Study on the prognostic influencing factors of esophageal squamous cell carcinoma and the predictive value of inflammatory reaction indexes on its postoperative recurrence / 中华肿瘤杂志

Objective: To explore the influence factors of poor prognosis of esophageal squamous cell carcinoma (ESCC) and the predictive value of inflammatory reaction indexes including neutrophils and lymphocytes ratio (NLR), platelet and lymphocyte ratio (PLR), monocyte and lymphocyte ratio (MLR) provision and differentiation degree, infiltration depth, lymph node metastasis number on the postoperative recurrence of ESCC. Methods: A total of 130 patients with ESCC who underwent radical resection from February 2017 to February 2019 in Nanyang Central Hospital were selected and divided into good prognosis group (66 cases) and poor prognosis group (64 cases) according to the prognostic effect. The clinical data and follow-up data were collected. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor prognosis. Spearman correlation analysis was used to determine the correlation between preoperative NLR, PLR and MLR with the degree of differentiation, depth of invasion and number of lymph node metastases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of NLR, PLR and MLR in predicting poor prognosis of ESCC. Results: Univariate analysis showed that the degree of differentiation, the degree of invasion and the number of lymph node metastasis were related to the prognoses of patients with ESCC (P<0.05). Multivariate logistic regression analysis showed that the degree of differentiation, depth of invasion and number of lymph node metastases were independent influencing factors for poor prognosis of patients with ESCC, moderate differentiation (OR=2.603, 95% CI: 1.009-6.715) or low differentiation (OR=9.909, 95% CI: 3.097-31.706), infiltrating into fibrous membrane (OR=14.331, 95% CI: 1.333-154.104) or surrounding tissue (OR=23.368, 95% CI: 1.466-372.578), the number of lymph node metastases ≥ 3 (OR=9.225, 95% CI: 1.693-50.263) indicated poor prognosis. Spearman correlation analysis showed that NLR was negatively correlated with the degree of differentiation and the number of lymph node metastases (r=-0.281, P=0.001; r=-0.257, P=0.003), PLR was negatively correlated with the degree of differentiation, depth of invasion and number of lymph node metastasis (r=-0.250, P=0.004; r=0.197, P=0.025; r=-0.194, P=0.027), MLR was positively correlated with the degree of differentiation and the number of lymph node metastasis (r=0.248, P=0.004; r=0.196, P=0.025). ROC curve analysis showed that the areas under the curve of NLR, PLR and MLR in predicting poor prognosis of ESCC were 0.971, 0.925 and 0.834, respectively. The best cut-off value of NLR was 2.87. The sensitivity and specificity of NLR in predicting poor prognosis of ESCC were 90.6% and 87.9%, respectively. The optimal cut-off value of PLR was 141.75. The sensitivity and specificity for predicting poor prognosis of ESCC were 92.2% and 87.9%, respectively. The best cut-off value of MLR was 0.40. The sensitivity and specificity of MLR in predicting poor prognosis of esophageal squamous cell carcinoma were 54.7% and 100.0%, respectively. Conclusions: The degree of differentiation, the degree of invasion and the number of lymph node metastases are closely related to the poor prognosis of patients with esophageal squamous cell carcinoma. NLR, PLR and MLR can provide important information for predicting the poor prognosis of esophageal squamous cell carcinoma.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

The Role of Platelet Exosomes in Atherogenic Thrombosis --Review / 中国实验血液学杂志

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.

The role of platelet parameters in thrombosed hemorrhoids / O papel dos parâmetros plaquetários nas hemorróidas trombosadas

