RESUMEN
BACKGROUND: Resveratrol, a naturally occurring polyphenolic compound, has been shown to inhibit cancer growth by targeting several cancer-related signalling pathways. In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant leukocyte population that are associated with poor prognosis in over 80% of breast cancer cases. However, little is known about the effect of resveratrol in the TME. METHODS: In this study, MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR), and T47D were used to examine the antitumor effect of resveratrol. The effectiveness of resveratrol, together with cisplatin as breast cancer treatment was investigated in vivo. Gene expressions of M1 (iNOS and CXCL10) and M2 (ARG1, CD163 and MRC1) markers in differentiated macrophages derived from THP-1 cells were examined to investigate the effect of resveratrol on TAM polarization in breast cancer progression. RESULTS: Our results demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in breast cancer cells by inhibiting production of IL-6 and STAT3 activation. Treatment of resveratrol increased CXCL10 (M1 marker) expression. Further, resveratrol decreased IL-6 levels in LPS-treated differentiated macrophages. The use of resveratrol with cisplatin inhibited suppressed tumor growth when compared with cisplatin alone. CONCLUSION: This study revealed that resveratrol inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and suppressing IL-6/pSTAT3 pathway.
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Neoplasias de la Mama , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cisplatino/farmacología , Femenino , Humanos , Interleucina-6/metabolismo , Macrófagos/patología , Resveratrol/metabolismo , Resveratrol/farmacología , Microambiente TumoralRESUMEN
OBJECTIVE: To assess the quality of tuberculosis (TB) surveillance in Haiti, including whether underreporting from facilities to the national level contributes to low national case registration. METHODS: We collected 2010 and 2012 TB case totals, reviewed laboratory registries, and abstracted individual TB case reports from 32 of 263 anti-tuberculosis treatment facilities randomly selected after stratification/weighting toward higher-volume facilities. We compared site results to national databases maintained by a non-governmental organization partner (International Child Care [ICC]) for 2010 and 2012, and the National TB Program (Programme National de Lutte contre la Tuberculose, PNLT) for 2012 only. RESULTS: Case registries were available at 30/32 facilities for 2010 and all 32 for 2012. Totals of 3711 (2010) and 4143 (2012) cases were reported at the facilities. Case totals per site were higher in site registries than in the national databases by 361 (9.7%) (ICC 2010), 28 (0.8%) (ICC 2012), and 31 (0.8%) cases (PNLT 2012). Of abstracted individual cases, respectively 11.8% and 6.8% were not recorded in national databases for 2010 (n = 323) and 2012 (n = 351). CONCLUSIONS: The evaluation demonstrated an improvement in reporting registered TB cases to the PNLT in Haiti between 2010 and 2012. Further improvement in case notification will require enhanced case detection and diagnosis.
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Instituciones de Salud/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud/normas , Vigilancia en Salud Pública/métodos , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Haití/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Adulto JovenRESUMEN
BACKGROUND: We recently described the Mycobacterium tuberculosis RD(Rio) genotype, a clonally derived sublineage within the Latin American-Mediterranean (LAM) family. Genetic diversity of M. tuberculosis likely affects the clinical aspects of tuberculosis (TB). Prospective studies that address this issue are scarce and remain controversial. OBJECTIVE: To determine the association of differential clinical features of pulmonary TB with the RD(Rio) M. tuberculosis etiology. METHODS: Culture-proven pulmonary TB patients (n = 272) were clinically evaluated, including history, physical examination, chest X-ray and anti-human immunodeficiency virus serology. Isolates were classified as RD(Rio) or non-RD(Rio) M. tuberculosis by multiplex polymerase chain reaction and further spoligotyped. Clinical and M. tuberculosis genotype data were analyzed. RESULTS: RD(Rio) M. tuberculosis caused disease in 26.5% (72/270) of all TB cases. The LAM genotype, of which RD(Rio) strains are members, was responsible for 46.0% of the TB cases. Demographic data, major signs and symptoms, radiographic presentation, microbiological features and clinical outcomes were not significantly different among patients with TB caused by RD(Rio) and non-RD(Rio) strains. CONCLUSIONS: Disease caused by M. tuberculosis RD(Rio) strains was not clinically distinctive or more severe than disease caused by non-RD(Rio) strains in this series of TB patients. Larger prospective studies specifically designed to disclose differential clinical characteristics of TB caused by specific M. tuberculosis lineages are needed.
