An evaluation of RBM implementation in the civil service sector in Zimbabwe

This study evaluates the reasons for failure to implement the Results Based Management (RBM) system in the public service ministries in Zimbabwe. This is against the implementation of the RBM in 2004 by the government of Zimbabwe in pursuit to improve its public performance. The new approach to management, RBM was believed to be a panacea to the challenges being faced in public sector ministries in Zimbabwe. However the RBM has been a controversial area since its inception in the public sector, with public servants not keen to implement the system.  The findings indicated incentives, skills, culture, resources and performance indicators as challenges to implementation of RBM in Zimbabwean public service ministries. Key words: Results based management, Public Service, Public Servants, Implementation, Performance

Technological and cost comparison of cytochrome P450 2B6 (516G>T) genotyping methods in routine clinical practice

Pharmacogenetics requires robust and affordable tests to determine genetic variability. This study compares three genotyping methods: gene re-sequencing, real time polymerase chain reaction (PCR) allelic discrimination and PCR-RFLP for the detection of a genetic variation (516G>T) in the gene which codes for the enzyme, CYP2B6, the main enzyme in the metabolic pathway of the antiretroviral drug, efavirenz. The CYP2B6 (516G>T) variant has reduced metabolic capacity. Twenty (20) samples obtained from human immunodeficiency virus acquired immunodeficiency syndrome (HIV/AIDS) positive patients on an efavirenz containing regimen were used to establish whether these methods produce the same CYP2B6 genotype results on the same samples. Results were directly compared for concordance and revealed a 100% correlation with all three methods. Comparison for cost of equipment and reagents required for each method revealed an order of: sequencing > real time-PCR > PCR-RFLP. This study demonstrates the reproducibility of these three methods and provides an opportunity for the clinical applicability in routine clinical practice.Keywords: Polymorphism, drug response, efavirenz, Zimbabwe.African Journal of Biotechnology Vol. 12(19), pp. 2706-271

Pharmacogenetic considerations in the treatment of co-infections with HIV/AIDS, tuberculosis and malaria in Congolese populations of Central Africa

Background: HIV-infection, tuberculosis and malaria are the big three communicable diseases that plague sub-Saharan Africa. If these diseases occur as co-morbidities they require polypharmacy, which may lead to severe drug-drug-gene interactions and variation in adverse drug reactions, but also in treatment outcomes. Polymorphisms in genes encoding drug-metabolizing enzymes are the major cause of these variations, but such polymorphisms may support the prediction of drug efficacy and toxicity. There is little information on allele frequencies of pharmacogenetic variants of enzymes involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in the Republic of Congo (ROC). The aim of this study was therefore to investigate the occurrence and allele frequencies of 32 pharmacogenetic variants localized in absorption distribution, metabolism and excretion (ADME) and non-ADME genes and to compare the frequencies with population data of Africans and non-Africans derived from the 1000 Genomes Project. Results: We found significant differences in the allele frequencies of many of the variants when comparing the findings from ROC with those of non-African populations. On the other hand, only a few variants showed significant differences in their allele frequencies when comparing ROC with other African populations. In addition, considerable differences in the allele frequencies of the pharmacogenetic variants among the African populations were observed. Conclusions: The findings contribute to the understanding of pharmacogenetic variants involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in ROC and their diversity in different populations. Such knowledge helps to predict drug efficacy, toxicity and ADRs and to inform individual and population-based decisions

Identification and differentiation of Fusarium species using selected molecular methods

The taxonomy of Fusarium at the species level is based on morphological characteristics which include hyphae, conidia and microconidia. These features require expertise in taxonomy for an accurate and reliable diagnosis which is crucial as it aids in disease management and genetic diversity studies. This study aimed to develop alternative and/ or complementary taxonomic tools through the use of molecular based techniques. Initially, 113 morphologically identified Fusarium isolates were selected for polymerase chain reaction (PCR) amplification with a set of six inter-simple sequence repeat (ISSR) primers and four universally-primed (UP-PCR) primers to establish identifiable differences and similarities. Genetic variation was also assessed by amplification and sequencing of internally transcribed spacer (ITS) regions of rDNA from 13 isolates using Fusarium specific primers. ISSR amplifications employing four primers and UP-PCR analysis using one primer pair revealed scorable polymorphisms among an average of 86 isolates per primer. Some of the isolates did not yield amplifiable DNA with the selected primers used. The four ISSR primers yielded a total of 500 polymorphic bands and the UP-PCR primer pair revealed 126 polymorphic bands. Genetic similarities among the isolates were calculated using Jaccard’s coefficient while cluster analysis was used to generate dendrograms showing genetic relationships. The isolates were grouped according to similarity levels. Results obtained indicated a high degree of genetic variability in the genus Fusarium. High intraspecies diversity was observed in Fusarium oxysporum and Fusarium solani isolates. Some unexpected genetic similarities were observed among the isolates indicating non-agreement between morphological and molecular identification of the isolates. This suggests the need to use species-specific primers in further analyzing the revealed genetic relationships. Sequencing of the amplified ITS regions among the 13 Fusarium species revealed two groups with 85% genetic similarity. The ITS regions in the two groups showed a relative similarity ranging from 87 to 100%. A 100% genetic similarity was noted between two F. oxysporum isolates which indicated an agreement between morphological and molecular identification. Another 100% genetic similarity was noted among three species, F. moniliforme, F. pallidoroseum and F. lateritium suggesting that species designation can be unreliable if based on morphological data alone. Based on the overall results, the use of molecular methods constitutes an important complement of the morphological criteria needed to allow fungi to be more easily identifie

Effect of HLA/KIR genotypes on HIV disease progression in perinatally infected children from sub-Saharan Africa

The role of Human Leucocyte Antigen (HLA) and Killer-Cell Immunoglobulin-Like Receptor (KIR) molecules in adult HIV disease progression has been defined in many studies. Mechanisms proposed include the selection of viral escape mutants that reduce viral replicative capacity and increased CD8+ T-cell cytotoxic capacity. However, the factors contributing to variable disease progression in paediatric HIV infection are less well understood and remain contradictory. Disease progression in children has been associated with both viral and host genetic characteristics, suggesting the mediation of multiple immunological mechanisms in controlling HIV-1 viral replication. Functional characteristics of HIV-1-specific T cell responses are providing more insight to distinguish children with rapid and slow disease progression. This review discusses various reports on the role of HLA and KIR and other underlying factors in paediatric HIV-1 disease progression particularly in African populations where the disease remains endemic

Part I, Interrupted Nazarov cyclization on silica gel: Part II, Tandem alkylation-cyclization process via an O,C dianion

Thesis (M.S.)--University of Hawaii at Manoa, 2006.Includes bibliographical references (p. 63).xi, 101 leaves, bound ill. 29 cmPart I: Exposure of a mixture of propargyl vinyl ketone and a nucleophilic primary or secondary amine to activated dry silica gel in the absence of solvent leads to a cascade of reactions that results in the formation of an aminocyclopentenone. The reaction with triethylamine leads to a cross-conjugated cyclopentadienone. Part II: A general protocol for preparing densely functionalized cyclopentenones through a tandem alkylation-cyclization process is described. Addition of lithioallene 1.11 to enamide 1.5 generates tetrahedral intermediate 1.12. Deprotonation of the γ-carbon atom of the allene function in situ. followed by trapping by a suitable electrophile and cyclization during workup leads to C6 substituted cyclopentenone 1.14