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Blood Circulation (blood + circulation)
Selected AbstractsMechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular diseaseACTA PHYSIOLOGICA, Issue 1 2010D. Lominadze Abstract Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. [source] Enteric-formulated lactoferrin was more effectively transported into blood circulation from gastrointestinal tract in adult ratsEXPERIMENTAL PHYSIOLOGY, Issue 6 2006Takashi Takeuchi We have previously demonstrated that intestinally infused bovine lactoferrin (bLF) is transported into the blood circulation via the lymphatic pathway, not via the portal circulation. Therefore, in the present study, we further investigated whether intragastrically infused enteric-formulated bLF (EF-bLF) was more efficiently absorbed than bLF from the intestine in adult rats. The rats were randomly divided into three groups: 30 and 300 mg kg,1 non-enteric-formulated bLF (non-EF-bLF) groups and a 30 mg kg,1 EF-bLF group. Thoracic lymph was collected from a thoracic lymph duct under general anaesthesia. Bovine lactoferrin was infused into the stomach or duodenal lumen via a needle for a period of over 1 min in a volume of 1 ml kg,1. The bLF transported into the lymph was assayed quantitatively by double-antibody enzyme-linked immunosorbent assay (ELISA). Following the intragastric administration of bLF, the three groups showed almost the same lymph flow, but the bLF concentration in the lymph fluid in the EF-bLF group increased significantly and peaked 3 h after administration. With intraduodenal administration, the bLF concentration in the lymph fluid of the higher non-EF-bLF group was significantly higher than those of the other groups. The amount of absorbed bLF in the EF-bLF group was, however, about 10 times higher than that in the lower non-EF-bLF group, when it was administered intragastrically. These data show that enteric-formulated bLF is less susceptible to gastric pepsin and is more efficiently absorbed from the intestine than is non-enteric-formulated bLF. [source] De novo synthesis, uptake and proteolytic processing of lipocalin-type prostaglandin D synthase, ,-trace, in the kidneysFEBS JOURNAL, Issue 23 2009Nanae Nagata Lipocalin-type prostaglandin D synthase (L-PGDS) is a multifunctional protein that produces prostaglandin D2 and binds and transports various lipophilic substances after secretion into various body fluids as ,-trace. L-PGDS has been proposed to be a useful diagnostic marker for renal injury associated with diabetes or hypertension, because the urinary and plasma concentrations are increased in patients with these diseases. However, it remains unclear whether urinary L-PGDS is synthesized de novo in the kidney or taken up from the blood circulation. In crude extracts of monkey kidney and human urine, we found L-PGDS with its original N-terminal sequence starting from Ala23 after the signal sequence, and also its N-terminal-truncated products starting from Gln31 and Phe34. In situ hybridization and immunohistochemical staining with monoclonal antibody 5C11, which recognized the amino-terminal Ala23,Val28 loop of L-PGDS, revealed that both the mRNA and the intact form of L-PGDS were localized in the cells of Henle's loop and the glomeruli of the kidney, indicating that L-PGDS is synthesized de novo in these tissues. However, truncated forms of L-PGDS were found in the lysosomes of tubular cells, as visualized by immunostaining with 10A5, another monoclonal antibody, which recognized the three-turn ,-helix between Arg156 and Thr173. These results suggest that L-PGDS is taken up by tubular cells and actively degraded within their lysosomes to produce the N-terminal-truncated form. Structured digital abstract ,,MINT-7266187: L-PGDS (uniprotkb:P41222) and Cathepsin D (uniprotkb:Q4R4P0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7266176: L-PGDS (uniprotkb:P41222) and Cathepsin B (uniprotkb:Q4R5M2) colocalize (MI:0403) by fluorescence microscopy (MI:0416) [source] Measurements in the Magnetic FieldGERMAN RESEARCH, Issue 2 2005Wolfgang Bauer Prof. Dr. Dr. Doctors are banking on the new possibilities offered by magnetic resonance imaging to give them a better view of the blood circulation in the human cardiac muscle [source] Progress toward liver-based gene therapyHEPATOLOGY RESEARCH, Issue 4 2009Takeshi Suda The liver is involved in the synthesis of serum proteins, regulation of metabolism and maintenance of homeostasis and provides a variety of opportunities for gene therapy. The enriched vasculature and blood circulation, fenestrated endothelium, abundant receptors on the plasma membranes of the liver cells, and effective transcription and translation machineries in the hepatocytes are some unique features that have been explored for delivery, and functional analysis, of genetic sequences in the liver. Both viral and non-viral methods have been developed for effective gene delivery and liver-based gene therapy. This review describes the fundamentals of gene delivery, and the preclinical and clinical progress that has been made toward gene therapy using the liver as a target. [source] Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di- tert -butyl 4-nitrophenol, in