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OBJECTIVE: The first decision to be made in the case of community-acquired pneumonia (CAP) is whether hospitalization of the patient is mandatory. In this study, we aimed to investigate whether the addition of oxygenation parameters to CURB-65 has diagnostic value in predicting mortality in CAP. PATIENTS AND METHODS: A total of 903 CAP patients were included in the study. Patients with a CURB-65 score of 0 and 1 were classified as Group 1 and patients with a CURB-65 score of 2 or more were classified as Group 2. The prediction of mortality through Pneumonia Severity Index (PSI), CURB-65 and CURBS-65/CURBP-65 with the addition of SaO2 and PaO2 values; hence the four different models, was compared among all patient groups. RESULTS: As a result, 3.3% of the cases in Group 1 and 12.7% of the cases in Group 2 died. In both CURB-65 groups, it was noted that the frequency of patients with SaO2 <90% was significantly higher in the dead group than in the alive patient group (p=0.009 and p=0.001, respectively). In the univariate analysis, PaO2<60, and SaO2<90 were significantly associated with mortality. Model 2 (CURBS-65) and Model 3 (CURBP- 65) were examined, SaO2<90 (OR 2.08) was found to have an effect on death. In predicting mortality by the receiver operating characteristics (ROC) analysis, it was understood that the CURBS-65 score had a slightly higher area under the curve (AUC) value than CURB-65. CONCLUSIONS: As a result, it has been shown that the use of CURBS-65 scoring instead of CURB-65 clinical scoring may be more useful in predicting mortality.
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Infecciones Comunitarias Adquiridas , Neumonía , Humanos , Índice de Severidad de la Enfermedad , Infecciones Comunitarias Adquiridas/diagnóstico , Curva ROC , Neumonía/diagnóstico , Oxígeno , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Water-pipe (WP) smoking is the most common method of tobacco consumption in the Middle-East and is rapidly spreading on a global scale. Although, water-pipe smoking is linked to various diseases, such as emphysema and various types of cancers, its effect on testosterone levels has yet to be investigated. This study explores the effect of water-pipe smoking on serum testosterone levels in males in Qatar. METHODS: In this cross-sectional sample within a cohort study, we retrieved data for a total of 1000 male volunteers from the Qatar BioBank (QBB) project. A self-reported questionnaire was used to determine the water-pipe smoking status of participants. Moreover, participants were stratified based on the frequency of smoking. Total testosterone and sex hormone binding globulin (SHBG) were measured clinically, whereas free testosterone and bioavailable testosterone were calculated using Vermeulen's equation. Hormone values of 541 males (277 water-pipe smokers and 264 non-smokers) were compared using multiple regression analysis based on water-pipe smoking status after adjusting for confounding factors. RESULTS: No statistically significant difference was observed between WP smokers and non-water-pipe smokers in the likelihood of having lower or higher total testosterone, after adjustment for confounding factors. Similar results were found in free testosterone, bioavailable testosterone, and sex hormone binding globulin (all p>0.05). When compared with the reference group, both light and heavy water-pipe smokers had a similar likelihood of circulating low total testosterone levels (OR=0.83, 95% CI: 0.46-1.49; and OR=0.80, 95% CI: 0.43-1.49; respectively). CONCLUSIONS: Our results reveal, for the first time, that there is no significant change in total testosterone, free testosterone, bioavailable testosterone and sex hormone binding globulin in waterpipe smokers compared to non-water-pipe smokers. Therefore, we believe that further studies are needed to confirm the effect of water-pipe smoking on testosterone in different populations.