ABSTRACT Objectives: The most common disease of anus is hemorrhoids. The definition of external hemorrhoids suggests the acute phase, often characterized by thrombosis or edema. External thrombosed hemorrhoid is a specific complication. In this study, we aimed to investigate the effects of different platelet parameters in the presence of internal or external thrombosed hemorrhoids. Methods: Patients examined were divided into two groups: Group 1: Thrombosed hemorrhoids group (THG), Group 2: Hemorrhoidectomy group (HG). Demographic and clinical data were identified. In terms of laboratory findings, preoperative hemoglobin, hematocrit and all platelet parameters were recorded. Main results: Fifty-two patients in THG, and 75 patients in HG were included in the study. In female sex and young age group, the risk of developing thrombosed hemorrhoids was statistically significant (p= 0.029, p= 0.039, respectively). When the platelet parameters were evaluated; while PDW was higher in THG (p= 0.008), any significant difference could not found in all other values (p> 0.05). Thrombosed hemorrhoids were mostly (59.25%) found to be located in the left laterodorsal part of anus. Conclusion: Internal hemorrhoids are frequently seen in the ages of 45-65 with similar rates in both sexes, while external thrombosed hemorrhoids occur at a younger age (<45) and more often in women. Comparing in terms of platelet indexes, PDW value was found to be significantly higher in THG. In young people, thrombosed hemorrhoids may develop more frequently, as the connective tissue that forms the anal pads is not loose enough to form an internal hemorrhoid, as more seen in older patients.

RESUMO Objetivos: A doença anal mais comum são as hemorróidas. A definição de hemorróidas externas sugere a fase aguda, muitas vezes caracterizada por trombose ou edema. A hemorroida externa trombosada é uma complicação específica. Neste estudo, objetivamos investigar os efeitos de diferentes parâmetros plaquetários na presença de hemorróidas trombosadas internas ou externas. Métodos: Os pacientes examinados foram divididos em dois grupos: Grupo 1, Grupo de Hemorróidas Trombosadas (GHT); Grupo 2, Grupo de hemorroidectomia (GH). Os dados demográficos e clínicos foram identificados. Em termos de achados laboratoriais, a hemoglobina pré-operatória, o hematócrito e todos os parâmetros plaquetários foram registrados. Resultados principais: Cinquenta e dois pacientes em GHT e 75 pacientes em GH foram incluídos no estudo. No sexo feminino e na faixa etária jovem, o risco de desenvolver hemorróidas trombosadas foi estatisticamente significativo (p = 0,029, p = 0,039, respectivamente). Os parâmetros plaquetários avaliados mostraram que, enquanto a Amplitude de Distribuição de Plaquetas (PDW, do inglês platelet distribution width) foi maior no GHT (p = 0,008), nenhuma diferença significativa foi encontrada para todos os outros valores (p > 0,05). A maioria das hemorróidas trombosadas (59,25%) localizava-se na região lateral-dorsal esquerda do ânus. Conclusão: As hemorróidas internas são frequentemente vistas nas idades de 45 a 65 anos com taxas semelhantes em ambos os sexos, enquanto as hemorróidas externas trombosadas ocorrem em uma idade mais jovem (<45) e mais frequentemente em mulheres. Comparando em termos de índices de plaquetas, foi observado que o valor de PDW foi significativamente maior no GHT. Em pessoas jovens, as hemorróidas trombosadas podem se desenvolver com mais frequência, pois o tecido conjuntivo que forma as almofadas anais não é flácido o suficiente para formar uma hemorroida interna, como ocorre com mais frequência em pacientes mais velhos.

Características citomorfológicas de las alteraciones plaquetarias cuantitativas y su relación con otras alteraciones celulares / Cytomorphological characteristics of quantitative platelet alterations and its association with other cell alterations

Introducción: Las alteraciones cuantitativas de plaquetas son producidas por el incremento o disminución de los conteos globales de plaquetas. El incremento o trombocitosis se produce por redistribución o aumento de la producción medular; la disminución puede ser el resultado de una reducción de la producción, redistribución o acortamiento de la sobrevida de las plaquetas en circulación. Objetivo: Describir los hallazgos citomorfológicos más importantes en las alteraciones cuantitativas de plaquetas. Métodos: Se realizó una revisión de la literatura, en inglés y español, en la base de datos PubMed y el motor de búsqueda Google Académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las alteraciones cuantitativas de plaquetas se caracterizan por variaciones en el número y morfología de estas células. Estas se asocian a causas congénitas o adquiridas, en la que la detallada anamnesis de los pacientes es un elemento importante en el diagnóstico. En la trombocitosis se debe diferenciar una trombocitosis reactiva de una enfermedad medular primaria; mientras que en la trombocitopenia se debe considerar el origen étnico de los pacientes y la morfología de los leucocitos. Son numerosas las causas hereditarias de trombocitopenia con anomalías morfológicas de plaquetas y granulocitos. Conclusiones: Las alteraciones cuantitativas de plaquetas son un amplio número de entidades con semejanzas y diferencias en cuanto a presentación y manifestaciones clínicas. Los exámenes de laboratorio constituyen una herramienta importante en el diagnóstico, pronóstico y el seguimiento de los pacientes afectados(AU)

