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1.
Scand J Clin Lab Invest ; 81(4): 282-289, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33974458

RESUMEN

BACKGROUND: Early identification of patients with COVID-19 who may develop critical illness is of great importance. METHODS: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in a cohort of 154 cases admitted at Valme and Virgen del Rocio University Hospital. RESULTS: A total of 62 (23.5%) patients developed a critical illness during their hospitalization stay, 21 (8.0%) patients needed invasive ventilation, 34 (12.9%) were admitted at the ICU and the overall mortality was of 14.8% (39 cases). 5 variables were included in the final model: age >59.5 years (OR: 3.11;95%CI 1.39-6.97), abnormal CRP results (OR: 5.76;95%CI 2.32-14.30), abnormal lymphocytes count (OR: 3.252;95%CI 1.56-6.77), abnormal CK results (OR: 3.38;95%CI 1.59-7.20) and abnormal creatinine (OR: 3.30;95%CI 1.42-7.68). The AUC of this model was 0.850 with sensitivity of 65% and specificity of 87% and the IDI and NRI were 0.1744 and 0.2785, respectively. The validation indicated a good discrimination for the external population. CONCLUSIONS: Biomarkers add prognostic information in COVID-19 patients. Our risk-score provides an easy to use tool to identify patients who are likely to develop critical illness during their hospital stay.


Asunto(s)
Biomarcadores/sangre , COVID-19/etiología , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/terapia , Creatina Quinasa/sangre , Creatinina/sangre , Enfermedad Crítica , Femenino , Hospitalización , Humanos , Laboratorios , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Adulto Joven
2.
Eur J Immunol ; 47(2): 345-352, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27859043

RESUMEN

Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8+ T cells and trigger the switch in immunodominance of the CD8+ T-cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Pulmón/inmunología , Monocitos/inmunología , Infecciones por Orthomyxoviridae/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T , Animales , Células Cultivadas , Células Dendríticas/virología , Epítopos Inmunodominantes/inmunología , Memoria Inmunológica , Pulmón/virología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas del Núcleo Viral/inmunología
3.
PLoS Pathog ; 12(5): e1005656, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27191716

RESUMEN

Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology.


Asunto(s)
Modelos Animales de Enfermedad , Fiebre de Lassa/inmunología , Fiebre de Lassa/patología , Animales , Citometría de Flujo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Quimera por Radiación
4.
Emerg Infect Dis ; 23(4): 702-704, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28322700

RESUMEN

Ross River virus, a mosquitoborne alphavirus, causes epidemic polyarthritis in Australia and the Pacific region. We analyzed serum cytokine, chemokine, and growth factor levels in travelers returning to Germany from Australia. Serum samples showed elevated concentrations in the acute phase of the illness and, more pronounced, in the long-lasting convalescent phase.


Asunto(s)
Infecciones por Alphavirus/complicaciones , Infecciones por Alphavirus/virología , Artralgia/etiología , Citocinas/sangre , Virus del Río Ross , Adulto , Anciano , Infecciones por Alphavirus/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Viaje , Adulto Joven
5.
Med Microbiol Immunol ; 205(3): 269-73, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26702627

RESUMEN

Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase.


Asunto(s)
Citocinas/sangre , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/patología , Adulto , Asia , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Islas del Pacífico , Linfocitos T Colaboradores-Inductores/inmunología , Factores de Tiempo , Viaje
6.
J Immunol ; 193(3): 1324-32, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24958904

RESUMEN

Live-attenuated influenza vaccines (LAIVs) have the potential to generate CD8 T cell immunity that may limit the virulence of an antigenically shifted influenza strain in a population lacking protective Abs. However, current LAIVs exert limited T cell immunity restricted to the vaccine strains. One approach to improve LAIV-induced T cell responses is the use of specific adjuvants to enhance T cell priming by respiratory dendritic cells, but this hypothesis has not been addressed. In this study, we assessed the effect of the TLR3 ligand polyinosinic-polycytidylic acid (poly IC) on CD8 T cell immunity and protection elicited by LAIVs. Mucosal treatment with poly IC shortly after vaccination enhanced respiratory dendritic cell function, CD8 T cell formation, and production of neutralizing Abs. This adjuvant effect of poly IC was dependent on amplification of TLR3 signaling by nonhematopoietic radioresistant cells and enhanced mouse protection to homosubtypic, as well as heterosubtypic, virus challenge. Our findings indicate that mucosal TLR3 ligation may be used to improve CD8 T cell responses to replicating vaccines, which has implications for protection in the absence of pre-existing Ab immunity.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Mucosa Nasal/inmunología , Poli I-C/administración & dosificación , Poli I-C/uso terapéutico , Replicación Viral/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/virología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/virología , Células HEK293 , Humanos , Inmunidad Celular/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/uso terapéutico , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Poli I-C/inmunología , Regulación hacia Arriba/inmunología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico , Replicación Viral/efectos de los fármacos
7.
Am J Physiol Heart Circ Physiol ; 306(11): H1582-93, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24727493

