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BACKGROUND: A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. METHODS: Filter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes. RESULTS: A total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%). CONCLUSION: The high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended.
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Proteínas de Membrana Transportadoras/análise , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise , Plasmodium falciparum/genética , Proteínas de Protozoários/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Nigéria , Adulto JovemRESUMO
BACKGROUND: In West and Central Africa areas of endemic Loa loa infections overlap with regions of high prevalence of human immunodeficiency virus type 1 (HIV-1) infections. Because individuals in this region are exposed to filarial parasites from birth, most HIV-1 infected individuals invariably also have a history of filarial parasite infection. Since HIV-1 infection both depletes immune system and maintains it in perpetual inflammation, this can hamper Loa loa filarial parasite mediated immune modulation, leading to enhanced loaisis. METHODS: In this study we have assessed in plasma from asymptomatic anti-retroviral (ARV) naïve Loa loa microfilaraemic HIV-1 infected people the filarial antibody responses specific to a filariasis composite antigen consisting of Wbgp29-BmR1-BmM14-WbSXP. The antibody responses specific to the filariasis composite antigen was determined by enzyme linked immunosorbent assay (ELISA) in plasma from ARV naïve Loa loa microfilaraemic HIV-1 infected participants. In addition the filarial antigen specific IgG antibody subclass profiles were also determined for both HIV-1 positive and negative people. RESULTS: Both Loa loa microfilaraemic HIV-1 positive and negative individuals showed significantly higher plasma levels of IgG1 (P < 0.0001), IgG2 (P < 0.0001) and IgM (P < 0.0001) relative to amicrofilaraemic participants. A significant increase in IgE (P < 0.0001) was observed exclusively in Loa loa microfilaraemic HIV-1 infected people. In contrast there was a significant reduction in the level of IgG4 (p < 0.0001) and IgG3 (P < 0.0001) in Loa loa microfilaraemic HIV-1 infected individuals. CONCLUSIONS: Loa loa microfilaraemia in ARV naïve HIV-1 infected people through differential reduction of plasma levels of filarial antigen specific IgG3, IgG4 and a significant increase in plasma levels of filarial antigen specific IgE could diminish Loa loa mediated immune-regulation. This in effect can result to increase loaisis mediated immunopathology in antiretroviral naive HIV-1 infected people.
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Antirretrovirais/uso terapêutico , Antígenos de Helmintos/imunologia , Infecções por HIV/tratamento farmacológico , Loíase/diagnóstico , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Formação de Anticorpos , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/complicações , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Loa/imunologia , Loa/isolamento & purificação , Loíase/complicações , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
CONTEXT: Some edible mushrooms are reputed to possess useful medicinal properties which are related to their ability to modulate the protective responses of the immune system. OBJECTIVE: This study explored the immunomodulatory and immunorestorative properties of a hot aqueous extract (APTR) and of a ß-d-glucan-enriched polysaccharide fraction (BGP) of a local oyster mushroom Pleurutus tuberregium (Fr.) Singer (Pleurotaceae). MATERIALS AND METHODS: Immunomodulatory activities were investigated by assessing specific and none-specific immune responses in immunocompetent and immunosuppressed mice; as well as in vitro in culture of RAW264.7 macrophages stimulated with BGP. RESULTS: In a homologous prime-boost immunization schedule, oral supplementation with APTR (100, 200, or 400 mg/kg) and BGP (100 or 200 mg/kg) resulted in significantly higher titers of total IgG, IgG1, and IgG2a by as much as 2-4-folds compared with the levels in untreated control mice. The mean hemagglutination (HA) titer in immunized mice that were treated with dexamethasone (DEX; 5 mg/kg) was significantly (p < 0.05) lower than the titer in groups that did not receive dexamethasone; however, short-term alternate day administration of APTR (200 mg/kg) to mice that had been immunosuppressed with 5 mg DEX/kg produced significant increases in secondary anti-SRBC antibody compared with the mean titer of mice immunized and treated with DEX alone. In in vitro studies, stimulation of RAW264.7 macrophages with BGP caused significant increases in iNO and TNF-α expression, and phagocytic functions of the cell. CONCLUSION: Taken together, the results of these studies showed that P. tuberregium imparts immunostimulatory and immunorestorative effects that could be explained, in part, by the actions of its ß-d-glucan constituent(s) on macrophages.
