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At least 721 records · Page 40Linked to original sources
PubMed1999

Effect of prostaglandin E1 and nitroglycerin on portal venous flow during hypothermic extracorporeal circulation: assessment by transesophageal echography.

BACKGROUND: Although several vasodilators are used to control vascular resistance during cardiac surgery, their effects on splanchnic circulation during extracorporeal circulation are unknown. We designed the present noninvasive study to evaluate the effect of prostaglandin E1 and nitroglycerin on portal venous flow during extracorporeal circulation using transesophageal echography. METHODS: We included 26 patients undergoing cardiac surgery with moderate hypothermic extracorporeal circulation in this study. After obtaining hemodynamic stability under extracorporeal circulation, we measured portal venous diameter, mean flow velocity and the velocity time integral using transesophageal echography and calculated portal venous flow. The patients were assigned to two groups where either prostaglandin E1 (N = 13) or nitroglycerin (N = 13) was administered intravenously to maintain perfusion pressure at the level of 70 mmHg. We measured the same parameters 20 and 40 min following administration of the drug. RESULTS: Visualization of the portal vein was obtained by transesophageal echography in anesthetized patients. Calculated portal venous flow significantly increased in the prostaglandin E1 group, while it did not alter in the nitroglycerin group. CONCLUSION: The present results indicate that transesophageal echography may be a feasible tool to assess portal venous flow, and that prostaglandin E1 may improve the blood distribution to the splanchnic area and the liver during hypothermic extracorporeal circulation.

Alprostadil↗
PubMed1986

Similarity and dissimilarity of the vasoconstrictor effects of Bay K 8644 on coronary, femoral, mesenteric and renal circulations of dogs.

The effect of the dihydropyridine calcium agonist Bay K 8644 on the coronary, femoral, mesenteric and renal circulations was investigated and compared with that of noradrenaline in pentobarbitone-anaesthetized dogs. The left anterior descending coronary, femoral, cranial mesenteric and renal arteries were cannulated and their arterial beds perfused with autologous blood at a constant pressure slightly higher than the mean systemic arterial blood pressure. Bay K 8644 (0.1-300 nmol) and noradrenaline (0.1-300 nmol) were injected intra-arterially. Bay K 8644 decreased blood flow (vasoconstriction) in all 4 arterial beds. A maximum decrease was attained at 100 nmol and a further increase in dose did not appear to result in a further decrease in blood flow. At maximum effects blood flow decreased to about 35% of the basal value in coronary, 30% in femoral, 20% in renal and 15% in mesenteric circulation. Normalized ED50 values (ED50 divided by basal flow) of Bay K 8644 were 0.07 +/- 0.02 nmol in the femoral, 0.08 +/- 0.01 nmol in the coronary, 0.16 +/- 0.06 nmol in the mesenteric and 0.55 +/- 0.19 nmol in the renal circulation. At 100 nmol, the values for the half-duration of Bay K 8644 vasoconstrictor effects were about 196 s in the renal, 78 s in the mesenteric, 84 s in the femoral and 21 s in the coronary circulation. Noradrenaline produced a dose-dependent decrease in blood flow in femoral, mesenteric and renal circulations, and was about 2 times in femoral, 4 times in mesenteric and 9 times in renal circulation more potent than Bay K 8644. 8. Bay K 8644 produced slight increases in the maximum rate of rise of left ventricular pressure and intraluminal pressure of the ileum. However, the increases did not appear to impede blood flow. 9. Bay K 8644 produced slightly but significantly greater femoral vasoconstriction in normal dogs than in reserpine-pretreated dogs. 10. From these results it was concluded that differences in potency, effectiveness and duration of the vasoconstrictor effects of Bay K 8644 between the 4 arterial beds probably derive from differences in characteristics ofthe smooth muscle ofresistance vessels there. In arterial beds where alpha-adrenoceptors are dominant, potentiation of the vasoconstrictor effect ofendogenous catecholamines by Bay K 8644 seems to contribute to its vasoconstrictor effect.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2004

Circulating messenger RNA of alpha-fetoprotein: a possible risk factor of recurrence after resection of hepatocellular carcinoma.