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BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) disease is rare, but there are serious side-effects of BP therapy in patients. In some patients, surgery is needed and could not be cured. A standard test is not available showing the risk of jaw osteonecrosis in routine use. The measurement of serum C-terminal telopeptide (CTX) levels has been used in diseases of BRONJ resorption and antiresorptive therapy. AIM: This paper is aimed at investigating the relationship between traumatic procedures and presence of BP-related osteonecrosis. MATERIALS AND METHODS: Thirty male Wistar albino rats with weighing 200 ± 20 g were used for the experimental procedures. Rats were randomly divided into three groups each containing 10 rats as follows: Group 1 (traumatic extraction group), Group 2 (atraumatic extraction group), and Group 3 (control group). All groups, zoledronic acid (ZA) (0.3 mg/kg/week) [1] was diluted with physiological saline and given subcutaneously for 2 months. After the 2 months, Group 1 was subjected to traumatic extraction of right first lower molars, and Group 2 was subjected to atraumatic extractions of the right first lower molars. Group 3 was subjected to no extractions as a control group. Animals were euthanized 32 days after tooth extractions, and the ZA administration protocol was maintained until the animals' death. After sacrifice, blood samples were collected for C-terminal cross-linking telopeptide of type I collagen (CTX-1) levels, clinical and radiological findings were recorded. RESULTS: The bone resorption marker CTX-1 showed a significant difference among the groups. CTX-1 was measured significantly higher in blood samples of Group 2 (4.15 ± 0.34; P = 0.001) than Group 1 (3.77 ± 0.34; P = 0.0001). No, statistically significant changes were found between Groups 1 and 2 as for clinical and radiological assessment. CONCLUSION: This study provides preliminary observations for the development of an animal model of BRONJ. Although clinical and radiological findings were not relevant, serum CTX values are reliable biochemical markers for predicting BRONJ and also atraumatic surgical procedures are important to prevent BRONJ.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Extracción Dental/efectos adversos , Animales , Biomarcadores/sangre , Osteonecrosis de los Maxilares Asociada a Difosfonatos/sangre , Colágeno Tipo I/sangre , Masculino , Péptidos/sangre , Ratas Wistar , Ácido ZoledrónicoRESUMEN
OBJECTIVE: To examine the effects of caffeic acid phenethyl ester (CAPE; a component of honey bee-hive propolis with antioxidant, anti-inï¬ammatory, antiviral and anticancer properties) on bone regeneration and fibrotic healing in a rat model. METHODS: Male Sprague-Dawley rats (n = 63; mean age 7 weeks; weight 280-490 g) were randomly divided into three groups: A, cranial defect with no bone healing treatment (n = 21); B, cranial defect treated with CAPE (n = 21); C, cranial defect treated with CAPE and ß-tricalcium phosphate/hydroxyl apatite (n = 21). Rats were anaesthetized with ketamine (8 mg/100 g) by intraperitoneal injection and a cranial critical size bone defect was created. Following surgery, CAPE (10 µmol/kg) was administered by daily intraperitoneal injection. Seven rats in each group were killed at days 7, 15 and 30 following surgery. Bone regeneration, fibrotic healing and osteoblast activity were evaluated by histopathology. RESULTS: Statistically significant differences in healing were found between all groups. There were no statistically significant within-group differences between day 7 and 15. At day 30, bone healing scores were significantly higher in groups B and C compared with group A. CONCLUSION: CAPE significantly improved bone-defect healing in a rat model, suggesting that CAPE has beneficial effects on bone healing.
