Stephen G. Kiama

Hydrophilic poly(DL-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells.

Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres have a proven track record for drug delivery and are suggested to be ideal carrier systems to target therapeutics into phagocytic cells such as macrophages (MPhis) and dendritic cells (DCs). Microspheres prepared by spray-drying from different PLGA-type polymers were evaluated regarding their effect on phagocytosis, intracellular degradation and viability of human-derived macrophages MPhis and DCs. Even the microspheres prepared from the most hydrophilic polymer RG502H, were efficiently phagocytosed by primary human MPhis and DCs. Interestingly, uptake of PLGA microspheres by DCs as potent immune modulator cells was almost as efficient as uptake by the highly phagocytic MPhis. Phagocytosed microspheres remained inside the cells until decay with none of the microsphere preparations induced significant apoptosis or necrotic cell death. Acidic pH and the phagosomal environment inside the cells enhanced microsphere decay and release of encapsulated material. Degradation of microspheres consisting of the most hydrophilic PLGA polymer RG502H occurred in a reasonable time frame of less than 2 weeks ensuring the release of encapsulated drug during the life span of the cells. To explore important technical and biological aspects of DNA microencapsulation, we have studied DNA loading and in vitro DNA release of microspheres from different PLGA type polymers. Hydrophobicity and molecular weight of the PLGA polymers had profound influence on both the encapsulation efficiency of DNA and its release kinetics in vitro: the hydrophilic polymers showed higher encapsulation efficiency and faster release of intact DNA compared to the hydrophobic ones. These results suggest that microspheres from the PLGA polymer RG502H have improved characteristics for DNA delivery to human MPhis and DCs.

Skin shedding and tissue regeneration in African spiny mice (Acomys)

Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

Antimalarial herbal remedies of Msambweni, Kenya

Malaria is a serious cause of mortality globally. The disease is of regional concern in Africa and of national interest in Kenya due to its high morbidity and mortality as a result of development of resistant strains of Plasmodium falciparum to many existing drugs such as chloroquine. Alternative medicine using herbal remedies are commonly used to treat malaria in Kenya. However, plants used in some rural areas in Kenya are not documented. Many antimalarial drugs have been derived from plants. This study was conducted to document medicinal plants that are traditionally used by the Msambweni community of Kenyan South Coast to treat malaria, where the disease is endemic. Herbalists were interviewed by administration of semistructured questionnaires in order to obtain information on medicinal plants traditionally used for the treatment of malaria. Focused group discussions held with the herbalists supplemented the interview and questionnaire survey. Twenty-seven species of plants in 24 genera distributed in 20 families were reported to be used in this region for the treatment of malaria. Labiatae, Rutaceae and Liliaceae families had each eleven percent of the plant species reported and represented the species that are most commonly used. Thirteen plant species, namely; Aloe deserti Berger (Liliaceae), Launea cornuta (Oliv and Hiern) C. Jeffrey (Compositae), Ocimum bacilicum L. (Labiatae), Teclea simplicifolia (Eng) Verdoon (Rutaceae), Gerranthus lobatus (Cogn.) Jeffrey (Cucurbitaceae), Grewia hexaminta Burret. (Tiliaceae), Canthium glaucum Hiern. (Rubiaceae), Amaranthus hybridus L. (Amaranthaceae), Combretum padoides Engl and Diels. (Combretaceae), Senecio syringitolius O. Hoffman. (Compositae), Ocimum suave Willd (Labiatae), Aloe macrosiphon Bak. (Liliaceae) and Laudolphia buchananii (Hall.f) Stapf. (Apocynaceae) are documented from this region for the first time for the treatment of malaria. These results become a basis for selection of plants for further pharmacological, toxicological and phytochemical studies in developing new plant based antimalarial drugs.

A systematic review of Rift Valley Fever epidemiology 1931-2014.

Background Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis that was first isolated and characterized in 1931 in Kenya. RVF outbreaks have resulted in significant losses through human illness and deaths, high livestock abortions and deaths. This report provides an overview on epidemiology of RVF including ecology, molecular diversity spatiotemporal analysis, and predictive risk modeling. Methodology Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched for relevant RVF publications in repositories of the World Health Organization Library and Information Networks for Knowledge (WHOLIS), U.S Centers for Disease Control and Prevention (CDC), and Food and Agricultural Organization (FAO). Detailed searches were performed in Google Scholar, SpringerLink, and PubMed databases and included conference proceedings and books published from 1931 up to 31st January 2015. Results and discussion A total of 84 studies were included in this review; majority (50%) reported on common human and animal risk factors that included consumption of animal products, contact with infected animals and residing in low altitude areas associated with favorable climatic and ecological conditions for vector emergence. A total of 14 (16%) of the publications described RVF progressive spatial and temporal distribution and the use of risk modeling for timely prediction of imminent outbreaks. Using distribution maps, we illustrated the gradual spread and geographical extent of disease; we also estimated the disease burden using aggregate human mortalities and cumulative outbreak periods for endemic regions. Conclusion This review outlines common risk factors for RVF infections over wider geographical areas; it also emphasizes the role of spatial models in predicting RVF enzootics. It, therefore, explains RVF epidemiological status that may be used for design of targeted surveillance and control programs in endemic countries.

Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya

ETHNOPHARMACOLOGICAL RELEVANCE Traditional medicine plays a critical role in treatment of chronic debilitating and life threatening conditions and diseases. Cancer is one such condition whose therapeutic intervention is commonly through inexpensive traditional herbal remedies. Increasingly industrialised societies are developing drugs and chemotherapeutics from these traditional herbal plants. Plant biogeography determines the abundance and availability of medicinal plants which in turn determine their use by local communities. The present study was carried out in Kakamega County of Kenya to identify and document medicinal plants used for treatment and management of cancer states by communities living adjacent to Kakamega Tropical rainforest of Kakamega County, Kenya. MATERIALS AND METHODS An ethnobotanical survey was done using semi-structured questionnaires administered to 32 randomly selected herbalists from Kakamega County. RESULTS AND DISCUSSION Sixty five (65) plants of 59 genera and 32 families were identified as candidates in therapeutic intervention against cancer states. Most commonly cited plant species were Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Microglossa pyrifolia (Lam.) Kuntze, Harungana madagascariensis Lam. ex poir, Prunus africana (Hook. f.) kalkman, Cyphostemma serpens (A. Rich), Catharanthus roseus (L.) G. Don and Aloe volkensii Engl. The following were documented for the first time; Aeschynomene abyssinica (A. Rich.) Vatke, Synsepalum cerasiferum (welw.) T. D penn., Albizia coriaria Welw. ex Oliv., Aloe volkensii Engl. Bridelia micrantha (Hochst.) Baill, Croton macrostachyus Delile, Cyphostemma serpens (A. Rich), Dicliptera laxata C.B. Clarke, Ekebergia capensis Sparrm., Gardenia volkensii K. schum. ssp. volkensii, Glycine wightii (wight & Arn.), Ocimum gratissimum Suave, Olea hotcsh spp. hochstetteri, Pavetta abyssinica Fresen., Phyllanthus fischeri Pax, Psydrax schimperiana (A. Rich), Rhus vulgaris Meikle, Senna didymobotyra (Fresen.) Irwin and Barneby, Solanecio nandensis (S. Moore) C. Jeffrey, Solanum mauritianum Scop, Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Spermacoce princea (K. Schum.) Verdc., Tabernaemontana stapfiana Britten, Tragia brevipes Pax and Zanthoxylum gilletii (De Wild.) P.G.Waterman. The most frequently used plant parts were fresh or dried leaves and stem barks. Administration to patients was almost exclusively oral, with the exceptions being topical application especially for breast cancer and skin sarcomas. CONCLUSIONS This study identified diverse medicinal plants used in therapeutic and management intervention against cancer by communities living adjacent to Kakamega Tropical Rainforest. The primary mode of administration was oral.

Evaluation of Phagocytic Activity in Human Monocyte-Derived Dendritic Cells

Dendritic cells play a central role in initiation of primary T lymphocyte responses to foreign antigens. Their potency in antigen presentation vis-à-vis reported low or lack of ability to phagocytize particulate matter has limited our understanding of the role that they play in inducing immunity to particulate antigens. One hypothesis is that dendritic cells may possess a high phagocytic capacity when immature and located in peripheral tissues, which they lose on maturation. Our goal was to characterize the phagocytic capacity in human immature dendritic cells. The phagocytic capacity of human monocyte-derived immature dendritic cells was studied by morphological and morphometric means, and compared to that of professional phagocytes, human alveolar macrophages, their progenitors, the peripheral blood monocytes, and mature dendritic cells. Phagocytic index (proportion of phagocytic cells) was decreased by 42.8% (immature dendritic cells) and 74.2% (mature dendritic cells) with respect to monocytes. Similarly, the phagocytic index was decreased by 46.5% (immature dendritic cells) and 75.9% (mature dendritic cells) with respect to macrophages. Volume density of phagocytized particles was decreased by 76.1% (immature dendritic cells) and 96.7% (mature dendritic cells) with respect to the monocytes. However, volume density was decreased by 34.3% (immature dendritic cells) and 91% (mature dendritic cells) with respect to alveolar macrophages. These results show that human monocyte-derived immature dendritic cells possess a phagocytic capacity that is lower than that of peripheral blood monocytes and alveolar macrophages but higher than that of mature dendritic cells.

