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- ItemOpen AccessAnalysis of Pesticide Residues in Maize and Beans Types in Lagos(School of Postgraduate Studies University of Lagos., 2008) Ogah, C.O
- ItemOpen AccessAnalysis of Pesticide Residues in Maize and Beans Types in Lagos Markets(University of Lagos Postgraduate School, 2008) Ogah, C. O.Pesticides used in agriculture for the control of various pests often leave residues in foodstuffs and these have been shown to pose health hazards. Analysis of pesticide residues in food is one way to determine the level of human exposure to these chemicals and hence their potential human health hazards. Maize (Zea mays L.) and beans (Phaseolus vulgaris L.) samples purchased from different markets in Lagos State were analyzed for residues of organochlorine, organophosphate and carbamate pesticides. Analysis was done using gas chromatograph with mass spectrometric detector (GC-MS) after careful extraction and cleanup. Most of the maize samples (96%) were found to contain residues of one or more pesticides with concentrations ranging from 2.2-3951.0 μg/kg. The white types of maize contained higher concentrations of residues than the yellow types. Three classes of pesticides were detected in maize. All the samples of beans analyzed contained at least one pesticide residue (100% incidence). White beans were found to contain higher concentrations of residues than the brown types. The concentrations of organochlorine, organophosphate and carbamate pesticides residues in beans ranged from 2.3-1480.5μg/kg. The most commonly found residue among both maize and beans samples was the organophosphate, pirimiphos-methyl. Its percent occurrence was 43 in maize and 54 in beans. There was a decline in the mean levels of organochlorine pesticides in both maize (6.9-41.3μg/kg) and beans (4.8-39.7μg/kg) compared to the results of a previous similar study (10.0-93.0μg/kg for maize and 25.0-303.0μg/kg for beans). Maximum residue limits (MRLs) of the various pesticides were exceeded in up to 10% of samples of both maize and beans. The incidence of pesticide residues in maize and beans was found to be higher in some markets than others but mean concentrations were not different from market to market. The pesticide residue contents were decreased by boiling. Percent reduction ranged from 9 to 100. The extent of reduction was higher in the organophosphates (24-100%) and carbamates (20-100%) than in the organochlorines (9- 32%). The estimated total diet intakes (ETDIs) for most of the pesticides were well below their maximum permissible intakes (MPIs). On the other hand, the ETDIs for aldrin, dichlorvos and dieldrin exceeded their MPIs by 100%, 363% and 17% respectively. Conclusively, most of the maize and beans in Lagos markets contain pesticide residues at different levels and maximum residue limits were exceeded in about 10% of samples. There is therefore a need for more stringent monitoring of the use of pesticides in agriculture and food storage in Nigeria.
- ItemOpen AccessAntimalarial resistance genes polymorphism and imunoendocrine biomarker profile in patients with uncomplicated plasmodium falciparum malaria in Lagos, Nigeria(School of Postgraduate Studies of the University of Lagos, Akoka, 2020-01) Idowu, A.O.The threat of a possible emergence of resistance to currently recommended artemisinin based combination therapies (ACTs) against malaria, has made proactive surveillance for resistance markers imperative for early detection of resistance before they become widespread. The changing pattern of malaria transmission due to reduction in cases has also made reassessment of cytokine and endocrine response in malaria infection important. This study assessed antimalarial resistance genes polymorphism and immunoendocrine biomarker profile in patients with uncomplicated Plasmodium falciparum malaria in Lagos, Nigeria. Blood samples collected between July, 2015 and August, 2016 in 3 health facilities in Lagos from a cross section of 2,534 consenting patients with symptoms consistent with malaria were screened for P. falciparum by microscopy and RDT. Thirty-seven samples positive for P. falciparum from patients with self- reported antimalarial medication use were selected for molecular studies. Genomic DNA of malaria positive samples were extracted from dried blood spots (DBS) using QIAamp DNA mini-kit (Qiagen, Valencia, CA). Sanger and next generation sequencing (NGS) methods were used to screen for mutations in three genes (Pfcrt, Pfmdr1 and Pfk13) that have been previously associated with antimalarial resistance. Amplification and sequencing of the Pfk13, Pfcrt, and Pfmdr1 genes was successfully performed in 26 samples. Plasma concentration for cytokines (IL-12p70, IFN-γ, TNF-α, IL-10, TGF-β), and corticosteroids (cortisol and dexamethasone) were evaluated using enzyme-linked immunosorbent assay (ELISA) in twenty-six patients’ samples categorized as treated, untreated and control. Of the common fragments sequenced by both methods, more mutations and haplotypes were detected by NGS than by Sanger. The NGS method detected three Pfk13, seven Pfcrt, and six Pfmdr1 mutations in our clinical isolates which include rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which, to our knowledge, were previously unreported. Nineteen of the 26 (73.1%) isolates had one or more Pfk13 mutations, 9 of the 26 (34.6%) isolates had one or more Pfcrt mutations, and 22 of the 26 (84.6%) isolates had one or more Pfmdr1 mutations. There was moderate prevalence of the K76T mutation (34.6%) and CVIET haplotype (30.8%) associated with chloroquine and amodiaquine resistance and high prevalence of the Pfmdr1 N86 wild type allele (92.3%) and NF (84.6%) haplotype associated with lumefantrine resistance. None of the mutations in the Pfk13 gene associated or confirmed with resistance to artemisinin in South-East Asia was seen. There was a correlation pattern showing that IL-10, IFN-γ and TGF-β levels were markedly lower while the level of cortisol increased but that of dexamethasone-induced protein decreased in treated compared with untreated patients. This result suggests that the interplay between cytokine and endocrine response could have a modulating effect on malaria unresponsive to treatment. This study describes polymorphism in three antimalarial resistance associated genes and how sensitive detection methods such as the NGS can strengthen surveillance for resistant alleles and enhance malaria control efforts.
