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Circulating Angiopoietins-1 and -2, Angiopoietin Receptor Tie-2 and Vascular Endothelial Growth Factor-A as Biomarkers of Acute Myocardial Infarction: a Prospective Nested Case-Control Study
Carlos Iribarren, Bruce H Phelps, Jeanne A Darbinian, Edward R McCluskey, Charles P Quesenberry, Evangelos Hytopoulos, Joseph H Vogelman, Norman Orentreich
BMC Cardiovascular Disorders , 2011, DOI: 10.1186/1471-2261-11-31
Abstract: We performed a case-control study (nested within a large cohort of persons receiving care within Kaiser Permanente of Northern California) including 695 AMI cases and 690 controls individually matched on age, gender and race/ethnicity.Median [inter-quartile range] serum concentrations of vascular endothelial growth factor-A (VEGF-A; 260 [252] vs. 235 [224] pg/mL; p = 0.01) and angiopoietin-2 (Ang-2; 1.18 [0.66] vs. 1.05 [0.58] ng/mL; p < 0.0001) were significantly higher in AMI cases than in controls. By contrast, endothelium-specific receptor tyrosine kinase (Tie-2; 14.2 [3.7] vs. 14.0 [3.1] ng/mL; p = 0.07) and angiopoietin-1 levels (Ang-1; 33.1 [13.6] vs. 32.5 [12.7] ng/mL; p = 0.52) did not differ significantly by case-control status. After adjustment for educational attainment, hypertension, diabetes, smoking, alcohol consumption, body mass index, LDL-C, HDL-C, triglycerides and C-reactive protein, each increment of 1 unit of Ang-2 as a Z score was associated with 1.17-fold (95 percent confidence interval, 1.02 to 1.35) increased odds of AMI, and the upper quartile of Ang-2, relative to the lowest quartile, was associated with 1.63-fold (95 percent confidence interval, 1.09 to 2.45) increased odds of AMI.Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors.Angiogenesis, the induction and growth of new blood vessels from pre-existing ones, is a complex, highly regulated system essential for embryonic development, normal physiological growth, wound healing and tumor progression [1,2]. In addition, it is now well-documented that angiogenic factors are up-regulated (as a compensatory mechanism to increase collateral circulation) in the context of acute skeletal muscle [3] and myocardial ischemia [4-6]. Atherosclerotic vessels often present intra-plaque angiogenesis, a phenomenon that has been hypothesized to contribute to progression and eventual rupture of coronary artery lesions [7,8]. It is therefore plausible t
Can Platelet Indices Be New Biomarkers for Severe Endometriosis?  [PDF]
Sümeyra Nergiz Avcio?lu,Sündüz ?zlem Altinkaya,Mert Kü?ük,Selda Demircan-Sezer,Hasan Yüksel
ISRN Obstetrics and Gynecology , 2014, DOI: 10.1155/2014/713542
Abstract: Objective. The aim of this study was to investigate whether platelet indices-mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) would be useful as noninvasive biomarkers for determining the severity of endometriosis. Methods. A retrospective review of the medical charts of 164 patients diagnosed with endometriosis and who were operated on between 2001 and 2013 was performed. The stage of endometriosis was determined according to revised American Society for Reproductive Medicine criteria. Results. In patients with advanced endometriosis (Stages 3-4), PLT, PCT levels were found to be significantly higher and MPV, PDW values to be significantly lower when compared to initial endometriosis (Stages 1-2). In addition, there was a significant positive correlation between PLT (r: 0.800, P: 0.001) and PCT (r: 0.727, P: 0.002) and the inflammatory marker white blood cell count (WBC). Conclusion. Our finding may not sufficient for employing platelet indices solely in this differential diagnosis, but our finding could provide a suggestion for clinical physicians so that attention is paid to the value of platelet indices and that these may be taken into account when making decisions about the initial or advanced stages of endometriosis. 1. Introduction Endometriosis is one of the most important benign chronic diseases affecting 6–10% of women of reproductive age, being mainly associated with pelvic pain, adhesion formation, and infertility. Endometriosis is characterized by the ectopic presence of endometrial stroma and epithelium [1, 2]. It can be classified into four stages: minimal, mild, moderate, and severe [3]. More advanced endometriosis can be deeply invasive or can present as ovarian endometriotic cysts (endometrioma) [4]. Many theories have been set forth about endometriosis. The implantation theory of Sampson, the coelomic metaplasia theory of Mayer, and the theory of induction constitute the three classic theories that attempt to explain the origin of endometriosis [5, 6]. However, classic theories have failed to establish a definitive pathogenetic mechanism for endometriosis. Recent studies addressing the matter of genetic predisposition have reported that genetic abnormalities may contribute to the development of endometriosis [7]. Besides genetics, growing evidence indicates the significant role played by immunological and inflammatory factors in the development of endometriosis [8]. In particular, chronic pelvic inflammation is a hallmark of endometriosis pathophysiology and thus inflammation is a factor that
Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2
Vicky PKH Nguyen, Stephen H Chen, Jason Trinh, Harold Kim, Brenda L Coomber, Daniel J Dumont
BMC Cell Biology , 2007, DOI: 10.1186/1471-2121-8-10
Abstract: BmLEC, bmVEC and bmAEC cell populations all express Tie-2 and were shown to express the appropriate cellular markers Prox-1, VEGFR3, and Neuropilin-1 that define the particular origin of each preparation. We showed that while bmLECs responded slightly more readily to angiopoietin-2 (Ang2) stimulation, bmVECs and bmAECs were more sensitive to Ang1 stimulation. Furthermore, exposure of bmLECs to Ang2 induced marginally higher levels of proliferation and survival than did exposure to Ang1. However, exposure to Ang1 resulted in higher levels of migration in bmLECs than did to Ang2.Our results suggest that although both Ang1 and Ang2 can activate the Tie-2 receptor in bmLECs, Ang1 and Ang2 may have distinct roles in mesenteric lymphatic endothelial cells.Tek or Tie-2 is the receptor tyrosine kinase (RTK) for the angiopoietin family of ligands (Ang1, 2, 3, and 4). The role of Tie-2 in endothelial cells has been extensively studied over the years, and the discovery of impaired lymphatic vessel patterning and function in Angiopoietin-2 (Ang2) knockout mice has since added extra complexity to this growing field [1]. Tie-2 has also been shown to be expressed in lymphatic endothelial cells [2]. In vivo studies using slow-release pellets of an engineered form of Ang1, cartilage oligomeric matrix protein-Angiopoietin-1 (COMP-Ang1), have further showed induction of angiogenesis and ectopic lymphangiogenesis in mouse cornea [2]. In addition, over-expression of Ang1 in the skin of mouse ears via recombinant adeno-associated virus gene delivery induced lymphatic endothelial cell proliferation, lymphatic vessel enlargement, sprouting, and branching [3].Prior to the discovery of the involvement of Tie-2 and its ligands in lymphangiogenesis, the role of Tie-2 and it ligands in angiogenesis was the focus of mouse genetic studies. Ang1 deficient mice exhibited phenotypes similar to those of Tie-2 knockout mice. These phenotypes included impaired myocardial trabeculation and endocardial d
Peritoneal and serum interleukin-18 levels are not increased in women with minimum or mild endometriosis
Glitz, C.;Souza, C.A.;Rodini, G.P.;Genro, V.;Bilibio, J.P.;Senger, M.;Cunha-Filho, J.S.;
Brazilian Journal of Medical and Biological Research , 2009, DOI: 10.1590/S0100-879X2009001100007
Abstract: interleukin-18 (il-18) is a cytokine that belongs to the il-1 family. endometriosis is strongly associated with sub-fertility, and affects about 15% of women of reproductive age. il-18 may favor the progression of endometriosis. the objective of the present study was to determine the concentration of il-18 in the serum and peritoneal fluid of infertile women with endometriosis. forty infertile and 25 fertile women were screened in a teaching hospital. thirty-four infertile patients with minimal or mild endometriosis and 22 fertile controls were enrolled in the study. the primary outcome was the estimate of il-18 levels and the secondary outcome was the correlation between serum and peritoneal levels of il-18. there were no differences between the two groups regarding age, body mass index and levels of peritoneal fluid il-18 (mean ± sd): 290.85 ± 173.02 pg/ml for infertile women vs 374.21 ± 330.15 pg/ml for controls; or serum il-18: 391.07 ± 119.71 pg/ml for infertile women vs 373.42 ± 129.11 pg/ml for controls. however, a positive association was found between serum and peritoneal il-18 levels in patients with endometriosis: r = 0.794, p = 0.0001. all measurements were carried out at the same time by the human il-18 immuno assay elisa kit (mbl co. ltd., japan). the present study did not find evidence supporting the hypothesis that il-18 levels are associated with infertility in women with minimal and mild endometriosis, although a positive correlation was detected in these women between peritoneal and serum levels of il-18.
