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1.
Infect Drug Resist ; 17: 1147-1152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38529069

RESUMEN

Background: Urinary tract infection (UTI) caused by V. cholerae is rare and less common. V. cholerae is a Gram-negative bacterium motile using single polar flagellum and, originally, is a waterborne microbe found in aquatic and estuarine environments. Toxigenic V. cholerae is well-known as a causative agent of acute and excessive watery diarrhea after ingesting food and water contaminated with this bacterium. Case Presentation: A 27-year-old male patient presented to the emergency department on 17th July 2021 with burning micturition, normal vital signs, and no fever, vomiting, or diarrhea. In 2017, the patient complained of short stature and vitamin D deficiency. He was on human growth hormone from January 2018 till October 2019. The diagnosis was V. cholerae Non-O1/non-O139 urinary tract infection (UTI). Considering a urinary tract infection, empirical treatment with Lornoxicam and Ciprofloxacin was initiated, while the result of urine culture was still pending. The patient was discharged on the same day and without any complications. Conclusion: V. cholerae non-O1/non-O139 is primarily a marine inhabitant and is associated with sporadic cases resulting in cholera-like diarrhea after consumption of contaminated seafood and exposure to seawater. Extraintestinal infection associated with this bacterium should no longer be ignored as this change in the behavior of cholera bacteria mechanism of pathogenicity might be related to some associated virulence genes.

2.
Heliyon ; 9(11): e21953, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38034617

RESUMEN

Rhodococcus equi is a Gram-positive coccobacillus that falls within the category of aerobic actinomycetes. The Rhodococcus genus belongs to the nocardioform bacteria group. This microorganism has been found in various settings, including natural environments, animals, and particularly in individuals with compromised immune systems, such as those living with HIV. Notably, there is an increasing number of reports concerning R. equi infections in transplant recipients and even individuals with a normally functioning immune system. Traditionally, R. equi has been primarily associated with pulmonary infections, but there is a growing body of evidence documenting its involvement in extrapulmonary infections. In this report, we present a case involving a newly diagnosed HIV patient who experienced R. equi -induced necrotizing pneumonia, bacteremia, and a brain abscess in newly diagnosed HIV patient. It is important to note that a direct Gram stain may potentially lead to misclassification of such microorganisms as contaminants. Microbiologists should therefore prioritize the careful examination of colony morphology, biochemical reactions, and consider the limitations of automated machine databases. Furthermore, they should correlate their identification findings with clinical data to ensure optimal patient care and management, especially in the context of an immunocompromised state.

3.
Infect Drug Resist ; 16: 1449-1454, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36942023

RESUMEN

Clostridium paraputrificum (C. paraputrificum) is clinically important due to its association with underlying medical conditions. Infection with C. paraputrificum may worsen HIV prognosis, leading to acquired immunodeficiency syndrome. However, it is not frequently isolated and its susceptibility to antibiotics has not been well studied. Our report examines the case of a patient with human immunodeficiency virus (HIV) infection, who was diagnosed with Clostridium paraputrificum bacteremia. A 59-year-old male was admitted to hospital with a medical history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and neck pain. Following episodes of high fever, the patient received a full work up to test for sepsis. Blood culture revealed bacterial growth, and MALDI-TOF mass spectrometry confirmed the diagnosis of Clostridium paraputrificum bacteremia. The patient received treatment with meropenem and vancomycin antibiotics, which cleared the infection after 48 hours; however, inflammatory markers remained high. To date, a limited number of reported cases of C. paraputrificum exist; thus, this case report contributes valuable information to the literature to improve our understanding of its action and resistance profiles and aid future bacteremia management.

