Antiadhesive and antibacterial multilayer films via layer-by-layer assembly of TMC/heparin complexes.

N-Trimethyl chitosan (TMC), an antibacterial agent, and heparin (HP), an antiadhesive biopolymer, were alternately deposited on modified polystyrene films, as substrates, to built antiadhesive and antibacterial multilayer films. The properties of the multilayer films were investigated by Fourier transform infrared spectroscopy, atomic force microscopy, scanning electron microscopy, and Kelvin force microscopy. In vitro studies of controlled release of HP were evaluated in simulated intestinal fluid and simulated gastric fluid. The initial adhesion test of E. coli on multilayer films surface showed effective antiadhesive properties. The in vitro antibacterial test indicated that the multilayer films of TMC/HP based on TMC80 can kill the E. coli bacteria. Therefore, antiadhesive and antibacterial multilayer films may have good potential for coatings and surface modification of biomedical applications.

Bivalirudin in contemporary percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes: what is the current role of platelet glycoprotein IIb/IIIa receptor inhibitor agents?

Currently, the wide variety of antithrombotic agents as adjunctive pharmacological therapy for non-ST-segment elevation acute coronary syndromes (ACS) in the setting of contemporary percutaneous coronary intervention (PCI) available for clinical use has made choosing the optimal drug therapy a complex and difficult task. In the stent era, bivalirudin, a semisynthetic direct thrombin inhibitor, has recently been shown to provide similar efficacy with less bleeding compared with unfractionated heparin plus platelet glycoprotein IIb/IIIa inhibitors in ACS patients treated with PCI. Although there are some controversial results and limitations in the studies with bivalirudin, this drug certainly is a plausible option in the treatment of ACS. With current findings in contemporary PCI, there may be a steady increase in the utilization of bivalirudin. On the other hand, in the real world, there may be reinforcement in the sole use of unfractionated heparin confining glycoprotein IIb/IIIa inhibitors and other intravenous antithrombotics to bailout therapy for periprocedural PCI complications in ACS patients.

Dynamics of heparin-binding proteins on boar sperm.

The presence, topology and dynamics of heparin-binding proteins (HBP) on boar sperm were evaluated. HBP distribution was analyzed by subcellular parting, using biotinylated heparin followed by colorimetric detection. HBP were detected as peripherical and integral periacrosomal membrane proteins. Indirect fluorescence microscopy of sperm incubated with biotinylated heparin was used to evidence heparin binding on sperm at different physiological stages. Two different fluorescent patterns (A and B) were found, which probably correspond to non-capacitated and capacitated sperm as assessed by the ability to undergo acrosome reaction with calcium ionophore A23187 and by the increase of p32 phosphorylated protein. In A pattern, corresponding to untreated sperm, fluorescence located mostly on the post-acrosomal region; in B pattern, corresponding to incubated sperm, on the acrosomal region. Upon incubation under capacitating conditions (TALP), sperm having the B pattern was augmented compared with non-incubated sperm (p<0.001). Differences in the HBP patterns (p<0.0001) were observed in sperm incubated under non-capacitating conditions in relation to sperm incubated in TALP, indicating that the modification of HBP patterns is probably related to capacitation. No difference was observed when untreated sperm were permeabilized prior to staining, suggesting that HBP are present on the sperm surface. The effect of heparin on capacitation dependent protein tyrosine phosphorylation was also analyzed, finding a decrease in p32 phosphorylation in the presence of heparin. This suggests that the capacitation enhancement mediated by this glycosaminoglycan involves an alternative intracellular pathway. The finding that heparin binds to sperm differently according to its physiological state, is a new evidence of the remodelling of sperm membrane surface upon capacitation and may provide a useful and relatively simple method to evaluate in vitro modification of boar sperm physiological state.

