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Circulating concentrations of 17-estradiol influence pattern of LH in circulation of cows.

The objective of the research was to determine the relationship between circulating 17 beta-estradiol (E2) and secretion of luteinizing hormone (LH) in cows. A second objective was to determine if response to E2 was influenced by interval between ovariectomy and the start of E2 treatment. Thirty-one nulliparous cows 3 yr of age were randomly assigned to a 2 x 4 factorial arrangement of treatments. Sixteen cows were ovariectomized at 18 mo of age (long term), and the other 15 cows were ovariectomized at 36 mo of age (short term). At the time of ovariectomy of cows in the short term group, 11 cows in the short term group and 12 cows in the long term group were implanted subcutaneously with 1, 2 or 4 polydimethylsiloxane capsules containing E2. The other eight cows served as non-implanted controls (n = 4-short term, n = 4-long term). All cows were fitted with jugular vein catheters on day 29 of treatment, and on day 30 blood samples were collected at 12-min intervals for 6 hr. At the end of 6 hr, luteinizing hormone-releasing hormone (LHRH) was administered and blood sampling continued at 12-min intervals for an additional hour. Serum was analyzed for LH and E2. Variables of LH secretion analyzed were mean concentration, frequency of pulses, amplitude of pulses and maximum concentration after LHRH. There were no significant interactions for any of the variables of LH among cows ovariectomized for the long and short term. There was a significant linear increase in mean concentration of LH with increased circulating concentration of E2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Circulating hematopoietic progenitor cells in a fetus with alpha thalassemia: comparison with the cells circulating in normal and non-thalassemic anemia fetuses and implications for in utero transplantations.

Our aim was to evaluate the number of progenitor cells circulating in an alpha-thalassemic fetus during its infusion in utero with paternal CD34(+) and adult red cells and to compare those values with those circulating in normal and non-thalassemic anemic fetuses of matched gestational age. The treatment of the alpha-thalassemic fetus has been described elsewhere. Fetal blood was obtained from normal and anemic fetuses by fetal blood sampling for diagnostic or therapeutic purposes according to a protocol approved by the human subject committee. The number of progenitor cells in fetal blood was estimated on the basis of the number of colonies they gave rise to in semisolid cultures. The alpha-thalassemic fetus, as did the other fetuses analyzed, contained high numbers (10(6)-10(7) depending on the age) of progenitor cells, values which were higher than the number (10(4)-10(5)) of paternal progenitor cells being transplanted. Progenitor cells with adult characteristics (adult kinetics of differentiation) were detected rapidly (10 min) after the CD34(+) cell infusion, but were not detectable 2-3 weeks after the transplant. These results indicate that adult progenitor cells do not have a numerical advantage when transplanted into alpha-thalassemic fetuses.

Antigens, CD34↗

Diurnal variation in circulating leptin is dependent on gender, food intake and circulating insulin in mice.

Leptin is an adipocyte hormone involved in the regulation of energy homeostasis. Its circulating levels show a diurnal rhythm with a nocturnal peak. We examined the influences of gender, feeding state, and plasma insulin and glucose on the diurnal rhythm in normal mice. Plasma was sampled at 4-h interval for 24 h in female (n=80) and male (n=80) mice, which were freely fed or fasted. In both genders, plasma leptin displayed a diurnal rhythm with a nadir at 8 or 10 AM and a nocturnal peak at 10 PM to 2 AM. The nocturnal increase in leptin was higher in females (+160+/-18%) than in males (61+/- 16%; P<0.001), completely abolished by fasting, and correlated significantly to the diurnal variation in plasma insulin both in females (r=0.44, P=0.003) and males (r=0.46, P<0.001). Baseline plasma leptin in non-fasted animals were not different between the genders, whereas during fasting, the reduction in leptin was more pronounced in males than in females, resulting in a higher plasma leptin after fasting in females. Plasma insulin was higher in males under non-fasted conditions (P=0.003), but not significantly different between genders in fasted animals. In conclusion, plasma leptin displays a nocturnal increase in mice, which is more pronounced in female mice than in male mice, is completely abolished by fasting and correlates to the diurnal variation in circulating insulin. It is suggested that the nocturnal rise in leptin shows gender dependency and is caused by the increase in plasma insulin caused by food intake.

