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1.
Cortés-Gutiérrez EI Cerda-Flores RM González-Ramírez D Zúñiga-Charles MA Lazcano-Martínez S Sampayo-Reyes A Leal-Garza CH 《Mutagenesis》2004,19(3):203-205
The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h). 相似文献
2.
Sigifredo Pedraza-Sánchez Amy G. Hise Lakshmi Ramachandra Fabian Arechavaleta-Velasco Christopher L. King 《Clinical and Vaccine Immunology : CVI》2013,20(7):962-971
The human innate immune response to pathogens is not fully effective and mature until well into childhood, as exemplified by various responses to Toll-like receptor (TLR) agonists in newborns compared to adults. To better understand the mechanistic basis for this age-related difference in innate immunity, we compared tumor necrosis factor alpha (TNF-α) production by monocytes from cord blood (CB) and adult blood (AB) in response to LAM (lipoarabinomannan from Mycobacterium tuberculosis, a TLR2 ligand) and LPS (lipopolysaccharide from Escherichia coli, a TLR4 ligand). LPS or LAM-induced TNF-α production was 5 to 18 times higher in AB than in CB monocytes, whereas interleukin-1α (IL-1α) stimulated similar levels of TNF-α in both groups, suggesting that decreased responses to LPS or LAM in CB are unlikely to be due to differences in the MyD88-dependent signaling pathway. This impaired signaling was attributable, in part, to lower functional TLR4 expression, especially on CD14+ CD16+ monocytes, which are the primary cell subset for LPS-induced TNF-α production. Importantly, the frequency of CD14+ CD16+ monocytes in CB was 2.5-fold lower than in AB (P < 0.01). CB from Kenyan newborns sensitized to parasite antigens in utero had more CD14+ CD16+ monocytes (P = 0.02) and produced higher levels of TNF-α in response to LPS (P = 0.004) than CB from unsensitized Kenyan or North American newborns. Thus, a reduced CD14+ CD16+ activated/differentiated monocyte subset and a correspondingly lower level of functional TLR4 on monocytes contributes to the relatively low TNF-α response to LPS observed in immunologically naive newborns compared to the response in adults. 相似文献
3.
The lignan otobaphenol, (8R,8'R,7R)-4'-hydroxy-5'-methoxy-3,4-methylenedioxy-2',7,8,8'-neolignan, extracted from Virola Aff. Pavonis leaves, completely inhibits at a concentration of 2.5 micro M the Fe(3+)-ascorbate-induced lipoperoxidation of rat liver mitochondria that was determined by oxygen consumption and accumulation of thiobarbituric acid-reactive species. At 25 micro M, it delays the mitochondrial permeability transition induced by tert-butyl hydroperoxide or Ca(2+), substantially inhibits the state 3 respiration, does not affect the state 4 respiration and the ADP/O ratio (with succinate), diminishes the rate of Ca(2+) uptake by mitochondria, and delays the ruthenium red-insensitive uncoupler-induced release of the loaded Ca(2+). Dose-dependent delaying of the calcium-induced swelling of mitochondria in the presence of otobaphenol nonlinearly correlates with its 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. At 75 micro M and higher, this lignan causes mitochondrial aggregation and is able to aggregate itself, without mitochondria. The formed aggregates of otobaphenol do not cause an aggregation of subsequently added mitochondria. Thus, otobaphenol seems to be a promising target to prevent the oxidative stress death of cells. 相似文献
4.
Gisela D De La Rosa Marta L Valencia Clara M Arango Carlos I Gomez Alex Garcia Sigifredo Ospina Susana Osorno Adriana Henao Fabián A Jaimes 《BMC infectious diseases》2008,8(1):18
Background
Recent data have suggested that 18 million of new sepsis cases occur each year worldwide, with a mortality rate of almost 30%. There is not consensus on the clinical definition of sepsis and, because of lack of training or simply unawareness, clinicians often miss or delay this diagnosis. This is especially worrying; since there is strong evidence supporting that early treatment is associated with greater clinical success. There are some difficulties for sepsis diagnosis such as the lack of an appropriate gold standard to identify this clinical condition. This situation has hampered the assessment of the accuracy of clinical signs and biomarkers to diagnose sepsis. 相似文献5.