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Fatores Imunológicos/imunologia , Pleurotus , Polissacarídeos/imunologia , beta-Glucanas/imunologia , Animais , Linhagem Celular , Feminino , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Proteoglicanas , beta-Glucanas/isolamento & purificação , beta-Glucanas/farmacologiaRESUMO
BACKGROUND: Malaria treatment policy recommends regular monitoring of drug utilization to generate information for ensuring effective use of anti-malarial drugs in Nigeria. This information is currently limited in the retail sector which constitutes a major source of malaria treatment in Nigeria, but are characterized by significant inappropriate use of drugs. This study analyzed the use pattern of anti-malarial drugs in medicine outlets to assess the current state of compliance to policy on the use of artemisinin-based combination therapy (ACT). METHODS: A prospective cross-sectional survey of randomly selected medicine outlets in Enugu urban, southeast Nigeria, was conducted between May and August 2013, to determine the types, range, prices, and use pattern of anti-malarial drugs dispensed from pharmacies and patent medicine vendors (PMVs). Data were collected and analyzed for anti-malarial drugs dispensed for self-medication to patients, treatment by retail outlets and prescription from hospitals. RESULTS: A total of 1,321 anti-malarial drugs prescriptions were analyzed. ACT accounted for 72.7%, while monotherapy was 27.3%. Affordable Medicines Facility-malaria (AMFm) drugs contributed 33.9% (326/961) of ACT. Artemether-lumefantrine (AL), 668 (50.6%) was the most used anti-malarial drug, followed by monotherapy sulphadoxine-pyrimethamine (SP), 248 (18.8%). Median cost of ACT at $2.91 ($0.65-7.42) per dose, is about three times the median cost of monotherapy, $0.97 ($0.19-13.55). Total cost of medication (including co-medications) with ACT averaged $3.64 (95% CI; $3.53-3.75) per prescription, about twice the mean cost of treatment with monotherapy, $1.83 (95% CI; $1.57-2.1). Highest proportion 46.5% (614), of the anti-malarial drugs was dispensed to patients for self-treatment. Treatment by retail outlets accounted for 35.8% while 17.7% of the drugs were dispensed from hospital prescriptions. Self-medication, 82%, accounted for the highest source of monotherapy and a majority of prescriptions, 85.6%, was adults. CONCLUSION: Findings suggest vastly improved use of ACT in the retail sector after eight years of policy change, with significant contributions from AMFm drugs. However the use of monotherapy, particularly through self-medication remains significant with increasing risk of undermining treatment policy, suggesting additional measures to directly target consumers and providers in the sector for improved use of anti-malarial drugs in Nigeria.
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Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Uso de Medicamentos , Lactonas/uso terapêutico , Malária/tratamento farmacológico , Farmácias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Combinação de Medicamentos , Feminino , Fidelidade a Diretrizes , Política de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria , Estudos Prospectivos , População Urbana , Adulto JovemRESUMO
This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer-Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher (p < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection.
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The study was carried out to determine the effect of ginger on the plasma pharmacokinetics of ciprofloxacin and Isoniazid in a rat model in phase 1. The effects of the herb on the penetration of ciproflacin and Isoniazid into the lung tissues were also determined in phase 2. In phase 1, Albino rats of both sexes (n = 20) were divided into 4 groups of 5 rats per group. Two groups received oral ciprofloxacin (20 mg/kg) and isoniazid (15 mg/kg). Other groups were fed with ginger (5 mg/kg) for 10 days followed by the drug administration on the 11th day. Blood samples were collected from each group at 0-, 0.5-, 1-, 2-, 5-, 8-, 12-, and 24-hour intervals. Plasma concentrations of the drugs were determined by a spectrophotometric method and the pharmacokinetic parameters determined using noncompartmental method as implemented in the winNonlin program. In phase 2, where the effects of the herb on the penetration of the drugs were determined, the concentrations of ciprofloxacin and isoniazid attained in the lung fluid of rats in the presence and absence of the herb were compared after a single oral dose of the drugs used in the same dose range as in phase 1. In the first phase, treatment with ginger significantly increased the area under the concentration-time curve of ciprofloxacin, whereas Vz and Cl were decreased. Ginger significantly decreased the area under the concentration-time curve of isoniazid, whereas Vz and Cl were increased. Ginger enhanced the penetration of ciprofloxacin and Isoniazid into the lung tissues; however, their rates of penetration were delayed.
