Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “circulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1995

Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis.

In a recent study from our group, the combination of methotrexate and sulphasalazine (MTX + SASP) seemed superior to MTX alone in the treatment of rheumatoid arthritis (RA). To assess the impact of these therapies on the cytokine cascade, the in vitro production and circulating concentrations of several cytokines and endogenous cytokine antagonists were measured in 30 healthy controls and longitudinally in a subset of 26 patients enrolled in this study. Compared to controls, RA patients had significantly higher circulating concentrations of interleukin-6 (IL-6), soluble receptors for tumour necrosis factor (sTNFR), soluble receptors for interleukin-2 (sIL-2R) and interleukin-1 receptor antagonists (IL-1RA), and their peripheral blood mononuclear cells (PBMNC) showed a higher spontaneous production of interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and IL-1RA (both secreted and cell-associated) and a higher stimulated production of cell-associated TNF alpha, IL-1RA and (to a lesser extent) IL-1 beta. Treatment with MTX alone (n = 12) or combined with SASP (n = 14), resulted in significant reductions of circulating IL-6 and sIL-2R but did not alter IL-1 beta, TNF alpha or IL-1RA concentrations. Decreases in circulating levels of sTNFR and in the in vitro production of cell-associated IL-1 beta and IL-1RA after stimulation were only observed in patients treated with MTX + SASP. The concentrations of IL-1RA and sTNFR in the circulation exceeded moderately those of IL-1 beta and TNF alpha but this is probably insufficient to block IL-1 and TNF alpha activity. In conclusion, therapy with MTX alone or with SASP modulates IL-6 and sIL-2R concentrations in RA. Decreased production of IL-1 beta and IL-1RA and circulating sTNFR levels were only observed during therapy with MTX + SASP. Whether this relates to the better clinical effect observed with the combination therapy remains to be investigated. Circulating levels of IL-6, sIL-2R and sTNFR seem useful markers of disease activity in RA.

Adult↗
PubMed2004

Effects of a circulating-water garment and forced-air warming on body heat content and core temperature.

BACKGROUND: Forced-air warming is sometimes unable to maintain perioperative normothermia. Therefore, the authors compared heat transfer, regional heat distribution, and core rewarming of forced-air warming with a novel circulating-water garment. METHODS: Nine volunteers were each evaluated on two randomly ordered study days. They were anesthetized and cooled to a core temperature near 34 degrees C. The volunteers were subsequently warmed for 2.5 h with either a circulating-water garment or a forced-air cover. Overall, heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 18 intramuscular needle thermocouples, 15 skin thermal flux transducers, and "deep" hand and foot thermometers. RESULTS: Heat production (approximately 60 kcal/h) and loss (approximately 45 kcal/h) were similar with each treatment before warming. The increases in heat transfer across anterior portions of the skin surface were similar with each warming system (approximately 65 kcal/h). Forced-air warming had no effect on posterior heat transfer, whereas circulating-water transferred 21+/-9 kcal/h through the posterior skin surface after a half hour of warming. Over 2.5 h, circulating water thus increased body heat content 56% more than forced air. Core temperatures thus increased faster than with circulating water than forced air, especially during the first hour, with the result that core temperature was 1.1 degrees +/- 0.7 degrees C greater after 2.5 h (P < 0.001). Peripheral tissue heat content increased twice as much as core heat content with each device, but the core-to-peripheral tissue temperature gradient remained positive throughout the study. CONCLUSIONS: The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4 degrees C/h faster than forced air. A substantial peripheral-to-core tissue temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.

Body Temperature↗
PubMed1995

Kinetics of endotoxin and tumor necrosis factor appearance in portal and systemic circulation after hemorrhagic shock in rats.

