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1.
Sci Rep ; 12(1): 22125, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550135

RESUMO

The need to better understand the binding mode of antioxidants (sulfur oxyanions) kinetically is a concern in medicine. Hence, a spectrophotometric method was used to study the application of the Piszkiewicz model on the electron transfer reaction of dithionite ion (S2O42-) and bis-(2-pyridinealdoximato)dioxomolybdate(IV) complex at 303 K and an absorption maxima of 560 nm. It follows an acid dependent reductive pathway that is medium sensitive. Charge distribution from the reaction species contributes to the redox efficiency of the system, resulting in a primary salt effect (NaCl) with an enhanced reaction rate. Alteration of the reaction medium with ethanol led to an elevation of reduction time as the charge catalysis was distorted by a drop in the system permittivity. Likewise, sodium dodecyl sulfate in the system decreased the reduction rate of the complex due to the low impact of hydrophobic and ion interaction between the micelle and substrates. First order reaction kinetics was observed in the concentration of the redox partners and a 2:1 (complex: S2O42-) stoichiometry was obtained with the involvement of hydrogenated sulfite radical which resulted in the formation of sulfur dioxide and a Mo2+ deactivated complex. The occurrence of counterion catalysis is pronounced in the reaction system owing to the participation of like-charged substrates in the rate-controlling phase. The standard enthalpy (69.12 [Formula: see text] 0.05 kJ mol-1) and Gibbs energy (80.10 [Formula: see text] 0.07) kJ mol-1 suggest that the process is endothermic dependent. The investigation of the anionic surfactant effect on the reaction medium was quantitatively ascertained from the Piszkiewicz model of the complex interaction sequence.


Assuntos
Elétrons , Ditionita , Transporte de Elétrons , Oxirredução , Fenômenos Químicos , Cinética
2.
West Afr J Med ; 38(8): 775-784, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34504383

RESUMO

BACKGROUND: Helicobacter pylori is common in developing countries like Nigeria with significant morbidity and risk of mortality. With rising antimicrobial resistance, risk factors of infection should be explored to develop prevention strategies and improve the health of developing communities. OBJECTIVE: To identify determinants and clinical correlates of H. pylori among study participants. METHODS: We conducted a hospital-based cross-sectional study between May and July 2017 of 280 dyspeptic adults in Garki Hospital Abuja. They were tested using serum H. pylori Immunoglobulin G antibody test kits. Data on patient characteristics were collected using pre-tested interviewer administered questionnaires. The data were analysed using SPSS version 25. Logistic regression and odds ratios with 95% confidence intervals were computed to identify risk factors and clinical features associated with H. pylori infection. RESULTS: The overall prevalence of H. pylori infection was 53.6%. H. pylori was positively associated with age and monthly income. Family history of dyspepsia (OR = 0.32: 95% CI = 0.13 to 0.78), regular consumption of fruits and vegetables (OR = 0.11: 95% CI = 0.046 - 0.281) and regular handwashing with soap and water (OR = 0.02: 95% CI = 0.006 -0.040) were found to be protective against H. pylori infection. CONCLUSION: There is a high H. pylori prevalence amongst patients with dyspepsia in Garki Hospital Abuja. Interventions to reduce the incidence of H. pylori infection should emphasise regular handwashing with soap and water and regular fruit and vegetable consumption.


