Influence of Aspilia pluriseta Schweinf (Asteraceae) on the healing of dermal excision wounds (mouse model) and skin sensitization activity (Guinea pig model)

Background: The skin is highly predisposed to injury because of its direct contact with the environment. The aim of treating of wounds is to both hasten healing, and to minimise the occurrence of perturbations of the healing process. Many plants traditionally used to treat wounds have been proven to support the healing process using scientific models. Aspilia pluriseta has been used by a number of communities in East and Southern Africa to treat wounds. Objectives: This study aimed at testing ethnomedical claims of wound healing activity of A. pluriseta using preclinical models. Methods: Aerial parts of the plant were ground and incorporated into an ointment base (10% and 20% w/w) to evaluate the influence of the plant on the healing of acute excision wounds in mice compared to Silverex Cream® and Simple Ointment (B.P.). The 20% ointment was tested for skin sensitization in guinea pigs. Results: The effects of the plant-based ointments on wound contraction and gross epithelialisation time were less than significantly different from the controls (p≥0.05), but histopathologic examination revealed remarkable epithelialisation and collagen deposition in the wounds treated with the these ointments. The 20% A. pluriseta-based ointment induced moderate allergic contact dermatitis. Key words: Aspilia pluriseta, wound healing, skin sensitization, excision wound mode

Complex Tissue Regeneration in Mammals Is Associated with Reduced Inflammatory Cytokines and an Influx of T Cells

While mammals tend to repair injuries, other adult vertebrates like salamanders and fish regenerate damaged tissue. One prominent hypothesis offered to explain an inability to regenerate complex tissue in mammals is a bias during healing toward strong adaptive immunity and inflammatory responses. Here we directly test this hypothesis by characterizing part of the immune response during regeneration in spiny mice (Acomys cahirinus and Acomys percivali) vs. fibrotic repair in Mus musculus. By directly quantifying cytokines during tissue healing, we found that fibrotic repair was associated with a greater release of pro-inflammatory cytokines (i.e., IL-6, CCL2, and CXCL1) during acute inflammation in the wound microenvironment. However, reducing inflammation via COX-2 inhibition was not sufficient to reduce fibrosis or induce a regenerative response, suggesting that inflammatory strength does not control how an injury heals. Although regeneration was associated with lower concentrations of many inflammatory markers, we measured a comparatively larger influx of T cells into regenerating ear tissue and detected a local increase in the T cell associated cytokines IL-12 and IL-17 during the proliferative phase of regeneration. Taken together, our data demonstrate that a strong adaptive immune response is not antagonistic to regeneration and that other mechanisms likely explain the distribution of regenerative ability in vertebrates

Acute toxicity of the aqueous-methanolic Moringa oleifera (Lam) leaf extract on female Wistar albino rats

Background: Herbal preparations are widely assumed to be safe on oral administration and therefore the documentation of the toxic potential of some herbal concoctions used as medicine and nutrients is limited. Moringa oleifera (MO) is a plant that is gaining tremendous popularity in rural communities in Kenya as a means of offsetting nutritional and medicinal needs. However, very little is known about the safety of the plant on oral administration. Thus, the aim of the current study was to assess the biochemical and histological changes in the liver following the administration of an aqueous-methanolic (AQ-ME) MO leaf extract in female Wistar albino rats.Methods: Acute oral toxicity study on the AQ-ME MO leaf extract was conducted by the use of the limit test dose of the up and down procedure (OECD guideline number 425) with slight modifications. Briefly, ten (10) healthy, nulliparous, non-pregnant female Wistar strain albino rats aged               8-12 weeks and weighing 180±20 grams were used for the study. These animals were randomly selected into two groups; control and treatment group each having five (5) animals. They were then labelled to enable identification and control group animals were orally administered with physiological buffer saline once daily over a 48-hour period. The five (5) rats in the treatment group were dosed orally one at a time and once daily with a 2000 mg/kg dose of the AQ-ME MO leaf extract to determine the median lethal dose over a 48 hour period. Blood was then collected and used to prepare serum for biochemical analysis of aspartate amino transferase (AST), alanine amino transferase (ALT) and total bilirubin (TB) which are important biomarkers of liver dysfunction. Biochemical assays of these enzymes were performed using the method of the International Federation of Clinical Chemists (IFCC). Death was used as an endpoint, livers harvested and used to prepare transverse sections for histopathological examination. These sections were stained using the haematoxylin and eosin (H&E) method and observed for pathological changes using an optical microscope.Results: A 2000 mg/kg oral dose of AQ-ME MO leaf extract caused a significant (p0.05) increase in the mean levels of total bilirubin in the treatment group relative to the control group. On the other hand, the extract caused a non-significant (p>0.05) decrease in the mean levels of ALT in the treatment group relative to the control. The post mortem analysis of the hepatic index (liver to body weight ratio) revealed that there was a non-significant increase (p>0.05) in the hepatic index of the treatment group relative to the control. However, the transverse liver sections of treatment group animals showed mild distortions in the architecture of liver cells.Conclusions: Based on these results, the LD50 of the AQ-ME MO leaf extract was found to be >2000 mg/kg in female wistar albino rats

