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1.
Tumour Biol ; 43(1): 37-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935122

RESUMO

BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58µg/ml and PC3 cells with an IC50 of 48.17µg/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.


Assuntos
Annona/química , Antineoplásicos/farmacologia , Caspase 9/genética , Quimiocina CXCL1/genética , Nanopartículas Metálicas , Receptores de Interleucina-8B/genética , Prata/farmacologia , Adenocarcinoma/patologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Química Verde , Humanos , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Neoplasias da Próstata/patologia , Neoplasias do Colo do Útero/patologia
2.
Virus Genes ; 47(3): 439-47, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23955068

RESUMO

Human parainfluenza virus type 1 (HPIV-1), a paramyxovirus, is a leading cause of pediatric respiratory hospitalizations globally. Currently, there is no clinically successful vaccine against HPIV-1. Hence, there is a need to characterize circulating strains of this virus to establish the feasibility of developing a vaccine against the virus. The variable HPIV-1 hemagglutin-neuraminidase (HN) protein is found in the envelope of HPIV-1, where it initiates the infection process by binding to cellular receptors. HN is also the major antigen against which the human immune response is directed against. The present study focused on identifying mutations in the HN gene that would be useful in understanding the evolution of HPIV-1. 21 HPIV-1 isolates were obtained after screening nasopharyngeal samples from patients with influenza-like illness. The samples were collected from Mbagathi District Hospital Nairobi from the period July 2007 to December 2010. RT-PCR was carried out on the isolates using HN-specific primers to amplify a 360 nt in the most polymorphic region and the amplicons sequenced. Genomic data were analysed using a suite of bioinformatic software. Forty eight polymorphic sites with a total of 55 mutations were identified at the nucleotide level and 47 mutations at 23 positions at the amino acid level. There was more radical nonsynonymous amino acid changes (seven positions) observed than conservative nonsynonymous changes (one position) on the HN gene fragment. No positively selected sites were found in the HN protein. The result from the analysis of 21 HPIV-1 Mbagathi isolates demonstrated that the HN gene which is the major antigenic target was under purifying (negative) selection displaying evolutionary stasis.


Assuntos
Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Infecções por Respirovirus/virologia , Sequência de Bases , Pré-Escolar , Feminino , Hospitais de Distrito , Humanos , Lactente , Quênia , Dados de Sequência Molecular , Vírus da Parainfluenza 1 Humana/classificação , Filogenia , Estudos Retrospectivos
3.
BMC Complement Altern Med ; 13: 285, 2013 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-24160735

RESUMO

BACKGROUND: The Quinine tree (Rauvolfia caffra) is used as a medicinal plant among traditional communities in many countries to manage tumors and other diseases associated with oxidative stress. To validate indigenous knowledge and possibly position this herb for technology uptake and utilization, we established the level of antioxidant activity in R. caffra, and probed for the presence of associated phytochemicals. METHODS: Antioxidant activity was determined on 1,1-diphenyl-2-picrylhydrazyl (DPPH) while major phytochemicals were identified by multiple tests on methanol fractions. RESULTS: R. caffra showed promise as a cure, with antioxidant activity comparable to the commercially used drug quercetin (R. caffra = 79.7% ±1.9; quercetin = 82.6% ± 2.0). However, we found two phytochemicals with possible antagonistic effect: co-occurrence of alkaloids and saponins significantly reduced antioxidant activity (alkaloids only = 63%; alkaloids plus saponins = 15%; steroids, terpenoids and cardiac glycosides = 82%), thus alkaloids and saponins should be exclusive to each other in drug formulations. CONCLUSIONS: Antagonistic relationship among phytochemicals would affect the efficacy of crude extracts as used in traditional medicine. Unlike in herbal medicine, use of modern biotechnology in extraction, purification and design of optimal combinations will ensure efficient drug formulations with optimum bioactivity and minimum toxicity. Metabolic pathway engineering under a controlled environment may optimize availability of desired compounds.