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Anti-Infecciosos/farmacocinética , Ciprofloxacina/farmacocinética , Interações Ervas-Drogas , Isoniazida/farmacocinética , Extratos Vegetais/farmacologia , Zingiber officinale , Administração Oral , Animais , Área Sob a Curva , Feminino , Meia-Vida , Pulmão/metabolismo , Masculino , Taxa de Depuração Metabólica , RatosRESUMO
BACKGROUND: CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability. OBJECTIVE: The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity. METHODS: CSIC self-emulsifying oil formulations (SEFs) were formulated and evaluated for droplet size, zeta potential, polydispersity index (PDI), viscosity, emulsification time, stability and bioactivity. RESULTS: Results showed significantly improved solubility of CSIC in the SEFs.The concentration of co-surfactant affected the droplet size, zeta potential and polydispersity index. In vitro bioactivity studies showed that the CSIC SEFs retained full anti-HIV activity. CONCLUSION: The in vitro data from this first attempt to formulate CSIC SEFs suggest that improvement on the aqueous solubility of CSIC through this delivery system may accentuate its antiretroviral effectiveness in vivo via bioavailability enhancement. The formulation is therefore intended as an oral anti-HIV agent for prophylactic and therapeutic uses.
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In this study, some depsidones and diaryl ether derivatives isolated from Corynespora cassicola, a fungi endophyte of Gongronema latifolium, were assessed for their anti-inflammatory potentials. The isolated metabolites corynesidone A (1), corynesidone C (2), corynesidone D (3) and corynether A (4) were screened for their effects on tumour necrosis factor-α (TNF-α), inducible nitric oxide (iNO), and reactive oxygen species (ROS) and reactive nitrogen species (RNS) production by stimulated RAW264.7 macrophages. Concentration of 1, 2, 3 and 4 up to 100 µM did not remarkably affect the viability of treated macrophages. The compounds were found to cause a concentration-dependent decrease in lipopolysaccharide-induced TNF-α and iNO in RAW264.7 cells. Pre-treatment with 100 µM of 1, 2, 3 and 4 suppressed iNO by as much as 96.28%, 95.71%, 78.14% and 73.28%; with IC(50) of 8.16, 9.49, 15.29 and 26.52 µM, respectively. Similarly, pre-treatment with 100 µM of 1, 2, 3 and 4 caused an inhibition of 99.17%, 99.59%, 95.02% and 74.07% in the formation of iNO production, respectively, with IC(50) of 1.88, 3.99, 7.48 and 37.22 µM. Treatment of with compounds 1-4 (10, 30 and 100 µM) followed by stimulation with phorbol 12-myristate 13-acetate (1 µM) caused significant (p < 0.05) suppression of ROS/RNS-evoked chemiluminescence of luminol by as much as 100.96 ± 1.88%, 98.59 ± 1.38%, 87.35 ± 1.41% and 79.22 ± 0.30%, respectively at 100 µM. The depsidone derivatives (1-4) showed more potent inhibition of TNF-α and NO production and better scavenging ROS/RNS than the diaryl ether derivative (4). These chemical scaffolds can serve as suitable lead molecules for further development into novel anti-inflammatory and/or anti-cancer agents.