Terapêutica antitrombótica nas doenças cardiovasculares: estado atual; Parte I / Antithrombotic therapy in cardiovascular diseases: an up-to-date; Part I

Os autores mostram a importância e aplicaçäo clínica no momento atual dos antiplaquetários, anticoagulantes orais, heparina venosa e subcutânea, heparina de baixo peso molecular e os trombolíticos. Chamam a atençäo quanto à interaçäo necessária entre cardiologistas, hematologistas, angiologistas e cirurgiöes no tratamento antitrobótico.

Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.

OBJECTIVE: To compare low-molecular-weight preparations of heparin (LMWH) with standard heparin in children requiring anticoagulant treatment for thromboembolic disease. METHODS: We treated 25 children who required heparin, but were at significant risk of bleeding, with LMWH (enoxaparin, Rhone-Poulenc Rorer). The median age was 4 years (range, newborn to 17 years), with nine infants less than 2 months of age. Fourteen children had a deep vein thrombosis or pulmonary embolism, nine had thrombotic complications in the central nervous system, and two had complex congenital heart disease, for which they received prophylaxis at a lower dosage (0.5 mg/kg given subcutaneously twice a day). The remaining 23 children received an initial dose of 1 mg/kg, every 12 hours subcutaneously, with subsequent doses adjusted to achieve a 4-hour anti-factor Xa level between 0.5 and 1.0 unit/ml. RESULTS: Newborn infants had increased dose requirements; an average of 1.60 units/kg was required to achieve therapeutic heparin levels. For the remaining children, the initial dose of 1.0 mg/kg was sufficient. After the initial dose adjustment, LMWH was administered with twice-weekly monitoring. The median duration of therapy with LMWH was 14 days. Two children with previously documented gastrointestinal ulcers bled and required transfusion therapy. Therapy with LMWH was continued without further events. There were no new thrombotic events during the treatment with LMWH. The cost of administering LMWH compared with heparin was reduced by 30% because of decreased laboratory monitoring, blood sampling times, intravenous starts, and nursing time. Needle punctures were reduced with LMWH therapy by the placement of a subcutaneous catheter. CONCLUSION: These results provide the basis for a randomized, controlled trial comparing LMWH with standard heparin in pediatric patients.

Análise transcutânea de sangue utilizando espectroscopia Raman / Blood transcutaneous analysis using Raman spectroscopy

Neste trabalho é apresentada a proposta para a determinação de componentes do sangue humano in vivo, através da utilização da espectroscopia Raman. A obtenção das quantidades de glucose e de gases dissolvidos no sangue por via transcutânea, remotamente e em tempo real, utilizando fibras ópticas, demonstra-se de grande utilidade para a rápida tomada de decisão em um ambiente hospitalar. A utilização de um dispositivo especialmente projetado para aumentar a coleta de luz pelo sistema de fibras ópticas amplia as perspectivas de utilização da técnica.

ln this work we present the proposal for obtaining human blood components in vivo, using Raman spectroscopy. The determination of glucose and disolved gases quantities in the whole blood transcutaneously, remotely and in real time by meaning of fiber optics, shows be very important for rapid decision in an hospital environment. The use of a

Anticoagulación en hemodiálisis con dósis única de heparina de bajo peso molecular / Anticoagulation during hemodialysis with a single dose of low molecular weight heparin

The aim of this work was to compare the benefits and problems of low molecular weight heparin use in chronic hemodialysis, compared to conventional heparin. We studied 35 patients that received low molecular weight heparine (Enoxaparine, molecular weight 4000) during 115 consecutive hemodialysis procedures and conventional heparin during the subsequent 35 procedures. We assessed the heparin dose, partial thromboplastin time before dialysis and at 3 and 120 min during the procedure, arterio-venous fistula compression time, clot formation in the circuit and residual volume of filters. Median total dose of conventional heparin was 6289 U (range 3000-10000) compared to 5555 U (range 2000-8000) of low molecular weight heparin. When the dose was calculated per kg of body weight, it was lower for low molecular weight heparin than for conventional heparin (87.8 U (range 33-100) vs 100 U (range 50-176). Partial thromboplastin time achieved was lower with low molecular weight heparin, compared with conventional heparin, at 3 (64.26 vs 125.2 sec) and 120 min (39.1 vs 84.45 sec). Clot formation, arteriovenous fistula compression time and residual volume of filters were similar for both types of heparin. It is concluded that a single dose of low molecular weight heparin simplifies anticoagulation during hemodialysis, modifies less the partial thromboplastin time and does not alter filter re-utilization

