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1.
J Med Virol ; 91(3): 518-521, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30381830

RESUMO

To our knowledge, there are no published data on hepatitis C virus (HCV) genotypes in Angola. This study aimed at assessing the distribution of HCV genotypes in seropositive hemodialysis patients in Luanda. Among 51 HCV-positive subjects included, viremia was detected in 27 (53%). HCV genotyping was performed by bidirectional sequencing of the 5'-untranslated region by the Sanger method. HCV genotype 4 was largely predominant (20 cases; 74%), followed by genotypes 1b (5 cases; 18.5%), 1a and 2 (one case each; 3.7%). These results suggest that the distribution of HCV genotypes in Angola is similar to that reported from other Central African countries.


Assuntos
Hepatite C/epidemiologia , Hepatite C/virologia , Diálise Renal , Angola/epidemiologia , Estudos Transversais , Genótipo , Hepacivirus , Anticorpos Anti-Hepatite/sangue , Hepatite C/complicações , Humanos , Prevalência , Estudos Soroepidemiológicos , Viremia/epidemiologia
2.
Clin Exp Pharmacol Physiol ; 44(2): 275-284, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27864828

RESUMO

The Na+ -ATPase, a secondary pump in the proximal tubule, is only weakly responsive to angiotensin II in adult offspring exposed perinatally to high Na+ intake. We have investigated whether the offspring from mothers given 0.3 mol/L NaCl show an ineffective angiotensin II action to increase in blood pressure. It was hypothesized that functional alterations at adult life are associated with the number of angiotensin II-positive cells in the developing kidney, with increased oxidative stress in maternal/foetal organs, or with morphometrical changes in placentas. Wistar female rats were maintained on 0.3 mol/L NaCl in their drinking water from 20 days before conception until weaning. After weaning, some of the male offspring were treated with enalapril for 21 days. Glomerular filtration rate was recorded up to 210 days of age, when mean arterial pressure was measured after infusion of angiotensin II. To investigate the placenta and foetal kidneys, mothers on tap water or NaCl were also treated with alpha-tocopherol, pregnancy being interrupted on the 20th day. There were no changes in the number of cells positive for angiotensin II in the foetal kidney and unchanged lipid peroxidation in the placenta of offspring exposed to NaCl, but the intermediate trophoblast area in the junctional zone was increased, possibly reducing maternal-foetal exchange. Glomerular filtration rate was reduced and there was an attenuated effect of angiotensin II on elevation of blood pressure, which could be mediated by an elevated angiotensin II during early life, once these disturbances had been prevented by early and short-term treatment with enalapril.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Rim/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Insuficiência Renal/prevenção & controle , Cloreto de Sódio na Dieta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/embriologia , Rim/crescimento & desenvolvimento , Rim/fisiopatologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos Wistar , Insuficiência Renal/sangue , Insuficiência Renal/embriologia , Insuficiência Renal/etiologia
3.
Head Neck ; 46(1): 145-160, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37905455

RESUMO

BACKGROUND: Still, little is known about microbial dysbiosis in oropharyngeal and laryngeal tissue as risk factor for development of local squamous cell carcinoma. The site-specific microbiota at these regions in healthy and cancer tissue and their modulation by environmental factors need to be defined. METHODS: The local microbiota of cancer tissue and healthy controls was profiled by 16S rRNA gene amplicon sequencing and statistical analysis using 111 oropharyngeal and 72 laryngeal intraoperative swabs. RESULTS: Oropharynx and larynx harbor distinct microbial communities. Clear effects of both smoking and cancer were seen in the oropharynx whereas effects in the larynx were minor. CONCLUSION: The distinct microbial communities at larynx and oropharynx partially explain why the effects of cancer and smoking were distinct at those sites. Thus, the use of microbiota supposed to mirror community changes in another target location should be avoided and more studies on the actual cancerous environment are necessary.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Laringe , Microbiota , Neoplasias Orofaríngeas , Humanos , RNA Ribossômico 16S/genética , Carcinoma de Células Escamosas/patologia , Laringe/patologia , Fumar/efeitos adversos , Orofaringe/patologia , Neoplasias Orofaríngeas/patologia
4.
Biochim Biophys Acta ; 1814(12): 1947-54, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21835273

