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1.
BMC Res Notes ; 11(1): 783, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384859

RESUMO

OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.

2.
Hum Immunol ; 79(1): 70-75, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29080719

RESUMO

Human Immunodeficiency Virus type 1 (HIV-1) infection and progression varies widely among individuals. Interferon-λ3 exerts anti-HIV function by activating JAK/STAT pathway-mediated innate immunity. Therefore, we aimed to investigate the association between single nucleotide polymorphisms of the interleukin 28B (IL28B) gene, and the risk of acquisition, AIDS development and therapeutic outcome of HIV-1 in a Moroccan population. A total of 266 HIV-1 seropositive and 158 HIV-1 seronegative subjects were enrolled. Genotyping of rs12979860 of the IL28B was performed using a predesigned TaqMan SNP genotyping assay. No significant association was found between IL28B rs12979860 polymorphism and susceptibility to HIV-1 infection and AIDS development (p > .05). However, in HIV-1 treated patients carrying CC genotype had a more pronounced high levels of CD4+ T-cell compared to subjects with TT genotype (p = .0004). Interestingly, regarding HIV-1 viral load no significant differences between IL28B genotypes in treated and untreated patients were observed (p < .05). IL28B rs12979860 polymorphism not influences the susceptibility to HIV-1 and the AIDS development. However, this polymorphism may affect the response to treatment as measured by CD4+ T cell counts.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , Linfócitos T CD4-Positivos/imunologia , Genótipo , HIV-1/fisiologia , Interleucinas/genética , Síndrome de Imunodeficiência Adquirida/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade , Feminino , Frequência do Gene , Predisposição Genética para Doença , Soropositividade para HIV , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Carga Viral/genética , Adulto Jovem
3.
Pharmacognosy Res ; 9(4): 390-395, 2017 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29263634

RESUMO

Background: Caralluma europaea (CE) has been studied for its chemical constituents, and no information is available on its toxicity or its pharmacological activities. Objective: To determine the toxicity of an aqueous extract of CE stems in vitro and in vivo after acute and subchronic oral gavages in Swiss albino's mice and its immunomodulatory and inflammatory activities. Materials and Methods: The extract was administrated in single oral dose at 5 g/kg body weight for the acute toxicity test and by gavages daily at doses of 1, 2.5, or 5 g/kg for 30 consecutive days for the subchronic toxicity test. The immunomodulatory activities and inflammatory activities were tested by the evaluation of hemagglutination antibodies (HAs) titers and delayed-type hypersensitivity (DTH) response. Results: For the dose of 1 g/kg, no visible toxic effects were observed. However, for the higher doses, clinical observations of toxicity were noted after 1 week of treatment. This was confirmed by the biochemical parameters values and the histology analyses of the spleen, liver, and kidney tissues. The high cellular mortality rate in vitro when treated with CE extract confirmed their toxicity potential. There was also increase of "HA titer" and "DTH" response in mice treated with nontoxic dose of CE (1 g/kg) compared to control group. This immune activity was confirmed by the high number of lymphocytes infiltrates noted in the different organs. Conclusion: We conclude that CE at the dose up of 1 g/kg produced toxic effect in mice that induced an immune inflammatory reaction. SUMMARY: Caralluma europaea (CE) has been studied for its chemical constituents, and no information is available on its toxicity or its pharmacological activities. The objective is to determine the toxicity of an aqueous extract of CE stems in vitro and in vivo after acute and subchronic oral gavages in Swiss albino's mice and its immunomodulatory and inflammatory activities. For the dose of 1 g/kg, no visible toxic effects were observed. However, for the higher doses, clinical observations of toxicity were noted after 1 week of treatment. This was confirmed by the biochemical parameters values and the histology analyses of the spleen, liver, and kidney tissues. The high cellular mortality rate in vitro confirmed their toxicity potential. There was also increase of "hemagglutination antibody titer" and "delayed-type hypersensitivity" response in mice treated with nontoxic dose of CE (1 g/kg) compared to control group. This immune activity was confirmed by the high number of lymphocytes infiltrates noted in the different organs. We conclude that CE at the dose up of 1 g/kg produced toxic effect in mice that induced an immune inflammatory reaction. Abbreviations Used: CE: Caralluma europaea, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, RRBCs: Rat red blood cells, DTH: Delayed-type hypersensitivity response, PBS: Phosphate buffer solution.