OBJECTIVE: This study was performed to investigate gut-derived bacterial translocation and the time course of endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF) appearance, both in portal and systemic circulation. SUMMARY BACKGROUND DATA: The significance of intestinal bacteria/endotoxin translocation or TNF formation in the development of systemic sepsis has been disputed. METHODS: A rat model of hemorrhagic shock (30-35 mm Hg for 90 min) and resuscitation was used. RESULTS: Bacterial translocation was histologically observed in the small intestinal wall 30 minutes after resuscitation. A significant increase in LPS concentrations was found in the portal vein (91.7 +/- 30.6 pg/mL) at 90 minutes, which remained steady until 150 minutes after shock. Lipopolysaccharide increased in the systemic circulation, the levels became significant at 120 minutes, and peaked (66.5 +/- 39.2 pg/mL) 150 minutes after shock. Tumor necrosis factor concentrations were found to be significantly elevated in both portal and systemic circulation (75.6 +/- 22.1 vs. 58.4 +/- 14.1 pg/mL) at 90 minutes post-shock. Although there was no further increase in TNF concentration in the portal blood. TNF peaked (83.5 +/- 17.7 pg/mL) in systemic circulation at 120 minutes and still was markedly increased at 150 minutes post-shock. In addition, higher LPS and TNF concentrations in systemic circulation were found in the nonsurvivors than in the surviving animals at the end of resuscitation. CONCLUSIONS: These results suggest that hemorrhagic shock may lead to early bacterial translocation in the intestinal wall and transient access of gut-derived LPS and LPS-induced mediators into the circulation predominantly via the portal circulation.

Animals↗
PubMedDate not supplied

Hemoglobin based oxygen carrying solution stability in extracorporeal circulation: an in vitro evaluation and implications for clinical use.

This study evaluated the stability of a hemoglobin based oxygen carrying (HBOC) solution during extracorporeal circulation. HBOC solution was diluted 1:1 with normal saline, 2 L of the resulting solution was oxygenated in either a bubble oxygenator (n=5) or membrane oxygenator (n=5), and it was placed in extracorporeal circulation at a rate of 2 L/min for 5 hr at 37 degrees C. To assess the effect of added human blood, 500 ml of fresh human whole blood was added to 1.5 L of diluted HBOC solution, and circulated as described. Methemoglobin level, hemoglobin integrity (percent of HBOC solution tetramer), and oxygen affinity (PO2 at 50% hemoglobin saturation) were measured. Extracorporeal circulation using the bubble oxygenator slightly altered (<1%) hemoglobin integrity compared with controls. Oxygen affinity decreased during extracorporeal circulation with both the membrane and bubble oxygenators; there was no significant difference between the oxygenators. Methemoglobin formation in controls and in extracorporeal circulation with either oxygenator was significant, with a slight advantage of the membrane compared with the bubble oxygenator; however, the presence of blood significantly decreased the rate of methemoglobin formation. In the presence of blood, HBOC solution remains structurally stable and efficacious for oxygen delivery during extracorporeal circulation.

Blood↗
PubMed1994

Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin: an oxygen-carrying resuscitative fluid.

OBJECTIVE: To evaluate the circulation persistence and organ biodistribution of a freeze-dried, oxygen carrying resuscitative fluid: liposome-encapsulated hemoglobin. DESIGN: Randomized, animal studies. SETTING: Accredited animal research facilities. SUBJECTS: Normal female Balb/c mice and male New Zealand rabbits. INTERVENTIONS: Two groups of normal female Balb/c mice were injected in the tail vein with either lyophilized liposome-encapsulated hemoglobin (n = 9) that was reconstituted just before administration, or with unlyophilized liposome-encapsulated hemoglobin (n = 9) as a comparison. Two groups of male New Zealand rabbits were injected in the ear vein with either lyophilized 99mTc-liposome-encapsulated hemoglobin (n = 6) or unlyophilized 99mTc-liposome-encapsulated hemoglobin as a comparison (n = 6). After injection, mice were anesthetized by brief inhalation of halothane followed by blood sampling through the retro-orbital sinus. Rabbits were anesthetized 30 mins before liposome-encapsulated hemoglobin administration with an intramuscular injection of a 5:1 mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg). Rabbits were then dynamically imaged for 90 mins, housed, and at 20 hrs, imaging again followed by autopsy and tissue sampling to validate imaged organ biodistributions. MEASUREMENTS: Circulation persistence in the mouse was measured by removing a blood sample at various time points up to 24 hrs after injection. The blood sample was centrifuged in a hematocrit capillary tube and the disappearance of the sedimented liposome-encapsulated hemoglobin fraction was measured. The change in the sedimented fraction of the liposomes with time was used to generate circulation persistence profiles in mice. The circulation persistence and organ biodistribution of 99mTc-liposome-encapsulated hemoglobin was measured by circling regions of interest on computer-generated gamma camera images. These image intensities were then calculated as a function of total injected dose which was measured from a known volume and activity of 99mTc-liposome-encapsulated hemoglobin. Actual tissue uptake was estimated from images by subtracting blood pool contribution which was measured by injecting 99mTc-labeled rabbit red cells. Imaged organ biodistribution was validated at 20 hrs by measuring activity in weighed portions of tissue after autopsy. MAIN RESULTS: The mean circulation half-life of liposome-encapsulated hemoglobin in mice injected at a dose of 1.0 g phospholipid/kg mouse and 1.95 g hemoglobin/kg was approximately 10.4 +/- 0.5 (SD) hrs. The circulation half-life of lyophilized liposome-encapsulated hemoglobin was 10.7 +/- 0.7 hrs. The circulation profiles demonstrate a rapid removal phase over the first 4 hrs after injection, followed by a secondary slow removal measured up to 24 hrs. The rapid removal phase of liposome-encapsulated hemoglobin and lyophilized liposome-encapsulated hemoglobin in the rabbit (injected at the same dose) indicated that lyophilized liposome-encapsulated hemoglobin persists longer than the unlyophilized form in the first 4 hrs after injection. The organ biodistributions of unlyophilized 99mTc-liposome-encapsulated hemoglobin and lyophilized 99mTc-liposome-encapsulated hemoglobin in the rabbit demonstrate that the reticuloendothelial system is the primary site of removal, with significant uptake of lyophilized 99mTc-liposome-encapsulated hemoglobin by the liver (15.6 +/- 1.0%), bone marrow (12.6 +/- 1.6%), and spleen (9.7 +/- 1.1%). The kidneys showed little accumulation of unlyophilized 99mTc-liposome-encapsulated hemoglobin or lyophilized 99mTc-liposome-encapsulated hemoglobin (1.6 +/- 0.2% and 1.8 +/- 0.1%, respectively), an important result for the efficacy and safety of this hemoglobin-based blood substitute. (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

