesophageal nerve fibers as well as their clinical significance require further investigations.


Assuntos
Acalasia Esofágica/fisiopatologia , Vesícula Biliar/fisiopatologia , Esvaziamento Gástrico/fisiologia , Colecistocinina , Acalasia Esofágica/diagnóstico por imagem , Feminino , Vesícula Biliar/diagnóstico por imagem , Humanos , Iminoácidos , Masculino , Manometria , Pessoa de Meia-Idade , Compostos de Organotecnécio , Cintilografia , Ácido Dietil-Iminodiacético Tecnécio Tc 99m
10.
Minerva Chir ; 46(7 Suppl): 83-91, 1991 Apr 15.
Artigo em Italiano | MEDLINE | ID: mdl-2067701

RESUMO

Esophageal manometry is an established method of investigation in patients with suspected motor abnormalities. However, some degree of standardization of technique and method of analysis are still needed among different Laboratories. It is actually the gold standard for assessing the esophageal motor function but a correlation with other esophageal tests (i.e. radiology, endoscopy, pH-metry, scintigraphy) is usually required to reach a clinical diagnosis. Because of the large interindividual variability of manometric findings it is suggested that each laboratory could obtain its "own normal population". Recent evidences support that values outside the normal range may not always be associated with a functional abnormality. New physiopathological insights and widely accepted scheme of classification of manometric data are needed to improve its diagnostic usefulness.


Assuntos
Esôfago/fisiologia , Manometria/métodos , Adolescente , Adulto , Idoso , Humanos , Manometria/instrumentação , Pessoa de Meia-Idade , Peristaltismo , Valores de Referência
11.
Ital J Gastroenterol ; 22(6): 342-5, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2131952

RESUMO

In two patients with achalasia we found intermittent, complete lower oesophageal sphincter (LES) relaxations at manometric evaluation. These patients had no weight loss, minimal oesophageal dilation, lower LES pressure and faster radionuclide oesophageal emptying when compared with other achalasia patients. Concurrent performing of radionuclide oesophageal emptying and manometry showed that the complete relaxations (CRs) were too short and functionally unsuccessful. Our findings suggest that these patients may be at an earlier disease stage and that intermittent CRs of LES may occasionally occur in achalasia.


Assuntos
Acalasia Esofágica/fisiopatologia , Junção Esofagogástrica/fisiopatologia , Sulfato de Bário , Deglutição/fisiologia , Acalasia Esofágica/diagnóstico por imagem , Junção Esofagogástrica/diagnóstico por imagem , Humanos , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia , Peristaltismo/fisiologia , Pressão , Radiografia , Cintilografia , Estudos Retrospectivos , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Fatores de Tempo
12.
J Appl Toxicol ; 9(4): 265-70, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2778262

RESUMO

Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.


Assuntos
Carcinógenos , Óleos/toxicidade , Neoplasias Cutâneas/induzido quimicamente , Animais , Testes de Carcinogenicidade , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Compostos Policíclicos/toxicidade
13.
Radiol Med ; 77(6): 650-4, 1989 Jun.
Artigo em Italiano | MEDLINE | ID: mdl-2667044

RESUMO

The authors have evaluated both sensitivity and specificity of ERCP in comparison with other imaging methods, such as US and CT, on the basis of a study of 63 patients with suspected pancreatobiliary pathologies. Our results show ERCP of chronic pancreatitis to have 83% sensitivity and 66% specificity. As for biliary pathologies, sensitivity was 94% and specificity 88%. In pancreatic pathologies, CT sensitivity was 99% and its specificity was 70%. The combined use of ERCP and CT determines a considerable rise in the percentages, and allows the evaluation of both the excretory tree and the parenchyma. As for biliary pathologies, the role of ERCP is fundamental, since its combination with the other methods (CT: sensitivity 72%, specificity 3.5%; US: sensitivity 70%, specificity 3.5%) has not determined but a slight increase in sensitivity, and no significant increase in specificity.


Assuntos
Doenças Biliares/diagnóstico por imagem , Colangiopancreatografia Retrógrada Endoscópica , Pancreatopatias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto , Idoso , Doenças Biliares/diagnóstico , Colelitíase/diagnóstico , Colelitíase/diagnóstico por imagem , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pancreatopatias/diagnóstico , Pseudocisto Pancreático/diagnóstico , Pseudocisto Pancreático/diagnóstico por imagem
16.
Int J Tissue React ; 5(4): 353-5, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6423560

RESUMO

Twenty-three endoscopically healed duodenal ulcer patients entered a long-term treatment with pirenzepine for 1 year (two 25-mg tablets at breakfast and two tablets at bedtime). One day before and 7 days after the long-term treatment started, gastric pH and BAO were measured in each patient after fasting. The patients were clinically examined monthly and underwent endoscopy 4, 8 and 12 months after the trial started or when they complained of ulcer symptoms. Blood and urine laboratory tests were carried out before treatment began and 6 and 12 months afterwards. Eighteen of the 22 patients that completed the trial (82%) did not relapse. The statistical analysis tended to show a relationship between absence of pH increase and relapses. No severe side-effects or changes in the results of laboratory tests were observed.


Assuntos
Antiulcerosos/uso terapêutico , Benzodiazepinonas/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Adulto , Idoso , Feminino , Determinação da Acidez Gástrica , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pirenzepina , Recidiva
17.
Radiol Med ; 65(12): 867-72, 1979 Dec.
Artigo em Italiano | MEDLINE | ID: mdl-400034

RESUMO

In 12 X-ray and gastroenterology departments 1570 patients, clinically suspected to have a gastric pathology, have been examined by double contrast (surface) examination of the stomach followed by gastroscopy. Diagnostic accuracy was 93% in respect of endoscopic data, assumed correct by hypothesis. On the basis of a cost and benefit evaluation, made according to the well known criteria, a wider routine use of the double contrast technique is proposed.


Assuntos
Meios de Contraste/administração & dosagem , Gastroscopia/métodos , Estômago/diagnóstico por imagem , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Erros de Diagnóstico , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Itália , Pessoa de Meia-Idade , Radiografia , Gastropatias/diagnóstico por imagem
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