Assuntos
Extratos Vegetais/química , Plantas Medicinais/química , Rauwolfia/química , Saponinas/química , Alcaloides/química , Alcaloides/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Biotecnologia , Interações Medicamentosas , Medicina Tradicional , Fitoterapia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Árvores/química
4.
PLoS One ; 18(9): e0290575, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37682928

RESUMO

Kenya has registered over 300,000 cases of COVID-19 and is a high-burden tuberculosis country. Tuberculosis diagnosis was significantly disrupted by the pandemic. Access to timely diagnosis, which is key to effective management of tuberculosis and COVID-19, can be expanded and made more efficient through integrated screening. Decentralized testing at community level further increases access, especially for underserved populations, and requires robust systems for data and process management. This study delivered integrated COVID-19 and tuberculosis testing to commercial motorbike (Bodaboda) riders, a population at increased risk of both diseases with limited access to services, in four counties: Nairobi, Kiambu, Machakos and Kajiado. Testing sheds were established where riders congregate, with demand creation carried out by the Bodaboda association. Integrated symptom screening for tuberculosis and COVID-19 was conducted through a digital questionnaire which automatically flagged participants who should be tested for either, or both, diseases. Rapid antigen-detecting tests (Ag-RDTs) for COVID-19 were conducted onsite, while sputum samples were collected and transported to laboratories for tuberculosis diagnosis. End-to-end patient data were captured using digital tools. 5663 participants enrolled in the study, 4946 of whom were tested for COVID-19. Ag-RDT positivity rate was 1% but fluctuated widely across counties in line with broader regional trends. Among a subset tested by PCR, positivity was greater in individuals flagged as high risk by the digital tool (8% compared with 4% overall). Of 355 participants tested for tuberculosis, 7 were positive, with the resulting prevalence rate higher than the national average. Over 40% of riders had elevated blood pressure or abnormal sugar levels. The digital tool successfully captured complete end-to-end data for 95% of all participants. This study revealed high rates of undetected disease among Bodaboda riders and demonstrated that integrated diagnosis can be delivered effectively in communities, with the support of digital tools, to maximize access.


Assuntos
COVID-19 , Veículos Off-Road , Humanos , Quênia/epidemiologia , Estudos Transversais , COVID-19/diagnóstico , COVID-19/epidemiologia , Motocicletas
5.
Heliyon ; 8(12): e12124, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36561696

RESUMO

Background: Dermaseptins (Drs) are peptides found in the skin secretions of a variety of Hylid frogs, particularly those belonging to the Agalychnis and Phyllomedusa families. Dermaseptin B2 (Drs B2), an amphipathic, α-helical polypeptide was reported as the most active of the Dermaseptin B family. We have previously shown that Drs B2 has strong anti-proliferative activities against RD cells in vitro and thus required further evaluations for future medical applications. Aim: The aim the study was to evaluate the 14-day sub-acute and 90-day sub-chronic toxicities Drs B2 in vivo. Materials and Methods: BALB/c mice were treated with increasing concentrations of 5-25 mg/kg of Drs B2. Rats were treated with 2, 4 and 10-fold concentrations of the calculated LD50 of Drs B2 following OECD recommendations. At the end of the experimentation periods, the animals were sacrificed and dissected to collect blood and selected organs for analysis of any effects caused by Drs B2 treatment on the biochemical, haematological, and histological parameters. Results: The 14-day sub-acute toxicity tests did not cause significant alteration in the biochemical, hematological and histological parameters. The 90-day sub-chronic toxicity study showed lower ALT and AST than control at doses 1.9 mg/kg and 4.6 mg/kg, respectively. Their haematology results also showed higher platelet count than the controls but the differences were not statistically significant. Histological analysis showed increased megakaryocytes in the spleen for both the mice and the rats. Conclusion: The results of this study indicate that short term treatment of Drs B2 could be safe to the animals, however, long-term treatment can have mild effects on the liver parameters and cause an inflammatory response in the spleen.