Assuntos
Apocynaceae , Ascomicetos/química , Depsídeos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Lactonas/farmacologia , Folhas de Planta , Espécies Reativas de Oxigênio/metabolismo , Animais , Apocynaceae/química , Apocynaceae/microbiologia , Linhagem Celular , Depsídeos/química , Sequestradores de Radicais Livres/química , Lactonas/química , Macrófagos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Folhas de Planta/microbiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Morinda lucida Benth (Rubiaceae) is a versatile plant used in traditional medicine of many countries for the treatment of a variety of ailments and the claims of efficacy are particularly remarkable in the treatment of infections and immuno-inflammatory disorders. In this study, we investigated the immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida (AML) in cultures of murine splenic lymphocytes and in cyclophosphamide-induced immunosupression models, respectively. Administration of AML (100 and 250 mg/kg; per os) in alternate days significantly (P < 0.05) increased specific total IgG, IgG1, and IgG2a responses to ovalbumin by as much as 2-10 fold when compared to untreated controls. In cyclophophamide treated mice, the rate of wound healing, leukopoiesis , and body weight recovery were all enhanced by oral supplementation with AML (100 and 250 mg/kg) in a dose-dependent manner. In vitro cultures of BALB/C splenocytes treated with AML (12.5 and 50 µg/ml) for 24 h resulted in 5-10 fold increase in IFNγ and IL-4 measured by cytokine capture ELISA. Surface expression of immunostimulatory markers, CD69 and CD25, measured flow cytometrically by FACS analyis, were also significantly (P < 0.05) upregulated on splenic T and B cells by as much as 8-20 fold. Taken together, the results of these studies show the potent immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida, which may explain some of the beneficial effects of the plant in the treatment of infections and immuno-inflammatory disorders.
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Morinda/química , Extratos Vegetais/administração & dosagem , Folhas de Planta/química , Baço/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Células Cultivadas , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citocinas/metabolismo , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunização , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/efeitos adversos , Ratos , Ratos Endogâmicos , Baço/imunologia , Água , Cicatrização/efeitos dos fármacosRESUMO
We studied the presence of extended spectrum beta lactamases (ESBLs) in 44 clinical isolates of Escherichia coli collected from out-patients in two university teaching hospitals in South-Eastern Nigeria. Species identification was performed by standard microbiology methods and re-confirmed by MALDI-TOF technology. Phenotypic characterization of ESBL enzymes was done by double disc synergy test and presence of ESBL genes was determined by specific PCR followed by sequencing. Transfer of plasmid DNA was carried out by transformation using E. coli DH5 as recipient strain. Phenotypic characterization identified all isolates to be ESBL positive. 77% of strains were from urine, 13.6% from vaginal swabs and 9.0% from wound swabs. 63.6% were from female patients, 68% were from outpatients and 95.5% from patients younger than 30 years. All ESBL producers were positive in a PCR for bla(CTX-M-1) cluster, in exemplary strains bla(CTX-M-15) was found by sequencing. In all strains ISEcp1 was found upstream and ORF477 downstream of bla(CTX-M). PCR for bla(TEM) and bla(OXA-1) was positive in 93.1% of strains, whereas bla(SHV) was not detected, aac(6')-Ib-cr was found in 97.7% of strains. RAPD analysis revealed seven different clonal groups named A through G with the majority of the strains (65.9%) belonging to clone A. Transfer of an ESBL plasmid with co-resistance to gentamicin, kanamycin, tobramycin, doxycycline and trimethropim-sulfamethoxazole was successful in 19 (43.2%) strains. This study showed a high rate of CTX-M-1 cluster - ESBLs in South-Eastern Nigeria and further confirms the worldwide spread of CTX-M ESBL in clinical isolates.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Adolescente , Adulto , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Pacientes Ambulatoriais , Adulto Jovem , beta-Lactamases/genéticaRESUMO
Emilia sonchifolia L. (Asteraceae) is used in ethnomedicine for the treatment of a wide array of inflammatory disorders. This practice has also been supported by scientific reports which showed that extracts of E. sonchifolia possess anti-inflammatory effects in rodents. However, the mechanism(s) through which the extracts produce these effects is not known. In this study, the effect of a methanol/methylene chloride extract of E. sonchifolia (ES) on the levels of IL-1ß and TNF-α after an intraperitoneal lipopolysaccharide (LPS; 1 mg/kg) challenge was investigated in mice. The effect of ES on TNF-α and inducible nitric oxide (iNO) production by LPS-stimulated bone marrow-derived macrophages (BMMDM) was also investigated in vitro. BMMDM were pre-incubated for 2 h with ES (20, and 100 µg/mL) or with Pyrrolidine dithiocarbamate, PDTC (100 µM) and then activated with LPS, and then the IL-1ß, TNF-α and NO production measured in the cell-free conditioned culture supernatant after 24 h of incubation. In groups of mice pre-treated with ES, the systemic levels of IL-1ß and TNF-α induced by LPS were found to be significantly (p < 0.05) lower. In vitro, ES treatment caused a concentration-dependent decrease in LPS-inducible IL-1ß, TNF-α, and NO production by BMDM compared to the effects of treatment of the cells with LPS alone without affecting the viability of the cells. The results of these studies suggest that treatment with ES alleviated inflammatory responses possibly through a suppression of pro-inflammatory mediators and cytokines such as IL-1ß, TNF-α, and iNO.