HYPOTHESIS: Isolated tumor cells may be associated with micrometastasis. Circulating alpha-fetoprotein messenger RNA (AFP mRNA) in patients with hepatocellular carcinoma (HCC) has been considered to represent isolated tumor cells. We propose that circulating AFP mRNA may have prognostic value after curative resection of HCC. DESIGN: A prospective cohort study. SETTING: Referral center. PATIENTS: Eighty-one consecutive patients who underwent curative resection of HCC. MEASUREMENTS: A nested reverse-transcriptase polymerase chain reaction (RT-PCR) assay for circulating AFP mRNA before and again 12 weeks after surgery in 81 patients and in a control group. Clinicopathological variables and postoperative course (recurrence and recurrence-free survival) were examined for correlation with the levels of circulating AFP mRNA. RESULTS: Of the 81 patients, 22 (27.2%) and 19 (23.4%) had AFP mRNA detected preoperatively and postoperatively, respectively. The recurrence-free survival at 1, 2, and 3 years after resection was significantly shorter in the latter patients (52.6%, 15.6%, and 0%, respectively; P<.001) but not in the former (81.8%, 54.5%, and 29.2%; P = .28). In univariate analysis, a significantly higher recurrence rate was found in patients with liver cirrhosis (P = .03), Edmondson-Steiner differentiation grade III or IV (P<.001), incomplete or absent capsule (P = .001), vascular invasion (P<.001), daughter nodules (P = .003), or a positivity for postoperative circulating AFP mRNA (P<.001). Postoperative positivity for circulating AFP mRNA remained a significant risk factor (P = .002; hazard ratio 3.13; 95% confidence interval, 1.52-6.47) in the multivariate analysis. CONCLUSION: The detection of circulating AFP mRNA 12 weeks postoperatively is associated with an increased and earlier risk of HCC recurrence.

Carcinoma, Hepatocellular↗
PubMed1984

Lack of activation of C1, despite circulating immune complexes detected by two C1q methods, in patients with rheumatoid arthritis.

The activation of C1 by circulating immune complexes in patients with rheumatoid arthritis was investigated. C1rC1s(C1-In)2 complexes in EDTA-plasma, reflecting C1 activation in vivo, were slightly raised in 35 of 57 patients with rheumatoid arthritis, though most patients had elevated levels of circulating immune complexes as measured with either the 125I-C1q binding test or the C1q solid phase assay. The activation of C1 by circulating immune complexes in vitro was investigated by measuring the generation of C1rC1s(C1-In)2 complexes during 60 minutes at 37 degrees C in diluted recalcified EDTA-plasma. In 16 of the 57 patients, a slightly increased C1 activation in vitro was observed. These patients tended to have high levels of circulating immune complexes. However, the majority of the patients with high levels of circulating immune complexes showed a normal C1 activation in vitro. Therefore, it was concluded that measurement of circulating immune complexes by either of the two C1q methods in patients with rheumatoid arthritis does not imply that these circulating immune complexes are able to activate C1.

Aged↗
PubMed1992

Detection of circulating intercellular adhesion molecule-1 in chronic liver diseases.

The leucocyte adhesion molecule intercellular adhesion molecule-1 is induced on bile ducts in patients with primary biliary cirrhosis and primary sclerosing cholangitis and may be involved in targeting immune damage to these structures. It has recently been reported that, when activated, in vitro lymphocytes release a soluble form of intercellular adhesion molecule-1 that can also be detected in human serum. Because it is functionally active, this circulating intercellular adhesion molecule-1 might play a role in regulating inflammation by blocking adhesion. We used an enzyme-linked immunosorbent assay to detect circulating intercellular adhesion molecule-1 in the serum of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Levels of circulating intercellular adhesion molecule-1 were markedly elevated in primary biliary cirrhosis and primary sclerosing cholangitis when compared with other chronic liver diseases. Circulating intercellular adhesion molecule-1 is probably derived from activated lymphocytes rather than from bile ducts because biliary epithelial cells from patients with primary biliary cirrhosis did not release circulating intercellular adhesion molecule-1 when stimulated to express the membrane-bound molecule in vitro. These studies are the first to demonstrate circulating intercellular adhesion molecule-1 in chronic inflammatory diseases that are characterized by strong tissue expression of intercellular adhesion molecule-1 and as such suggest a potential immunoregulatory role for circulating adhesion molecules. The very high levels detected in primary biliary cirrhosis and primary sclerosing cholangitis probably reflect lymphocyte activation, which is further evidence of immune pathogeneses for these diseases.