Animals↗

Raised levels of circulating VCAM-1 and circulating E-selectin in patients with recurrent oral ulceration.

Endothelial cell (EC) adhesion molecules VCAM-1 (vascular cell adhesion molecule-1), E-selectin and ICAM-1 (intercellular adhesion molecule-1) are essential for the binding of inflammatory cells to ECs. Recently, circulating forms of these molecules have been detected in a number of vasculitic disease processes. Recurrent oral ulceration (ROU) has some features of a vasculitic disease process. The purpose of this study was, therefore, to compare cVCAM-1, cE-selectin and cICAM-1 levels in 50 patients with ROU and 50 age- and sex-matched controls. Levels of circulating adhesion molecules were quantified using specific "sandwich" ELISA assays. The cVCAM-1 and cE-selectin levels were significantly raised in ROU patients (P < 0.00005 and P < 0.05, respectively) but there was no significant increase in cICAM-1 levels. These findings may result from endothelial cell activation or damage at the ulcer site.

Adult↗

Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity.

PURPOSE: Circulating endothelial cells (CEC) comprise at least two distinct populations: bone marrow-derived circulating endothelial progenitors (CEP) and mature CECs derived from existing vasculature. We hypothesized that antiangiogenic agents may have differential effects on CEPs and mature CECs and that these changes may serve as a marker of biological activity. EXPERIMENTAL DESIGN: The effect of angiogenesis inhibitors on CECs was evaluated by flow cytometry after vascular endothelial growth factor (VEGF)-induced mobilization and in mice bearing Lewis lung carcinoma (LLC). Tumor angiogenesis was evaluated in parallel by immunohistochemistry. RESULTS: In nontumor-bearing mice, VEGF administration increased both mature CECs and CEPs. This increase was inhibited by the VEGF receptor 2 inhibitor ZD6474 as well as the VEGF inhibitor-soluble Flt-1. ZD6474 had no significant effect on CECs in the absence of exogenous VEGF stimulation. In contrast, LLC-bearing mice had an increase in mature CECs but not CEPs after 3 days of treatment with ZD6474. The increase in mature CECs was dose-dependent, accompanied by a decrease in tumor microvessel density, and preceded reduction in tumor volume. Treatment of LLC-bearing mice with the vascular targeting agent ZD6126 also increased mature CECs. CONCLUSIONS: VEGF inhibitors can have differential effects on mature CECs and CEPs, and agents inhibiting tumor angiogenesis may cause a concomitant increase in mature CECs. This increase occurs in tumor-bearing but not in nontumor-bearing mice, suggesting that tumor endothelium is a potential source of mature CECs. Therefore, assessing both mature CECs and CEPs may provide insights into the mechanism of antiangiogenic agents and serve as an early surrogate marker of biological activity.

Animals↗

Circulating complement breakdown products in patients with rheumatoid arthritis. Correlation between plasma C3d, circulating immune complexes, and clinical activity.

Quantitative determination of the small C3 breakdown product, C3d, was used to investigate complement activation in 45 plasma samples from 30 patients with rheumatoid arthritis (RA). The mean plasma C3e level in these samples (3.0 +/- 1.3 mg/100 ml) was significantly increased (P less than 0.001) as compared to patients with degenerative joint disease (0.9 +/- 0.4 mg/100 ml) and healthy blood donors (0.8 +/- 0.5 mg/100 ml). C3d levels were increased by more than s SD in 79% of RA samples. Plasma C3d levels were compared with C3d concentrations in synovial fluid. In most RA patients, the C3d levels were higher in synovial fluid than in plasma. A very significant correlation between plasma C3d levels and circulating immune complexes, as measured by determination of Clq binding activity (Clq BA), was observed (P less than 0.001). C3d levels were more elevated in RA patients with extra-articular disease manifestations (3.8 +/- 1.2 mg/100 ml) as compared to patients with joint disease alone (2.2 +/- 1.0 mg/100 ml). C3d levels and Clq BA were also significantly correlated (P less than 0.001) with the RA disease activity expressed by an index derived from sedimentation rate, joint score, and duration of morning stiffness. A close relationship between C3d levels, Clq BA, and the clinical activity further appeared during follow-up studies. The present observations suggest that a parallel but rather independent activation of the complement system may be induced by immune complexes in circulating blood and in the joint spaces during the course of rheumatoid arthritis.

