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1.
J Stomatol Oral Maxillofac Surg ; 120(4): 341-346, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30965155

RESUMO

INTRODUCTION: In surgical approaches to condylar fractures, there is a risk of damage to the transverse facial artery (TFA) which may in turn account for impaired blood supply to the temporomandibular joint (TMJ). In order to investigate the risk of damage to the TFA, and prevent lesions to this artery resulting from TMJ surgical procedures, we studied the distance between the TFA and the head of the condylar process. METHODOLOGY: A dissection study was conducted on 10 fresh cadavers (20 condylar specimens dissected), involving fifty CT scans of the face with intravenous contrast. Vertical distance from the TFA to the top of the mandibular condyle head and distance from the TFA to the lateral aspect of the mandibular condyle were measured. RESULTS: The lateral aspect of the mandibular condyle is vascularized by branches emanating from the superficial temporal artery (STA) and the TFA. The TFA was located 1.84 ± 0.6 cm below the condylar process of the mandible and ran 1.09 ± 0.54 mm lateral to the head of the mandibular condyle. DISCUSSION: In order to spare the TFA in fractures involving the condylar neck, surgical approaches to the condyle should preserve the uppermost 2 cm of the lateral surface of the condyle during dissection. Due to the necessity for periosteal elevation of the lateral surface of the condyle in condylar head fractures, it is possible to spare the TFA, running lateral to the condylar neck, and the medial condylar surface in order to leave the branches that derive from the maxillary artery (MA) intact.


Assuntos
Fraturas Ósseas , Côndilo Mandibular , Humanos , Mandíbula , Artéria Maxilar , Articulação Temporomandibular
2.
J Gynecol Obstet Biol Reprod (Paris) ; 45(5): 467-77, 2016 May.
Artigo em Francês | MEDLINE | ID: mdl-26897467

RESUMO

OBJECTIVES: To achieve a 3D vectorial model of a female pelvis by Computer-Assisted Anatomical Dissection and to assess educationnal and surgical applications. MATERIALS AND METHOD: From the database of "visible female" of Visible Human Project(®) (VHP) of the "national library of medicine" NLM (United States), we used 739 transverse anatomical slices of 0.33mm thickness going from L4 to the trochanters. The manual segmentation of each anatomical structures was done with Winsurf(®) software version 4.3. Each anatomical element was built as a separate vectorial object. The whole colored-rendered vectorial model with realistic textures was exported in 3Dpdf format to allow a real time interactive manipulation with Acrobat(®) pro version 11 software. RESULTS: Each element can be handled separately at any transparency, which allows an anatomical learning by systems: skeleton, pelvic organs, urogenital system, arterial and venous vascularization. This 3D anatomical model can be used as data bank to teach of the fundamental anatomy. CONCLUSION: This 3D vectorial model, realistic and interactive constitutes an efficient educational tool for the teaching of the anatomy of the pelvis. 3D printing of the pelvis is possible with the new printers.


Assuntos
Instrução por Computador , Dissecação , Imageamento Tridimensional , Modelos Anatômicos , Pelve/anatomia & histologia , Osso e Ossos/anatomia & histologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/educação , Ginecologia/educação , Humanos , Pessoa de Meia-Idade , Músculos/anatomia & histologia , National Library of Medicine (U.S.) , Pelve/irrigação sanguínea , Estados Unidos , Vísceras/anatomia & histologia
3.
Vet Comp Oncol ; 14(1): 81-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24118677

RESUMO

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.


