Background
Cancer is a major public health concern globally and chemotherapy remains the principal mode of the treatment of various malignant diseases.

Methods
This study was designed to investigate the cytotoxicity of 14 naturally occurring quinones including; 3 anthraquinones, 1 naphthoquinone and 10 benzoquinones against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspases activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) were measured by spectrophotometry.

Results
Anthraquinone: emodin (2), naphthoquinone: plumbagin (4), and benzoquinones: rapanone (9), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione (10), 5-O-methylembelin (11), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene (13), as well as doxorubicin displayed interesting activities with IC50 values below 100 μM in the six tested cancer cell lines. The IC50 values ranged from 37.57 μM (towards breast adenocarcinoma MCF-7 cells) to 99.31 μM (towards small cell lung cancer A549 cells) for 2, from 0.06 μM (MCF-7 cells) to 1.14 μM (A549 cells) for 4, from 2.27 μM (mesothelioma SPC212 cells) to 46.62 μM (colorectal adenocarcinoma DLD-1 cells) for 9, from 8.39 μM (SPC212 cells) to 48.35 μM (hepatocarinoma HepG2 cells) for 10, from 22.57 μM (MCF-7 cells) to 61.28 μM (HepG2 cells) for 11, from 9.25 μM (MCF-7 cells) to 47.53 μM (A549 cells) for 13, and from 0.07 μM (SPC212 cells) to 1.01 μM (A549 cells) for doxorubicin. Compounds 4 and 9 induced apoptosis in MCF-7 cells mediated by increased ROS production and MMP loss, respectively.

Conclusion
The tested natural products and mostly 2, 4, 9, 10, 11 and 13 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.

Keywords

Carcinoma cytotoxicity Mode of action Plumbagin Quinones Rapanone

Description
Background
Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy.
Objectives
The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts.
Materials and methods
The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry.
Results
Chalcones: 2′,4′-dihydroxy-6′-methoxychalcone (1); 4′,6′-dihydroxy-2′,5′-dimethoxychalcone (2); 2′,4 …
Scholar articles
Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells
V Kuete, LK Omosa, JO Midiwo, O Karaosmanoğlu… - Journal of Ayurveda and integrative medicine, 2019
Related articles All 3 versions

Abstract

The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 μM. Durmillone was the most active with IC50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 μM), LO2 hepatocytes (IC50 78.7 μM) and CCD19Lu fibroblasts (IC50 >100 μM).
Keywords: Millettia dura, Leguminosae, isoflavone, cytotoxicity.

Description
The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 μM. Durmillone was the most active with IC50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 μM), LO2 hepatocytes (IC50 78.7 μM) and CCD19Lu fibroblasts (IC50 >100 μM).

Description
The first phytochemical investigation of the flowers of Millettia dura resulted in the isolation of seven isoflavones, a flavonol and a chalcone. Eleven isoflavones and a flavonol isolated from various plant parts from this plant were tested for cytotoxicity against a panel of cell lines, and six of these showed good activity with IC50 values of 6-14 μM. Durmillone was the most active with IC50 values of 6.6 μM against A549 adenocarcinomic human alveolar basal epithelial cancer cell line with low cytotoxicity against the non-cancerous cell lines BEAS-2B (IC50 = 58.4 μM), LO2 hepatocytes (IC50 78.7 μM) and CCD19Lu fibroblasts (IC50 >100 μM).

While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells.

Description
Background
While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells.
Purpose
The aim of this study was to determine the cytotoxicity of isoflavones: osajin (1), 5,7-dihydroxy-4ˈ-methoxy-6,8-diprenylisoflavone (2) and biflavonoids: chamaejasmin (3), 7,7″-di-O-methylchamaejasmin (4) and campylospermone A (5), a dimeric chromene [diphysin(6)] and an ester of ferullic acid with long alkyl chain [erythrinasinate (7)] isolated from the stem bark and roots of the Kenyan medicinal plant, Ormocarpum kirkii. The mode of action of compounds 2 and 4 was further investigated.
Methods
The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow …

In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia.