grafted human skinJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2006Lynn K. Pershing Abstract Disposition and uptake/elimination profiles of topical 2,6-di- t -butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 µg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 ± 602 µg cm,3, and ,30 and ,300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0,24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hypothalamic sensing of circulating lactate regulates glucose productionJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Andrea Kokorovic Abstract Emerging studies indicate that hypothalamic hormonal signalling pathways and nutrient metabolism regulate glucose homeostasis in rodents. Although hypothalamic lactate-sensing mechanisms have been described to lower glucose production (GP), it is currently unknown whether the hypothalamus senses lactate in the blood circulation to regulate GP and maintain glucose homeostasis in vivo. To examine whether hypothalamic sensing of circulating lactate is required to regulate GP, we infused intravenous (i.v.) lactate in the absence or presence of inhibition of central/hypothalamic lactate-sensing mechanisms in normal rodents. Inhibition of central/hypothalamic lactate-sensing mechanisms was achieved by three independent approaches. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of i.v. and central/hypothalamic administrations on glucose metabolism in vivo. In the presence of physiologically relevant increases in the levels of plasma lactate, inhibition of central lactate-sensing mechanisms by lactate dehydrogenase inhibitor oxamate (OXA) or ATP-sensitive potassium channels blocker glibenclamide increased GP. Furthermore, direct administration of OXA into the mediobasal hypothalamus increased GP in the presence of similar elevation of circulating lactate. Together, these data indicate that hypothalamic sensing of circulating lactate regulates GP and is required to maintain glucose homeostasis. [source] Compression therapy promotes proliferative repair during rat Achilles tendon immobilizationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2010Nikos Schizas Abstract Achilles tendon ruptures are treated with an initial period of immobilization, which obstructs the healing process partly by a reduction of blood circulation. Intermittent pneumatic compression (IPC) has been proposed to enhance tendon repair by stimulation of blood flow. We hypothesized that daily IPC treatment can counteract the deficits caused by 2 weeks of immobilization post tendon rupture. Forty-eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon transection, were divided in three equal groups. Group A was allowed free cage activity, whereas groups B,C were immobilized at the operated hindleg. Group C received daily IPC treatment. Two weeks postrupture the rats were euthanatized and the tendons analyzed with tensile testing and histological assessments of collagen organization and collagen III-LI occurrence. Immobilization significantly reduced maximum force, energy uptake, stiffness, tendon length, transverse area, stress, organized collagen diameter and collagen III-LI occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free mobilization. IPC treatment improved maximum force 65%, energy 168%, organized collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150% compared to immobilization only. The results confirm that immobilization impairs healing after tendon rupture and furthermore demonstrate that IPC-treatment can enhance proliferative tendon repair by counteracting biomechanical and morphological deficits caused by immobilization. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:852,858, 2010 [source] Mechanisms of protection by melatonin against acetaminophen-induced liver injury in miceJOURNAL OF PINEAL RESEARCH, Issue 3 2006Tatsuya Matsura Abstract:, The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity. [source] Surgery-related shedding of breast cancer cells as determined by RT-PCR assayJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2003Xi-Chun Hu MD Abstract Background and Objectives Surgery could result in the shedding of cancer cells into the circulation. These cells were investigated with reverse transcriptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (CK19) and ,-subunit of human chorionic gonadotropin (,-hCG). Patients and Methods Peripheral blood was sampled from 49 patients with breast cancer before operation (d,1), 1 day after operation (d1), and 7 days after operation (d7). Total RNA was extracted from peripheral blood mononuclear cells, followed by RT-PCR assay. The products for ,-hCG were digested with Sty I endonuclease. The patients were followed up for a median of 33 months for signs of recurrence and metastasis. Results The results for CK19 at d,1, d1, and d7 were 8.2, 20.4, and 10.2%, respectively. For ,-hCG, the corresponding results were 12.2, 26.5, and 16.3%, respectively. There was a higher positive rate in d1 samples than in d,1 samples for CK19 and ,-hCG (P,<,0.05 and P,=,0.092, respectively). Conversions of signals from being negative to positive were found in all stages. These did not demonstrate a statistical correlation with prognostic factors associated with a poor prognosis. Only two of the five recurrence occurred in the 15 patients with the signal conversions, while the other three occurred in the patients showing no signals in all samples. Conclusions Cancerous breast cells that enter into the blood circulation as a result of an operation are unlikely to be involved in the formation of metastatic deposits. J. Surg. Oncol. 