RESUMO

Indoleamine 2,3-dioxygenase (IDO1) catalyzes the first step in tryptophan breakdown along the kynurenine pathway. Therapeutic inhibition of IDO1 is receiving much attention due to its proposed role in the pathogenesis of several diseases including cancer, hypotension and neurodegenerative disorders. A related enzyme, IDO2 has recently been described. We report the first purification and kinetic characterization of human IDO2 using a facile l-tryptophan consumption assay amenable to high throughput screening. We found that the K(m) of human IDO2 for l-tryptophan is much higher than that of IDO1. We also describe the identification and characterization of a new IDO1 inhibitor compound, Amg-1, by high throughput screening, and compare the inhibition profiles of IDO1 and IDO2 with Amg-1 and previously described compounds. Our data indicate that human IDO1 and IDO2 have different kinetic parameters and different inhibition profiles. Docking of Amg-1 and related analogs to the known structure of IDO1 and to homology-modeled IDO2 suggests possible rationales for the different inhibition profiles of IDO1 and IDO2.


Assuntos
Descoberta de Drogas , Inibidores Enzimáticos/isolamento & purificação , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/química , Indolamina-Pirrol 2,3,-Dioxigenase/isolamento & purificação , Descoberta de Drogas/métodos , Inibidores Enzimáticos/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Isoenzimas/isolamento & purificação , Isoenzimas/metabolismo , Cinética , Modelos Biológicos , Modelos Moleculares , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
5.
Fetal Pediatr Pathol ; 31(5): 265-72, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22432721

RESUMO

Problems with the foreskin are common reasons for pediatric surgery consultations. We collected the foreskin of 40 patients for 2 years and these samples were divided into groups with and without previous topical corticosteroid. We carried out histochemical hematoxylin & eosin and Picrosirius analyses of the foreskin. Collagen fibers and inflammatory infiltrate was higher in samples from patients who had complications related to phimosis. Fibrosis was higher in patients who used topical corticosteroid. A histopathologic study of the foreskin may provide an additional analysis of patients undergoing circumcision and it can also improve the accuracy of surgical indication.


Assuntos
Betametasona/administração & dosagem , Circuncisão Masculina , Prepúcio do Pênis/patologia , Glucocorticoides/administração & dosagem , Fimose/tratamento farmacológico , Administração Tópica , Adolescente , Criança , Pré-Escolar , Colágeno/metabolismo , Fibrose/induzido quimicamente , Fibrose/patologia , Prepúcio do Pênis/metabolismo , Humanos , Masculino , Fimose/etiologia , Fimose/cirurgia , Estudos Retrospectivos
6.
J Virol ; 84(18): 9463-71, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20631139

RESUMO

Elite controllers maintain undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, but the correlates of immune protection in this patient population are ill defined. Here, we demonstrate that in comparison to patients with progressive HIV-1 infection or healthy persons not infected with HIV-1, elite controllers have circulating myeloid dendritic cells with significantly increased antigen-presenting properties, while their ability to secrete proinflammatory cytokines is substantially diminished. This unique functional profile is associated with a distinct surface expression pattern of immunomodulatory leukocyte-immunoglobulin-like receptors (LILR) and a strong and selective upregulation of LILRB1 and LILRB3. Blockade of these two receptors by monoclonal antibodies or short interfering RNA (siRNA) abrogated the specific antigen-presenting properties of dendritic cells, implying an important regulatory role of these molecules. These data reveal previously unrecognized innate components of immune protection against HIV-1 in elite controllers and offer novel perspectives for the manipulation of host immunity for the prevention and treatment of HIV-1 infection.


Assuntos
Apresentação de Antígeno , Antígenos CD/metabolismo , Células Dendríticas/imunologia , Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Receptores Imunológicos/metabolismo , Adulto , Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Citocinas/metabolismo , Feminino , Inativação Gênica , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/imunologia , Adulto Jovem
7.
Pain Physician ; 24(5): E625-E629, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34323450

