Background: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1G93A mice during defined disease stages. Methods: hSOD1G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results: We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions: These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1G93A mouse. Hence, reducing complement-induced inflammation could be an important therapeutic strategy to treat ALS.
Objective Pesticide poisoning is a global health problem, and its progressive deterioration is a major cause of concern. The objective of this study is to assess epidemiological characteristics and identify risk factors of pesticide poisoning in Malaysia. Setting Pesticide poisoning database of Malaysia National Poison Centre (NPC) from 2006 to 2015. Participants Telephone enquiries regarding pesticide poisoning were made by healthcare professionals. Information received by the NPC was entered into a retrievable database of standardised Poison Case Report Form, as adapted from the World Health Organization (WHO). Outcomes The outcome of the study is to provide an overview of national epidemiological profile of pesticide poisoning. High-risk groups of people and their circumstances were also identified to ensure that appropriate measures are strategised. Results Within the study period, a total of 11 087 pesticide poisoning cases were recorded. Sixty per cent of these cases were intentional in nature and most were found among male individuals (57%) of the Indian race (36.4%) aged between 20 and 29 years (25.5%), which occurred at home (90%) through the route of ingestion (94%). The highest number of poisoning was due to herbicides (44%) followed by agricultural insecticides (34%), rodenticides (9.9%), household insecticides (9.5%) and fungicides (0.5%). In addition, 93.6% of intentional pesticide poisoning cases were caused by suicide attempts. The results of this study show that there was an increasing trend in pesticide poisoning incidents over the 10-year duration. This indicates that pesticide poisoning is a prevalent public health problem in Malaysia, resulting in an average incidence rate of 3.8 per 100 000 population. Conclusions Deliberate pesticide ingestion as a method of suicide has become a disturbing trend among Malaysians. Therefore, regulation of highly hazardous pesticides must be enforced to ensure controlled and limited access to these chemicals by the public.
30 July 2020 in Journal of Sustainability Science and Management