6.
Wellcome Open Res ; 5: 259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33959684

RESUMO

Background: Malaria is a major public health threat in sub-Saharan Africa. Asymptomatic Plasmodium falciparum gametocyte carriers are potential infectious reservoirs for sustaining transmission in many malaria endemic regions. The aim of the study was to assess the prevalence of gametocyte carriage and some of its associated risk factors among asymptomatic schoolchildren in Western Kenya and further analyse the association between gametocyte density, multiplicity of infection (MOI) and mosquito infection prevalence. Methods: Rapid diagnostic tests were used to screen for P. falciparum parasite infection among schoolchildren (5-15 years old) and the results were verified using microscopy. Microscopy positive gametocyte carriers were selected to feed laboratory reared An. gambiae s.l. mosquitoes using membrane feeding method. Genomic DNA was extracted from dry blood spot samples and P. falciparum populations were genotyped using 10 polymorphic microsatellite markers. Assessment of the association between MOI and gametocyte density and mosquito infection prevalence was conducted. Results: A significantly higher prevalence of P. falciparum infection was found in males 31.54% (764/2422) ( p-value < 0.001) compared to females 26.72% (657/2459). The microscopy gametocyte prevalence among the study population was 2% (84/4881). Children aged 5-9 years have a higher prevalence of gametocyte carriage (odds ratios = 2.1 [95% CI = 1.3-3.4], P = 0.002) as compared to children aged 10-15 years. After challenging An. gambiae s.l. by membrane feeding assay on gametocyte positive patient blood, our results indicate that 68.1% of the variation in mosquito infection prevalence is accounted for by gametocyte density and MOI (R-SQR. = 0.681, p < 0.001). Conclusions: Age was a significant risk factor for gametocyte carriage, as indicated by the higher risk of gametocyte carriage among the younger children (5-9 years). Gametocyte density and MOI statistically significantly predicted mosquito infection prevalence. Both of the variables added significantly to the prediction ( p < 0.05).

7.
PLoS One ; 15(3): e0229355, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155160

RESUMO

Human respirovirus type 3 (HRV3) is a leading etiology of lower respiratory tract infections in young children and ranks only second to the human respiratory syncytial virus (HRSV). Despite the public health importance of HRV3, there is limited information about the genetic characteristics and diversity of these viruses in Kenya. To begin to address this gap, we analyzed 35 complete hemagglutinin-neuraminidase (HN) sequences of HRV3 strains isolated in Kenya between 2010 and 2013. Viral RNA was extracted from the isolates, and the entire HN gene amplified by RT-PCR followed by nucleotide sequencing. Phylogenetic analyses of the sequences revealed that all the Kenyan isolates grouped into genetic Cluster C; sub-clusters C1a, C2, and C3a. The majority (54%) of isolates belonged to sub-cluster C3a, followed by C2 (43%) and C1a (2.9%). Sequence analysis revealed high identities between the Kenyan isolates and the HRV3 prototype strain both at the amino acid (96.5-97.9%) and nucleotide (94.3-95.6%) levels. No amino acid variations affecting the catalytic/active sites of the HN glycoprotein were observed among the Kenyan isolates. Selection pressure analyses showed that the HN glycoprotein was evolving under positive selection. Evolutionary analyses revealed that the mean TMRCA for the HN sequence dataset was 1942 (95% HPD: 1928-1957), while the mean evolutionary rate was 4.65x10-4 nucleotide substitutions/site/year (95% HPD: 2.99x10-4 to 6.35x10-4). Overall, our results demonstrate the co-circulation of strains of cluster C HRV3 variants in Kenya during the study period. This is the first study to describe the genetic and molecular evolutionary aspects of HRV3 in Kenya using the complete HN gene.