Medicinal plants used in the management of chronic joint pains in Machakos and Makueni counties, Kenya

ETHNOPHARMACOLOGICAL RELEVANCE Traditional medicines play an important role in the management of chronically painful and debilitating joint conditions, particularly in the rural Africa. However, their potential use as sources of medicines has not been fully exploited. The present study was carried to find the medicinal plants traditionally used to manage chronic joint pains in Machakos and Makueni counties in Kenya. MATERIALS AND METHODS To obtain this ethnobotanical information, 30 consenting traditional herbal medical practitioners were interviewed exclusively on medicinal plant use in the management of chronic joint pains, in a pre-planned workshop. RESULTS AND DISCUSSION In this survey, a total of 37 plants belonging to 32 genera and 23 families were cited as being important for treatment of chronic joint pains. The most commonly cited plant species were Pavetta crassipes K. Schum, Strychnos henningsii Gilg., Carissa spinarum L., Fagaropsis hildebrandtii (Engl.) Milve-Redh. and Zanthoxylum chalybeum Engl. Acacia mellifera (Vahl) Benth., Amaranthus albus L., Balanites glabra Mildbr. & Schltr., Grewia fallax K. Schum., Lactuca capensis, Launaea cornuta (Oliv. & Hiern) O. Jeffrey, Lippia kituiensis Vatke, Pappea capensis Eckl. & Zeyh. and Pennisetum glaucum (L.) R. Br. are documented for the first time as being important in the management of chronic joint pains. CONCLUSIONS The findings of this study show that a variety of medicinal plants are used in the management of chronic joint pains and the main mode of administration is oral.

Genetic background of attenuated Salmonella typhimurium has profound influence on infection and cytokine patterns in human dendritic cells

Salmonella typhimurium (ST) can cause infection inman, and attenuated strains are under consideration as live vaccinevectors. However, little is known about the interaction of ST withhuman dendritic cells (DC). Here, we compared the consequences ofexposure of human, monocyte‐derived DC with different attenuatedstrains of ST. Infection was observed with all four strains tested(wild type, PhoP−, PhoPc, and AroA), but the PhoPc strainwas by far the most efficient. Intracellular persistence of wild typeand PhoP− was longer than that of PhoPc and AroA, both ofwhich were largely eliminated within 24 h. Most DC survivedinfection by the attenuated strains, although apoptosis was observed ina fraction of the exposed cells. All strains induced DC maturation,independent from the extent of infection. Although all strainsstimulated secretion of TNF‐α and IL‐12 strongly, PhoPc inducedsignificantly less IL‐10 than the other three strains and as much as 10times less IL‐10 than heat‐killed PhoPc, suggesting that this mutantsuppressed the secretion of IL‐10 by the DC. These data indicate thatinfectivity, bacterial elimination, and cytokine secretion in human DCare controlled by the genetic background of ST.

Cross-Cultural Differences in a Global “Survey of World Views”

We know that there are cross-cultural differences in psychological variables, such as individualism/collectivism. But it has not been clear which of these variables show relatively the greatest differences. The Survey of World Views project operated from the premise that such issues are best addressed in a diverse sampling of countries representing a majority of the world’s population, with a very large range of item-content. Data were collected online from 8,883 individuals (almost entirely college students based on local publicizing efforts) in 33 countries that constitute more than two third of the world’s population, using items drawn from measures of nearly 50 variables. This report focuses on the broadest patterns evident in item data. The largest differences were not in those contents most frequently emphasized in cross-cultural psychology (e.g., values, social axioms, cultural tightness), but instead in contents involving religion, regularity-norm behaviors, family roles and living arrangements, and ethnonationalism. Content not often studied cross-culturally (e.g., materialism, Machiavellianism, isms dimensions, moral foundations) demonstrated moderate-magnitude differences. Further studies are needed to refine such conclusions, but indications are that cross-cultural psychology may benefit from casting a wider net in terms of the psychological variables of focus.

Traditional antimalarial phytotherapy remedies used by the South Coast community, Kenya

AIM OF THE STUDY This study was conducted to document herbal medicines used in the treatment of malaria as well as the existing knowledge, attitudes and practices related to malaria recognition, control and treatment in South Coast, Kenya. METHODS Data was collected using semistructured questionnaires and interviews. A focused group discussion held with the community members, one in each of the study villages supplemented the interview and questionnaire survey. RESULTS The respondents were found to have a good understanding of malaria and could distinguish it from other fever types. They were also aware that malaria was spread by mosquitoes. Malaria prevalence was high, and affected individuals an average of four times a year. Community members avoided mosquito bites by using mosquito nets, clearing bushes around their homesteads and burning plant parts to generate smoke. They prevented and treated malaria by taking decoctions or concoctions of traditional herbal remedies. Forty plant species in thirty-five genera distributed in twenty-four families were used as antimalarials in the study area. Five plant species, namely; Heeria insignis Del. (Anacardiaceae), Rottboelia exaltata L.F (Gramineae), Pentanisia ouranogyne S. Moore (Rubiaceae), Agathisanthenum globosum (A. Rich) Hiern (Rubiaceae), and Grewia trichocarpa Hochst ex A. Rich (Tiliaceae) are documented for the first time in South Coast, Kenya, for the treatment of malaria. CONCLUSIONS The plants documented in the current study are a potential source for new bioactive compounds of therapeutic value in malaria treatment. The results provide data for further pharmacological and toxicological studies and development of commercial antimalarial phytotherapy products.