4.
J Epidemiol Glob Health ; 12(4): 524-540, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36239916

RESUMEN

Vibrio parahaemolyticus belongs to the halophilic genus of Vibrionaceae family that inhabits coastal and marine environments and is a major food-borne pathogen. In the Gulf Cooperation Council (GCC) countries and Saudi Arabia in particular, there is a lack of information regarding the detection of pandemic clone or serovariants of V. parahaemolyticus pandemic clones. Here, 400 seawater samples were collected and examined for the presence of V. parahaemolyticus from 10 locations along the coast of Eastern Province in Saudi Arabia. The recovered isolates were serotyped, and studied for antimicrobial resistance, virulence genes, and markers of pandemicity using PCR and Arbitrarily primed (AP)-PCR typing patterns. All 40 isolates were tested negative for tdh, trh, and toxRS genes. Six serotypes were identified and three were clinically significant. Antibiotic susceptibility testing of isolates revealed high resistance towards penicillins, cephalosporins, and polymyxin; 60% of isolates were multi-drug resistant, whereas all isolates were susceptible to quinolones, carbapenems, sulfonamides, and tetracycline. The multiple antibiotic resistance (MAR) index among antibiotic resistance patterns of isolates revealed that 12 (30%) isolates had recorded significant MAR index higher than 0.2. AP-PCR fingerprinting could group all isolates into five distinct and identical pattern clusters with more than 85% similarity. Our findings demonstrate that pandemic serovariants of pandemic clones were not exclusively limited to strains isolated from fecal specimens of infected patients. Nine environmental strains of serotype O1:KUT, O1: K25, and O5:K17 were isolated from costal seawater, and thus the spread of these serovariants strains of pandemic clone of V. parahaemolyticus in the environment is to avoid any kind of threat to public health.


Asunto(s)
Vibriosis , Vibrio parahaemolyticus , Humanos , Vibrio parahaemolyticus/genética , Arabia Saudita/epidemiología , Serotipificación , Farmacorresistencia Microbiana
5.
Am J Case Rep ; 22: e933694, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34887373

RESUMEN

BACKGROUND Prototheca spp. are common and found in various environments, including animal and human intestines, on the skin and in respiratory tissues, and colonizing fingernails. Few strains pathogenic for humans have been discovered. Here, we describe an infection by the pathogenic fungus species Prototheca zopfii in a patient. The infection was initially classified as a fungus based on colony morphology, fungal staining results, and growth in some fungi culture media (Sabouraud dextrose agar [SDA]). Reports of Prototheca spp. infections are increasing, often with poor outcomes. The use of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) technique for identification has been widely described. Phenotypic identification depends on microscopic examination of the direct wet mount and after subculturing in blood and SDA using different stains that show a typical morphological characteristic of Prototheca spp. CASE REPORT A 48-year-old woman was diagnosed with a P. zopfii infection after 22 days of hospitalization in the critical care unit. The patient had profound febrile neutropenia and absolute neutrophil count (ANC) was zero, associated with hypotension and disseminated intravascular coagulation (DIC) 10 days after receiving the first cycle of chemotherapy for metastatic breast adenocarcinoma. Unfortunately, the patient died within 2 days of the initiation of treatment with amphotericin B. CONCLUSIONS This case report highlights algae infections as a possible opportunistic infection type in patients with profound neutropenia, and we discuss the use of MALDI-TOF MS-based technology in detecting such infections and predicting poor prognosis, especially in patients with the disseminated form with underlying febrile neutropenia.


Asunto(s)
Neutropenia Febril , Neumonía , Prototheca , Anfotericina B , Animales , Femenino , Humanos , Persona de Mediana Edad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
6.
Am J Case Rep ; 20: 406-411, 2019 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-30923306

RESUMEN

BACKGROUND Mycoplasma hominis, which rarely causes infection after neurosurgical procedures, is a small free-living organism, belonging to the genus Mycoplasma. M. hominis lacks a rigid cell wall and cannot be clearly visualized by routine light microscopy. Thus, it is challenging to diagnose infections caused by this pathogen. Here, we report a case of Mycoplasma hominis causing iatrogenic ventriculitis secondary to extraventricular drain. CASE REPORT A 25-year-old man who was a victim of a road traffic accident developed M. hominis ventriculitis secondary to extraventricular drain. Despite a delay in the diagnosis due to the difficulty of identifying M. hominis, the patient was successfully treated with intravenous ciprofloxacin 400 mg for 14 days. CONCLUSIONS The findings of this case report, coupled with a thorough review of the literature, demonstrate the pathogenic potential of M. hominis. Particularly in developing countries, in which laboratories may have limited access to advanced technologies, such rare infectious diseases remain major diagnostic challenges.