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Antiinflamatorios no Esteroideos/farmacología , Regeneración Ósea/efectos de los fármacos , Ácidos Cafeicos/farmacología , Alcohol Feniletílico/análogos & derivados , Cráneo/efectos de los fármacos , Animales , Materiales Biocompatibles , Regeneración Ósea/fisiología , Fosfatos de Calcio/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Alcohol Feniletílico/farmacología , Ratas , Ratas Sprague-Dawley , Cráneo/lesionesRESUMEN
BACKGROUND AND OBJECTIVES: Dental laboratory technicians (DLTs) have much exposure to mineralogical dust that may have adverse effects on their lung health. The aim of our study was to investigate occupational dust exposure, and to determine the frequency of respiratory function disorders and radiologic abnormalities among DLTs. MATERIALS AND METHODS: The study enrolled 94 DLTs who were exposed to dust in dental laboratories and 94 control subjects. Dust concentrations in the workplaces were measured. RESULTS: The mean age of DLTs was 30.70 ± 9.84 years. No significant difference was found between the DLTs and the control groups for age or smoking status (p > 0.05). Spirometric values for the DLTs were found to be lower than the control group (p < 0.05). The mean working period for DLTs was 9.19±5.9 years. The pulmonary function test results for the DLTs showed that 65.9% had a normal pattern, 22.4% were restrictive, and 11.7% showed obstructive type pulmonary function disorder. Negative correlations were found between the working period time and Forced Expiratory Volume in 1 second in the DLTs (R = -0.675 p = 0.000). Negative correlations were also found between working period time and Forced Vital Capacity in the DLTs (R = -0.720 p = 0.000). All DLTs had chest X-rays and 16 (17%) of them showed radiological pneumoconiosis. CONCLUSIONS: This study showed a negative association between level of respiratory function and working period in DLTs.
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Técnicos Dentales , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Trastornos Respiratorios/etiología , Adulto , Polvo , Femenino , Humanos , Laboratorios , Personal de Laboratorio , MasculinoRESUMEN
In this study, Molecular weight (MW) distributions of a full-scale landfill leachate treatment plant consisting of membrane bioreactor (MBR) and nanofiltration (NF) membrane were investigated. The leachate was sampled from the equalization tank, and effluents of MBR and NF membrane in the landfill leachate treatment plant. Parameters of COD, TOC, TKN, NH4(+)-N and UV(254, 280 and 320) absorbance were analyzed to evaluate both the removal performance of the plant and MW distributions. MW distribution of samples were determined by ultrafiltration (UF) (100 kDa, 10 kDa, 5 kDa, 1 kDa and 500 Da) membranes. The results indicated that organic matter of one third percent is particulate or colloidal form and almost half of the organic fraction has a lower MW than 500 Da. In addition, organic matter had hydrophilic character. Most part of TKN was>500 Da with the corresponding rate of 92%. Further, UV absorbance of raw leachate (RW) decreased 85% after 500 Da.
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Reactores Biológicos , Administración de Residuos , Contaminantes Químicos del Agua/análisis , Filtración , Membranas Artificiales , Peso Molecular , Compuestos de Nitrógeno/análisis , Espectrofotometría UltravioletaRESUMEN
PURPOSE: The aim of this study was to compare the correlation between bispectral index (BIS) monitor and four commonly used subjective clinical scales (Ramsay Sedation Scale (RSS), Richmond Agitation Sedation Scale (RASS), Sedation Agitation Scale, Adaptation to Intensive Care Environment scale) in mechanically ventilated patients in intensive care unit (ICU). In addition, comparison of responsiveness of the clinical scales in respect to BIS changes is another goal of this study. MATERIALS AND METHODS: Mechanically ventilated thirty patients who required sedation for any reason were enrolled to study. Patients who needed neuromuscular blockade, patients with known hearing and visual problems, neurological diseases, anoxic encephalopathy, mental retardation and who developed hemodynamic instability (mean arterial pressure below 60 mmHg) and hypoxemia (sPO2 below 90%) during follow-up were excluded. Starting before the initiation of sedation, first BIS scores then clinical sedation scales were evaluated. This procedure is repeated every 2 hours for 24 hours. RESULTS: All of the four clinical scales were significantly correlated with BIS. BIS and clinical scale values, except Adaptation to Intensive Care Environment scale, showed significant changes compared to baseline after the initiation of sedation. Ramsay and Richmond scales showed the highest correlation with BIS (respectively, r = 0.758, r = 0.750). Adaptation to Intensive Care Environment revealed the lowest correlation (r = 0.565). CONCLUSIONS: All of the scales were significantly correlated with BIS. RSS and RASS showed higher correlation than other scales. As a conclusion: RSS and RASS can be used for monitoring the depth of sedation in mechanically ventilated patients in ICU.
