Mesenchymal Stromal Cells Modulate PAF-stimulated Equine Alveolar Macrophages

Abstract Platelet-activating factor (PAF) is a potent proinflammatory mediator that is produced in increased amounts in the lungs of asthmatic humans and horses. The present pilot study, shows that mesenchymal stromal cells can modulate alveolar macrophage function in asthma, interfering in the activity of PAF, being another potential pathway for mesenchymal stromal cells benefits in asthma.

Aplicación del lisado de plaquetas en la fistula pilonidal / Application of platelet lysate in intergluteal pilonidal disease

La enfermedad pilonidal o fístula pilonidal es una afección que se presenta a lo largo del pliegue entre los glúteos, desde el hueso sacro hasta el ano. Esta afección involucra los folículos pilosos de la región presacra, los cuales penetran en el tejido celular subcutáneo y forman un quiste alrededor. Se presenta como una o varias fositas o depresiones de diámetro pequeño, puntiforme por la que emergen pelos. Como parte del tratamiento médico se describen medidas locales, la antibióticoterapia de amplio espectro y tratamiento quirúrgico, en el cual se describen técnicas de resección abiertas y cerradas. Se presenta el caso de una adolescente femenina de 16 años de edad, diagnosticada hace año y medio con una fístula pilonidal que requirió tratamiento con vitaminoterapia, medidas locales e intervención quirúrgica en tres ocasiones. En la última de ellas se produjo dehiscencia del sitio quirúrgico, escaso tejido de granulación y pobre cicatrización. Por tal motivo se decidió la aplicación de lisado de plaquetas en toda el área de la fístula a razón de 1 mL en días alternos, durante dos semanas, se continuó una aplicación semanal durante las 4 semanas siguientes hasta que se obtuvo el cierre total. La utilización del lisado de plaquetas favorece el tejido de granulación y la cicatrización en la fistula pilonidal(AU)

Intergluteal pilonidal disease or pilonidal fistula is a condition presenting along the cleft between the buttocks, which runs from the bone at the bottom of the spine (sacrum) to the anus. This condition involves the hair follicles of the presacral region, which penetrates into the subcutaneous tissue and forms a cyst around. It is presented as one or more pits or depressions of small diameter emerging punctuate by hairs. As part of medical treatment local measures, broad-spectrum antibiotic therapy and surgical treatment, which may be open and closed resection techniques, are described. We present a case of a 16- year- old female teenager, diagnosed a year and half ago, with a pilonidal fistula that required surgical treatment in 3 occasions, with local measures and vitamin therapy; dehiscence of the surgical site, poor tissue granulation and poor healing. It was applied platelet lysate throughout the area of the fistula at 1 mL alternate days, for two weeks, infiltration was continued for 4 weeks obtaining the total closure of the same. Therefore the use of platelet lysate promotes granulation tissue and scarring in pilonidal fistula(AU)

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Association between platelet-activating factor acetylhydrolase gene polymorphisms and gastrointestinal bleeding in children with Henoch-Schönlein purpura / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP).</p><p><b>METHODS</b>A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe. The plasma PAF-AH activity was measured, as well as the levels of platelet-activating factor (PAF), granular membrane protein-140 (GMP-140), β-thromboglobulin (β-TG), and platelet factor 4 (PF4).</p><p><b>RESULTS</b>The Val279Phe genotype and allele frequencies were in Hardy-Weinberg equilibrium, and the homozygous genotype TT and heterozygotes accounted for 0.97% and 6.05% respectively. The gastrointestinal bleeding group had a significantly higher allele frequency than the control group (5.22% vs 3.33%; P<0.01). The HSP patients with GG genotype in the gastrointestinal bleeding group had significantly higher levels of plasma PAF and GMP-140 than those in the non-gastrointestinal bleeding group (P<0.05), while the non-gastrointestinal bleeding group had a significantly higher PAF-AH activity than the gastrointestinal bleeding group (P<0.05). There were no significant differences in β-TG and PF4 between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>Val279Phe gene polymorphisms in PAF-AH are associated with PAF-AH activity and PAF and GMP-140 levels and may be a risk factor for HSP with gastrointestinal bleeding.</p>

Damage of vascular endothelial barrier induced by explosive blast and its clinical significance / 中华创伤杂志(英文版)

In recent years, injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities. Tear, bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage. Vascular endothelial barrier is the main defense of tissues and organs' integrity. This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier, bloodeair barrier, and intestinal vascular barrier impairments. In addition, the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast.