Assuntos
Neoplasias Ósseas/veterinária , Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Osteossarcoma/veterinária , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Cães , Doxorrubicina/administração & dosagem , Osteossarcoma/tratamento farmacológico
5.
Surg Radiol Anat ; 37(3): 231-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25047542

RESUMO

OBJECTIVE: The aim of the present study was to show the feasibility and describe the first results of a 3D reconstruction of the venous network of the lower limbs in human fetus using the computer-assisted anatomical dissection (CAAD) technique. MATERIALS AND METHODS: We used limbs from two human fetuses, respectively, 14 and 15 weeks gestation old. Specimens were fixed in 10% formalin, embedded in paraffin wax and serially sectioned at 10 m. The histological slices were stained using HES and Masson Trichrome for soft tissues identification. Immunolabeling techniques using the Protein S-100 marker and the D2-40 marker were used to identify nerves and vessels, respectively. Stained slices were aligned manually, labeled and digitalized. The segmentation of all anatomical structures was achieved using the WinSurf(®) software after manual drawing. RESULTS: A 3D interactive vectorial model of the whole leg, including skin, bone, muscles, arteries, veins, and nerves was obtained. In all limbs, we observed the presence of a big axial vein traveling along the sciatic nerve. In addition, the femoral vein appeared as a small plexus. Although this is a common anatomical feature at the end of organogenesis, this feature is observed in only 9% of adults. Usually interpreted as an "anatomical variation of the femoral vein" it should be considered as a light truncular malformation. These observations bring further support to our proposed "angio-guiding nerves" hypothesis. CONCLUSION: This preliminary study shows that the CAAD technique provided an accurate 3D reconstruction of the fetal leg veins anatomy. It should bring a new insight for the understanding of the different steps of development of the human venous system.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Extremidade Inferior/anatomia & histologia , Extremidade Inferior/irrigação sanguínea , Veias/anatomia & histologia , Cadáver , Dissecação/métodos , Veia Femoral/anatomia & histologia , Veia Femoral/diagnóstico por imagem , Veia Femoral/embriologia , Feto , Humanos , Extremidade Inferior/diagnóstico por imagem , Flebografia/métodos , Veia Safena/anatomia & histologia , Veia Safena/diagnóstico por imagem , Veia Safena/embriologia , Cirurgia Assistida por Computador/métodos , Veias/embriologia
7.
J Eur Acad Dermatol Venereol ; 25(8): 964-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21108661

RESUMO

BACKGROUND: Cutaneous angiosarcoma (AS) is a rare aggressive malignant vascular tumour of the skin. METHODS: We analysed the cases of cutaneous AS in two large dermatological departments of Saxony during the last 10 years. RESULTS: A total of eight AS cases were identified, mostly with head and neck involvement. Because of age and late diagnosis, only a minor part was completely resectable. As a palliative therapy pegylated liposomal doxorubicin was used. The drug was well tolerated. Our cases and those published in the literature suggest a high rate of responses and a possible sensitisation to subsequent radiation therapy. CONCLUSIONS: Although complete surgical resection followed by wide-field radiation therapy has been established as a therapeutic standard for AS, delay in diagnosis and older age with comorbidities warrant for a safe and effective adjuvant treatment. Pegylated liposomal doxorubicin combined with radiotherapy seems to be a useful and safe alternative.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Hemangiossarcoma/terapia , Cuidados Paliativos , Polietilenoglicóis/uso terapêutico , Neoplasias Cutâneas/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Tardio , Doxorrubicina/uso terapêutico , Feminino , Hemangiossarcoma/patologia , Humanos , Masculino , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
8.
Eur Respir J ; 37(4): 835-40, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20650995

RESUMO

Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions. Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context. Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce. Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.


Assuntos
Granuloma/genética , Microcirculação , Sarcoidose Pulmonar/genética , Adulto , Anticorpos Monoclonais Murinos/química , Antígenos CD34/biossíntese , Biópsia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Vasos Linfáticos/metabolismo , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Estudos Retrospectivos
9.
Eur J Vasc Endovasc Surg ; 33(5): 619-24, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17224284