Assuntos
Evolução Molecular , Variação Genética , Proteína HN/genética , Vírus da Parainfluenza 3 Humana/genética , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Infecções por Respirovirus/virologia , Seleção Genética , Glicosilação , Humanos , Quênia , Filogenia
8.
Sci Rep ; 10(1): 5924, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246127

RESUMO

Multiplicity of infection (MOI) and genetic diversity of P. falciparum infections are important surrogate indicators for assessing malaria transmission intensity in different regions of endemicity. Determination of MOI and diversity of P. falciparum among asymptomatic carriers will enhance our understanding of parasite biology and transmission to mosquito vectors. This study examined the MOI and genetic diversity of P. falciparum parasite populations circulating in Mbita, a region characterized as one of the malaria hotspots in Kenya. The genetic diversity and multiplicity of P. falciparum infections in 95 asymptomatic school children (age 5-15 yrs.) residing in Mbita, western Kenya were assessed using 10 polymorphic microsatellite markers. An average of 79.69% (Range: 54.84-95.74%) of the isolates analysed in this study were polyclonal infections as detected in at least one locus. A high mean MOI of 3.39 (Range: 2.24-4.72) and expected heterozygosity (He) of 0.81 (Range: 0.57-0.95) was reported in the study population. The analysed samples were extensively polyclonal infections leading to circulation of highly genetically diverse parasite populations in the study area. These findings correlated with the expectations of high malaria transmission intensity despite scaling up malaria interventions in the area thereby indicating the need for a robust malaria interventions particularly against asymptomatic carriers in order to attain elimination in the region.


Assuntos
Infecções Assintomáticas/epidemiologia , DNA de Protozoário/genética , Variação Genética , Malária Falciparum/epidemiologia , Plasmodium falciparum/genética , Adolescente , Criança , Pré-Escolar , DNA de Protozoário/isolamento & purificação , Feminino , Humanos , Quênia , Malária Falciparum/sangue , Malária Falciparum/microbiologia , Malária Falciparum/transmissão , Masculino , Repetições de Microssatélites/genética , Epidemiologia Molecular , Plasmodium falciparum/isolamento & purificação , Plasmodium falciparum/patogenicidade
9.
Data Brief ; 26: 104442, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31528676

RESUMO

In this article, we present data on the anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata and standard anticancer drug 5-Fluorouracil (5-FU) on two cancer cell lines, i.e. cervical adenocarcinoma (HeLa cells) and prostate adenocarcinoma (PC3 cells) as well as on an immortalized normal prostate cell line, PNT1A. The cytotoxicity on the cells was determined by measuring the absorbance signal of resazurin dye. It has long been known that metabolically active cells change the resazurin from blue (oxidized) to red (reduced) forms, corresponding to the absorbance signals at a wavelength of 570nm (A570) and 600nm (A600) respectively, from which therefore the effects of any treatments on percentage cell viability/death can be elucidated. The raw data values of the treatments against the HeLa, PC3 and PNT1A cells are shown in the different Tables. Examples of how the data can be analyzed have been illustrated using different growth inhibition curves. The data can be used by academics, students, and researchers working on development of anticancer drugs.

10.
Data Brief ; 25: 104194, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31321276

RESUMO

In this data article, data obtained from an efficient, eco-friendly and low-cost method for the synthesis and recovery of Silver nanoparticles (AgNPs) using ethanolic extracts of Annona muricata fruits and leaves as reducing, stabilizing and capping agents has been reported. 99.7% pure silver nitrate was used as the inorganic ion source. The data was obtained using different spectroscopic and microscopic techniques. The data is presented in form of images, Microsoft excel sheets, graphs,.raw files,.dpt files, PDF files, among others. Methods of analysis and interpretation of the data have also been presented. The data can be most useful to researchers, research students, industrialists and academicians to acquire knowledge on the green synthesis of AgNPs and related applications. The data is deposited in the Mendeley Data Repository as two independent datasets accessible at https://doi.org/10.17632/jkj2x782wh.1 Gavamukulya et al., 2019 and https://doi.org/10.17632/f4mb6b488n.1 Gavamukulya et al., 2019.

