Catálogo de publicaciones - libros

Desialylation of the RBC membrane by neuraminidase may alter RBC shape, RBC capacity for deformability, and RBC biochemistry. Some of these alterations are observed early in clinical situations. These RBC modifications are reproduced within a few hours. Moreover, desialylation could facilitate uptake by the reticuloendothelial system, as observed in the senescent process. Further studies including the measurement of neuraminidase activity are needed to understand the process of RBC sialic acid decrease in critically ill patients. As a potential consequence, blockade of neuraminidase activity could represent an interesting therapeutic option to limit anemia and improve RBC rheology in critically ill patients.

In conclusion, sepsis is still an important clinical challenge for ICUs with few therapeutic options. This chapter has summarized the current knowledge on RAGE, an inflammation perpetuating receptor, which plays a pivotal role in sepsis. RAGE is involved in signal transduction from pathogen substrates to cell activation during the onset of inflammation and perpetuates the immune response. Targeting this receptor might attenuate hyperinflammation. Essentially, understanding of the basic signal transduction of these receptors may offer new diagnostic and therapeutic options in septic patients.

Taken together, proteins of the antioxidant defense system can be damaged by oxidative stress, and, in fact, there is evidence that they are even specifically susceptible. The oxidative loss of protein moiety is partially compensated by synthesis. This compensatory mechanism complicates any attempt to relate mRNA profiles assessed by cDNA technology or protein expression profiles assessed by 2D-gel electrophoresis to the functionally active protein content. The dynamic cellular response with sepsis can only be revealed by disentangling the enormously complex response at the protein level. The only method able to deliver appropriate information is a proteomic platform based on differential and quantitative approaches, which is extended by synthesis or turnover measurements.

Our ultimate aim is to use this dynamic approach:

In Section 6.1 we sum up with brief indications of the proofs some facts on the open sets in where a differential equation () = with constant coefficients can always be solved. Depending on whether is allowed to be an arbitrary distribution or a function (or a distribution of finite order), we get two classes of admissible open sets depending on . Those which are admissible for every are precisely the genuinely convex sets. However, more general domains are admissible for individual operators . In Section 6.2 we prove by methods close to those used in Section 4.2 that in a pseudo-convex open set in C all equations of the form can be solved. In fact, we prove more general results for operators in a product space × which have this structure with respect to the complex variables. In Section 6.3 we pass to the existence of analytic solutions of equations of the form (,..., ) = in a pseudo-convex open set ⊂ where is analytic. We show that it is precisely in the C convex sets that a solution exists for arbitrary and .

The heat shock, or stress response is an ancient, highly conserved, primitive endogenous cellular defense mechanism. Traditionally, stress proteins, e.g. HSP70, have been considered to be exclusively intracellular proteins. However, increasing evidence supports a role for extracellular stress proteins, including HSP70, in the innate and acquired immune response. For example, stress proteins have been reported to stimulate the immune system via innate receptors, such as the TLR. Recent data, however, challenge this notion by claiming that it is the bacterial molecules that are trapped by the stress proteins, and not the stress proteins themselves that activate the immune system. In this brief review, we have presented evidence to suggest that stress proteins are indeed modulators of immune function. Whether activation of the immune response by extracellular stress proteins such as HSP70 serves a cytoprotective function, a pro-inflammatory function, or both, depending on context, remains to be determined.

The presence of correlations between the rates of protein synthesis and relevant clinical parameters suggests that determination of the ongoing metabolic activity in immune competent cells reflects changes in the functional activity of the immune system, being of importance for the severity and time course of the critical illness. Our results encourage future studies, in order to characterize the alterations in the metabolic activity in immune competent cells in later phases of the ICU stay, characterized by a general anti-inflammatory activity and decreased resistance to opportunistic infections.

Fluid resuscitation induces immunomodulation in the critically ill. Current evidence is robust enough to suggest that interventions that induce/prolong inflammatory responses are associated with adverse outcomes in critically ill patients. Therefore, an ‘ideal’ resuscitation fluid in addition to being an effective volume expander should minimize iatrogenic metabolic acidosis and pro-inflammatory mediator expression. While normal saline and perhaps even lactated Ringer’s solution appear to be associated with pro-inflammatory effects, fluids such as hypertonic saline may be associated with anti-inflammatory effects. Solutions such as Hextend may be less likely to be immunomodulating. Further large human studies are required to characterize these effects and their impact on outcomes in the critical care setting.

Muscle weakness following critical illness is a significant clinical problem. It is likely to contribute to the continuing morbidity and mortality of prolonged ICU stay. However, its pathophysiology remains poorly understood. Several major issues remain unresolved. These include the question of whether critical illness myopathy is a distinct illness or represents a continuum of skeletal MOF.

Also unresolved is the differentiation of a postulated specific, sepsis-related muscle failure from other causes of muscle dysfunction in the critically ill. In particular, differences between diffuse atrophy, the normal ageing process, and sepsis-induced injury need to be explored. Finally, the question of possible mitochondrial DNA damage in human sepsis should be addressed. Normal human ageing is characterized by gradual damage to mitochondrial DNA. Could the long-term adverse consequences of prolonged critical care be partially a result of an increase in this process — a sort of ‘ageing in the fast lane’?

Measurement of plasma lactate remains a primordial component for a sound diagnostic and therapeutic line of conduct in critical care. The concept of lactate as merely a metabolic waste product (bad lactate) has now evolved towards lactate being viewed as an energy shuttle (good lactate). In most clinical critical care situations, hyperlactatemia must be perceived as an adaptive response to an aggressive state and not as a marker of tissue hypoxia. Nevertheless, irrespective of its mechanism of formation, hyperlactatemia remains an excellent prognostic marker.

ANP and BNP are secreted from cardiac myocytes in response to atrial or ventricular wall stretch. The physiologic effects of both cardiac natriuretic peptides include natriuresis, diuresis, and inhibition of the activities of several neuroendocrine systems, including the renin-angiotensin-aldosterone system, endothelins, cytokines, and the sympathetic nervous system. Single and serial plasma measurement of BNP is a promising tool for diagnosis and risk stratification of patients with heart failure and acute coronary syndromes. Levels of BNP could also be used to guide drug therapy in these patients. Finally, the administration of nesiritide, a synthetic recombinant human BNP, appears to offer a novel approach in the management of acute heart failure.