Circulating adhesion molecules and severity of coronary atherosclerosis.

BACKGROUND: Circulating leukocytes are recruited at atherosclerotic sites through a family of adhesion molecules. Circulating forms of adhesion molecules in peripheral blood can be quantified now. OBJECTIVE: To evaluate the relationship between circulating adhesion molecules and severity of coronary atherosclerosis. METHODS: Subjects included 81 patients undergoing diagnostic coronary angiography, 12 of whom had normal coronary arteries (control group). The remaining 69 patients with demonstrable coronary atherosclerosis were divided into two groups by use of Gensini scores, namely mild atherosclerosis (n = 36, Gensini score 1-20) and severe atherosclerosis (n = 33, Gensini score > 20). Serum levels of circulating intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin of groups measured before angiography were compared. RESULTS: Circulating levels of ICAM-1 in members of mild and severe atherosclerosis groups were significantly higher than those in members of the control group, whereas there was no significant difference among circulating levels of VCAM-1 in members of the three groups. Circulating levels of E-selectin in members of the mild atherosclerosis group were significantly higher than those in members of the severe atherosclerosis and control groups. CONCLUSIONS: These findings suggest that E-selectin is related to the early stage, and ICAM-1 is related to the advanced stage, of coronary atherosclerosis. With progression of atherosclerosis, one-step adhesion by ICAM-1 could become more important than multistep adhesion involving E-selectin, ICAM-1, and VCAM-1. These molecules may serve as markers for severity of coronary atherosclerosis.

Adult↗
PubMed2006

Renal transplantation reverses functional deficiencies in circulating dendritic cell subsets in chronic renal failure patients.

BACKGROUND: Dendritic cell (DC) subsets play critical roles in regulation of innate and adaptive immune responses. These important antigen-presenting cells have not been extensively analyzed in chronic renal failure (CRF), during dialysis, or before and after renal transplantation. METHODS: The incidence of circulating precursor (pre)-DC subsets relative to total peripheral blood mononuclear cells was analyzed in healthy controls, haemodialysis patients, peritoneal dialysis patients, CRF patients, and renal transplant (RT) recipients. DC subsets were identified and characterized phenotypically by multicolour flow cytometric analysis and purified by immunomagnetic bead isolation respectively. Cytokine production and circulating DC mobilizing cytokines were determined by ELISA. RESULTS: The incidence of circulating prePDC was reduced in all patients, but the incidence of circulating preMDC was comparable in RT and dialysis patients compared to healthy controls. CRF patients exhibited the lowest incidence of circulating preMDC and prePDC. Immunomagnetic bead-isolated preMDC and prePDC from haemodialysis patients were functionally impaired (reduced expression of surface costimulatory molecules and interleukin-12p70 production following bacterial lipopolysaccharide stimulation, and reduced interferon-alpha production following herpes simplex virus stimulation respectively, compared to healthy controls and RT recipients. Glomerular filtration rate correlated significantly with the incidence of circulating preMDC, but not prePDC. CONCLUSIONS: Deficiencies in the incidence and function of precursor DC can be reversed with successful renal transplantation achieving normal renal function. However, the finding of reduced incidence of circulating prePDC in the peripheral blood in RT recipients may be of significance in the pathogenesis of infections and malignancies.