Effects of Tongxinluo Capsule on Platelet Activating Factor, Vascular Endothelial Function, Blood Flow of Thrombolysis in Myocardial Infarction in Acute Myocardial Infarction Patients after Delayed Percutaneous Coronary Intervention / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore effects of Tongxinluo Capsule (TC) on platelet activating factor (PAF), vascular endothelial function, thrombolysis in myocardial infarction (TIMI) blood flow, and heart function in acute myocardial infarction (AMI) patients after delayed percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Totally 80 AMI inpatients were recruited at Department of Cardiology, People's Hospital of Jiangxi Province, from Jan. 2008 to Sep.2013. Those in line with inclusion criteria were randomly assigned to TC treatment group and the conventional treatment group by random digit table, 40 in each group. Besides, another 40 healthy subjects from examinees at Outpatient Department were recruited as a healthy control group. PCI was performed after 1-week treatment. Then blood samples were collected, and then blood contents of CD62P, CD63, GP II b/III a, ET-1, NO, and plasma von Willebrand factor (vWF) levels were detected. Coronary TIMI blood flow and corrected TIMI frame count (CTFC) were determined during PCI. Meanwhile, noninvasive blood pressure (BP) and heart rate (HR) were recorded before and after PCI, and cardiac function measured. They were compared with the healty control group.</p><p><b>RESULTS</b>Compared with the healthy control group, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, and ET-1 significantly increased, but NO significantly decreased in AMI patients (all P < 0.05). After 1-week intervention of TC, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, NO, and ET-1 significantly decreased (P < 0.05, P < 0.01). Compared with the conventional treatment group at the same time point, blood contents of CD62p, CD63, GP II b/IIIa receptor compound, vWF, and ET-1 decreased more significantly in the TC group (P < 0.05, P < 0.01), increased NO levels were also more obviously seen (P < 0.01). The aforesaid parameters changed more obviously at day 30, as compared with those changes at week 1 (P < 0.05, P < 0.01). The TIMI blood flow grade and CTFC were more obviously improved after PCI in the two treatment groups. Better TIMI blood flow was seen in the TC group. TIMI level 3 blood flow rate was higher in the TC group than in the conventional treatment group with statistical difference (P < 0.05). The left ventricular ejective factor (LVEF) after PCI was obviously elevated in the TC group and the conventional treatment group (P < 0.01), and the improvement was more obviously seen in the TC group (P < 0.05). There were 6 cases of recurrent angina, 3 cases of ventricular tachycardial (VT)/ventricular fibrillation (VF), 6 cases of heart failure (HF), 1 case of cardiac sudden death in the conventional treatment group, with the total incidence of cardiovascular events being 40% (16/40). There were 2 cases of recurrent angina, 2 cases of VT/VF, 2 cases of HF, no cardiac sudden death in the TC treatment group, with the total incidence of cardiovascular events being 15% (6/40). There was statistical difference in the recurrent rate of cardiovascular events between the two groups (χ² = 2.27, P < 0.05).</p><p><b>CONCLUSION</b>TC not only could prevent coronary embolism of AMI patients after delayed PCI, attenuate vascular endothelial injury, but also could improve TIMI blood flow, and strengthen cardiac systolic function.</p>

Lipoprotein associated phospholipase A2 activity & its correlation with oxidized LDL & glycaemic status in early stages of type-2 diabetes mellitus.

