Study on Protection of Human Umbilical Vein Endothelial Cells from Amiodarone-Induced Damage by Intermedin through Activation of Wnt/ß-Catenin Signaling Pathway.

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti-inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone-induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone-induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone-induced endothelial cell apoptosis, improved amiodarone-induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/ß-catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/ß-catenin inhibitor IWR-1-endo, and si-RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone-induced endothelial injury via activating the Wnt/ß-catenin pathway. Thus, IMD could be used as a potential agent for the treatment of phlebitis.

Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1ß, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

La importancia de la trombosis venosa superficial. A propósito de un caso / The importance of superficial venous thrombosis: Presentation of a case

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Enfermedad de Mondor de la mama: una entidad clínica poco frecuente / Mondor disease of the breast: an uncommon clinical entity

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Cómo reducir los riesgos de la punción venosa periférica con un nuevo catéter de sistema cerrado / How to reduce the risks of the peripheral venous puncture with a new closed system catheter

En el presente artículo se exponen algunas de las complicaciones asociadas a la terapia endovenosa por vía periférica y se describen las características de un catéter de sistema cerrado, que consigue mejorar la seguridad tanto de los pacientes como de los profesionales sanitarios. El catéter dispone en su interior de una membrana antirreflujo que mejora su manipulación, y un novedoso sistema de conexión, con una gran plataforma de fijación, que reduce las complicaciones relacionadas con una sujeción deficiente. Además, está dotado de un dispositivo de seguridad de activación automática que protege de forma inmediata y eficaz, lo que elimina el riesgo de pinchazos accidentales (AU)

This article explains some complications associated with peripheral intravenous venipuncture and also describes the characteristics of a closed system catheter providing an improved safety, both for patient and health care professional. The catheter is designed with a multi-access septum providing a closed-system and with a new hub including a stabilisation platform for better fixation in order to reduce any complication resulting from insufficient fixation. Additionally it is a passive safety device that automatically protects from the risk of needle stick injuries (AU)

Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.

PURPOSE: We investigated E-selectin expression in mice and rabbits with vinorelbine-induced phlebitis and the effect of cimetidine. To find the relationship between E-selectin expression and vinorelbine-induced phlebitis. METHODS: Mouse and rabbit model of vinorelbine-induced phlebitis was established by intravenous infusion of vinorelbine. Pathological observation, molecular-biological determination of E-selectin and protein function of it was evaluated. RESULTS: Grossly, we observed swelling, edema and cord-like vessel changes in mice receiving vinorelbine but only mild edema in mice pretreated with cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine-treated mice and 17 for mice pretreated with cimetidine (P < 0.05). ELISA revealed that rabbits treated with vinorelbine had markedly higher serum contents of E-selectin than normal saline (NS) controls (vinorelbine 1.534 ± 0.449 vs. NS 0.746 ± 0.170 ng/mL, P < 0.05), which was markedly attenuated by cimetidine (cimetidine 0.717 ± 0.468 vs. vinorelbine 1.534 ± 0.449 ng/mL, P < 0.05). Rose Bengal staining assays showed that vinorelbine markedly increased the adhesion rate of neutrophils for endothelial cells (vinorelbine 38.70 ± 8.34% vs. controls 8.93 ± 4.85%, P < 0.01), which, however, was significantly suppressed by cimetidine (9.93 ± 5.91%, P < 0.01 vs. vinorelbine). In E-selectin knockout mice, we found no apparent difference in tail swelling in mice receiving vinorelbine or cimetidine and vinorelbine. CONCLUSIONS: In conclusion, cimetidine attenuates vinorelbine-induced phlebitis in mice probably by suppressing increased expression of E-selectin.

[A case of IgG4-related sclerosing disease with lymphadenopathy and thymus involvement].

The paper describes a case of generalized lymphadenopathy clinically recognized as malignant lymphoma in a 59-year-old woman. Her death occurred from bilateral pneumonia. Autopsy also showed a tumor-like mass in the thymus. On histological examination, the lymph nodes, thymus, and spleen exhibited an intensive polyclonal IgG4+ plasma cell infiltration. Lymphoid plasma cell infiltration with increased count of IgG+ plasma cells, progressive sclerosis, and phlebitis obliterans were found in the pancreas and peripancreatic adipose tissue, liver, kidney, epicardium, thyroid, pituitary, skin, and other organs. The case was regarded as IgG4-related sclerosing disease manifesting itself as lymphadenopathy and thymus enlargement.