In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia …

Description
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia …

Description
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia …

Description
Background
Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy.
Objectives
The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts.
Materials and methods
The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry.
Results
Chalcones: 2′,4′-dihydroxy-6′-methoxychalcone (1); 4′,6′-dihydroxy-2′,5′-dimethoxychalcone (2); 2′,4 …

Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.
S L Rowland-Jones, T Dong, K R Fowke, J Kimani, P Krausa, H Newell, T Blanchard, K Ariyoshi, J Oyugi, E Ngugi, J Bwayo, K S MacDonald, A J McMichael, and F A Plummer
Author information ► Copyright and License information ►
See commentary "What immunity can protect against HIV infection." on page 1643.
This article has been cited by other articles in PMC.
Abstract
Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.

To determine the effect of human immunodeficiency virus type 1 (HIV-1) infection upon pelvic inflammatory disease (PID), a laparoscopic study of acute PID was conducted in Nairobi, Kenya. Subjects underwent diagnostic laparoscopy, HIV-1 serology, and testing for sexually transmitted diseases. Of the 133 women with laparoscopically verified salpingitis, 52 (39%) were HIV-1-seropositive. Tubo-ovarian abscesses (TOA) were found in 33% of HIV-1-infected and 15% of HIV-1-uninfected women (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.5). Among seropositive women, TOA was found in 55% of those with CD4 cell percent <14% vs. 28% with CD4 cell percent>14% (OR 3.1, 95% CI 0.6-15.3). Neisseria gonorrhoeae was detected in 37 women (28%) and Chlamydia trachomatis in 12 (9%); neither was significantly related to HIV-1 seropositivity. Length of hospitalization was not affected by HIV-1 serostatus overall but was prolonged among HIV-1-infected women with CD4 cell percent <14%. Among patients with acute salpingitis, likelihood of TOA was related to HIV-1 infection and advanced immunosuppression. In general, HIV-1-seropositive women with acute salpingitis responded well to treatment.

Abstract
Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.

Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC₅₀ 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.

Description
A new isoflavone, 4′-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2′-dimethoxy-3′,4′-methylenedioxyisoflavone, 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol. (6aR,11aR)-Edunol was also isolated from the stem bark of L. eriocalyx. The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC50 values below 10 …

Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1–4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, where compounds 4 and 5 had the highest activities (IC50 values of 7.17 μM and 5.16 μM, respectively) against CCRF-CEM leukemia cells. Compound 5

Description
Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1–4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, where compounds 4 and 5 had the highest activities (IC50 values of 7.17 μM and 5.16 μM, respectively) against CCRF-CEM leukemia cells. Compound 5 …

The known flemingins A-C (1-3) and nine new chalcones, named flemingins G-O (4-12), along with deoxyhomoflemingin (13) and emodin (14) were isolated from a leaf extract of Flemingia grahamiana. The isolated chalcones were found to have a geranyl substituent modified into a chromene ring possessing a residual chain, as shown by spectroscopic methods. The leaf extract showed an IC50 value of 5.9 μg/mL in a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The chalcones flemingins A, B, C, G, and H were active in the DPPH radical scavenging assay (ED50 4.4-8.9 μM), while flemingins A and C showed cytotoxicity against MCF-7 human breast cancer cells (IC50 8.9 and 7.6 μM, respectively).

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Background: Palpable breast lump, breast pain, and nipple discharge are common symptoms of breast disease. Breast cytology (fine-needle aspiration, nipple discharge smear, and touch preparation) accurately identifies benign, atypical, and malignant pathological changes in breast specimens. This study aims to determine the types of breast lesions diagnosed by breast cytology and assess the clinical adequacy of narrative reporting of breast cytology results.Methods: Medical records of 390 patients presenting to breast or general surgery clinics in Kenyatta National Hospital, Nairobi, Kenya, between January 2010 and March 2014 were evaluated retrospectively.Results: Of the 390 diagnosed breast lesions, 89.7% (n = 350) occurred in females, while 10.3% (n = 40) occurred in males, giving rise to a female-to-male ratio of 8.8:1. Neoplastic breast lesions (n = 296) comprised 75.9%, while non-neoplastic breast lesions (n = 94) comprised 24.1% of all diagnosed breast lesions. The neoplastic lesions were classified as 72.3% (n = 214) benign and 27.7% (n = 82) malignant, resulting in a benign-to-malignant ratio of 2.6:1. Fibroadenoma (n = 136) and gynecomastia (n = 33) were the most frequently diagnosed breast lesions for women and men, respectively.Conclusions: Breast cytology effectively diagnosed neoplastic and non-neoplastic breast lesions. Neoplastic breast lesions occurred more frequently in women whereas non-neoplastic lesions occurred more frequently in men. To address the limitations associated with narrative reporting of breast cytology results, a synoptic reporting format incorporating the United Kingdom's National Health Service Breast Screening Programme's diagnostic categories (C1 to C5) is recommended for adoption by this hospital