Asunto(s)
Ventriculitis Cerebral/microbiología , Enfermedad Iatrogénica , Infecciones por Mycoplasma/etiología , Mycoplasma hominis , Ventriculitis Cerebral/diagnóstico por imagen , Niño , Infección Hospitalaria/microbiología , Drenaje/efectos adversos , Humanos , Masculino , Tomografía Computarizada por Rayos X
7.
Ann Clin Microbiol Antimicrob ; 17(1): 7, 2018 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-29544544

RESUMEN

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) constitutes a major global health concern causing hospital and community acquired infections. A wide diversity of MRSA genotypes are circulating in geographically related regions. Therefore understanding the molecular epidemiology of MRSA is fundamental to design control and clearance measures. METHODS: A total of 106 MRSA isolates from infection (51) and carrier colonization sites (55) are characterized genetically based on SCCmec and MLST genotyping methods in addition to detection of PVL, TSST-1 and enterotoxins. RESULTS: Sccmec-IV was the most frequently detected genotype (77.3%) followed by genotype V (13.2%) and III (9.4%). SCCmec-IVa was more prevalent among the carrier group (p value 0.002). CC80 was the most commonly identified clonal complex (CC). CC6 and CC22 were significantly more prevalent among the carrier group (p value 0.02 and 0.01, respectively). PVL was highly prevalent among the isolates (58.5%). PVL was detected in 70.6% of isolates from infection sites and 47.3% of isolates from carriers. All strains were sensitive to vancomycin, however, MRSA strains isolated from infection sites had significantly higher MICs compared to strains isolated from carrier colonization sites (p value 0.021). Five new sequence types mainly from the carrier group were identified and described in the study. CONCLUSIONS: MRSA population is genetically very diverse among carriers and infected individuals. With SCCmec type IV being most prevalent, this suggests a community origin of most MRSA strains. Therefore very well designed surveillance and clearance strategies should be prepared to prevent emergence and control spread of MRSA in the community.


Asunto(s)
Genotipo , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Epidemiología Molecular , Infecciones Estafilocócicas/microbiología , Adulto , Alelos , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Infecciones Comunitarias Adquiridas , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , ADN Bacteriano , Farmacorresistencia Bacteriana Múltiple/genética , Enterotoxinas/genética , Exotoxinas/genética , Femenino , Genes Bacterianos/genética , Humanos , Leucocidinas/genética , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Proteínas de Unión a las Penicilinas/genética , Filogenia , Infecciones Estafilocócicas/epidemiología , Superantígenos/genética
8.
J Infect Public Health ; 7(4): 289-95, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24835036

RESUMEN

BACKGROUND/AIMS: A few recent reports have demonstrated an elevated prevalence of latent tuberculosis infection (LTBI) among laboratory personnel. We sought to evaluate the prevalence of LTBI among laboratory personnel using the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and to assess the risk factors associated with positive test results. METHODS: The study population included laboratory personnel who were working in the routine diagnostic laboratories of different departments of a university hospital. Subjects were interviewed using a standardized questionnaire that assessed information related to risk factors for LTBI and underwent the QFT-GIT assay. RESULTS: Positive QFT-GIT tests results were detected in 19.4% (26/134) of the laboratory personnel. The following factors were significantly associated with positive QFT-GIT results: age≥30 years [odds ratio (OR): 4.741, 95% CI: 1.41-17.50, P=0.004]; duration of employment in the healthcare profession >10 years (P<0.0001); and non-Saudi nationality (OR: 21.67, 95% CI: 6.69-73.94, P<0.0001). CONCLUSION: These data highlight the need for effective institutional TB infection control plans. Additionally, our data reinforce the necessities of pre-employment and regular LTBI screening of laboratory personnel and the importance of offering preventive therapies to positive subjects to prevent the progression to active disease.


