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BACKGROUND: Sri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining vigilance is important. All malaria cases are investigated epidemiologically and followed up by integrated drug efficacy surveillance (iDES). Occasionally, that alone is not adequate to differentiate Plasmodium falciparum reinfections from recrudescences. This study evaluated the World Health Organization and Medicines for Malaria Venture (MMV) recommended genotyping protocol for the merozoite surface proteins (msp1, msp2) and the glutamate-rich protein (glurp) to discriminate P. falciparum recrudescence from reinfection in POR phase. METHODS: All P. falciparum patients detected from April 2014 to December 2019 were included in this study. Patients were treated and followed up by iDES up to 28 days and were advised to get tested if they develop fever at any time over the following year. Basic socio-demographic information including history of travel was obtained. Details of the malariogenic potential and reactive entomological and parasitological surveillance carried out by the Anti Malaria Campaign to exclude the possibility of local transmission were also collected. The msp1, msp2, and glurp genotyping was performed for initial and any recurrent infections. Classification of recurrent infections as recrudescence or reinfection was done based on epidemiological findings and was compared with the genotyping outcome. RESULTS: Among 106 P. falciparum patients, six had recurrent infections. All the initial infections were imported, with a history of travel to malaria endemic countries. In all instances, the reactive entomological and parasitological surveillance had no evidence for local transmission. Five recurrences occurred within 28 days of follow-up and were classified as recrudescence. They have not travelled to malaria endemic countries between the initial and recurrent infections. The other had a recurrent infection after 105 days. It was assumed a reinfection, as he had travelled to the same malaria endemic country in between the two malaria attacks. Genotyping confirmed the recrudescence and the reinfection. CONCLUSIONS: The msp1, msp2 and glurp genotyping method accurately differentiated reinfections from recrudescence. Since reinfection without a history of travel to a malaria endemic country would mean local transmission, combining genotyping outcome with epidemiological findings will assist classifying malaria cases without any ambiguity.
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Demência Frontotemporal , Malária Falciparum , Proteína 1 de Superfície de Merozoito , Distrofia Muscular do Cíngulo dos Membros , Miosite de Corpos de Inclusão , Osteíte Deformante , Masculino , Humanos , Proteína 1 de Superfície de Merozoito/genética , Plasmodium falciparum/genética , Reinfecção , Proteínas de Protozoários/genética , Proteínas de Protozoários/uso terapêutico , Antígenos de Protozoários/genética , Antígenos de Protozoários/uso terapêutico , Genótipo , Ácido Glutâmico , Sri Lanka/epidemiologia , Variação Genética , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/tratamento farmacológico , RecidivaRESUMO
Longitudinal changes of serum angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) associated with endothelial stability in dengue patients with different disease stages were studied. Serum Ang-1 and Ang-2 levels were measured in confirmed dengue fever (DF) patients on admission (DFA, n = 40) and discharge (DFD, n = 20); in dengue hemorrhagic fever (DHF) patients on admission (DHFA, n = 40), at critical stage (DHFC, n = 36), and on discharge (DHFD, n = 20); and in healthy controls (HC, n = 25). DHFC had the highest serum Ang-2 and lowest Ang-1 levels compared to DFA, DHFA, and HC (P < 0.050). The ratio of serum Ang-2/Ang-1 in DHFC was the highest among all study categories tested (P < 0.001). Significant positive correlations were observed between serum Ang-1 and platelet count in DHFA (Pearson r = 0.653, P < 0.001) and between Ang-1 and pulse pressure in DHFC (r = 0.636, P = 0.001). Using a cutoff value of 1.01 for the Ang-2/Ang-1 ratio for DHFC, a sensitivity of 83.2% and a specificity of 81.2% discerning DF from DHF were obtained. Therefore, serum Ang-2/Ang-1 could be used as a biomarker for endothelial dysfunction in severe dengue at the critical stage.
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Dengue , Dengue Grave , Angiopoietina-1 , Angiopoietina-2 , Dengue/diagnóstico , Humanos , Soro , Dengue Grave/diagnósticoRESUMO
The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases (P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses (P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered (r = -0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.