Introduction: Quantitative platelet alterations are produced by the increase or decrease in global platelet counts. Platelet count increase or thrombocytosis is produced by redistribution or increased marrow production. Platelet decrease may result from production, redistribution, or shortened survival of circulating platelets. Objective: To describe the most significant cytomorphological findings in quantitative platelet alterations. Methods: A literature review was carried out, in English and in Spanish, in the database PubMed and with the search engine of Google Scholar, of articles published in the last ten years. An analysis and summary of the revised bibliography was made. Information analysis and synthesis: Quantitative platelet alterations are characterized by variations in the number and morphology of these cells. These are associated with congenital or acquired causes, in which detailed anamnesis of patients is an important element in the diagnosis. In thrombocytosis, reactive thrombocytosis must be differentiated from primary marrow disease; while in thrombocytopenia, the ethnic origin of the patients and the morphology of the leukocytes must be considered. Hereditary causes of thrombocytopenia with morphological abnormalities of platelets and granulocytes are numerous. Conclusions: Quantitative platelet alterations are a large number of entities with similarities and differences in terms of presentation and clinical manifestations. Laboratory tests are an important tool for diagnosis, prognosis, and follow-up of affected patients(AU)

Utilidad diagnóstica del volumen plaquetario medio en embarazadas con preeclampsia / Diagnostic utility of mean platelet volume in pregnant women with preeclampsia

RESUMEN OBJETIVO: Establecer la utilidad diagnóstica del volumen plaquetario medio en embarazadas con preeclampsia. MÉTODOS: Se realizó un estudio de de casos y controles en el Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Se seleccionó un total de 180 embarazadas. Se incluyeron 90 preeclámpticas como grupo de estudio (grupo A) y un grupo de control seleccionado por tener edad e índice de masa corporal similares al grupo de estudio, que consistió en 90 embarazadas normotensas sanas (grupo B). Las muestras de sangre se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo A, para determinar los valores de volumen plaquetario medio. Se determinaron las características generales, valores de volumen plaquetario medio y eficacia diagnóstica. RESULTADOS: Se encontraron diferencias estadísticamente significativas en los valores de volumen plaquetario medio entre las pacientes del grupo A (10,35 +/− 1,11 fL) y las pacientes del grupo B (9,54 +/− 0,96 fL; p < 0,001). No se observaron correlaciones significativas con los valores de presión arterial sistólica y diastólica (p = ns). Un valor de corte de 10,3 fL presentó un valor por debajo de la curva de 0,71, sensibilidad del 53,3%, especificidad del 63,1%, valor predictivo positivo del 63,2% y valor predictivo negativo del 59,6%, con una exactitud diagnóstica del 61,1%. CONCLUSIÓN: Los valores volumen plaquetario medio no son útiles para discriminar el diagnóstico de preeclampsia en las embarazadas, a pesar que las preeclámpticas presentaron valores significativamente más elevados de al compararlo con embarazadas normotensas sanas.