Adult↗
PubMed2005

Circulating surfactant protein-B levels increase acutely in response to exercise-induced left ventricular dysfunction.

1. As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv). 2. Because surfactant protein-B (SP-B) leaks into the blood stream from the alveoli in response to alveolocapillary barrier damage and exercise leads to increased Pmv, we sought to determine whether exercise results in increased plasma SP-B. Moreover, in the setting of exercise-induced left ventricular dysfunction, the consequent increase in left heart filling pressure and, therefore, P(mv) would be expected to further increase plasma SP-B levels. 3. Twenty consecutive subjects referred for treadmill exercise stress echocardiography (ESE) had venous blood sampled immediately before and after ESE for batch atrial natriuretic peptide (ANP) and SP-B assay. Echocardiographic measures of pulmonary haemodynamics (pulmonary artery flow acceleration time (pafAT) and right ventricular outflow tract velocity time integral (rVTI)) were also taken pre- and post-exercise. 4. Although circulating ANP levels increased following exercise (P < 0.001), there was no change in circulating SP-B levels in the entire cohort. 5. Ten subjects had a positive ESE for ventricular dysfunction. Although circulating ANP was increased post-exercise in both the negative and positive ESE groups (P < 0.05 and P < 0.01, respectively), circulating SP-B only increased post-exercise in the positive ESE group (P < 0.05). Echocardiographic parameters supported an increment in P(mv) in the cohort with exercise-induced left ventricular dysfunction because this group had an increase in pafAT (P < 0.05; reflecting pulmonary artery pressure) and no change in rVTI. 6. Physical exertion associated with a Bruce protocol ESE is insufficient to increase circulating SP-B, despite evidence of increased left atrial and pulmonary vascular pressure. However, in the setting of exercise-induced myocardial dysfunction, there is a detectable increase in circulating SP-B. 7. The exaggerated increase in pulmonary vascular pressure in exercise-induced myocardial dysfunction may result in increased SP-B leakage from the alveoli into the circulation by altering the integrity of the alveolocapillary barrier to protein.

Atrial Natriuretic Factor↗
PubMed2004

Psoriatic patients with arthropathy show significant expression of free HLA class I heavy chains on circulating monocytes: a potential role in the pathogenesis of psoriatic arthropathy.

BACKGROUND: Surface free heavy chains on monocytes were recently implicated in playing a role in the pathogenesis of several forms of arthritis. OBJECTIVES: To determine the expression of surface free heavy chains (recognized by monoclonal antibody HC10) on peripheral blood mononuclear cells of psoriatic patients with or without arthropathy. METHODS: Twenty-eight psoriatic patients from the dermatology outpatient clinic were included in this study. Blood samples were collected during outpatient visits and clinical characteristics of the patients were documented. Quantitative analyses of circulating mononuclear cells were performed using flow cytometry. RESULTS: Circulating monocytes showed higher expression of HC10 compared with circulating lymphocytes (P < 0.05). Psoriatic patients with arthropathy showed elevated expression of HC10 on peripheral blood monocytes compared with those without arthropathy (P < 0.05). Among the arthropathic group, those without the human leucocyte antigen (HLA)-B27 allele showed even higher expression of HC10 on circulating monocytes compared with those possessing HLA-B27 (P < 0.05). The polyarthropathic subgroup showed the highest HC10 expression, but the level of expression was not high enough to be of statistical significance compared with other arthropathic subgroups. No correlation was found between psoriatic skin involvement and the expression of HC10 on circulating monocytes. CONCLUSIONS: The presence of free heavy chains on circulating monocytes is closely associated with psoriatic arthropathy, while the expression of free heavy chains on circulating monocytes has no significant influence on psoriatic skin lesions.

