Behandlung des akuten Hirninfarktes [Treatment of acute stroke -- an overview]

This paper provides an overview on the actual state of acute therapy in patients with ischemic stroke. The discussion focusses on intravenous and intraarterial thrombolysis, antithrombotic therapy, and the treatment of medical and neurological complications, and therapy recommendations are presented. Finally ongoing studies, particularly those concerning thrombolysis with glycoprotein IIb/IIIa receptor blockers and ultrasound-assisted thrombolysis, are presented.

Cell-derived microparticles in haemostasis and vascular medicine.

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

Nevera, mp3, mòbil... quin és el seu paper actual?

Des dels seus inicis, l’ésser humà ha tingut una sèrie de necessitats. Ha requerit d’aliment per sobreviure, d’un sostre on refugiar-se, de roba per vestirse, etc. Conforme han passat els anys, ha anat generant tècniques per a millorar la seva estància al planeta, des del descobriment del foc per escalfarse fins al desenvolupament de màquines complexes. És per això, que ha anat introduint invents a la seva vida que han cobert les necessitats sorgides al llarg del temps.El treball que desenvolupem a continuació es centra en un seguit d’aparells que han sorgit al llarg del segle XX i que han revolucionat la nostra vida. Concretament, els set aparells escollits com a objecte del nostre estudi són: la nevera, la rentadora, l’automòbil, la televisió, el reproductor d’àudio portàtil, el telèfon mòbil i l’ordinador.L’aparició d’electrodomèstics, com la nevera o la rentadora, no només ens ha permès dedicar menys esforç a les tasques domèstiques, sinó també estalviarnos temps a l’hora de realitzar-les. Aquest fet, que ara potser ni tan sols considerem, va ser del tot determinant a l’època que van sorgir, ja que va permetre alliberar mà d’obra domèstica promovent la inserció al mercat laboral d’un sector de la població com el del sexe femení.Per la seva banda, la introducció de l’automòbil també ha estat un gran avenç. Aquest, ha revolucionat la manera de desplaçar-nos, proporcionant-nos una autonomia fins aleshores impensable.Aquest mateix patró segueixen la resta d’altres aparells escollits; tots van provocar un canvi profund a la societat amb la seva aparició i, encara avui, segueixen mantenint un paper destacat al nostre dia a dia. La importància que tenen a les nostres vides ha estat la motivació que ens ha conduït a dur a terme un treball que els tingués com a protagonistes.El nostre treball consta de dues parts:A la primera, de caràcter teòric, ens hem proposat estudiar la història d’aquests aparells, és a dir, hem volgut donar resposta a una sèrie de preguntes com: quan van aparèixer, quins van ser els seus creadors i quines transformacions han anat experimentant al llarg del temps, entre d’altres.A la segona part, més pràctica, hem realitzat un treball de camp (les característiques del qual expliquem detalladament a l’apartat següent) amb l’objectiu d’analitzar la rellevància que tenen aquests aparells a la societat actual. És a dir, hem volgut saber quins aparells, dels escollits, són els més valorats per la població avui dia i quins són els que menys. Pensem que l’ús que els enquestats fan d’aquests béns serà un criteri clau a l’hora de puntuarlos, encara que no l’únic. Hem realitzat aquest anàlisi diferenciant els individus per franges d’edat i sexes. A més, també hem treballat altres qüestions comserien, entre d’altres, si el seu ús s’entén com una necessitat o va encaminat cap a l’oci; quant temps triguen els usuaris a renovar-los, quin és el motiu, etc. En relació amb aquesta segona part, hem formulat un seguit d’hipòtesis amb l’objectiu de contrastar-les posteriorment amb els resultats de les enquestes.Les hipòtesis són:- Avui dia, els individus donen més importància a aquells aparells que són més moderns, (entenent com a tals, aquells que han sorgit més recentment i estan lligats a les noves tecnologies i la innovació contínua), com poden ser l’ordinador i el telèfon mòbil, que els electrodomèstics més tradicionals com serien la nevera o la rentadora. Tot això, a més, considerant que pel que fa als primers, entenem que part del seu ús està destinat a l’oci; mentre que pels segons el seu ús està motivat per una necessitat, com seria l’alimentació en el cas de la nevera.- Pel que fa a les franges d’edat, les valoracions mostraran diferències importants en els diversos aparells. Entre la franja més jove (de 16 a 25 anys) i la de més edat (més de 60 anys), les valoracions seran més extremes, gairebé oposades.- Pel que fa als dos sexes, les valoracions que donin als aparells seran molt semblants.Hem considerat que per a dur a terme un bon anàlisi, el més adequat és presentar la informació de cada aparell per separat. És per això que cada bé constitueix un apartat independent que consta d’una primera part referent a la seva història, i una segona referent als resultats obtinguts de les enquestes.A continuació, hem procedit a ajuntar els resultats extrets dels diferents aparells i a presentant-los de forma conjunta per a comparar-los. Així, hem pogut contrastar les nostres hipòtesis inicials i hem raonat possibles causes que justificarien dels resultats obtinguts.