Adult↗

Short stature associated with high circulating insulin-like growth factor (IGF)-binding protein-1 and low circulating IGF-II: effect of growth hormone therapy.

We report a case of short stature associated with high circulating levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-10 and low levels of IGF-II responsive to pharmacological treatment with GH. Our patient suffered severe growth failure from birth (2.06 SD below the mean for normal full-term boys, and 5.2 and 7.3 SD below the mean at 5 and 10 months). Studies carried out before referral to our pediatric unit included normal 46,XY karyotype and normal encephalic imaging. Other endocrine and metabolic alterations and other systemic diseases were excluded. At 1.7 yr of age (length, 6.1 SD; weight, 4.6 SD; head circumference, 1.4 SD below the mean, respectively) the patient was referred to our pediatric unit. The baseline GH concentration was 31 microg/L, and the peak after an arginine load was 59.6 microg/L. In the same samples GH bioactivity was nearly superimposable (RIA/Nb2 bioactivity ratio = 0.9). Fasting insulin and glucose concentrations were 7.4 microU/mL and 65 mg/dL, respectively, both normally responsive to an oral glucose load. GH insensitivity was excluded by a basal IGF-I concentration (64 ng/mL) in the normal range for 0- to 5-yr-old boys and its increase after 2 IU/day hGH administration for 4 days. IGFBP-3 (0.5 microg/mL) was slightly reduced, whereas IGFBP-1 (2218 and 1515 ng/mL in two different basal samples) was well above the normal values for age and was suppressible by GH (maximum suppression, -77% at 84 h) and glucose load (maximum suppression, -46% at 150 min). The basal IGF-II concentration was below the normal range (86 ng/mL), whereas IGFBP-2 was normal (258 ng/mL). Analysis of the promoter region of IGFBP-1 and IGF-II failed to find major alterations. Neutral gel filtration of serum showed that almost all IGF-I activity was in the 35- to 45-kDa complex, coincident with IGFBP-1 peak, while the 150-kDa complex was absent, although the acid-labile subunit was normally represented. At 2.86 yr (height, 65.8 cm; height SD score, -7.3; height velocity SD score, -5) the patient underwent treatment with 7 IU/week human GH; after 4 months, the patient's height was 68.5 cm (height SD score, -6.9) corresponding to a growth velocity of 8.3 cm/yr (0.3 height velocity SD score). IGFBP-1 was reduced (216 ng/mL), although still in the high range, whereas IGF-I (71 ng/mL), IGFBP-3 (0.62 microg/mL), and IGF-II (111 ng/mL) were only slightly increased. The IGF-I profile showed activity in the 150-kDa region. In conclusion, we speculate that the increased IGFBP-1 values found in this patient produce 1) inhibition of IGF-I biological activity and, therefore, a resistance to IGF-I not due to a receptor defect for this hormone; 2) inhibition of formation of the circulating 150-kDa ternary complex and, therefore, an accelerated clearance rate of IGF peptides; 3) inhibition of the feedback action on GH, leading to increased GH levels, which could suggest the diagnosis of GH insensitivity syndrome; and 4) inhibition of body growth.

Body Height↗

Comparative concentrations of growth hormone-binding protein in maternal circulation, fetal circulation, and amniotic fluid.