ABSTRACT OBJECTIVE: To establish the diagnostic utility of the mean platelet volume in pregnant women with preeclampsia. METHODS: Case-control study was done at Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. A total of 180 patients were selected. Ninety preeclamptic patients were selected as the study group (group A) and 90 healthy normotensive pregnant women with the same age and body mass index as the study group were selected as controls (group B). Blood samples were extracted from all patients before labor and immediately after diagnosis in group A to determine mean platelet volume. General characteristics, mean platelet volume values and diagnostic efficacy were determined. RESULTS: There was a statistically significant difference in mean platelet volume values between patients in study group (group A: 10.35 +/− 1.11 fL) and patients in control group (group B: 9.54 +/− 0.96 fL; p < 0.001). There was no significant correlation with systolic and diastolic blood pressure values (p = ns). A cutoff value of 10.3 fL had an area under the curve of 0.71, sensitivity 53.3%, specificity 63.1%, positive predictive value 63.2% and negative predictive value 59.6%, with diagnostic accuracy of 61.1%. CONCLUSION: Mean platelet volume values are not useful for discriminating the diagnosis of preeclampsia in pregnant women, although the preeclamptic values were significantly higher when compared with healthy normotensive pregnant women.

Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma

Abstract: Background: c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. Objective: To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. Methods: A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. Results: Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). Conclusion: c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.

Immature Platelet Fraction in Septic Patients: Clinical Relevance of Immature Platelet Fraction is Limited to the Sensitive and Accurate Discrimination of Septic Patients From Non-Septic Patients, Not to the Discrimination of Sepsis Severity

BACKGROUND: The immature platelet fraction (IPF) reflects the degree of reticulated platelets. We evaluated performances of IPF as a biomarker for the discrimination of septic patients from non-septic patients and sepsis severity. METHODS: Total 312 patients admitted between March and July 2013 were enrolled and samples were obtained at admission. Lactate (LA), procalcitonin (PCT), C-reactive protein (CRP), immature granulocyte fraction (IG), immature reticulocyte fraction (IRF), and IPF were analyzed as sepsis biomarkers and their performances were compared. RESULTS: The performance of IPF (area under the curve [AUC]=0.868) in the discrimination of septic patients from non-septic patients was comparable to PCT/CRP/LA/IG (AUC=0.923/0.940/0.781/0.812, P=0.233/0.106/0.186/0.353, respectively), and was significantly better than the IRF (AUC=0.658, P=0.007). Sensitivity (89.8%, 95% confidence interval [CI] 84.9-99.8%) and accuracy (83.2%, 95% CI 78.8-90.0%) of IPF were the best among all biomarkers. The performance of IPF in discriminating septic patients from non-septic patients with local infection showed similar results. However, the IPF could not efficiently discriminate sepsis severity (AUC=0.599), similar to other biomarkers (AUC=0.519-0.752). CONCLUSIONS: The IPF possessed high sensitivity/accuracy in discriminating septic patients from non-septic patients, regardless of local infection status. However, the IPF did not efficiently discriminate sepsis severity. The clinical relevance of IPF as a sepsis biomarker is, therefore, limited to sensitive and accurate discrimination of septic patients from non-septic patients, not discrimination of sepsis severity.

Microparticles as Potential Biomarkers of Cardiovascular Disease / Micropartículas como Possíveis Biomarcadores da Doença Cardiovascular

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

A prevenção primária da doença cardiovascular constitui uma opção de grande relevância pelos seus impactos na saúde. Alguns biomarcadores têm sido considerados úteis na avaliação da doença cardiovascular, dentre eles micropartículas originadas de diferentes populações de células. Micropartículas são estruturas liberadas pela membrana de diferentes tipos celulares após ativação ou apoptose, presentes tanto no plasma de indivíduos saudáveis (níveis considerados fisiológicos) quanto em portadores de diferentes doenças. Muitos estudos têm sugerido uma associação entre micropartículas e diferentes condições patológicas, destacando-se a relação com o desenvolvimento das doenças cardiovasculares. Além disso, têm sido descritos os efeitos de diferentes terapias hipolipemiantes na mensuração de micropartículas. Os estudos ainda são controversos quanto aos níveis de micropartículas que possam ser considerados patológicos, e os métodos utilizados ainda são variados, o que sugere a necessidade da padronização dos diferentes protocolos utilizados, visando à utilização de micropartículas como biomarcadores úteis na prática clínica.