RESUMEN

Glitazones have anti-inflammatory properties by interfering with the transcription of proinflammatory genes, such as cyclooxygenase (COX)-2, and with ROS production, which are increased in hypertension. This study analyzed whether pioglitazone modulates COX-2 expression in hypertension by interfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.5 mg·kg(-1)·day(-1), 28 days) reduced the greater levels of COX-2, pre-pro-ET-1, and NADPH oxidase (NOX) expression and activity as well as O2 (·-) production found in aortas from spontaneously hypertensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1 levels more in cultured vascular smooth muscle cells from hypertensive rats compared with normotensive rats. The ETA receptor antagonist BQ-123 reduced ANG II-induced COX-2 expression in SHR cells. ANG II also increased NOX-1 expression, NOX activity, and superoxide production in SHR cells; the selective NOX-1 inhibitor ML-171 and catalase reduced ANG II-induced COX-2 and ET-1 transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2, phospho-c-Jun, and p65 NF-κB subunit nuclear protein expression. SP-600125 and lactacystin, JNK and NF-κB inhibitors, respectively, reduced ANG II-induced ET-1, COX-2, and NOX-1 levels and NOX activity. Pioglitazone reduced the effects of ANG II on NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNA levels, JNK activation, and nuclear phospho-c-Jun and p65 expression. In conclusion, ROS production and ET-1 are involved in ANG II-induced COX-2 expression in SHRs, explaining the greater COX-2 expression observed in this strain. Furthermore, pioglitazone inhibits ANG II-induced COX-2 expression likely by interfering with NF-κB and activator protein-1 proinflammatory pathways and downregulating ROS production and ET-1 transcription, thus contributing to the anti-inflammatory properties of glitazones.


Asunto(s)
Angiotensina II/farmacología , Ciclooxigenasa 2/metabolismo , Endotelina-1/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Tiazolidinedionas/farmacología , Transcripción Genética/efectos de los fármacos , Animales , Aorta/citología , Aorta/efectos de los fármacos , Aorta/metabolismo , Endotelina-1/genética , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , NADPH Oxidasas/metabolismo , Pioglitazona , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY
8.
Clin Transl Oncol ; 26(10): 2685-2692, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38724825

RESUMEN

INTRODUCTION: Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. The RIETE and SOME scores aim to identify patients with acute VTE at high risk of occult cancer. In the present study, we evaluated the performance of both scores. METHODS: The scores were evaluated in a retrospective cohort from two centers. The area under the receiver-operating characteristics curve (AUC) evaluated the discriminatory performance. RESULTS: The RIETE score was applied to 815 patients with provoked and unprovoked VTE, of whom 56 (6.9%) were diagnosed with cancer. Of the 203 patients classified as high-risk, 18 were diagnosed with cancer, representing 32.1% (18/56) of the total cancer diagnoses. In the group of 612 low-risk patients, 67.9% of the cancer cases were diagnosed (38/56). Sensitivity, specificity, negative and positive predictive values, and AUC were 32%, 76%, 94%, 9%, and 0.430 (95% confidence interval [CI], 0.38‒0.47), respectively. The SOME score could be calculated in 418 patients with unprovoked VTE, of whom 33 (7.9%) were diagnosed with cancer. Of the 45 patients classified as high-risk, three were diagnosed with cancer, representing 9.1% (3/33) of the total cancer diagnoses. In the group of 373 low-risk patients, 90.9% of the cancer cases were diagnosed (30/33). Sensitivity, specificity, negative and positive predictive values, and AUC were 33%, 88%, 94%, 20%, and 0.351 (95% CI, 0.27‒0.43), respectively. CONCLUSIONS: The performance of both scores was poor. Our results highlight the need to develop new models to identify high-risk patients who may benefit from an extensive cancer screening strategy.


Asunto(s)
Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Neoplasias/complicaciones , Neoplasias/epidemiología , Curva ROC , Medición de Riesgo/métodos , Área Bajo la Curva , Adulto , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/epidemiología
9.
Clin Dev Immunol ; 2013: 348562, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24363759

RESUMEN

OBJECTIVE: Helicobacter pylori provokes a host of immune alterations upon colonizing the gastric mucosa. DESIGN: We report 22 individuals with confirmed Helicobacter pylori infection who were also managed for the concurrent elevation of immunoglobulin free light chain (kappa and lambda) levels. RESULT: Of the 22 patients, 15 patients (68.2%) had elevated free light chain levels: 6 patients (40%) had only kappa chain elevation, 2 patients (13.3%) had only lambda chain elevation, and 7 patients (46.7%) had both kappa and lambda chain elevation. Twenty out of the 22 patients (90.9%) were microbiologically confirmed cured with 3 patients being lost to follow-up for repeat levels. Of the 3 patients who were lost to follow-up, 1 patient had only kappa chain elevation, 1 patient had only lambda chain elevation, and 1 patient had both kappa and lambda chain elevation. For those who were cured (19 patients), 5 patients with kappa elevation had normalized values, 4 patients with lambda elevation had normalized values, and 2 patients with combined kappa and lambda elevation had normalized values. For 6 out of the 19 patients, the light chain levels remained elevated. CONCLUSION: We speculate that the Helicobacter pylori infection disrupts the immunoglobulin system with potential implications being discussed below.