4.
J Toxicol Sci ; 41(3): 403-16, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27193732

RESUMO

Ochratoxin A (OTA) is a natural fungal secondary metabolite that contaminates food and animal feed. Human exposure and involvement of this mycotoxin in several pathologies have been demonstrated worldwide. We investigated OTA immunotoxicity on H9 cells, a human cutaneous CD4+ T lymphoma cell line. Cells were treated with 0, 1, 5, 10, and 20 µM OTA for up to 24 hr. Western blotting revealed increased phosphorylation of all three major mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38). OTA triggered mitochondrial transmembrane potential loss and caspase-3 activation. The 24-hr OTA treatment caused marked changes in cell morphology and DNA fragmentation, suggesting the occurrence of apoptotic events that involved a mitochondria-dependent pathway. Moreover, OTA triggered significant modulation of survivin, interleukin 2 (IL-2) and tumor necrosis factor α (TNF-α): mRNA expression of survivin and IL-2 were decreased, while TNF-α was increased. OTA also caused caspase-8 activation in a time-dependent manner, which evokes the death receptor pathway activation; we suspect that this occurred via the autocrine pro-apoptotic effect of TNF-α on H9 cells.


Assuntos
Apoptose/efeitos dos fármacos , Interleucina-2/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ocratoxinas/toxicidade , RNA Mensageiro/metabolismo , Linfócitos T/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Comunicação Autócrina/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática , Regulação da Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Interleucina-2/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/imunologia , Mitocôndrias/patologia , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Survivina , Linfócitos T/enzimologia , Linfócitos T/imunologia , Linfócitos T/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética
5.
J Toxicol Sci ; 41(1): 123-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26763399

RESUMO

Paraphenylene daimine (PPD) is an aromatic amine that is widely used in several industrial products; however, its toxicity has been reported in several cases of cardiac arrests. As platelets play a key role in cardiovascular diseases, we aimed to determine the impact of PPD in vitro and in vivo on platelet function. Our findings demonstrated that platelet activation and aggregation were strongly enhanced by PPD. Treatment with PPD primed human platelets that became more reactive in response to low doses of collagen. Furthermore, PPD exacerbated thrombus formation in rats in comparison with those untreated. Our results suggest that PPD is an important platelet primer predisposing platelets to promote thrombus formation in response to vascular injury. This should prompt the authorities to consider controlling the marketing of this product.


Assuntos
Colágeno/farmacologia , Fenilenodiaminas/toxicidade , Agregação Plaquetária/efeitos dos fármacos , Trombose/etiologia , Animais , Feminino , Humanos , Técnicas In Vitro , Masculino , Ativação Plaquetária/efeitos dos fármacos , Ratos Sprague-Dawley
6.
Pharmacognosy Res ; 7(2): 213-6, 2015 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25829798

RESUMO

BACKGROUND: The aerial parts of Thymelaea hirsuta (TH) are used as a decoction in the treatment of different pathologies in folk medicine in Morocco. OBJECTIVE: The aqueous extracts were evaluated for its anti-inflammatory activity and in inhibition of adjuvant induction arthritis in male Wistar rats. MATERIALS AND METHODS: The anti-inflammatory activity was carried out using carrageenan-induced rat paw edema model, and the antiarthritic activity was carried out using complete Freund's adjuvant-induced arthritis model. RESULTS: The plant extract (500 mg/kg body weight) exhibited significant activity in acute inflammation produced 60% of inhibition after 4 h as compared with that of the standard anti-inflammatory drug, the diclofenac (100 mg/kg) which showed 40% of inhibition. In arthritis model, the extract produced 85% inhibition after 18 days when compared with the diclofenac (10 mg/kg; 72%). CONCLUSION: These results indicate that the aqueous extract of TH had an anti-inflammatory activity and inhibited the induction of adjuvant arthritis in male Wistar rats.