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Anti-Infecciosos/uso terapêutico , Citocinas/sangue , Leptospirose/sangue , Leptospirose/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , MasculinoRESUMO
A new resveratrol trimer, vateriferol (1), having four cis-oriented methine protons and constituting four contiguous stereocenters, was isolated from the bark extract of Vateria copallifera by bioassay-guided fractionation using a combination of normal, reversed phase, and size exclusion column chromatography. The structure was established based on its spectroscopic data. Vateriferol (1) was evaluated in vitro for its antioxidant capacity, enzyme inhibitory activity, growth inhibitory activity on a number of cancer cell lines, neuroprotective activity, and anti-inflammatory activity. Vateriferol (1) exhibited AChE inhibitory activity (IC50 8.4 ± 0.2 µM), ORAC activity (2079 ± 0.20 TE/g), and neuroprotective activity at 1.5 µM using PC12 cells deprived of oxygen and glucose and lowered NO levels in lipopolysaccharide-stimulated SIM-A9 microglial cells at 14.7 and 73.6 µM. Vateriferol (1) exhibited weak cytotoxic potency (<50% growth inhibition) against the tested cell lines at 147.2 µM.
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Dipterocarpaceae/química , Resveratrol/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Células PC12 , Casca de Planta/química , Ratos , Sri LankaRESUMO
BACKGROUND: Leptospirosis is often treated based on clinical diagnosis. There is a need for rapid laboratory diagnosis for this condition. The aim of this study was to compare the diagnostic accuracy of two rapid IgM based immunodiagnostic assays with the microscopic agglutination test (MAT), in acute leptospirosis infection. METHODS: MAT, IgM based immunochromatographic test (Leptocheck-WB) and IgM ELISA were performed using acute sera of patients clinically suspected to have leptospirosis (n = 83). Bayesian latent class modeling was used to compare the accuracy of these tests. RESULTS: Percentage positivity for MAT, Leptocheck-WB, and IgM ELISA were 48.1, 55.3, and 45.7 % respectively. Bayesian latent class modeling showed a combined positivity rate of leptospirosis of 44.7 %. The sensitivity of MAT, Leptocheck-WB and IgM ELISA were 91.4, 95 and 81.1 %, and specificity were 86.7, 76.4 and 83.1 %, respectively. CONCLUSIONS: Leptocheck-WB has high sensitivity, and, because it is quick and easy to perform, would be a good screening test for acute leptospirosis infection. IgM ELISA has good specificity, and is comparable with MAT; given that it is easier to perform and more widely available than MAT, it would be a more appropriate confirmatory test for use in hospitals with limited access to a specialized laboratory.
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Anticorpos Antibacterianos/sangue , Imunoglobulina M/sangue , Leptospirose/diagnóstico , Adulto , Idoso , Testes de Aglutinação , Teorema de Bayes , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitais , Humanos , Leptospirose/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sri LankaRESUMO
Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical countries. The research base on leptospirosis is not as strong as other tropical infections such as malaria. However, it is a lethal infection that can attack many vital organs in its severe form, leading to multi-organ dysfunction syndrome and death. There are many gaps in knowledge regarding the pathophysiology of leptospirosis and the role of host immunity in causing symptoms. This hinders essential steps in combating disease, such as developing a potential vaccine. Another major problem with leptospirosis is the lack of an easy to perform, accurate diagnostic tests. Many clinicians in resource limited settings resort to clinical judgment in diagnosing leptospirosis. This is unfortunate, as many other diseases such as dengue, hanta virus, rickettsial infections, and even severe bacterial sepsis, can mimic leptospirosis. Another interesting problem is the prediction of disease severity at the onset of the illness. The majority of patients recover from leptospirosis with only a mild febrile illness, while a few others have severe illness with multi-organ failure. Clinical features are poor predictors of potential severity of infection, and therefore the search is on for potential biomarkers that can serve as early warnings for severe disease. This review concentrates on these three important aspects of this neglected tropical disease: diagnostics, developing a vaccine, and potential biomarkers to predict disease severity.