Teichoic acids are not required for Streptococcus pneumoniae and Staphylococcus aureus cell walls to trigger the release of tumor necrosis factor by peripheral blood monocytes.

In gram-negative bacteria, the outer membrane lipopolysaccharide is the main component triggering cytokine release from peripheral blood mononuclear cells (PBMCs). In gram-positive bacteria, purified walls also induce cytokine release, but stimulation requires 100 times more material. Gram-positive walls are complex megamolecules reassembling distinct structures. Only some of them might be inflammatory, whereas others are not. Teichoic acids (TA) are an important portion (> or =50%) of gram-positive walls. TA directly interact with C3b of complement and the cellular receptor for platelet-activating factor. However, their contribution to wall-induced cytokine-release by PBMCs has not been studied in much detail. In contrast, their membrane-bound lipoteichoic acids (LTA) counterparts were shown to trigger inflammation and synergize with peptidoglycan (PGN) for releasing nitric oxide (NO). This raised the question as to whether TA are also inflammatory. We determined the release of tumor necrosis factor (TNF) by PBMCs exposed to a variety of TA-rich and TA-free wall fragments from Streptococcus pneumoniae and Staphylococcus aureus. TA-rich walls from both organisms induced measurable TNF release at concentrations of 1 microg/ml. Removal of wall-attached TA did not alter this activity. Moreover, purified pneumococcal and staphylococcal TA did not trigger TNF release at concentrations as high as > or =100 microg/ml. In contrast, purified LTA triggered TNF release at 1 microg/ml. PGN-stem peptide oligomers lacking TA or amino-sugars were highly active and triggered TNF release at concentrations as low as 0.01 microg/ml (P. A. Majcherczyk, H. Langen, et al., J. Biol. Chem. 274:12537-12543,1999). Thus, although TA is an important part of gram-positive walls, it did not participate to the TNF-releasing activity of PGN.

P-selectin glycoprotein ligand-1 decameric repeats regulate selectin-dependent rolling under flow conditions.

P-selectin glycoprotein ligand-1 (PSGL-1) interacts with selectins to support leukocyte rolling along vascular wall. L- and P-selectin bind to N-terminal tyrosine sulfate residues and to core-2 O-glycans attached to Thr-57, whereas tyrosine sulfation is not required for E-selectin binding. PSGL-1 extracellular domain contains decameric repeats, which extend L- and P-selectin binding sites far above the plasma membrane. We hypothesized that decamers may play a role in regulating PSGL-1 interactions with selectins. Chinese hamster ovary cells expressing wild-type PSGL-1 or PSGL-1 molecules exhibiting deletion or substitution of decamers with the tandem repeats of platelet glycoprotein Ibalpha were compared in their ability to roll on selectins and to bind soluble L- or P-selectin. Deletion of decamers abrogated soluble L-selectin binding and cell rolling on L-selectin, whereas their substitution partially reversed these diminutions. P-selectin-dependent interactions with PSGL-1 were less affected by decamer deletion. Videomicroscopy analysis showed that decamers are required to stabilize L-selectin-dependent rolling. Importantly, adhesion assays performed on recombinant decamers demonstrated that they directly bind to E-selectin and promote slow rolling. Our results indicate that the role of decamers is to extend PSGL-1 N terminus far above the cell surface to support and stabilize leukocyte rolling on L- or P-selectin. In addition, they function as a cell adhesion receptor, which supports approximately 80% of E-selectin-dependent rolling.