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Anti-Inflamatórios/farmacologia , Asteraceae/química , Mediadores da Inflamação/metabolismo , Interleucina-1beta/biossíntese , Macrófagos/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Anti-Inflamatórios/química , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células Cultivadas , Relação Dose-Resposta a Droga , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Extratos Vegetais/químicaRESUMO
Natural products from Nigerian plants are significant in the search for drug compounds, as they contribute new compounds with biological properties to the fight against resistant pathogens, hence the study. Fresh leaves of M. indica were prepared for fungal isolation, identification, fermentation, and secondary metabolites extraction. The extract, subjected to HPLC analysis revealed the presence of two bioactive compounds: p-Hydroxylbenzoic acid, and Protocatechuic acid. The extract exhibited antibacterial activity against P. aeruginosa and E. coli producing IZD of 4 mm respectively at 1 mg/ml. It produced an interesting antioxidant activity in the DPPH assay with 86.7% activity at 0.5 mg/ml. At 0.01 mg/ml, the extract showed 85.3% cytotoxic activity against L5178Y mouse lymphoma cells and showed 96.5% ± 0.173 HIV-1 reverse transcriptase inhibition activity at 0.25 mg/ml. This study confirms Aspergillus sp. from M. indica produces bioactive compounds that could serve as novel drug molecules in the fight against drug resistance.
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Mangifera , Animais , Camundongos , Cromatografia Líquida de Alta Pressão , Escherichia coli , Aspergillus/química , Extratos Vegetais/farmacologiaRESUMO
Background and Objectives: This study investigated the incidence and antibiotic susceptibility profile of extended spectrum ß-lactamase (ESBL) producing uropathogenic Escherichia coli recovered from HIV/AIDS patients in Awka metropolis, Nigeria. Materials and Methods: A total of 363 urine samples were bacteriologically analyzed for the isolation of E. coli isolates which were further characterized using standard microbiology techniques. The isolated uropathogenic E. coli was tested for susceptibility to a range of clinically important antibiotics using the modified disk diffusion technique. All E. coli isolates were phenotypically screened for ESBL production using the combined disk technique, and strains which were positive were further confirmed for the presence of ESBL genes using PCR technique. Results: A total 160 (44.1%) non-duplicate isolates were bacteriologically confirmed to be uropathogenic E. coli (UPEC). The E. coli isolates showed reduced susceptibility to important antibiotics including ceftazidime (76.88%), cefuroxime (77.5%), cefixime (61.88%), amoxicillin-clavulanic (32.5%) and ciprofloxacin (34.38%). Twenty-seven of the UPEC isolates were phenotypically confirmed to be ESBL producers. PCR test confirmed some important genes mediating ESBL production in Gram negative bacteria including bla TEM (5.0%) and bla CTX-M-15 (6.9%) genes. Conclusion: We report a high prevalence of ESBL producers among HIV/AIDS patients in Awka, Nigeria. This result is important as antibiotic resistance (ABR) particularly those mediated by multidrug resistant bacteria as reported in this current study could complicate treatment outcome, worsen the individual's health, and even increase cost of treatment and hospitalization. It is therefore important to lookout for ESBL positive UPEC amongst HIV/AIDS patients in Nigeria.