RESUMO

OBJECTIVE: To study the short term results of combined peroperative foam sclerotherapy (PFS) and surgical treatment for recurrent varicose veins. METHODS: PFS was used to treat 129 limbs with recurrent varices: 100 great saphenous (GSV), 29 small saphenous veins (SSV). Foam was prepared with 1% polidocanol mixed with 4 times its volume of air. The 100 GSVs comprised 28 trunks directly connected with the femoral vein, 28 connected to a lymph node venous network, 11 associated with perforators and 33 isolated trunks. The 29 SSVs comprised 4 trunks directly connected to the popliteal vein, 7 isolated trunks, 15 popliteal perforators and 3 recanalisations after SSV stripping. All operations included phlebectomies. In twenty limbs re-ligation of the SFJ and 4 SPJs was carried out. All were performed under local anaesthesia in an ambulatory setting. Patients were assessed clinically and by colour duplex ultrasound after 3 and 40 days follow-up. RESULTS: 120 patients (93%) showed complete obliteration of saphenous trunks, junctions and varices. The 9 incomplete obliterations were 3 venous recanalisations in the SSV compartment and 6 perforators (4 popliteal and 2 femoral). Two asymptomatic deep venous thromboses were detected by colour duplex 3 days after operation. CONCLUSION: PFS facilitates surgical treatment of recurrent varicose veins. There is a small risk of post-operative deep vein thrombosis.


Assuntos
Escleroterapia , Varizes/terapia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polidocanol , Polietilenoglicóis/uso terapêutico , Recidiva , Veia Safena , Soluções Esclerosantes/uso terapêutico , Resultado do Tratamento , Varizes/cirurgia
10.
Eur J Vasc Endovasc Surg ; 28(2): 177-81, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15234699

RESUMO

BACKGROUND: One of the shortcomings of the CEAP classification is that some of the clinical conditions in the original version were not defined and, therefore, were used in different ways by those who work with CEAP. AIM: To clarify the definitions of the seven clinical classes in the CEAP classification and to improve universal understanding of these in phlebology. METHODS: The authors prepared a short questionnaire regarding the 'C' part of CEAP with five main questions, dealing with definitions of clinical items: telangiectases, corona phlebectatica, reticular veins, varicose veins and the use of CEAP. The questionnaire was translated into 11 different languages and sent around the world by means of International Venous Digest by fax. Two hundred and six answers were received from 67 countries out of 3681 faxes sent (5.6%). RESULTS: There were a wide variety of opinions returned thus demonstrating that the same term is used with various meanings by different physicians. All physicians classify telangiectases of thigh and foot as class C1, but discrepant answers were obtained concerning the differences between reticular veins and reticular varicose veins as well as the diameter of small and large varicose veins. Sixty per cent of physicians answering this survey use the CEAP classification. CONCLUSION: Further clarification and refinement of the CEAP classification are necessary. The authors hope that this will result in broader acceptance of CEAP.


Assuntos
Doenças Vasculares/classificação , Humanos , Inquéritos e Questionários , Telangiectasia/classificação , Terminologia como Assunto , Varizes/classificação , Insuficiência Venosa/classificação
11.
Infect Immun ; 69(9): 5857-63, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11500464

RESUMO

Modifications of mucosal phospholipids have been detected in samples from patients with Helicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2 activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2 expression and PLA2 activity in the gastric mucosae of patients with and without H. pylori infection. In gastric biopsies from 10 H. pylori-positive patients, cPLA2 levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2 activity were higher than in 10 H. pylori-negative gastritis patients. To clarify whether H. pylori had a direct effect on the cellular expression of cPLA2, we studied cPLA2 expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with different H. pylori strains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2 protein expression was observed in AGS or MKN 28 cells treated with wild-type H. pylori. In conclusion, our study shows increased cPLA2 expression and PLA2 activity in the gastric mucosae of patients with H. pylori infection and no change in epithelial cell lines exposed to H. pylori.