CONTEXTE: Helicobacter pylori est commun dans les pays en développement comme le Nigeria avec une morbidité et un risque de mortalité importants. Avec l'augmentation de la résistance aux antimicrobiens, les facteurs de risque d'infection devraient être explorés pour développer des stratégies de prévention et améliorer la santé des communautés en développement. OBJECTIF: Identifier les déterminants et les corrélats cliniques de H. pylori chez les participants à l'étude. MÉTHODES: Nous avons mené une étude transversale en milieu hospitalier entre mai et juillet 2017 auprès de 280 adultes dyspeptiques à l'hôpital Garki d'Abuja. Ils ont été testés à l'aide de kits de test d'anticorps sériques H. pylori Immunoglobulin G. Les données sur les caractéristiques des patients ont été recueillies à l'aide de questionnaires pré-testés et administrés par des enquêteurs. Les données ont été analysées à l'aide de SPSS version 25. La régression logistique et les rapports de cotes avec des intervalles de confiance à 95 % ont été calculés pour identifier les facteurs de risque et les caractéristiques cliniques associés à l'infection à H. pylori. RÉSULTATS: La prévalence globale de l'infection à H. pylori était de 53,6%. H. pylori était positivement associé à l'âge et au revenu mensuel. Antécédents familiaux de dyspepsie (OR = 0,32 : IC à 95 % = 0,13 à 0,78), consommation régulière de fruits et légumes (OR = 0,11 : IC à 95 % = 0,046 à 0,281) et lavage régulier des mains à l'eau et au savon (OR = 0,02 : IC à 95 % = 0,006 ­ 0,040) se sont avérés protecteurs contre l'infection à H. pylori. CONCLUSION: Il existe une prévalence élevée de H. pylori parmi les patients atteints de dyspepsie à l'hôpital Garki d'Abuja. Les interventions visant à réduire l'incidence de l'infection à H. pylori devraient mettre l'accent sur le lavage régulier des mains à l'eau et au savon et la consommation régulière de fruits et légumes. Mots clés: Dyspepsie, H.pylori, ulcère gastroduodénal, gastrite, séroprévalence.


Assuntos
Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Adulto , Estudos Transversais , Dispepsia/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Nigéria/epidemiologia , Prevalência
3.
Heliyon ; 6(9): e04621, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32939409

RESUMO

The kinetics of reduction of N, N 1 -phenylenebis-(salicylideneiminato)cobalt (III), referred to as [Co(Salophen)]+ by L-ascorbic acid (H2A) was studied in mixed aqueous medium (DMSO:H2O; 1:4 v/v) under pseudo-first-order conditions at 33 ± 1 °C, µ = 0.1 mol dm-3 (NaCl) and λ max = 470 nm. L-ascorbic acid was oxidized to dehydroascorbic acid with kinetics that was first order in both the [H2A] and [Co(Salophen)+] and second-order overall. The reaction involves two parallel reaction pathways; an acid-dependent and the inverse acid-dependent pathways. The inverse acid pathway shows that there is a pre-equilibrium step before the rate determining-step in which a proton is lost. The kinetics followed negative Brønsted-Debye salt effect. Evidence was obtained for the presence of free radicals but none to support the formation of an intermediate complex of significant stability during the reaction. Overall, the data obtained suggest an outer-sphere mechanism for the reaction. A plausible mechanism is proposed.

4.
Heliyon ; 6(4): e03850, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32382681

RESUMO

The redox kinetics involving the reaction of N, N'-phenylenebis(salicyalideneiminato)cobalt(III) ([CoSalophen]+) and l-cysteine (LSH) was studied using pseudo-first order approach under the following conditions, [H+] = 1.0 × 10-3 mol/dm3, µ = 0.1 C2 mol/dm3 (NaCl), λmax = 470 nm and T = 27 ± 1 °C in DMSO: H2O; 1:4 v: v medium. The redox reaction was 1st order in both [CoSalophen+] and [LSH], with the overall 2nd order. Hydrogen ion concentration effect revealed the activeness of both the protonated and deprotonated form of the reductant, positive Brønsted-Debye salt effect and was also ion catalyzed. There was no evidence suggesting an intermediate complex of significant stability in the reaction. Free radical was detected to take part and as such the reasonable mechanistic pathway for the reaction is suggested to be outer-sphere, hence proposed.