RESUMO

BACKGROUND: Interventional radiofrequency (RF) ablation techniques are indicated when an adequate effect is not obtained with conservative measures. OBJECTIVES: The primary objective of this study was to evaluate pain relief after RF denervation of the sacroiliac joint. The secondary objective was to evaluate pain intensity and relief duration. STUDY DESIGN: The study was retrospective. SETTING: The study was conducted at Vera Cruz Hospital, Campinas, Brazil. METHODS: Data were collected from the medical records of patients undergoing RF denervation for low back pain originating in the sacroiliac joint, from January 2015 to December 2017. There were 78 patients studied, between 18 and 65 years old, of both genders, ASA I or II, who underwent knee arthroscopic meniscectomy. The patients were submitted to denervation of sacroiliac joint by 3 types of RF (conventional, pulsed, and cooled). The following parameters were evaluated, number of patients who obtained ? 50% pain relief; pain intensity, measured using the visual analog scale (before the procedure and 15, 30, 90 and 180 days after, performed by the same evaluator); and the use of complementary analgesic for 2 weeks. RESULTS: Of the 78 included patients, 56 (71.8%) underwent conventional RF, 9 (11.5%) underwent pulsed RF, and 13 (16.7%) underwent cooled RF. There were losses to follow-up including 40 patients who underwent conventional RF, 5 who underwent pulsed RF, and 12 who underwent cooled RF, who were retained for 6 months. There was significant pain relief with the three types of RF for up to 6 months of follow-up, with no difference among the types. After 6 months, 90.2% of patients who underwent conventional RF, 100% who underwent pulsed RF, and 91.7% who underwent cooled RF maintained ≥ 50% pain relief. Complementary analgesics were used by 95% of the patients who underwent conventional RF, 80% who underwent pulsed RF, and 91% who underwent cooled RF 2 weeks after the procedure. There were mild adverse effects, such as edema, hematoma, and local pain, without complications. LIMITATIONS: As for limitations, the number of pulsed and cooled RF is low and in a retrospective study some data may be missing, especially from follow-up. CONCLUSIONS: RF denervation of the sacroiliac joint is effective and promotes a long-lasting analgesic effect.


Assuntos
Dor Lombar , Articulação Sacroilíaca , Adolescente , Adulto , Idoso , Denervação , Feminino , Humanos , Dor Lombar/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Articulação Sacroilíaca/cirurgia , Resultado do Tratamento , Adulto Jovem
8.
Biochemistry ; 49(18): 3797-804, 2010 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-20337434

RESUMO

Stimulation of red cell production through agonism of the erythropoietin receptor (EpoR) has historically been accomplished through administration of erythropoietin (EPO), the native ligand. The short half-life of EPO has led to the development of a variety of other agonists, including antibodies. It is of considerable interest to understand how these agents might activate the EpoR and whether or not it is important to bind in a manner similar to the native ligand. The binding epitopes of a panel of eight agonistic, single-chain antibody (scFv-Fc) constructs were determined through scanning alanine mutagenesis as well as more limited arginine mutagenesis of the receptor. It was found that while some of these constructs bound to receptor epitopes shared by the ligand, others bound in completely unique ways. The use of a panel of agonists and scanning mutagenesis can define the critical binding regions for signaling; in the case of the EpoR, these regions were remarkably broad.


Assuntos
Epitopos/metabolismo , Eritropoetina/agonistas , Receptores da Eritropoetina/metabolismo , Transdução de Sinais , Anticorpos de Cadeia Única/metabolismo , Animais , Sítios de Ligação , Células COS , Chlorocebus aethiops , Epitopos/química , Epitopos/genética , Humanos , Cinética , Conformação Molecular , Ligação Proteica , Receptores da Eritropoetina/química , Receptores da Eritropoetina/genética , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética
9.
J Biol Chem ; 284(50): 34839-48, 2009 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-19833736

RESUMO

The leukocyte immunoglobulin-like receptor (LILR) B4 belongs to a family of cell surface receptors that possesses cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). LILRB4 is believed to down-regulate activation signals mediated by non-receptor tyrosine kinase cascades through the recruitment of SHP-1. However, the exact mechanisms of LILRB4-mediated inhibition are not fully elucidated. In this study, we demonstrate high level surface expression of LILRB4 on THP-1 cells and primary peripheral blood monocytes, which profoundly inhibited production of a key pro-inflammatory cytokine (TNFalpha) induced by FcgammaRI (CD64). We also report that LILRB4 aggregated to sites of activation upon co-ligation with CD64 and that this may enhance its inhibitory effects. Cross-linking of CD64 on THP-1 cells markedly increased phosphorylation of multiple proteins including tyrosine kinases and signaling molecules (Lck, Syk, LAT, and Erk), an adaptor protein that targets protein-tyrosine kinases for degradation (c-Cbl) and a protein involved in the formation of actin cytoskeletal rearrangement (alpha-actinin-4). Co-ligation of LILRB4 considerably reduced CD64-mediated phosphorylation of Lck, Syk, LAT, Erk, and c-Cbl but not alpha-actinin-4, suggesting selective inhibition of signaling molecules. Treatment of cells with a broad-spectrum phosphatase inhibitor, sodium pervanadate (SP), significantly reversed LILRB4-mediated inhibition of TNFalpha production and protein tyrosine phosphorylation. In comparison, treatment with an SHP-1 specific inhibitor, sodium stibogluconate (SS) has no effects indicating involvement of phosphatase(s) other than SHP-1 in LILRB4 signaling. Collectively, our data show LILRB4 is a potent inhibitor of monocytes activation. This may provide a new potential therapeutic strategy for inflammatory conditions characterized by excessive TNFalpha production.