Assuntos
Mucosa Gástrica/enzimologia , Gastrite/microbiologia , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Fosfolipases A/metabolismo , Adulto , Idoso , Citosol/enzimologia , Células Epiteliais/enzimologia , Gastrite/enzimologia , Humanos , Pessoa de Meia-Idade , Fosfolipases A2 , Células Tumorais Cultivadas
12.
J Biol Chem ; 276(38): 35917-23, 2001 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-11451961

RESUMO

The cell density-dependent growth inhibition of human SK-N-MC neuroblastoma cells is initiated by increased ganglioside sialidase activity leading to elevated cell surface presentation of ganglioside GM1, a ligand of galectin-1. We herein show that the extent of the cell surface expression of the galectin coincides with marked increases of the sialidase activity. Reverse transcriptase-polymerase chain reaction analysis excludes a regulation at the transcriptional level. Exposure of cells to purified galectin-1 reveals its carbohydrate-dependent activity to reduce cell proliferation. Assays to detect DNA fragmentation biochemically and cytometrically and to block caspases render it unlikely that galectin-1 acts as a classical proapoptotic factor on these cells. Because the chimeric galectin-3 shares binding sites and binding parameters with galectin-1 for these cells, we tested whether this galectin will elicit the same response as the homodimeric cross-linking galectin-1. Evidently, galectin-3 fails to affect cell growth by itself but interferes with galectin-1 upon coincubation. Its proteolytically truncated variant, the C-terminal lectin domain with impaired capacity to form aggregates when surface bound, has only weak binding properties. Thus, the way in which the galectin-1 interacts topologically with an apparently common set of ligands relative to galectin-3 is crucial for eliciting post-binding events. We conclude that galectin-1 is a probable effector in the sialidase-dependent growth control in this system. Moreover, the experiments with galectin-3 reveal functional divergence, most probably based on different topologies of presentation of homologous carbohydrate-binding sites.


Assuntos
Antígenos de Diferenciação/metabolismo , Metabolismo dos Carboidratos , Divisão Celular , Hemaglutininas/metabolismo , Neuroblastoma/patologia , Sequência de Bases , Membrana Celular/metabolismo , Primers do DNA , Galectina 1 , Galectina 3 , Humanos , Ligação Proteica , Células Tumorais Cultivadas
13.
J Clin Microbiol ; 39(7): 2618-26, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11427579

RESUMO

We developed a rapid thermocycling, real-time detection (also known as real-time PCR) method for the detection of Legionella species directly from clinical specimens. This method uses the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.) and requires approximately 1 to 2 h to perform. Both a Legionella genus PCR assay and Legionella pneumophila species-specific PCR assay were designed. A total of 43 archived specimens from 35 patients were evaluated, including 19 bronchoalveolar lavage (BAL) specimens and 24 formalin-fixed, paraffin-embedded open lung biopsy specimens. Twenty-five of the specimens were culture-positive for Legionella (9 BAL specimens and 16 tissue specimens). BAL specimens were tested by LightCycler PCR (LC-PCR) methods and by a direct fluorescent antibody (DFA) assay, which detects L. pneumophila serogroups 1 to 6 and several other Legionella species. Tissue sections were tested by the two LC-PCR methods, by DFA, by an in situ hybridization (ISH) assay, specifically designed to detect L. pneumophila, and by Warthin-Starry (WS) staining. The results were compared to the "gold standard" method of bacterial culture. With BAL specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by Legionella genus LC-PCR, 100 and 100%; Legionella genus detection by DFA assay, 33 and 100%; and L. pneumophila detection by L. pneumophila species-specific LC-PCR, 100 and 100%. With open lung biopsy specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by LC-PCR 68.8 and 100%; Legionella genus detection by DFA assay, 44 and 100%; Legionella genus detection by WS staining, 63 and 100%; L. pneumophila species-specific detection by LC-PCR, 17 and 100%; and L. pneumophila species-specific detection by ISH, 100 and 100%. The analytical sensitivity of both LC-PCR assays was <10 CFU/reaction. LC-PCR is a reliable method for the direct detection of Legionella species from BAL specimens. The Legionella genus LC-PCR assay could be performed initially; if positive, L. pneumophila species-specific LC-PCR could then be performed (if species differentiation is desired). The speed with which the LC-PCR procedure can be performed offers significant advantages over both culture-based methods and conventional PCR techniques. In contrast, for the methods evaluated, culture was the best for detecting multiple Legionella species in lung tissue. WS staining, Legionella genus LC-PCR, and L. pneumophila species-specific ISH were useful as rapid tests with lung tissue.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Legionella/isolamento & purificação , Legionelose/microbiologia , Pulmão/microbiologia , Antígenos de Bactérias/análise , Biópsia , Meios de Cultura , Humanos , Hibridização In Situ/métodos , Legionella/genética , Legionella/imunologia , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/microbiologia , Reação em Cadeia da Polimerase/métodos
14.
Graefes Arch Clin Exp Ophthalmol ; 238(2): 138-42, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10766282