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ADN Bacteriano/análisis , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Dermatoglifia del ADN , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Adulto JovenRESUMEN
Interleukin (IL) 10 and interferon-gamma (IFN-) levels in induced sputum supernatants of 21 tuberculosis (TB) patients at diagnosis and during chemotherapy were correlated to recurrence rates. IL-10 decreased until day 60 of treatment (T60), and between T60 and T180 it increased again in 7 cases (Pattern 1) and further decreased in 14 cases (Pattern 2). Follow-up of 69 months was performed in 20/21 cases; 6 had recurrence of TB, of which 5/7 (71%) had Pattern 1 and 1/13 (7.7%) Pattern 2 (OR 30.0, 95%CI 2.19411.3, P 0.0072). This was not observed for IFN-. High IL-10 levels at the end of treatment may function as a risk factor for TB recurrence.
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Antituberculosos/uso terapéutico , Interferón gamma/inmunología , Interleucina-10/inmunología , Tuberculosis/inmunología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia , Factores de Riesgo , Esputo/inmunología , Tuberculosis/tratamiento farmacológico , Adulto JovenRESUMEN
CONTEXT: Corticosteroid-binding globulin (CBG; SERPIN A6) gene mutations are rare; only four mutations have been described, often in association with fatigue and chronic pain, albeit with incomplete penetrance. PATIENT: We report a kindred with a novel SERPINA6 mutation. The proband, a 9-yr-old male, had excessive postexertional fatigue, weakness, and migraine. MAIN OUTCOME MEASURES AND RESULTS: Investigations revealed low morning and ACTH-stimulated peak cortisol levels. SERPIN A6 sequencing detected a novel exon 2 single base deletion (c.13delC) leading to a frameshift generating a stop codon within the signal peptide coding region (p.Leu5CysfsX26) and 50% reduced CBG levels in heterozygotes. The patient's father and two sisters share the mutation. Symptom expression within the family may have been modified by a polymorphic CBG allele (c.735G>T). Exogenous hydrocortisone had no effect on the fatigue. CONCLUSION: This report documents the fifth CBG gene mutation in humans and the second causing major effects on CBG levels. Individuals with low CBG levels may be misdiagnosed as having secondary hypocortisolism. The association with fatigue and idiopathic pain is again noted and may relate to altered stress system function. Variability of the phenotype may relate to other genetic variations of the CBG gene or environmental factors.
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Mutación Missense , Transcortina/genética , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Chile , Análisis Mutacional de ADN , Fatiga/complicaciones , Fatiga/genética , Humanos , Masculino , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/genética , Debilidad Muscular/complicaciones , Debilidad Muscular/genética , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
Costimulatory and antigen-presenting molecules are essential to the initiation of T cell immunity to mycobacteria. The present study analyzed by immunocytochemistry, using monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase method, the frequency of costimulatory (CD86, CD40, CD40L, CD28, and CD152) and antigen-presenting (MHC class II and CD1) molecules expression on human lung cells recovered by sputum induction from tuberculosis (TB) patients (N = 22) and non-TB controls (N = 17). TB cases showed a statistically significant lower percentage of HLA-DR+ cells than control subjects (21.9 ± 4.2 vs 50.0 ± 7.2 percent, P < 0.001), even though similar proportions of TB cases (18/22) and control subjects (16/17, P = 0.36) had HLA-DR-positive-stained cells. In addition, fewer TB cases (10/22) compared to control subjects (16/17) possessed CD86-expressing cells (P = 0.04; OR: 0.05; 95 percentCI = 0.00-0.51), and TB cases expressed a lower percentage of CD86+ cells (P = 0.04). Moreover, TB patients with clinically limited disease (£1 lobe) on chest X-ray exhibited a lower percentage of CD86-bearing cells compared to patients with more extensive lung disease (>1 lobe) (P = 0.02). The lower expression by lung cells from TB patients of HLA-DR and CD86, molecules involved in antigen presentation and activation of T cells, may minimize T cell recognition of Mycobacterium tuberculosis, fostering an immune dysfunctional state and active TB.