5.
Niger J Med ; 25(2): 119-27, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29944308

RESUMO

Background: Malaria carries a high case fatality among patients with sickle cell disease. In Jos University Teaching Hospital, at the time of this study, the use of Proguanil was the acceptable mode of chemoprophylaxis for preventing malaria in these patients. Intermittent Preventive Treatment (IPT) with Sulphadoxine-Pyrimethamine [SP] has shown great potential for reducing the prevalence of malaria and anaemia among pregnant women, infants and travellers. We hypothesised that monthly SP was superior to daily Proguanil in reducing malaria parasitaemia, clinical malaria attacks and sickle cell crises in such patients. Objective: To assess the efficacy and affordability of monthly SP versus daily Proguanil for malaria chemoprophylaxis in patients attending Sickle Cell Clinic at Jos University Teaching Hospital, Plateau State, Nigeria. Methods: One hundred and fifty four patients [114 children and 40 adults] with Sickle Cell Disease in their steady state were randomized to monthly SP or daily Proguanil for malaria chemoprophylaxis. Active detection of malaria parasite in the peripheral blood and packed cell volumes were done at each monthly visit to the clinic over a period of three months. The primary outcome measure was the proportion of patients with malaria parasite in the peripheral blood at the end of 3 months. The secondary outcome measures included episodes of clinical malaria attacks, frequency and type of sickle cell crises and adverse effects of the medication. Results: Ninety four percent [72/77] of patients in the SP group and 91% [70/77] in the Proguanil group respectively completed three months of follow up. SP reduced the prevalence of malaria parasitaemia by 25% [(14%) 10/72] compared to 6.4% [(30%) 21/70] in the proguanil group. [X2 54; p = 0.01]. Seventeen percent [12/72] of the patients receiving monthly SP had malaria attacks compared to 57% [40/70] on prophylaxis with Proguanil. [X2 =25; p< 0.0003]. Thirty three percent [24/72] of the patients receiving SP had at least an episode of bone pain crises compared to 69% [48/70] of the patients receiving Proguanil. [X2 =17.6; p<0.0001]. SP was 8 times cheaper than Proguanil. Conclusion: Monthly chemoprophylaxis with SP was more efficacious than daily Proguanil in reducing the prevalence of asymptomatic malaria parasitaemia, clinical malaria attack and sickle cell crises in patients with sickle cell disease. SP was 8 times cheaper than Proguanil. No significant side effect was recorded in both groups. The current practice of routinely prescribing daily Proguanil to SCD patients for malaria chemoprophylaxis needs to be reviewed.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antimaláricos/administração & dosagem , Malária/prevenção & controle , Proguanil/administração & dosagem , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Adulto , Anemia Falciforme/complicações , Quimioprevenção , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Lactente , Malária/complicações , Masculino , Nigéria , Parasitemia/epidemiologia , Parasitemia/prevenção & controle , Gravidez , Resultado do Tratamento
6.
West Indian Med J ; 65(1): 128-133, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-26681373

RESUMO

OBJECTIVE: The objective of this study was to develop a sonographic technique for the measurement of fetal interorbital distance (IOD) for gestational age (GA) determination and to establish a normogram of IOD for the local population. METHODS: The fronto-transverse sonographic technique was established as a feasible and reproducible technique for IOD measurement. Two independent and experienced sonographers tested the technique and had a coefficient of variation of 17.64% and 19.72%, respectively, which is statistically insignificant. The established technique was used to measure the IOD of 320 fetuses from the 13th week to 40th week GA, while standard technique was used to measure biparietal diameter (BPD), head circumference (HC) and femur length (FL) of the fetuses. The data obtained were used to determine the regression equation GA = 6.24 + 4.89 IOD for the prediction of the gestational age. RESULTS: There was good correlation between IOD, BPD, HC and FL. The predicted normogram of IOD was compared with normogram of the Caucasian population. The result showed that there was no statistical difference between them (p < 0.05). CONCLUSION: Results from the study suggest that the fronto-transverse technique is a feasible and reproducible technique for IOD measurement and the established normogram of IOD can be a veritable statistic for GA prediction in our locality.

