Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice

Background & objectives: Human and livestock African trypanosomiasis, otherwise known as sleeping sickness,is a neglected tropical disease of public health importance in west and central Africa. In view of the adverse sideeffects of the antitrypanosomal drugs, the relatively few side effects observed in ivermectin use, and becauseboth onchocerciasis and typanosomiasis occur in overlapping foci in Africa, it would be desirable if the ivermectinthat has been used successfully on onchocerciasis management could also be used in the control and treatmentof trypanosomiasis.Method: In this study, prophylactic and therapeutic effects of ivermectin (Mectizan) were investigated in albinomice infected with a Nigerian strain of Trypanosoma brucei brucei.Results: A 300 μg/ml/kg dose had the most effective impact because it showed the highest mean survival time of12 days in both the treatment and prophylactic groups of mice. This dose also enhanced the defence capacity ofthe treated groups. It also had positive influence on the packed cell volume (PCV) and the state of anaemia inthe trypanosome infected mice, hence, improving their survivability.Interpretation & conclusions: Our report indicates that using the 300 μg/ml/kg dose of ivermectin increases themean survival period from 5 to 12 days. This suggests that ivermectin could be possibly used in the treatment oftrypanosomiasis. Further studies will be required to show whether proper treatment may entail a single dose, asused in this study; an increased number of doses, or combinations with other drugs

Spectral Analysis of the Residual Magnetic Anomalies Overpategi and Egbako Area of the of the Mddle Niger Basin, Nigeria

Statistical spectral analysis of theresidual magnetic field was employedto determine the depth to magnetic basement rocks withinPategi and Egbako areas which is part of the lower Middle Niger basin. The study area lies within latitudes 8.300 and 9.300 North and longitudes 5.300 and 6.000 East. For the purpose of this analysis, the study area was divided into 15 rectangular sections. The spectral analysis reveals two prominent layers; the first layer depth varies from 0.28km to 0.89km with an average value of 0.59km while the second layer depth varies from 1.55km to 4.70km.The first layer is attributed to lateritic ironstone,Ferruginoussandstone and effect of the surrounding basement rocks while the second is attributed to magnetic rocks intruded into the basement surface, lateral discontinuities in basement susceptibility and intra basement features such as faults and fractures. The second layerrepresents the average thickness of the sedimentary formation overlying the basement complex within the Pategi and Egbako areas of the Middle Niger basin. This depth increases thepossibility of hydrocarbon potential. Keywords: spectral depth, buried magnetic rocks, magnetic dat

Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide

Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes

Učinci oralnog davanja mononatrijeva glutamata na morfologiju jaja i rezervu spermija u nuzjajčanom repu mladih i odraslih štakora.

The effects of oral administration of varied doses of monosodium glutamate (MSG) on the morphology of the testes and cauda epididymal sperm reserves of rats were studied using 28 four-week old (young) male Sprague-Dawley rats and 28 twelve-week-old (adult) male Sprague-Dawley rats. Increasing doses (1 mg/g body mass, 2 mg/g body mass, and 4 mg/g body mass) of a 40% aqueous solution of monosodium glutamate were administered to the male Sprague-Dawley rats every 48 hours for 6 weeks, using a rat gavage needle. The results showed that age variation did not influence the effect of MSG on the parameters studied in male rats. There was a significant reduction in the cauda epididymal sperm reserves (P<0.05) and the serum testosterone levels (P<0.05) of the rats that received monosodium glutamate relative to the control rats. The histomorphology of the testes of the rats that were given monosodium glutamate did not differ from those of the rats in the control group. No overt pathological lesions were seen in the testicular sections. These observations suggest that monosodium glutamate may have adversely affected spermatogenesis by disrupting the hypothalamic-pituitarytestis regulatory axis, and not through any direct toxic effect on the testis.Učinci oralnog davanja različitih doza mononatrijeva glutamata na morfologiju jaja i rezervu spermija už nuzjajčanom repu bili su istraživani u pokusima na 28 štakora Sprague-Dawley u dobi od četiri tjedna (mladi) i na 28 štakora Sprague-Dawley u dobi od 12 tjedana (odrasli). Štakorima su bile primijenjene povećavajuće doze (1 mg/g tjelesne mase, 2 mg/g tjelesne mase i 4 mg/g tjelesne mase) 40% tne vodene otopine mononatrijeva glutamata svakih 48 sati kroz šest tjedana iglom prilagođenom za štakore. Rezultati su pokazali da razlika u dobi nije utjecala na učinak mononatrijeva glutamata na pretraživane pokazatelje. Ustanovljeno je značajno smanjenje rezervi spermija u nuzjajčanom repu (P<0,05) kao i razina serumskog testosterona (P<0,05) u štakora kojima je primijenjen mononatrijev glutamat u odnosu na kontrolnu skupinu. Histološki nalaz tkiva jaja štakora kojima je bio primijenjen mononatrijev glutamat nije se razlikovao od onog u štakora kontrolne skupine. Nisu bili uočeni patološki poremećaji u histološkim rezovima tkiva. Ovi nalazi upućuju na zaključak da mononatrijev glutamat može imati nepovoljan utjecaj na spermatogenezu prekidanjem regulacijske osi hipotalamus-hipofizatestis, a ne putem ikakvoga izravnoga toksičnoga učinka na testese

Functional Annotation Analytics of Rhodopseudomonas palustris Genomes

Rhodopseudomonas palustris, a nonsulphur purple photosynthetic bacteria, has been extensively investigated for its metabolic versatility including ability to produce hydrogen gas from sunlight and biomass. The availability of the finished genome sequences of six R. palustris strains (BisA53, BisB18, BisB5, CGA009, HaA2 and TIE-1) combined with online bioinformatics software for integrated analysis presents new opportunities to determine the genomic basis of metabolic versatility and ecological lifestyles of the bacteria species. The purpose of this investigation was to compare the functional annotations available for multiple R. palustris genomes to identify annotations that can be further investigated for strain-specific or uniquely shared phenotypic characteristics. A total of 2,355 protein family Pfam domain annotations were clustered based on presence or absence in the six genomes. The clustering process identified groups of functional annotations including those that could be verified as strain-specific or uniquely shared phenotypes. For example, genes encoding water/glycerol transport were present in the genome sequences of strains CGA009 and BisB5, but absent in strains BisA53, BisB18, HaA2 and TIE-1. Protein structural homology modeling predicted that the two orthologous 240 aa R. palustris aquaporins have water-specific transport function. Based on observations in other microbes, the presence of aquaporin in R. palustris strains may improve freeze tolerance in natural conditions of rapid freezing such as nitrogen fixation at low temperatures where access to liquid water is a limiting factor for nitrogenase activation. In the case of adaptive loss of aquaporin genes, strains may be better adapted to survive in conditions of high-sugar content such as fermentation of biomass for biohydrogen production. Finally, web-based resources were developed to allow for interactive, user-defined selection of the relationship between protein family annotations and the R. palustris genomes

Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts