Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis / 中国当代儿科杂志

OBJECTIVES@#To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis.@*METHODS@#Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue.@*RESULTS@#The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05).@*CONCLUSIONS@#In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Molecular dynamics simulation of force-regulated interaction between glycoprotein Ib α and filamin / 生物医学工程学杂志

In resting platelets, the 17 th domain of filamin a (FLNa17) constitutively binds to the platelet membrane glycoprotein Ibα (GPIbα) at its cytoplasmic tail (GPIbα-CT) and inhibits the downstream signal activation, while the binding of ligand and blood shear force can activate platelets. To imitate the pull force transmitted from the extracellular ligand of GPIbα and the lateral tension from platelet cytoskeleton deformation, two pulling modes were applied on the GPIbα-CT/FLNa17 complex, and the molecular dynamics simulation method was used to explore the mechanical regulation on the affinity and mechanical stability of the complex. In this study, at first, nine pairs of key hydrogen bonds on the interface between GPIbα-CT and FLNa17 were identified, which was the basis for maintaining the complex structural stability. Secondly, it was found that these hydrogen bonding networks would be broken down and lead to the dissociation of FLNa17 from GPIbα-CT only under the axial pull force; but, under the lateral tension, the secondary structures at both terminals of FLNa17 would unfold to protect the interface of the GPIbα-CT/FLNa17 complex from mechanical damage. In the range of 0~40 pN, the increase of pull force promoted outward-rotation of the nitrogen atom of the 563 rd phenylalanine (PHE 563-N) at GPIbα-CT and the dissociation of the complex. This study for the first time revealed that the extracellular ligand-transmitted axial force could more effectively relieve the inhibition of FLNa17 on the downstream signal of GPIbα than pure mechanical tension at the atomic level, and would be useful for further understanding the platelet intracellular force-regulated signal pathway.

Effect of Vitamin D Status on Von Willebrand Factor and ADAMTS13 in Diabetic Patients on Chronic Hemodialysis

Von Willebrand factor (vWF) is a glycoprotein with a crucial role in the formation of platelet thrombi, and ADAMTS13 is the main enzyme responsible for vWF cleavage. Both are important in the relationship between diabetic nephropathy, hypercoagulability, and cardiovascular disease. This study evaluated a potential relationship between vitamin D (vitD) levels, vWF, ADAMTS13 activity, and inflammation in diabetic patients on chronic hemodialysis (HD). Blood samples from 52 diabetic patients on chronic HD were obtained to determine vitD levels, vWF, and ADAMTS13 activity, and inflammatory markers. HD patients were grouped according to 25-hydroxyvitamin D [25(OH) VitD]25 nmol/L (n=36). vWF antigen and vWF activity were elevated in both groups, with an average of 214.3±82.6% and 175.8±72.6%, respectively. Average ADAMTS13 activity was within the normal range in both groups. Blood samples from the vitD <25 nmol/L group showed a positive correlation between c-reactive protein (CRP) and vWF levels (P=0.023; r=0.564; 95% confidence interval=0.095-0.828), with a negative correlation between HbA1c and 25(OH) VitD (P=0.015; r=-0.337; 95% confidence interval=-0.337-0.19). Diabetic patients on chronic HD had elevated vWF levels and activity with no significant change in ADAMTS13 activity. The correlation between CRP and vWF levels in the 25(OH) VitD<25 nmol/L group suggests inflammatory-related endothelial dysfunction in these patients.

Parotid Incidentaloma Identified by Positron Emission/Computed Tomography: When to Consider Diagnoses Other than Warthin Tumor

Introduction Parotid gland incidentalomas (PGIs) are unexpected hypermetabolic foci in the parotid region that can be found when scanning with whole-body positron emission/computed tomography (PET/CT). These deposits are most commonly due to benign lesions such as Warthin tumor. Objective The aim of this study was to determine the prevalence of PGIs identified in PET/CT scans and to assess the role of smoking in their etiology. Methods We retrospectively reviewed all PET/CT scans performed at our center in search of PGIs and identified smoking status and standardized uptake value (SUVmax) in each case. We also analyzed the database of parotidectomies performed in our department in the previous 10 years and focused on the pathologic diagnosis and the presence or absence of smoking in each case. Results Sixteen cases of PGIs were found in 4,250 PET/CT scans, accounting for 0.4% . The average SUVmax was 6.5 (range 2.8 to 16). Cytology was performed in five patients; it was benign in four cases and inconclusive in one case. Thirteen patients had a history of smoking. Of the parotidectomies performed in our center with a diagnosis of Warthin tumor, we identified a history of smoking in 93.8% of those patients. Conclusions The prevalence of PGIs on PET/CT was similar to that reported by other authors. Warthin tumor is frequently diagnosed among PGIs on PET/CT, and it has a strong relationship with smoking. We suggest that a diagnosis other than Warthin tumor should be considered for PGIs in nonsmokers. .