- ItemOpen AccessBiopharmaceutical and Pharmacokinentic Studies on Various Formulations of Amodiaquine in Artemisinin Combination Therapies.(School of Postgraduate Studies University of Lagos., 2008) Akinyele, M.O
- ItemOpen AccessDeveloping novel mucoadhesive chitosan based formulations for drug delivery to the urinary bladder(2019-02) Kolawole, O.M.My PhD project aims to develop novel chitosan derivatives (with superior mucoadhesiveness) for transmucosal application. The intravesical route was chosen as the exemplar transmucosal mode of drug delivery due to the limited therapeutic efficiency of conventional bladder cancer formulations. Drug carriers with improved mucoadhesive properties may prolong drug residence in the bladder. First, three chitosan grades were used to prepare chitosan/β-glycerophosphate in situ gelling mixtures and from these grades, the high molecular weight graded chitosan (HCHI) was chosen for chemical derivatisation based on its superior gelation, mucoadhesive and drug release potential. HCHI was conjugated with varying amounts of methacrylate or phenylboronate groups in order to evaluate the influence of the type and amount of conjugated hydrophobic pendant group on their physicochemical and mucoadhesive properties. The boronated and methacrylated chitosans were characterised using 1H NMR and FT- IR. There was good correlation in the extent of hydrophobic modification for methacrylated and boronated chitosans using 1H NMR and ninhydrin test. Methacrylated and boronated chitosan exhibited comparable resistance to pH influence on their solubility. The degree of methacrylate or boronate conjugation had a significant influence on themucoadhesiveness of the drug carriers studied using a urine flow-through technique/fluorescent microscopy as well as a texture analyser, on porcine bladder in vitro. Boronate groups conferred Boronate groups conferred superior mucoadhesive behaviour on chitosan relative to methacrylate groups. Methacrylated chitosan displayed a similar safety profile to the parent chitosan based on MTT assay on UMUC3 bladder cancer cells. The biocompatibility studies of boronated chitosan will be carried out in future studies using bladder cell lines despite the fact that several in vitro and in vivo studies have established the safety of phenylboronic molecules. Methacrylation and boronation of chitosan has been identified as efficient strategies to generatemoremucoadhesive drug carriers which could prolong drug residence time in the bladder thereby improving therapeutic outcomes of bladder cancer patients. These novel polymers were easily synthesised requiringminimal equipment suitable for industrial scale- up. These excipients could be used to formulate affordable transmucosal dosage forms with superior mucoadhesiveness for a variety of biomedical applications.
- ItemOpen AccessDevelopment of Electrospun Nanofibres for the Pre-Concentration of Organochlorines.(2012) Adeyemi, D.KThere has been an increasing concerns on public health implication of Organochlorines contamination of the environment. Organochlorines are widely used in Pharmaceutical industries and agricultural purposes worldwide most especially as disinfectants, pesticides and industrial fluids. As a result of its acute toxicities, the compounds are attracting strict legislation by various regulatory bodies across the world. As a consequence, there is a greater need to develop and improve the existing pre-concentration methods for the analysis of these compounds. The extraction of Organochlorines is traditionally carried out to isolate the trace analytes from the complex matrices. Solid Phase extraction (SPE) has gained a wide recognition for extraction of Organochlorines due to its simplicity of operation and good reproducibility. However, the conventional sorbents in SPE have limitations of specificity for analyte. In recent times, electrospun nanofibres is sought as an alternative sorbent for pre-concentration of trace analytes. Hence, in this study, we developed and characterized electrospun polystyrene nanofibers incorporating different potassium salts of imidazole-1-carbodithioate for pre-concentration of Organochlorines. The diameter of Electrospun Polystyrene nanofibers ranged from 130-500 nm. The sorption and desorption of a model Organochlorine pesticide; pp-1,1-dichloro-2,2 bis-(4-chlorophenyl) ethylene, DDE (0.25-2.0 µg L-1) on the nanofibers were optimized and and monitored with Gas Chromatography. Optimum sorption of DDE (0.50 µg L-1) on electrospun Polystyrene and carbodithioate incorporated Polystyrene nanofibres was at 43.7% and 94.6% respectively in 20 min, while optimal desorption on the Pressurized Hot Water Extraction system was 96.5 % in 30 min. The incorporation of diazole carbodithioate (diazoles) doubled the sorption efficiency of electrospun polystyrene nanofibres and achieved a Limit of Detection of 0.234 ng L-1 for DDE. The study shows that the functionalized electrospun nanofibrers has a great potential for pre-concentration of Organochlorines and the application of PHWE provides an opportunity to eliminate organic solvents in procedures aimed at monitoring of organic pollutants in the environment. The analysis for Organochlorines in fish and water samples of Lagos lagoon revealed the accumulation trends of the contaminants. The residual concentration of Organochlorines in water and fish samples varied from Non-detectable to 0.996 µg/L and 0.01 to 8.92 mg/kg wet weight respectively. The residual concentrations of Organochlorine in 37.3% of water samples analyzed were greater than European Community allowable residue limit in drinking water, while the residue concentrations of Organochlorines (except for HCHs) in fish samples were below the codex alimentarious commission of FAO-WHO allowable residue limit.