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Monitores de Conciencia , Estado de Conciencia/efectos de los fármacos , Indicadores de Salud , Hipnóticos y Sedantes/uso terapéutico , Unidades de Cuidados Intensivos , Monitoreo Fisiológico , Respiración Artificial , APACHE , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Valor Predictivo de las Pruebas , Agitación Psicomotora , Factores de Tiempo , TurquíaRESUMEN
OBJECTIVES: The main objective of this study was to make a comparison between the relaxation rates in jaw cysts and abscesses. Such a comparison should provide quantitative information for MR image analysis. METHODS: A phantom containing 20 odontogenic jaw cysts and 11 jaw abscesses was imaged with 1.5 T MR. T(1) measurements were performed by using a mixed sequence of inversion recovery and spin echo, while T(2) measurements were carried out by the Carr-Purcell Meiboom-Gill (CPMG) sequence. Cystic fluids and abscesses were compared statistically. RESULTS: In cysts and abscesses, respectively, the mean 1/T(1) was 0.9355 s(-1) and 0.8245 s(-1) and the mean 1/T(2) was 2.4575 s(-1) and 4.7073 s(-1). The 1/T(2) in cysts was very highly significantly different from that in abscesses (p = 0.0001). Both T(1) and T(2) were linearly proportional to material contents. T(2) relaxivities [26.458 ml (g s)(-1) for abscesses and 21.455 ml (g s)(-1) for cysts] were higher than T(1) relaxivities [5.4766 ml (g s)(-1) for abscesses and 10.075 ml (g s)(-1) for cysts]. DISCUSSION: Present T(2) measurements differentiate cysts from abscesses with a confidence interval of 95%. Because in vivo and in vitro image contrasts are changed by the same parameters, the T(2) findings should present valuable information for in vivo MRI. Hence the significant difference and the relaxivities may provide quantitative information for clinicians and researchers making image analyses. CONCLUSION: T(2) may differentiate cysts from abscesses. The difference in T(2) is related to the material content of samples.
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Absceso/diagnóstico , Quistes Maxilomandibulares/diagnóstico , Enfermedades Maxilomandibulares/diagnóstico , Imagen por Resonancia Magnética/métodos , Análisis de Varianza , Diagnóstico Diferencial , Humanos , Fantasmas de ImagenRESUMEN
BACKGROUND AND OBJECTIVES: Bone healing is still one of the most important problems of the oral and maxillofacial surgery procedures. This study was designed to evaluate the effect of sildenafil citrate (which is used for erectile dysfunction) on bone defect healing in an experimental animal model. MATERIALS AND METHODS: A total of 42 male Wistar-albino rats were randomly assigned to the control group (n=21) or the study group (n=21). The control group was fed on a standard laboratory diet until 12 h before surgery, whereas the study group received Sildenafil citrate via orogastric tube 10 mg/kg once a day for 30 days. Under anaesthesia, a 3 x 3 x 2 mm depth defect was made on tibia of each rat. 7 animals from each group were euthanised on postoperative days 7,15 and 30. Bone samples were taken for examination, histologically on day 7, by 3D dental tomography on day 15, and for bone strength resistance on day 30. RESULTS: Statistically significant differences were determined between the groups from the inflammatory and repair phase, with the healing process being more advanced in the Sildenafil group. CONCLUSIONS: Sildenafil citrate can be used as a supporting factor to accelerate the healing process of bone. In future comprehensive studies will need to demonstrate the Sildenafil citrate affect on bone defect healing.