Transcriptional regulation of Rat Endothelial Nitric Oxide Promoter in Pulmonary Myofibroblasts cells and its implications in Pulmonary Fibrosis

Background: Nitric oxide (NO) levels may exert control on the persistence of pulmonary myofibroblast cells in pulmonary fibrosis.Objective: This study set out to examine the regulation of NO levels by transcription factors that influence the expression of the endothelial nitric oxide synthase (eNOS3) gene.Methods: Using a pGL3-Basic vector plasmid DNA, rat and human eNOS3 gene promoters were inserted upstream of a luciferase reporter gene and cloned in competent E. coli cells (DH5α). Transfection assays were performed and the cells treated with potential regulators of eNOS3 gene. Promoter activity of eNOS3 gene was assayed using the Dual Luciferase reporter gene assay.Results: The results indicated that the rat NOS3 promoter was active in the cells, with the human NOS3 promoter showing little or no activity. The results demonstrated that transforming growth factor-β, EGTA and lipopolysaccharide up-regulated transcriptional activity while Phorbol 12-myristate-13-acetate, 23187 and S-nitroso-N-acetylpenicillamine, suppressed eNOS3 transcriptional activity. Treatment with Nw-Nitro-L-arginine methyl ester had no effect on the gene expression.Discussion: The results of this study demonstrates that high concentrations of NO inhibit NOS3 gene activity, hence an enhanced expression of eNOS in response to pharmacological interventions using some transcriptional factors from these study could provide protection against interstitial pulmonary.Key words: Nitric oxide, transcription, NOS3 gene promoter, pulmonary fibrosi

Morphofunctional adaptations of the olfactory mucosa in postnatally developing rabbits

Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit

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

Data from: Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals

Why mammals have poor regenerative ability has remained a long-standing question in biology. In regenerating vertebrates, injury can induce a process known as epimorphic regeneration to replace damaged structures. Using a 4-mm ear punch assay across multiple mammalian species, here we show that several Acomys spp. (spiny mice) and Oryctolagus cuniculus completely regenerate tissue, whereas other rodents including MRL/MpJ ‘healer’ mice heal similar injuries by scarring. We demonstrate ear-hole closure is independent of ear size, and closure rate can be modelled with a cubic function. Cellular and genetic analyses reveal that injury induces blastema formation in Acomys cahirinus. Despite cell cycle re-entry in Mus musculus and A. cahirinus, efficient cell cycle progression and proliferation only occurs in spiny mice. Together, our data unite blastema-mediated regeneration in spiny mice with regeneration in other vertebrates such as salamanders, newts and zebrafish, where all healthy adults regenerate in response to injury

Effects of anticancer drug docetaxel on the structure and function of the rabbit olfactory mucosa

Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitotic cancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting high cellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26mg/kg, i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67 immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days (PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE), apoptotic death of cells of the OE, Bowman's glands and axon bundles, and the presence (including on PED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densities and cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was also evident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivity decreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from the impairment by PED 15. These observations show that DCT transiently alters the structure and function of the OM suggesting a high regenerative potential for this tissue