Acesso ao cuidado à saúde da criança em serviços de atenção primária / Access to child's health care in primary care services / Acceso al cuidado de la salud del niño en servicios de atención primaria

Realizou-se uma pesquisa de abordagem qualitativa com base no referencial metodológico da hermenêutica dialética, com o objetivo de identificar o atributo acesso da atenção primária para a resolução dos problemas de saúde de crianças menores de um ano a partir dos relatos de pais e cuidadores. Envolveram-se 16 cuidadores de crianças atendidas em unidades de pronto atendimento de Cascavel-PR, em 2010. Foram reconhecidas quatro categorias temáticas: Aconselhamento familiar ao buscar atenção à saúde da criança; Ausência de acolhimento ao primeiro contato; Presença de classificação de risco para atenção à saúde da criança; Barreiras que impedem o acesso à atenção à saúde. Concluiu-se que as famílias exibiram dificuldades para alcançar resolutividade aos problemas de saúde dos filhos, mediante a falta de acesso aos serviços de atenção primária.

It was conducted a qualitative study based on the methodological framework of dialectical hermeneutics, aiming to identify the attribute access from primary care to solve the health problems of children under one year old from the reports of parents and caregivers. Sixteen caregivers of children were involved, all of them seen in the emergency units of Cascavel-PR, in 2010. Four thematic categories were recognized: Family counselling in seeking health care for the child; Absence of reception on the first contact; Presence of risk classification to the child´s health attention; Barriers that block the access to health care. It was conclude that, families showed difficulties to reach the solution for their children´s health, because of the lack of access to primary care services.

Llevó-se a cabo un estudio cualitativo basado en el marco metodológico de la hermenéutica dialéctica, con el objetivo de identificar el atributo de acceso a la atención primaria para resolver los problemas de salud de los niños menores de un año, a partir de los informes de los padres y cuidadores. Se involucró 16 cuidadores de niños atendidos en las unidades de emergencia de Cascavel-PR, en 2010. Cuatro categorías temáticas fueron reconocidas: Asesoramiento de la familia en la búsqueda de atención de salud para el niño; Ausencia de acogimiento al primero contacto; Presencia de clasificación de riesgo para el cuidado de la salud del niño; Barreras que impiden el acceso a la atención sanitaria. Se concluyó que las familias tuvieron dificultades para lograr la solución de los problemas de salud de los niños, mediante la falta de acceso a los servicios de atención primaria.

Epithelioid hemangioendothelioma of the liver

No abstract available.

Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury

PURPOSE: This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5x10(5)) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. RESULTS: Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. CONCLUSION: The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70.

The infection of microvascular endothelial cells with ExoU-producing Pseudomonas aeruginosa triggers the release of von Willebrand factor and platelet adhesion

An increased plasma concentration of von Willebrand factor (vWF) is detected in individuals with many infectious diseases and is accepted as a marker of endothelium activation and prothrombotic condition. To determine whether ExoU, a Pseudomonas aeruginosa cytotoxin with proinflammatory activity, enhances the release of vWF, microvascular endothelial cells were infected with the ExoU-producing PA103 P. aeruginosa strain or an exoU-deficient mutant. Significantly increased vWF concentrations were detected in conditioned medium and subendothelial extracellular matrix from cultures infected with the wild-type bacteria, as determined by enzyme-linked immunoassays. PA103-infected cells also released higher concentrations of procoagulant microparticles containing increased amounts of membrane-associated vWF, as determined by flow cytometric analyses of cell culture supernatants. Both flow cytometry and confocal microscopy showed that increased amounts of vWF were associated with cytoplasmic membranes from cells infected with the ExoU-producing bacteria. PA103-infected cultures exposed to platelet suspensions exhibited increased percentages of cells with platelet adhesion. Because no modulation of the vWF mRNA levels was detected by reverse transcription-polymerase chain reaction assays in PA103-infected cells, ExoU is likely to have induced the release of vWF from cytoplasmic stores rather than vWF gene transcription. Such release is likely to modify the thromboresistance of microvascular endothelial cells.