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Mycobacterium tuberculosis (Mtb) infects nearly 2 million people annually and is the most common cause of death in HIV-infected individuals. Tuberculosis (TB) diagnostics cater to HIV-uninfected individuals in non-endemic countries, are expensive, slow, and lack sensitivity for those most affected. Patterns of soluble immune markers from Mtb-stimulated immune cells are not well defined in HIV co-infection. We assessed immune differences between HIV-infected and HIV-uninfected individuals with active TB utilizing IFNγ-based QuantiFERON®-TB Gold In-Tube (QFT) testing in Nairobi, Kenya. Excess QFT supernatants were used to measure cytokine and chemokine responses by a 17-plex bead array. Mtb/HIV co-infected participants were significantly less likely to be QFT+ (47.2% versus 84.2% in the HIV-uninfected group), and demonstrated lower expression of all cytokines except for IFNα2. Receiver operator characteristic analyses identified IL-1α as a potential marker of co-infection. Among HIV-infected individuals, CD4+ T cell count correlated weakly with the expression of several analytes. Co-expression analysis highlighted differences in immune profiles between the groups. These data suggest that there is a unique and detectable Mtb-specific immune response in co-infection. A better understanding of Mtb immunology can translate into much needed immunodiagnostics with enhanced sensitivity in HIV-infected individuals, facilitating their opportunity to obtain live-saving treatment.

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Background: Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women.
Methods: Study subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression.
Results: Women with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 μg/mL) compared to those with heterozygous 516GT (9.18 μg/mL; n=25) and wild- type 516GG (7.95 μg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 μg/mL), compared to women with the homozygous 983TT (8.35 μg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/μL, 95% CI, 27.3–211.5 cells/μL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/μL, 95% CI, 3.9–133.4 cells/μL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity.
Conclusions: CYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.
Keywords: CYP2B6, Pharmacogenetics, Nevirapine, HIV infection, Antiretroviral therapy, Women

Background: Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women.
Methods: Study subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression.
Results: Women with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 μg/mL) compared to those with heterozygous 516GT (9.18 μg/mL; n=25) and wild- type 516GG (7.95 μg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 μg/mL), compared to women with the homozygous 983TT (8.35 μg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/μL, 95% CI, 27.3–211.5 cells/μL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/μL, 95% CI, 3.9–133.4 cells/μL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity.
Conclusions: CYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.
Keywords: CYP2B6, Pharmacogenetics, Nevirapine, HIV infection, Antiretroviral therapy, Women

There has been a decrease in the prevalence of cysticercosis (T. saginata and T solium) in Kenya since independence in the early 1960s. this has been due to improvement of hygiene, strict meat inspection procedures, public educational nd a ban on free range pig keeping.

The prevalence of C. bovis decreased from 25% in the 1960s to 8.8% in the 1970s and to 1.1% in the early 1990s. the decline has been attributed in addition to the above to the take over of control of meat inspection in the country by the department of veterinary services from the ministry of health in 19;74. The training of meat inspectors was also centralized. Among the provinces , the prevalence has been highest in the Rift Valley which is a net exporter of animals to other provinces and this is where the pastoral communities are found. The infection seems to spread from this province.

Outbreaks of porcine cysticercosis (T.solium) were recorded in the early 1960s mainly among the free range pig farmers in the north western Rift Valley (Tranzoia) Kakamega and Busia. A government ban on free range pig raising in the country after independence and proper hygience led to a sharp devreas in cases of T> Solium.

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ABSTRACT:  Eleven medicinal plants used by traditional healers in Machakos and Kitui District were screened, namely: Ajuga remota Benth, Aloe secundiflora Engl, Amaranthus hybridus L, Cassia didymobotrya Fes, Croton macrostachyus Del, Entada leptostachya Harms, Erythrina abyssinica DC, Harrisonia abyssinica Oliv, Schkuhria pinnata O. Ktze, Terminalia kilimandscharica Engl and Ziziphus abyssinica Hochst for potential antibacterial activity against four medically important bacterial strains, namely: Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, Micrococcus lutea ATCC 9341 and Pseudomonas aeruginosa ATCC 27853. The antibacterial activity of methanol extracts was determined as the minimum inhibitory concentration (MIC). The plant extracts were more active against Gram-positive (G+) than Gram-negative (G−) bacteria. The positive controls were streptomycin and benzylpenicillin for G− and G+ bacteria, respectively, both had a significant MIC at <1 mg/mL. The most susceptible bacteria were B. cereus, followed by M. lutea, while the most resistant bacteria were Ps. aeruginosa, followed by E. coli. The present study supports the use of these plants by the herbalists in the management of bacterial ailments. H. abyssinica and T. kilimandscharica showed the best antibacterial activity; hence these plants can be further subjected to phytochemical and pharmacological evaluation.