Assuntos
Monócitos/metabolismo , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Actinina/metabolismo , Animais , Linhagem Celular , Inibidores Enzimáticos/metabolismo , Humanos , Separação Imunomagnética , Glicoproteínas de Membrana , Camundongos , Monócitos/citologia , Fosforilação , Receptores de Superfície Celular/genética , Receptores de IgG/genética , Receptores Imunológicos , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Crit Care Med ; 38(2): 491-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19789441

RESUMO

OBJECTIVE: To evaluate the predictive value of central venous saturation to detect extubation failure in difficult-to-wean patients. DESIGN: Cohort, multicentric, clinical study. SETTING: Three medical-surgical intensive care units. PATIENTS: All difficult-to-wean patients (defined as failure to tolerate the first 2-hr T-tube trial), mechanically ventilated for >48 hrs, were extubated after undergoing a two-step weaning protocol (measurements of predictors followed by a T-tube trial). Extubation failure was defined as the need of reintubation within 48 hrs. INTERVENTIONS: The weaning protocol evaluated hemodynamic and ventilation parameters, and arterial and venous gases during mechanical ventilation (immediately before T-tube trial), and at the 30th min of spontaneous breathing trial. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were enrolled in the study over a 6-mo period. Reintubation rate was 42.5%. Analysis by logistic regression revealed that central venous saturation was the only variable able to discriminate outcome of extubation. Reduction of central venous saturation by >4.5% was an independent predictor of reintubation, with odds ratio of 49.4 (95% confidence interval 12.1-201.5), a sensitivity of 88%, and a specificity of 95%. Reduction of central venous saturation during spontaneous breathing trial was associated with extubation failure and could reflect the increase of respiratory muscles oxygen consumption. CONCLUSIONS: Central venous saturation was an early and independent predictor of extubation failure and may be a valuable accurate parameter to be included in weaning protocols of difficult-to-wean patients.


Assuntos
Oxigênio/sangue , Desmame do Respirador , Gasometria , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Consumo de Oxigênio , Valor Preditivo dos Testes , Resultado do Tratamento , Desmame do Respirador/métodos
11.
Mol Cancer Res ; 6(8): 1337-46, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18708365

RESUMO

Damage to the gastrointestinal mucosa is a common dose-limiting toxicity of several anticancer therapies. Until recently, adequate control of oral mucositis was considered a significant unmet medical need, with most available treatments providing only palliative benefits without protecting the gastrointestinal epithelium from the damaging effects of cancer therapy. In 2005, palifermin [recombinant human keratinocyte growth factor (KGF)] was approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Current trials are investigating the use of palifermin in solid tumor settings. The objective of this study was to determine whether combining palifermin with different chemotherapeutic or biological agents affected the antitumor activity of these agents in human head and neck (FaDu) and colorectal (HT29) carcinoma xenograft models. Nude CD1 mice were injected with 1 x 10(7) of either FaDu or HT29 cells, which express both KGF and epithelial growth factor receptors. Animals were treated with palifermin in various combinations with chemotherapeutic (5-fluorouracil and cisplatin) and/or biological (bevacizumab, cetuximab, and panitumumab) agents. Palifermin alone had no effect on either FaDu or HT29 tumor growth. Palifermin did not affect the therapeutic efficacy of 5-fluorouracil, cisplatin, cetuximab, bevacizumab, or panitumumab in any of the two- or three-way drug combinations tested in either model. The results of this study showed that palifermin did not promote the growth of two carcinoma cell lines that express functional KGF receptors and did not protect these tumor cells from the antitumor effects of several chemotherapeutic and biological agents.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fator 7 de Crescimento de Fibroblastos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Bevacizumab , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cetuximab , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Quimioterapia Combinada , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Fator 7 de Crescimento de Fibroblastos/farmacologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Camundongos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo
12.
Eur J Immunol ; 38(12): 3459-73, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19009525