Uso de desmopresina durante el embarazo en enfermedad de Von Willebrand / Desmopressin use during pregnancy in Von Willebrand diseases

La enfermedad de Von Willebrand es el desorden hemorragíparo más frecuente. Las mujeres constituyen una población particularmente sintomática debido al desafío hemostático de las menstruaciones y el parto. Nosotros revisamos las historias médicas de 54 mujeres con niveles disminuidos de factor von Willebrand (VWF) e historia de sangrado, quienes hubieran usado desmopresina durante el embarazo. No se observaron efectos adversos ni en las mujeres ni en los recién nacidos, incluso en los 5 expuestos a la medicación en el primer trimestre de gestación. No se observaron complicaciones locales asociadas a la colocación del catéter epidural. La DDAVP fue efectiva para prevenir el sangrado posparto. La desmopresina merece ser considerada como la primera elección de tratamiento; en aquellas pacientes con bajo niveles de VWF presentan complicaciones hemorrágicas, incluyendo mujeres embarazadas. Aunque el sangrado posparto aparece en una pequeña proporción de mujeres con VWD, no hay un modo apropiado de identificar quiénes van a sangrar. El uso de profilaxis con DDAVP debería ser tenido en cuenta como una alternativa segura y efectiva.

The von Willebrand disease (VWD) is the most frequent hemorrhagic disorder. Women with VWD are more symptomatic than men because the challenged of menses and delivery. We reviewed the records of 54 women with a low plasmatic VWF level and bleeding history, who had used desmopressin during pregnancy. No adverse effects were observed in mothers or newborns, incluiding those exposed to the drug during the first trimester. No local complication of epidural placement was observed. DDAVP was effective to prevent post-partum hemorrhage. DDAVP merits to be considered as the first choice of therapy, when patients with a previous or current low plasmatic VWF level present bleeding complications, including pregnant women. Although post-partum bleeding will appear in a small proportion of VWD women, there is no accurate way to identify who is going to bleed. The use of DDAVP should be regarded as a highly valuable option.

Sindrome uremico hemolitico: ubicación nosologica actual / Hemolytic uremic syndrome (HUS): an up-dated nosological classification

An up-date of the causes and pathogenesis of the HUS is reported. After more than 40 years of research we are able to define the infectious agents and the toxin involved. The mechanisms and the molecules involved in the non-diarrheal (atypical) entities producing HUS have also been characterized. This new situation allows us to develop a diagnostic algorithm that enables us to better define preventive and therapeutic measures, based on more rational evidence.

Angiosarcoma of scalp: a case report.

Cutaneous angiosarcomas are rare and constitute less than 1% of all malignant mesenchymal tumours. Most angiosarcomas of skin arise in the following clinical settings: 1. face and scalp of elderly 2. following lymphoedema and 3. post radiation. We present a case of an elderly man presenting with scalp lesion of 18 months duration. Histological examination of the biopsy revealed features of an angiosarcoma, which showed imunohistochemical positivity for factor VIII related antigen.

Prevalence and spectrum of von Willebrand disease from western India.

BACKGROUND AND OBJECTIVE: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders in the west. Limited studies from India showed a prevalence of approximately 10 per cent of VWD among the cases with hereditary bleeding disorders. VWD remains an underdiagnosed entity in India. The prevalence of different subtypes of VWD is also not known which is essential for a proper management of these cases. The present study was thus undertaken to know the prevalence of VWD and its various subtypes in the western part of our country. METHODS: A total of 796 consecutive patients presented with various bleeding manifestations were analysed. The initial screening and confirmation tests for the diagnosis of VWD included bleeding time (BT), screening coagulation tests i.e., prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII: C assay, ristocetin-induced platelet aggregation (RIPA) and VWF antigen (VWF:Ag) estimations. VWF multimer analysis, ristocetin cofactor activity (RCOF), VWF collagen binding assay (VWF: CBA), factor VIII : VWF binding assay were also done to classify and subtype these cases. RESULTS: The patients were subtyped as per the International Society of Thrombosis and Haemostasis (ISTH) criteria. Of the 796 patients screened, 58 were diagnosed as VWD. Of the 15 families with a positive family history of bleeding, 26 additional cases were diagnosed as VWD. Majority of the patients were type 3 (59.5%) with severe clinical manifestations, about 18 per cent of type 1 VWD patients were detected in this group while the prevalence of the qualitative variants of VWD i.e., type 2 VWD was found to be 19 per cent and the prevalence of various subtypes were type 2A (9.52%), type 2B (4.76%), type 2M (1.2%), type 2N (3.6%). INTERPRETATION AND CONCLUSION: The high prevalence of type 3 and a low prevalence of type 1 VWD which is in contrast to the western reports, suggests the low awareness of the disease as also the underdiagnosis of the mild cases in our country.