Asunto(s)
Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Cadenas Ligeras de Inmunoglobulina/inmunología , Paraproteinemias/complicaciones , Paraproteinemias/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Comorbilidad , Femenino , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Cadenas Ligeras de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Paraproteinemias/sangre
10.
Sci Total Environ ; 813: 152610, 2022 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-34963596

RESUMEN

In bears, reproduction is dependent on the body reserves accumulated during hyperphagia. The Cantabrian brown bear mainly feeds on nuts during the hyperphagia period. Understanding how landscape heterogeneity and vegetation productivity in human-dominated landscapes influence the feeding habits of bears may therefore be important for disentangling species-habitat relationships of conservation interest. We determined the spatial patterns of nut consumption by brown bears during the hyperphagia period in relation to landscape structure, characteristics of fruit-producing patches and vegetation productivity. For this purpose, we constructed foraging models based on nut consumption data (obtained by scat analysis), by combining vegetation productivity data, topographical variables and landscape metrics to identify nut foraging patterns during this critical period for bears. The average wooded area of patches where scats were collected and where the nuts that the bears had consumed were produced was larger than that of the corresponding patches where nuts were not produced. For scats collected outside of nut-producing patches, the distance between the scats and the patches was greatest for chestnut-producing patches. Elevation, Gross Primary Production (GPP) and the Aggregation Index (AI) were good predictors of acorn consumption in the models. Good model fits were not obtained for data on chestnut consumption in bears. The findings confirm that brown bears feeding on nuts show a preference for relatively large, highly aggregated patches with a high degree of diversity in the landscape pattern, which may help the bears to remain undetected. The nut prediction model highlights areas of particular importance for brown bears during hyperphagia. The human presence associated with sweet chestnut forest stands or orchards may make bears feel more vulnerable when feeding.


Asunto(s)
Ursidae , Animales , Ecosistema , Frutas , Humanos , Hiperfagia , Nueces
11.
Ther Adv Infect Dis ; 9: 20499361221135885, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36387060

RESUMEN

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy.

13.
Hepatology ; 50(4): 1056-63, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19670415

RESUMEN

UNLABELLED: A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02). CONCLUSION: Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.


Asunto(s)
Progresión de la Enfermedad , VIH/patogenicidad , Hepacivirus/patogenicidad , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Hígado/patología , Hígado/virología , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Antivirales/uso terapéutico , Biopsia , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/patología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/uso terapéutico , Factores de Riesgo
15.
AIDS Read ; 19(6): 230-2, 244, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19642241

RESUMEN

We present a patient with fully controlled HIV disease and a normal CD4 count whose initial treatment for syphilis failed. Biopsy-proven syphilitic colitis and severe gastroparesis developed, requiring the insertion of a temporary percutaneous gastrostomy tube. The patient responded to a course of high-dose aqueous crystalline penicillin followed by doxycycline, and he completely recovered. The occurrence of failure of conventional syphilis treatment in HIV-infected patients is discussed.


Asunto(s)
Colitis , Gastroparesia , Infecciones por VIH/complicaciones , Sífilis/complicaciones , Sífilis/fisiopatología , Carga Viral , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Recuento de Linfocito CD4 , Colitis/complicaciones , Colitis/tratamiento farmacológico , Colitis/microbiología , Doxiciclina/administración & dosificación , Doxiciclina/uso terapéutico , Gastroparesia/complicaciones , Gastroparesia/tratamiento farmacológico , Gastroparesia/microbiología , Gastrostomía , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Masculino , Penicilinas/administración & dosificación , Penicilinas/uso terapéutico , Sífilis/tratamiento farmacológico , Sífilis/microbiología , Resultado del Tratamiento , Treponema pallidum/aislamiento & purificación
16.
Sci Rep ; 9(1): 16461, 2019 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-31712626

RESUMEN

Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPARγ activation on the vascular effects of ET-1 in hypertension. In spontaneously hypertensive rats (SHR), but not in normotensive rats, ET-1 enhanced phenylephrine-induced contraction through ETA by a mechanism dependent on activation of TP receptors by COX-2-derived prostacyclin and reduction in NO bioavailability due to enhanced ROS production. In SHR, the PPARγ agonist pioglitazone (2.5 mg/Kg·day, 28 days) reduced the increased ETA levels and increased those of ETB. After pioglitazone treatment of SHR, ET-1 through ETB decreased ROS levels that resulted in increased NO bioavailability and diminished phenylephrine contraction. In vascular smooth muscle cells from SHR, ET-1 increased ROS production through AP-1 and NFκB activation, leading to enhanced COX-2 expression. These effects were blocked by pioglitazone. In summary, in hypertension, pioglitazone shifts the vascular ETA/ETB ratio, reduces ROS/COX-2 activation and increases NO availability; these changes explain the effect of ET-1 decreasing phenylephrine-induced contraction.