- ItemOpen AccessEfficacy Studies of Dihydroartemisinin Plus Mefloquine Combination in Children with Uncomplicated Plasmodium Falciparum Malaria in Lagos State, Nigeria(School of Postgraduate Studies, 2009-04) Aina, O.OFull texts attached
- ItemOpen AccessEmulsifying and suspending properties of Okra Mucilage in Liquid drug delivery systems(School of Postgraduate Studies of the University of Lagos, Akoka, 1992) Brown, S.ADrugs are chemical substances which may be natural in origin, or semi-synthetic. the sole aim of the use of drugs is to cure or ameliorate and prevent disease conditions.
- ItemOpen AccessEvaluation of the Phamacological and Toxicological Actions of Byrsocarpus Coccineus Schum and Thonn. (Connaraceae)(School of Postgraduate Studies, 2009-11) Akindele, A.JFull texts attached
- ItemOpen AccessFormulation of Quinine Suppository and Evaluation of Quinine uptake in the Mouse Brain.(2011) Soremekun, R.OThe occurrence of resistance to chloroquine and sulfadoxine/pyrimethamine by Plasmodium falciparum stimulated new interest in quinine for treating multi-resistant falciparum infection. Parenteral quinine is the gold treatment in the management of severe and complicated malaria. There is the need for early initiation of treatment in management of complicated malaria. An antimalarial drug to be used at home must be safe, effective, affordable and easy to administer A rectal formulation of quinine will serve the purpose of home initiation of treatment. The main objective of this work was to develop a stable quinine suppository that will ensure adequate release of quinine and evaluate quinine uptake into the four sections of the mouse brain Cocoa butter and Fattibase TM were used in the preparation of suppositories containing 200mg quinine bisulphate. The release profiles of the formulations with varying concentrations of polysorbate 80 (0, 1, 2 and 5%) were evaluated by in-vitro dissolution in pH 8 buffer medium. Evaluation of brain uptake was carried out in various stages using the murine mice model. Quantification of uptake into the four brain sections was done with a High Pressure Liquid Chromatography technique. Uptake was compared in the four brain sections of parasitized and non-parasitized murine mice as a function of time (30, 60, 120, 180, 240 min). Quinine uptake from suppository was also compared with uptake from peritoneal injection in parasitized and non-parasitized. The values obtained were subjected to statistical analysis using the 3-way ANOVA. The Formulations of suppositories in cocoa butter and FattibaseTM released quinine in adequate quantity. Addition of polysorbate 80 improved release of quinine significantly (P = 0.005 for cocoa butter and P = 0.003 for FattibaseTM). Cocoa butter with 1% Polysorbate 80 released 36.8% quinine bisulphate in 60 min while release from suppositories with 2% and 5% surfactant was erratic. FattibaseTM suppositories with 5% polysorbate 80 released 85% quinine content in 60min. This formulation was stable in the refrigerator for three months while samples stored at ambient temperature were stable for one month. From the release profiles, three formulations have very high potentials in management of cerebral malaria: cocoa butter+1%, FattibaseTM + 2% and 5% respectively. Fluorescence microscopy revealed green fluorescence characteristic of quinine in the brain sections of parasitized and non-parasitized mice treated with quinine. Quinine crossed the blood brain barrier into the brain in parasitized and non-parasitized mice. This confirms that inflammation is not required for the transport of quinine bisulphate into brain. Quinine from the suppository was available in the brain in 30 min. Uptake had a significant time–dependence (P=0.000). Uptake in parasitized mice was significantly higher than that in the non-parasitized mice (0.000). Quinine uptake varied significantly in the four brain sections with olfactory lobe recording the highest uptake in the two groups of mice (0.000). Quinine uptake in the parasitized mice is biphasic while a steady decline was observed in non-parasitized mice over the time period. The concentration of quinine taken up by other brain sections: cerebrum, cerebellum and medulla oblongata was significantly lower than the concentration in the olfactory lobe with cerebrum having the lowest uptake in the parasitized mice. This intra-rectal formulation will be useful in pre-referral management procedures in primary health facilities, homes and rural areas.