7.
J Toxicol ; 2013: 803835, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348549

RESUMO

The subchronic effect of aqueous stem bark extract of Khaya senegalensis on some biochemical, haematological, and histopathological parameters of rats was investigated. The rats were divided into six groups of five rats per group. Groups I to VI were administered graded doses of 0, 400, 800, 1200, 1600, and 2000 mg/kg bw, respectively. The result of study revealed that administration of the Khaya senegalensis for twenty-eight days at the experimental dose resulted in significant (P < 0.05) increase in urea, electrolytes (Na(+), K(+)), and creatinine levels. The extract also significantly (P < 0.05) increased serum activity of ALT, AST, and ALP. The levels of protein, albumin, and bilirubin were significantly changed when compared to their control values, but they were not dose dependent. The hematological indices assayed in this study were not significantly affected at the experimental dose when compared to the control values. Histological studies of the liver showed cellular degeneration and necrosis and bile duct hyperplasia and fibrosis with lymphocytic infiltration of the hepatocyte, providing supportive evidence for discussing the biochemical findings, indicative of functional derangement. The histological architecture of the kidney and that of the heart were however preserved. The result of this study indicates that the aqueous stem bark extract of K. senegalensis may affect the cellular integrity of vital organs of the body.

8.
Roum Arch Microbiol Immunol ; 65(3-4): 79-82, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-18389720

RESUMO

Since the events of avian influenza (AI) caused by H5N1 subtype from Hong Kong (1997), the people worldwide have been confronted with new waves of epizootic influenza. In 2005 in Romania an unprecedent H5N1 epizootic occurred in domestic and wild birds. Therefore an immediate investigation by molecular approach of this highly pathogenic H5N1 strain was necessary. The virus isolation and the RNA extraction were performed in the Institute of Diagnosis and Animal Health while PCR and sequencing were carried out in Cantacuzino Institute. Herein we report the first evidence of H5N1 presence in Romanian fowls. The phylogenetic analysis of haemagglutinin and neuraminidase gene indicated a close relationship of Romanian strains to those from Siberia and China. The virological and molecular analysis of the first strains of avian virus from Romania confirmed the presence of H5N1 subtype, belonging to the genetic line Z. These results indicate that the avian virus from this genetic line is directly derived from the highly pathogenic viruses isolated in China and Russia in 2005.


Assuntos
Galinhas/virologia , Patos/virologia , Virus da Influenza A Subtipo H5N1/genética , Animais , Virus da Influenza A Subtipo H5N1/classificação , Filogenia , Reação em Cadeia da Polimerase
9.
Phytother Res ; 15(8): 698-704, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11746863

RESUMO

A pilot study was performed to evaluate the efficacy of Pycnogenol treatment in systemic lupus erythematosus (SLE) patients. Eleven SLE patients were treated with first line medication according to disease activity and in addition, six of them received Pycnogenol and five a placebo. The SLE disease activity index (SLEDAI), serum anti-dsDNA antibodies, fibrinogen, C-reactive protein levels, erythrocyte sedimentation rate, production of reactive oxygen species (ROS) by neutrophils, spontaneous apoptosis and p56(lck) specific activity in peripheral blood lymphocytes were evaluated. Pycnogenol treatment determined a significant reduction of ROS production, apoptosis, p56(lck) specific activity and erythrocyte sedimentation rate. In addition, the decrease of SLEDAI was significant in the Pycnogenol treated group compared with the placebo group (p = 0.018). The results obtained suggest that Pycnogenol could be useful for second line therapy to reduce the inflammatory feature of SLE.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Flavonoides/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Idoso , Apoptose , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , DNA/imunologia , Feminino , Fibrinogênio/metabolismo , Humanos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Projetos Piloto , Extratos Vegetais , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença
10.
Autoimmunity ; 34(1): 27-38, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11681490