Alejandro Lugo-Baruqui José Francisco Muñoz-Valle Sigifredo Arévalo-Gallegos Juan Armendáriz-Borunda 《Hepatology research》2010,40(1):95-104
Angiotensin II (AT-II) is a peptide that plays an important role in the renin-angiotensin-aldosterone (RAA) system. Traditionally, the RAA system has been related with states of systemic hypertension and hypoperfusion as a counterbalance mechanism. Recently, AT-II has been studied for its properties in the process of fibrosis in several organs, especially in the liver. AT-II is capable to stimulate the activated hepatic stellate cells, which increase expression of profibrogenic molecules like tumor growth factor-β, tissue inhibitor of metalloproteinase-1 and collagen I, among others. At the same time, AT-II is implied in the hemodynamic balance of cirrhosis and portal hypertension. Due to its profibrogenic and vasoactive properties, blockade of AT-II actions constitutes an important therapeutic target to inhibit fibrotic processes and reduction of risk of complications of portal hypertension as well. Some drugs like angiotensin-converting enzyme inhibitors or the angiotensin II receptor blockers have been studied as alternatives for the treatment of patients with cirrhosis with promising results. Nonetheless, additional research is required in order to consider these drugs as a part of the integral treatment of the patient with cirrhosis and portal hypertension. 相似文献
6.
Pedraza-Sánchez S González-Hernández Y Escobar-Gutiérrez A Ramachandra L 《International immunopharmacology》2006,6(4):635-646
The compound RU41740 from Klebsiella pneumoniae, when used as an immunostimulant, improves responses to bacterial and yeast infections in murine models and in human trials. The aim of this study was to determine in vitro, the capacity of RU41740 to stimulate human leukocytes in whole blood. Blood samples from healthy adult donors were incubated with RU41740 for 4 or 24 h and leukocytes were assessed for levels of activation markers and cytokine production by flow cytometry and ELISA. The early activation marker CD69 was induced at 4 h in NK cells > B cells > T cells > monocytes whereas at 24 h CD80 and CD86 levels were augmented on monocytes and IL-12 was induced; HLA-DR levels increased on both B cells and monocytes. The pro-inflammatory cytokines TNF-alpha and IL-6 were produced at 4 h at similar levels to that induced by LPS and monocytes appeared to be a source of TNF-alpha. IFN-gamma, was induced at 5 h just in NK cells. Activation induced by RU41740 was not abolished by polymixin B, ruling out the possible contamination with LPS. These data indicate that RU41740 can impact not only the innate immune responses but potentially enhance adaptive immune responses by up-regulating expression of molecules involved in antigen presentation on antigen presenting cells. 相似文献
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8.
Karen Bobadilla Eduardo Sada Maria E. Jaime Yolanda González Lakshmi Ramachandra Roxana E. Rojas Sigifredo Pedraza‐Sánchez Colette Michalak Alfonso González‐Noriega Martha Torres 《Immunology》2013,138(1):34-46
Intracellular pathogens, such as Mycobacterium tuberculosis, reside in the phagosomes of macrophages where antigenic processing is initiated. Mycobacterial antigen–MHC class II complexes are formed within the phagosome and are then trafficked to the cell surface. Interferon‐γ (IFN‐γ) and interleukin‐10 (IL‐10) influence the outcome of M. tuberculosis infection; however, the role of these cytokines with regard to the formation of M. tuberculosis peptide–MHC‐II complexes remains unknown. We analysed the kinetics and subcellular localization of M. tuberculosis peptide–MHC‐II complexes in M. tuberculosis‐infected human monocyte‐derived macrophages (MDMs) using autologous M. tuberculosis‐specific CD4+ T cells. The MDMs were pre‐treated with either IFN‐γ or IL‐10 and infected with M. tuberculosis. Cells were mechanically homogenized, separated on Percoll density gradients and manually fractionated. The fractions were incubated with autologous M. tuberculosis ‐specific CD4+ T cells. Our results demonstrated that in MDMs pre‐treated with IFN‐γ, M. tuberculosis peptide–MHC‐II complexes were detected early mainly in the phagosomal fractions, whereas in the absence of IFN‐γ, the complexes were detected in the endosomal fractions. In MDMs pre‐treated with IL‐10, the M. tuberculosis peptide–MHC‐II complexes were retained in the endosomal fractions, and these complexes were not detected in the plasma membrane fractions. The results of immunofluorescence microscopy demonstrated the presence of Ag85B associated with HLA‐DR at the cell surface only in the IFN‐γ‐treated MDMs, suggesting that IFN‐γ may accelerate M. tuberculosis antigen processing and presentation at the cell membrane, whereas IL‐10 favours the trafficking of Ag85B to vesicles that do not contain LAMP‐1. Therefore, IFN‐γ and IL‐10 play a role in the formation and trafficking of M. tuberculosis peptide–MHC‐II complexes. 相似文献
9.