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INTRODUCTION: The genetic diversity of Plasmodium falciparum poses a threat to the development and implementation of malaria control strategies. Thus, there is a need for continuous surveillance of its genetic diversity, especially amongst the parasite's reservoir's asymptomatic population. METHODOLOGY: Three cohorts comprising children under ten years old, pregnant women and other adults were recruited into this study. Blood sample was collected from all consenting individuals and screened by the polymerase chain reaction (PCR) method. The genetic diversity of P. falciparum was determined by genotyping the merozoite surface protein-1 (msp-1), merozoite surface protein-2 (msp-2) and glutamate-rich protein (glurp). The size of alleles was visualized on the agarose gel. The multiplicity of infection (MOI) and expected heterozygosity (He) were determined. RESULTS: The majority of the patients showed polyclonal infections, while the multiplicity of infection with msp-2 and glurp of isolates from pregnant women were 2.5 and 1.8, respectively. Children and adults were 2.3 and 1.1; 2.4 and 1.3, respectively. The estimated number of genotypes was 10 msp-1 (4 KI; 4 MAD; 2 RO33), 27 msp-2 (14 FC27; 13 IC/3D7) and 8 glurp. K1 (36/100) was more frequent than the MAD20 (22.33/100) allele, which was, in turn, more frequent than the RO33 (13.59/100). The samples with the 3D7 allele (53.40/100) of msp-2 occurred more frequently than the FC27 type (45.63/100). Polymorphism in the glurp gene occurred most frequently (72.82/100). CONCLUSION: The study samples exhibited a high degree of genetic polymorphism in msp-2 allele typing with multiple clones, reflecting the complexity of parasite populations.
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Antígenos de Protozoários , Malária Falciparum , Plasmodium falciparum , Adulto , Antígenos de Protozoários/genética , Criança , Feminino , Frequência do Gene , Variação Genética , Genótipo , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Proteína 1 de Superfície de Merozoito/genética , Nigéria/epidemiologia , Plasmodium falciparum/genética , Gravidez , Proteínas de Protozoários/genéticaRESUMO
T. Angelica Herbal Tonic (TAHT) is a herbal product indicated for indigestion and constipation and highly patronized in Nigeria. In this study, the efficacy and safety of the herbal tonic in relation to the label claims were assessed. The effect on peristalsis in mice was evaluated by the charcoal meal model and in vitro using guinea pig ileum. The effects of TAHT on behavior, fertility, birth and organ weights were also determined. Teratogenic potential and reproductive toxicity were studied in pregnant rats. Acute toxicity studies showed that at doses above 5000 mg kg(-1), the herbal tonic did not cause lethality and produced no signs of intoxication in mice. The study did not show any gross behavioral changes in mice treated with 1000 mg kg(-1) of TAHT as compared with the negative control treatment. TAHT (400 mg kg(-1)) exhibited a dose-dependent enhancement in the gastrointestinal tract motility in mice when compared with the negative control. At concentrations up to 300 µg mL(-1), TAHT did not cause any significant effect on acetylcholine, histamine and nicotine-evoked contractions of guinea pig ileum preparation. It took an average of 31.25 ± 4.52 days for the TAHT-treated animals to litter, which is significantly (P < .05) different from the 55 ± 4.51 days recorded for the control treatment group. TAHT exhibited a modest fertility-promoting effect and showed lack of abortifacient and teratogenic properties in the study. Generally, the results of this study showed some favorable pharmacological effects of TAHT in animals which may authenticate some of the label claims.