- ItemOpen AccessGenotoxic Investigation of some Environmental Pollutants and Therapeutic Agents: Roles of antioxidants on the Mutagenicity and Toxicity of Rifampicin(School of Postgraduate Studies, 2009-12) Awodele, OFull texts attached
- ItemOpen AccessHepatotoxicity and Hematological Effects of Combination First-Line Antituberculosis Drugs in Healthy Sprague-Dawley Albino Rats(School of Postgraduate Studies, 2009-04) Lawal, B.AFull texts attached
- ItemOpen AccessHome Management of Uncomplicated Childhood Malaria by Mothers and Fathers in Lagos State, Nigeria(2015) Ailoje, K.OMalaria is a major public health disease. About 90% of all malaria deaths globally occur in Sub- Saharan Africa where Nigeria is located. Children are particularly susceptible resulting in high mortality. Mothers stay at home to care for children with malaria, thereby increasing absenteeism resulting in economic loss at the micro and macro levels. World Health Organization (WHO) in an attempt to ensure prompt treatment of uncomplicated childhood malaria, introduced home management of malaria involving care givers. The work was designed to study home management of uncomplicated childhood malaria by 485 mothers and 324 fathers in Lagos State, Nigeria using artemisinin combination therapy (ACT) drugs and to determine compliance with the National Treatment Guidelines for malaria. Lagos State is situated in the south-west of Nigeria with 20 local government areas (LGAs). Four LGAs were randomly selected. A town was selected from each LGA. Each town was zoned into 4 (east, west, north and south). From each zone, 30 mothers and 30 fathers were randomly selected. The instrument used for data collection was a structured questionnaire which was either self-administered or interviewer-administered (non-formal education respondents). Data were analysed statistically as means, standard deviation, standard error, Chi-Square test, Pearson analysis were done as appropriate and P<0.05 was accepted as the level of significance. Majority of respondents (87%) were in the age range 18 – 40 years, and 93% had one or two children. Mothers and fathers had a good knowledge of home management of uncomplicated childhood malaria (HMM). Irrespective of educational background, they commenced treatment between 0 and 7hrs after noticing the signs of malaria. Majority of them used artemether-lumefantrine (an ACT) in compliance with the National Treatment Guidelines for malaria. Chloroquine, though withdrawn, was used by 22% of respondents, whilst artesunate-amodiaquine, the second official drug, was rarely used. Educational background was a determinant of their knowledge of the cause and prevention of malaria. Fever ranked highest among the signs of malaria, followed by chills/rigors, vomiting, pallor, dehydration and body temperature in descending order. Majority (72%) of respondents always noticed improvement irrespective of gender and education. Unresolved cases (76%) were referred to a formal health facility. An average of 86% did not notice any of the signs of complicated malaria suggesting that they managed uncomplicated malaria. Fathers (83%) always practised HMM, while 12% did occasionally, 66% preferred paracetamol and/or antimalarial drugs, followed by tepid sponging and others. The rest were counselled as to the importance of referral. Drugs were mostly obtained from the pharmacy > doctors > primary health centre >> “chemist” > others. Factors determining access to drugs included cost, availability, brand, previous efficacy and packaging, were significantly influenced by the educational status. In conclusion, mothers and fathers understood and practised HMM of uncomplicated childhood malaria in Lagos State, using ACTs in compliance with The National Treatment Guidelines for malaria, with referral in unresolved cases.
- ItemOpen AccessHome Management of Uncomplicated Childhood Malaria by Mothers and Fathers in Lagos State, Nigeria(School of Postgraduate Studies University of Lagos, 2014-11) Ailoje, K.O.Malaria is a major public health disease. About 90% of all malaria deaths globally occur in Sub- Saharan Africa where Nigeria is located. Children are particularly susceptible resulting in high mortality. Mothers stay at home to care for children with malaria, thereby increasing absenteeism resulting in economic loss at the micro and macro levels. World Health Organization (WHO) in an attempt to ensure prompt treatment of uncomplicated childhood malaria, introduced home management of malaria involving care givers. The work was designed to study home management of uncomplicated childhood malaria by 485 mothers and 324 fathers in Lagos State, Nigeria using artemisinin combination therapy (ACT) drugs and to determine compliance with the National Treatment Guidelines for malaria. Lagos State is situated in the south-west of Nigeria with 20 local government areas (LGAs). Four LGAs were randomly selected. A town was selected from each LGA. Each town was zoned into 4 (east, west, north and south). From each zone, 30 mothers and 30 fathers were randomly selected. The instrument used for data collection was a structured questionnaire which was either self-administered or interviewer-administered (non-formal education respondents). Data were analysed statistically as means, standard deviation, standard error, Chi-Square test, Pearson analysis were done as appropriate and P<0.05 was accepted as the level of significance. Majority of respondents (87%) were in the age range 18 – 40 years, and 93% had one or two children. Mothers and fathers had a good knowledge of home management of uncomplicated xx childhood malaria (HMM). Irrespective of educational background, they commenced treatment between 0 and 7hrs after noticing the signs of malaria. Majority of them used artemether-lumefantrine (an ACT) in compliance with the National Treatment Guidelines for malaria. Chloroquine, though withdrawn, was used by 22% of respondents, whilst artesunate-amodiaquine, the second official drug, was rarely used. Educational background was a determinant of their knowledge of the cause and prevention of malaria. Fever ranked highest among the signs of malaria, followed by chills/rigors, vomiting, pallor, dehydration and body temperature in descending order. Majority (72%) of respondents always noticed improvement irrespective of gender and education. Unresolved cases (76%) were referred to a formal health facility. An average of 86% did not notice any of the signs of complicated malaria suggesting that they managed uncomplicated malaria. Fathers (83%) always practised HMM, while 12% did occasionally, 66% preferred paracetamol and/or antimalarial drugs, followed by tepid sponging and others. The rest were counselled as to the importance of referral. Drugs were mostly obtained from the pharmacy > doctors > primary health centre >> “chemist” > others. Factors determining access to drugs included cost, availability, brand, previous efficacy and packaging, were significantly influenced by the educational status. In conclusion, mothers and fathers understood and practised HMM of uncomplicated childhood malaria in Lagos State, using ACTs in compliance with The National Treatment Guidelines for malaria, with referral in unresolved cases.