Bilirubin↗
PubMed1999

Effects of immune complex formation and complement activation on circulating platelets in the primate.

Primate platelets are different from rodent and rabbit platelets in that they do not express receptors for C3a or C5a or immune adherence receptors. This study assessed the effects of immune complex (IC)-induced complement activation on primate platelets in the circulation. Cynomolgus monkeys (CYN, N = 4) immunized to bovine gamma globulin (BGG) were infused with BGG over 5 min to induce acute intravascular IC formation and complement activation. The studies were carried out under normal complement conditions (N = 12), partial complement inhibition (CAB-2 treated, N = 3), or total complement inhibition (CVF treated, N = 1). Under normal complement conditions, BGG infusion increased C3a levels from undetectable to an average of 11.9 +/- 2.6 micrograms/ml. At this time, decreases occurring in both circulating neutrophils (85 +/- 6%) and monocytes (78 +/- 6%) were significantly greater than decreases in circulating platelets (13 +/- 3%, p < 0.001). Partial complement inhibition had an equivocal effect on the BGG-induced changes in circulating leukocytes, while total complement inhibition abrogated these changes. In contrast, platelet changes were unaffected by complement inhibition. We conclude that, compared to circulating leukocytes, circulating platelets are insensitive to intravascular complement activation induced by IC in the nonhuman primate. These results contrast with previous studies in rodents which demonstrate strong effects of IC-induced intravascular complement activation on both circulating neutrophils and platelets.

Animals↗
PubMed2006

No correlation between circulating ACE activity and VO2max or mechanical efficiency in women.

The insertion (I) variant of the angiotensin-1 converting enzyme (ACE) I/D genetic polymorphism is associated with lower circulating and tissue ACE activity. Some studies have also suggested associations of ACE I/D genotype with endurance phenotypes. This study assessed the relationships between circulating ACE activity, ACE I/D genotype, mechanical efficiency and the maximal rate of oxygen uptake in sedentary individuals. Sixty-two untrained women were tested for mechanical efficiency during submaximal cycle ergometry (delta and gross efficiencies during exercise between 40 and 80 W) and the maximal rate of oxygen uptake during incremental treadmill running. Respiratory variables were measured using indirect calorimetry. Venous blood was obtained for direct assay of circulating ACE activity, allowing for the assessment of correlations between two continuous variables, rather than a categorical analysis of endurance phenotype by genotype alone. ACE I/D genotype was also determined, and was strongly associated with circulating ACE activity (P < 0.0005). Neither circulating ACE activity (27.4 +/- 8.4 nM His-Leu-ml(-1)) nor ACE genotype showed a statistically significant association with any of the endurance phenotypes measured. The weak correlations observed included r = -0.122 (P = 0.229) for the relationship between delta efficiency (23.9 +/- 2.5%) and circulating ACE activity and r = 0.134 (P > 0.6) for the relationship between maximal aerobic power (149.1 +/- 22.9 ml kg(-2/3) min(-1)) and circulating ACE activity. The data do not support a role for systemic ACE activity in the regulation of endurance performance in sedentary individuals, extending this observation to a large female cohort.

Adult↗
PubMed2006

Symptomatic intracerebral hematomas in posterior circulation stroke patients anticoagulated with heparin.

