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T he stroma of the heart maintains the structure of the myocardium, determining tissue tensile strength and stiffness. 1 In addition, it contributes to ventricular function through the transmission of myocyte-generated force to the atrial and ventricular chambers and to the relengthening of myocytes in diastole. 2 The three-dimensional configuration of cardiac collagen has been determined by scanning electron microscopy 3-5 : the epimysium envelops the entire cardiac muscle; the perimysium, which is an extension of the epimysium, serves to enwrap groups of myocytes; and the endomysium, as final arborization of the perimysium, supports and connects individual cells. The endomysial weave envelops each individual myocyte and is connected to adjacent myocytes by lateral struts.Because this knowledge was obtained through studies on whole fixed myocardial tissue without removal of its nonfibrous elements, we attempted to dissolve the cellular elements and leave behind a noncollapsed matrix, aiming for a better three-dimensional view. For this, we used a modification of the NaOH maceration technique reported by Ohtani. 6 This method was reported to be able to remove cellular elements much more effectively than any other method. Small fragments, 10ϫ5ϫ3 mm in size, of the anterior wall at the midventricular region were obtained from three human hearts, weighing between 300 and 350 g, without any pathological changes. All samples were fixed in 10% neutral formalin. After being rinsed in distilled water, the specimens were immersed in a 10% NaOH solution for 4 to 6 days at room temperature and then rinsed in distilled water until they became transparent. Then they were immersed in 1% tannic acid for 4 hours. Subsequently, the specimens were rinsed in distilled water overnight, rinsed, post-fixed in 1% osmium tetroxide for 2 hours, dehydrated in graded concentrations of ethanol, sectioned transversely or longitudinally with a very sharp, clean blade under a dissecting microscope, freeze-dried, coated with gold, and observed under a Zeiss 940-A scanning electron microscope.The figure clearly shows, for the first time, the threedimensional architecture of collagen fibrils in human myo-Connective tissue skeleton of human heart sectioned transversely. Its organization is quite similar to a honeycomb. The perimysium (P) envelops groups of myocytes. The endomysium, as final arborization of the perimysium, supports and connects individual cells. The endomysial weave (W) envelops each individual myocyte and is connected to adjacent myocytes by lateral struts (s) presenting branches of variable size and extension. The range of length and diameter of these struts is very wide. Collagen struts also connect myocytes to interstitial microvessels (thin arrow) or perimysium (thick arrow). A, Barϭ20 m; magnification ϫ1415; B, barϭ10 m, magnification ϫ2830.

Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2)-integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H-(1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3'5'-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas.

Introduction In 2002, the Surviving Sepsis Campaign defi ned a strategy that aimed to reduce the high mortality due to sepsis. One point of this strategy was a recommendation to recognize that sepsis is a frequent cause of death and high economic costs in the pediatric intensive care unit. Knowledge of the disease is the fi rst step to impact it. There are few studies on pediatric sepsis epidemiology in the world and none in Colombia. Hypothesis The epidemiological features of Colombian children are diff erent from other countries. Methods We constructed a website where 14 intensive care units across the country reported in a prospective way the epidemiological features of children with sepsis using an electronic process [1]. We asked for sociodemographics, microbiological data, sepsis classifi cation, complications, and outcome. Results We collected 253 patients from March to May 2009. Fifty-fi ve percent of the cases were male and 45% were female; 53% were less than 1 year old. A total of 67.2% came from urban areas and 33% came from rural villages. Eighty-fi ve percent were very poor (score 1 and 2 over 6 used in Colombia as socioeconomic classifi cation). Forty-fi ve percent have governmentsupported insurance. In total, 23.72% of the population presented with sepsis; 30.04% with severe sepsis; and 46.5% with septic shock. The infection origin was respiratory in 54.55%, followed by abdominal in 17.39%. In 50.2% no cause was identifi ed. A total of 75.1% required mechanical ventilation. The mortality rate was 20.4%. Conclusions Sepsis, severe sepsis, or septic shock is a common diagnosis in Colombian intensive care units. The majority of pediatric patients are 2 years or younger and from the poorest communities. It aff ected males more. In the majority, the process starts in the respiratory system. We had diffi culty identifying the cause. The disease causes high mortality and cost for a developing society. We need a complete survey to fi nd a correct approach to the problem. Reference 1. Sepsis en Columbia [www.sepsisencolombia.com] P2 Randomized controlled trials are not designed to prove the safety of third-generation hydroxyethyl starch for resuscitation: results from a systematic review

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