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Customer Relationship Management (CRM), also referred to as Relationship Marketing, is heralded by some marketing academics and practitioners as the new paradigm of marketing. However, despite the intense growth in the adoption of CRM practices by organizations all over the world and the widely accepted conceptual underpinnings of CRM strategy, conflicting opinions and increased pessimism about the effectiveness of CRM strategy abound the marketing literature. To this effect, scholars have called for more rigorous studies
to establish the usefulness of CRM as a strategic orientation.
The general objective of this study was to develop a comprehensive conceptual framework of the influence of CRM practices on organizational competitiveness and conduct an empirical assessment of the framework on the commercial banks in Kenya. The study utilized a descriptive correlational research design. A survey methodology was employed for data collection.
The study found statistically significant positive linear relationships between CRM practices and organizational competitiveness. The study also established that the relationships between CRM practices and marketing productivity, marketing productivity and organizational competitiveness, organizational factors and marketing productivity and the moderating role of organizational factors on the relationship between CRM practices and marketing productivity were all significant. However, the relationship between organizational factors and organizational competitiveness was found not statistically significant. The overall conclusion of the study was that organizational competitiveness is not significantly influenced by the mere existence of a range of organizational factors within the firm such as age, size, and ownership structure, type of customers served, corporate reputation, and duration of CRM implementation or even technology level. Rather, organizational
competitiveness is achieved through appropriate CRM practices and marketing productivity.
Nonetheless, organizational factors positively enhance the relationship between CRM practices and marketing productivity thus indirectly influences organizational competitiveness. The results of the study have significant managerial and theoretical implications.
Key words: Customer Relationship Management, Relationship Marketing, Organizational Competitiveness, Marketing Productivity, Organizational Factors.

Customer Relationship Management(CRM), is heralded by some marketing academics and practitioners as the new paradigm of marketing. However, despite the intense growth in the adoption of CRM practices by organizations all over the world and the widely accepted conceptual underpinnings of CRM strategy abound the marketing literature. To this effect, scholars have called for more rigorus studies to establish the usefulness of CRM as a strategic orientation. This study sought to establish the usefulness of CRM practices on competitiveness of comercial banks in Kenya. The study utilized a descriptive correlational research design. A survey methodology was employed for data collection. The results showed statistically significant positive linear relationships between CRM practices and organizational competitiveness. The study also established that the relationshipss between CRM practices and marketing productivity, marketing productivity and organizational competitiveness, organizational factors and marketing productivity and the moderation role of organizational factors on the relationship between CRM practices and marketing productivity were all significant. However, the relationship between organizational factors and organizational competitiveness was statistically insignificant. THe overall conclusion of the study was that organizational competitiveness is not significatly influenced by the mere existence of a range of organizational fctors within the firm such as age, size and ownership structure, type of customers served, corporate reputation and duration of CRM implementation or even technology level. Rather, organizational competitiveness is achieved through appropriate CRM practices and marketing productivity. Nonetheless, organizational factors positively inhance the relationship between CRM practises and marketing productivity thus indirectly influences organizational competitiveness. The findings of the study have significant managerila and theoretical implications.

Antibody responses to a conventional rabies preexposure regimen of a new purified Vero cell rabies vaccine (PVRV) and a human diploid cell vaccine (HDCV) were compared in 80 healthy Kenyan veterinary students. Forty-three of the students received the PVRV and 37 received the HDCV on days 0, 7, and 28. Antibody responses were monitored using the rapid fluorescent-focus inhibition test (RFFIT) and an inhibition enzyme immunoassay (INH EIA) on days 0, 7, 28, and 49. Both vaccines elicited a rapid antibody response. A good correlation between the RFFIT titers and the INH EIA titers was obtained (r = 0.90). Our results also showed that the INH EIA was more reproducible and might therefore be a suitable substitute for the more expensive and less reproducible RFFIT. The geometric mean titers determined by both tests in the two groups of students were statistically similar during the test period. The RFFIT and the INH EIA gave comparable geometric mean titers, which differed significantly only on day 28 in the PVRV group. The effect of the new PVRV is comparable to that of the more expensive HDCV, as determined by the present test systems. The PVRV could therefore be the vaccine of choice, especially in tropical rabies-endemic areas, where the high cost of the HDCV has confined its use to a privileged few.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

This paper investigates the possibilities of applying emerging management theories and techniques to constitutionally created offices in Kenya and East African region. The benefits from application of these theories, particularly in the judicial services are highlighted.