Adolescent↗
PubMed1984

Response of circulating somatostatin, insulin, gastrin and GIP, to intraduodenal infusion of nutrients in normal man.

We have studied the effect of direct infusion of nutrients into the duodenum of normal subjects on circulating plasma somatostatin, insulin, gastrin and gastric inhibitory polypeptide (GIP) levels. Six normal subjects were given on four separate occasions 150 ml of isotonic solutions containing 100 calories of carbohydrate, protein, or fat, and a control solution of saline, by infusion into the second part of the duodenum. Plasma somatostatin rose slightly after carbohydrate, mean basal 30 +/- 3 pg/ml, peak 46 +/- 16 pg/ml at 15 min; and more markedly after protein, peak 57 +/- 9 pg/ml at 30 min. However, fat was the most potent intraduodenal stimulus to plasma somatostatin release into circulation, peak 101 +/- 11 pg/ml at 30 min. The plasma insulin rise was greatest after carbohydrate, peak 68 +/- 10 i.u., but there was a significant rise after protein also, peak 34 +/- 6 i.u. Plasma gastrin rose significantly after protein only, peak 70 +/- 22 pg/ml. Plasma GIP rose markedly after carbohydrate, basal 506 +/- 50 pg/ml, peak 1480 +/- 120 pg/ml. Protein was also a potent stimulus of circulating plasma GIP release, peak 1200 +/- 190 pg/ml, while fat was the least potent, peak 730 +/- 190 pg/ml. Thus, calorie for calorie, fat is the most potent intraduodenal nutrient stimulus of circulating somatostatin. We postulate therefore that somatostatin may be an enterogastrone--a circulating hormone released by intraduodenal fat which inhibits gastric acid secretion. Fat is the least potent intraduodenal nutrient stimulus of circulating GIP release. This is evidence against the hypothesis that circulating GIP acts as an enterogastrone.

Adult↗
PubMed1994

Circulating human megakaryocytes in cardiac diseases.

Both bone marrow and circulating megakaryocytes may produce platelets. Changes in number and properties of the circulating megakaryocytes in cardiac diseases may provide information about thrombopoiesis in these disease states. Circulating megakaryocytes were obtained by retrograde aspiration through wedged pulmonary artery catheters from patients without cardiac abnormalities, patients with cardiac diseases and patients with disorders known to affect the megakaryocyte-platelet axis or marrow-blood barrier. Their number, ploidy distribution and expression of the beta 1-integrin adhesion antigens were estimated. We found evidence for an increased number of circulating megakaryocytes during acute myocardial infarction and in patients with triple vessel disease. A significantly higher proportion of circulating megakaryocytes obtained within 60 h after acute myocardial infarction, expressed CDw49b (alpha-chain of VLA2), CDw49e (alpha-chain of VLA5), and CDw49f (alpha-chain of VLA6) compared to megakaryocytes of patients without cardiac diseases. In myocardial infarction the increase in number of circulating megakaryocytes together with the higher proportion that expressed the beta 1-integrin adhesion antigens favour the hypothesis that these megakaryocytes are acutely released from the bone marrow. This could reflect either a selective response to an increased demand for circulating platelets or be the result of an a selective mechanism resulting from damage to the marrow-blood barrier following the acute infarction or thrombolytic therapy administered.

Adult↗
PubMed1989

Further evidence for the origin of circulating calcitonin gene-related peptide in the rat.

1. We have attempted to determine the origin of a potent circulating vasodilator, calcitonin gene-related peptide (CGRP), by assessing the effects of administration of capsaicin and colchicine, and of thyroidectomy on plasma levels. Plasma CGRP, neurokinin A and calcitonin levels were measured using highly sensitive and specific radioimmunoassays, and the circulating forms of CGRP characterized by size-exclusion gel and high-performance liquid chromatography. 2. Seven minutes following the intraperitoneal injection of capsaicin (10 mg/kg body weight) plasma CGRP and neurokinin A levels were found to rise by 15- and 4-fold respectively, while there was no change in circulating calcitonin levels. Chromatography revealed that the immunochemical forms of CGRP released into the circulation by capsaicin were similar to those found in normal plasma, which included a peak co-eluting with the intact CGRP molecule. 3. Six hours after the intraperitoneal administration of colchicine (10 mg/kg body weight), CGRP was not detectable in the circulation of 40-day-old rats and plasma levels were significantly lowered in the group of greater than or equal to 200-day-old rats. Chromatography revealed that peaks of circulating immunoreactivity corresponding to monomeric CGRP and its fragments were substantially reduced following colchicine treatment. 4. The magnitude of capsaicin-evoked elevation of plasma CGRP was only marginally (significant at 0.1 greater than P greater than 0.05) reduced by pre-treatment with colchicine. 5. Thyroidectomy alone caused a significant reduction of plasma CGRP levels in greater than or equal to 200-day-old rats; a greater reduction was observed when thyroidectomy was combined with colchicine administration. However, when 40-day-old rats were thyroidectomized, there was an unexplained elevation of plasma CGRP levels. 6. The results suggest that while CGRP is normally released into the circulation from nerve terminals, both in young adult (40-day-old) and old (greater than or equal to 200-day-old) animals, a thyroidal origin is obvious only in old rats.