- ItemOpen AccessIsolation and Characterization of Antimalarial Compounds from Root Bark of Callichilia Stenopetala Stapf. (Family Apocynaceae)(2015-09) Orabueze, I.CPlants and their metabolic products have served as therapeutic weapons for treatment of various human and animal diseases. Callichilia stenopetala Stapf (family Apocynaceae) has been used by traditional practitioners in the South-eastern part of Nigeria as a remedy for the treatment of various ailments including different types of resistant malaria with their “re-current” fever. Malaria with emergence of its drug resistant parasites is a major health issue in the tropics and subtropical areas of the world. This study was aimed at evaluating in vivo antiplasmodial activities of methanolic extracts of some Nigerian medicinal plants. Antioxidant activity was included as a supporting factor, considering the relationship between oxidative stress and chronic diseases. Seven plants were initially evaluated for their antimalarial and antioxidant activities and the plant with the most promising activity was studied further. Phytochemical analysis and oral acute toxicity of methanolic extract of C. stenopetala was carried out using standard procedures. The methanolic extract of C. stenopetala was fractionated with water and organic solvents viz:- hexane, chloroform and ethyl acetate successively to obtain various fractions. Antiplasmodial activities of the crude extract and the obtained fractions of C. stenopetala were studied in detail against chloroquine sensitive Plasmodium berghei berghei NK 65 – infected mice using 4-day suppressive test procedure. The result was compared with some standard antimalarial agents, chloroquine phosphate and artesunate. An attempt was also made towards isolating and elucidating the structure(s) of constituent(s) thought to be responsible for the antimalarial activity of the plant. Bio-activity guided chromatographic isolation of two most active fractions – hexane and chloroform was done. The isolates obtained were subjected to spectral analysis for characterization using various spectrometric and chromatographic techniques: one-Dimensional (1D) and two-Dimensional (2D) NMR techniques, Attached Proton Test (APT), Correlation Spectroscopy (COSY), Nuclear Overhauser Effect Spectroscopy (NOESY), Heteronuclear Multiple Bond Correlation (HMBC), Heteronuclear Single Quantum Coherence (HSQC), Infra-red (IR), Gas Chromatography-Mass Spectroscopy (GC-MS) and X-ray crystallography. In vitro anti-oxidant activity of the crude extract, the obtained fractions and the pure isolates were also assessed using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and total phenolic content (TPC). The root bark of C. stenopetala was selected for the study based on its promising bioactivity. Results of its phytochemical analysis test showed presence of alkaloid, saponins, tannins, triterpenes and phenolic compounds. No mortality or evidence of adverse effects was observed in acute toxicity test. The crude extract, the hexane fraction and chloroform fraction demonstrated intrinsic antimalarial properties that were dose-dependent. A comparative analysis indicated that at dose 250 mg kg-1, the crude extract, hexane and the chloroform fractions produced 69.3, 82.24 and 39.9% suppression of parasitaemia respectively against 82.1% for chloroquine (5 mg kg-1) and 73.80% for artesunate (10 mg kg-1). Three active compounds, structurally elucidated as vobtusine, α-amyrin acetate and lupeol acetate were isolated and they exhibited significant (P< 0.05) chemosuppression at 7 – 10 mg kg-1 (62.2, 67.61 and 68.65% respectively) compared with the standard drugs chloroquine and artesunate. The antioxidant activities of the crude extract and the fractions were dose-dependent, and the effect resides mainly in the aqueous and ethyl acetate fractions. Only vobtusine exhibited a significant free radical scavenging effect (68.7%) at 0.2 mg mL-1. These results suggest that C. stenopetala root bark has antimalarial and antioxidant activities which may be due to the isolated compounds. This is the first report on antimalarial constituents of C. stenopetala, to the best of my knowledge.