ENDOMETRIOSIS
DIAA E. E. RIZK
The Professional Medical Journal , 2005,
Abstract: Endometriosis is a common gynecological disorder but above all a confusingone. Despite massive volumes of literature, the cause is still unknown, none of the pathogenic mechanisms suggestedconvincingly explain symptomatology and indeed most lines of investigations have yielded contradictory results. Notsurprisingly, therefore, there are many different approaches to treatment and attempts to provide rational therapy hasnot always been rewarded by permanent cure. Against this background of diagnostic and therapeutic dilemmas,endometriosis is likely to be encountered in general practice because the disease frequently affects other organsystems. Since the management of endometriosis is dependant on a basic understanding of the gynecological aspectsof the disease, an attempt will be made to describe this condition here.
Endometriosis
N Matebese
Continuing Medical Education , 2009,
Abstract: Endometriosis is a benign disease defined as the presence of endometrial glands and stroma outside the uterus. Its pathogenesis and optimal management remain controversial, and its true prevalence is unknown. Endometriosis can be debilitating and can affect the psychosocial functioning of women. It is estimated to occur in 1 - 7% of women undergoing bilateral tubal ligation, in 12 - 32% of women in the reproductive age group undergoing laparoscopy for pelvic pain, and in about 20 - 40% of infertile women.
ENDOMETRIOSIS
Shaheena Asif
The Professional Medical Journal , 1999,
Abstract: A prospective study was carried out during 1 September 1995 to 31 August in private patients of Sir Ganga sl stRam Hospital, Lahore. The purpose was to study the safety and efficacy of decapeptyl in the treatment ofendometriosis. Six women with proven endometriosis were treated with a delayed release preparation of thesuper active agonist D. Trp-6-LH-RH in biodegradable microcapsules, administered intra-muscularly atintervals of 30 days for a period of 6 months. All patients showed clinical improvement and reduction instage and score of endometriosis. Hot flushes and dyspareunia were the main side effects. Resumption ofmenses occurred in all patients after the last injection. Results demonstrate that a long lasting, reversiblehypogonadism can be induced in cyclic women by intramuscular injections of D. Trp-6-LH-RHmicrocapsules at monthly intervals. This simple and conventient treatment should be useful in treatingendomentriosis.
Mitotic and antiapoptotic effects of nanoparticles coencapsulating human VEGF and human angiopoietin-1 on vascular endothelial cells
Khan AA, Paul A, Abbasi S, Prakash S
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S15054
Abstract: otic and antiapoptotic effects of nanoparticles coencapsulating human VEGF and human angiopoietin-1 on vascular endothelial cells Original Research (4462) Total Article Views Authors: Khan AA, Paul A, Abbasi S, Prakash S Published Date May 2011 Volume 2011:6 Pages 1069 - 1081 DOI: http://dx.doi.org/10.2147/IJN.S15054 Afshan Afsar Khan, Arghya Paul, Sana Abbasi, Satya Prakash Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering Faculty of Medicine, McGill University Montreal, Québec, Canada Background: Research towards the application of nanoparticles as carrier vehicles for the delivery of therapeutic agents is increasingly gaining importance. The angiogenic growth factors, human vascular endothelial growth factor (VEGF) and human angiopoietin-1 are known to prevent vascular endothelial cell apoptosis and in fact to stimulate human vascular endothelial cell (HUVEC) proliferation. This paper aims to study the combined effect of these bioactive proteins coencapsulated in human serum albumin nanoparticles on HUVECs and to evaluate the potential application of this delivery system towards therapeutic angiogenesis. Methods and results: The angiogenic proteins, human VEGF and human angiopoietin-1, were coencapsulated in albumin nanoparticles for better controlled delivery of the proteins. The application of a nanoparticle system enabled efficient and extended-release kinetics of the proteins. The size of the nanoparticles crosslinked with glutaraldehyde was 101.0 ± 0.9 nm and the zeta potential was found to be -18 ± 2.9 mV. An optimal concentration of glutaraldehyde for the nanoparticle coating process was determined, and this provided stable and less toxic nanoparticles as protein carriers. The results of the study indicate that nanoparticles crosslinked with glutaraldehyde produced nanoparticles with tolerable toxicity which provided efficient and controlled release of the coencapsulated proteins. The nanoparticles were incubated for two weeks to determine the release profiles of the proteins. At the end of the two-week incubation period, it was observed that 49% ± 1.3% of human angiopoietin-1 and 59% ± 2.1% of human VEGF had been released from the nanoparticles. The proliferation and percent apoptosis of the HUVECs in response to released proteins was observed. Conclusion: The results indicate that the released proteins were biologically active and the combined application of both the proteins demonstrated a significant highly proliferative and antiapoptotic effect on HUVECs as compared with the effect demonstrated by the individual proteins released. These studies could serve as a basis to encourage further research into the potential in vivo application of these protein-loaded nanoparticles in the field of therapeutic angiogenesis.