Fetal growth is thought to be independent of the concentration of GH, although circulating levels of GH are high in the human fetus. To elucidate the role of GH in fetal development, levels of GH-binding protein (GHBP) were measured in the serum of nonpregnant and pregnant women and neonates as well as in amniotic fluid obtained at various stages of gestation. Total GHBP (the sum of free GHBP and GHBP bound to GH) is measured by a ligand-mediated immunofunctional assay. GHBP concentrations in adult serum were not changed by pregnancy or the stage of gestation. A significant correlation was observed between the concentration of GHBP in the umbilical artery and vein. No correlations were observed between the GHBP concentration and such measures of fetal growth as fetal weight and fetal age. Although the neonatal concentrations of GHBP were significantly lower than those of pregnant women, no correlation was observed between them. GHBP was also present in the amniotic fluid from early to late gestation at concentrations higher than in the cord serum of the neonate. The amniotic GHBP concentration in late gestation was significantly higher than in early gestation. GHBP appears to be derived from GH receptors of fetal organs (most probably fetal liver). The low level of GHBP in fetal serum may be the result of a decrease in GH receptors caused by high levels of circulating GH. GHBP levels in amniotic fluids may be related to the development or maturation of the fetus.

Amniocentesis↗

[Pathogenic factors of blood circulation disturbance in lumbar intervertebral disc herniation and mechanism of Tuina manipulation in promoting circulation].

Tuina manipulation has long been used in the treatment of lumbar intervertebral disc herniation, although its therapeutic mechanisms remain uncertain. The specific characteristic syndrome of this disease is lumbocrural pain in varying degrees, which is due to mechanical compression, aseptic inflammation, blood circulation disturbance and dystrophy. These factors can act on the involved nerve roots and give rise to nerve conduction disturbance. Since the blood circulation disturbance and nerve roots dystrophy are the most important pathogenic aspects of this disease, the therapeutic effect of Tuina manipulation on lumbar intervertebral disc herniation is related to them directly or indirectly.

Decompression, Surgical↗

Schistosoma mansoni: ultrastructural localization of the circulating anodic antigen and the circulating cathodic antigen in the mouse kidney glomerulus.

In this study two major antigens of Schistosoma mansoni, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA), were localized ultrastructurally in glomeruli of S. mansoni infected mice. These antigens were studied by direct gold labeling in which anti-CAA and anti-CCA monoclonal antibodies were labeled with 5 and 15 nm gold particles, respectively. CAA and CCA were demonstrable in glomeruli at week 3 in the basement membrane and from 5 weeks in moderately electron-dense material of the mesangial matrix. Both antigens were also encountered in fenestrae of the endothelial cells, in filtration slit pores, and on the luminal membranes of the epithelial cells. It appears that CAA and CCA are arrested by the glomerular basement membrane and deposited in the mesangial matrix. CAA was seen in considerably smaller amounts than CCA. This was ascribed to the fact that CAA, but not CCA, is repelled by the negative charge of the capillary walls and the glomerular basement membrane.

Animals↗

[Effects of cigarette smoking on ocular circulation chronic effect on choroidal circulation].

The effects of long-term smoking on choroidal circulation were studied. For this purpose, Wistar rats were made to inhale mainstream smoke for 30 minutes daily. After periods of inhalation (16 weeks and 25 weeks), choroidal blood flow (CBF) was measured by the hydrogen clearance method and the index of choroidal vascular resistance (systolic tail arterial pressure/CBF) was calculated. There was no significant difference in CBF between either smoking group (16 weeks and 25 weeks) and controls. However the index of choroidal vascular resistance increased significantly after inhalation of smoke for 25 weeks. No histopathological abnormalities were detected in the choroid and outer layer of the retina. The results suggested that long-term smoking might induce disturbance of choroidal circulation.

Animals↗

Lymphatic filariasis: detection of circulating and urinary antigen and differences in antibody isotypes complexed with circulating antigen between symptomatic and asymptomatic subjects.

A two-site immunoradiometric assay using a monoclonal antibody (MoAb) against Brugia malayi microfilariae allowed the detection of parasite molecules both in the serum and the urine of patients from Sri Lanka infected with Wuchereria bancrofti. Whereas 50% of patients had no antigen in their serum, all of them excreted detectable amounts of antigen in their urine, the levels being higher in symptomatic than in asymptomatic patients. The poor detection in serum appeared to be related to the presence of circulating immune complexes. It was shown that the isotype of the antibodies complexed with the circulating antigen was IgM in the asymptomatic group, while it was mainly IgG in the symptomatic patients (swelling and lymphoedema or elephantiasis). These results suggest the existence of regulatory immune mechanisms affecting the clinical expression of lymphatic filariasis.