Predictive value of pretreatment inflammation-based prognostic scores (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio) for invasive bladder carcinoma

PURPOSE: Inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are associated with oncologic outcomes in diverse malignancies. We evaluated the predictive value of pretreatment prognostic scores in differentiating nonmuscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). MATERIALS AND METHODS: Consecutive transurethral resection of bladder tumour (TURBT) cases from January 2011 to December 2013 were analysed retrospectively. Patient demographics, tumour characteristics and prognostic scores results were recorded. Receiver operating characteristics curves were used to determine prognostic score cutoffs. Univariate and multivariate binomial logistic regression analysis was performed to evaluate the association between variables and MIBC. RESULTS: A total of 226 patients were included, with 175 and 51 having NMIBC (stages Ta and T1) and MIBC (stage T2+) groups, respectively. Median age was 75 years and 174 patients were male. The NLR cutoff was 3.89 and had the greatest area under the curve (AUC) of 0.710, followed by LMR (cutoff218; AUC, 0.642). Full blood count samples were taken a median of 12 days prior to TURBT surgery. Multivariate logistic regression analysis identified tumour grade G3 (odds ration [OR], 32.848; 95% confidence interval [CI], 9.818-109.902; p=0.000), tumour size> or =3 cm (OR, 3.353; 95% CI, 1.347-8.345; p=0.009) and NLR> or =3.89 (OR, 8.244; 95% CI, 2.488-27.316; p=0.001) as independent predictors of MIBC. CONCLUSIONS: NLR may provide a simple, cost-effective and easily measured marker for MIBC. It can be performed at the time of diagnostic flexible cystoscopy, thereby assisting in the planning of further treatment.

Reduction in platelet count in post CABG patients with or without IABP- an experience at AFIC/NIHD Rawalpindi

To study the reduction in platelet count in patients after coronary artery bypass grafting having IABP placed peri operatively with and without IABP placed. Descriptive Study. Armed Forces Institute of Cardiology/National Institute of Heart Diseases [AFIC/NIHD] from Jan 2012 to Dec 2013. All cases with intra-aortic balloon pump [IABP] placed peri operatively [coronary artery bypass grafting, CABG] during this time period were examined in detail. Only those patients who had a platelet count of 150,000 or more pre operatively were included in the study. Patients taking medicines pre operatively that lead to decrease in platelet count were excluded. Platelet counts of each patient were analyzed till the third post-operative day. One hundred and fifty patients were divided into two equal groups, group A without IABP and group B with IABP. Patients without IABP [group A] pre operatively had mean platelet count of 223.57 +/- 83.02, on first post op day the mean platelet count was 171.0 +/- 59.0 which was 76.48% of preoperative level, on second post op day the mean platelet count was 168.1 +/- 59.4 which was 75.20% of preoperative level and on third post op day the mean platelet count was 167.5 +/- 60.0 which was 74.95% of pre-operative level. Patients with IABP [group B], pre operatively had mean platelet count of 205.32 +/- 50.257, on first post op day the mean platelet count of 152.71 +/- 43.77 which was 74.37% of preoperative level, on second post op day the mean platelet count was 112.11 +/- 42.571 which was 54.60% of preoperative level and on third post op day the platelet count was 90.87 +/- 41.538 which was 44.25% of preoperative level. There was significant reduction in platelet count from the pre-operative level in both the groups. Reduction in platelet count in post CABG patients is similar in both the groups i.e. in whom IABP is and those patients who are not treated with IABP

Papel do fator de ativação de plaquetas na infecção de macrófagos por leishmania infantum e identificação de uma Paf-Acetilhidrolase no parasita / Role of platelet-activating factor in macrophage infection by Leishmania infantum and identification of the parasite PAF acetylhydrolase