Background & objectives: Lipoprotein associated phospholipase A2 (Lp-PLA2) is an important risk predictor of coronary artery disease (CAD). This study was aimed to evaluate Lp-PLA2 activity and oxidized low density lipoprotein (oxLDL) in newly diagnosed patients of type 2 diabetes mellitus and to determine the correlation of Lp-PLA2 activity with oxLDL and plasma glucose levels. Methods: Blood samples were collected in patients with newly diagnosed type 2 diabetes (n=40) before any treatment was started and healthy controls (n=40). These were processed for estimating plasma glucose: fasting and post prandial, ox LDL, and Lp-PLA2 activity. The parameters in the two groups were compared. Correlation between different parameters was calculated by Pearson correlation analysis in both groups. Results: Lp-PLA2 activity (24.48 ± 4.91 vs 18.63 ± 5.29 nmol/min/ml, P<0.001) and oxLDL levels (52.46 ± 40.19 vs 33.26 ± 12.54 μmol/l, P<0.01) were significantly higher in patients as compared to those in controls. Lp-PLA2 activity correlated positively with oxLDL in both controls (r=0.414, P<0.01), as well in patients (r=0.542, P<0.01). A positive correlation between Lp-PLA2 activity and fasting plasma glucose levels was observed only in patients (r=0.348, P<0.05). Interpretation & conclusions: Result of this study implies that higher risk of CAD in patients with diabetes may be due to increase in Lp-PLA2 activity during the early course of the disease. A positive correlation between enzyme activity and fasting plasma glucose indicates an association between hyperglycaemia and increased activity of Lp-PLA2. This may explain a higher occurrence of CAD in patients with diabetes. A positive correlation between oxLDL and Lp-PLA2 activity suggests that Lp-PLA2 activity may be affected by oxLDL also.

Las bases científicas de la homeopatía / The scientific basis of homeopathy

A través de un recorrido por los principios de la Homeopatía y la evolución de sus ideas es posible delimitar las líneas de investigación que podrían desarrollarse para responder las dudas e interrogantes que surgen de la aplicación de esta disciplina,situada entre las ciencias médicas, humanas, biológicas y físicas.A continuación se presenta el resumen de diversas investigaciones que han comprobado, por ejemplo, que los medicamentos homeopáticos sí actúan en células, modelos animales y seres humanos, aunque no se ha logrado explicarcómo; además, se pone de manifiesto que los criterios para evaluar no pueden ser idénticos a los que se emplean en la farmacología clásica, si bien existe cierta similitud.Se concluye que a pesar de que hay demasiados aspectos de la Homeopatía que siguen sin tener una explicación coherente en términos científicos clásicos, no deben rechazarse sin miramientos, sino estudiarse.

Through a tour of the principles of homeopathy and the evolution of his ideas is possible to delineate the lines of research that could be developed to answer the doubts and questions that arise from the application of this discipline, between the medical and social sciences, biological and physical.The summary of several studies that have found, for example is presented, that homeopathic medicines do act on cells, animal models and humans, but has not been able to explainhow; moreover, shows that the criteria for evaluating may not be identical to those used in classical pharmacology, while there is some similarity.We conclude that although there are too many aspects of homeopathy that still lack a coherent explanation in classical scientific terms, should not be rejected without consideration, but studied.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

[Effect of short-term supplementation of cocoa on platelet factors [Plt, MPV, PDW] of athlete male's blood after an exhaustive aerobic exercise]

Cardiovascular diseases [CVD] are among the most important causes of death and disability all around the world. Blood cells, especially platelets, may play a crucial role in pathophysiology of these disorders. Considering the increased risk of thrombosis after acute physical activities, and the role of the platelets in these disorders, many nutritional approaches had been evaluated for the prevention of thrombosis. Recently, the effects of cocoa consumption on hemostasis have recently attracted the attention of many researchers. In this study we evaluated the effects of cocoa consumption on platelet count, mean platelet volume [MPV], and platelet distribution width [PDW], during one session of incremental exhausting aerobic exercise in male soccer players. This semi-experimental study included 20 healthy volunteer male soccer players [age: 22 +/- 1years; BF%: 22.5 +/- 1.2; VO2max:52.6 +/- 1.5 ml.kg-1.min]. After written consent, all subjects performed Bruce Test within two successive weeks. After the first blood sampling [stage one], 0.5 mg/kg of placebo [0.5 g cocoa powder in 300 ml of 4% sucrose solution] or cocoa solution [18.75 g cocoa powder in 300 ml 4% sucrose solution] was randomly given to the subjects. All cases performed Bruce Test two hours later. Blood samples were collected just before Bruce Test [second stage], immediately after Bruce Test [third stage] and 1 hour after Bruce Test [fourth stage]. After preparation of peripheral blood smears, platelet count, MPV and PDW were measured by Mindray cell counter. Using spss 16, data were analyzed by means of two-factor analysis of variance [ANOVA] and Bonfferoni test at the level 0.01. Our results indicated a significant decrease in platelet count, MPV, and PDW after cocoa consumption [P<0.01]. In addition, there was a significant difference between the 2 groups in these values after Bruse Test [P<0.01]. However, in spite of significant increase in platelet count, MPV, and PDW after Bruse Test, cocoa consumption 2 hours before the test decreased these values significantly [P<0.01]. Cocoa consumption before exhaustive physical exercises may prevent exercise induced increase in the platelet indices; hence, potentially can prevent cardiovascular and thrombotic events and sudden death in the athletes