[Experimental study of Duffy antigen receptor for chemokines in tissue and the inflammatory reaction of limb with venous hypertension].

OBJECTIVE: To explore the role and mechanism of Duffy antigen receptor for chemokines (DARC) of tissue in promoting the inflammatory reaction of the limb with venous hypertension. METHODS: moral arteriovenous fistula was surgically created to establish the rat model of venous hypertension. A total of 36 SD rats were randomly divided into pcDNA3.1-DARC (Group A), empty plasmid of pcDNA3.1 (Group B) and control (Group C) groups. The animals were sacrificed at Days 14 and 42 post-operation respectively. The expressions of DARC at the RNA and protein level were detected by real-time polymerase chain reaction (PCR) and Western blot. And the serum level of interleukin (IL)-8 was detected by enzyme linked immunosorbent assay (ELISA) and the degrees of apoptosis and leukocytic infiltration of local tissue were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and hematoxylin and eosin (HE) staining. RESULTS: With the elapsing time of venous hypertension, the DARC expression in tissue, the extent of apoptosis and leukocytic infiltration in tissue showed an increasing trend in Groups A and B. Group A was obviously higher than Group B during the corresponding period. And the differences were statistically significant (P < 0.05). The serum levels of IL-8 of Groups A and B showed a decreasing trend. And Group A was obviously lower than Group B. Both groups were higher than the control group. The differences were statistically significant (P < 0.05). CONCLUSIONS: The level of DARC in tissue and the degree of inflammatory reaction of venous hypertension have a positive correlation. And DARC may promote the development of venous hypertension inflammation through augmenting the adhesion and migration of leukocytes.

High-pressure distention of the saphenous vein during preparation results in increased markers of inflammation: a potential mechanism for graft failure.

BACKGROUND: Coronary artery disease is the single leading cause of death in the United States. Commonly it is treated with coronary bypass grafting using the saphenous vein (SV) or internal mammary artery (IMA) as a conduit. Unfortunately, the SV has much lower patency rates compared with the IMA. Several hypotheses exist as to why occlusion occurs more commonly in SV grafts than in IMA grafts. However detailed studies in this area have been limited. This study investigates the effects of pressure distention on inflammation in SV conduit used in coronary artery bypass grafting (CABG). METHODS: Saphenous vein distention pressure was measured intraoperatively during 48 CABG procedures. A segment of SV was excised from the conduit before distention. Because the vein was used for coronary artery grafting, sequential pieces were archived for evaluation. Real-time polymerase chain reaction (RT-PCR) and immunohistochemical analyses were performed to investigate a change in the expression of biomarkers. RESULTS: Upregulation of various biomarkers occurred. These biomarkers included scavenger receptors A and B (SR-A, SR-B), toll-like receptors 2 and 4 (TLR2, TLR4), platelet endothelial cell adhesion molecule (PECAM), vascular cell adhesion molecule (VCAM), and intercellular cell adhesion molecule (ICAM) in segments of SV that were subjected to distention. Immunohistochemical results mirrored RT-PCR findings. A significant correlation was observed between biomarkers and pressure values. CONCLUSIONS: These studies demonstrate that markers of inflammation are upregulated in response to SV distention. The data suggest that the pressure used in graft preparation procedures should be regulated to avoid inflammation and its potential to induce graft failure.

Pathogenic mechanisms in varicose vein disease: the role of hypoxia and inflammation.

AIMS: Although the aetiology of varicose veins remains unknown, recent studies have focused on endothelial cell integrity and function. Among the regulatory factors of vessel tone, synthesises, pro- and anti-inflammatory, adhesion molecules and the transcription factor hypoxia inducible factor-1 alpha (HIF-1alpha), which are responsible for recruiting leukocytes, are very important. METHODS: Investigation in this study focused on the expression of ICAM-1, E-selectin and HIF-1alpha on endothelial cells using immunostaining and RT-PCR in varicose vein specimens compared with controls. RESULTS: Findings of this study showed alterations of the intima, such as focal intimal discontinuity and denudation of endothelium in varicose veins. Based on data derived from immunostaining and RT-PCR, no major differences were identified between ICAM-1 and E-selectin expression in varicose vein specimens compared with controls. In contrast, immunostaining results identified HIF-1alpha expression in five (5/20) varicose vein specimens, whereas no control saphenous vein specimens expressed HIF-1alpha. CONCLUSIONS: These findings could explain other evidence of hypoxia in varicose veins. Finally, results already obtained in this investigation suggest that the process of pathogenesis of varicose veins is not restricted to the role of adhesion molecules.