2003;82:228,232. © 2003 Wiley-Liss, Inc. [source] Opposed bilateral transposition flap: a simple and effective way to close large defects, especially of the limbsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2008R Verdolini Abstract Background, Excision of large tumours, particularly of the limbs, can be challenging because of problems related to wound repair. This is especially true of the lower legs, where skin is often tight and difficult to mobilize. Closure by flap, which would represent the first choice for defects usually between 12,15 mm to 38,40 mm diameter, is at risk of developing complications, such as end-flap necrosis or dehiscence due to skin tension. For larger defects, usually more than 40 to 45 mm diameter, grafting still remains the only realistic option in the majority of cases, with all the various problems associated with this procedure, such as lengthy healing times and the risk of developing leg ulcers, above all in elderly patients with impaired blood circulation. Second intention healing implies extraordinarily long healing times with often unacceptable delays in normal ambulation and activity. Objective, To find an alternative to the usual repair techniques and to try to reduce the risk of complications. Conclusions, We developed a relatively simple but effective technique for the closure of large wounds resulting from the excision of tumours. Our technique consists of two longitudinal, parallel, transposition flaps obtained from two opposite sides of the wound, with major axes orientated in the cephalic-caudal direction. The two flaps are then rotated around two fulcra placed at two extremes of the wound by approximately 90°. This relatively simple technique has never caused any of the ordinarily associated problems in terms of necrosis or ulcer development. In addition, dehiscence of sutures never occurred, given the fact that suture tension is minimal. Quick healing has resulted in the majority of cases, avoiding all the problems associated with grafting or other traditional flap techniques. [source] Electrostatic binding of nanoparticles to mesenchymal stem cells via high molecular weight polyelectrolyte chainsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2009Boon C. Heng Abstract Combining stem cell transplantation with nanoparticle-mediated delivery of drugs and pharmaceuticals is envisioned to be one of the next major developmental steps in regenerative medicine. However, a major challenge would be to keep nanoparticles co-localized with stem cells upon transplantation or transfusion in situ. Since nanoparticles are physically much smaller in size than cells and would not specifically bind to extracellular matrix, it is easier for them to disperse from the transplantation site via the blood circulation. Conjugating nanoparticles directly to the cell membrane can potentially interfere with cellular function by physically obstructing cell surface receptors from interacting with the extracellular matrix, various growth factors and cytokines and other cells. Moreover, drug-loaded nanoparticles may be internalized into the cytoplasm via endocytosis or phagocytosis, which may wreak damage on the cellular machinery, leading to impaired physiological function or cell death. A novel solution may be to utilize high molecular weight polyelectrolyte chains to electrostatically bind nanoparticles to cells. For this purpose, hyaluronan, poly- L -lysine and chitosan are of special interest, because these molecules are generally recognized to be biocompatible for application in various pharmaceutical and surgical products. This study investigated the use of these molecules to bind nanoparticles to mesenchymal stem cells (MSCs), and a novel technique of conjugating half the cell surface with nanoparticles through the use of polyelectrolyte chains was also developed. This would avoid blocking MSC interaction with cytokines, growth factors, extracellular matrix and other cells within the recipient tissue/organ upon delivery in situ. Copyright © 2009 John Wiley & Sons, Ltd. [source] Fas/FasL interaction: A novel immune therapy approach with immobilized biologicals,MEDICINAL RESEARCH REVIEWS, Issue 3 2005Martin Scholz Abstract Systemically applied agents to modulate the Fas/FasL system, e.g., by stimulation of Fas on activated leukocytes or tumor cells failed as strategies in immune therapy due to severe toxic effects in the host. Recently, a novel strategy has been developed by using immobilized immune active biologicals in a medical device that may allow immune management without expensive systemic therapy. This review reports on the potential role of Fas/FasL in immune therapy and summarizes current experimental and clinical data with the leukocyte inhibition module (LIM), an immobilized anti-Fas antibody containing device yet used in extracorporeal