- ItemOpen AccessIsolation and Characterization of Privileged Structures from Hunteria Umbellata (Apocynaceae) and the Evaluation of their Cancer Multidrug Resistance Inhibitory Activities.(2012) Ajala, O.SChemotherapy remains the best means of treatment of metastatic cancer. It is however bedevilled by the phenomenon of multidrug resistance (MDR) whereby cancer cells evade the cytotoxic effects of chemotherapeutic agents of diverse chemical structures and mechanisms of action. The MDR phenomenon has been found to be principally mediated by the over experession, by cancer cells, of the ATP-Binding Cassette (ABC) superfamily of trans membrane transporter proteins, the most important member of which is the Permeability glycoprotein (P-gp). The biogenetic and structural analogy between serotonin, an established substrate of a known ATP-dependent transmembrane transporter (i.e. serotonin reuptake pump), and monoterpenoid indolealkaloids (MTIAs) provided the rationale for a structure-guided exploration of the leaf, stem-bark, and seeds of the plant Hunteria umbellata (Apocynaceae) for MTIAs as highly probable inhibitors of the P-gp. Furthermore, an observation of the fact that MTIAs are essentially privileged structures prompted similar structure-guided exploration of the same plant materials for iridoid- and terpenoid- privileged structures to enhance the chances of isolating putative P-gp inhibitors from the plant. The main structural-guide was 1H NMR profiling at 600MHz; isolation and purification were largely by High Performance Liquid Chromatography (HPLC); gross structure elucidation was done by a combination of 1D and 2D NMR (1H , 13C , 1H-1H gCOSY, DEPT-edited 1H-13C HSQC and 1H-13C gHMBC) data acquisition with subsequent interpretation aided by molecular formula information from High Resolution ElectroSpray Ionization Mass Spectrometry (HRESIMS). Assignment of relative configuration, where necessary, was done by coupling constants analysis, supported in a few cases by the 1H-1H ROESY 2D NMR spectral analysis. P-gp inhibition evaluation was by slightly modified standard procedures; using calcein (a fluorescing dye) accumulation in SW620 AD300 (a MDR subline of human colon carcinoma cells selected at 300ng/ml of adriamycin) as indicator. In all, three new MTIAs (N-[2-(2-carbomethoxy-3-indolyl)ethyl]-3-ethylpyridinium, 4-chloromethylakuammineammonium ion, and desmethylserpentinine), four known MTIAs (serpentine, pseudoakuammigine, 4-methylhuntrabrineammonium ion and strictosidinic acid), one known triterpenoid (ursolic acid) and one new lactone iridoid glucoside (1-glucopyranosyl-8-methyliridan-3-en-4,7-carbolactone) were isolated and chemically characterized. Four of the compounds (N-[2-(2-carbomethoxy-3-indolyl)ethyl]-3-ethylpyridinium, serpentine, strictosidinic acid and pseudoakuammigine) demonstrated highly significant P-gp inhibitory activities (P < 0.01), each at 25μg/ml. The discovered afore-mentioned four compounds with highly significant P-gp inhibitory activities could be employed as leads the development of clinically applicable P-gp inhibitors for co-administration as adjuncts with anticancer drugs for effective cancer chemotherapy.
- ItemOpen AccessIsolation and Characterization of the Anti-diabetic Principle(s) in the Aqueous Extract of Graptophyllum Pictum (linn.) Griff. (Acanthaceae) Leaf.(2011) Olagbende – Dada, S.OThis research was embarked upon in order to verify the anti-diabetic property reported on the aqueous extract of Graptophyllum pictum leaf and establish an effective dose for the active extract. It aimed to identify and isolate some chemical constituents in the active extract. It also proposed to start the toxicity study of the active extract by testing for acute toxicity. The anti-diabetic investigation was carried out in 4 groups of alloxan induced diabetic rats that were orally administered 4 different doses (50, 100, 150 and 200 mg/kg) of the aqueous extract. Two other groups of the diabetic rats were administered distilled water (vehicle of administration) and metformin (a well known anti-diabetic drug) at 10 mg/kg to serve as controls. The acute toxicity screening of the active extract was carried out on 4 groups of mice at doses that are much higher (1, 2, 3 and 4 g/kg) than the anti-diabetic doses. The methanolic extract of the leaf was investigated for chemical constituents using simple phytochemical tests. The extract was subjected to column and high performance chromatographic techniques and in tandem with chemical ionization mass spectrometry in order to separate and isolate some of its chemical constituents. The structural elucidation of the isolated compounds were achieved with the aid of proton (1H) and carbon (13C) nuclear magnetic resonance (NMR) spectroscopy using 2-dimensional (2D) techniques such as proton-proton correlation spectroscopy (1H-1H COSY), heteronuclear multiple quantum correlations (HMQC) and heteronuclear multiple-bond correlations (HMBC). The tested aqueous extract was found to possess anti-diabetic action which was comparable to that of metformin. The effective dose was established at 100 mg/kg. The phytochemical investigation of the extract revealed the presence of polyphenolic compounds, saponins, reducing sugars and alkaloids; the absence of anthraquinones, cardiac glycosides and cyanogenetic glycosides. The separation/isolation exercise resulted in the isolation of a yellow crystalline compound which did not yield to acid hydrolysis suggesting the likelihood of a C-glycoside as opposed to an O-glycoside. The melting point was found to be 226.3oC. The high resolution atmospheric pressure in tandem with chemical