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Vacinas Bacterianas/imunologia , Técnicas Genéticas , Imunoensaio/métodos , Leptospira/genética , Leptospirose/diagnóstico , Animais , Vacinas Bacterianas/genética , Biomarcadores/sangue , Humanos , Leptospira/imunologia , Leptospira/isolamento & purificação , Leptospirose/sangue , Leptospirose/imunologia , Leptospirose/microbiologiaRESUMO
Enterobiasis (pinworm infection) caused by Enterobius vermicularis is a common parasitic infection prevalent worldwide especially in children. Infection is diagnosed by microscopic detection of E. vermicularis eggs on perianal swabs. This study aimed to characterize the antigens of E. vermicularis eggs as a preliminary step towards identifying diagnostic targets for detection in infected individuals. The study was conducted between October 2019 and February 2020, following approval from Ethics Review Committee of the Faculty of Medicine, University of Colombo (EC-19-034). E. vermicularis eggs were harvested from perianal swabs using acetone and purified with 1× PBS (pH 7.2). A portion of eggs was used for preparing antigen slides, while the rest were sonicated and vortexed with glass beads and inoculated subcutaneously (with weekly booster doses) into a Wistar rat for developing antibodies. Blood drawing from rat was done weekly for 5 weeks. Confirmation of the presence of antibodies was done by surface immunofluorescence against eggs on the antigen slides. Protein bands were determined using SDS-PAGE assay and immunogenic antigen bands were determined by reacting with antiserum after immunoblotting. The band sizes of the proteins were determined against corresponding bands of a protein ladder. Surface immunofluorescence was positive with serum obtained from day 14 post-inoculation from the Wistar rat as well as that obtained from a person with chronic enterobiasis. The most prominent and immunogenic protein bands identified from egg antigens were 21 kDa, 66 kDa, 83 kDa, 96 kDa, 112 kDa, 121 kDa, 140 kDa and 151 kDa. Methods used in this study were effective in obtaining E. vermicularis egg antigens which were immunogenic. Furthermore, surface antigens of intact eggs reacted with antibodies developed against crushed egg antigens. These findings may pave the way for the development of effective immunodiagnostics.
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Enterobíase , Enterobius , Animais , Enterobíase/diagnóstico , Enterobíase/parasitologia , Humanos , Ratos , Ratos WistarRESUMO
Ion transport modulators are most commonly used to treat various noncommunicable diseases including diabetes and hypertension. They are also known to bind to receptors on various immune cells, but the immunomodulatory properties of most ion transport modulators have not been fully elucidated. We assessed the effects of thirteen FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, omeprazole, pantoprazole, phenytoin, verapamil, drug X, and drug Y on superoxide production, nitric oxide production, and cytokine expression by THP-1-derived macrophages that had been stimulated with ethanol-inactivated Mycobacterium bovis BCG. Ambroxol HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, pantoprazole, phenytoin, verapamil, and drug Y had an inhibitory effect on nitric oxide production, while all the test drugs had an inhibitory effect on superoxide production. Amiloride HCl, diazoxide, digoxin, furosemide, phenytoin, verapamil, drug X, and drug Y enhanced the expression of IL-1ß and TNF-α. Unlike most immunomodulatory compounds currently in clinical use, most of the test drugs inhibited some inflammatory processes while promoting others. Ion pumps and ion channels could therefore serve as targets for more selective immunomodulatory agents which do not cause overt immunosuppression.
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Inflamação/tratamento farmacológico , Macrófagos/imunologia , Moduladores de Transporte de Membrana/uso terapêutico , Mycobacterium bovis/imunologia , Ambroxol/uso terapêutico , Células Cultivadas , Humanos , Imunomodulação , Interleucina-1beta/metabolismo , Transporte de Íons , Macrófagos/efeitos dos fármacos , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia zeylanica (L.) Less (Family: Compositae) is a medicinal plant used as external applications for boils, bone fractures, eczema and internally for asthma in traditional medicine in Sri Lanka. Anti-nociceptive, anti-bacterial and anti-proliferative activities have been reported previously. AIM OF THE STUDY: To investigate the anti-inflammatory activity of methanol/dichloromethane extract (MDE) of leaves of V. zeylanica by assessing in vivo inhibition of rat paw-edema, in vitro inhibition of the production of nitric oxide (NO) and superoxide and inhibitory effect on inducible nitric oxide synthase (iNOS) gene expression. MATERIALS AND METHODS: In vivo anti-inflammatory activity of MDE was tested at the dose of 1500 mg/kg using rat paw-edema model. Indomethacin and Gum acacia was used as the positive and vehicle control respectively. In vitro NO inhibitory activity of 7.8-250 µg/ml MDE was tested using lipopolysaccharide (LPS)-stimulated (1 µg/ml) mouse macrophages (RAW264.7 cells) and rat peritoneal cells (RPC) obtained following carrageenan-induction (5 mg/Kg). Griess method was used to quantify the nitrite levels in culture supernatants. In vitro inhibition of