The in vitro effects of quinupristin/dalfopristin, erythromycin and levofloxacin at low concentrations on the expression of different cell adhesion molecules on the surface of endothelial cells (Eahy926).

OBJECTIVES: Infusion phlebitis is a common clinical problem associated with some antimicrobial agents. The pathomechanism of infusion phlebitis has not yet been elucidated, however, it has been proposed that chemical irritation of the endothelium leads to subsequent sterile inflammation with recruitment and migration of leukocytes. In the present study, cultured endothelial cells were exposed to antibiotics at clinically relevant concentrations to detect changes in various cell surface markers. METHODS: Cells from the endothelial hybrid cell line Eahy926 were exposed to quinupristin/dalfopristin, erythromycin and levofloxacin at increasing concentrations (3, 10, 30 and 100 mg/l) for 24 h. After washing, the cells were marked with monoclonal antibodies against different cell surface antigens (intercellular cell adhesion molecule-1 [ICAM-1], platelet-endothelial cell adhesion molecule-1 [PECAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, L-selectin, CD34, alpha(2), alpha(5), beta(1) and beta(4) integrin chains and analysed by flow cytometry. For comparison, cells were either untreated or incubated with tumor necrosis factor alpha (TNF-alpha) at a concentration of 10 ng/ml and analysed for ICAM-1, VCAM-1 and E-selectin expression. RESULTS: There was an increase in ICAM-1 expression on endothelial cells with increasing concentrations of quinupristin/dalfopristin. VCAM-1, E-selectin, L-selectin and CD34 showed an excursive upregulation at the concentration of 100 mg/l only, while no consistent changes were observed for PECAM-1 and the integrins. Markedly less prominent changes in the expression of these adhesion molecules were seen with erythromycin while no relevant changes at all occurred with levofloxacin. The absolute change in ICAM-1 activation with quinupristin/dalfopristin at 100 mg/l (34.4%) was less pronounced than that observed after stimulation with TNF-alpha (>80%). CONCLUSIONS: The results of this study indicate that antibiotics with a high potential for local cytotoxicity may cause an inflammatory response by endothelial cells even at rather low concentrations. The increase in expression of cell surface markers involved in cell-cell interaction could be an important mechanism in the development of infusion phlebitis.

Neutrophilic phlebitis is characteristic of intestinal Behçet's disease and simple ulcer syndrome.

AIM: To characterize the histological features of intestinal Behcet's disease and simple ulcer syndrome and to clarify the possible mechanisms involved in their development by analysing the type of inflammatory infiltrates in the diseased intestine and the expression of adhesion molecules on endothelial cells. METHODS AND RESULTS: Tissue samples from 10 patients diagnosed as having intestinal Behcet's disease or simple ulcer syndrome were studied. Immunohistochemical studies were performed on paraffin-embedded tissue using a labelled streptavidin-biotin method. In all cases, phlebitis was remarkably seen in submucosal inflammatory lesions, but the adjacent arteries were not affected. Inflammatory infiltrates around the affected vessels consisted of neutrophils and mononuclear cells, and neutrophils predominated over CD68+ macrophages and lymphocytes. The majority of mononuclear cells were CD3+ T cells, and CD4+ cells were more frequent than CD8+ T cells. As for adhesion molecule expression, intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1, was expressed in most endothelial cells of the vessels with phlebitis, some of which were also positive for HLA-DR. CONCLUSION: Neutrophilic phlebitis may be involved in the pathogenesis of intestinal Behcet's disease and simple ulcer syndrome.