RESUMO

Leukocyte immunoglobulin-like receptor A5 (LILRA5) belongs to a family of receptors known to regulate leukocyte activation. There are two membrane-bound and two soluble forms of LILRA5. The transmembrane LILRA5 contain a short cytoplasmic domain and a charged arginine residue within the transmembrane region. Cross-linking of LILRA5 on monocytes induced production of pro-inflammatory cytokines, suggesting that LILRA5 plays a role in inflammation. However, expression of LILRA5 in diseases with extensive inflammatory component is unknown. Rheumatoid arthritis (RA) is a chronic inflammatory synovitis characterized by unregulated activation of leukocytes leading to joint destruction. Here we demonstrate extensive LILRA5 expression on synovial tissue macrophages and in synovial fluid of patients with active RA but not in patients with osteoarthritis. We also show that LILRA5 associated with the common gamma chain of the FcR and LILRA5 cross-linking induced phosphorylation of Src tyrosine kinases and Spleen tyrosine kinase (Syk). Furthermore, LILRA5 induced selective production of pro-inflammatory cytokines as well as IL-10. LILRA5 mRNA and protein expression was tightly regulated by TNF-alpha, IL-10 and IFN-gamma. Increased expression of LILRA5 in rheumatoid tissue, together with its ability to induce key cytokines involved in RA, suggests that this novel receptor may contribute to disease pathogenesis.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Citocinas/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Receptores Imunológicos/metabolismo , Membrana Sinovial/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Membrana Celular/imunologia , Células Cultivadas , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Macrófagos/citologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , Membrana Sinovial/imunologia
13.
J Leukoc Biol ; 83(2): 334-43, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17998301

RESUMO

The leukocyte Ig-like receptors (LILRs) comprise a family of cell-surface immunoregulatory receptors with activating and inhibitory members. The inhibitory LILRs possess cytoplasmic ITIMs that down-regulate signaling by nonreceptor tyrosine kinase cascades. The activating members have a truncated cytoplasmic domain and signal through the FcR gamma chain. We examined the expression of LILRs on human mast cells during their development in vitro. Progenitor mast cells expressed cell surface inhibitory LILRB1, -B2, -B3, and -B4 and activating LILRA1. However, although mature cord blood-derived mast cells (hMCs) had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. Culture of progenitor mast cells or hMCs with various cytokine combinations failed to retain or induce cell surface expression of the LILRs. It is interesting that hMCs expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. Our results demonstrate that LILRs are developmentally regulated in human mast cells and that LILRB5 is expressed in mast cell granules and the release of soluble LILRB5 following IgE FcR-dependent stimulation, which has potential for amplification of mast cell-dependent, inflammatory responses.


Assuntos
Antígenos CD/biossíntese , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/metabolismo , Mastócitos/metabolismo , Glicoproteínas de Membrana/biossíntese , Receptores de Superfície Celular/biossíntese , Receptores Imunológicos/biossíntese , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/genética , Diferenciação Celular/genética , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Citocinas/farmacologia , Grânulos Citoplasmáticos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Hematopoéticas/citologia , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/biossíntese , Agregação de Receptores , Receptores de Superfície Celular/genética , Receptores de IgE/fisiologia , Receptores Imunológicos/genética , Proteínas Recombinantes/farmacologia , Fator de Células-Tronco/farmacologia
14.
Oper Dent ; 34(3): 293-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19544818

RESUMO

The current study evaluated in-vitro microleakage of indirect composite inlays fixed with flowable composite and resinous cement and cured by LEDs and QTH units, thus modifying the internal conditioning of the inlays. Thirty-two non-carious teeth were selected and 64 cavity preparations were performed in both enamel and cementum. These teeth were divided into four groups: I--Elipar FreeLight appliance and Filtek Flowable composite; II--Ultralux appliance and Filtek Flowable composite; III--Elipar FreeLight appliance and RelyX cement and IV--Ultralux appliance and RelyX cement. The inlays were internally sandblasted with aluminum oxide, etched with 37% phosphoric acid, washed and silanized. The dental etching was carried out with 37% phosphoric acid for 15 seconds in dentin and 30 seconds in enamel. After being washed and dried, Single Bond dentinal adhesive was then applied, and the inlays were fixed with their respective luting agents, cured in close contact with their surfaces for 60 seconds, thermocycled and immersed in 0.5% basic fuchsine solution. The teeth were then washed and sectioned through the center of the restoration in order for the microleakage readings to be performed using the Image Tool Software. Then, ANOVA and Tukey's statistical tests were applied. In enamel, there was no significant difference for both groups with regard to microleakage; in cementum, the significant difference was 5% (p > 0.005). In agreement with the results, the inlays can be fixed with RelyX and Filtek Flowable resins.