superoxide production of Phorbal 12-myristate 13-acetate (PMA)-stimulated RAW cells was determined by quantitative Nitroblue Tetrazolium (NBT) assay. N-monomethyl-L-arginine acetate (NMMA) (1 mM) and Diphenyleneiodonium chloride (DPI) (10 µM) were used as the positive controls for inhibitory activity of NO and superoxide production respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was carried out to test the inhibitory effect on mRNA expression of iNOS gene. RESULTS: Treatment with MDE of V. zeylanica at 1500 mg/kg showed significant inhibition of paw-edema from 1st-5th hour (P < 0.01) compared with the control. The reference drug, indomethacin showed a biphasic pattern and its highest inhibition was (98.3 ± 7.1%) at 4th h (P < 0.01). MDE of V. zeylanica showed similar inhibition of paw-edema with highest inhibition recorded as 94.5 ± 5.28%, at 5th h (P < 0.01). The inhibitory concentration (IC50) of MDE for in vitro NO inhibitory activity was 105 µg/ml for RAW cells and 80 µg/ml for RPCs. Both NO inhibitory activities showed significant dose-dependency (r = 0.998 and r = 0.915 respectively; p < 0.05). MDE concentration of 250 µg/ml showed 55% inhibition of ROS production in RAW cells. NMMA showed 78% and 70.1% inhibition of NO production with RAW cells and RPCs whereas DPI showed 61% superoxide inhibitory activity with RAW cells. NO inhibitory activity of MDE on RAW cells was confirmed by the significant reduction (99.1%) in iNOS gene expression. CONCLUSION: These results demonstrated potent anti-inflammatory activity of MDE of V. zeylanica reflected by its significant in vivo inhibition of rat paw-edema, in vitro inhibition of NO and superoxide production, and the reduction of iNOS gene expression. Thus, further purification and isolation of bioactive compounds from V. zeylanica are emphasized.
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Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vernonia , Animais , Anti-Inflamatórios/farmacologia , Carragenina , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/genética , Edema/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Cavidade Peritoneal/citologia , Extratos Vegetais/farmacologia , Folhas de Planta , Células RAW 264.7 , Ratos Wistar , Superóxidos/metabolismoRESUMO
This study aimed at investigating the anti-inflammatory potential of essential oil from rhizome and leaf of Alpinia calcarata Rosc. (ACEO) with the focus of its topical anti-inflammatory activity along with its dominant compounds 1,8-cineole and α-terpineol using mouse ear edema model. ACEOs were analyzed by GC-MS. The anti-inflammatory activity was determined by studying the inhibition of overproduction of proinflammatory mediators-nitric oxide, reactive oxygen species, prostaglandins, cyclooxygenases, and cytokines induced by lipopolysaccharides in murine macrophages. Topical anti-inflammatory and antinociceptive activity was studied by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation and formalin-induced pain model in mice, respectively. Rhizome oil has 1,8-cineole (31.08%), α-terpineol (10.31%), and fenchyl acetate (10.73%) as major compounds whereas the ACEO from leaves has 1,8-cineole (38.45%), a-terpineol (11.62%), and camphor (10%). ACEOs reduced the production of inflammatory mediators in vitro in a concentration-dependent manner. Further, ACEO and its major compounds reduced ear thickness, weight, myeloperoxidase, and cytokines significantly (p < 0.01) in mouse ear. Dose-dependent reduction in flinching and licking in both the phases of pain sensation concludes the topical analgesic effect. Our findings suggest the potency of topical use of ACEOs for inflammatory disease conditions.
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There is an urgent need for better and safer therapeutic interventions for tuberculosis (TB). We assessed the effects of FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide (HCTZ), metformin, omeprazole, pantoprazole, phenytoin, verapamil, and drug X and Y on the growth of free and intracellular Mycobacterium bovis BCG. Free and intracellular M. bovis BCG were cultured in the presence or absence of the test drugs for 3 to 9 days and then quantified. For both free and intracellular bacteria, cultures that were exposed to furosemide, phenytoin, or drug Y yielded lower bacteria counts compared to drug-free controls (p < 0.05). The same was observed with diazoxide, HCTZ, verapamil, and drug X, but only for intracellular M. bovis BCG (p < 0.05). To assess the effects of the drugs on bactericidal activity of rifampicin, free and intracellular M. bovis BCG were treated with rifampicin alone or in combination with each of the thirteen test drugs for 3 to 9 days. For extracellular bacteria, higher bacteria clearance rates were observed in cultures exposed to rifampicin in combination with amiloride HCl, diazoxide, digoxin, furosemide, HCTZ, metformin, pantoprazole, phenytoin, drug X, or drug Y than those exposed to rifampicin alone, indicating that rifampicin had a synergistic effect with these test drugs. Rifampicin was also synergistic with ambroxol HCl, diazoxide, digoxin, furosemide, HCTZ, omeprazole, pantoprazole, phenytoin, verapamil, and drug X against intracellular M. bovis BCG. The antimycobacterial properties exhibited by the ion transport modulators in this study make them viable candidates as adjuncts to the current anti-TB regimens.