Farmacocinética de la heparina no fraccionada y modificaciones de su farmacodinamia en el curso de la hemodiálisis y en el período interdialítico / Pharmacokinetic of the non-fractional heparin and modifications of our pharmacodynamia in the course of the hemodialysis and the interdialysis period

Los estudios farmacocinéticos de la heparina no fraccionada en insuficiencia renal crónica han dado resultados variables, no habiendo uniformidad en las dosis utilizadas ni comparación con grupos de controles. La cinética de heparina en el transcurso de hemodiálisis es poco conocida, dado el empleo de esquemas de heparinización que consisten en pulsos iniciales seguidos por infusiones con bomba. Asimismo, tampoco se conocen las variaciones de la actividad heparínica en los diferentes tiempos de diálisis luego de una dosis única inicial. En este trabajo demostramos, con diferentes técnicas (TCK, TPTWB, heparinemias con PTTK en diluciones de plasma y actividad anti-Xa) que la vida media de la heparina no fraccionada a dosis bajas no es modificada por la función renal, siendo la eliminación exponencial de primer orden. A dosis altas la vida media está prolongada en pacientes con insuficiencia renal crónica respecto al grupo de control, presentando una cinética compleja, con diferentes pendientes de eliminación. El estudio de cinética en hemodiálisis con dosis única inicial mostró que la vida media esta prolongada 3 veces por sobre los niveles basales y que dicha prolongación estaría vinculada a la persistencia de heparinemias altas por contracción de volumen en la primera hora, provocando mayor influencia en los mecanismos de depuración que la dosis misma. La actividad de la heparina inyectada sufre considerables variaciones en el curso de la hemodiálisis, con un marcado efecto neutralizante del plasma urémico sobre la actividad anti-Xa en el comienzo (relación de actividad Anti-Xa/PTTK disminuida) y aumento progresivo de la actividad anti-Xa al final de la misma. De la comparación de pruebas ex vivo e in vitro de la actividad de heparina no fraccionada y del efecto in vitro de fragmentos de clivaje con heparinasa sobre plasma urémico surge que el efecto neutralizante del plasma urémico sobre la actividad anti-Xa es dependiente del peso molecular y que el aumento progresivo de la actividad anti-Xa hacia el final de la hemodiálisis probablemente se deba a la persistencia de los fragmentos de menor peso molecular de la heparina inyectada o a la liberación de glicosaminoglicanos endógenos por la propia heparina (AU)

Farmacocinética de la heparina no fraccionada y modificaciones de su farmacodinamia en el curso de la hemodiálisis y en el período interdialítico / Pharmacokinetic of the non-fractional heparin and modifications of our pharmacodynamia in the course of the hemodialysis and the interdialysis period