A China em África- que Desenvolvimento Comum? o caso Cabo Verde

Depois de alcançada a ideologia de Estado e ter defenido assim a sua posição política, com as conhecidas consequências acarretadas, a nova RPC de Mao Zedong caminha, depois da sua morte, para um outro processo de mudança, a mudança económica. A administração Deng assume as responsabilidades de abertura do dragão asiático ao mundo, pela implementação de um conjunto de reformas que conduzam ao desenvolvimento económico. Em algumas cidades, consideradas como “laboratórios experimentais”, apesar das contrariedades constantes à actividade privada levada a cabo, o impacto das reformas foi tão intenso que essas passaram a ser consideradas como modelos de desenvolvimento. São exemplos os casos de Wenzhou, Sunan, e de algumas regiões do Sul da China. Todos esses casos têm em comum os factores envolvidos, que são: o Estado/PCC; as autoridades locais; as famílias; as empresas familiares e a capacidade empreendedora das mesmas. Esse desenvolvimento da China, sem precedentes, faz com que a potência procure fora do seu território recursos que dêem prosseguimento ao mesmo, nesse contexto, encontra em África um novo parceiro. A cooperação entre África e China, apesar de não recente, é a partir de então intensificada, numa relação que se pretende de igualdade e de ganhos comuns. Sempre com vários pontos que definem o objectivo desta parceria, destaca-se o desenvolvimento comum como aquele que perdura desde a era maoísta. Com esse objectivo China investe em África, oferece condições de parceria aliciantes e compromete-se em transmitir ao continente o seu modelo de desenvolvimento. Mas, tendo em conta que África, apesar de poder aprender com o desenvolvimento chinês, não pode fazer depender do discurso chinês o seu desenvolvimento, consideramos os mesmos factores destacados no caso da China, o caminho prosseguido pelo continente para um desenvolvimento sustentável, e analisámos o caso específico de Cabo Verde, onde a presença chinesa, a sua actuação empreendedora e competitividade se fazem sentir na vida diária dos cabo-verdianos, com algumas lições a transmitir para o desenvolvimento futuro do país, perspectivando este futuro a curto, médio-prazo.

Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation.

Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-alpha or PPAR-delta activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-gamma activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-gamma activation stimulates keratinocyte differentiation. Additionally, PPAR-gamma activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-gamma activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-gamma activators are mediated by PPAR-gamma, we next examined animals deficient in PPAR-gamma. Mice with a deficiency of PPAR-gamma specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-gamma-deficient epidermis. Although PPAR-gamma activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-gamma-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-gamma activators is mediated by PPAR-gamma. In contrast, PPAR-gamma activators inhibited inflammation in both PPAR-gamma-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-gamma activators does not require PPAR-gamma in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-gamma activators maybe useful in the treatment of cutaneous disorders.

Vacuum assisted venous drainage does not increase trauma to blood cells.

Although gravity drainage has been the standard technique for cardiopulmonary bypass (CPB), the development of min imally invasive techniques for cardiac surgery has renewed interest in using vacuum assisted venous drainage (VAVD) Dideco (Mirandola, Italy) has modified the D903 Avant oxygenator to apply a vacuum to its venous reservoir. The impact of VAVD on blood damage with this device is analyzed. Six calves (mean body weight, 71.3 +/- 4.1 kg) were con nected to CPB by jugular venous and carotid arterial cannu lation, with a flow rate of 4-4.51 L/min for 6 h. They were assigned to gravity drainage (standard D903 Avant oxygen ator, n = 3) or VAVD (modified D903 Avant oxygenator, n = 3). The animals were allowed to survive for 7 days. A standard battery of blood samples was taken before bypass, throughout bypass, and 24 h, 48 h, and 7 days after bypass. Analysis of variance was used for repeated measurements. Thrombocyte and white blood cell counts, corrected by hematocrit and normalized by prebypass values, were not significantly different between groups throughout all study periods. The same holds true for hemolytic parameters (lactate dehydrogenase [LDH] and plasma hemoglobin). Both peaked at 24 hr in the standard and VAVD groups: LDH, 2,845 +/- 974 IU/L vs. 2,537 +/- 476 IU/L (p = 0.65), respectively; and plasma hemoglobin, 115 +/- 31 mg/L vs. 89 +/- 455 mg/L (p = 0.45), respectively. In this experimental setup with prolonged perfusion time, VAVD does not increase trauma to blood cells in comparison with standard gravity drainage.