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Huesos/efectos de los fármacos , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Animales , Huesos/irrigación sanguínea , Huesos/patología , Hiperemia , Masculino , Óxido Nítrico Sintasa/metabolismo , Purinas/uso terapéutico , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Citrato de Sildenafil , Tibia/irrigación sanguínea , Tibia/patología , Fracturas de la Tibia/tratamiento farmacológico , Fracturas de la Tibia/patología , Tomografía Computarizada por Rayos XRESUMEN
AIM: To determine the relationship between bruxism and cardiovascular diseases. MATERIALS AND METHODS: 120 patients who referred to the Dentistry Faculty with the complaint of bruxism were selected. All patients gave informed consent for participation in the study. All of the patients were examined and bruxism was classified. And also these were examined by B-mode ultrasound to measure the Intima Media Thickness (IMT) at the far wall of the common carotid artery. A wide range of vascular risk factors including age, gender, body mass index, and previous history were surveyed. Spearman correlation analysis was performed to ascertain quantitative comparison, Mann-Whitney U and Kruskal-Wallis test were used for comparison of means RESULTS: There were 66 (55%) male and 54 (45%) female patients, with a female to male ratio of 1/1.2. The mean age was 35.6 +/- 1,25 years (range 18-65 years). In the analysis of bruxism classification and IMT there was a statistical significance between bruxism classification subgroup 1, 2, 3 and IMT. There was no statistical significance between bruxism classification Subgroup 4 and IMT due to the small number of the patients (n = 12). CONCLUSIONS: Stressful situations can cause both bruxism and cardiovascular disease such as coronary artery diseases, hypertension, arrhythmias, cardiomyopathy. The statistical analysis supported this hypothesis. However, we need to new studies with large number of samples to confirm this hypothesis. Clearly, future studies in this field will need to take into consideration the influence of the following variables: age, use of medication or drugs, smoking habits, and other sleep disorders.
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Bruxismo/etiología , Enfermedades Cardiovasculares/diagnóstico , Grosor Intima-Media Carotídeo , Estrés Psicológico/etiología , Adolescente , Adulto , Anciano , Bruxismo/clasificación , Bruxismo/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
We present a theory to quantify a fundamental limit on correlated photon pairs generated through four-wave mixing inside optical fibers in the presence of spontaneous Raman scattering (SpRS). Our theory is able to explain current experimental data. We show that if correlated photon pairs are generated with polarization orthogonal to the pump the effect of SpRS is significantly reduced over a broad spectral region extending from 5 to 15 THz.
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Transfer of intensity noise from pumps to signal in dual-pump fiber-optic parametric amplifiers is simulated numerically for a realistic configuration in which both pumps are amplified and filtered before they enter the fiber. The walk-off effects induced by different group velocities of pumps, signal, and idler are fully taken into account. It is found that the optical signal-to-noise ratio can be as low as 15 dB when the amplifier length is close to 0.5 km, but it can be improved by 3 dB or so by use of longer fibers.
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We consider the evolution of optical solitons inside a nonlinear dispersive fiber with random birefringence, causing polarization-mode dispersion. We convert the pair of coupled nonlinear Schrödinger equations satisfied by the orthogonally polarized components into a Fokker-Planck equation using the collective-variable approach. We solve this equation and derive expressions for the probability density functions associated with the differential group delay and the pulse width in the limit of large propagation distances.
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Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin's lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisolona/administración & dosificación , Radioterapia Adyuvante , Inducción de Remisión , Análisis de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: A potential problem for malaria vaccine development and testing is between-host variation in antibody responses to specific malaria antigens. Previous work in adults in an area highly endemic for Plasmodium falciparum in Papua New Guinea found that genetic regulation partly explained heterogeneity in responsiveness. We have now assessed the relative contributions of environmental and genetic factors in total IgG responses to specific malaria antigens in children, and quantified temporal variation within individuals of total IgG responses. METHODS: Total IgG responses against schizont extract, merozoite surface protein-1, merozoite surface protein-2, ring-infected erythrocyte surface antigen, and SPf66 were measured by ELISA. Variance component analysis was used to estimate the variation explained by genetic and environmental factors in these antibody responses. Intra- and inter-class correlations of antibody responses within relative pairs were estimated. We adjusted for age, P. falciparum density, sex and village differences either within or prior to the analysis. RESULTS: For all malaria antigens, temporal variation in the total IgG response was the predominant source of variation. There was substantial familial aggregation of all IgG responses, but it remained unclear how much this clustering was attributable to genetic factors and how much to a common environment in the household. The remaining variance, which could not be explained by either of the above, was very small for most of the antigens. CONCLUSIONS: Temporal variation and clustering of immune responses to specific malaria antigens need to be taken into account when planning, conducting and interpreting immuno-epidemiological and vaccine studies.