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Adulto , Femenino , Humanos , Masculino , Células Presentadoras de Antígenos/inmunología , Antígenos CD/inmunología , Antígenos HLA-DR/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Linfocitos T/inmunología , Tuberculosis Pulmonar/inmunología , Fosfatasa Alcalina/inmunología , Anticuerpos Monoclonales/inmunología , Células Presentadoras de Antígenos/metabolismo , Antígenos CD/metabolismo , Estudios de Casos y Controles , Antígenos HLA-DR/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Inmunidad Celular , Inmunohistoquímica , Activación de Linfocitos/inmunología , Mycobacterium tuberculosis/inmunología , Esputo/microbiologíaRESUMEN
Costimulatory and antigen-presenting molecules are essential to the initiation of T cell immunity to mycobacteria. The present study analyzed by immunocytochemistry, using monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase method, the frequency of costimulatory (CD86, CD40, CD40L, CD28, and CD152) and antigen-presenting (MHC class II and CD1) molecules expression on human lung cells recovered by sputum induction from tuberculosis (TB) patients (N = 22) and non-TB controls (N = 17). TB cases showed a statistically significant lower percentage of HLA-DR+ cells than control subjects (21.9 +/- 4.2 vs 50.0 +/- 7.2%, P < 0.001), even though similar proportions of TB cases (18/22) and control subjects (16/17, P = 0.36) had HLA-DR-positive-stained cells. In addition, fewer TB cases (10/22) compared to control subjects (16/17) possessed CD86-expressing cells (P = 0.04; OR: 0.05; 95%CI = 0.00-0.51), and TB cases expressed a lower percentage of CD86+ cells (P = 0.04). Moreover, TB patients with clinically limited disease ( pound1 lobe) on chest X-ray exhibited a lower percentage of CD86-bearing cells compared to patients with more extensive lung disease (>1 lobe) (P = 0.02). The lower expression by lung cells from TB patients of HLA-DR and CD86, molecules involved in antigen presentation and activation of T cells, may minimize T cell recognition of Mycobacterium tuberculosis, fostering an immune dysfunctional state and active TB.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Antígenos CD/inmunología , Antígenos HLA-DR/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Linfocitos T/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Fosfatasa Alcalina/inmunología , Anticuerpos Monoclonales/inmunología , Células Presentadoras de Antígenos/metabolismo , Antígenos CD/metabolismo , Estudios de Casos y Controles , Femenino , Antígenos HLA-DR/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Inmunidad Celular , Inmunohistoquímica , Activación de Linfocitos/inmunología , Masculino , Mycobacterium tuberculosis/inmunología , Esputo/microbiologíaRESUMEN
Approximately 5% of people infected with human T lymphotropic virus type 1 (HTLV-1) develop clinical myelopathy or tropical spastic paraparesis (HAM/TSP) that is associated with high-levels of Th1 cytokines, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Chemokines are known to induce cytokine secretion and direct the trafficking of immune cells to sites of disease. The present study measured serum chemokines correlated with autonomously released IFN-gamma in cell cultures. HTLV-1 infection was defined by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. Subjects included HTLV-1 carriers (n = 56), patients with HAM/TSP (n = 31) and healthy HTLV-1 seronegative volunteer controls (n = 20). Serum chemokines and IFN-gamma autonomously released by mononuclear cells in culture were quantified by ELISA. Compared to HTLV-1 carriers, serum chemokines in HAM/TSP patients showed significantly increased levels of CXCL9 and CXCL10, significantly diminished levels of CCL2 and similar amounts of CCL11 and CCL24. In contrast, CCL11 and CCL24 were significantly lower in serum of HAM/TSP patients than either control. IFN-gamma was positively correlated with CXCL9 and CXCL10 when HAM/TSP and HTLV-1 carriers were used as a combined group. However, despite a large proportion of HTLV-1 carriers having high IFN-gamma levels, these chemokines were not increased in carriers. This study showed that high levels of CXCL9 and CXCL10 in the systemic circulation and low serum CCL2 levels are features of HAM/TSP. HTLV-1 infection and Tax and/or additional viral encoded factor-mediated pathological processes triggering T cell activation with autogenous IFN-gamma release are probably involved in regulating chemokine release.