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CONTEXT: Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized. AIMS: The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM®) parameters in leptospirosis patients. SETTINGS AND DESIGN: This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals. SUBJECTS AND METHODS: Blood samples were collected between the 3rd and 10th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM. STATISTICAL ANALYSIS USED: ANOVA post hoc comparison using Bonferroni was applied to compare groups. RESULTS: PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations. CONCLUSIONS: Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.
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Leptospirosis is endemic in Sri Lanka. There is a need for updated seroprevalence studies in endemic areas, to improve the understanding of disease dynamics, risk factors, control methods, and for clinical diagnosis. The cut-off titres for the microscopic agglutination test (MAT) for diagnosis of acute leptospirosis depend on community seroprevalence, and can vary based on locality and serovar. This study aimed to identify the seroprevalence, geographical determinants, and associations of seropositivity of leptospirosis in the district of Colombo in Sri Lanka, and to determine diagnostic cut-off titres for MAT in the community studied. This study utilized a stratified cluster sampling model in the Colombo district of Sri Lanka, to sample individuals living in urban and semi-urban areas. Serovar specific MAT titres were measured on recruited individuals using a panel of saprophytic (Leptospira biflexa) and 11 pathogenic Leptospira spp. serovars. Associations between environmental risk factors and MAT positivity were examined, with location mapping using GIS software. A total of 810 individuals were included. The mean age was 51.71 years (SD 14.02) with male predominance (60%). A total of 429 (53%) tested positive at a titer of 1/40 or more for the saprophytic Leptospira biflexa serovar Patoc. Pathogenic serovar MAT was positive at a titer of 1/40 or more for at least one serovar in 269 (33.2%) individuals. From the perspective of screening for clinical disease, serovar-specific cut-off titres of 1/80 for Leptospira spp. serovars Hebdomadis, Icterohaemorrhagiae, Pomona, Ratnapura and Patoc, 1/160 for serovars Pyrogenes and Cynopteri, and 1/40 for other serovars were determined, based on the 75th quartile MAT titre for each serovar. Serovar Pyrogenes (15.9%) had the highest seroprevalence, with serovars Ratnapura, Bankinang and Australis accounting for 9.9%, 9.6% and 9.3% respectively. When the proposed new cut-offs were applied, Bankinang(9.6%) Australis(9.3%), Pyrogenes(6.9%) and Ratnapura(6.9%) were the most prevalent serovars. No significant differences in seroprevalence or serovar patterns were noted between urban and semi-urban settings. Individuals seropositive for Australis, Ratnapura and Icterohaemorrhagiae were clustered around main water bodies as well as around smaller tributaries and paddy fields. Those positive for the serovar Pyrogenes were clustered around inland tributaries, smaller water sources and paddy fields. Associations of MAT positivity included high risk occupational exposure, environmental exposure including exposure to floods, bathing in rivers and lakes, using well-water for bathing, contact with stagnant water, propensity to skin injuries, presence of rats in the vicinity, and proximity to water sources. For pathogenic serovars, high-risk occupational exposure remained statistically significant following adjustment for other factors (adjusted OR = 2.408, CI 1.711 to 3.388; p<0.0001; Nagelkerke R2 = 0.546). High risk occupational exposure was determined to be independently associated with seropositivity. Baseline community MAT titres vary according to serovar, and presumably the locality. Testing against saprophytic serovars is unreliable. Thus, diagnostic MAT titre cut-offs should be determined based on region and serovar, and the use of a single diagnostic MAT cut-off for all populations is likely to result in false negatives.