Animals↗
PubMed1983

Neutrophil circulation and release from bone marrow during hypothermia.

The effect of hypothermia on neutrophil circulation and release from bone marrow has been studied. Pigs were anesthetized and maintained at 37 degrees C or surface cooled to 29 degrees C over 60 min. As the core temperature was reduced to 29 degrees C, the number of circulating neutrophils (X 10(9) per liter) fell from 6.0 +/- 0.6 to 2.3 +/- 0.3 by 60 min. No significant change in the number of circulating mature or immature neutrophils was observed over the 4 h of observation at 29 degrees C. Neutrophil demargination after administration of intravenous catecholamines was similar at 37 and 29 degrees C. Steroid stimulation of bone marrow to release neutrophils was markedly impaired at 29 degrees C. Circulating mature neutrophils in normothermic pigs increased from 5.6 +/- 1.2 to 10.4 +/- 1.2 by 120 min after administration of intravenous hydrocortisone sodium succinate. Circulating immature neutrophils increased from 1.7 +/- 0.3 to 5.3 +/- 0.4. At 29 degrees C, no significant changes in the number of circulating mature or immature neutrophils occurred. Endotoxin also failed to stimulate neutrophil release from the bone marrow. Furthermore, a marked neutropenia occurred in hypothermic pigs after intravenous endotoxin, which persisted for the 3 h of observation. Neutrophil circulation and release from bone marrow are compromised by hypothermia, which may increase the risk for bacterial infection.

Animals↗
PubMed2006

Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice.

Leptin-deficient obese mice (ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (approximately 1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.

Animals↗
PubMed2004

Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics.

Adiponectin is a novel adipocytokine negatively correlated with parameters of the metabolic syndrome, such as body mass index (BMI), body fat mass (BFM), and circulating insulin levels. Furthermore, metabolic actions directly on the liver have been described. The aim of the present study was to characterize circulating adiponectin levels, hepatic turnover, and the association of adiponectin with key parameters of hepatic as well as systemic metabolism in cirrhosis, a catabolic disease. Circulating adiponectin levels and hepatic turnover were investigated in 20 patients with advanced cirrhosis. Hepatic hemodynamics [portal pressure, liver blood flow, hepatic vascular resistance, indocyanine green (ICG) half-life], body composition, resting energy expenditure, hepatic free fatty acids (FFA) and glucose turnover, and circulating levels of hormones (catecholamines, insulin, glucagon) and proinflammatory cytokines (IL-1beta, TNF-alpha, IL-6) were also assessed. Circulating adiponectin increased dependently on the clinical stage in cirrhosis compared with controls (15.2 +/- 1.7 vs. 8.2 +/- 1.1 microg/ml, respectively, P < 0.01), whereas hepatic extraction decreased. Adiponectin was negatively correlated with parameters of hepatic protein synthesis (prothrombin time: r = -0.62, P = 0.003; albumin: r = -0.72, P < 0.001) but not with transaminases or parameters of lipid metabolism. In addition, circulating adiponectin increased with portal pressure (r = 0.67, P = 0.003), hepatic vascular resistance (r = 0.60, P = 0.008), and effective hepatic blood flow (ICG half-life: r = 0.69, P = 0.001). Adiponectin in cirrhosis was not correlated with BMI, BFM, parameters of energy metabolism, insulin levels, hepatic FFA and glucose turnover, and circulating proinflammatory cytokines. These results demonstrate that 1) adiponectin plasma levels in cirrhosis are significantly elevated, 2) the liver is a major source of adiponectin extraction, and 3) adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function and altered hepatic hemodynamics.