Animals↗

[Comparative measurement of optic nerve head circulation using laser speckle circulation analyser of ocular fundus and a hydrogen clearance method].

The microcirculation in the optic nerve head (ONH) was measured using the recently developed laser speckle circulation analyser for the ocular fundus. The measurements were compared to those of the capillary blood flow (CBF) obtained by the hydrogen clearance method. The ONH blood flow was measured using both methods simultaneously in six normal albino rabbits. The blood flow was increased by inhalation of carbon dioxide (CO2) and reduced by systemic administration of endothelin-1 (ET-1). 10%CO2 inhalation showed a CBF increase of about 22% in the ONH in the hydrogen clearance method, and intravenous injection of ET-1 at 10(-10) mol/kg decreased the reading by about 19%. A significant correlation (r = 0.92, p < 0.01) was found between the relative values of NB (Normalized blur, by laser speckle method) and CBF in the ONH. This result indicates that the change of NB in the ONH shares the same accuracy as hydrogen clearance method within the range of our present experiment. This study provides a fundamental basis for the clinical application of the laser speckle method in measuring ONH circulation.

Animals↗

[The results of monitoring enterovirus circulation circulation among the population and in the environment of Tula Province over 10 years (1985-1994)].

The study of the isolation rate of polioviruses and other enteroviruses in patients with different diagnosed diseases, among healthy child population, as well as the circulation of these viruses in the environment was carried out on the territory of Tula Province for the period of 1985-1994. The epidemiological analysis of the data obtained in this study are presented. The study revealed that the vaccinal prophylaxis of poliomyelitis, carried out for the period of many years, did not lead to the elimination of poliovirus strains, differing in their genetic properties from vaccine strains, on the territory of Tula Province. A decrease in the immune stratum with respect to polioviruses of types I, II and III, observed in 1985-1994, was accompanied by the circulation of polioviruses of these three types among the population.

Child↗

FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing.

FTY720, given i.v. or orally at 0.03 mg/kg or more, significantly prolonged skin allograft survival in a dose-dependent manner and showed more potent immunosuppressive activity than cyclosporin A (CsA) or tacrolimus (FK506) in MHC-incompatible rat strains of WKAH donors and F344 recipients. However, unlike CsA or FK506, FTY720 up to 1000 nM did not affect IL-2 production in allogeneic MLC. Within 3 to 24 h after a single oral administration of FTY720 at 0.1 to 1 mg/kg, the number of lymphocytes in the rats was markedly decreased in the peripheral blood and thoracic duct lymph and partially in spleen. By contrast, the number of lymphocytes in peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN), and Peyer's patches (PP) was significantly increased at the same time. Intravenous transfusion of calcein-labeled rat lymphocytes into rats revealed that FTY720 significantly accelerated lymphocyte homing to PLN, MLN, and PP, dose dependently. Since FTY720-induced lymphocyte homing was completely blocked by simultaneous treatment of the calcein-labeled lymphocytes with mAbs against CD62L, CD49d, and CD11a before the transfusion, the acceleration of lymphocyte homing by FTY720 appears to be mediated by lymphocyte-homing receptors. These findings indicate that FTY720 sequesters circulating mature lymphocytes into PLN, MLN, and PP by acceleration of lymphocyte homing and thereby decreases the number of lymphocytes in peripheral blood, thoracic duct lymph, and spleen. Based on these observations, sequestration of circulating mature-lymphocytes is presumed to be a main mechanism of the immunosuppressive activity of FTY720.

Animals↗

[Experimental study on the maintenance of sufficient hepatic circulation with arterial blood during the temporary occlusion of the hilar hepatic circulation].