A leishmaniose visceral é causada pelo parasita Leishmania infantum. A infecção ocorre quando flebótomos infectados se alimentam na derme do hospedeiro vertebrado, inoculando o parasita. A infecção produz uma resposta com diversas moléculas inflamatórias, como os mediadores lipídicos. O fator de ativação de plaquetas (PAF) é um potente mediador lipídico derivado de um lisofosfolipídio. PAF participa da fisiologia normal da célula e possui um perfil pró-inflamatório. A participação de mediadores lipídicos, como eicosanóides e PAF, já foi identificada na imunopatogênese das leishmanioses. PAF gerado pelo hospedeiro tem efeito leishmanicida e de controle da infecção por L. amazonensis. PAF-acetilhidrolases (PAF-AH) são fosfolipases A2 que hidrolisam PAF e foi demonstrado que PAF-AH podem ser um fator de virulência devido a essa habilidade. O objetivo desse estudo foi avaliar o papel do PAF e de uma PAF-AH na infecção de macrófagos por L. infantum. Foi observado que PAF 1μM, quando adicionado durante e após a infecção, foi capaz de diminuir 50% da infecção após 72 horas, bem como a viabilidade dos parasitas dentro dos macrófagos num mecanismos independente do seu receptor PAFR e da produção de óxido nítrico. PAF 10μM interrompeu o crescimento de promastigotas de L. infantum em cultura axênica. Uma PAFAH, com elevada identidade e semelhança com PLA2/PAF-AH de outros tripanossomatídeos, foi identificada no genoma de L. infantum. A clonagem e expressão recombinante produziu uma proteína de cerca de 69kDa, com atividade PAF-AH. Frações celulares do parasita, enriquecidas com estruturas de membrana também apresentaram atividade PAF-AH. Os resultados indicam que PAF é capaz de diminuir a infecção de macrófagos por L. infantum e que o parasita possui uma PAF-AH funcional possivelmente envolvida com sua virulência.

Visceral leishmaniasis is caused by Leishmania infantum parasites. Infection occurs when infected sandflies feed on vertebrate host skin delivering the parasite which survive, multiply and spread on the parasitophorous vacuoles of macrophages. The inflammatory response during the infection leads to the production of diverse bioactive molecules, as lipid mediators. The platelet activating factor (PAF) is a lipid mediator derived from a lysophospholipid. PAF has a role in normal cellular physiology, acting as proinflamatory molecule. The participation of some lipid mediators, as eicosanoids and PAF has been identified in leishmaniasis. PAF produced by the host is able to kill the parasite and control the infection by L. amazonensis. PAF-acetylhydrolases (PAF-AH) are phospholipases A2 (PLA2) that hydrolyse PAF, and possibly involved in pathogen virulence. The aim of this study was to evaluate the role of PAF on macrophages infection by L. infantum and identify a PAF-AH expressed by the parasite. PAF 1μM, added during and after the infection, was able to reduce approximately 50% of infection, as well as, the viability of parasites inside macrophages. Apparently this reduction occurs by an classical PAF receptor and nitric oxide production independent mechanism. PAF 10μM inhibited L. infantum promastigotes growing in axenic culture. A PAF-AH with high identity to PLA2/PAF-AH of others trypanosomatids was identified in L. infantum genome. The cloning and recombinant expression produced a 69kDa protein with PAF-AH activity. Cellular fractions from parasites, with membrane structures also presented PAF-AH activity. The results suggest that PAF is able to decrease machophage infection by L. infantum witch has a functional PAFAH possibly related to its virulence.

Unusual yet isolated oral manifestations of persistent thrombocytopenia: a rare case report

Patients with platelet-mediated disorders often present clinical manifestations of bruising and bleeding. Although these changes are detected most frequently on the skin, the oral cavity also may exhibit signs of bleeding. In this report, we describe a patient who presented isolated oral features of hemorrhagic bullae with bleeding, indicative of a bleeding disorder. Results of laboratory tests revealed severe thrombocytopenia and a careful history disclosed dengue fever as the cause. The importance of recognizing the oral manifestations of thrombocytopenia is highlighted here, since the oral cavity is a frequent site of hemorrhage and could be the only manifestation of the disease.