7.
Eur J Immunol ; 45(2): 592-602, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403978

RESUMO

In addition to its classical receptor, CD40, it is now well established that CD154 also binds αIIbß3, α5ß1, and αMß2 integrins. Although these integrins are all members of the same family, they bind CD154 differently. The current investigation aims to analyze the interaction of CD154 with α5ß1 and αMß2 and investigate its role in bidirectional signals in various human cell lines. Results obtained herein indicate that the CD154 residues involved in the interaction with α5ß1 are N151 and Q166, whereas those involved in αMß2 binding are common to residues required for CD40, namely Y145 and R203. Soluble CD40/CD154 or αMß2/CD154 complexes do not interfere with the binding of CD154 to α5ß1-positive cells, but inhibit the binding of CD154 to CD40- or αMß2-positive cells, respectively. Ligation of CD154 on CD154-positive cells with soluble CD40, αIIbß3, α5ß1, or αMß2 stimulates intracellular signaling, including MAPK phosphorylation. Given that CD154 exists as a trimer, our data strongly suggest that CD154 may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors. The characterization of CD154/receptor interactions helps the identification of new therapeutic targets for the prevention and/or treatment of CD154-associated autoimmune and inflammatory diseases.


Assuntos
Antígenos CD40/metabolismo , Ligante de CD40/metabolismo , Integrina alfa5beta1/metabolismo , Antígeno de Macrófago 1/metabolismo , Animais , Antígenos CD40/genética , Antígenos CD40/imunologia , Ligante de CD40/genética , Ligante de CD40/imunologia , Linhagem Celular Tumoral , Drosophila melanogaster , Expressão Gênica , Humanos , Integrina alfa5beta1/genética , Integrina alfa5beta1/imunologia , Antígeno de Macrófago 1/genética , Antígeno de Macrófago 1/imunologia , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transdução de Sinais
8.
Rheumatology (Oxford) ; 51(9): 1595-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22711844

RESUMO

OBJECTIVE: Behçet's disease (BD) is a multisystemic inflammatory disease, mainly characterized by recurrent oral and genital ulcers (GUs), skin lesions and uveitis. Several genetic factors such as the TNF-α gene have been evaluated as contributors to the pathogenesis of BD. We aimed to evaluate the association between six TNF-α SNPs and susceptibility to BD, or the major clinical manifestations, in Moroccan patients. The six SNPs studied were: c.-1211C>T (rs1799964), c.-1043C>A (rs1800630), c.-1037C>T (rs1799724), c.-556G>A (rs1800750), c.-488G>A (rs1800629) and c.-418G>A (rs361525), known as -1031T>C, -863C>A, -857C>T, -376G>A, 308G>A and -238G>A, respectively. METHODS: SNPs were genotyped by direct sequencing in 120 unrelated Moroccan BD and 112 ethnically matched healthy controls. Allele and genotype distributions were compared between groups using chi-square or Fisher's exact tests. RESULTS: The frequency of the -1211C allele was higher in (i) BD patients than in controls [P = 0.02, odds ratio (OR) = 1.68, 95% CI 1.10, 2.56] and in (ii) patients with GUs than in those without (P = 0.002, OR = 3.84, 95% CI 1.55, 9.49). The -418A frequency was lower in patients with uveitis (P = 0.0003, OR = 0.19, 95% CI 0.07, 0.5). CONCLUSION: We report the first association between BD and TNF-α SNPs in Moroccan patients. We mainly observed that -1211C constitutes a susceptibility allele for both BD and GU, as previously reported for other populations. The -418A allele could be considered as a good prognostic factor for anterior uveitis, in Moroccan BD patients.