Elevated platelet activating factor level in ischemia-related arrhythmia and its electrophysiological effect on myocardium / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism.</p><p><b>METHODS</b>(1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillary muscles.</p><p><b>RESULTS</b>In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD90)under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions.</p><p><b>CONCLUSION</b>AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.</p>

Changes of prostaglandin D2,carboxypeptidase A3 and platelet activating factor in guinea pig in anaphylactic shock / 法医学杂志

OBJECTIVE@#To detect the changes of leukotriene E4(LTE4), prostaglandin D2(PGD2), carboxypeptidase A3(CPA3) and platelet activating factor (PAF) in guinea pigs died from anaphylactic shock.@*METHODS@#Guinea pigs were used for establishing anaphylactic shock models. The levels of LTE4, PGD2 and CPA3, and PAF were detected in urine, plasma, and brain tissues with ELISA kit, respectively. The significant biomarkers were selected comparing with control group. The changes of PGD2, CPA3 and PAF in the guinea pigs at time zero, 12 and 24 hours after death were observed and compared respectively. The effect of platelet activating factor acetylhydrolase (PAF-AH) to PAF in guinea pig brain was examined and compared.@*RESULTS@#There were no statistically differences of LTE4 levels in urine observed between experimental group and control group. The levels of CPA3, PGD2 and PAF in the experimental group were significantly higher than that in the control group at 0 h. The levels of PAF at 12 and 24 hours after anaphylactic shock were significantly higher than that in the control group. The levels of PAF decreased significantly after pretreatment with PAF-AH.@*CONCLUSION@#LTE4 in urine cannot be selected as a biomarker to determine the anaphylactic shock. PGD2 and CPA3 in plasma, and PAF in brain tissue may be used as biomarkers to determine the anaphylactic shock. PAF-AH may be potentially useful for clinical treatment of anaphylactic shock.

Effects of glycomacropeptide on damage to intestinal tissue and apoptosis of intestinal epithelial cells in neonatal rats with necrotizing enterocolitis / 中华儿科杂志

<p><b>OBJECTIVE</b>To establish an appropriate neonatal rat model of necrotizing enterocolitis (NEC) and to investigate the protective effects of glycomacropeptide (GMP) on the gut from injury in neonatal rats with NEC.</p><p><b>METHOD</b>A total of 36 neonatal SD rats were randomly divided into 3 groups: NEC model group (Group M), NEC + GMP group (Group G) and normal control group (Group N), each group had 12 rats. All the neonatal rats were fed with breast milk in the first 3 days after birth. During the second 3 days after birth, the rats of Group N were still maternal breast-fed, but the rats of Group M and Group G were separated from their mothers and lived in incubator and began to be formula fed, and were subjected to cold exposure shortly after hypoxic-reoxygenation treatment. After being fed in such means for 6 days, all the neonatal rats were placed into the incubator and fasted for 24 hours. Then all the rats were sacrificed by cervical dislocation. Intestinal tissue located at the boundary of ileum and cecum was obtained for: (1) histological examination after HE staining, (2) TUNEL detection, (3) electron microscopic observation; and the tissue homogenate was obtained for checking TNF-α and IL-1β levels by ELISA and platelet activating factor (PAF) mRNA expression by quantitative fluorescence (QF)-PCR.</p><p><b>RESULT</b>(1) The pathological scores of the 3 groups were 2.17 ± 0.83 (Group M), 0.92 ± 0.79 (Group G) and 0.17 ± 0.39 (Group N) separately. There was significant difference between Group M and Group G (H = 8.819, P = 0.003). (2) TNF-α levels of 3 groups were (41.94 ± 13.51) pg/ml (Group M), (31.69 ± 11.68) pg/ml (Group G) and (17.42 ± 7.18) pg/ml (Group N) separately, and TNF-α level in Group G was significantly lower than that of Group M (F = 3.959, P = 0.030). (3) IL-1β levels of 3 groups were (150.33 ± 36.41) pg/ml (Group M), (118.36 ± 33.00) pg/ml (Group G) and (28.44 ± 15.04) pg/ml (Group N) separately, and IL-1β level in Group G was lower than that of Group M (F = 5.080, P = 0.013). (4) Expression levels of intestinal PAF mRNA (2(-ΔΔCt) value): 3.01 ± 0.96 (Group M), 1.56 ± 0.29 (Group G), 1.01 ± 0.13 (Group N), the level of Group G was significantly lower than that of Group M (F = 25.251, P = 0.000). (5)Electron microscopy: Group N showed that its cell volume was mostly occupied by the nucleus, the structure was clear, nuclear membrane existed, suggesting the normal phase of cell; Group M showed that apoptotic body existed, suggesting that the advanced stage phase of apoptosis; Group G showed that condensed chromatin marginated around the nuclear envelope, nuclear pores expanded, suggesting the early phase of apoptosis. (6) The apoptosis rate of intestinal epithelial cells by TUNEL detection: 38.79 ± 9.79 (Group M), 29.54 ± 7.30 (Group G), 6.37 ± 1.96 (Group N); the apoptosis rate of intestinal epithelial cells of Group G was significantly lower than that of Group M (F = 6.888, P = 0.003).</p><p><b>CONCLUSION</b>GMP has protective effects on guts of neonatal rats with NEC, which may probably work by reducing TNF-α, IL-1β and PAF expression, inhibiting the apoptosis of intestinal epithelial cells and reducing intestinal tissue injury.</p>