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Aglutininas/sangue , Doenças Endêmicas , Leptospira/imunologia , Leptospirose/epidemiologia , População Suburbana , População Urbana , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Aglutinação , Cidades/epidemiologia , Feminino , Humanos , Leptospira/classificação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Sri Lanka/epidemiologia , Adulto JovemRESUMO
Context. Pleurotus ostreatus (P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. OBJECTIVES: The present study investigates the anti-inflammatory potential of P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. Materials and Methods. Anti-inflammatory activity was evaluated using suspensions of freeze-dried and powdered (SFDP) P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. in vivo and in vitro assays. RESULTS: At doses of 500-1000 mg/kg, the SFDP of P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. in vitro assays. P < 0.05). Dose-dependent inhibition of NO production was seen with in vitro assays. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. r = 0.95; P < 0.05). Dose-dependent inhibition of NO production was seen with Discussion and Conclusion. The promising activity of culinary mushroom P.o against inflammation suggests its potential application as a functional food during inflammatory conditions.P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae.
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OBJECTIVE: To investigate the immunomodulatory activity of a traditional Sri Lankan concoction of Coriandrum sativum L. and Coscinium fenestratum (Gaertn.) Colebr., which is a Sri Lankan traditional medicine used to relieve inflammation and cold. METHODS: In vivo anti-inflammatory activity was tested using carrageenan-induced rat paw-edema model. Mechanism of anti-inflammatory activity was assessed by investigating the production of nitric oxide (NO), expression of iNOS enzyme, and reactive oxygen species (ROS) by rat peritoneal cells. The membrane stabilizing activity was also tested. The antibody response was determined by assessing the specific haemagglutination antibodies raised against sheep red blood cells. RESULTS: The three doses of freeze-dried concoction used ((human equivalent dose (HED)-183 mg/kg) 2 × HED and 1/2HED; n = 6 rats/group) showed significant inhibition of paw edema compared to water control at 3rd-5th hours (p < 0.05). Both HED and 1/2HED exhibited marked anti-inflammatory activity (72-83% inhibition at 4th-5th hours; p < 0.05). The HED of the concoction showed significant inhibition of NO (77.5 ± 0.73%, p < 0.001) and ROS production (26.9 ± 2.55%; p < 0.01) by rat peritoneal cells. Inhibition of NO production in the concoction treated rat peritoneal cells was confirmed by the lack of iNOS expression. The concoction also exhibited significant membrane stabilizing activity (IC50 = 0.0006 µg/ml; p = 0.001). HED resulted in a significantly high induction of specific antibody production against SRBC antigens as detected by SRBC haemagglutination assay (mean day 14 titers 253.3 compared to control: 66.7) (p < 0.01). CONCLUSIONS: The traditional Sri Lankan concoction of C. sativum and C. fenestratum demonstrated potent in vivo anti-inflammatory activity, significant reduction of ROS, and NO production by rat peritoneal cells and the lack of iNOS expression confirmed the low NO production. The increased membrane stability also supports the anti-inflammatory activity of the concoction. Further, this concoction induced a significantly high antibody response reflecting its immunostimulatory activity. Together these results scientifically validate the therapeutic use of the concoction of C. sativum and C. fenestratum in Sri Lankan traditional medicinal system for immunomodulatory effects.
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We report here, for the first time, a comparison of naturally acquired antibody responses to the 42 and 19 kDa C-terminal processing products of Plasmodium vivax Merozoite Surface Protein-1 assayed by ELISA using p42 and p19 baculovirus-derived recombinant proteins, respectively. Test populations comprised patients with microscopy confirmed acute P. vivax infections from two regions endemic for vivax malaria where low transmission and unstable malaria conditions prevail, and a non-endemic urban area, in Sri Lanka. The antibody prevalence to the two proteins, both at the individual and population levels, tend to respond more to p42 than to p19 in all test areas, where >14% of individuals preferentially recognized p42, compared with <2% for p19. In patients with no previous exposure to malaria, 21% preferentially recognized p42, whereas none exclusively recognized p19. A significantly lower prevalence of anti-p19 IgM, but not anti-p42 IgM, was observed among residents from endemic areas compared with their non-endemic counterparts. Individuals from both endemic areas produced significantly less anti-p19 IgM compared with anti-p42 IgM. IgG1 was the predominant IgG isotype for both antigens in all individuals. With increasing exposure to malaria in both endemic areas, anti-p19 antibody responses were dominated by the functionally important IgG1 and IgG3 isotypes, with a concurrent reduction in IgM that was lacking in the non-endemic residents. This antibody switch was also reflected for PvAMA-1 as we previously reported with the identical battery of sera. In contrast, the antibody switch for p42 was restricted to endemic residents with more extensive exposure. These results suggest that an IgM-dominated antibody response against the p42 polymorphic region in endemic residents may interfere with the development of an IgG-dominated "protective" isotype shift to p19, that may complicate vaccine development.