O volume plaquetário médio abaixo do normal está associado com extensão reduzida de doença arterial coronariana / Lower than normal mean platelet volume is associated with reduced extent of coronary artery disease

FUNDAMENTO: A extensão da doença arterial coronariana aterosclerótica em pacientes com angina estável tem importantes implicações prognósticas e terapêuticas. Em modelos atuais de evolução de placas, os trombócitos desempenham um papel importante no crescimento de placas. O volume plaquetário médio é um marcador facilmente determinado, com evidência de correlação com a agregabilidade plaquetária in vitro, além de valores comprovadamente maiores após eventos vasculares agudos. OBJETIVO: No presente estudo, investigou-se a relação entre o volume plaquetário médio e a extensão angiográfica da doença arterial coronariana em pacientes com angina estável. MÉTODOS: Foram analisados prontuários, hemograma completo e dados angiográficos anteriores de 267 pacientes elegíveis com angina estável. A extensão angiográfica da doença arterial coronariana foi avaliada à luz de dados angiográficos, com o uso por um especialista do escore de Gensini em uma cardiologia invasiva. Os valores para o volume plaquetário médio foram obtidos a partir de hemogramas completos, obtidos um dia antes da angiografia. Com relação ao intervalo populacional para o volume plaquetário médio, os pacientes foram agrupados dentro (n = 176) e abaixo (n = 62) do referido intervalo. Foi realizada uma comparação entre grupos e uma análise correlacional. RESULTADOS: Não houve correlação linear entre o escore de Gensini total e o volume plaquetário médio (p = 0,29), ao passo que a contagem total de trombócitos apresentou correlação inversa com o volume plaquetário médio (p < 0,001, r = 0,41). Os pacientes com volume plaquetário médio abaixo do normal apresentaram um escore de Gensini (36,73 ± 32,5 vs. 45,63 ± 32,63; p = 0,023) e doença coronariana triarterial (18% VS. 36%; p = 0,007) significativamente inferiores se comparados com aqueles apresentando valores de volume plaquetário médio dentro dos intervalos populacionais. CONCLUSÃO: Nossas constatações não demonstraram nenhuma relação linear entre o volume plaquetário médio e a extensão da doença arterial coronariana, ao passo que os pacientes com volume plaquetário médio abaixo do normal apresentaram uma extensão reduzida da doença arterial coronariana.

BACKGROUND: Extent of atherosclerotic coronary artery disease in patients with stable angina has important prognostic and therapeutic implications. In current models of plaque evolution, thrombocytes play an important role in plaque growth. Mean platelet volume is a readily obtainable marker that was shown to correlate with platelet aggregability in vitro and increased values were demonstrated after acute vascular events. OBJECTIVE: In this study, we investigated the relationship of mean platelet volume and angiographic extent of coronary artery disease in patients with stable angina. METHODS: Past medical records, complete blood count and angiographic data of 267 eligible stable angina patients were reviewed. Angiographic extent of coronary artery disease was evaluated form angiographic data using Gensini score by an expert in invasive cardiology. Mean platelet volume values were obtained from complete blood counts that obtained one day before angiography. Patients were grouped as those within (n = 176) and lower than (n = 62) population-based range for mean platelet volume. Comparison between groups and correlation analysis was performed. RESULTS: There were no linear correlation between total Gensini score and mean platelet volume (p = 0.29), while total thrombocyte count was inversely correlated with mean platelet volume (p < 0.001; r = 0.41). Patients with lower than normal mean platelet volume had significantly lower Gensini score (36.73 ± 32.5 vs. 45.63 ± 32.63; p = 0.023) and three-vessel disease (18% vs. 36%; p = 0.007) compared with those mean platelet volume values within population-based ranges. CONCLUSION: Our findings show no linear relationship exists between mean platelet volume and extent of coronary artery disease, while patients with lower than normal mean platelet volume had reduced extent of coronary artery disease.

Factores genéticos del sistema hemostático en pacientes jóvenes con infarto agudo del miocardio / Genetic factors of the hemostatic system in young patients with myocardial infarction