This study was performed to clarify the lowest limit of the blood flow volume to maintain the normal energy metabolism in the liver of mongrel dogs under the condition of total hilar clamping when the hepatic circulation was supplied only through the extracorporeal catheter bypass from the artery to the hepatic portal vein in flow control. The proper hepatic artery was ligated. The levels of adenosine triphosphate and total adenine nucleotide in the liver tissue were maintained as in the same level as the pre-bypass value during 120 minutes of this procedure even though the rate of bypass flow varied between 25% to 100% of normal total hepatic blood flow. When the bypass flow decreased below 10% of the normal flow, the hepatic energy metabolism was observed broken and the anaerobic glycolysis progressed within 30 minutes. Regional hepatic blood flow measured by the hydrogen clearance method was decreased slightly in the 25%-bypass flow and extremely in the 10%-flow after 30 minutes of the bypass. The lowest limit of the arterial blood inflow volume to maintain the hepatic function was confirmed to be in the range between 10% and 25% of the normal total hepatic blood flow volume.

Adenine Nucleotides↗

[Effect of the imidazoline receptor agonist moxonidine on hemodynamics, coronary circulation, metabolic ischemia markers and the neurohumoral system in patients with essential hypertension. Effects of moxonidine on coronary circulation].

Moxonidine is a new centrally active imidazoline-receptor agonist being effectively applied in the treatment of arterial hypertension due to its sympathicolytic potency. This is the first investigation regarding the effects of moxonidine on coronary and systemic hemodynamics, metabolic markers of ischemia and neurohumoral parameters in patients with essential hypertension (WHO I-II). We studied moxonidine (single dose of 0.4 mg p.o.) in 22 patients with left ventricular (LV) hypertrophy, ST segment depressions during exercise, pectanginal complaints and negative coronarograms. Assessments included arterial blood pressure, cardiac output, pulmonary artery pressure mean (PAPm), pulmonary capillary wedge pressure (PCWP) and coronary sinus flow (CSF) by intravascular Doppler technique. The moxonidine-induced parameter changes 2 hours later were as follows: a decrease in systolic/diastolic pressure by 28/10 mmHg, and in heart rate by 5 bpm, associated with a decline of PAPm by 17% and of PCWP by 26%. LV work was reduced by 26%, MVO2 by 18% and CSF by 16%. Average peak velocity in CS fell by 18% and coronary flow reserve (with adenosine) increased by 12%. CS-O2 saturation rose by 4%, accompanied by an increase in lactate extraction by 17%, a decrease in norepinephrine spillover by 30% and in arterial endotheline by 20%. In conclusion, moxonidine produces clinically relevant sympathicolysis with beneficial effects on hemodynamics, coronary circulation and neurohumoral parameters.

Aged↗

Circulating soluble gp130, soluble IL-6R, and IL-6 in patients undergoing cardiac surgery, with or without extracorporeal circulation.

OBJECTIVE: Soluble forms of interleukin-6 (IL-6) receptors are known to modulate biological activities of IL-6. The purpose of the study was to measure circulating levels of IL-6, sIL-6R and sgp130 in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB group) or without CPB (non-CPB group). METHODS: The CPB group included 19 patients and the non-CPB group 12 patients. Sera levels of IL-6, sIL-6R and sgp130 were measured by specific ELISA at the beginning of the operation (T0, 15 min before skin incision) and 6 h later (T1). RESULTS: IL-6 sera levels were respectively 9+/-20 pg/ml (mean+/-SD) and 13+/-19 pg/ml at T0 and reached 340+/-250 pg/ml and 965+/-1060 pg/ml at T1 in CPB and non-CPB groups, indicating a significant increase from T0 to T1, but no differences between the two groups. When compared to T0 values, sgp130 levels decreased in both groups (respectively 105+/-37 and 115+/-35 ng/ml at T0 for CPB and non-CPB groups, and 72+/-25 and 84+/-29 ng/ml at T1) while we are not able to detect differences between the groups. Whatever the group or the time, sIL-6R concentrations remained unchanged. CONCLUSIONS: We showed that the increase of IL-6 after artery bypass grafting was similar between patients operated with CPB or without CPB. We conclude that the main inductor of IL-6 release is linked to surgical trauma rather than a reaction to CPB. Since it is known that gp130 inhibits IL-6-biological activities, we suggest that the decrease of sgp130 sera levels could further enhance the inflammatory effects of IL-6 in cardiac surgery.

Aged↗