ABSTRACT
@#Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-β) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.
ABSTRACT
@#In addition to the scarcity of forensic entomology baseline data on oviposition of necrophagous insects and completion of their life cycles in the Borneo region, similar data derived from caves remain unreported. Since entomological baseline data can differ from one biogeoclimatic region to another, the lack of such data would limit the practical values of applying entomological evidence in estimating minimum postmortem interval (mPMI). Therefore, this present research that investigated oviposition and completion of life cycles of necrophagous flies infesting rabbit carcasses decomposing in Mount Kapur Cave and its surrounding forest habitat in Kuching, Sarawak merits forensic consideration. In general, 13 taxa of necrophagous flies were identified viz. Hypopygiopsis violacea, Hypopygiopsis fumipennis, Hemipyrellia ligurriens, Hemipyrellia tagaliana, Chrysomya megacephala, Chrysomya villeneuvi, Chrysomya rufifacies, Chrysomya chani, Chrysomya pinguis, Chrysomya nigripes, Ophyra spinigera and Ophyra chalcogaster, as well as unidentified Sarcophagidae. In addition, Hyp. violacea and Hyp. fumipennis were the two earlier necrophagous flies that oviposited in all rabbit carcasses decomposing in both habitats. While all these necrophagous flies were observed infesting carcasses in Mount Kapur Cave, Hem. ligurriens and Hem. tagaliana were not found infesting carcasses in the surrounding forest habitat. Complete life cycles for six and five different necrophagous fly species were successfully observed in Mount Kapur Cave and its surrounding forest habitat, respectively. Significant delay in oviposition, as well as longer durations for completing the life cycles in several necrophagous fly species were observed in Mount Kapur Cave when compared with those of surrounding forest habitat (p < 0.05). These findings deserve consideration as the first ever forensic empirical baseline data on oviposition and completion of life cycles for necrophagous flies in Sarawak as well as in a cave habitat, in view of its practical values for estimating mPMI for forensic practical caseworks.
ABSTRACT
@#Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied. However, their specific association with survival and severe infection remained obscure.Methods: Thestudy investigated the cytokine profiles and histopathological features of malaria in the severe infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar histopathological severity during peak parasitemia. The severe model produced highly elevated levels of pro-inflammatory cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection. These could be a basis for immunotherapy of malaria in the future
ABSTRACT
@#Influence of citronella and chlorpyrifos on oviposition and duration for completing life cycles for Chrysomya megacephala and Chrysomya rufifacies infesting decomposing rabbit carcasses was studied. Male rabbit carcasses (n = 12) were equally divided into control, citronella- and chlorpyrifos–treated groups, and left to decompose for 14 consecutive days. C. megacephala was the first necrophagous fly oviposited in all control and citronellatreated carcasses followed by C. rufifacies. Although initial oviposition of C. megacephala was delayed (4-6 hours) in citronella-treated carcasses (P < 0.05), prolongation in completing its life cycle was not observed. Neither delayed initial oviposition nor prolonged life cycle for C. rufifacies in citronella-treated carcasses was observed. Oviposition was delayed for chlorpyrifos-treated carcasses (0.42 g/L), and eclosion of eggs remained unsuccessful. The findings deserve consideration because these chemicals are easily accessible and can be used by cunning criminals to confuse forensic entomologists while estimating minimum postmortem interval.
ABSTRACT
Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.