11.
Cancer Res ; 66(6): 3071-7, 2006 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-16540656

RESUMO

Growth-related oncogene (GRO), a member of the CXC chemokine subfamily, plays a major role in inflammation and wound healing. CXC chemokines have been found to be associated with tumorigenesis, angiogenesis, and metastasis. Although elevated expression of GRO has been reported in several human cancers, the expression and role of GRO and its receptor, CXCR2, in esophageal cancer are poorly understood. This study used real-time reverse transcription-PCR (RT-PCR) and immunohistochemical approaches to show that GROalpha, GRObeta, and CXCR2 are up-regulated in esophageal tumor tissue. Furthermore, GROalpha, GRObeta, and CXCR2 are constitutively expressed in WHCO1, an esophageal cancer cell line that was used as a model system here. GRObeta enhances transcription of EGR-1, via the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which can be blocked by a specific antagonist of CXCR2 (SB 225002) or specific antibody to GRObeta. WHCO1 cells treated with SB 225002 exhibited a 40% reduction in cell proliferation. A stable WHCO1 GROalpha RNA interference (RNAi) clone displayed a 43% reduction in GROalpha mRNA levels as determined by real-time RT-PCR, reduced levels of GROalpha by fluorescence microscopy, and a 60% reduction in the levels of phosphorylated ERK1/2. A stable clone expressing GRObeta RNAi displayed >95% reduction in GRObeta mRNA levels, reduced levels of GRObeta by fluorescence microscopy, and an 80% reduction in the levels of phosphorylated ERK1/2. Moreover, these GROalpha RNAi- and GRObeta RNAi-expressing clones displayed a 20% and 50% decrease in cell proliferation, respectively. Our results suggest that GROalpha-CXCR2 and GRObeta-CXCR2 signaling contributes significantly to esophageal cancer cell proliferation and that this autocrine signaling pathway may be involved in esophageal tumorigenesis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Quimiocinas CXC/biossíntese , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Receptores de Interleucina-8B/biossíntese , Carcinoma de Células Escamosas/genética , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Quimiocina CXCL1 , Quimiocina CXCL2 , Quimiocinas CXC/genética , Neoplasias Esofágicas/genética , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Receptores de Interleucina-8B/genética , Transdução de Sinais , Transfecção
12.
J Med Entomol ; 55(4): 855-861, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29529232

RESUMO

Tsetse flies (Glossina) are vectors of African trypanosomiasis. Olfaction plays a critical role in Glossina behavior, including larviposition, feeding, and reproduction. Odorant receptors (ORs) are important in insect chemoreception as they bind volatile odorants and transport them to olfactory receptor neurons to elicit behavioral response. To better understand Glossina chemoreception, we used quantitative polymerase chain reaction to examine the expression levels of ORs in female and male Glossina morsitans morsitans Wiedemann, 1850 (Diptera: Glossinidae) antennae and legs. Results showed that G. m. morsitans ORs code for a transmembrane domain and are involved in odorant binding. The ORs had homologs in Drosophila, mosquitoes, other Glossina species, and the reduced number of tsetse ORs could be linked to its restricted blood-feeding diet. The OR genes were more highly expressed in antennae than the legs with GmmOR33 and GmmOR45 transcript levels being high in the female and male antennae, respectively, whereas GmmOR26 and GmmOR34 levels were high in female and male G. m. morsitans legs, respectively. These findings identified sex- and tissue-specific G. m. morsitans ORs. The expression levels of OR genes in female and male G. m. morsitans could be conserved in function with the antenna being the main olfactory organ. Thus, this study provides a blueprint to explore the functional roles of tsetse ORs with the potential to identify molecular targets that can be used to control the vector based on disruption of its chemosensory system.