Asunto(s)
Ensayos de Liberación de Interferón gamma/métodos , Personal de Laboratorio , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Adulto , Estudios Transversales , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Factores de Riesgo , Arabia Saudita/epidemiología , Encuestas y Cuestionarios , Adulto Joven
9.
J Infect Dev Ctries ; 7(8): 618-29, 2013 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-23949298

RESUMEN

INTRODUCTION: Few reports about the prevalence and genetic basis of extended spectrum beta-lactamases (ESBLs) are available from Saudi Arabia. We sought to determine the prevalence of ESBL-producing Enterobacteriaceae in a university hospital in eastern Saudi Arabia and to characterize the ESBLs produced by these isolates at the molecular level. METHODOLOGY: All clinical isolates of Escherichia coli, Klebsiella spp., and Proteus spp. collected over two years were evaluated for susceptibility to a panel of antimicrobials and were analyzed for the ESBL phenotype using screening and confirmatory tests. ESBL-positive isolates were then screened for the presence of genes encoding CTX-M, SHV, and TEM beta-lactamases by PCR. RESULTS AND CONCLUSIONS: The overall prevalence of ESBL-producing isolates was 4.8% (253/5256). Most isolates (80%) were from the inpatient department. The ESBL phenotype was more frequently detected in K. pneumonia. CTX-M genes were the most prevalent ESBL genes, detected in 82% of the studied isolates. The ESBL producers demonstrated a high multidrug resistance rate (96.6%). In transconjugation assay, the same ESBL gene pattern was transmitted from 29.7% of K. pneumoniae donors to the recipient strain, and the latter exhibited concomitant decreased aminoglycosides and co-trimoxazole susceptibility. We observed the presence of ESBL screen-positive but confirmatory-negative isolates (8.9%). Phenotypic tests for the production of AmpC ß-lactamase tested positive in 52% of these isolates. Further studies are needed for appropriate detection of concomitant ESBL and AmpC enzyme production among such isolates. Continued surveillance and judicious antibiotic usage together with the implementation of efficient infection control measures are absolutely required.


Asunto(s)
Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/enzimología , beta-Lactamasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Conjugación Genética , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Transferencia de Gen Horizontal , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Fenotipo , Prevalencia , Arabia Saudita/epidemiología , Adulto Joven , beta-Lactamasas/análisis
10.
J Nutr ; 136(3): 700-3, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16484546

RESUMEN

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated, autoimmune disorder characterized by central nervous system inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). Prior work in the EAE model has suggested that encephalitogenic T cells are of the T helper (Th)-1 phenotype. Our group has performed several studies in the EAE model that suggest that a strategy for treating autoimmune disorders is to convert the pathogenic cells from the Th1 to Th2 phenotype. Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear hormone receptor superfamily that include receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Recently, we examined the role of PPARgamma in EAE and observed that administration of the PPARgamma agonist 15-deoxy-Delta(12,14) prostaglandin J2 exerted a significant therapeutic effect predominantly by inhibiting the activation and expansion of encephalitogenic T cells. One potential advantage in studying PPARalpha agonists is that they have been very well tolerated when used in humans to treat conditions such as elevated triglycerides. Building on prior work in immune deviation and with PPAR agonists, we have demonstrated that PPARalpha agonists can alter the cytokine phenotype of myelin-reactive T cells, alter their encephalitogenicity, and be useful in the treatment of EAE. The fact that PPARalpha agonists have been used as therapeutic agents in humans to treat metabolic conditions for over 25 years with little toxicity makes them attractive candidates for use as adjunctive therapies in MS.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Esclerosis Múltiple/tratamiento farmacológico , Receptores Activados del Proliferador del Peroxisoma/agonistas , Receptores Citoplasmáticos y Nucleares/inmunología , Citocinas/genética , Regulación de la Expresión Génica/inmunología , Humanos , Modelos Inmunológicos , Esclerosis Múltiple/inmunología , PPAR alfa/inmunología
11.
J Immunol ; 172(9): 5790-8, 2004 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-15100326