blood circulation. This proof of principal may stimulate the development of other devices based on the regulation of Fas/FasL or other targets relevant for immune disorders. © 2004 Wiley Periodicals, Inc. [source] Biological and Optical Properties of Fluorescent Nanoparticles Developed for Intravascular ImagingMICROSCOPY RESEARCH AND TECHNIQUE, Issue 9 2007Dino J. Ravnic Abstract Intravascular tracers in the blood circulation can provide a description of the flow field over time and space. To address the limitations of existing intravascular tracers, we have developed fluorescent nanoparticles capable of providing detailed information regarding the intravascular flow field. The nanoparticles were designed to maximize plasma half-life as well as minimize interactions with other blood components. The bioavailability of the particles in the blood circulation required nanoscale size and low surface charge density. Intravital imaging of nanoparticles in the microcirculation demonstrated that the fluorescence intensity of the nanoparticles was a major determinant of both temporal and spatial resolution of the flow field. We conclude that nanoparticles prepared with these physical and optical properties can provide an accurate description of the localized intravascular flow field. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] Anatomic study and clinical application of distally-based neuro-myocutaneous compound flaps in the legMICROSURGERY, Issue 6 2007Ai-Xi Yu M.D., Ph.D. Objective: Anatomical study on the anastomosis between the neurovascular axis and the musculocutaneous perforators in leg. The distally-based neuron-myocutaneous flap was used for repairing special patients with soft tissue defect in foot and ankle. Methods: Systematical observation was carried out on 30 injected lower legs about the anastomosis between the neurovascular axis and the musculocutaneous perforators, and we summarized the clinical experiences from February 2004 on 12 cases using distally-based neuron-myocutaneous flap for repairing special patients with soft tissue defect in foot and ankle. Results: The neuron-vessels of sural nerve anastomosed permanently with the musculocutaneous perforators of medial and lateral head of gastrocnemius. There were two to three anastomoses found, respectively. The medial anastomotic branches were found larger in caliber than the lateral ones. The spatium intermuscular branches of the posterior tibial artery gave off their junior branches and anastomosed with the vessels in or out of the soleus muscle. There were two to three muscular branches perforated out of the soleus muscle, with mean caliber 0.5 ± 0.2 mm and accompanying with one to two veins. The neuron-vessels of the superficial fibular nerve gave off alone its course two to three muscular branches to the long extensor muscle digits and the long fibular muscle, and one to two fasciocutaneous to the skin. The diameter of the muscular branches was 0.4 ± 0.2 mm in average. Accounting for the operating models in the 12 cases, we had distally-based sural neuron-myocutaneous flap in 7 cases, saphenous neuron-myocutaneous flap in 4 cases, and superficial fibular neuron-myocutaneous flap in 1 case. All these cases were followed up at least for 2,6 months and had the significant results of nice limb's shape and cured osteomyelitis. Conclusion: Distally-based neuro-myocutaneous flap in leg can live with reliable blood circulation. These flaps offer excellent donor sites for repairing special the soft tissue defect in foot and ankle. © 2007 Wiley-Liss, Inc. Microsurgery, 2007. [source] Some biological characteristics of transferred free flapsMICROSURGERY, Issue 5 2007Jefta V. Kozarski M.D., Ph.D. At the Clinic for plastic surgery and burns of the MMA, we examined 33 patients with transferred 5 cutaneous, 18 miocutaneous, and 10 osteocutaneous free flaps out of which 10 were done on foot, 13 on the lower leg, and 10 on the face. We analyzed the blood circulation (patency of arterial microanastomosis and perfusion) of transferred free flaps, recovery of sensitivity, functioning of the sebaceous and sweat glands as well as histomorphologic changes in the skin of the transferred free flaps during the period of 6 up to 36 months after the free flap transfer and compared with the same characteristics of the skin and tissue of the surrounding area of the recipient region. © 2007 Wiley-Liss, Inc. Microsurgery, 2007. [source] Soluble Adhesion Molecules: Surrogate Markers of Cardiovascular Disease?NUTRITION REVIEWS, Issue 2 2003Mohsen Meydani D.V.M. Expression of adhesion molecules on the surface of endothelial and immune cells is important for the interaction between immune and endothelial cells during the inflammatory process. Several of these adhesion molecules have been identified and are believed to be important in the pathogenesis of atherosclerosis. The soluble forms of adhesion molecules are shed from cell surfaces and released into blood circulation; their measurement may have use as markers in predicting cardiovascular disease. Experimental and some clinical data have indicated that reducing expression of some adhesion molecules is another mechanism by which dietary fats such asn -3 polyunsaturated