BACKGROUND: A lot of clinicians use heparin in patients with posterior circulation stroke. Frequency and risk factors of symptomatic intracerebral hematoma (ICH) in posterior circulation infarct patients anticoagulated with unfractionated heparin are not known. METHODS: To determine the incidence and the risk factors of the heparin-related ICH in posterior circulation infarct patients, we retrospectively reviewed the clinical features of 37 patients who had acute posterior circulation infarct and received intravenous heparin after they underwent brain computed tomographic scans and diffusion-weighted imaging (DWI). Follow-up brain scans were obtained at any time if clinical symptoms worsened. Volumes of acute posterior circulation infarction were calculated on DWI. RESULTS: Of 37 patients, four (10.8%) developed symptomatic ICH during heparin infusion. The location of ICH was cerebellum in all the hemorrhagic worsening patients. We found that the size of an acute infarction calculated on DWI is the risk factor of symptomatic ICH during intravenous heparin therapy in patients with posterior circulation infarct. CONCLUSIONS: Until a large prospective study is performed, it may be prudent to avoid heparin infusion in patients with large posterior circulation infarct documented on DWI.

Aged↗
PubMed1992

Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation.

OBJECTIVE: We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation. STUDY DESIGN: Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 (10(-8) mol/L) or endothelin-1 (10(-8) mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate (10(-6) mol/L), acetylcholine (10(-4) mol/L), the calcium ionophore A23187 (10(-6) mol/L), and histamine (10(-8) to 10(-4) mol/L) were also determined in the preconstricted fetal-placental circulation. RESULTS: Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L) increased resting perfusion pressure (p less than 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p less than 0.0004) or endothelin-1 (p less than 0.06). Nitric oxide generated by addition of glyceryl trinitrate (10(-6) mol/L) attenuated the vasoconstrictor effects of U46619 (p less than 0.026) or endothelin-1 (p less than 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations (10(-6) to 10(-4) mol/L) above those shown to release nitric oxide in other systems. CONCLUSION: The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation.

Acetylcholine↗
PubMed1983

Circulating immune complexes in patients with colorectal cancer.

We have attempted to better define host humoral immune response in neoplasia by quantitating serial circulating immune complex values before and after surgery in patients with primary or metastatic colorectal cancer. Circulating immune complex levels were correlated with serial carcinoembryonic antigen values and tumor courses in patients with primary resectable colorectal cancer (four patients), resectable liver metastases (three patients), diffuse liver metastases treated with regional chemotherapy (three patients), and untreated intrahepatic (one patient) and extrahepatic metastases (one patient). Circulating immune complex levels, as measured by an antigen-nonspecific assay, which utilized 4 percent polyethylene glycol insolubilization, were increased in all patients at presentation (734 delta OD450 +/- 381) when compared with normal human control sera (202 +/- 4, p less than 0.05). No particular relation was found between presenting circulating immune complex levels and tumor burden. Progressive circulating immune complex increases were demonstrated only in patients whose tumors were either completely removed or dramatically responded to regional therapy (that is, when the tumor antigen load, as reflected by the carcinoembryonic antigen value, rapidly diminished). Serum samples obtained at times of presumed antibody excess in the patients with gastrointestinal cancers were found to contain unexpectedly high concentrations of IgA. We believe these data demonstrate the kinetics of circulating immune complex change during tumor course and they have allowed us to begin to identify circulating immune complex components in patients with colorectal cancer. The results confirm our earlier findings in patients with gestational tumors and differ from accepted relations between immune complexes and tumor growth.

Antigen-Antibody Complex↗
PubMed1993

Effect of chemically modified GM1 and neoglycolipid analogs of GM1 on liposome circulation time: evidence supporting the dysopsonin hypothesis.