Asunto(s)
Quimiocinas/sangre , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/diagnóstico , Biomarcadores/sangre , Portador Sano/diagnóstico , Portador Sano/inmunología , Estudios de Casos y Controles , Quimiocina CCL11 , Quimiocina CCL2/sangre , Quimiocina CCL24 , Quimiocina CXCL10 , Quimiocina CXCL9 , Quimiocinas CC/sangre , Quimiocinas CXC/sangre , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Humanos , Interferón gamma/sangre , Interleucina-8 , Paraparesia Espástica Tropical/inmunología , Estadísticas no ParamétricasRESUMEN
The immunological response in HTLV-1 infected individuals is characterized by a prominent Type-1 cytokine response with high production of IFN-gamma and TNF-alpha. In contrast, helminthic infections and in particular chronic schistosomiasis are associated with a predominant production of IL-4, IL-5, IL-10 and IL-13. Liver fibrosis is the main pathological finding in schistosomiasis that occurs after many years of infection. This pathology is T cell dependent but the immune response mechanisms are not completely understood. The North-east region of Brazil is endemic for both HTLV-1 and schistosomiasis. In the present study the immune response, clinical severity, and therapeutic response to praziquantel of patients with schistosomiasis coinfected with HTLV-1 were compared with patients infected only with S. mansoni. Patients with HTLV-1 and S. mansoni had lower levels of IL-5 (P < 0.05) and higher levels of IFN-gamma (P < 0.05) in cultures stimulated with S. mansoni antigen and decreased S. mansoni antigen specific IgE levels when compared with patients with schistosomiasis without HTLV-1 coinfection. Liver fibrosis was mild in all HTLV-1 coinfected patients and efficacy of praziquantel was lower in patients dually infected than in patients infected only with S. mansoni.
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Infecciones por HTLV-I/complicaciones , Esquistosomiasis mansoni/complicaciones , Adulto , Animales , Antihelmínticos/uso terapéutico , Antígenos Helmínticos/inmunología , Células Cultivadas , Femenino , Infecciones por HTLV-I/inmunología , Humanos , Inmunoglobulina E/biosíntesis , Interferón gamma/biosíntesis , Interleucina-5/biosíntesis , Cirrosis Hepática/parasitología , Masculino , Persona de Mediana Edad , Praziquantel/uso terapéutico , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/inmunología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Rapid diagnosis of Mycobacterium tuberculosis remains an obstacle for therapy of tuberculosis (TB). Adenosine deaminase isoform 2 (ADA2) is produced by activated macrophages and has been used for diagnosis of TB from extra-pulmonary sites. However, few studies adequately address whether serum ADA2 activity is useful for diagnosis of active pulmonary tuberculosis (PTB). We prospectively measured serum ADA2 activity in 110 patients with pulmonary disease (65 cases with active PTB and 45 cases with other respiratory diseases) and 78 healthy volunteers (eight with tuberculin skin test positive). The serum ADA2 for the diagnosis of PTB had the sensitivity of 36.9%, the specificity of 84.5%, the positive predictive value of 10.9% and the negative predictive value of 96.2%. We concluded that serum ADA2 activity is neither useful to diagnosis of active PTB nor to differentiate from other respiratory diseases.