We present two cases of neurofibromatosis type 1 (NF-1), one a 35 year old male who first recognised his problem at the age of fifteen years and at the time of assessment, satisfied the National Institute of Health (NIH) diagnostic criteria for NF-1 and had a nodular plexiform neurofibroma involving the left fifth dorsal nerve root and a diffuse plexiform neurofibroma involving the left lower limb. The second patient, a 45 year old female recognised her problem at the age of 39 years, did not quite satisfy the NIH diagnostic criteria for NF 1 and had diffuse plexiform neurofibroma involving both lower limbs and buttocks almost symmetrically, a finding which has not previously been described to the best of our knowledge. The scarcity of management options are briefly outlined.

   

 

 

The principal objective of this study was to identify the factors that the management of verticaly integrated firms consider in making decisions to integrate either backword or forward. In order to meet this objective, the information sought for the study was collected through the use of a questionnaire. The sample consisted of 52 vertically integrated firms. 31 questionnaires were completed and provided the information used in this report. The study found out that he fator that influence a firm's decision to integrate vertically include certainity of demand for the firm's products, availability of adequate manufacturing facilities, investment costs, and the need for high market share. For textile and steel manufacturers, certain factor were important. The factors were: the need for improved co-ordination for a firm's activities, need for synergies, need for greater control over the firm's economic resources, level of competition in the industries and the mining firms, the need to control the firm's economic resources, the need to build new infrastructures, sze of buiness, and the level of competition in the industry are important

In order to increase generation capacity from reliable sources, Kenya has proposed to install a low-end nuclear power plant to supplement the envisaged short fall. At the moment, most of the power is generated from hydro and geothermal sources. Although an expansion of …

Description: This book describes four types of indigenous water retention structures used in East Africa. These structures are the Berkad tank, the Charco dam, sand wiers and hillside water retention ditches.

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No abstract available. PMID: 6535699 [PubMed - indexed for MEDLINE]

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Although early diagnosis and treatment are key factors in the effective control of human African trypanosomiasis (HAT), many cases of the disease delay taking appropriate action, leading to untold suffering. As a better understanding of treatment-seeking behaviour should help in identifying the obstacles to early diagnosis and effective treatment, the treatment pathways followed by 203 former HAT cases in western Kenya and eastern Uganda have recently been explored. About 86% of the HAT cases had utilized more than two different healthcare options before being correctly diagnosed for HAT, with about 70% each using more than three different health facilities. Only about 8% of the cases reported that they had been correctly diagnosed the first time they sought treatment. Just over half (51%) of the HAT cases had been symptomatic for >2 months before being correctly diagnosed for HAT, and such time lags in diagnosis contributed to 72% of the cases receiving their first appropriate treatment only in the late stage of the disease. The likelihood of a correct diagnosis increased with the time the case had been symptomatic. These observations indicate an urgent need to build the diagnostic capacity of the primary healthcare facilities in the study area, so that all HAT cases can be identified and treated in the early stage of the disease.