fatty acids and oleic acid, as well as vitamin E and other antioxidants found in fruits and vegetables, may lower the risk of cardiovascular disease. [source] Ultraviolet A exposure might increase metastasis of mouse melanoma: a pilot studyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2005Riikka Pastila Background: The major sources of long-wave ultraviolet A radiation (UVA; 320,400 nm) exposure are extensive sunbathing and tanning in solaria. While the carcinogenic effects of mid-wave ultraviolet B radiation (UVB; 280,320 nm) are well recognized, the potentially hazardous effects of UVA are less understood. Several studies have shown that a variety of physiological processes in the cell are modified by UVA exposure, some of which might be involved in the regulation of tumor metastasis. In this study we suggest that UVA radiation could lead to the increase of metastatic capability of melanoma cells in mice. Method/result: A pilot in vivo study was executed using C57BL/6 mice and syngeneic B16 melanoma cell lines. Mice were intravenously (i.v.) injected with either B16-F1 or B16-F10 melanoma cells into the tail vein and then immediately exposed to UVA. Fourteen days after melanoma injection, lungs were collected and the quantity and quality of metastases were determined under a dissecting microscope. As an outcome of the pilot study we observed that i.v. injected melanoma cells formed more lung metastases in the UVA-exposed mice in comparison with the control mice. Conclusion: This result suggests that the UVA exposure of mice, with melanoma cells present in blood circulation, increases the formation of melanoma metastases in lungs. Further studies should determine whether a similar pro-metastatic effect, as observed in mice, could occur in humans and whether other than melanoma tumors might be susceptible. [source] Carthamus tinctorius flower extract prevents H2O2 -induced dysfunction and oxidative damage in osteoblastic MC3T3-E1 cellsPHYTOTHERAPY RESEARCH, Issue 7 2010Eun Mi Choi Abstract The flowers of Carthamus tinctorius L. (Compositae) have been widely used for enhancing blood circulation and postmenopausal disorder in women. In the present study, the potential protective effects of C. tinctorius flower extract (CFE) against reactive oxygen species (ROS) induced osteoblast dysfunction were investigated using osteoblastic MC3T3-E1 cells. The osteoblast function was assessed by measuring alkaline phosphatase activity, collagen content, calcium deposition, and RANKL production, and the oxidative status was assessed by measuring intracellular lipid peroxidation, and protein oxidation in osteoblastic MC3T3-E1 cells. A significant reduction in the alkaline phosphatase activity, collagen, and calcium deposition and an increase in the production of receptor activator of nuclear factor-kB ligand (RANKL) were observed after 0.3,mM H2O2 addition. The H2O2 -induced alterations were prevented by pre-incubating the osteoblasts with 2,10,,g/ml CFE for 48,h. When the oxidative stress was induced by H2O2, the increased production of protein carbonyl and malondialdehyde was also reduced at the same CFE concentration. These results demonstrate that C. tinctorius flower can act as a biological antioxidant in a cell culture experimental model and protect osteoblasts from oxidative stress-induced toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Soluble Human Leukocyte Antigen-G Isoforms in Maternal Plasma in Early and Late PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009Roberta Rizzo Problem Human Leukocyte Antigen (HLA)-G is a class Ib gene located in the human major histocompatibility complex (MHC). Several lines of investigation indicate that the HLA-G molecule is involved in the maternal acceptance of the semi-allogenic fetus during pregnancy and in the development of tolerance. Expression of soluble HLA-G (sHLA-G) is positively correlated with successful in vitro fertilization (IVF) treatments, and aberrant expression of HLA-G in certain complications of pregnancy, such as pre-eclampsia and spontaneous abortion, has been reported. The main purpose of this study was to investigate the levels of different soluble HLA-G isoforms in maternal plasma in early and late pregnancy. Method of study Soluble HLA-G (sHLA-G) can be detected in maternal blood, and in this study, two different isoforms of sHLA-G, namely sHLA-G1 generated by shedding of membrane-bound HLA-G1 and HLA-G generated by specific HLA-G transcripts, have been investigated early [median of 16.4 weeks of gestation (GW)] and late (median: 38.9 GW) in pregnancy in an original cohort of 580 pregnant Caucasian women. Results Lower concentrations of sHLA-G1 were found late in pregnancy (>32 GW) in a group of women with severe pre-eclampsia compared with controls with uncomplicated pregnancies (P = 0.029, PC = 0.09; Mann,Whitney; Logistic regression analysis: P = 0.024, OR = 0.920, 95% CI: 0.855,0.989). However, this was not the case with HLA-G5, and significantly more of the cases with severe pre-eclampsia had detectable plasma HLA-G5 compared with that of the control group (P = 0.013, PC = 0.04; Mann,Whitney). Similar findings were not observed in women with gestational hypertension or existing