Assuntos
Resinas Compostas/efeitos da radiação , Lâmpadas de Polimerização Dentária/classificação , Infiltração Dentária/classificação , Materiais Dentários/efeitos da radiação , Restaurações Intracoronárias , Condicionamento Ácido do Dente , Óxido de Alumínio/química , Bis-Fenol A-Glicidil Metacrilato/química , Corantes , Resinas Compostas/química , Preparo da Cavidade Dentária/métodos , Cemento Dentário/patologia , Esmalte Dentário/patologia , Corrosão Dentária , Materiais Dentários/química , Adesivos Dentinários/química , Humanos , Teste de Materiais , Ácidos Fosfóricos/química , Polímeros/química , Polímeros/efeitos da radiação , Cimentos de Resina/química , Cimentos de Resina/efeitos da radiação , Corantes de Rosanilina , Silanos/química , Propriedades de Superfície , Temperatura
15.
Afr J Paediatr Surg ; 16(1): 17-22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32952135

RESUMO

INTRODUCTION: Histopathological analysis of the foreskin has become more common in the last two decades. OBJECTIVES: This study aims to analyze the morphology of the foreskin and determine the effects of topical corticosteroid therapy on this tissue. MATERIALS AND METHODS: We retrospectively evaluated forty foreskin samples from children aged from 2 years to 15 years with phimosis undergoing circumcision at our institution over a 2-year period. In the foreskin samples, we analyzed the elastic fibers (Verhoeff), epidermal thickness (hematoxylin and eosin), and Annexin 1 and Langerhans cells (LCs) (immunohistochemistry). RESULTS: In the present study, 18 (45%) patients made use of topical corticosteroids, and 22 (55%) did not, while 4 (10%) had a history of balanoposthitis as previous complication. Forty patients were divided according to the parameter analyzed: with or without previous complication and with or without previous topical corticotherapy. Annexin 1 expression was significantly higher in group with a history of complications when compared with group without complications (P = 0.024) and lower in the group of those who used corticosteroids when compared with those who did not used corticosteroids (P = 0.364). In the analysis of all samples, the density of mature LCs was significantly higher when compared with immature LCs (P < 0.0001). The density of immature LCs was significantly higher in patients without previous complications when compared with group with complications (P = 0.028). CONCLUSIONS: These findings contribute to a better understanding of the histopathological aspects of previous complications and of treatment with corticosteroids in children with phimosis.

16.
Cancer Chemother Pharmacol ; 84(2): 287-298, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31011814

RESUMO

PURPOSE: Anticancer-drug efficacy seems to involve the direct interaction with host immune cells. Although topoisomerase I (Top I) inhibitors have been suggested to block LPS-evoked inflammation, the interaction between these drugs and toll-like receptor 4 (TLR4) is unaddressed. METHODS: SN-38, the active metabolite of the Top I inhibitor irinotecan, and TLR4 interaction was assessed using the in vitro luciferase nuclear factor-κB reporter assay, neutrophil migration to murine air-pouch, in silico simulation, and the thermal shift assay (TSA). Topotecan was used as a positive anti-inflammatory control. RESULTS: Non-cytotoxic concentrations of SN-38 attenuated LPS (a TLR4 agonist)-driven cell activation without affecting peptidoglycan (a TLR2 agonist)-activating response. Similarly, topotecan also prevented LPS-induced inflammation. Conversely, increasing concentrations of LPS reversed the SN-38 inhibitory effect. In addition, SN-38 abrogated LPS-dependent neutrophil migration and reduced TNF-α, IL-6, and keratinocyte chemoattractant levels in the air-pouch model, but failed to inhibit zymosan (a TLR2 agonist)-induced cell migration. A two-step molecular docking analysis indicated two potential binding sites for the SN-38 in the MD-2/TLR4 complex, the hydrophobic MD-2 pocket (binding energy of - 8.1 kcal/mol) and the rim of the same molecule (- 6.9 kcal/mol). The topotecan also bound to the MD-2 pocket. In addition, not only the lactone forms, but also the carboxylate conformations of both Top I inhibitors interacted with the MD-2 molecule. Furthermore, the TSA suggested the interaction of SN-38 with MD-2. CONCLUSIONS: Therefore, SN-38 inhibits acute inflammation by blocking LPS-driven TLR4 signaling. This mechanism seems to be shared by other Top I inhibitors.