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Objective: To describe the characteristics and pattern of maxillofacial and concomitant injuries sustained in Road Traffic Accidents (RTAs).
Study Area: Kenyatta National Hospital (KNH).
Study Design: A descriptive cross sectional study including all patients involved in RTAs
brought to casualty and dental departments of KNH as well as accident victims admitted to the
KNH mortuary over a four- month period from September 2004 to December 2004.
Results: A total of 482 people involved in RTAs were included in the study. Four hundred and
thirteen (85.7%) had non-fatal injuries whereas 69 (14.3%) had sustained fatal injuries.
Nonfatal injuries. The 21-30-year-old age group was the most affected. The male to female ratio
was 4:1. Day time injuries were recorded among 60.3% of the participants. The incidence of
RTAs was highest on Fridays. There were 245 (59.5%) pedestrians and 139 (33.7%) passengers
involved. Most accidents were caused by passenger service vehicles (matatu) which were
responsible for 256 (62%) casualties whereas private saloon cars were involved in 150 (36.3%)
cases. Non- use of safety belts was reported in 90 (56.6%) cases whereas over-speeding was
reported by 120 (29.1 %) casualties. Alcohol use by drivers was reported in 26 (6.3%) cases
whereas vehicle defects accounted for 62 (15%) cases.Three hundred and seventy (89.6%)
casualties had soft tissue injuries (STls) involving the craniofacial region with facial cuts being the
majority (69.2%). Two hundred and seventy three (66.1 %) incidents of other STls than those of
the head region were noted, the lower limbs accounting for 45.4% of these. Only 5.1% of the
casualties had fractures involving the maxillofacial skeleton. Skeletal injuries other than those
involving the maxillofacial region were found in 142 (34.1%) incidents. The lower limbs were
more affected with 61 (43%) incidents followed by the upper limbs (24.6%). Pedestrians were
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most involved in sustaining skeletal injuries than other categories of road users.
Fatal RTAs: Sixty nine (14.3%) of the 482 participants were fatally injured. The 21-30- year-old
age group was the most affected (20%). The male to female ratio was 3.3:1. Matatus and minibuses
were the leading cause of fatal accidents together having been responsible for 28 (40.6%) of
the accidents. Pedestrians (71.4%) were by far more involved than other categories of road users.
Most participants had multiple injuries with chest injuries having been the most common (50
cases). Fourty six (66.7%) victims had injuries to the head region with subdural haemorrhage
having been the commonest injury found at autopsy (47.8%). Injuries to the chest were found in
fifty (72.2%) victims whereas abdominal and limb injuries were recorded in 42 (60.9%) and 34
(49.3%) victims respectively. Head injury alone was the leading cause of death (37.7%) followed
by head and chest injuries combined (13.0%)
Conclusion: The majority of people involved in RTAs were in their third decade of life with
males having been the predominant group affected. Pedestrians were the leading casualties
amongst road users. Most of the accidents were caused by passenger service vehicles. The lower
limbs sustained most soft tissue and skeletal injuries compared to other anatomic sites other than
the craniofacial area. The leading cause of death was head injury.

Hypertensive disorders occur in 6-8% of all pregnancies with the incidence varying with geographic location. Studies conducted at Kenyatta National Hospital have noted a prevalence of 5.4% of hypertensive disease and 0.56% for eclampsia. Pregnant mothers with hypertension are predisposed towards the development of potentially lethal complications, notably abruption placentae, disseminated vascular coagulation, cerebral haemorrhage, hepatic failure and acute renal failure. The baby many have intra-uterine growth retardation, suffer the consequences of being born to early, or die in utero. Causes of hypertensive disease especially pre-eclampia remain unknown.

OBJECTIVE: To provide an overview of the current global status of female genital mutilation (FGM) or female circumcision practised in various countries. DATA SOURCE: Major published series of peer reviewed journals writing about female genital mutilation (FGM) over the last two decades were reviewed using the index medicus and medline search. A few earlier publications related to the FGM ritual as practised earlier were also reviewed including the various techniques and tools used, the "surgeons or perpetrators" of the FGM ritual and the myriad of medical and sexual complications resulting from the procedure. Global efforts to abolish the ritual and why such efforts including legislation has resulted in little or no success were also critically reviewed. CONCLUSION: FGM remains prevalent in many countries including African countries where over 136 million women have been 'circumcised' despite persistent and consistent efforts by various governments, WHO and other bodies to eradicate the ritual by the year 2000 AD. This is as a result of deep rooted cultures, traditions and religions. Although FGM should be abolished globally, it must involve gradual persuasion which should include sensitisation and adequate community-based educational and medical awareness campaign. Mere repression through legislation has not been successful, and women need to be provided with other avenues for their expression of social status approval and respectability other than through FGM.