hypertension continuing into pregnancy. Furthermore, there was a trend toward lower maternal plasma sHLA-G1 in a group of women with premature birth (<37 GW) compared with that of the control group (P = 0.028, PC = 0.17; Mann,Whitney). On the contrary, HLA-G5 was lower in the control group compared with that in the premature group (P = 0.004, PC = 0.02; Mann,Whitney). Conclusion This study shows in line with other published studies that a high, detectable soluble HLA-G concentration in maternal plasma or serum is not mandatory for a successful pregnancy. However, complications during pregnancy, such as (severe) pre-eclampsia, spontaneous abortion, IUGR, and premature birth, are associated with a low or undetectable level of soluble HLA-G in the maternal blood circulation. Also, this study indicates that sHLA-G1 is the interesting soluble HLA-G isoform in pre-eclampsia, and that low or undetectable levels of HLA-G5 at the end of pregnancy seem to be associated with an uncomplicated normal pregnancy, whereas in severe pre-eclampsia and possibly other pregnancy complications, such as preterm birth and IUGR, the level of HLA-G5 is higher. [source] Serum-mediated osteogenic effect in traumatic brain-injured patientsANZ JOURNAL OF SURGERY, Issue 6 2009Oliver P. Gautschi Abstract Background:, Patients with a traumatic brain injury (TBI) and bone fractures often show an enhanced fracture healing, as well as an increased incidence of heterotopic ossifications (HO). It has been suggested that unknown osteoinductive factors may be released by the injured brain into the systemic blood circulation and act peripherally on the affected tissues. The aim of this study was to investigate whether serum from TBI patients is osteoinductive. Methods:, Sixty-one consecutive patients were classified into four groups: TBI and long-bone fracture (group I, n = 12), isolated severe TBI (group II, n = 21), isolated long-bone fracture (group III, n = 19) and controls (group IV, n = 9). Blood samples were collected at 6, 24, 72 and 168 h post-injury. The osteogenic potential was determined by measuring the in vitro proliferation rate of the human fetal osteoblastic cell line hFOB1.19, and primary human osteoblasts. Additionally, serum induced osteoblastic differentiation was assessed by measuring the mRNA expression of specific osteoblastic markers, including alkaline phosphatase, runt-related transcription factor 2, cathepsin K and serine protease 7. Results:, The sera of group I induced a higher mean proliferation rate of primary human osteoblasts at all time points of sampling than group III (P < 0.05). Group I had a higher mean proliferation rate of hFOB1.19 cells than all other groups at 6, 24 and 72 h post-injury (P < 0.05). The expression of alkaline phosphatase, cathepsin K and runt-related transcription factor 2 mRNA was increased in group I compared with group III and serine protease 7 was exclusively expressed in group I. Conclusion:, The study results strongly support a humoral mechanism in enhanced fracture healing and the induction of HO after TBI. Increased proliferation of osteoblastic cells and an accelerated differentiation of osteoprogenitor cells may be responsible for increased osteogenesis in TBI. [source] Left Ventricle Afterload Impedance Control by an Axial Flow Ventricular Assist Device: A Potential Tool for Ventricular RecoveryARTIFICIAL ORGANS, Issue 9 2010Francesco Moscato Abstract Ventricular assist devices (VADs) are increasingly used for supporting blood circulation in heart failure patients. To protect or even to restore the myocardial function, a defined loading of the ventricle for training would be important. Therefore, a VAD control strategy was developed that provides an explicitly definable loading condition for the failing ventricle. A mathematical model of the cardiovascular system with an axial flow VAD was used to test the control strategy in the presence of a failing left ventricle, slight physical activity, and a recovering scenario. Furthermore, the proposed control strategy was compared to a conventional constant speed mode during hemodynamic changes (reduced venous return and arterial vasoconstriction). The physiological benefit of the control strategy was manifested by a large increase in the ventricular Frank,Starling reserve and by restoration of normal hemodynamics (5.1 L/min cardiac output at a left atrial pressure of 10 mm Hg vs. 4.2 L/min at 21 mm Hg in the unassisted case). The control strategy automatically reduced the pump speed in response to reduced venous return and kept the pump flow independent of the vasoconstriction condition. Most importantly, the ventricular load was kept stable within 1%, compared to a change of 75% for the constant speed. As a key feature, the proposed control strategy provides a defined and adjustable load to the failing ventricle by an automatic regulation of the VAD speed and allows a controlled training of the myocardium. This, in turn, may represent a potential additional tool to increase the number of patients showing recovery. [source] The Hemolytic Characteristics of Monopivot Magnetic Suspension Blood Pumps With Washout HolesARTIFICIAL ORGANS, Issue 4 2005Osamu Maruyama Abstract:, The hemolytic