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPAR gamma ligands, which include the naturally occurring PG metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), as well as thiazolidinediones, have been shown to have anti-inflammatory activity. The PPAR alpha agonists, gemfibrozil, ciprofibrate, and fenofibrate, have an excellent track history as oral agents used to treat hypertriglyceridemia. In the present study, we demonstrate that these PPAR alpha agonists can increase the production of the Th2 cytokine, IL-4, and suppress proliferation by TCR transgenic T cells specific for the myelin basic protein Ac1-11, as well as reduce NO production by microglia. Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis. More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-gamma and promoting IL-4 secretion. These results suggest that PPAR alpha agonists such as gemfibrozil and fenofibrate, may be attractive candidates for use in human inflammatory conditions such as multiple sclerosis.


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Microcuerpos/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Factores de Transcripción/agonistas , Animales , Línea Celular , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Células Cultivadas , Citocinas/biosíntesis , Relación Dosis-Respuesta a Droga , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Fenofibrato/administración & dosificación , Fenofibrato/farmacología , Gemfibrozilo/administración & dosificación , Gemfibrozilo/farmacología , Inhibidores de Crecimiento/administración & dosificación , Inhibidores de Crecimiento/farmacología , Humanos , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microglía/metabolismo , Óxido Nítrico/biosíntesis , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células Th2/inmunología , Células Th2/metabolismo
12.
J Neuroimmunol ; 148(1-2): 116-26, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14975592

RESUMEN

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors (RXRs) as PPAR-RXR heterodimers. In experimental autoimmune encephalomyelitis (EAE), the gene expression of PPAR-gamma was demonstrated in spinal cord during the course of EAE. Administration of 15-deoxy-(12,14)-prostaglandin J2 (15d-PGJ2) or 9-cis-retinoic acid (RA) alone at the onset of clinical signs of EAE reduced the severity of disease, however, their combination resulted in enhanced amelioration of disease. These results suggest that use of RXR specific ligands may be highly effective when combined with PPAR-gamma agonists in the treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Prostaglandina D2/análogos & derivados , Prostaglandina D2/uso terapéutico , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores de Ácido Retinoico/agonistas , Factores de Transcripción/agonistas , Tretinoina/uso terapéutico , Alitretinoína , Análisis de Varianza , Animales , Células Cultivadas , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Interacciones Farmacológicas , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/complicaciones , Encefalomielitis Autoinmune Experimental/fisiopatología , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunización/métodos , Inmunohistoquímica/métodos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/etiología , Ligandos , Ganglios Linfáticos/citología , Ganglios Linfáticos/efectos de los fármacos , Ratones , Ratones Transgénicos , Microglía/citología , Microglía/efectos de los fármacos , Proteína Básica de Mielina , Óxido Nítrico/metabolismo , Fragmentos de Péptidos/genética , ARN Mensajero/biosíntesis , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores X Retinoide , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Bazo/citología , Bazo/efectos de los fármacos , Factores de Tiempo
13.
J Immunol ; 170(6): 2833-42, 2003 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-12626533