A glance at the von Willebrand factor in dengue virus infection.

To identify the level of von Willebrand factor (vWF) in dengue infection, especially severe DHF, and correlate the increase in vWF with thrombocytopenia, children admitted with dengue fever/DHF were examined for hemoglobin, hematocrit, platelet, and vWF for three consecutive days. Anti-dengue IgM and IgG were determined. Correlations between vWF and thrombocytopenia were analyzed using multivariate analysis. Forty-one patients were eligible for the study; of whom almost three fourths had a secondary infection, as proved serologically. At the beginning of the study, a high level of vWF along with a low platelet count were seen, which seemed to fit the hypothesis that an increase in vWF in the serum will be followed by a decrease in platelets, as a result of the platelet aggregation process in the peripheral blood vessels, predisposed by the immune complex events in DHF. Observations for three consecutive days revealed significant changes of vWF levels (p = 0.000) as well as platelet counts (p = 0.002). However in the context of dengue infections, these changes did not correlate well (p = 0.988). Could there have been a significant correlation if cases were followed for a longer period of time? Being a part of a more comprehensive study, it appeared that in patients with dengue infections, vWF and platelets were not the only factors involved in bleeding, indicating that activation of endothelium is one factor in a multifactorial process.

Expression and characterization of a mutant recombinant blood coagulation factor VIII (rFVIII (m))

In an earlier study, a site directed mutant rFVIII (rFVIII(m), Arg(336) -> Gln(336)) expressed in baculovirus-insect cell (Sf9) system was found to sustain high level activity during incubation at 37 for 24 h while the cofactor activity of normal plasma was declined steadily. In this study, a mutant B-domain deleted rFVIII(m), Arg(336) -> Gln(336) expressed in baculovirus-insect cell (Sf9) system was characterized for its enzymatic and chemical properties. The expressed rFVIII(m) and plasma FVIII (pFVIII) were purified by immunoaffinity column chromatography and identified by Western blot analysis. The partially purified rFVIII(m) exhibited cofactor specific activity of 2.01 X 10(3)units/mg protein. The molecular weight of rFVIII(m) ranged between 40 to 150 kDa with a major band at 150 kDa. Treatment of both rFVIII(m) and pFVIII with thrombin increased their cofactor activity in a similar pattern. Treatment of both the activated rFVIII(m) and native FVIII with APC decreased their cofactor activities, however, the former exhibited a slower decrease than the latter, although no significant difference was present. rFVIII(m) formed a complex with vWF, resulting in a stabilized form, and the lag period of thrombin-mediated activating was extended by vWF association. These results implicated that rFVIII(m) expressed in baculovirus-insect cell system had a comparable capacity as FVIII cofactor activity and might be a good candidate for the FVIII replacement therapy for hemophilia A patients.

von Willebrand factor antigen levels in plasma of patients with malignant breast disease

von Willebrand factor (vWF) is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag) by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 + or - 78 U/dl in patients with cancer, 148.4 + or - 59 U/dl in patients with benign disease and 130.6 + or - 45 U/dl in controls (P<0.005). We also detected a significant increase in the levels of vWF:Ag (P<0.0001) in patients with advanced stages of the disease (stage IV = 263.3 + or - 113 U/dl, stage IIIB = 194.0 + or - 44 U/dl) as compared to those with earlier stages of the disease (stage I = 155.3 + or - 65 U/dl, stage IIA = 146.9 + or - 75 U/dl). In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression

Detection of haemophilia A traits in carriers.

Obligate carriers of haemophilia A and normal women matched for age were studied in order to find a suitable parameter for detection of carriers of haemophilia A. The ratio of factor VIII coagulant activities (F VIIIC) to factor VIII related antigen (F VIII R : Ag) was 0.55 in obligate carriers and 1.0 in non-carrier females.