Adiponectin↗
PubMed1992

On the purported discovery of the bronchial circulation by Leonardo da Vinci.

Among modern physiologists and anatomists, there has been a nearly universal acceptance that Leonardo da Vinci was the first to identify the anatomy of the bronchial circulation. However, because of certain ambiguities in both his anatomic drawing that was supposed to have shown this circulation and the accompanying descriptive text, we questioned whether he really could have been the first to discover this small but important vasculature. To address this question, we set out to repeat Leonardo's dissections in the ox. We reasoned that perhaps the normally tiny bronchial vessels would be considerably more noticeable in this very large species. Our dissections, however, failed to provide any evidence that Leonardo's drawing was that of the bronchial circulation. Furthermore we observed a set of distinct small pulmonary veins to the left upper and right middle lobes that Leonardo, given his lack of understanding of the function of the lung and its circulation, could have easily mistaken for a separate circulation. We thus conclude that Leonardo da Vinci did not describe the anatomy of the bronchial circulation. We believe that the first person to clearly and unequivocally describe the anatomy of this circulation was the Dutch Professor of Anatomy and Botany, Frederich Ruysch.

Anatomy, Artistic↗
PubMed1998

Modeling bronchial circulation with application to soluble gas exchange: description and sensitivity analysis.

The steady-state exchange of inert gases across an in situ canine trachea has recently been shown to be limited equally by diffusion and perfusion over a wide range (0.01-350) of blood solubilities (betablood; ml . ml-1 . atm-1). Hence, we hypothesize that the exchange of ethanol (betablood = 1,756 at 37 degrees C) in the airways depends on the blood flow rate from the bronchial circulation. To test this hypothesis, the dynamics of the bronchial circulation were incorporated into an existing model that describes the simultaneous exchange of heat, water, and a soluble gas in the airways. A detailed sensitivity analysis of key model parameters was performed by using the method of Latin hypercube sampling. The model accurately predicted a previously reported experimental exhalation profile of ethanol (R2 = 0.991) as well as the end-exhalation airstream temperature (34.6 degrees C). The model predicts that 27, 29, and 44% of exhaled ethanol in a single exhalation are derived from the tissues of the mucosa and submucosa, the bronchial circulation, and the tissue exterior to the submucosa (which would include the pulmonary circulation), respectively. Although the concentration of ethanol in the bronchial capillary decreased during inspiration, the three key model outputs (end-exhaled ethanol concentration, the slope of phase III, and end-exhaled temperature) were all statistically insensitive (P > 0.05) to the parameters describing the bronchial circulation. In contrast, the model outputs were all sensitive (P < 0.05) to the thickness of tissue separating the core body conditions from the bronchial smooth muscle. We conclude that both the bronchial circulation and the pulmonary circulation impact soluble gas exchange when the entire conducting airway tree is considered.

Administration, Inhalation↗
PubMed2001

Strenuous exercise decreases the percentage of type 1 T cells in the circulation.

Prolonged strenuous exercise is followed by a temporary functional immune impairment. Low numbers of CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells are found in the circulation. These cells can be divided according to their cytokine profile into type 1 (Th1 and Tc1), which produce interferon-gamma and interleukin (IL)-2, and type 2 (Th2 and Tc2) cells, which produce IL-4. The question addressed in the present study was whether exercise affected the relative balance between the circulating levels of these cytokine-producing T cells. Nine male runners performed treadmill running for 2.5 h at 75% of maximal oxygen consumption. The intracellular expression of cytokines was detected following stimulation with ionomycin and phorbol 12-myristate 13-acetate in blood obtained before, during, and after exercise. The percentage of type 1 T cells in the circulation was suppressed at the end of exercise and 2 h after exercise, whereas no changes were found in the percentage of type 2 T cells. Plasma epinephrine correlated negatively with the percentage of circulating CD8+ T cells producing IL-2, whereas peak IL-6 correlated with the percentage of CD8+ IL-4-producing T cells in the circulation. Peak plasma IL-6 correlated with plasma cortisol postrunning. In conclusion, the postexercise decrease in T lymphocyte number is accompanied by a more pronounced decrease in type 1 T cells, which may be linked to high plasma epinephrine. Furthermore, IL-6 may stimulate type 2 T cells, thereby maintaining a relatively unaltered percentage of these cells in the circulation compared with total circulating lymphocyte number.

Adult↗