Minimum tillage is a system that limits the number of physical soil manipulations to the minimum. Work done in temperate regions and the tropics has demonstrated the benefits of minimum tillage over conventional tillage under specific conditions. The Kenya Government has recognized the need for more research in this area of minimum tillage and this has led to the initiation of trials in an attempt to develop easily adopted tillage systems. This paper gives the results of trials done at the Embu Research Station to determine the feasibility of minimum tillage in a medium-potential area of Kenya. Also tries to establish and confirm the yield advantages of minimum tillage over conventional tillage as observed elsewhere

Department of Human Anatomy, University of Nairobi, Kenya. Despite extensive investigation, pain cannot always be adequately diagnosed or cured. Subsequently, the management of pain can be daunting. The diagnosis of pain, however, is crucial to its effective management because of the grave influence that pain has on the quality of life. The biggest drawback in the management of pain is the lack of understanding, on the part of the practitioner, of the peripheral and central modulation of pain. The objective of this paper is to briefly review the current concepts in the recognition of and classification of pain, with emphasis on orofacial pain. PMID: 8033773 [PubMed - indexed for MEDLINE]

Curcuma longa L. (Zingiberaceae), commonly known as turmeric, is native to Southwest India with its rhizomes being the source of a bright yellow spice with various medicinal applications. It is widely cultivated throughout the tropics and similarly used for it medicinal value, in the cosmetic industry, and as a dye. Herein, the medicinal potentials of this plant as well as that of one of its bioactive constituents, curcumin, has been compiled. Turmeric can be regarded as a drug for the management of many diseases, such as cancer, inflammations, microbial infections, diabetes, arthritic, muscular disorders, biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, and sinusitis. Curcumin also displayed various pharmacological activities including antioxidant, antineoplastic, antiviral, antiinflammatory, antibacterial, antifungal, antidiabetic, anticoagulant, antifertility, cardiovascular protective, hepatoprotective, and immunostimulant activities in animals. This chapter provides baseline information to encourage the use of this plant in the management of various human ailments.

Heme oxygenase (HO) is thought to be induced in severe malaria, but the pathophysiologic consequences have not been examined. It is induced by hemolysis, oxidative stress, and inflammation. It degrades heme, producing carbon monoxide (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective study of 1,520 children admitted to a Kenyan district hospital, COHb levels were no higher in children with malaria than with other infections. The COHb levels in children with severe malarial anemia were higher than in other children with malaria, but significantly lower than in children with other causes of severe anemia such as sickle cell disease. Levels of COHb were not significantly higher in children with cerebral malaria or in those dying of malaria. These results do not support a systemic increase in HO activity in malaria compared with other infectious diseases, but the roles of HO and CO in malaria require further study.

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This integrative review on the teaching of reading in Kenyan primary schools provides a foundation for the growing movement there to improve reading education. In gathering sources for this review, we took an inclusive historical stance. Thus, we did not dismiss research reports that lacked traditional indicators of quality such as being published in peer-reviewed journals. We used multiple methods to find relevant research and associated documents, including two trips to Kenya. The review is organized by six topics: (a) language of instruction, (b) reading instruction, (c) reading materials, (d) reading culture, (e) assessment, and (f) teacher development. The review concludes with six proposals for policymakers, educational researchers, and teacher educators for the development of reading instruction based on what we learned in reviewing the literature. The first proposals are intended specifically to address the teaching of reading in Kenya, but they may be relevant to other sub-Saharan nations. The final proposal encourages others to conduct similar reviews to make possible a handbook of reading in Africa.

African countries are currently experiencing proliferation of mobile phone
subscriptions but no prevalence of personal computers or electricity (Parker, 2011). It is
estimated that, by the end of 2015 in Sub-Saharan Africa, the percentage of people with
mobile network access will surpass that of access to electricity in homes (Rao, 2011). This
phenomenon is also experienced in learning institutions, particularly universities, where
almost every student owns a mobile phone (Kashorda & Waema, 2009). Although there is

A random sample survey using personal interviews was conducted in Machakos and Makueni Districts of Kenya in 1992 to estimate the level of rabies vaccination of the dog population. To substantiate the results of the interviews, a sample of the surveyed dogs 3 months old and above were bled for serum rabies antibody determination using an inhibition enzyme immunoassay (INH EIA). Of the 266 surveyed 3 months old and above, only 29% (77/266) were reportedly vaccinated against rabies. Out of the 197 dog sera titrated for rabies antibody, only 29% (57/197) had detectable antibodies and only 16% (32/197) had antibody tires equal to or greater than the threshold considered protective of 0.5 I.U/ml. There was a strong positive association between a history of previous vaccination and the detection of rabies antibodies. Of 133 dogs with no history of previous vaccination, 20% (26/133) had detectable antibodies. With the rabies incidence in Machakos and Makueni Districts still unacceptably high, the level of vaccination estimated in this survey is clearly inadequate for rabies control and measures designed to increase it are discussed.