characteristics of monopivot magnetic suspension blood pumps as a function of impeller washout hole configuration and female pivot shape are observed. The pump impellers are designed with three washout hole configurations for blood circulation, and four female pivot shapes to reduce blood stagnation and to enhance antithrombogenicity. The hemolytic characteristics of the monopivot pumps were observed to be better than those of a currently available commercial centrifugal blood pump, BP-80, and changed to be nearly equal when the female pivot shape was changed. This indicates that hemolysis in monopivot pumps is mainly caused by shear stress, between, the, male, and, female, pivots. [source] Therapeutic Left Ventricular Assist Device and Apheresis on Dilated CardiomyopathyARTIFICIAL ORGANS, Issue 2 2004Yoshica Matoba Abstract:, Pathogenesis and therapies of dilated cardiomyopathy (DCM) have been discussed for a long time, but both of the ultimate answers are still unknown. In the last decade, the pathogenic role of immunological factors, such as cardiac autoimmune antibodies and cytokines, have been discussed attentively. This has led to one possible new therapy, immunoadsorption, which removes antibodies, and it has made a remarkable effect. However, there are other factors to remove. For the removal of cytokines and neurohormones, the most effective method is hemofiltration (HF). Also, double-filtration plasmapheresis (DFPP) removes immunoglobulin as well as low-density lipoprotein (LDL) and coagulation factors that may improve blood circulation, including the coronary arteries. Therefore, to eliminate all deteriorative factors, both apheresis therapies, HF and DFPP, should be performed. Due to the shortage of donor hearts, left ventricular assist systems (LVAD) have been used as a bridge to transplantation. It has now been reported that the total unloading of the left ventricle does not only maintain, but also recovers, the cardiac function, even from end-stage heart failure. However, the patients who have obtained a long-lasting recovery of cardiac function from an LVAD are still in a minority. To make this the majority, therapeutic LVAD should be combined with the apheresis therapies, DFPP and HF. We believe that this concept, a combination of HF and DFPP with therapeutic LVAD, will be the next generation of treatment that has a potential to postpone, or even avoid, heart transplantation. [source] Delivery of a Growth Factor Fusion Protein Having Collagen-Binding Activity to Wound TissuesARTIFICIAL ORGANS, Issue 2 2003Tetsuya Ishikawa Abstract: Recently, we established a collagen-binding growth factor consisting of epidermal growth factor and the fibronectin collagen-binding domain (FNCBD-EGF). FNCBD-EGF is a biologically active fusion protein that could stably bind to collagen materials, and exert its growth factor activity even after collagen binding. In this study, we investigated the concept that FNCBD moiety with high collagen affinity may enhance the effective local concentration of EGF at the site of administration in the following tissues: skin wounds, catheter-injured arteries, and hind limb muscles. In an animal model of impaired wound healing, application of FNCBD-EGF in combination with collagen gel induced granulation tissue formation in the wounds due to its sustained retention. In the injured artery, infused FNCBD-EGF remained bound to collagen exposed on the injured tissues even after blood circulation was restored. Injection of the fusion protein into the hind limbs revealed that our delivery system was effective for direct administration to muscular tissue. [source] The role of insulin as an antithrombotic humoral factorBIOESSAYS, Issue 1 2004Kushal Chakraborty Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the formed thrombus in the system. These insulin-induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates ,2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91,98, 2004. © 2003 Wiley Periodicals, Inc. [source] Reduction of Active Elastase Concentration by Means of Immobilized Inhibitors: A Novel Therapeutic ApproachBIOTECHNOLOGY PROGRESS, Issue 3 2004Valentina Grano The inhibitory power of three different active Nylon membranes, separately loaded with three different protease inhibitors, was studied with the aim of reducing the increased elastase concentration occurring during hemodialysis or extracorporeal blood circulation in patients undergoing cardiopulmonary bypass. Chemical grafting was carried out to make the inert Nylon membrane suitable for the immobilization of the inhibitors. The behavior of immobilized ,1 -antitrypsin, bovine pancreatic trypsin inhibitor (BPTI), or elastatinal was separately studied. ,1 -Antitrypsin and BPTI were covalently immobilized by means of a diazotization process, whereas elastatinal was covalently attached via a condensation process mediated by glutaraldehyde. The inhibitory power of each membrane type was studied as a function of the amount of immobilized inhibitor and temperature. All active membranes have shown good inhibitory power. The most efficient membrane was that loaded with ,1 -antitrypsin, the less efficient that with BPTI. [source] Liver invasion by malarial parasites , how