Changes of platelet α-particle membrane protein, platelet activating factor and platelet parameters in patients with hyperuricemia / 中国实验血液学杂志

This study was aimed to investigate the changes of the platelet particle membrane protein (GMP-140), platelet activating factor (PAF) and platelet parametes in the patients with hyperuricemia (HUA), ELISA was used to detect the levels of GMP-140 and PAF in 55 patients with HUA and 30 healthy individuals. Platelet parameters were measured with automatic blood cell analyzer, and the biochemical indexes were detected at the same time. The results showed that the levels of serum uric acid, triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in HUA patients were higher than that in the normal group (P < 0.01). Serum uric acid level of HUA group was higher in men than that in women. The levels of GMP-140 and PAF in HUA patients were much higher than that in the normal group (P < 0.01), the indexes of platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) in HUA patients were higher than that in the normal group (P < 0.01), there was no statistically significant difference in platelet count, plateletcrit (PCT), mean platelet volume (MPV) between the two groups. There was positive correlation between serum uric acid and levels of GMP-140, PAF, P-LCR and PDW, respectively (r = 0.667, 0.879, 0.310, 0.460, P < 0.01 or P < 0.05). Multivariate stepwise regression analysis revealed that serum uric acid, creatinine, P-LCR, urea nitrogen contributed to GMP-140 level (adjusted R(2) = 0.822). Serum uric acid and LDL-C also contributed to PAF level (adjusted R(2) = 0.451). It is concluded that a close relationship exists between HUA and the change of platelet function, and HUA plays a certain role in cardiovascular disease thrombosis complications.

Atividade pró-trombótica da toxina ExoU de Pseudomonas aeruginosa detectada em modelos experimentais in vivo e in vitro / Prothrombotic activity of the Pseudomonas aeruginosa toxin ExoU detected in experimental models in vivo and in vitro