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Inmunoglobulina G/inmunología , Vacunas contra la Malaria/inmunología , Malaria/inmunología , Animales , Formación de Anticuerpos , Antígenos de Protozoos/inmunología , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/genética , Masculino , Linaje , Plasmodium falciparum/inmunología , Factores de TiempoRESUMEN
A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.
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Anticuerpos Antiprotozoarios/biosíntesis , Antígenos de Protozoos/inmunología , Vacunas contra la Malaria/inmunología , Proteína 1 de Superficie de Merozoito/inmunología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Vacunación , Adyuvantes Inmunológicos , Adulto , Animales , Anticuerpos Antiprotozoarios/inmunología , Citocinas/sangre , Citotoxicidad Inmunológica , Humanos , Inmunización Secundaria , Vacunas contra la Malaria/efectos adversos , Malaria Falciparum/prevención & control , Masculino , Manitol/análogos & derivados , Manitol/inmunología , Persona de Mediana Edad , Ácidos Oléicos/inmunología , Papúa Nueva Guinea , Plasmodium falciparum/crecimiento & desarrollo , Seguridad , Linfocitos T/inmunología , Vacunación/efectos adversosRESUMEN
Serum levels of reactive nitrogen intermediates (RNI; nitrate + nitrite), interferon gamma (IFN gamma) and tumour necrosis factor (TNF) were measured in 177 Papua New Guinean children with different clinical manifestations of malaria. The groups investigated were asymptomatic parasitaemic, mild malaria, cerebral malaria survivors and cerebral malaria non-survivors. The levels of TNF were highest among the cases of cerebral malaria who died and lowest among the asymptomatic parasitaemic children (mean log TNF levels 2.183 pg/mL vs. 1.455 pg/mL; P = 0.001). Similarly, the levels of IFN gamma were highest among the cerebral and lowest among the asymptomatic patients (mean log TNF levels 0.338 pg/mL vs 0.054 pg/mL; P < 0.0001). RNI levels were high among both the asymptomatic parasitaemic group and those who died due to cerebral malaria (mean log RNI levels 1.56 microM vs. 1.412 microM; P = 0.18). The ratio of RNI to TNF, however, was significantly higher among the asymptomatic parasitaemic children and lowest among those who died due to cerebral malaria (mean log (RNI:TNF) ratio 0.118 vs. -0.789; P < 0.001). We concluded that the ratio of serum RNI to serum TNF is a more useful indicator of outcome of falciparum malaria in this population than the absolute levels of either alone.
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Interferón gamma/sangre , Malaria Falciparum/diagnóstico , Óxido Nítrico/sangre , Factor de Necrosis Tumoral alfa/análisis , Biomarcadores/sangre , Preescolar , Femenino , Humanos , Masculino , Papúa Nueva Guinea , PronósticoRESUMEN
The interaction between malnutrition and malaria is complex and there is evidence that malnutrition decreases the susceptibility to malaria. To investigate the relation between anthropometric measurements and subsequent malaria morbidity and to examine whether the effect observed was due to interaction with host immunity, we followed for 1 y a cohort of 136 children aged 10 to < 120 mo in Wosera, East Sepik Province, Papua New Guinea. At baseline, 21% were stunted, 10% were wasted, and 5% were both stunted and wasted. After adjustment for age and use of bed nets, height-for-age z score (HAZ) at baseline predicted the number of clinical episodes of falciparum malaria during the following year: incidence rate increased with increasing HAZ. Humoral responses to specific malarial antigens were lowest in the wasted children. The prevalence of lymphoproliferative responders was not significantly different between well-nourished and undernourished children. In contrast, the prevalence of cytokine producers was higher in the undernourished than in the well-nourished children. Our findings support the view that stunting but not wasting protects against falciparum malaria. The mechanism may be related to an improved ability of malnourished children to produce certain cytokines in response to stimulation by specific malarial antigens.