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Adenosina Desaminasa/sangre , Tuberculosis Pulmonar/diagnóstico , Adulto , Biomarcadores/sangre , Pruebas Enzimáticas Clínicas , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
A new species of caligid copepod, Lepeophtheirus simplex sp. n., parasitic on bullseye puffer, Sphoeroides annulatus (Jenyns) in Sinaloa, Mexico is described. The new species is distinguished from its congeners by the possession of (1) a maxillule with simple dentiform process; (2) a sternal furca with sharply pointed, curved tines; (3) a 2-segmented exopod of leg 3 with simple, slender spine on proximal segment; (4) a 3-segmented exopod of leg 4 with a long proximal, outer spine; and (5) the terminal claw of male antenna with a large, tridentate, medial protuberance.
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Crustáceos/anatomía & histología , Enfermedades de los Peces/parasitología , Genitales/anatomía & histología , Tetraodontiformes/parasitología , Animales , Crustáceos/clasificación , Femenino , Genitales/ultraestructura , Masculino , MéxicoRESUMEN
Limited data are available on the cellular and immunocytological characteristics of bronchoalveolar lavage (BAL) fluid in individuals infected with the human immunodeficiency virus (HIV) and pulmonary tuberculosis (TB). The immune host response against tuberculosis in early HIV-infection may differ from that in later stages of HIV disease, as is strongly suggested by different clinical and radiographic patterns. We studied the cellular elements in the lungs of 15 HIV-infected patients with advanced immunosuppression and pulmonary tuberculosis (TB/AIDS). The findings were compared with data from four other groups: 1) 15 HIV-seronegative patients with pulmonary TB; 2) 12 HIV-seropositive TB patients without previous AIDS-defining illnesses and with CD4+ >200 cells mm(-3); 3) five AIDS patients without pulmonary lesions; and 4) five healthy controls. BAL fluid and differential cell counts, as well as lymphocyte subsets, were determined. Despite a low CD4/CD8 ratio, the TB/AIDS group had a higher absolute number of CD8+ lymphocytes in the BAL fluid than the other groups. Alveolar macrophages and neutrophils were significantly increased in TB/AIDS patients compared to control groups. The number of eosinophils was increased in TB/HIV--patients but not in TB/AIDS patients. We conclude that tuberculosis in late stage HIV-infected patients has a distinct inflammatory cell profile, suggesting an enhanced compensatory mechanism that amplifies the unspecific inflammatory reaction.