Servicio enfermero ofertado en una unidad de hospitalización de Nefrología / Nursing services offered in a hospital unit for nephrology

La aportación de la disciplina enfermera se concreta en la prestación de cuidados, y el proceso de enfermería permite reconocer la aportación de las enfermeras a los resultados de salud del paciente. En el Servicio Vasco de Salud (Osakidetza) se trabaja con el programa informático Zaineri, que recoge bajo soporte informático todos los cuidados y actividades que la enfermera realiza en la práctica diaria. Es fundamental que en las unidades se analice qué servicio estamos ofertando a nuestros clientes. Por ello el objetivo de este trabajo es describir el trabajo que realizan las enfermeras de Nefrología, a través del análisis de las necesidades alteradas de los pacientes ingresados y de los diagnósticos de enfermería planteados durante el año 2002. Material y método: estudio descriptivo de los planes de cuidados de los pacientes ingresados en la unidad entre el 1 de Enero de 2002 y el 31 de Diciembre de 2002. Resultados: del total de necesidades planteadas, el 65,30% pertenecen al área independiente de Enfermería mientras un 34,70% pertenecen al área interdependiente. Los diagnósticos derivados de Necesidades Humanas corresponden al 56,63% sobre el total, mientras aquellos diagnósticos (complicaciones) derivados de los sistemas, tienen un porcentaje del 43,37% (AU)

Nursing skills are offering a number of services to the patient, including its care. Nursing processes allow the identification of results on the patient´s health. In the Vasc Service of Health (Osakidetza) we work with the programme Zaineri that collects all processes done by nurses in their daily activities. Is is important to analyze what kind of service we are offering to our clients, therefore, the aim of this work is to describe the work done by nurses of nephrology through the analysis of the patient´s needs and nursing diagnosis during 2002. Material and methods: descriptive study of the care plan for patients from Jan 1st 2002 to Dec 31st 2002. Results: from all needs analyze, 65% belong to the nurse independent area, while 34% belong to the interdependent area. Diagnosis obtained from human needs are 57% while those obtained from systems are 43% (AU)

Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis.

OBJECTIVES: Antimicrobial agents are important risk factors for infusion phlebitis, but the risk varies between different antibiotics. Erythromycin and dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic effects on cultured endothelial cells. The pathogenesis of infusion phlebitis is unclear, but chemical toxicity is thought to lead to inflammation and subsequent thrombosis. In the present study, endothelial cells were exposed to antibiotics at the range of concentrations used for intravenous administration, followed by analysis of pro-inflammatory and pro-coagulant surface molecules. METHODS: Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing. After 5 or 24 h additional incubation, cells were analysed for E-selectin (CD62E), tissue factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow cytometry. RESULTS: Despite constitutive expression of ICAM-1 (34%) in HUVEC, 6250 mg/L of dicloxacillin or erythromycin significantly increased the number of cells with ICAM-1 expression by 37% and 30%, respectively. In contrast, cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background levels. A similar pattern was seen with the endothelial cell line EaHy926. The E-selectin and TF density were not affected by the antibiotics examined. CONCLUSIONS: The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1. This is a novel finding in the pathogenesis of infusion phlebitis.

Purification and characterization of a novel 88 kDa protein from serum and vitreous of patients with Eales' disease.

Eales' disease is a perivasculitis that affects the peripheral retina of young adults and results in recurrent vitreous hemorrhage. Although increased oxidative stress and decreased antioxidant defense have been reported to be associated with Eales' disease, the exact cause for the disease and its pathogenesis are not known. Here is reported the identification, purification and characterization of a new protein from the serum and vitreous of patients with Eales' disease. This protein was purified using preparative electrophoresis and HPLC. The purified protein had a retention time of 9.2 min in RP HPLC. Its molecular weight as determined by gel permeation chromatography was 88 kDa hence, it was termed as 88 kDa protein. Alcian blue and Schiffs staining revealed 88 kDa protein to be a glycoprotein. Proteins purified from both serum and vitreous exhibited anti lipid peroxidation effect on erythrocyte when added during in vitro assay of thiobarbuteric acid reactive substances (TBARS). In addition to this property the protein also has Fe(2+)sequestering effect. The anti TBARS activity of 88 kDa protein was completely inhibited by 0.1 m M concentration of parachlromercuric benzoate (PCMB) and 5,5' dithiobis(2-nitrobenzoic acid) DTNB. The total thiol content (cysteine) of the purified 88 kDa protein was found to be 8% by mass. Eighty eight kDa protein from both the sources namely vitreous and serum are immunologically identical when studied using polyclonal antibodies raised in goat against purified serum protein. The N terminal sequence of 88 kDa protein by automated Edman's degradation chemistry is A D D P N S L S P S A F A E A L A L L R D S X L A R F V. The protein and DNA data base search revealed no match to 88 kDa protein and hence this was considered as unique protein. Further knowledge on the in vivo function of 88 kDa protein is very important to understand its role in the pathogenesis of Eales' disease.