Assuntos
Inflamação/tratamento farmacológico , Irinotecano/uso terapêutico , Receptor 4 Toll-Like/genética , Inibidores da Topoisomerase I/uso terapêutico , Animais , Humanos , Irinotecano/farmacologia , Masculino , Camundongos , Inibidores da Topoisomerase I/farmacologia
17.
Mov Disord ; 23(10): 1384-90, 2008 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-18512755

RESUMO

Rett syndrome (RS) is one of the best human models to study movement disorders. Patients evolve from a hyperkinetic to a hypokinetic state, and a large series of abnormal movements may be observed along their lives such as stereotypies, tremor, chorea, myoclonus, ataxia, dystonia, and rigidity. The aim of this work was to analyze movement disorders in RS patients with a detected MECP2 mutation, as well as their correlation with genotype, in a clinically and genetically well-characterized sample of patients, and thus contribute to redefine the clinical profile of this disease. In this study, we included 60 patients with detected MECP2 mutations. These were categorized and grouped for analysis, according to (1) type of change (missense or truncating, including nonsense and frameshift but also large deletions) and (2) location of the mutation. Differences were found concerning the frequency of independent gait, dystonia, type of tremor, and global score severity when comparing the group of patients with missense and truncating mutations. We also found differences in the presence, distribution, severity, or type of movement disorders in the two groups of patients according to the median duration of the disease (less than 60 months; 60 months or more). We conclude that movement disorders seem to reflect the severity and rate of progression of Rett disorder, patients with truncating mutations presenting a higher rate and more severe dystonia and rigid-akinetic syndrome, when comparing groups with similar time of disease evolution.


Assuntos
Proteína 2 de Ligação a Metil-CpG/genética , Transtornos dos Movimentos/etiologia , Mutação , Síndrome de Rett/complicações , Adolescente , Idade de Início , Criança , Pré-Escolar , Códon sem Sentido , Progressão da Doença , Feminino , Mutação da Fase de Leitura , Genótipo , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG/fisiologia , Mutação de Sentido Incorreto , Síndrome de Rett/genética , Deleção de Sequência , Índice de Gravidade de Doença , Transtorno de Movimento Estereotipado/etiologia , Fatores de Tempo
18.
Acta Med Port ; 31(3): 176-179, 2018 Mar 29.
Artigo em Português | MEDLINE | ID: mdl-29790470

RESUMO

Hidradenocarcinoma is a rare neoplasm of the eccrine cells of the sweat glands, usually asymptomatic with slow growing and higher incidence between 50 and 80 years, occurring in both sexes and preferentially located in the palmar, plantar, frontal, axillary and nuchal regions. It has an aggressive behavior, with high rate of local recurrence and distance metastasis, associated with a poor prognosis. We present a case of hidradenocarcinoma of the scrotum manifested by lymph node metastasis through an exercise of clinical and histological differential diagnosis of an inguinal adenopathy in a young adult.


O hidradenocarcinoma é uma neoplasia rara das células écrinas das glândulas sudoríparas, geralmente assintomática e de crescimento lento, com maior incidência entre os 50 e os 80 anos, atingindo ambos os sexos e com localização preferencial nas regiões palmar, plantar, frontal, axilar e nuca. Tem um comportamento agressivo, com alta taxa de recorrência local e metastização à distância, associando-se a mau prognóstico. Apresentamos um caso raro de hidradenocarcinoma do escroto manifestado por metastização ganglionar justificando exercício de diagnóstico diferencial clínico e histológico de adenopatia inguinal num adulto jovem.