Nancy L. Tateosian Virginia Pasquinelli Rodrigo E. Hernández Del Pino Nella Ambrosi Diego Guerrieri Sigifredo Pedraza-Sánchez Natalia Santucci Luciano D’Attilio Joaquín Pellegrini María A. Araujo-Solis Rosa M. Musella Domingo J. Palmero Rogelio Hernandez-Pando Verónica E. Garcia H. Eduardo Chuluyan 《The American journal of pathology》2014,184(5):1268-1273
Interferon (IFN)-γ displays a critical role in tuberculosis (TB), modulating the innate and adaptive immune responses. Previously, we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). Herein, we determined whether IFN-γ modulated the levels of SLPI in TB patients. Plasma levels of SLPI and IFN-γ were studied in healthy donors (HDs) and TB patients. Peripheral blood mononuclear cells from HDs and patients with TB or defective IFN-γ receptor 1* were stimulated with Mtb antigen and SLPI, and IFN-γR expression levels were measured. Both SLPI and IFN-γ were significantly enhanced in plasma from those with TB compared with HDs. A direct association between SLPI levels and the severity of TB was detected. In addition, Mtb antigen stimulation decreased the SLPI produced by peripheral blood mononuclear cells from HDs, but not from TB or IFN-γR patients. Neutralization of IFN-γ reversed the inhibition of SLPI induced by Mtb antigen in HDs, but not in TB patients. Furthermore, recombinant IFN-γ was unable to modify the expression of SLPI in TB patients. Finally, IFN-γR expression was lower in TB compared with HD peripheral blood mononuclear cells. These results show that Mtb-induced IFN-γ down-modulated SLPI levels by signaling through the IFN-γR in HDs. This inhibitory mechanism was not observed in TB, probably because of the low expression of IFN-γR detected in these individuals.Tuberculosis (TB) is among the most common causes of morbidity and mortality in patients with HIV infection. Although protective immunological mechanisms against Mycobacterium tuberculosis (Mtb) are not fully understood, resistance to mycobacterial infections is primarily mediated by the interaction of antigen-specific T cells and macrophages.1,2 This interaction depends on the cross talk of cytokines produced by these cells, and interferon (IFN)-γ is essential for protection.2,3 Thus, during the immune response of the host against Mtb, IFN-γ produced by type 1 helper T cells is recognized by its receptor on macrophages. The IFN-γ receptor (IFN-γR) is composed of two ligand-binding IFNGR1 chains associated with two signal-transducing IFNGR2 chains, and an associated signaling machinery.2–5 IFN-γ binds to its receptor and activates macrophages to efficient killing of intracellular mycobacteria. In humans, the loss-of-function mutations in IFNGR1 or IFNGR2 genes are closely associated with severe susceptibility to poorly virulent mycobacteria highlighted in childhood.4,6,7Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor secreted by inflammatory and epithelial cells, mainly in the respiratory tract mucosa, and it is primarily active against neutrophilic elastase, cathepsin G, trypsin, and chymotrypsin.8 The expression and secretion of SLPI are down-modulated during chronic obstructive pulmonary disease.9–11 In addition, cathepsins B, L, and S and cigarette smoke exposure result in the cleavage and inactivation of SLPI.12,13 Moreover, it has been demonstrated that IFN-γ is a prominent stimulator of cathepsins and matrix metalloproteinase-12 and an inhibitor of SLPI.14 Remarkably, SLPI may also function as an endogenous immunomodulatory, anti-inflammatory, and/or antimicrobial substance.15–18 The antimicrobial effects of SLPI against several bacteria have been demonstrated.15 In particular, Nishimura et al17 described that recombinant mouse SLPI inhibited the growth of bacillus Calmette-Guérin (BCG) and Mtb through the disruption of the mycobacterial cell wall structure. Furthermore, we reported that human SLPI is a secreted pattern recognition receptor for mycobacteria that increases both the phagocytosis and killing of the pathogen.18 Remarkably, exposure of murine peritoneal macrophages to Mtb led to an increase in SLPI secretion.19 Thus, given the anti-inflammatory and anti-mycobacterial roles of SLPI in humans and taking into account the fact that SLPI is inhibited by IFN-γ,20 a crucial cytokine in the protective immunity against Mtb, herein we studied the effect of IFN-γ on the expression of SLPI during human active disease. 相似文献
10.
Joaquín R. Rodelo Gisela De la Rosa Martha L. Valencia Sigifredo Ospina Clara M. Arango Carlos I. Gómez Alex García Edilberto Nuñez Fabián A. Jaimes 《The American journal of emergency medicine》2012