Assuntos
Regulação da Expressão Gênica , Proteínas de Insetos/genética , Receptores Odorantes/genética , Transcriptoma , Moscas Tsé-Tsé/genética , Animais , Feminino , Proteínas de Insetos/metabolismo , Masculino , Receptores Odorantes/metabolismo , Moscas Tsé-Tsé/metabolismo
13.
BMC Res Notes ; 11(1): 134, 2018 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-29452597

RESUMO

OBJECTIVE: We conducted a retrospective cohort study to evaluate the efficacy of the World Health Organization (WHO) "Universal Test and Treat" (UTT) policy, initiated in Kenya in September 2016. Under this policy, every human immunodeficiency virus (HIV)-infected person should be initiated on antiretroviral therapy (ART). We compared intra- and inter-group viral suppression and ART adherence rates for pre-UTT (initiated on ART in March-August 2016) and UTT groups (initiated in September 2016). The study was conducted in a community outreach Program in Nairobi with 3500 HIV-infected children enrolled. RESULTS: 122 children and adolescents were initiated on first-line ART pre-UTT, and 197 during the UTT period. The 6 month viral suppression rate was 79.7% pre-UTT versus 76.6% UTT (P < 0.05). Suboptimal adherence was higher in the UTT than pre-UTT period (88 of 197, 44.7% and 44 of 122, 34%; P < 0.001). The decrease in adherence was greater among orphans (91.7% pre-UTT and 87.2% UTT, P = 0.001) and children 11-18 years. Our results show that successful implementation of the UTT policy in Africa is challenged by an increased risk of suboptimal adherence. There is a need to develop extra strategies to support adherence, especially among orphans and teenagers.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etnologia , Adesão à Medicação/etnologia , Avaliação de Resultados em Cuidados de Saúde , Desenvolvimento de Programas , Nações Unidas , Organização Mundial da Saúde , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Quênia , Masculino , Estudos Retrospectivos
14.
Int J Infect Dis ; 74: 109-116, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30017946

RESUMO

OBJECTIVES: This study sought to determine the endemic Leishmania species, the clinical features of cutaneous leishmaniasis (CL) in the Central Rift Valley in Kenya and to give an account on unresponsiveness to treatment in the region. METHODS: Participants were clinically identified and grouped into untreated, classical and recidivate based on clinical manifestation and clinical data. Leishmaniasis recidivans lesions were scaly hyperemic papules that appeared before the classic lesion had healed or after healing. The demographics and socio-economic data were recorded and lesion scraping samples screened through microscopy and Internal Transcribed Spacer 1-PCR. Leishmania species were identified using Restriction Fragment Length Polymorphism. RESULTS: A total of 52 participants were sampled, of which, 44.2% of the cases were recidivate and L. tropica the only species identified. All patients had been treated using sodium stibogluconate (SSG) which is the recommended first-line drug in Kenya. 60% of the patients experienced prolonged exposure to the drug (>30 days). CONCLUSION: L. tropica is the endemic Leishmania species for CL leading to classical and leishmaniasis recidivans. Treatment of CL in the area is not effective hence, alternative measures/therapy should be considered to cope with the unresponsiveness.


Assuntos
Leishmania tropica/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Adolescente , Adulto , Gluconato de Antimônio e Sódio/administração & dosagem , Antiprotozoários/administração & dosagem , Criança , Feminino , Humanos , Quênia/epidemiologia , Leishmania tropica/genética , Leishmania tropica/fisiologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologia , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Pele/parasitologia , Adulto Jovem
15.
Clin Cancer Res ; 12(3 Pt 1): 690-700, 2006 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-16467078

