Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Onchocerciasis: The Pre-control Association between Prevalence of Palpable Nodules and Skin Microfilariae

*Background*: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of

Mild Hypothermia Attenuates Mitochondrial Oxidative Stress by Protecting Respiratory Enzymes and Upregulating MnSOD in a Pig Model of Cardiac Arrest

Mild hypothermia is the only effective treatment confirmed clinically to improve neurological outcomes for comatose patients with cardiac arrest. However, the underlying mechanism is not fully elucidated. In this study, our aim was to determine the effect of mild hypothermia on mitochondrial oxidative stress in the cerebral cortex. We intravascularly induced mild hypothermia (33°C), maintained this temperature for 12 h, and actively rewarmed in the inbred Chinese Wuzhishan minipigs successfully resuscitated after 8 min of untreated ventricular fibrillation. Cerebral samples were collected at 24 and 72 h following return of spontaneous circulation (ROSC). We found that mitochondrial malondialdehyde and protein carbonyl levels were significantly increased in the cerebral cortex in normothermic pigs even at 24 h after ROSC, whereas mild hypothermia attenuated this increase. Moreover, mild hypothermia attenuated the decrease in Complex I and Complex III (i.e., major sites of reactive oxygen species production) activities of the mitochondrial respiratory chain and increased antioxidant enzyme manganese superoxide dismutase (MnSOD) activity. This increase in MnSOD activity was consistent with the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein expressions, and with the increase of Nrf2 nuclear translocation in normothermic pigs at 24 and 72 h following ROSC, whereas mild hypothermia enhanced these tendencies. Thus, our findings indicate that mild hypothermia attenuates mitochondrial oxidative stress in the cerebral cortex, which may be associated with reduced impairment of mitochondrial respiratory chain enzymes, and enhancement of MnSOD activity and expression via Nrf2 activation

Density-Dependent Mortality of the Human Host in Onchocerciasis: Relationships between Microfilarial Load and Excess Mortality

Human onchocerciasis (River Blindness) is a parasitic disease leading to visual impairment including blindness. Blindness may lead to premature death, but infection with the parasite itself (Onchocerca volvulus) may also cause excess mortality in sighted individuals. The excess risk of mortality may not be directly (linearly) proportional to the intensity of infection (a measure of how many parasites an individual harbours). We analyze cohort data from the Onchocerciasis Control Programme in West Africa, collected between 1974 and 2001, by fitting a suite of quantitative models (including a ‘null’ model of no relationship between infection intensity and mortality, a (log-) linear function, and two plateauing curves), and choosing the one that is the most statistically adequate. The risk of human mortality initially increases with parasite density but saturates at high densities (following an S-shape curve), and such risk is greater in younger individuals for a given infection intensity. Our results have important repercussions for programmes aiming to control onchocerciasis (in terms of how the benefits of the programme are calculated), for measuring the burden of disease and mortality caused by the infection, and for a better understanding of the processes that govern the density of parasite populations among human hosts