The sugar group of the ganglioside GM1 has been modified by periodate oxidation, reduction or reductive amination. The negative charge of sialic acid of GM1 has also been removed by methylation or reductive hydrolysis. A series of neoglycolipid analogs of GM1 were synthesized by coupling the GM1 oligosaccharide (GM1OS) to dioleoylphosphatidylethanolamine (DOPE) via different spacer arms. The individual GM1 derivatives were incorporated into egg phosphatidylcholine/cholesterol liposomes and tested in mice in order to see whether they were effective in prolonging liposome circulation. The oxidized GM1 did not show any ability to prolong circulation. However, the lost activity after oxidation was completely recovered by the subsequent reduction step. A series of aminated GM1 derivatives were prepared via oxidation followed by reductive amination with various substituted amines. beta-Alanyl GM1 showed a comparable activity to the native GM1, while other aminated GM1S showed reduced activity in terms of prolonging circulation of liposomes. Blocking the negative charge of sialic acid by methylation did not greatly lessen the activity, and removing the carboxyl group of sialic acid by reductive hydrolysis reduced the activity by only approx. 20%. Among the neoglycolipid analogs of GM1 only GM1OS directly conjugated to DOPE was effective in prolonging the circulation, whereas conjugates with a spacer of various length were not effective. These results emphasize the importance of the molecular structure of GM1 for its functional ability to prolong the liposome circulation. Furthermore, modifications which abolish the cholera toxin-binding activity of GM1 also decrease the ability to prolong the circulation time of the liposomes, and vice versa. Such strong correlation further supports the idea that the specific recognition of GM1 oligosaccharide by putative dysopsonin(s) is responsible for the ability to prolong the liposomes circulation time.

Amination↗
PubMed1993

Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats.

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, +/- 3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.

3,4-Methylenedioxyamphetamine↗
PubMed1983

Schistosoma japonicum: immunological characterization and detection of circulating polysaccharide antigens from adult worms.

The antigenic constituents of a trichloroacetic acid (TCA)-soluble fraction of adult Schistosoma japonicum were studied with immunoelectrophoresis, and compared with those of Schistosoma mansoni. Eight TCA-soluble antigens of S. japonicum were demonstrated, five of which showed immunological identity with S. mansoni antigens. Of the eight antigens, five antigens with anodic motility were found as circulating antigens in S. japonicum-infected hamster and rabbit sera; the major circulating antigen was the circulating anodic antigen (CAA). Two other antigens, with cathodic motility, including the circulating cathodic antigen (CCA), were demonstrable as circulating antigens in S. mansoni infections, but not in S. japonicum infections. Most of the circulating antigens were shown to be gut-associated. Only one antigen, line 2, which was not demonstrable as circulating antigen and which was present in the parenchyma of the worms, was found to be specific for S. japonicum. Using an ELISA for the detection of CAA in the sera of S. japonicum-infected rabbits, a lower detection level of 100 ng CAA/ml serum was achieved. Moreover, at 7-8 weeks after infection, a direct relationship between worm burden and CAA level was demonstrated.

Animals↗
PubMed1992

Enhanced localization of liposomes with prolonged blood circulation time in infected lung tissue.

In an experimental model of unilateral pneumonia caused by Klebsiella pneumoniae in rats we investigated whether intravenous administration of liposomes with prolonged blood circulation time resulted in significant localization of liposomes in infected lung tissue. Liposomes (100 nm) composed of hydrogenated phosphatidylinositol:hydrogenated phosphatidylcholine:cholesterol (molar ratio, 1:10:5) radiolabeled with gallium-67-deferoxamine showed relatively long blood circulation time. The degree of localization of these long circulating liposomes in the infected left lung was significantly higher compared to that of localization of 110 nm egg phosphatidylglycerol:egg phosphatidylcholine:cholesterol (molar ratio, 1:10:5) liposomes which exhibited relatively short blood circulation time. At 16 h after administration of the long circulating liposomes (when 10% of the injected dose was still present in the bloodstream) localization of liposomes in the infected left lung was increased up to 10-fold compared to the left lung of uninfected rats, and appeared to be highly correlated with the intensity of the infection. In the uninfected right lung the localization of long circulating liposomes was not increased. The degree of localization of liposomes in the infected tissue is dependent on the residence time of liposomes in the blood compartment. The extent of localization of long circulating liposomes in infected tissue appeared to be dependent on the liposomal dose administered.

Animals↗
PubMed2004

Acute reduction of circulating arginine in mice does not compromise whole body NO production.