Maternal Biomarkers of Endothelial Dysfunction and Preterm Delivery  [PDF]
Xinhua Chen, Theresa O. Scholl
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085716
Abstract: Background Endothelial dysfunction is key to the development of atherosclerosis. Preterm delivery foreshadows later maternal cardiovascular disease (CVD), but it is not known if endothelial dysfunction also occurs. We prospectively measured circulating biomarkers of endothelial dysfunction in pregnant women with preterm or term delivery. Methods We conducted a case-control study nested within a large prospective epidemiological study of young, generally healthy pregnant women. Women who delivered preterm (<37 completed weeks gestation, n = 240) and controls who delivered at term (n = 439) were included. Pregnancies complicated by preeclampsia were analyzed separately. Circulating endothelial dysfunction biomarkers included soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin). Results Elevated levels of sICAM-1 and sVCAM-1 were positively associated with preterm delivery independent of usual risk factors. At entry (~16 wks), the adjusted odds ratio (AOR) was 1.73 (95% confidence interval (CI) 1.09–2.74) for the highest quartile of sICAM-1 versus the lowest quartile and for sVCAM-1 the AOR was 2.17 (95% CI 1.36–3.46). When analysis was limited to cases with a spontaneous preterm delivery, the results were unchanged. Similar results were obtained for the 3rd trimester (~30 wks). Elevated sE-selectin was increased only in preterm delivery complicated by preeclampsia; risk was increased at entry (AOR 2.32, 95% CI 1.22–4.40) and in the 3rd trimester (AOR 3.37, 95% CI 1.78–6.39). Conclusions Impaired endothelial function as indicated by increased levels of soluble molecules commonly secreted by endothelial cells is a pathogenic precursor to CVD that is also present in women with preterm delivery. Our findings underscore the need for follow-up studies to determine if improving endothelial function prevents later CVD risk in women.
Mitotic and antiapoptotic effects of nanoparticles coencapsulating human VEGF and human angiopoietin-1 on vascular endothelial cells  [cached]
Khan AA,Paul A,Abbasi S,Prakash S
International Journal of Nanomedicine , 2011,
Abstract: Afshan Afsar Khan, Arghya Paul, Sana Abbasi, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering Faculty of Medicine, McGill University Montreal, Québec, CanadaBackground: Research towards the application of nanoparticles as carrier vehicles for the delivery of therapeutic agents is increasingly gaining importance. The angiogenic growth factors, human vascular endothelial growth factor (VEGF) and human angiopoietin-1 are known to prevent vascular endothelial cell apoptosis and in fact to stimulate human vascular endothelial cell (HUVEC) proliferation. This paper aims to study the combined effect of these bioactive proteins coencapsulated in human serum albumin nanoparticles on HUVECs and to evaluate the potential application of this delivery system towards therapeutic angiogenesis.Methods and results: The angiogenic proteins, human VEGF and human angiopoietin-1, were coencapsulated in albumin nanoparticles for better controlled delivery of the proteins. The application of a nanoparticle system enabled efficient and extended-release kinetics of the proteins. The size of the nanoparticles crosslinked with glutaraldehyde was 101.0 ± 0.9 nm and the zeta potential was found to be -18 ± 2.9 mV. An optimal concentration of glutaraldehyde for the nanoparticle coating process was determined, and this provided stable and less toxic nanoparticles as protein carriers. The results of the study indicate that nanoparticles crosslinked with glutaraldehyde produced nanoparticles with tolerable toxicity which provided efficient and controlled release of the coencapsulated proteins. The nanoparticles were incubated for two weeks to determine the release profiles of the proteins. At the end of the two-week incubation period, it was observed that 49% ± 1.3% of human angiopoietin-1 and 59% ± 2.1% of human VEGF had been released from the nanoparticles. The proliferation and percent apoptosis of the HUVECs in response to released proteins was observed.Conclusion: The results indicate that the released proteins were biologically active and the combined application of both the proteins demonstrated a significant highly proliferative and antiapoptotic effect on HUVECs as compared with the effect demonstrated by the individual proteins released. These studies could serve as a basis to encourage further research into the potential in vivo application of these protein-loaded nanoparticles in the field of therapeutic angiogenesis.Keywords: growth factors, encapsulation, nanoparticles, nanobiotechnology, angiogenesis, regenerat
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