RESUMO

BACKGROUND: Patients with relative anterior microphthalmus (RAM) are characterized by special anatomical features (corneal diameters <11 mm, anterior chamber depth <2 mm and normal axial length) that sometimes make intraocular lens (IOL) power calculation difficult. PATIENTS AND METHODS: Seventy-five patients aged 75.6+/-10.3 years with RAM were evaluated for preoperative target refraction and postoperative refraction after cataract surgery. We used biometric formulas as modified by Haigis for IOL power calculation. RESULTS: The average IOL power implanted was 25.2+/-2.8 dptr (one-piece all-PMMA IOL; range 19-31 dptr). The preoperatively calculated target refraction was -0.71+/-1.43 dptr (range -4.3 to +2.2 dptr). The average postoperative spherical equivalent was -0.41+/-1.50 dptr (range -5.5 to +6.0 dptr). The mean difference between target and end refraction was -0.30+/-1.54 dptr Fifty-seven percent of cases did not differ by more than 1 dptr from target refraction, 81.3% by not more than 2 dptr, and 94.7% by not more than 3 dptr; only 5.3% of cases deviated by more than 3 dptr. There was no correlation of the amount of deviation between target and postoperative refraction with axial length, corneal diameter and anterior chamber depth. There was, however, a significant correlation between target refraction and amount of deviation of spherical equivalent. The largest differences were found with target refractions greater than +2 dptr. CONCLUSIONS: In spite of the special anatomical conditions in patients with RAM the biometric formulas as modified by Haigis produced reliable IOL power calculations. The best accuracy was achieved when aiming at a target refraction in the range of +/-2 dptr.


Assuntos
Câmara Anterior/anormalidades , Extração de Catarata , Lentes Intraoculares , Microftalmia/complicações , Óptica e Fotônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Materiais Biocompatíveis , Catarata/complicações , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Polimetil Metacrilato , Refração Ocular , Reprodutibilidade dos Testes , Acuidade Visual
16.
J Clin Pathol ; 51(2): 127-33, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9602686

RESUMO

AIMS: Recent studies suggest that Helicobacter pylori is an invasive enteropathogen. However, the efficiency with which this pathogen invades mammalian cells remains unknown. Therefore, this study was designed to investigate the invasion frequencies of HEp-2 cells by clinical strains of H pylori. METHODS: An acridine orange assay and cultured HEp-2 cell monolayers were used to determine the HEp-2 cell penetration frequencies of 17 clinical isolates and one American Type Culture Collection (ATCC) strain of H pylori, and single clinical strains of Yersinia enterocolitica, Shigella flexneri, and a non-invasive ATCC Escherichia coli strain. RESULTS: The acridine orange assay demonstrated that invasion frequencies of HEp-2 cells by all H pylori isolates were significant and, in most instances, exceeded those for the S flexneri strain and equalled those for the Y enterocolitica strain. The assay also showed that internalised H pylori organisms remained viable for at least six hours, the maximum time that bacteria and HEp-2 cells were co-incubated. CONCLUSIONS: These results may have important implications for treatment and prevention strategies for this gastric pathogen. Furthermore, the acridine orange assay may be useful for assessing, in vitro, the ability of conventional and newer antibiotics, alone or in combination, to kill intracellular H pylori organisms.


