Effects of methanol and aqueous extracts of Acacia xanthophloea, Strychnos heninningsii and Microglossa pyrifolia on Immunoglobin E using asthma induced mice model

Background: The increasing prevalence of asthma in developing countries during the last decade continues to represent a significant public health problem, causing both economic and social burdens. It remains an area of considerable unmet medical need which affects 235–330 million and kills about 300,000 people worldwide. Low and middle income countries make up more than 80% of the mortality and the prevalence of Asthma in Kenya is 15.8%.Treatment of asthma still remains far from being satisfactory, which is severely limited by undesirable adverse effect and high cost. Methanol and aqueous extracts of Acacia xanthophloea, Strychnos heninningsii and Microglossa pyrifolia have shown efficacy on antimicrobial and antioxidant properties but have not been investigated for anti-asthmatic activities. Objectives: This study was aimed at evaluating the anti-asthmatic activities of extracts of Acacia xanthophloea, Strychnos heninningsii and Microglossa pyrifolia on asthma induced mice. Materials and Methods: Female Swiss Albino mice aged 8weeks old and weighing 20 +/- 2g, were asthma induced by using 1% Ovalbumin (grade VI; Sigma, Steinheim, Germany) followed by treatment using methanol and water extracts of A xanthophloea, S heninningsii and M pyrifolia in concentrations of 50, 100 and 200mg/kg body weight except for positive control group of mice which was induced and not treated. Standard reference drug control group was given 10mg/kg Prednisolone. After treatment, serum total Immunoglobin E (IgE) levels were determine using mouse OVA specific IgE Enzyme Linked Immunosorbent Assay (ELISA) (BioLegend).Cytotoxicity screening of the plant extracts was also done using Vero E6 cells and MTT dye. Data were analyzed and expressed as Means and Standard Deviation and the parametric data was statistically analyzed using one way Analysis of Variance (ANOVA) followed with unpaired student’s t-test at p-value < 0.001. Results: The results showed that the extracts were able to reduce the serum total IgE levels by upto100% in reference to the positive control. Conclusion: The extracts tested have the ability to reduce IgE levels in an asthmatic attack. The results can to be used for future possible large scale implementation in an effort to solve the burden of asthma as well as the current anti-asthmatic drug side effects. Keywords: Anti-asthma, Immunoglobin E, Acacia. xanthophloea, Strychnos heninningsii, Microglossa pyrifoli

Molecular Surveillance of Adamantane Resistance among Human Influenza A Viruses Isolated in Four Epidemic Seasons in Kenya

Background: Adamantanes impede influenza A virus replication and are important in the treatment and prophylaxis of disease caused by these viruses. Genotypic characterization of influenza A viruses for mutations associated with resistance to adamantanes has not been fully investigated in Kenya. Objective: To characterize susceptibility of influenza A virus subtypes that circulated in Kenya from 2008-2011 to adamantanes. Methods: Archived influenza A virus strains obtained from 2008 to 2011 were propagated in MDCK cells prior to sequencing of the matrix and hemagglutinin gene segments, followed by bioinformatics analyses. Results: Ninety two virus strains consisting of 21 A/H3N2, 18 A/H1N1 and 53 A/H1N1pdm09 were analyzed.  All A/H3N2 and A/H1N1pdm09 viruses displayed resistance to adamantanes due to the S31N/S31D amino acid substitution. All A/H1N1pdm09 virus strains belonged to the N-lineage characterized by S203T amino acid substitution in the HA1. All A/H1N1 viruses were sensitive to adamantane and were characterized by K140E amino acid substitution in the HA1. Conclusion: All Kenyan influenza A/H3N2 and A/H1N1pdm09 virus strains were resistant to adamantanes while seasonal A/H1N1 strains were sensitive to these drugs. During the study period, Amantadine and Rimantadine were inappropriate for prophylaxis and treatment of influenza disease caused by A/H3N2 and A/H1N1pdm09 virus subtypes in Kenya. Key words: Kenya, influenza A/H3N2, A/H1N1pdm09, A/H1N1, adamantane

Differentially expressed genes in oesophageal cancer

Oesophageal cancer (OC) is a leading cause of cancer death in the black population in South Africa. The lifetime risk of the disease amongst black males is 1 in 59. High incidence areas are the Transkei, Ciskei and KwaZulu-Natal where it is responsible for over 45 of all malignancies. Cancer develops through a multistep process of genomic instability of clonal evolution. Several oncogenes, tumour suppressor genes and transcription factors have been shown to be altered in oesophageal cancer. Their role however, in the development and/or susceptibility to the development of oesophageal cancer is poorly understood. The aim if this project is to identify candidate genes that are differentially expressed in oesophageal cancer patients with a view to understanding the development of oesophageal cancer. The ultimate objective of the project is to use this data to develop possible biomarkers for the disease

PGF2α Synthase-Like Proteins are Expressed in Promastigotes of Old World Leishmania Species but not in New World Species

Background: Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania and spread by the bite of infected sand fly species. The disease is characterized by an increase in prostaglandin production in the host. PGF2α is among the prostaglandins that are synthesized by Leishmania sp. Objectives: To compare the expression profiles of PGF2α synthase-like proteins in Old and New World species of Leishmania so as to provide insight into the role of these proteins. Methodology: To detect gene expression at transcription level, polymerase chain reaction was carried out using L. major PGF2α synthase gene specific primers and cDNA from L. major, L. donovani, L. tropica, L. amazonensis, L. braziliensis, L. mexicana and L. chagasi promastigotes. To detect expression at translation level, total protein from promastigotes of the above parasites was analyzed on a Western blot using T. brucei-specific rabbit anti-PGF2α synthase polyclonal antibodies. Results: At the transcription level, PGF2α synthase gene expression was detected in Old World species L. major, L. donovani and L. tropica, but was absent in the New World  L. amazonensis and L. mexicana. It was expressed at low levels in the New World L. chagasi. Western blot analysis confirmed the presence of PGF2α synthase - like proteins in Old World and not in New World species. Discussion: These findings suggest that New World Leishmania may have evolved new ortholog genes to produce PGF2α. Alternatively, the ancestral PGF2α synthase gene may be present in the New World species but has mutated or been lost due to speciation during evolution. Key words: Prostaglandins; PGF2α synthase; Leishmani

Evidence of reduced treatment adherence among HIV infected paediatric and adolescent populations in Nairobi at the onset of the UNAIDS Universal Test and Treat Program

Abstract 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

Molecular characterization of human parainfluenza virus type 1 in infants attending Mbagathi District Hospital, Nairobi, Kenya

Background. Human parainfluenza virus type 1 (HPIV-1), a Paramyxovirus, is a leading cause of paediatric respiratory hospitalizations globally. Currently, there is no HPIV-1 vaccine. Hence, there is 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 evolution of HPIV-1. Methods. 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 June 2006- December 2010. RT-PCR was carried out on the isolates using HN-specific primers to amplify a 360nt in the most polymorphic region and the amplicons sequenced. Genomic data was analysed using a suite of bioinformatic software. Results. 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 non-synonymous amino acid changes (7 positions) observed than conservative non-synonymous changes (1 position) on the HN gene fragment. No positively selected sites were found in the HN protein. Conclusion

Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola)

AbstractObjectiveTo determine the phytochemical composition, antioxidant and anticancer activities of ethanolic and water leaves extracts of Annona muricata (A. muricata) from the Eastern Uganda.MethodsPhytochemical 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.ResultsPhytochemical 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.ConclusionsThe results showed that A. muricata was a promising new antioxidant and anticancer agent