Lymphohistiocytic and granulomatous phlebitis in penile lichen sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory disease of unknown etiology that may affect the genital and/or extragenital skin of individuals of either sex at all ages. In boys, the prepuce is the most common site of involvement. The diagnostic criteria of LS include the presence of inflammatory infiltrates mainly composed of T lymphocytes. We report on two cases of LS of the prepuce because of the unusual feature of lymphocytic (CD45RO+ and CD20+), histiocytic (CD68+), and granulomatous phlebitis. This lesion was not present in a group of another 18 cases of childhood penile LS. We have not been able to find any references describing and illustrating inflammatory involvement of the dermal vein walls in LS. Unlike the data reported in the literature, the dermal inflammatory infiltrates of these two cases showed a similar proportion of B and T lymphocytes in addition to frequent CD68+ histiocytes.

[Inflammation and subcutaneous calcification of venous origins]. / Inflammation et calcifications sous-cutanees d'origine veineuse.

There have been few descriptions up to now of calcifications in chronic venous insufficiency, other than in cases where venous insufficiency is complicated be severe trophic disorders and in particular ulcers. It was therefore felt to be of interest to assess the presence of calcifications in venous insufficiency without trophic disorders. This study was based upon 40 cases recruited in the phlebology out-patient clinic of the Notre Dame de Bon Secours Hospital. Calcifications of the lower limbs were found in 7 patients, either by palpation, routine X-rays or ultrasonography. The etiopathogenic mechanisms of this occurrence not having been elucidated, a number of hypotheses are put forward on the basis of acquired data concerning: the process of formation of ectopic calcifications, changes in subcutaneous tissue, the ultimate consequences of venous stasis and of raised venous pressure, due essentially to anoxia and inflammation. One hypothesis can thus be put forward: that of inflammation. The release of cells and mediators of inflammation, the production of free radicals, causing damage to the cells of connective tissue and to the organic framework (collagen fibres) and changes in the chemical environment could combine to result in the formation of calcifications in subcutaneous tissue. However, inflammation has not been proven to be the primary etiological factor.

Heterotopic Tc-99m MDP uptake secondary to phlebitis.

A patient with blastomycosis complained of pain in his lower back after the administration of amphotericin B and parenteral alimentation via a femoral venous catheter. A bone scan that was performed to exclude bony involvement with blastomycosis showed abnormal tracer accumulation in the right paravertebral region. Computed tomography revealed the venous catheter to lie in the right ascending lumbar vein. There was calcification of a portion of the right psoas muscle. In addition, the epidural venous plexus was calcified from L2 to L4. It was this dystrophic calcification that caused the heterotopic accumulation of bone tracer.

C-reactive protein levels in venous ulceration: an indication of infection?

The role of bacteria in the pathogenesis of venous ulcers is unclear. It is difficult to be clinically certain of the presence of infection. Routine bacteriology is often unhelpful, and any simple investigation that improves diagnosis in this situation would be of value. C-reactive protein (CRP) levels are useful in detecting infection in other situations, and they may be of value in this context as well. C-reactive protein levels were measured in 50 patients with venous leg ulcers and in 20 patients with active venous eczema. There was no elevation of CRP levels in patients with eczema alone, nor in the majority of patients with ulcers. Sixteen patients had raised CRP levels: 7 had clinically obvious infection, and 9 had erythematous skin of uncertain cause surrounding their ulcers. All had positive bacterial cultures from the ulcer base, with beta-hemolytic streptococci the main contaminant. Treatment with an appropriate antibiotic reduced CRP levels to normal, cleared the bacteria from the ulcers, and was associated with resolution of erythema. CRP levels appear to distinguish between infectious and inflammatory causes of erythema in patients with gravitational disease.