Pseudomonas aeruginosa é um importante agente de pneumonia, particularmente em pacientes submetidos à ventilação mecânica, que pode evoluir para sepse, com elevadas taxas de letalidade. Na sepse, o processo inflamatório sistêmico exacerbado favorece o desequilíbrio entre as vias de coagulação e fibrinólise e a instalação de um estado pró-coagulante, com o aparecimento de trombose microvascular, coagulação intravascular disseminada e falência de múltiplos órgãos. Conhecendo a potente atividade pró-inflamatória da toxina ExoU produzida por P. aeruginosa, decorrente de sua atividade fosfolipásica A2, o objetivo desta tese foi investigar seu potencial de indução de alterações hemostáticas relacionadas à patogênese da sepse. Utilizando modelo de sepse em camundongos inoculados, por via intratraqueal, com suspensões de P. aeruginosa produtora de ExoU (PA103) ou de cepa com deleção do gene exoU, não produtora da toxina, foi mostrado que ExoU determinou maior gravidade da infecção, maior taxa de letalidade, leucopenia, trombocitose, hiperpermeabilidade vascular e transudação plasmática, evidenciadas, respectivamente, pela maior concentração de proteínas nos lavados broncoalveolares (LBAs) e acúmulo do corante Azul de Evans, previamente inoculado nos animais, por via endovenosa, no parênquima renal. ExoU favoreceu, também, a ativação plaquetária, confirmada pela maior concentração de plaquetas expressando P-seletina em sua supefície, maior número de micropartículas derivadas de plaquetas e maior concentração plasmática de tromboxano A2. A histopatologia dos pulmões e rins dos animais infectados com PA103 confirmou a formação de microtrombos, que não foram detectados nos animais controles ou infectados com a cepa mutante. Nos pulmões, a produção de ExoU determinou intensa resposta inflamatória com maior concentração de leucócitos totais e polimorfonucleados, interleucina-6 e fator de necrose tumoral-alfa nos LBAs. A análise imunohistoquímica mostrou intensa deposição...

Pseudomonas aeruginosa is an important agent of pneumonia, mainly in patients undergoing mechanical ventilation, which can progress to sepsis with high mortality rates. In sepsis, the systemic inflammatory process favors exacerbated imbalance between the coagulation and fibrinolysis pathways and the installation of a procoagulant state, leading to microvascular thrombosis, disseminated intravascular coagulation and multiple organ failure. Knowing the powerful proinflammatory activity of the P. aeruginosa toxin ExoU, secondary to its phospholipase A2 activity, the goal of this study was to investigate the ExoU potential to induce hemostatic changes related to sepsis pathogenesis. By using a murine model of pneumosepsis, obtained by the intratracheal injection of suspensions of the ExoU-producing PA103 P. aeruginosa strain or of its isogenic mutant PA103 exoU, defective in the toxin synthesis, ExoU was shown to enhance the severity of the infection and to induce higher mice mortality rate as well as leukopenia, thrombocytosis, vascular hyperpermeability and plasma transudation, evidenced, respectively, by the higher protein concentration in the bronchoalveolar lavage fluids (BALF) and accumulation of Evans blue dye, previously intravenous infectioned, in mice renal parenchyma. ExoU also favored platelet activation, evidenced by the higher concentration of platelets expressing P-selectin on their surface, greater number of platelet-derived microparticles and increased plasma concentration of thromboxane A2. Histopathology of the lungs and kidneys of PA103 - infected animals confirmed the formation of microthrombi, which were not detected in controls or in animals infected with the bacterial mutant. In lungs, ExoU induced an intense inflammatory response with high concentrations of total and polymorphonuclear leukocytes, interleukin-6 and tumor necrosis factor-alfa in mice BALF. Immunohistochemical analysis showed intense fibrin deposition in the alveoli...

Correlation between blood-stasis tongue figure and platelet activating factor (PAF) and acetyl hydrolase of PAF (PAF-AH) in patients with primary dysmenorrhea / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the pathologic mechanism of blood-stasis tongue figure (BSTF) formation in patients with primary dysmenorrhea.</p><p><b>METHODS</b>Blood levels of platelet activating factor (PAF) and acetyl hydrolase of PAF (PAF-AH) in 41 patients with primary dysmenorrhea and 20 healthy subjects were detected by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The level of PAF in the 22 patients with BSTF was 252. 214 +/- 37. 568 ng/L, which was higher than that in patients without BSTF (19 patients, 212.348 +/- 22.794 ng/L) and healthy subjects (182.126 +/- 18.306 ng/L) respectively, while level of PAF-AH showed an opposite sequence in them, i.e., 3.090 +/- 1.483, 5.382 +/- 1.873, and 5.607 +/- 2.073 ng/L, respectively (P < 0.05). Patients without BSTF showed only a higher level of PAF when compared with that in healthy subjects (P < 0.05). No significant difference in PAF or PAF-AH levels was shown among patients with BDTF of different Chinese medical syndrome types (P > 0.05).</p><p><b>CONCLUSION</b>PAF level obviously increased and PAF-AH level obviously decreased in primary dysmenorrhea patients of BSTF, suggesting that the imbalance of PAF and PAF-AH was correlated with the pathologic mechanism of the BSTF formation in primary dysmenorrhea patients.</p>