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Síndrome de Inmunodeficiencia Adquirida/inmunología , Fagocitos/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Femenino , Humanos , Recuento de Leucocitos , Linfocitos/inmunología , MasculinoAsunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , VIH-1/inmunología , Mycobacterium tuberculosis , Tuberculosis/etiología , Tuberculosis/inmunología , Recuento de Linfocito CD4 , Citocinas/biosíntesis , Citocinas/inmunología , Humanos , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
OBJECTIVES: The goal of this study was to identify parental behaviors that relate to adherence and metabolic control in a population of young adolescents with insulin-dependent diabetes mellitus (IDDM), and to understand the interrelationships among the variables of parental involvement, adherence to blood glucose monitoring, and glycemic control. STUDY DESIGN: A cross-sectional design was used to investigate parental involvement in diabetes regimen tasks in 89 youth, aged 10 to 15 years, with IDDM. Levels of parental involvement in blood glucose monitoring (BGM) and insulin administration were evaluated through interviews. Assessment of adherence was made by physicians or nurses, independent of patient or parent reports of adherence. Glycemic control was assessed with glycosylated hemoglobin (HbA1c) (reference range, 4% to 6%). RESULTS: There were significant differences in the mean HbA1c values between the older (13 to 15 years of age) (HbA1c = 8.9% +/- 1.03%) and younger (10 to 12 years) patients (HbA1c = 8.4% +/- 1.06%) (p < 0.02). Parental involvement in BGM was significantly related to adherence to BGM (number of blood sugar concentrations checked daily) in both groups of adolescent patients. The younger patients monitored their blood glucose levels more frequently than did the older patients, 39% of the younger patients checked sugar concentrations four or more times daily compared with only 10% of the older group (p < 0.007). In a multivariate model controlling for age, gender, Tanner staging, and duration of diabetes, the frequency of BGM was a significant predictor of glycemic control (R2 = 0.19, p < 0.02). Increased frequency of BGM was associated with lower HbA1c levels. When the frequency of BGM was zero or once a day, the mean HbA1c level was 9.9% +/- 0.44 (SE); when the frequency of BGM was two or three times a day, the mean HbA1c level was 8.7% +/- 0.17; and when the frequency of BGM was four or more times daily, the mean HbA1c level was 8.3% +/- 0.22. CONCLUSIONS: Parental involvement in BGM supports more frequent BGM in 10- to 15-year-old patients with IDDM. This increased adherence to BGM is associated with better metabolic control (i.e., lower HbA1c levels). These findings suggest that encouraging parental involvement in BGM with 10- to 15-year-old patients with IDDM may help to prevent the well-documented deterioration in glycemic control and adherence to treatment that often occurs in later adolescence.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Responsabilidad Parental , Cooperación del Paciente , Adolescente , Adulto , Automonitorización de la Glucosa Sanguínea/estadística & datos numéricos , Niño , Estudios Transversales , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Humanos , Insulina/administración & dosificación , Entrevistas como Asunto , Masculino , Análisis MultivarianteAsunto(s)
Infecciones por VIH/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Progresión de la Enfermedad , VIH/fisiología , Infecciones por VIH/tratamiento farmacológico , Humanos , Isoniazida/uso terapéutico , Estudios Longitudinales , Análisis de Supervivencia , Factores de Tiempo , Tuberculosis Pulmonar/prevención & control , Replicación ViralRESUMEN
Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demonstrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker (RFD9). These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis.
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Seronegatividad para VIH , Pulmón/patología , Fagocitos , Tuberculosis Pulmonar/patología , Adulto , Anticuerpos Monoclonales , Lavado Broncoalveolar , Recuento de Células , Femenino , Humanos , Activación de Macrófagos , Macrófagos Alveolares , Masculino , Monocitos , Fagocitos/microbiología , Fenotipo , Tuberculosis Pulmonar/microbiologíaRESUMEN
Twenty-four patients with acute visceral leishmaniasis and leukopenia (< 1500 neutrophils/mm3) due to Leishmania chagasi were studied, 4 in an open-label pilot study and 20 in a double-blind, placebo-controlled trial. Patients received granulocyte-macrophage colony-stimulating factor (GM-CSF), 5 micrograms/kg daily, or placebo for 10 days, plus 10-20 mg/kg pentavalent antimony daily for 20 days. In GM-CSF recipients, neutrophil counts increased threefold and fourfold over baseline at 5 and 10 days, respectively, and were significantly higher than those in placebo recipients (P < .02). Eosinophil and monocyte counts were significantly increase in GM-CSF recipients at 10 days (P < or = .03). Secondary infections occurred in 3 GM-CSF and in 8 placebo recipients (P = .04). All patients had complete resolution of their leishmaniasis at 3 months. Few adverse events were recorded. GM-CSF, 5 micrograms/kg daily for 10 days, was safe, rapidly reversed neutropenia, and reduced the number of secondary infections in patients with leishmaniasis.