Asunto(s)
Endotelina-1/metabolismo , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Pioglitazona/farmacología , Animales , Hipertensión/metabolismo , Hipertensión/patología , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Estrés Oxidativo/efectos de los fármacos , PPAR gamma/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo
17.
AIDS Read ; 17(8): 418-20, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17717886

RESUMEN

Lichen myxedematosus, or papular mucinosis, is a skin disorder characterized by accumulation of mucin in the dermis. We present the case of a patient with HIV infection and lichen myxedematosus whose skin condition completely resolved with antiretroviral therapy.


Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Escleromixedema/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Piel/patología
18.
Eur J Health Econ ; 7(4): 270-5, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16850331

RESUMEN

An observational descriptive study was carried out of the healthcare resources consumed during 1 year by a sample of patients with type II diabetes of a healthcare area in southern Spain. A total of 517 patients with a mean duration of disease of 9.7+/-8 years were assessed. A total annual health cost of 4,278 euro/patient was calculated (direct 2,504 euro; indirect 1,774 euro). Multiple regression analysis showed an independent association between total costs and obesity, male sex, number of hospitalizations related to diabetes, permanent disability, macrovascular complications, and both micro- and macrovascular complications. Our findings confirm both the high economic cost associated with type II diabetes and the direct relationship between the costs of the disease and the presence of obesity, male sex, hospitalizations related to diabetes, permanent disability and chronic complications.


Asunto(s)
Diabetes Mellitus Tipo 1/economía , Gastos en Salud , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Complicaciones de la Diabetes/economía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , España/epidemiología
19.
J Vis Exp ; (100): e52803, 2015 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-26168339

RESUMEN

Vaccines are one of the greatest achievements of mankind, and have saved millions of lives over the last century. Paradoxically, little is known about the physiological mechanisms that mediate immune responses to vaccines perhaps due to the overall success of vaccination, which has reduced interest into the molecular and physiological mechanisms of vaccine immunity. However, several important human pathogens including influenza virus still pose a challenge for vaccination, and may benefit from immune-based strategies. Although influenza reverse genetics has been successfully applied to the generation of live-attenuated influenza vaccines (LAIVs), the addition of molecular tools in vaccine preparations such as tracer components to follow up the kinetics of vaccination in vivo, has not been addressed. In addition, the recent generation of mouse models that allow specific depletion of leukocytes during kinetic studies has opened a window of opportunity to understand the basic immune mechanisms underlying vaccine-elicited protection. Here, we describe how the combination of reverse genetics and chimeric mouse models may help to provide new insights into how vaccines work at physiological and molecular levels, using as example a recombinant, cold-adapted, live-attenuated influenza vaccine (LAIV). We utilized laboratory-generated LAIVs harboring cell tracers as well as competitive bone marrow chimeras (BMCs) to determine the early kinetics of vaccine immunity and the main physiological mechanisms responsible for the initiation of vaccine-specific adaptive immunity. In addition, we show how this technique may facilitate gene function studies in single animals during immune responses to vaccines. We propose that this technique can be applied to improve current prophylactic strategies against pathogens for which urgent medical countermeasures are needed, for example influenza, HIV, Plasmodium, and hemorrhagic fever viruses such as Ebola virus.


Asunto(s)
Inmunidad Mucosa/efectos de los fármacos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Animales , Quimera , Células Dendríticas/inmunología , Femenino , Células HEK293 , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H2N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/genética , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
20.
Clin Vaccine Immunol ; 22(6): 674-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25903356

RESUMEN

Sarcocystis nesbitti is a parasite responsible for a biphasic eosinophilic febrile myositis syndrome in two recent outbreaks in Malaysia. We demonstrate Th2 cytokine polarization in infected travelers, an overall cytokine production decrease in the early phase of the disease suggestive of initial immunosuppression, and elevated levels of proinflammatory and chemotactic cytokines in the later myositic phase.


Asunto(s)
Citocinas/sangre , Sarcocystis/inmunología , Sarcocistosis/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Tolerancia Inmunológica , Malasia , Masculino , Sarcocistosis/inmunología , Células Th2/inmunología , Viaje , Adulto Joven
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