RESUMEN

Infections often precede the development of autoimmunity. Correlation between infection with a specific pathogen and a particular autoimmune disease ranges from moderately strong to quite weak. This lack of correspondence suggests that autoimmunity may result from microbial activation of a generic, as opposed to pathogen-specific host-defense response. The Toll-like receptors, essential to host recognition of microbial invasion, signal through a common, highly conserved pathway, activate innate immunity, and control adaptive immune responses. To determine the influence of Toll/IL-1 signaling on the development of autoimmunity, the responses of wild-type (WT) mice and IL-1R-associated kinase 1 (IRAK1)-deficient mice to induction of experimental autoimmune encephalomyelitis were compared. C57BL/6 and B6.IRAK1-deficient mice were immunized with MOG 35-55/CFA or MOG 35-55/CpG DNA/IFA. WT animals developed severe disease, whereas IRAK1-deficient mice were resistant to experimental autoimmune encephalomyelitis, exhibiting little or no CNS inflammation. IRAK1-deficient T cells also displayed impaired Th1 development, particularly during disease induction, despite normal TCR signaling. These results suggest that IRAK1 and the Toll/IL-1 pathway play an essential role in T cell priming, and demonstrate one means through which innate immunity can control subsequent development of autoimmunity. These findings may also help explain the association between antecedent infection and the development or exacerbations of some autoimmune diseases.


Asunto(s)
Encefalomielitis Autoinmune Experimental/inmunología , Predisposición Genética a la Enfermedad , Proteínas Quinasas/fisiología , Receptores de Interleucina-1/fisiología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/fisiología , Animales , Movimiento Celular/genética , Movimiento Celular/inmunología , Células Cultivadas , Islas de CpG/inmunología , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/inmunología , Glicoproteínas/inmunología , Inmunidad Innata/genética , Memoria Inmunológica/genética , Inyecciones Subcutáneas , Interferón gamma/biosíntesis , Quinasas Asociadas a Receptores de Interleucina-1 , Interfase/genética , Interfase/inmunología , Activación de Linfocitos/genética , Macrófagos/inmunología , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Glicoproteína Mielina-Oligodendrócito , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Especificidad de Órganos/genética , Especificidad de Órganos/inmunología , Fragmentos de Péptidos/inmunología , Proteínas Quinasas/deficiencia , Proteínas Quinasas/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/fisiología , Receptores de Interleucina-1/genética , Bazo/citología , Bazo/inmunología , Subgrupos de Linfocitos T/enzimología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
14.
J Immunol ; 168(5): 2508-15, 2002 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11859145

RESUMEN

Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear hormone receptor superfamily that includes receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Previous studies dealing with PPAR-gamma expression in the immune system have been limited. Recently, PPAR-gamma was identified in monocyte/macrophage cells. In this study we examined the role of PPAR-gamma in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. The hypothesis we are testing is whether PPAR-gamma plays an important role in EAE pathogenesis and whether PPAR-gamma ligands can inhibit the clinical expression of EAE. Initial studies have shown that the presence of the PPAR-gamma ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac(1-11) TCR-transgenic mice. 15d-PGJ2 suppressed IFN-gamma, IL-10, and IL-4 production by both Con A- and myelin basic protein Ac(1-11) peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay. Culture of encephalitogenic T cells with 15d-PGJ2 in the presence of Ag reduced the ability of these cells to adoptively transfer EAE. Examination of the target organ, the CNS, during the course of EAE revealed expression of PPAR-gamma in the spinal cord inflammatory infiltrate. Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease. These results suggest that PPAR-gamma ligands may be a novel therapeutic agent for diseases such as multiple sclerosis.


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Prostaglandina D2/análogos & derivados , Prostaglandina D2/uso terapéutico , Receptores Citoplasmáticos y Nucleares/agonistas , Factores de Transcripción/agonistas , Traslado Adoptivo , Animales , Antígenos CD40/metabolismo , Células Cultivadas , Citocinas/biosíntesis , Encefalomielitis Autoinmune Experimental/diagnóstico , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Genes Codificadores de los Receptores de Linfocitos T , Inmunohistoquímica , Cinética , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Transgénicos , Microglía/efectos de los fármacos , Microglía/inmunología , Proteína Básica de Mielina/inmunología , Fragmentos de Péptidos/inmunología , Prostaglandina D2/farmacología , Receptores Citoplasmáticos y Nucleares/inmunología , Receptores Citoplasmáticos y Nucleares/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/trasplante , Factores de Transcripción/inmunología , Factores de Transcripción/metabolismo
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