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Infección Hospitalaria/prevención & control , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Adolescente , Adulto , Antimonio/economía , Antimonio/uso terapéutico , Antiprotozoarios/economía , Antiprotozoarios/uso terapéutico , Médula Ósea/patología , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/economía , Costos de la Atención en Salud , Humanos , Leishmaniasis Visceral/sangre , Leishmaniasis Visceral/complicaciones , Recuento de Leucocitos , Masculino , Meglumina/economía , Meglumina/uso terapéutico , Antimoniato de Meglumina , Neutropenia/complicaciones , Neutropenia/etiología , Compuestos Organometálicos/economía , Compuestos Organometálicos/uso terapéutico , Proyectos Piloto , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
The efficacy of GM-CSF was investigated in 20 neutropenic patients (< 1500 neutrophils/microliters) with acute visceral leishmaniasis due to Leishmania chagasi. Patients were randomized to receive either GM-CSF, 5 micrograms/kg daily (intravenously or subcutaneously), or placebo for ten days, in combination with pentavalent antimony, 10-20 mg/kg daily for 20 days. Neutrophil counts were significantly greater on days 5 and 10 of treatment in the GM-CSF group compared with the placebo group (p < 0.02). Eosinophil and monocyte counts were also significantly increased in the GM-CSF group at day 10 (p < or = 0.03). Interestingly, at day 30, platelet counts were significantly increased in the GM-CSF group on days 5 and 10 (p = 0.04 and 0.02, respectively). Patients in the GM-CSF group experienced fewer secondary bacterial or viral infections than placebo patients. Infections occurred in only three patients given GM-CSF compared with eight patients given placebo (p < 0.04). All patients had complete resolution of disease symptoms at three months. Few adverse events were recorded. GM-CSF given subcutaneously at a dose of 5 micrograms/kg daily for ten days was well tolerated, reversed neutropenia rapidly and reduced the number of secondary infections in patients with leishmaniasis.
Asunto(s)
Antiprotozoarios/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Adolescente , Adulto , Antiprotozoarios/administración & dosificación , Antiprotozoarios/efectos adversos , Niño , Preescolar , Esquema de Medicación , Quimioterapia Combinada , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Pruebas Hematológicas , Humanos , Leishmaniasis Visceral/fisiopatología , Meglumina/administración & dosificación , Meglumina/efectos adversos , Antimoniato de Meglumina , Persona de Mediana Edad , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/efectos adversos , Sobreinfección/etiología , Resultado del TratamientoRESUMEN
Cocaine and its metabolites, benzoylecgonine (BZE) and ecgonine methylester (EME), were found in hair samples from ancient Peruvian coca-leaf chewers dating back to AD 1000. Hair was analyzed by gas chromatography/mass spectrometry (GC/MS) to quantitate the concentrations. The two metabolites were found in higher concentration than the parent drug. The metabolite levels appear to be below that of modern cocaine abusers. Gender does not appear to be a factor in the incorporation of drug into hair.
Asunto(s)
Cocaína/análogos & derivados , Cocaína/análisis , Cabello/química , Momias , Trastornos Relacionados con Sustancias/historia , Adulto , Cocaína/historia , Femenino , Historia Antigua , Humanos , Masculino , Persona de Mediana Edad , Perú , Detección de Abuso de Sustancias/métodosRESUMEN
An observational study of 140 HIV-seropositive asymptomatic women of childbearing age was conducted in Haiti from 1984 to 1992 as part of a larger natural history study. Forty-four women were pregnant or became pregnant during the study period. The progression to HIV-related disease, AIDS, and mortality from AIDS was compared in the pregnant and nonpregnant cohorts. The mean follow-up time was 44 months. Overall, 32 of the 140 women (38%) developed AIDS, and 26 (19%) died from AIDS during the study period, with a cumulative AIDS incidence rate of 16% at 3 years after study entry. There was a trend toward earlier manifestation of HIV-related symptoms among the pregnant cohort, but no significant difference was observed in the rate of progression to AIDS or death between the pregnant and nonpregnant women.