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Antígenos de Protozoários/imunologia , Malária Vivax/imunologia , Proteínas de Membrana/imunologia , Plasmodium vivax/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos de Protozoários/biossíntese , Feminino , Humanos , Imunoglobulina G/biossíntese , Malária Vivax/epidemiologia , Masculino , Proteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Proteínas de Protozoários/biossíntese , Sri Lanka/epidemiologiaRESUMO
Plasmodium vivax, the most widely distributed human malaria parasite, contains the subtelomeric multigene vir superfamily corresponding to circa 10% of its coding genome. In this work, we used a multi-character strategy to study the vir gene repertoire circulating in natural parasite populations obtained directly from 32 human patients from endemic regions of Brazil and Sri Lanka. Cladistic analysis confirmed the existence of vir subfamilies, which varied in size and allele polymorphisms. Moreover, different motifs, protein domain, and secondary structures were predicted for each subfamily. Of importance, not all vir sequences possess a recognizable Pexel motif recently shown to be important, though not essential, signal for transportation to the cell membrane of infected red blood cells. Furthermore, subfamilies A and D display common structural features with the recently described P. falciparum SURFIN and Pfmc-2tm subtelomeric multigene families. These results suggest that VIR proteins can have different subcellular localizations and functions. This is the first study on a population level of the P. vivax vir subtelomeric multigene superfamily.
Assuntos
Genes de Protozoários , Malária Vivax/sangue , Família Multigênica , Plasmodium vivax/genética , Motivos de Aminoácidos , Animais , Brasil , Genoma de Protozoário , Humanos , Plasmodium vivax/isolamento & purificação , Estrutura Terciária de Proteína , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Homologia de Sequência de Aminoácidos , Sri Lanka , Telômero/genéticaRESUMO
Melatonin is an indolamine produced by the pineal gland and it can exert a potent antioxidant effect. Its free radical scavenger properties have been used to advantage in different organ transplants in animal experiments. Several concentrations and administration pathways have been tested and melatonin has shown encouraging beneficial results in many transplants of organs such as the liver, lungs, heart, pancreas, and kidneys. The objective of the present study was to review the scientific literature regarding the use of melatonin in ovary transplantation. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was carried out using the Cochrane and Pubmed databases and employing the terms 'melatonin' AND 'ovary' AND 'transplantation.' After analysis, 5 articles were extracted addressing melatonin use in ovary transplants and involving 503 animals. Melatonin enhanced various graft aspects like morphology, apoptosis, immunological reaction, revascularization, oxidative stress, and survival rate. Melatonin's antioxidative and antiapoptotic properties seemingly produce positive effects on ovarian graft activity. Despite the promising results, further studies in humans need to be conducted to consolidate its use, as ovary transplantation for fertility preservation is gradually being moved from the experimental stage to a clinical setting.
Assuntos
Melatonina/metabolismo , Transplante de Órgãos , Ovário/metabolismo , Ovário/transplante , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Melatonina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.
Assuntos
Antioxidantes/metabolismo , Biomarcadores/sangue , Dengue/diagnóstico , Leptospirose/diagnóstico , Estresse Oxidativo , Carbonilação Proteica , Adulto , Estudos de Casos e Controles , Dengue/sangue , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Diagnóstico Diferencial , Feminino , Humanos , Leptospira/isolamento & purificação , Leptospirose/sangue , Leptospirose/microbiologia , MasculinoRESUMO
In order to explain the distribution of natural radiation level in the Asia, in situ measurements of dose rate in air due to terrestrial gamma radiation have been conducted in a total of 21 islands that belong to Ryukyu Islands (Ryukyu Archipelago), subtropical rejoin of southwest Japan. Car-borne surveys have also been carried out in Okinawa-jima, the biggest island of the archipelago. Based on the results for these measurements, arithmetic mean, the maximum and the minimum of the dose rates at 1 m in height from the unpaved soil ground in the archipelago were estimated to be 47, 165 and 8 nGy h(-1), respectively. A comparative study of car-borne data obtained prior to and subsequent to the 2011 Fukushima nuclear accident, as for Okinawa-jima, indicated that the nuclear accident has no impact on the environmental radiation at the present time.