Assuntos
Acrospiroma/patologia , Neoplasias dos Genitais Masculinos/patologia , Escroto , Neoplasias das Glândulas Sudoríparas/patologia , Acrospiroma/cirurgia , Adulto , Neoplasias dos Genitais Masculinos/cirurgia , Humanos , Metástase Linfática , Masculino , Neoplasias das Glândulas Sudoríparas/cirurgia
19.
Respir Care ; 63(12): 1471-1477, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30018175

RESUMO

BACKGROUND: Few studies have evaluated the effects of mechanical insufflation-exsufflation (MI-E) in subjects on mechanical ventilation. Therefore, this study aimed to evaluate the effectiveness of MI-E on airway mucus clearance among mechanically ventilated ICU subjects. METHODS: A randomized, parallel-group, open-label trial was conducted between June and November 2017 in a single, mixed ICU. Adult ICU subjects receiving mechanical ventilation for > 24 h with stable ventilatory and hemodynamic status were randomized to receive either standard respiratory physiotherapy alone (control group) or respiratory physiotherapy by using an MI-E device (intervention group). The primary outcome was the weight of aspirated airway mucus after study interventions. Secondary outcomes included variation in static lung compliance (ΔCL), airway resistance (ΔRaw), work of breathing (ΔWOB) in relation to the pre-intervention period, and hemodynamic and ventilator complications during the procedures. RESULTS: There were 90 subjects in each group. The mean ± SD weight of the aspirated airway mucus was higher in the intervention group than in the control group (2.42 ± 2.32 g vs 1.35 ± 1.56 g, P < .001). The ΔCL values in the intervention group were higher than those in the control group (1.76 ± 4.90 mL/cm H2O vs -0.57 ± 4.85 mL/cm H2O, P = .001). The ΔRaw and ΔWOB values were similar between the groups. No hemodynamic or ventilatory complications were observed. CONCLUSIONS: Among the general ICU subjects receiving mechanical ventilation, use of an MI-E device during respiratory physiotherapy resulted in a larger amount of airway mucus clearance than respiratory physiotherapy alone. (ClinicalTrials.gov registration NCT03178565.).


Assuntos
Depuração Mucociliar , Muco , Respiração Artificial , Terapia Respiratória/métodos , Idoso , Idoso de 80 Anos ou mais , Resistência das Vias Respiratórias , Feminino , Humanos , Insuflação , Unidades de Terapia Intensiva , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Terapia Respiratória/instrumentação , Método Simples-Cego , Trabalho Respiratório
20.
Sao Paulo Med J ; 135(3): 247-252, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28562733

RESUMO

BACKGROUND AND OBJECTIVES:: Postoperative analgesia and early recovery are important for hospital discharge. The primary objective of this study was to compare the analgesic effectiveness of perianal infiltration and subarachnoid anesthesia for hemorrhoidectomy. The secondary objective was to compare time to discharge, adverse effects and complications. DESIGN AND SETTING:: Randomized, prospective and comparative study at Dr. Mário Gatti Hospital. METHODS:: Forty patients aged 18-60, in American Society of Anesthesiologists physical status category 1 or 2, were included. The local group (LG) received local infiltration (0.75% ropivacaine) under general anesthesia; the spinal group (SG) received subarachnoid block (2 ml of 0.5% bupivacaine). Analgesic supplementation consisted of fentanyl for LG and lidocaine for SG. Postoperative pain intensity, sphincter relaxation, lower-limb strength, time to discharge, analgesic dose over one week and adverse effects were assessed. RESULTS:: Eleven LG patients (52.4%) required supplementation, but no SG patients. Pain intensity was higher for LG up to 120 min, but there were no differences at 150 or 180 min. There were no differences in the need for paracetamol or tramadol. Times to first analgesic supplementation and hospital discharge were longer for SG. The adverse effects were nausea, dizziness and urinary retention. CONCLUSIONS:: Pain intensity was higher in LG than in SG over the first 2 h, but without differences after 150 and 180 min. Time to first supplementation was shorter in LG. There were no differences in doses of paracetamol and tramadol, or in adverse effects. REGISTRATION:: ClinicalTrials.gov NCT02839538.


Assuntos
Analgesia/métodos , Anestesia Local/métodos , Raquianestesia/métodos , Hemorroidectomia/métodos , Dor Pós-Operatória/prevenção & controle , Adolescente , Adulto , Canal Anal , Analgésicos/uso terapêutico , Anestesia Local/efeitos adversos , Raquianestesia/efeitos adversos , Feminino , Hemorroidectomia/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Complicações Pós-Operatórias , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Espaço Subaracnóideo , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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