Kat is being used extensively in many countries as a central nervous system stimulant. The effect of three doses of crude kat extract on chromosomal division and abnormalities in bone marrow, as well as on DNA, RNA, and total protein content in brain and liver was studied in laboratory rats in order to test the possible mutagenicity of the drug. Kat was given as a single subcutaneous injection at 0.05 (usage dose), 0.52 (intermediate dose), and 1.00 (sublethal dose) g/kg body weight. Animals were sacrificed at 6, 24, and 48 hr after treatment. Also, some animals were exposed subacutely for 5 consecutive days with sacrifice occurring 6 hr after the last injection. The mitotic index was reduced by all treatments, with the greatest effect occurring in the subacute treatment. Chromosomal abnormalities were induced by kat at all three doses, administered acutely or subacutely. The significant chromosomal aberrations were in the form of gaps, breaks, centromeric attenuations, and centric fusions. The concentration of DNA, RNA, and total protein in liver and brain decreased at all doses, with the greatest decrease occurring after subacute treatment. These findings suggest that kat has a profound effect on cell proliferation, on chromosomal abnormalities, and on DNA, RNA, and total protein synthesis.

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BackgroundEnteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5 years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes-causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole-cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes as a combined vaccine candidate.ResultsWe immunized Balb/C mice subcutaneously with 109 CFU of combined vaccine candidate and found a significant increase in survival rate post challenge compared to unimmunized controls (100 % survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6 weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNγ) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2 weeks after mice immunization compared to controls (p < 0.05). We also evaluated alum and cholera toxin B subunit (CTB) as potential adjuvant systems for our candidate vaccine. We found that CTB-adjuvanted combined vaccine candidate showed significantly higher IgG and IFNγ levels than alum.ConclusionsOverall, our combined vaccine candidate offered protection against the five main diarrheagenic E. coli pathotypes in a single vaccine using mouse model. To the best of our knowledge, this is the first combined vaccine against the five main diarrheagenic E. coli pathotypes that is cost-effective with promise for further testing in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-1891-z) contains supplementary material, which is available to authorized users.

Rabies remains an important public health problem in the world due to uncontrolled enzootic rabies, lack of safe efficient vaccines and poor information on the risk of contracting rabies post animal exposure. The lethality and mutagenic potential of challenge virus standard (CVS) was evaluated in mice. Mice were intracerebrally infected (MIC) with low, medium and high viral LD 50 (MICLD 50 ). Mice were subjected to immunomodulation using interferon (IFNα-2a) pre-infection. The infected groups pretreated with IFN-α 2a showed a higher survival rate than the infected group. Statistically significant increase in structural and numerical chromosomal aberrations and a decreased mitotic activity of mice bone marrow cells was observed post infection. Pretreatment of the infected groups with IFN α-2a showed a marked and significant reduction of these cytogenetic changes. The increased survival rate and reduced cytogenetic changes suggest that protection induced by interferon against rabies virus activity could be, at least partially, attributable to blockage of the replication of CVS strain of rabies virus. It could be concluded that interferon can be used as an immune enhancer to the application of vaccine administration.

Background: Erythrocyte invasion byPlasmodium falciparum parasites is central to malaria pathogenesis. Thus, it is critical to understand this intricate biological process for the development of novel malaria intervention strategies. P. falciparum erythrocyte invasion is a complex, multistep process that is mediated by a number of redundant ligand-receptor interactions. Extensive research over three decades has aimed at identifying an essential parasite ligand that could be targeted across multiple parasite strains. In this regard, PfRH5 was identified as a critical ligand that binds with the erythrocyte receptor, Basigin and elicits potent cross-strain neutralizing antibodies. We have for the first time expressed fulllength recombinant PfRH5 in E. coli with a structural integrity that mimics the native parasite protein. Our recombinant PfRH5 protein is functional, binds with Basigin and elicits potent cross-strain transcending parasite neutralising antibodies that substantiates its claim as a leading vaccine candidate (IAI, 2014). In addition, PfRH5 lacks a transmembrane domain or GPI anchor and thus a major question has been that how PfRH5 is anchored on the merozoite surface during invasion such that it can engage with its receptor Basigin and mediate attachment. We have successfully solved this conundrum and identified an essential, novel, conserved GPI-anchored parasite molecule, CyRPA that tethers PfRH5 on the parasite surface as a multiprotein complex (PNAS 2015).Methods & Materials: We have produced different fragments of PfRH5/CyRPA recombinant proteins, functionally characterized their binding properties and measured the parasite neutralizing ability of their antibodies.Results: We demonstrate that PfRH5/CyRPA monoclonal and polyclonal antibodies potently block erythrocyte invasion synergistically in a strain-transcending manner by abrogating formation of the PfRH5/CyRPA essential complex. We have thus identified a new conserved mechanism overcoming the previous challenges of blood-stage vaccines (antigen diversity, redundancy, heterologous strain cross-reactivity) paving the way forward to develop new generation blood stage P. falciparum vaccines based on PfRH5 and CyRPA. Conclusion:Our previous discovery had elucidated the formation of a novel multi-protein PfRH5/CyRPA complex essential for erythrocyte invasionl, which we have validated in vitro as a new potent target for the development of novel blood-stage vaccines that could elicit protection alone or in combination with the advanced pre-erythrocytic RTS.S sub-unit vaccine.