RESUMO

PURPOSE: To elucidate the molecular mechanisms contributing to the unique clinicopathologic characteristics of mucinous ovarian carcinoma, global gene expression profiling of mucinous ovarian tumors was carried out. EXPERIMENTAL DESIGN: Gene expression profiling was completed for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among mucinous specimens and a series of previously profiled microdissected serous tumors and normal ovarian surface epithelium. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous LMP tumors and adenocarcinomas. RESULTS: Comparison of the gene profiles between mucinous tumors and normal ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas, respectively. Hierarchical clustering showed that mucinous and serous LMP tumors are distinct. In addition, there was a close association of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas. Binary tree prediction revealed increased heterogeneity among mucinous tumors compared with their serous counterparts. Furthermore, the cystadenomas coexpressed a subset of genes that were differentially regulated in LMP and adenocarcinoma specimens compared with normal ovarian surface epithelium. PathwayAssist highlighted pathways with expression of genes involved in drug resistance in both LMP and adenocarcinoma samples. In addition, genes involved in cytoskeletal regulation were specifically up-regulated in the mucinous adenocarcinomas. CONCLUSIONS: These data provide a useful basis for understanding the molecular events leading to the development and progression of mucinous ovarian cancer.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/classificação , Análise por Conglomerados , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Neoplasias Ovarianas/classificação , Valor Preditivo dos Testes
16.
Asian Pac J Trop Med ; 10(9): 835-848, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29080611

RESUMO

Annona muricata (A. muricata) is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses. This review focuses on the research history of its traditional uses, phytochemicals, pharmacological activities, toxicological aspects of the extracts and isolated compounds, as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment. A. muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer. More than 200 chemical compounds have been identified and isolated from this plant, the most important being alkaloids, phenols and acetogenins. Using in vitro studies, its extracts and phytochemicals have been characterized as antioxidant, anti-microbial, anti-inflammatory, insecticidal, larvicidal, and cytotoxic to cancer cells. In vivo studies have revealed anxiolytic, anti-stress, anti-inflammatory, immunomodulatory, antimalarial, antidepressant, gastro protective, wound healing, hepato-protective, hypoglycemic, anticancer and anti-tumoral activities. In silico studies have also been reported. In addition, clinical studies support the hypoglycemic as well as some anticancer activities. Mechanisms of action of some pharmacological activities have been elucidated. However, some phytochemical compounds isolated from A. muricata have shown a neurotoxic effect in vitro and in vivo, and therefore, these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects, optimal dosage, and mechanisms of action, long-term safety, and potential side effects. Additionally, more clinical studies are necessary to support the therapeutic potential of this plant. Some studies were also found to have successfully regenerated the plant in vitro, but with limited success. The reported toxicity notwithstanding, A. muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.

17.
PLoS Negl Trop Dis ; 10(7): e0004788, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27387337

RESUMO

BACKGROUND: Rickettsia africae, the etiological agent of African tick bite fever, is widely distributed in sub-Saharan Africa. Contrary to reports of its homogeneity, a localized study in Asembo, Kenya recently reported high genetic diversity. The present study aims to elucidate the extent of this heterogeneity by examining archived Rickettsia africae DNA samples collected from different eco-regions of Kenya. METHODS: To evaluate their phylogenetic relationships, archived genomic DNA obtained from 57 ticks a priori identified to contain R. africae by comparison to ompA, ompB and gltA genes was used to amplify five rickettsial genes i.e. gltA, ompA, ompB, 17kDa and sca4. The resulting amplicons were sequenced. Translated amino acid alignments were used to guide the nucleotide alignments. Single gene and concatenated alignments were used to infer phylogenetic relationships. RESULTS: Out of the 57 DNA samples, three were determined to be R. aeschlimanii and not R. africae. One sample turned out to be a novel rickettsiae and an interim name of "Candidatus Rickettsia moyalensis" is proposed. The bonafide R. africae formed two distinct clades. Clade I contained 9% of the samples and branched with the validated R. africae str ESF-5, while clade II (two samples) formed a distinct sub-lineage. CONCLUSIONS: This data supports the use of multiple genes for phylogenetic inferences. It is determined that, despite its recent emergence, the R. africae lineage is diverse. This data also provides evidence of a novel Rickettsia species, Candidatus Rickettsia moyalensis.