ionization mass spectrometry of the compound showed three molecular ion peaks at m/z 565 corresponding to the molecular formula C26 H28O14 and the fragmentation pattern together with the fragments produced confirmed the isolated compounds to be C-glycosides of apigenin a poly phenol (flavonoid). The analysis of the 13C NMR spectra of the sugar portions also support the suggestion that the sugar(s) were C-bonded for they were revealed as 1 unit of D glucopyranose and L-arabinopyranoside bonded directly to carbon atoms at positions 6 and 8. A search through spectral library helped to identify the isolated compounds as schaftoside, isoschaftoside and neoschaftoside. They were found to be isomers. The aqueous extract of Graptophyllum pictum exhibited anti-diabetic action at 100 mg/kg which is comparable to metfomin a standard anti-diabetic drug. From this active extract, three isomers of apigenin C-glycosides were detected, characterized and elucidated to be schaftoside, isoschaftoside and neoschaftoside.
- ItemOpen AccessThe kinetics and mechanics of survival of microbial contaminants in IV dextrose infusion fluids(School of Postgraduate Studies of the University of Lagos, Akoka, 1992) Udo, E.AThe problems of infection is a universal one, which can only be educed through adoption of scientifically established operational technique. Basically, the use of aseptic procedure in some aspects of patient care is a sine qua non for such control.
- ItemOpen AccessMalaria in Hiv/Aids: a Study of Anti-Retroviral Drugs on Malaria Parasitaemia.(2012) Akinyede, A.AThe Centre for Disease Control has reported that at least 500 million people suffer from malaria every year. The situation is worse in Africa which accounts for at least 300 million of those with malaria fever (WHO, 2006). The problem of malaria on the health of Africans has been compounded by HIV/AIDS, a leading cause of death in the region, especially since the two diseases co-exist in some individuals. A structured questionnaire was used to assess the knowledge, preventive and treatment seeking practice in respect of malaria among 469 patients attending the Human Immunodeficiency Virus (HIV) Clinic at the Lagos University Teaching Hospital. Also, the prevalence of malaria parasitaemia among patients without clinical malaria as well as the relationship between clinical diagnosis of malaria and malaria parasitaemia was investigated in 100 patients, respectively, attending the HIV Clinic by microscopic examination of blood smears for malaria parasites. Microscopic examination of blood smears of 100 patients was also carried out for malaria parasites, while hematological parameters were tested to determine the relationship between malaria parasitaemia and these hematological parameters. One hundred HIV infected patients were surveyed for their drug use and malaria parasitaemia probing for antiplasmodial effects of these drugs. Furthermore, the antiplasmodial effects of antiretroviral drugs, lamivudine, zidovudine, nevirapine and stavudine on plasmodia berghei inoculated into mice were investigated. Out of the respondents, 235 (47.6%) respondents did not know how malaria could be prevented. Only 42(8.5%) respondents knew of prevention by insecticide treated bed nets, while 138 (27.9%) had knowledge of non-insecticide treated bed nets. Sulphadoxin/pyrimethamine was the commonest known antimalaria, followed by choloroquine and artemisinin based combination therapy representing 28.5%, 15.4% and 11.7% respectively. Also, 34.8% of the respondents knew the appropriate antimalaria drug dosage. Most of the patients visited the HIV/AIDS Clinic, General hospitals or private hospitals whenever they perceived an attack of malaria fever representing 17.8%, 15.2% and 18.6% respectively. Only 244 (52%) of the patients used insecticide treated bed nets for prevention of malaria. There was significant association between the patients’ level of education and use of prophylactic antimalaria P=0.01. There was no demonstrable malaria parasitaemia in the blood smears of 91 out of the 100 HIV infected patients who had been clinically diagnosed as malaria fever, malaria parasitaemia among these patients was significantly less than it was in the control group, P = 0.000. The patients with the highest CD4 count, >350 had the highest malaria parasite density, while the remaining 2 groups with CD4 values of <200 and 200-350 had lower parasite densities. The patients with the lowest viral load <20, 000 had significantly higher malaria parasite density compared with the groups with viral load 20,000-40,000 and 60,000-80,000, P=0.18, 0.021 respectively. These patients, with <20, 000, were on antiretroviral drugs, while those with the higher viral load and less densities were not. Three of the patients on co-trimoxazole, in the last 28 days, had malaria parasitaemia, while malaria parasitaemia was not found in the blood smears of those on other antimalaria drugs during the period. There was significant dissociation between the use of antiretroviral drugs and the presence of malaria parasitaemia, P=0.006. Zidovudine as a single therapy and triple drugs combination of lamivudine, zidovudine, nevirapine completely eliminated plasmodia berghei infection in mice, when these drugs were given as prophylactic and curative regimens. The findings reveal the need to improve on the health education of patients infected with the Human Immunodeficiency Virus in respect of malaria and to carry out laboratory diagnosis of these patients before antimalaria therapy is administered. Also, the antiplasmodial effect of zidovudine and lamivudine, zidovudine, nevirapine combination has been shown.