Assuntos
Síndrome de Behçet/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Prognóstico , Uveíte Anterior/diagnóstico , Uveíte Anterior/etiologia , Uveíte Anterior/genética , Adulto Jovem
9.
Genet Test Mol Biomarkers ; 16(5): 383-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22103601

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) is a major public health problem around the world. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be associated with T2DM and its complications. This study aimed to investigate this association in the Moroccan population. METHODS: A case-control study was performed among 282 Moroccan diabetic patients and 232 healthy controls. The MTHFR C677T and A1298C polymorphisms were genotyped by polymerase chain reaction, followed by enzymatic digestion with HinfI and MboII enzymes, respectively. RESULTS: There was a significant association between C677T polymorphism and T2DM in both additive and dominant models. In addition, the 677T allele frequency differed significantly between the diabetic and control groups (26.06% vs. 33.20%, respectively). However, no significant association was found between A1298C polymorphism and T2DM. The frequencies of combined genotypes 677CC/1298AA and 677CT/1298AC differed significantly between the diabetic and control groups (32.62% vs. 20.61% and 9.57% vs. 17.55%, respectively). CONCLUSIONS: These results show an evident association between the MTHFR C677T polymorphism and T2DM in Moroccan patients but no significant association with the MTHFR A1298C polymorphism.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Reação em Cadeia da Polimerase , Fatores de Risco
10.
Ann Biol Clin (Paris) ; 69(4): 419-24, 2011 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21896406

RESUMO

Human leukocyte antigen HLA-B51 is the most strongly associated gene with Behçet disease (BD) in different ethnic populations. We analyze the influence of HLA-B alleles in BD predisposition in Moroccan population and its association with clinical manifestations. The HLA-B phenotype frequencies were analyzed by serologic HLA class I typing and by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot hybridization in 120 unrelated Moroccan patients: all of whom fulfilled the international study group criteria for Behçet's disease, and in 112 ethnically matched healthy controls. Besides HLA-B*51 allele (20%), a significant increased frequency of the HLA-B*27 allele was found in Moroccans patients with Behçet's disease when compared to controls (13.3% of patients versus 2.7% of controls, chi square = 8.75, OR = 5.59, 95% IC [1.58-19.75] and particularly in the patients who presented an anterior uveitis (25% vs. 5.5%, p < 0.005).


Assuntos
Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Antígeno HLA-B27/genética , Uveíte Anterior/genética , Uveíte Anterior/imunologia , Adolescente , Adulto , Alelos , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Fenótipo , Reação em Cadeia da Polimerase
11.
Ann Biol Clin (Paris) ; 69(3): 295-301, 2011 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21659045

RESUMO

We have studied the distribution of HLA-A, -B and DRB1 alleles and haplotypes by sequence specific oligonucleotide amplification in a sample of 125 unrelated healthy Moroccan individuals from Casablanca in Morocco. The city of Casablanca is known of its big ethnic diversity, especially Arabs and Berbers. The most frequent alleles found were: HLA-A*02 (18.4%), -A*01 (11.2%), -A*03 (10.8%), -B*51 (8.06%),-B*44 (7.66%), -B*08 (6.85%), -DRB1*04 (15.98%), DRB1*03 and DRB1*07 (13.92%) and -DRB1*01 (10%). High frequency for five two-locus haplotypes was observed for A*03-B*51 (5%), A*02-DRB1*03 (5.5%), A*02-DRB1*04 and A*01-DRB1*04 (5%) and B*35-DRB1*04 (4%). No predominant haplotype was observed for HLA A-B-DRB1. Our results confirm and extend the current knowledge about genetic pattern of the Moroccan of Casablanca. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations in the Moroccan population.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Alelos , Feminino , Cadeias HLA-DRB1 , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Adulto Jovem
12.
J Community Health ; 36(6): 943-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21442339

RESUMO

The aim of this study is to evaluate the degree of familial aggregation of type 2 diabetes mellitus in Morocco and to investigate transmission patterns of the disease and their relationships with patients' clinical profiles. Family history of diabetes and clinical data were collected from 232 unrelated type 2 diabetic Moroccan patients. Diabetes status was recorded for first degree (parents, siblings) and second degree relatives (aunts and uncles from both maternal and paternal sides). Among studied subjects, 50% reported at least one relative with diabetes and 24% had at least one parent with diabetes. Familial aggregation of type 2 diabetes was prominent and more important among first degree relatives than second degree relatives (P < 0.01). Moreover, diabetes was more frequent among mothers than fathers of probands (P = 0.02), but this maternal effect was not observed in second degree relatives. There are no significant differences in clinical and metabolic profiles between patients according to the transmission pattern of the disease. In conclusion, these results suggest familial aggregation and excess maternal transmission of type 2 diabetes in the Moroccan studied population.