Predictors of red blood cell transfusion after cardiac surgery: a prospective cohort study

Abstract OBJECTIVE To identify predictors of red blood cell transfusion (RBCT) after cardiac surgery. METHOD A prospective cohort study performed with 323 adults after cardiac surgery, from April to December of 2013. A data collection instrument was constructed by the researchers containing factors associated with excessive bleeding after cardiac surgery, as found in the literature, for investigation in the immediate postoperative period. The relationship between risk factors and the outcome was assessed by univariate analysis and logistic regression. RESULTS The factors associated with RBCT in the immediate postoperative period included lower height and weight, decreased platelet count, lower hemoglobin level, higher prevalence of platelet count <150x10 3/mm3, lower volume of protamine, longer duration of anesthesia, higher prevalence of intraoperative RBCT, lower body temperature, higher heart rate and higher positive end-expiratory pressure. The independent predictor was weight <66.5Kg. CONCLUSION Factors associated with RBCT in the immediate postoperative period of cardiac surgery were found. The independent predictor was weight.

Predicting Bacteremia in Children With Cancer and Fever in Chemotherapy-induced Neutropenia: Results of the Prospective Multicenter SPOG 2003 FN Study.

STUDY AIM:: To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance. METHODS:: Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of bacteremia was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. RESULTS:: Bacteremia was reported in 67 (16%) of 423 FN episodes. In 34 episodes (8%), bacteremia became known only after reassessment after 8 to 24 hours of inpatient management. Predicting bacteremia at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The reassessment score predicting future bacteremia in 390 episodes without known bacteremia used the following 4 variables: hemoglobin ≥90 g/L at presentation (weight 3), platelet count <50 G/L (3), shaking chills (5), and other need for inpatient treatment or observation according to the treating physician (3). Applying a threshold ≥3, the score-simplified into a low-risk checklist-predicted bacteremia with 100% sensitivity, with 54 episodes (13%) classified as low-risk, and a specificity of 15%. CONCLUSIONS:: This reassessment score, simplified into a low-risk checklist of 4 routinely accessible characteristics, identifies pediatric patients with FN at risk for bacteremia. It has the potential to contribute to the reduction of use of antimicrobials in, and to shorten the length of hospital stays of pediatric patients with cancer and FN.

Long-term swimming exercise does not modulate the Akt-dependent endothelial nitric oxide synthase phosphorylation in healthy mice.

Molecular mechanisms by which exercise exerts cardiovascular benefits are poorly understood. Exercise-induced increase of endothelial NO synthase (eNOS) phosphorylation through the protein kinase Akt has been shown to be a key mechanism underlying the beneficial effect of exercise in coronary artery disease patients. We examined whether this protective pathway might also be activated in long-term-exercised healthy mice. C57BL/6 wild-type mice swam for 24 weeks. A group of sedentary animals were used as controls. Aortic levels of total protein kinase Akt (protein kinase B), phosphorylated Akt at ser473 (p-Akt), total eNOS, phosphorylated eNOS at Ser1177 (p-eNOS), and PECAM-1 (platelet endothelial cell adhesion molecule-1) were assessed by Western blotting. Protein expressions of Akt, p-Akt, eNOS, p-eNOS, and PECAM-1 were not modulated by 24 weeks of exercise. The Akt-dependent eNOS phosphorylation did not seem to be a primary molecular adaptation in response to long-term exercise in healthy mice.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.