Los estudios farmacocinéticos de la heparina no fraccionada en insuficiencia renal crónica han dado resultados variables, no habiendo uniformidad en las dosis utilizadas ni comparación con grupos de controles. La cinética de heparina en el transcurso de hemodiálisis es poco conocida, dado el empleo de esquemas de heparinización que consisten en pulsos iniciales seguidos por infusiones con bomba. Asimismo, tampoco se conocen las variaciones de la actividad heparínica en los diferentes tiempos de diálisis luego de una dosis única inicial. En este trabajo demostramos, con diferentes técnicas (TCK, TPTWB, heparinemias con PTTK en diluciones de plasma y actividad anti-Xa) que la vida media de la heparina no fraccionada a dosis bajas no es modificada por la función renal, siendo la eliminación exponencial de primer orden. A dosis altas la vida media está prolongada en pacientes con insuficiencia renal crónica respecto al grupo de control, presentando una cinética compleja, con diferentes pendientes de eliminación. El estudio de cinética en hemodiálisis con dosis única inicial mostró que la vida media esta prolongada 3 veces por sobre los niveles basales y que dicha prolongación estaría vinculada a la persistencia de heparinemias altas por contracción de volumen en la primera hora, provocando mayor influencia en los mecanismos de depuración que la dosis misma. La actividad de la heparina inyectada sufre considerables variaciones en el curso de la hemodiálisis, con un marcado efecto neutralizante del plasma urémico sobre la actividad anti-Xa en el comienzo (relación de actividad Anti-Xa/PTTK disminuida) y aumento progresivo de la actividad anti-Xa al final de la misma. De la comparación de pruebas ex vivo e in vitro de la actividad de heparina no fraccionada y del efecto in vitro de fragmentos de clivaje con heparinasa sobre plasma urémico surge que el efecto neutralizante del plasma urémico sobre la actividad anti-Xa es dependiente del peso molecular y que el aumento progresivo de la actividad anti-Xa hacia el final de la hemodiálisis probablemente se deba a la persistencia de los fragmentos de menor peso molecular de la heparina inyectada o a la liberación de glicosaminoglicanos endógenos por la propia heparina (AU)

Farmacocinética de la heparina no fraccionada y modificaciones de su farmacodinamia en el curso de la hemodiálisis y en el período interdialítico / Pharmacokinetic of the non-fractional heparin and modifications of our pharmacodynamia in the course of the hemodialysis and the interdialysis period

Los estudios farmacocinéticos de la heparina no fraccionada en insuficiencia renal crónica han dado resultados variables, no habiendo uniformidad en las dosis utilizadas ni comparación con grupos de controles. La cinética de heparina en el transcurso de hemodiálisis es poco conocida, dado el empleo de esquemas de heparinización que consisten en pulsos iniciales seguidos por infusiones con bomba. Asimismo, tampoco se conocen las variaciones de la actividad heparínica en los diferentes tiempos de diálisis luego de una dosis única inicial. En este trabajo demostramos, con diferentes técnicas (TCK, TPTWB, heparinemias con PTTK en diluciones de plasma y actividad anti-Xa) que la vida media de la heparina no fraccionada a dosis bajas no es modificada por la función renal, siendo la eliminación exponencial de primer orden. A dosis altas la vida media está prolongada en pacientes con insuficiencia renal crónica respecto al grupo de control, presentando una cinética compleja, con diferentes pendientes de eliminación. El estudio de cinética en hemodiálisis con dosis única inicial mostró que la vida media esta prolongada 3 veces por sobre los niveles basales y que dicha prolongación estaría vinculada a la persistencia de heparinemias altas por contracción de volumen en la primera hora, provocando mayor influencia en los mecanismos de depuración que la dosis misma. La actividad de la heparina inyectada sufre considerables variaciones en el curso de la hemodiálisis, con un marcado efecto neutralizante del plasma urémico sobre la actividad anti-Xa en el comienzo (relación de actividad Anti-Xa/PTTK disminuida) y aumento progresivo de la actividad anti-Xa al final de la misma. De la comparación de pruebas ex vivo e in vitro de la actividad de heparina no fraccionada y del efecto in vitro de fragmentos de clivaje con heparinasa sobre plasma urémico surge que el efecto neutralizante del plasma urémico sobre la actividad anti-Xa es dependiente del peso molecular y que el aumento progresivo de la actividad anti-Xa hacia el final de la hemodiálisis probablemente se deba a la persistencia de los fragmentos de menor peso molecular de la heparina inyectada o a la liberación de glicosaminoglicanos endógenos por la propia heparina