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A new tetronic acid derivative (1) together with terrestric acid (2), a known metabolite of Penicillium species, was isolated from the soil fungus, FG9RK following fermentation on solid rice medium. The structure of 1 was elucidated by one- and two-dimensional NMR and MS measurements. The absolute configuration of the oxygenated carbon in the side chain of 1 was identified as S by converting the compound into its Mosher ester whereas the absolute configuration of the lactone ring was deduced based on biogenetic considerations and comparison with 2.
Assuntos
Penicillium , Solo , Fungos , Furanos , Estrutura MolecularRESUMO
Alchornea floribunda (Euphorbiaceae) leaves are widely used in African ethnomedicine for the management of acute and chronic inflammatory disorders. In the present study, bioactivity-guided fractionation led to the isolation of two known (1 and 3) and one new (2) stigmastane steroids from the hexane extract of Alchornea floribunda leaves. The anti-inflammatory activities of these compounds were evaluated using IN VITRO and IN VIVO animal models. The compounds 1, 2, and 3 at 50 and 100 microg/ear significantly (p < 0.05) inhibited xylene-induced ear edema in mice in a dose-dependent manner. The topical anti-inflammatory effect of 1 and 2 are significantly (p < 0.05) higher than that of indomethacin and prednisolone. At 20 mg/kg (i. p.), all the compounds significantly (p < 0.05) inhibited acute inflammation induced by subplantar injection of egg albumen in rats. Compound 1 exhibited an anti-inflammatory effect (50.9 % edema inhibition) comparable (p < 0.05) to that of prednisolone (48.0 % edema inhibition) at 3 h. Compounds 1, 2, and 3 (50 microg/mL) significantly (p < 0.05) inhibited heat-induced haemolysis of human erythrocytes in vitro, but had no effect on hypotonicity-induced hemolysis. The compounds were elucidated as (24R)-5alpha-stigmast-3,6-dione ( 1), 5alpha-stigmast - 23-ene-3,6-dione ( 2), and 3beta-hydroxy-5alpha-stigmast-24-ene ( 3) by spectral analysis. The results of this study show that these compounds may, in part, account for the anti-inflammatory effect of Alchornea floribunda leaves. This is the first report on the isolation and structure elucidation of these anti-inflammatory steroids from Alchornea floribunda leaves.
Assuntos
Anti-Inflamatórios/uso terapêutico , Membrana Celular/efeitos dos fármacos , Colestenonas/uso terapêutico , Edema/tratamento farmacológico , Euphorbiaceae/química , Fitosteróis/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Colestenonas/isolamento & purificação , Colestenonas/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos , Ratos Wistar , XilenosRESUMO
Decoctions of Phyllanthus niruri (PN) (Fam. Euphorbiaceae) is promoted in traditional medicine of Africa, Asia, and South America as beneficial supplement for different infectious diseases, especially for viral hepatitis, tumor, and for immune compromised patients. This stimulated the interest in understanding the mechanisms by which the whole extract of the plant could stimulate the immune system. Dendritic cells (DCs) are professional antigen-presenting cells and provide a link between the innate and the adaptive immune responses. In the present study, the effects of lyophilized aqueous extract of PN on structural and functional maturation of murine bone marrow-derived DCs (BM-DCs) were investigated. Bone marrow cells were cultured in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 (IL-4) and the generated immature DCs were stimulated with PN (25, 50, and 100 microg/mL) or lipopolysaccharide (10 microg/mL) for 48 h. Results showed that treatment with PN increased the expression of major histocompatibility complex-II and the various makers for DCs maturation (CD40), activation (CD83), and costimulation (CD86) in a concentration-dependent manner. Consistent with the increase in phenotypic makers, functional maturation assay showed that treatment of BM-DCs with PN caused a decrease in fluorescein isothiocyanate-dextran pinocytosis and an increase in IL-12 in the supernatant. In a transgenic T-cell activation model, PN-treated BM-DCs presented Ova antigen to Ova-specific CD8(+) T cells from OT-1 mice more efficiently as demonstrated by increased T-cells proliferation and IL-2 production. Therefore, PN enhances the structural and functional maturation of BM-DCs and their antigen-presenting function. These effects are relevant in immunodeficient conditions, tumor control, and in infectious diseases.