RESUMO

In this study we investigated one of the possible mechanisms of p56lck down-regulation in peripheral blood lymphocytes (PBLs) from Systemic Lupus Erythematosus (SLE) patients and we correlated p56lck dysregulation with accelerated apoptosis in SLE PBLs. PBLs from SLE patients and healthy donors were isolated. p56lck protein expression and lck mRNA level were estimated by immunoblotting and RT-PCR, respectively. FACS analysis was used to evaluate the apoptosis and p56lck levels in apoptotic and non-apoptotic PBLs. A non-radioactive Tyrosine Kinase Assay Kit was used to measure p56lck activity. Our results demonstrated that PBLs from SLE patients displayed lower levels of lck mRNA and p56lck protein as compared to healthy donors. The apoptosis of fresh or cultured PBLs was enhanced in SLE patients, especially in anti-DNA negative group. The expression of p56lck was inverse correlated with apoptosis of fresh and cultured SLE PBLs, especially in anti-DNA negative patients. Double staining FACS analysis showed that p56lck expression was lower in apoptotic than in non-apoptotic PBLs. p56lck specific activity was directly correlated to apoptosis in SLE PBLs. While the low expression of p56lck may be the result of lower degree of synthesis, the increased specific activity could directly correlated to the extent of apoptosis in SLE PBLs. Based on our observations, we assume that the p56lck dysregulation could play a role in SLE pathogenesis.


Assuntos
Lúpus Eritematoso Sistêmico/enzimologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/sangue , Apoptose , Estudos de Casos e Controles , Ciclo Celular , Regulação para Baixo , Feminino , Humanos , Técnicas In Vitro , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Linfócitos/metabolismo , Linfócitos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Autoimmunity ; 29(2): 111-20, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10433072

RESUMO

In this study we analyzed the activity and the expression of p56lck protein tyrosine kinase in peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients and from healthy donors. The p56lck activity, determined by a non-radioactive Tyrosine Kinase Assay Kit, was significantly higher in active SLE PBLs and discriminated this group of patients from inactive SLE patients (p = 0.002) and healthy donors (p = 0.009). p56lck level decreased in SLE lymphocytes (especially for inactive SLE lymphocytes, p = 0.005) when compared to healthy donors. These differences were also reflected by the specific activity of p56lck that was clearly elevated in active SLE lymphocytes when compared to inactive SLE (p = 0.022) or healthy donors lymphocytes (p = 0.006). A positive correlation between the activity of p56lck and the tyrosine phosphorylation level in active SLE lymphocytes was found.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Linfócitos/enzimologia , Animais , Feminino , Humanos , Fosforilação , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-fyn , Coelhos , Tirosina/metabolismo
13.
Cytokine ; 9(7): 507-13, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9237813

RESUMO

Interleukin 15 (IL-15) shares many functional properties with interleukin 2 (IL-2), although both cytokines probably also exert distinct functions. In order to screen for functional differences between IL-2 and IL-15 with respect to the control of T cell functions, we have stimulated human T lymphoblasts (hTBl) with IL-2 and/or IL-15 and have assessed the resulting changes in the following parameters: T cell proliferation; expression of various relevant surface markers; cytokine and receptor (alpha-chain) transcription; and IL-2 and IL-15 activity. Both cytokines equally upregulate standard activation markers such as CD25 and CD95 and downregulate CD27. However, IL-2 upregulates CD30, TNF receptor type II and CD40L expression significantly stronger than IL-15. IL-15 potentiates Con A-induced IL-2 secretion. Even though hTBl transcribe the IL-15 gene, they do not secrete IL-15 activity. These observations suggest that both cytokines can differentially regulate T cells, e.g. T cell functions relevant to the control of cell cycle progression and apoptosis, and/or that they can stimulate different T cell subsets. Moreover, IL-15 may potentiate IL-2-driven T cell responses.


Assuntos
Interleucina-15/fisiologia , Interleucina-2/fisiologia , Linfócitos T/fisiologia , Antígenos CD/biossíntese , Ligante de CD40 , Regulação para Baixo , Humanos , Interleucina-15/metabolismo , Interleucina-2/biossíntese , Interleucina-2/genética , Interleucina-2/metabolismo , Antígeno Ki-1/biossíntese , Ativação Linfocitária , Glicoproteínas de Membrana/biossíntese , RNA Mensageiro , Receptores de Interleucina-2/biossíntese , Receptores de Interleucina-2/genética , Receptores do Fator de Necrose Tumoral/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral , Linfócitos T/citologia , Linfócitos T/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/biossíntese , Regulação para Cima , Receptor fas/biossíntese
14.
J Immunol ; 158(1): 255-62, 1997 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8977197