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Antropometría , Malaria Falciparum/epidemiología , Formación de Anticuerpos , Antígenos de Protozoos/aislamiento & purificación , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Citocinas/sangre , Susceptibilidad a Enfermedades , Humanos , Inmunidad Celular , Lactante , Estudios Longitudinales , Malaria Falciparum/inmunología , Nueva Guinea/epidemiología , Trastornos Nutricionales/complicaciones , Estado NutricionalRESUMEN
In this review we summarise the arguments that inflammatory cytokines, triggered by material released from the parasite at schizogony (malarial toxin), might induce the illness and pathology seen in malaria. These pro-inflammatory cytokines can generate inducible nitric oxide synthase and cause nitric oxide to be released, as can low concentrations of malarial toxin itself provided interferon-gamma, which has only low activity in the absence of malarial toxin, is present. We suggest here that recently described hypermetabolic functions of these mediators provide a much more plausible explanation for malarial hyperlactataemia and hypoglycaemia, the chief prognostic indicators in falciparum malaria, than does hypoxia secondary to mechanical blockage of vessels by sequestering parasites, which is the dominant current theory. We also review the arguments that rationalise, through these mediators, the reversibility of the coma of cerebral malaria. Although not yet tested at a cellular level, the proposal that nitric oxide generated in cerebral vascular walls contributes to this coma continues to gather indirect support. In addition, new evidence incriminating nitric oxide in the mechanism of tolerance to endotoxin rationalises the raised nitric oxide generation seen in malarial tolerance.
Asunto(s)
Malaria/etiología , Animales , Metabolismo de los Hidratos de Carbono , Citocinas/fisiología , Humanos , Hipoglucemia/etiología , Tolerancia Inmunológica , Mediadores de Inflamación/fisiología , Ácido Láctico/sangre , Malaria/inmunología , Malaria/fisiopatología , Malaria Cerebral/etiología , Óxido Nítrico/fisiologíaRESUMEN
Plasmodium vivax Duffy binding protein (DBP) is a conserved functionally important protein. P. vivax DBP is an asexual blood-stage malaria vaccine candidate because adhesion of P. vivax DBP to its erythrocyte receptor is essential for the parasite to continue development in human blood. We developed a soluble recombinant protein of P. vivax DBP (rDBP) and examined serologic activity to it in residents of a region of high endemicity. This soluble rDBP product contained the cysteine-rich ligand domain and most of the contiguous proline-rich hydrophilic region. rDBP was expressed as a glutathione S-transferase (GST) fusion protein and was isolated from GST by thrombin treatment of the purified fusion protein bound on glutathione agarose beads. P. vivax rDBP was immunogenic in rabbits and induced antibodies that reacted with P. vivax and Plasmodium knowlesi merozoites. Human sera from adult residents of a region of Papua New Guinea where malaria is highly endemic or P. vivax-infected North American residents reacted with rDBP in an immunoblot and an enzyme-linked immunosorbent assay. The reactivity to reduced, denatured P. vivax rDBP and the cross-reactivity with P. knowlesi indicated the presence of immunogenic conserved linear B-cell epitopes. A more extensive serologic survey of Papua New Guinea residents showed that antibody response to P. vivax DBP is common and increases with age, suggesting a possible boosting of the antibody response in some by repeated exposure to P. vivax. A positive humoral response to P. vivax DBP correlated with a significantly higher response to P. vivax MSP-1(19). The natural immunogenicity of this DBP should strengthen its usefulness as a vaccine.