do malarial parasites break through the host barrier?CELLULAR MICROBIOLOGY, Issue 12 2004Masao Yuda Summary Malarial transmission to the human host is established by sporozoite infection of the liver. Sporozoites are released from the mosquito salivary glands and carried by the blood flow to the liver sinusoid. In the sinusoid, sporozoites leave the blood circulation by crossing the sinusoidal cell layer to infect hepatocytes, the site for their development into the erythrocyte-invasive forms. Traversal of the sinusoidal cell layer and subsequent hepatocyte infection are the most important events in sporozoite liver invasion, but the molecular basis of both events remains to be elucidated. The present review of sporozoite liver invasion focuses on recent advances in this topic obtained by application of reverse genetics. Sporozoites traverse host cells, rupturing the host cell membrane in the process. Three microneme proteins have important roles in this motility. Disruption of one of these genes abolishes or severely impairs cell traversal without affecting other types of invasive motility. Studies using these disruptant parasites indicate that cell-traversal ability is required for crossing the sinusoidal cell layer and accessing the hepatocytes for infection. This process is homologous to midgut epithelium penetration by the malarial ookinete, because identical or paralogous genes are critically involved in both processes. After arrival at the hepatocyte, the invasion mode of the sporozoites switches from cell traversal to hepatocyte infection. [source] Die Chemie des Katers: Alkohol und seine FolgenCHEMIE IN UNSERER ZEIT (CHIUZ), Issue 1 2007Klaus Roth Prof. Das Überfluten jeder einzelnen Zelle unseres Körpers mit einer großen Menge Ethanol führt zu Störungen im Stoffwechsel aller Organe. Dies erklärt die große Variationsbreite der Symptome nach zu großer Ethanolaufnahme. Gegen den Kater gibt es keine echte Heilung. "Chemie in unserer Zeit" empfiehlt: Viel reines Wasser gegen den Wasserverlust, eine Aspirin oder Ibuprofen gegen die pochenden Kopfschmerzen, Fruchtsaft gegen den Glucosemangel, Muttis kräftige Hühnerbrühe gegen den Elektrolytverlust, eine Vitamintablette wegen ihres sehr wirksamen Placebo-Effekts, Zuspruch und Mitleidsbekundungen der Lieben und dann , wenn der Kreislauf und die Kontrolle der unteren Extremitäten den aufrechten Gang es zulassen, einen Spaziergang an der frischen Luft. Dabei sollte man intensiv über die Sinnlosigkeit übermäßigen Trinkens nachdenken. Das hilft, und am nächsten Tag ist alles vorbei , zumindest bis zum nächsten Mal. Na dann: Helau und Alaaf! Flooding of every cell in our body with a huge amount of ethanol affects the entire metabolism of all organs. This explains the broad variation of symptoms after drinking to much. There is no real cure für hangover. "Chemie in unserer Zeit" recommends much pure water against the dehydration, aspirin or ibuprofen against the throbbing headaches, fruit juice against hypoglycemia, Mom's powerful chicken soup to compensate for electrolyte losses, a vitamine pill because of its powerful placebo-effect, compassion and words of comfort of the loved ones and finally , if blood circulation and control of the lower extremities admit an upright walk , a long stroll in fresh air. Meanwhile one should think deeply about the pointlessness of excessive drinking. This all helps and on the next day it will all be over , at least until next time. Well then: Cheers and Bottoms up! [source] 2134: Arachnoid cell changes following elevated pressure and oxidative stress: new implications for optic nerve degenerationACTA OPHTHALMOLOGICA, Issue 2010A NEUTZNER Purpose The study of meningothelial cells (MCs) and their connection to optic nerve function. MCs line the arachnoid layer of the meninges and form a barrier between the CSF and the blood circulation. A previous study revealed a significantly increased proliferation of MCs in the arachnoid surrounding the optic nerve glaucoma patients. Methods To explore a possible role of these cells in the pathogenesis of diseases of the optic nerve, we studied the effect of elevated hydrostatic pressure and oxidative stress on MCs using rotenone to inhibit mitochondrial function and compared them to untreated control cells. Cell viability and proliferation were measured using a MTS-based assay. As a measure of barrier function, we assessed the endocytotic activity of MCs by fluorescence and confocal microscopy following fluorescent-latex bead uptake. Results Exposure of MCs to elevated hydrostatic pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. Furthermore, mild oxidative stress severely inhibited endocytosis, thus negatively impacting MC barrier function. Conclusion MCs surround the optic nerve, thereby shielding it from but also conditioning the microenvironment of this sensitive area. As elevated pressure and oxidative stress occur in patients with increased intracranial pressure who have papilledema and probably in some cases of normal-tension glaucoma, these phenomena may impact the function of MCs and thus, contribute to the loss of retinal ganglion cells in the course of these and, perhaps, other optic nerve diseases. [source] | ||||||||||||||||