Assuntos
Diabetes Mellitus Tipo 2/genética , Impressão Genômica , Idade de Início , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Família , Pai/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , Mães/estatística & dados numéricos , Linhagem , Prevalência , Fatores Sexuais
13.
Ann Biol Clin (Paris) ; 68(3): 291-6, 2010 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20478772

RESUMO

Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. In Moroccan leukemic patients, the frequency of HLA alleles has not already been determined. We have analyzed HLA class I and class II alleles and haplotypes in 62 Moroccan leukemic patients and 98 unrelated normal subjects using PCR-SSO method. Significant positive association with the disease, in patients compared to controls, was found for three alleles: HLA-B*44 (12.7% vs 6.6%; p = 0.02), HLA-DRB1*13 (11.8% vs 9.79%; p = 0.04) and HLA-DRB*01 (4.5% vs 10.7%; p = 0.05). Regarding haplotypes analysis, no significant association was found between patients and control groups. It is suggested that HLA-B*44 and HLA-DRB1*13 alleles may play a presumptive predisposing factor while the HLA-DRB*01 allele could be a protective genetic factor against leukemia.


Assuntos
Frequência do Gene , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Haplótipos , Leucemia/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Marrocos , Reação em Cadeia da Polimerase
14.
Arterioscler Thromb Vasc Biol ; 22(11): 1824-31, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12426211

RESUMO

OBJECTIVE: Activated polymorphonuclear neutrophils (PMNs) are the main source of circulating neutral endopeptidase (NEP). We tested the hypothesis that NEP inhibition could potentiate the effect of atrial natriuretic peptide (ANP) on PMN-vascular cell interactions in vitro. METHODS AND RESULTS: ANP alone and its potentiation by retrothiorphan, the NEP inhibitor, significantly inhibited superoxide, lysozyme, and matrix metalloproteinase (MMP)-9 release by N-formyl-Met-Leu-Phe-stimulated PMNs. Activated PMNs degraded exogenous ANP, which was prevented by NEP inhibition. Hypoxia significantly increased the adhesion of PMNs to endothelial cells and their subsequent MMP-9 release by 60% and 150%, respectively (P<0.01). ANP and its potentiation by retrothiorphan limited PMN adhesion to hypoxic endothelial cells and thus decreased their MMP-9 release (P<0.01). Smooth muscle cells (SMCs) incubated with conditioned medium of N-formyl-Met-Leu-Phe-stimulated PMNs exhibited morphological and biochemical changes characteristic of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positivity, nuclear condensation/fragmentation, poly ADP-ribose polymerase cleavage, and DNA laddering). SMC detachment and subsequent apoptosis could be related to leukocyte elastase-induced pericellular proteolysis, inasmuch as both events are inhibited by elastase inhibitors. ANP and its potentiation by retrothiorphan were able to limit elastase release, fibronectin degradation, and SMC apoptosis. CONCLUSIONS: ANP potentiation by NEP inhibition could limit PMN activation and its consequences on vascular cells.


Assuntos
Fator Natriurético Atrial/farmacologia , Comunicação Celular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Tiorfano/análogos & derivados , Fator Natriurético Atrial/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Comunicação Celular/fisiologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/fisiologia , Meios de Cultivo Condicionados/farmacologia , Sinergismo Farmacológico , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Fibronectinas/metabolismo , Humanos , Hipóxia/fisiopatologia , Elastase de Leucócito/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/citologia , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/fisiologia , Neutrófilos/enzimologia , Neutrófilos/patologia , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/fisiologia , Tiorfano/farmacologia , Veias Umbilicais/citologia
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