La enfermedad arterial coronaria (EAC) es la primera causa de muerte en todo el mundo y representa un problema de salud pública en México. El infarto agudo del miocardio (IAM) representa la principal complicación trombótica de la EAC. Aproximadamente 9 % de los nuevos casos está constituido por sujetos menores de 45 años. El IAM se produce por el desarrollo de un trombo en el sitio de la placa aterosclerosa, generando oclusión arterial súbita con isquemia y muerte celular. El IAM resulta de la interacción entre factores genéticos y ambientales. Existen diversos factores de riesgo modificables como la hipertensión arterial, la diabetes mellitus, el tabaquismo, la obesidad y la hipercolesterolemia asociados con el IAM. Sin embargo, numerosos pacientes con IAM no presentan factores de riesgo modificables. En la última década se han identificado variantes genéticas en las proteínas relacionadas con los sistemas de coagulación y fibrinólisis, receptores plaquetarios, disfunción endotelial, flujo sanguíneo anormal, metabolismo de la homocisteína, estrés oxidativo, los cuales se asocian a desarrollo del IAM. La identificación de los polimorfismos asociados a la enfermedad arterial coronaria permitirá desarrollar mejores estrategias de tratamiento e identificación de individuos con alto riesgo para EAC y medidas preventivas en etapas tempranas.

BACKGROUND: Coronary artery disease (CAD) is the first cause of death worldwide and represents a public health issue in our country. Acute myocardial infarction (AMI) represents the main thrombotic complication of CAD. Approximately 9% of the new events of MI occur in patients <45 years of age. DISCUSSION: AMI is produced by development of a thrombus at the site of an atherosclerotic plaque that initiates abrupt arterial occlusion, with ischemia and cell death. AMI results from the interaction of gene-environment factors. There are several modifiable factors such as hypertension, diabetes, smoking, obesity, and hypercholesterolemia associated with AMI. However, in a large number of patients with AMI, modifiable risk factors are not present. In the last decade, several genetic variants (polymorphisms) have been identified associated with AMI in genes related to coagulation proteins, fibrinolytic system, platelet receptors, homocysteine metabolism, endothelial dysfunction, abnormal blood flow and oxidative stress. CONCLUSIONS: Identifying the genes associated with CAD will allow us to develop more efficacious treatment strategies and will also help to identify at-risk subjects, thereby enabling the introduction of early preventive measures. Thus, many research efforts continue to address the identification of acquired and inherited risk factors of this complex disease.

Frequency of increased mean platelet volume in patients suffering from hypertensive retinopathy

The pathophysiological mechanism of hypertensive retinopathy is not fully established. It is thought that increased platelet activation may play a role in its pathogenesis. As mean platelet volume is a marker of platelet activation, so this study was designed to answer the question: does mean platelet volume increase in hypertensive retinopathy. To determine frequency of increased mean platelet volume in hypertensive retinopathy. Cross-sectional study. Six months. Outpatient department of Medical. unit III, Allied Hospital, Faisalabad. 138 patients of essential hypertension with hypertensive retinopathy of all ages and both sexes were included. For grading of hypertensive retinopathy according to the Keith Wagener classification, direct ophthalmoscopy was performed in all the subjects and mean platelet volume was measured after taking the blood sample. The mean platelet volume was found to be normal [10 fl] were found in 41 patients [29.7%], of these 19 were males while 22 were females. In patients of grade 1 hypertensive retinopathy, the mean platelet volume was 9.1 +/- 0.6 fl. In grade 2, 3 and 4 hypertensive retinopathy the values of mean platelet volume were 9.6 +/- 0.5 fl, 10.1 +/- 0.3 fl and 10.7 +/- 0.6 fl respectively. This study concluded that frequency of mean platelet volume is increased in patients of hypertensive retinopathy and frequency increases with increasing the severity of hypertensive retinopathy

Policitemia vera: relato de caso / Polycythemia vera: case report

A policitemia vera (PV) é um transtorno mieloproliferativo das células hematopoiéticas, caracterizada poruma produção anormal e acentuada de eritrócitos, leucócitos e plaquetas. É uma doença rara, com uma incidênciade 2,3/100.000 pessoas por ano. Apresentamos um relato de caso de uma paciente de 45 anos com sintomas,sinais e achados sugestivos de policitemia vera.

The polycythemia vera is a myeloproliferative disturb from haematopoietic cells characterized by abnormal and overstated production of erythrocytes, leukocytes and platelets. It is a rare disease with an incidenceof 2.3/100.000 people per year. We present a case report of a 45 years old patient with symptoms, signs andsuggestive results of polycythemia vera.