The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We have now studied the role of acutely reducing circulating arginine on whole body NO production in mice. Measurements were performed in 4 groups of mice, treated with saline (SAL) or arginase (ASE), and SAL or bacterial endotoxin (LPS). After 5 h, a 57% reduction in circulating arginine was obtained by intravenous injections of arginase (SAL/SAL: 138+/-7; ASE/SAL: 59+/-10 microM, P<0.05). Reduced circulating arginine caused a reduction in plasma arginine flux (SAL/SAL: 82+/-6; ASE/SAL: 63+/-5 nmol/(10 g b.w. min), P<0.05), but did not change whole body NO production. LPS treatment caused an increase in NO production (SAL/SAL: 1.3+/-0.3 SAL/LPS 2.3+/-0.4 nmol/(10 g b.w. min), P<0.05), presumably by NOS-2 and was unaffected by reducing circulating arginine. Also, intestinal citrulline and renal arginine production were not increased in LPS-challenged mice with reduced circulating arginine levels. The present study indicates that an acute decrease in circulating arginine does not compromise whole body NO production and provides evidence against a role for renal arginine production to counteract an acute reduction of circulating arginine.

Animals↗
PubMed2005

Circulating levels of tumor necrosis factor-alpha correlate positively with severity of peripheral oedema in patients with right heart failure.

BACKGROUND: Several previous studies have shown that circulating levels of tumor necrosis factor-alpha (TNF) are elevated in patients with advanced congestive heart failure. However, the relationship between circulating levels of TNF and severity of peripheral oedema in these patients has not been previously evaluated. AIMS: To investigate the relationship between circulating levels of TNF, and severity of peripheral oedema in patients with right-sided heart failure (RHF). METHODS AND RESULTS: Circulating levels of TNF were measured in 15 healthy volunteers, and in 83 patients with RHF with various levels of peripheral oedema. At presentation, 13 patients had no peripheral oedema (grade 0), 22 patients had mild peripheral oedema (grade 1), 23 patients had moderate peripheral oedema (grade 2), and 25 patients had severe peripheral oedema (grade 3). The values of circulating TNF levels (mean +/- S.E.M.) at presentation in the control group and in the RHF patients (oedema grades 0-3) were 2.98+/-0.21, 4.22+/-0.55, 4.67+/-0.29, 7.66+/-0.44, and 10.94+/-0.67 pg/mL respectively. There was a significant difference between the groups (p < 0.0001, ANOVA), and a significant positive correlation was found between circulating TNF levels and severity of peripheral oedema (r = 0.77, p<0.0001). CONCLUSION: A significant relationship is present between circulating levels of TNF and severity of peripheral oedema in patients with RHF.

Adult↗
PubMed2004

Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis.

OBJECTIVE: Hematopoietic stem cells (HSC), normally resident in bone marrow, can be detected in the murine and human circulation. It is thought that HSC move in and out of bone marrow daily and that returning HSC are generally equivalent to their bone marrow counterparts in phenotype and function. However, large numbers of mononuclear blood cells are required to rescue animals from lethal irradiation, indicating either that the prevalence of circulating HSC is low, or they are inherently deficient in their repopulating ability. Accordingly, recent data suggest that circulating HSC may be unable to stably engraft WBM under homeostatic conditions. The purpose of this study was to explore these dynamics in detail using parabiosis and bone marrow transplantation. MATERIALS AND METHODS: The WBM and skeletal muscle HSC stem cell compartments of parabiosed CD45 congenic mice were analyzed functionally (via bone marrow transplantation) and phenotypically (via flow cytometry) for circulating stem cells at specific time points postparabiosis and after surgical separation. RESULTS: Surprisingly, we find that stem cells trafficking out of bone marrow and into the circulation do not stably return to bone marrow, although long-lived lymphoid precursors do stably re-engraft. Circulating HSC do, however, take up residence in skeletal muscle, wherein they account for HSC activity. CONCLUSION: Circulating HSC are not in flux with the bone marrow HSC and can persist in peripheral tissues.

Animals↗
PubMed2007

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status.

Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D(3) and its metabolic product-25(OH)D(3) has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6400IU vitamin D(3)/day for 6 months. Results (1) the relationship between circulating vitamin D(3) and 25(OH)D in both groups was not linear, but appeared saturable and controlled; (2) optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D(3) and 25(OH)D exceeded 0.3; at this point, the V(max) of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase operates well below its V(max) because of chronic substrate deficiency, namely vitamin D(3). When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what "normal" vitamin D status should be.

Cholecalciferol↗