Assuntos
Úlcera Duodenal/microbiologia , Células Epiteliais/microbiologia , Gastrite/microbiologia , Helicobacter pylori/fisiologia , Laranja de Acridina , Antibacterianos/farmacologia , Aderência Bacteriana , Células Cultivadas , Células Epiteliais/ultraestrutura , Corantes Fluorescentes , Gentamicinas/farmacologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/ultraestrutura , Microscopia de Contraste de Fase
17.
Bioorg Med Chem Lett ; 8(21): 3053-8, 1998 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-9873675

RESUMO

This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Indóis/síntese química , Inibidores de Fosfodiesterase/síntese química , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Animais , Artrite Infecciosa/tratamento farmacológico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Cães , Feminino , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Inibidores de Fosfodiesterase/farmacocinética
19.
Clin Immunol Immunopathol ; 69(2): 205-14, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8403558

RESUMO

The direct effect of the endogenous glucocorticoid (GC) hydrocortisone (HC) on interleukin-6 (IL-6) production was examined using purified populations of human peripheral blood monocytes (Mo). Lipopolysaccharide (LPS) induced IL-6 production by Mo in a dose-dependent fashion. IL-6 was detected in Mo supernatants as early as 2 hr after stimulation, with peak IL-6 production observed by 16 hr. Simultaneous addition of HC and LPS resulted in a significant decrease of IL-6 production 4 hr after LPS treatment, with maximum inhibition observed at 16-24 hr. An attenuation of the inhibitory effect of HC occurred with greater concentrations of LPS and with the delay of HC addition until after LPS. However, there was no correlation between the quantity of IL-6 produced by Mo and the level of HC inhibition. The inhibitory effect of HC was greater if LPS, rather than IL-1 beta, were used as a stimulus to induce IL-6 production. The EC50 of LPS-induced IL-6 production by HC was 2.0 x 10(-7) M. The inhibitory effect of HC on LPS-stimulated IL-6 production was GC specific and receptor mediated because: (i) equivalent inhibition was not observed with other endogenous steroids and (ii) equimolar amounts of the GC antagonist RU 486 blocked the GC-mediated effect.


Assuntos
Hidrocortisona/fisiologia , Interleucina-6/biossíntese , Monócitos/metabolismo , Adulto , Aldosterona/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1/biossíntese , Interleucina-1/farmacologia , Lipopolissacarídeos/farmacologia , Mifepristona/farmacologia , Progesterona/farmacologia , Proteínas Recombinantes/farmacologia , Análise de Regressão , Testosterona/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/farmacologia
20.
Pharm Res ; 9(9): 1177-83, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1409401

RESUMO

Recent studies have demonstrated that phagocytosis of colloidal particles by the mononuclear phagocytes of the liver and spleen can be controlled by either coating or stabilizing particulate carriers with the amphipathic polymeric surfactants, F108 and T908. These surfactants consist of copolymers of polypropylene oxide (PPO) and polyethylene oxide (PEO) and, when adsorbed to particulate surfaces, significantly decrease sequestration of particulates by the mononuclear phagocytes (MPS) of the liver. To evaluate these observations further, murine peritoneal macrophages were incubated for varying periods with surfactant-coated and noncoated polystyrene particles (PSPs). Phagocytosis was monitored using gamma counting and quantitative fluorescence microscopy. The data show that phagocytosis is decreased when PSPs are coated with F108 and T908. In addition, suppression of phagocytic activity was observed when cells were pretreated with the surfactant and then challenged with noncoated particles. The data confirm previous observations that polymeric surfactants consisting of PEO and PPO protect particulate carriers from rapid uptake by the MPS of the liver. Further, F108 and T908 suppress phagocytosis directly without affecting the integrity, viability, or functional state of the cell.


Assuntos
Fagocitose/efeitos dos fármacos , Tensoativos/farmacologia , Animais , Células Cultivadas , Etilenodiaminas/farmacologia , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Poloxaleno/farmacologia , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley
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