Assuntos
Apresentação de Antígeno/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Phyllanthus , Extratos Vegetais/farmacologia , Animais , Apresentação de Antígeno/imunologia , Antígenos CD/análise , Antígenos CD/imunologia , Antígeno B7-2/análise , Antígeno B7-2/imunologia , Antígenos CD40/análise , Antígenos CD40/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Interleucina-12/análise , Interleucina-12/imunologia , Interleucina-4/imunologia , Lipopolissacarídeos/imunologia , Complexo Principal de Histocompatibilidade/efeitos dos fármacos , Complexo Principal de Histocompatibilidade/imunologia , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pinocitose/efeitos dos fármacos , Pinocitose/imunologia , Extratos Vegetais/imunologia , Antígeno CD83RESUMO
The immune system is highly complex, intricately regulated group of cells whose integrated function is essential to health. Modulating the functions of these cells offers important pharmacological and therapeutic approaches in many disease conditions.This study reports on the in vitro immunostimulant activities of two flavonoid-rich fractions of Alchornea cordifolia (Euphorbiaceae) leaf extract: EAC and AAC, obtained by fractionating the methanol extract into ethylacetate and acetone soluble fractions, respectively.The lymphoproliferative effect of the fractions on naïve murine splenocytes and thymocytes as well as the modulatory effects on the phagocytic and lysosomal enzyme activities of elicited murine macrophages was investigated. A. cordifolia fractions, EAC and AAC, produced significant (P<0.05) and concentration-related (10-250 microg/ml) increases in the proliferation of splenocytes and thymocytes cultures which were comparable to the mitogenic effects of lipopolysaccharide, LPS (10 microg/ml) and concanavalin A, ConA (2 microg/ml) used as standard mitogens. EAC and AAC (15.6-250 microg/ml) significantly (P<0.05) increased phagocytosis and intracellular killing capacity measured as percentage increase in nitroblue tetrazolium (NBT) dye reduction. Lysosomal phosphatase activity of peritoneal macrophages, measured by p-nitrophenyl phosphate (p-NPP) hydrolysis, was also increased significantly (P<0.05) by EAC and AAC (15.6-250 microg/ml). Treatment of macrophage cultures with EAC and AAC (15.6-250 microg/ml) decreased the expression of nitric oxide significantly (P<0.05) in the supernatant. This study demonstrates strong immunomodulatory activities of A. cordifolia leaf extracts which could explain some of the therapeutic benefits attributed to the plant in traditional medicine and could also be exploited as a source of novel immunoregulating substances.
Assuntos
Euphorbiaceae , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Euphorbiaceae/química , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/biossíntese , Fitoterapia , Folhas de Planta/químicaRESUMO
There have been several modifications in the use of immune stimulating complexes as adjuvants, such as the replacement of phospholipids with saponin content. Not much research has been done on the use of local alternatives. This actually instigated the use of a local alternative saponin source from Carica papaya leaves to formulate Iscomatrix adjuvant. The Iscomatrix samples used in this study were formulated using different methods (the rapid injection, the reversed rapid injection, the slow/dropwise injection and the reversed slow/dropwise injection methods). Furthermore, the quantity of the components was also varied. These formulated samples were compared with other adjuvants and analysed for their ability to induce antibody and cell mediated immune responses using animal model i.e. mice. The results showed that the Iscomatrix samples formulated, were able to induce significant humoral and antibody mediated immune response (ranging from 16.7 % - 38.88 %) and they also elicited cell mediated immune response (ranging from 8.33 % - 16.7 %) when compared to the models that were administered with antigen only. Further characterizations were made, such as pH, UV scanning, Scanning Electron Microscopy. The analysis revealed that the samples were slightly soluble in distilled water with a neutral pH ranging from 7.26 - 7.43. The UV analysis also indicated that they all had a close range of absorption peaks (between 266.8-269.37 nm). Saponin from Carica papaya leaves can be used to formulate Iscomatrix adjuvant capable of stimulating cell mediated and antibody mediated immune responses.