RESUMO

The secretion of IL-15, a potent modulator of T, B, and NK lymphocyte functions, is likely to be tightly controlled. Here, we show that human T lymphoblasts transcribe the IL-15 gene and generate an alternative splicing product that codes for the same amino acid composition as the mature IL-15 protein, but produces an IL-15 precursor protein with a shorter signal peptide. Both alternative splicing products are transcribed by non-IL-15-secreting lymphocytes, suggesting that IL-15 secretion is not primarily controlled at the level of transcription. We generated an in vitro system for correlating the expression, translation, and secretion of IL-15 or IL-15-IgG1 fusion protein. This revealed that the two isoforms of IL-15 or a truncated IL-15 variant, both alone and fused to human IgG1, are all transcribed and translated, but not efficiently secreted. After replacing the IL-15 leader peptide with a foreign one, translation and secretion clearly increase. These results suggest that IL-15 is mainly controlled at the level of translation and secretion.


Assuntos
Interleucina-15/metabolismo , Sinais Direcionadores de Proteínas/farmacologia , Processamento Alternativo/genética , Sequência de Aminoácidos , Sequência de Bases , Humanos , Interleucina-15/agonistas , Interleucina-15/antagonistas & inibidores , Dados de Sequência Molecular , Biossíntese de Proteínas/genética , RNA Mensageiro/análise , Transcrição Gênica/genética , Células Tumorais Cultivadas
15.
Roum Arch Microbiol Immunol ; 56(1-2): 3-15, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9558971

RESUMO

Integrin-mediated activation of monocytes is an important aspect involved in the increase of proinflammatory cytokine messages. Tyrosine phosphorylation of proteins is one of the earliest events involved in these processes: Therefore, we selected two inhibitors, one for tyrosine kinases (quercitin) and another for tyrosine phosphatases (sodium orthovanadate) and we studied their capacity to modulate monocyte adhesion to fibronectin. Our results showed that quercitin strongly inhibits both tyrosine phosphorylation and cell adhesion. Sodium orthovanadate induces a modest increase of tyrosine phosphorylation and a weak enhancement of cell adhesion. When a combination of the two inhibitors was used, the tyrosine phosphorylation level displayed a strong enhancement. In contrast, cell adhesion was inhibited, but to the same degree. These observations indicate that tyrosine kinases may be more important than tyrosine phosphatases in the modulation of cell adhesion by flavonoid compounds.


Assuntos
Adesão Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Linhagem Celular , Humanos , Fosforilação , Quercetina/farmacologia , Vanadatos/farmacologia
16.
Roum Arch Microbiol Immunol ; 56(1-2): 37-45, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9558974

RESUMO

The bacterial product derived from Pseudomonas aeruginosa (trade mark-CANTASTIM) proved immunomodulatory effects in different systems, both in vitro and in vivo experimental animal models, as well as in clinical trials. Among the results obtained regarding CANTASTIM, the following immunomodulatory properties could be mentioned: an increase of the activated T cell subpopulations and humoral-mediated immune processes, facilitation of phagocytic processes, stimulation of cytotoxic activity reflected in the improvement of the capacity of defense in several tumoral and infectious diseases. To better elucidate the intimate mechanisms by which CANTASTIM modulates the cellular functions on different cellular populations, we used tyrosine phosphorylation as an estimate of cell activation on peripheral blood lymphocytes (PBL) and a monocyte cell line (THP-1). In PBL, the treatment with CANTASTIM renders them more susceptible to CD3 stimulation than non-treated cells. In monocytes, CANTASTIM and two phospholipid components of CANTASTIM modulated in a different manner the cellular adhesion on fibronectin and tyrosine phosphorylation leading to the conclusion that these phospholipid components do not fully explain CANTASTIM modulatory properties on cell adhesion processes.