Ensayo clínico sobre la bioequivalencia clínica de una dosis de clopidogrel leti cravid® (clop-l) 75 mg. Comprimidos frente a clopidogrel sanofi plavix® (clop-s) 75 mg. tabletas administradas en una dosis diaria por 7 días en voluntarios sanos / Clinical trial on clinical bioequivalence dose cravid ® leti clopidogrel (clop-l) 75 mg. Versus clopidogrel tablets sanofi plavix ® (clop-s) 75 mg. tablets administered at a daily dose for 7 days in healthy volunteers

Los pacientes sometidos a procedimientos de intervención coronaria percutánea, al igual que en pacientes con enfermedad coronaria, deben recibir en forma indefinida tratamiento con ácido acetilsalicílico (AAS) y Clopidogrel. El desarrollo de nuevos productos a base de Clopidogrel a menores costos ayudan a evitar la discontinuación prematura de la terapia antiplaquetaria; entre estos productos desarrollados tenemos la marca Cravid® de Laboratorios LETI S.A.V. y esta debe comparar su efectividad e inocuidad con el patrón internacional de Clopidogrel marca Plavix® de Laboratorios Sanofi Aventis. Se realizó un estudio: prospectivo, comparativo, cruzado, aleatorizado, en voluntarios sanos. Cada grupo recibió 1 comprimido de Clopidogrel Leti, CLOP-L o Clopidogrel Sanofi, CLOP-S de 75 mg. en una sola dosis al día durante 7 días continuos. Después de un período de lavado de 7 días recibieron el segundo tratamiento. Se midió la agregación plaquetaria al inicio de cada período y a los 7 días de tratamiento mediante agregometría óptica, con un agregómetro Óptico Modelo 490-2D marca Cronolog, con sistema de autocalibración que trabajó con plasma rico en plaquetas. Lectura 0-100% de paso de luz. En ambos grupos se produjo un descenso importante en la agregabilidad plaquetaria a los 7 días de tratamiento de más del 50 % independiente del reactivo de ADP (Helena y Cronolog) utilizado para agregar (P < 0.05). La relación de las medias e IC del porcentaje de agregación obtenida con las dos diferentes marcas comerciales de ADP se encontraron entre el 80 y 125%, por lo cual se concluye que ambas marcas de Clopidrogrel son bioequivalentes y por lo tanto, son perfectamente intercambiables

The undergoing percutaneous coronary intervention procedures, as in patients with coronary disease should receive treatment indefinitely with acetylsalicylic acid (ASA) and Clopidogrel. Developing new products based on lower costs clopidogrel to help prevent premature discontinuation of antiplatelet therapy, among these products we have developed the brand Cravid® of LETI S,A.V. Laboratories® and this should compare their effectiveness and safety with the international standard Clopidogrel brand Plavix® of Sanofi Aventis Laboratories. We conducted a study: a prospective, comparative, cross-randomized, in healthy volunteers. Each group received 1 tablet of Clopidogrel Leti, CLO-L or Clopidogrel Sanofi-LCLOP-S 75 mg. in a single dose daily for 7 days. Followed for 7 day-washout period before administration of second treatment. Platelet aggregation was measured at the beginning of each period and 7 days of treatment by agregometría optics. With a agregómetro Optical Model 490-2D. In both groups there was a decrease in platelets add to the 7 days of treatment for more than 50% independent of the reagent ADP (Helena and cronolog) used to add (P <0.05). The mean and CI at 90%, obtained with two different trademarks of ADP were between 80 and 125%, which was concluded that both brands are bioequivalent and are therefore perfectly interchangeable

Quebec platelet disorder

A case of Quebec platelet disorder is hereby reported. A 33 years old woman presented with history of epistaxis and gum bleeding since childhood and menorrhagia and bleeding per vaginum after puberty, also had history of excessive blood loss after birth of child. Her coagulation profile was normal but platelet function testing by platelet aggregation assay showed abnormal aggregation of platelet with epinephrine. This type of response is seen in "Quebec platelet disorder" which is a rare autosomal dominant disorder of platelet function characterized by increased bleeding after any injury or trauma