- ItemOpen AccessMolecular Characterization of Plasmodium Falciparum Resistant Genes to Chloroquine and Sulphadoxine-Pyrimethamine in Children with Uncomplicated Malaria in Lagos.(2012) Oladosu, O.OMalaria is one of the major causes of morbidity and mortality in young children in sub-Saharan Africa where it presents primarily with fever. The reports of malaria prevalence in Nigerian children are divergent with wide variation in prevalence reports despite the scaling-up of malaria control in many countries, including Nigeria. Despite the change in the National antimalarial treatment policy from Chloroquine (CQ) and Sulphadoxine-pyrimethamine (SP) to artemisinin combination therapies (ACTs), CQ and SP are still frequently used in health facilities in the general population because it is cheap, affordable and accessible. Resistance to CQ and SP has contributed to increase mortality caused by Plasmodium falciparum infections. The continuous use of non-efficacious antimalarials will consequently result in an increase in antimalarial- resistant Plasmodium parasites which could pose a threat to the partner drugs to the Artemisinin such as (Amodiaquine, Mefloquine etc). Genetic markers to predict Plasmodium parasites’ resistance especially for single nucleotide polymorphism (SNPs) have the potential to be employed in an integrated fashion to provide timely information that is useful to policy makers on P falciparum resistance to antimalaria. Children less than 12years old, who presented with documented fever or history of fever in the last 24 hours between July 2007 and April 2008 were enrolled in this study. Of the 1211 children (<12years) enrolled, 251(20.7%) were slide positive for malaria parasites. Children in the age groups 0-≤1 and >1-12years had a prevalence of 11% and 5.8% respectively (P=0.001). While children in the age group 0-≤5 and >5-12years had malaria prevalence of 16.9% and 42.1% respectively (P=0.001). Of the malaria positive children 33.9% had parasitaemia of less than 500p/µl (P=0.001). This indicated a shift in malaria prevalence from the usually reported 0-≤5years to the >5-12years old children. The occurrence of point mutations and haplotypes were investigated in DNA obtained from blood samples of slide positive children by assaying for Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and Plasmodium falciparum multi-drug resistance (Pfmdr1) genes associated with CQ and other 4-aminoquinolines resistance. The frequency of the mutant Pfcrt haplotype, CVIET, was 91.6% while, the frequency of Pfmdr1 in the positive microscopy samples was 62.2% and 69.0% for codon Y86 and F184 respectively. No mutation was seen at codons 1034, 1042 and 1246 of the Pfmdr1 genes in this study. The combined Pfcrt and Pfmdr1 haplotypes showed that most of the malaria positive children had CVIET + YFSND haplotypes (61.9%). There was no association between parasitaemia and Pfcrt and Pfmdr1 haplotypes. The high prevalence of the mutant genes (CVIET) seen among this children could limit the already poor efficacy of the partner drugs to the Artemisinin. Thus, the continuous use of CQ and other 4-aminoquinolines when used as monotherapy in Lagos State could increase the frequency of mutations in Pfcrt and Pfmdr1 genes. Sequenced results of the amplified Dihydrofolate reductase (Dhfr) and Dihydropteroate synthase (Dhps) genes for SNPs showed mutations at codons 108 (96.5%), 59 (92.9%) and 51 (94.7%). Four Dhfr haplotypes (ACIRNVI, ACICNVI, ACNCNVI and ACNCSVI) and eleven Dhps haplotypes (ISGKAA, VAGKGS, VAGKAA, IAGKAS, ISAKAA, IAAKAA, ISGKGA, IFGKAS, IAGKAA, VSGKGS and ISGKAS) were grouped. The grouped data showed that most of the isolates (92.9%) had the triple Dhfr mutation (51I, R59 and 108N), while the majority of the isolated P. falciparum in the Dhps gene had mutation at codon G437 (96.6%). The combined haplotypes assessment showed that ACIRNVI + ISGKAA (quadruple mutation) had the highest occurrence (56.7%). There was no mutation at V16, R50 and L164 of the Dhfr gene and at E540 of the Dhps gene. These reports showed a high frequency of mutations in Dhfr and Dhps genes in Nigeria. Furthermore, it provided information on haplotypes and its distribution on clinical samples from children in Lagos. The continuous use of SP as monotherapy against malaria and the reported high frequency of mutations in Dhfr and Dhps genes could compromise the efficacy of SP-artesunate combination.