Assuntos
Adjuvantes Imunológicos/farmacologia , Pseudomonas aeruginosa/química , Tirosina/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Ativação Linfocitária/efeitos dos fármacos , Fosfolipídeos , Fosforilação , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
17.
J Clin Invest ; 97(5): 1204-10, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8636431

RESUMO

Interleukin-2 (IL-2) plays a pivotal role in the cellular and humoral immune responses directed against foreign antigens. We characterized the in vitro and in vivo properties of a chimeric protein consisting of mouse IL-2 fused to the mouse IgG2b Fc domains. This fusion protein binds to IL-2 and Fc receptors and supports IL-2-dependent cell proliferation but does not mediate lysis of IL-2 receptor-positive cells in the presence of murine complement in vitro. However, in vivo the IL2-IgG2b fusion protein suppresses both cellular and humoral immune responses after immunization with sheep erythrocytes. Surprisingly, delayed hypersensitivity is inhibited despite a dramatic increase of splenic CD3+ and NK1.1+ lymphocytes, indicating that altered homing of IL2-IgG2b-activated lymphocytes rather than cytolysis prevents these cells from accumulating in areas of inflammation. Although in vitro the IL2-IgG2b fusion protein does not alter proliferation of B cells in response to mitogenic stimulation, IgM production in response to sheep erythrocytes is profoundly inhibited in mice treated with the IL2-IgG2b fusion protein. Since no side effects are observed, the IL2-IgG2b fusion protein may expand the therapeutic repertoire of reagents used for the treatment of allograft rejection and autoimmune diseases.


Assuntos
Imunoglobulina G/farmacologia , Imunossupressores/farmacologia , Interleucina-2/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Feminino , Hipersensibilidade Tardia , Imunoglobulina G/metabolismo , Interleucina-2/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
18.
Kidney Blood Press Res ; 19(3-4): 201-4, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8887261

RESUMO

The objective of immunosuppressive therapy in nephrology is to prevent autoimmune diseases and to suppress kidney allograft rejections while sparing other effects. Increased clarification of the underlying immune mechanism has made specific immunodulation possible using chimeric proteins in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines. The immunosuppressive effects of fusion proteins such as CTLA-4 IgG, CD40 IgG, interleukin (IL)-10 IgG, IL-2 IgG or tumor necrosis factor (TNF)-receptor IgG have been proven in various animal models. Moreover, the application of TNF-receptor IgG successfully limited the OKT3-induced cytokine release syndrome in kidney graft recipients. It seems likely that recombinant proteins with increasingly effective suppression of specific elements of the immune response will become an essential element in clinical protocols.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunoconjugados , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Abatacepte , Animais , Antígenos CD , Antígenos de Diferenciação/uso terapêutico , Antígenos CD40/uso terapêutico , Antígeno CTLA-4 , Citocinas/uso terapêutico , Glomerulonefrite Membranosa/prevenção & controle , Rejeição de Enxerto/imunologia , Humanos , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico
19.
Autoimmunity ; 24(4): 217-28, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9147580

RESUMO

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Linfócitos/metabolismo , Tirosina/metabolismo , Complexo CD3/imunologia , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Reagentes de Ligações Cruzadas , Humanos , Lúpus Eritematoso Sistêmico/sangue , Linfócitos/imunologia , Fosforilação
20.
Autoimmunity ; 22(2): 81-6, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8722577

RESUMO

We have recently identified in SLE sera naturally occurring anti-idiotypic antibodies against anti-phosphotyrosine antibodies. Analysis of immunochemical properties of these anti-idiotypic antibodies suggest that they are of beta/gamma type mimicking the antigen. The interaction between these anti-idiotypes and SH2 domains of various fusion proteins was analysed by immunoprecipitation and immunoblotting. Our data demonstrate that these anti-idiotypic antibodies specifically bind SH2 domains, with the highest affinity for SH2 domain of lck protein tyrosine kinase. The significance of this interaction is discussed.


Assuntos
Anticorpos Anti-Idiotípicos/fisiologia , Autoanticorpos/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , Fosfotirosina/imunologia , Domínios de Homologia de src/imunologia , Anticorpos Bloqueadores/fisiologia , Especificidade de Anticorpos , Autoanticorpos/sangue , Reações Cruzadas , Humanos , Imunidade Inata , Proteína Tirosina Quinase p56(lck) Linfócito-Específica , Quinases da Família src/imunologia
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