Assuntos
Filogenia , Infecções por Rickettsia/microbiologia , Rickettsia/classificação , Rickettsia/isolamento & purificação , Animais , Vetores Aracnídeos/microbiologia , Proteínas da Membrana Bacteriana Externa/genética , Humanos , Quênia , Rickettsia/genética , Carrapatos/microbiologia
18.
Springerplus ; 5: 158, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27026855

RESUMO

Enteroviruses (EV) are responsible for a wide range of clinical diseases in humans. Though studied broadly in several regions of the world, the genetic diversity of human enteroviruses (HEV) circulating in the sub-Saharan Africa remains under-documented. In the current study, we molecularly typed 61 HEV strains isolated in Kenya between 2008 and 2011 targeting the 3'-end of the VP1 gene. Viral RNA was extracted from the archived isolates and part of the VP1 gene amplified by RT-PCR, followed by sequence analysis. Twenty-two different EV types were detected. Majority (72.0 %) of these belonged to Enterovirus B species followed by Enterovirus D (21.3 %) and Enterovirus A (6.5 %). The most frequently detected types were Enterovirus-D68 (EV-D68), followed by Coxsackievirus B2 (CV-B2), CV-B1, CV-B4 and CV-B3. Phylogenetic analyses of these viruses revealed that Kenyan CV-B1 isolates were segregated among sequences of global CV-B1 strains. Conversely, the Kenyan CV-B2, CV-B3, CV-B4 and EV-D68 strains generally grouped together with those detected from other countries. Notably, the Kenyan EV-D68 strains largely clustered with sequences of global strains obtained between 2008 and 2010 than those circulating in recent years. Overall, our results indicate that HEV strains belonging to Enterovirus D and Enterovirus B species pre-dominantly circulated and played a significant role in pediatric respiratory infection in Kenya, during the study period. The Kenyan CV-B1 strains were genetically divergent from those circulating in other countries. Phylogenetic clustering of Kenyan EV-D68 strains with sequences of global strains circulating between 2008 and 2010 than those obtained in recent years suggests a high genomic variability associated with the surface protein encoding VP1 gene in these enteroviruses.

20.
Asian Pac J Trop Med ; 7S1: S355-63, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25312150

RESUMO

OBJECTIVE: To determine the phytochemical composition, antioxidant and anticancer activities of ethanolic and water leaves extracts of Annona muricata (A. muricata) from the Eastern Uganda. METHODS: Phytochemical screening was conducted using standard qualitative methods and a Chi-square goodness of fit test was used to assign the relative abundance of the different phytochemicals. The antioxidant activity was determined using the 2, 2-diphenyl-2-picrylhydrazyl and reducing power methods whereas the in vitro anticancer activity was determined using three different cell lines. RESULTS: Phytochemical screening of the extracts revealed that they were rich in secondary class metabolite compounds such as alkaloids, saponins, terpenoids, flavonoids, coumarins and lactones, anthraquinones, tannins, cardiac glycosides, phenols and phytosterols. Total phenolics in the water extract were (683.69±0.09) µg/mL gallic acid equivalents (GAE) while it was (372.92±0.15) µg/mL GAE in the ethanolic extract. The reducing power was 216.41 µg/mL in the water extract and 470.51 µg/mL GAE in the ethanolic extract. In vitro antioxidant activity IC50 was 2.0456 mg/mL and 0.9077 mg/mL for ethanolic and water leaves extracts of A. muricata respectively. The ethanolic leaves extract was found to be selectively cytotoxic in vitro to tumor cell lines (EACC, MDA and SKBR3) with IC50 values of 335.85 µg/mL, 248.77 µg/mL, 202.33 µg/mL respectively, while it had no cytotoxic effect on normal spleen cells. The data also showed that water leaves extract of A. muricata had no anticancer effect at all tested concentrations. CONCLUSIONS: The results showed that A. muricata was a promising new antioxidant and anticancer agent.

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