Passive avoidance response in mice infected with Schistosoma mansoni

Schistosomiasis is a parasitic disease of humans and rodents affecting more than 200 million people worldwide. Following the onset of infection, the worms induce granulomas around schistosome eggs in the liver, intestine and central nervous system (both brain and spinal cord), which are likely to cause changes in cognitive functions. In the present study, CD-1 female mice were percutaneously infected with 60 cercariae of Schistosoma mansoni and the effect on the mice's cognitive abilities were assessed by using the passive avoidance learning paradigm both in an early and a late phase of infection (independent groups). The results of the study show that infected animals without brain granulomas (early phase) had impairments in their passive avoidance response, whereas mice with brain granulomas (late phase) behaved as uninfected ones. Moreover, a decreased propensity to start exploration was observed in mice with granulomas in the brain. The results suggest that the murine model of infection may be a useful tool for studying human neuroschistosomiasis.     

Interobserver agreement in staging gastric malt lymphoma by EUS

BACKGROUND: EUS is highly accurate for staging gastric lymphoma. Because stage correlates to outcome, interobserver agreement is mandatory. However, previous studies suggest that interobserver agreement might vary according to T-stage. A multicenter evaluation of observer agreement with respect to endosonographic staging of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was therefore conducted. METHODS: Fifty-four patients were studied; 42 were also evaluated after eradication of Helicobacter pylori infection. EUS was performed at different institutions by 10 experienced endosonographers who collected the best photographs for each examination. Interobserver agreement was estimated with kappa statistics. RESULTS: Overall interobserver agreement for T-stage was fair, both before and after treatment (kappa = 0.38 and kappa = 0.37, respectively). Overall interobserver agreement for N-stage was substantial before treatment, but only fair after treatment (kappa = 0.63 and kappa = 0.34, respectively). The lowest values of agreement occurred with T1sm (submucosa) and T2 stage lesions. CONCLUSIONS: Interobserver agreement for staging of gastric MALT lymphoma by EUS is suboptimal before as well as after treatment of H pylori infection. This evidence suggests that gastric EUS may be more difficult technically compared with EUS of other organs. Lack of agreement is crucial because it influences the choice of therapy and assessment of response to treatment. Good interobserver agreement would permit better communication concerning the clinical status of patients, comparison of the results of different studies, and stratification of patients within clinical trials.     

Pathophysiology of proteinuria

Proteinuria is consequence of two mechanisms: the abnormal transglomerular passage of proteins due to increased permeability of glomerular capillary wall and their subsequent impaired reabsorption by the epithelial cells of the proximal tubuli. In the various glomerular diseases, the severity of disruption of the structural integrity of the glomerular capillary wall correlates with the area of the glomerular barrier being permeated by "large" pores, permitting the passage in the tubular lumen of high-molecular-weight (HMW) proteins, to which the barrier is normally impermeable. The increased load of such proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism by the tubular cells, and, in the most severe or chronic conditions, to their toxic damage, that favors the increased urinary excretion of all proteins, including low-molecular-weight (LMW) proteins, which are completely reabsorbed in physiologic conditions. Recent clinical studies showed that in patients with glomerular diseases the urinary excretion of some HMW proteins [immunoglobulins G and M (IgG and IgM)] and of some LMW proteins, alpha1-microglobulin, beta2-microglobulin, correlates with the severity of the histologic lesions, and may predict, better than the quantity of proteinuria, the natural course, the outcome, and the response to treatment. It is suggested that some patients have already, at the time of clinical presentation, a structural damage of the glomerular capillary wall (injury of podocytes) and of the tubulointerstitium, the severity and scarce reversibility of which are reliably indicated by an elevated urinary excretion of HMW and LMW proteins.     

Heme oxygenase-1 attenuates ischemia/reperfusion-induced apoptosis and improves survival in rat renal allografts

BACKGROUND: Kidneys can be preserved only for a limited time without jeopardizing graft function and survival. Induction of heat shock proteins (HSPs) can protect against ischemia/reperfusion (I/R) injury. Therefore, we investigated whether the induction of the HSP, heme oxygenase-1 (HO-1), improves outcome following isotransplantation after an extended period of cold storage. METHODS: Rats were subjected to heat preconditioning (HP; 42 degrees C for 20 minutes). Kidneys harvested after 24 hours, were preserved in cold University of Wisconsin (UW) solution at 4 degrees C for 45 hours and transplanted into bilateral nephrectomized rats. Cobalt protoporphyrin (CoPP) was administered in another group of animals in order to induce HO-1 pharmacologically, while other groups of animals received the HO-1 inhibitor, tin protophorphyrine (SnPP), following HP or CoPP. RESULTS: Cold ischemia caused a complete attenuation of graft function within 3 days following transplantation and subsequent death of all animals, whereas HP protected graft function and five of nine rats survived for 3 weeks. HP inhibited the induction of osteopontin and induced the expression of HO-1, HSP 70 and 90, and the antiapoptotic factor Bcl-XL. Grafts exposed to HP were protected against structural I/R injuries as revealed by histologic assessment using a semiquantitative score. Furthermore, induction of apoptosis was attenuated and activation of caspase-3 was inhibited. Comparable results were observed after administration of CoPP, whereas SnPP inhibited the effects of HP and CoPP. CONCLUSION: HP or administration of CoPP induced both HO-1, preserved kidney graft function, and prevented postreperfusion apoptosis after cold preservation.     

Do circulating cytokines really matter in sepsis?

Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. In this review, we will address the significance of circulating cytokines in the pathophysiology of sepsis and its relevance to new approaches in extracorporeal therapies.     

Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.