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PubMed1979

Response of pulmonary (circulating) megakaryocytes to experimentally induced consumption coagulopathy in rabbits.

The effects of slow temporary infusion of a tissue thromboplastin solution into the superior vena cava on pulmonary as well as circulating megakaryocytes were studied in 40 rabbits (2-48 hours after infusion) and related to 6 noninfused and 7 infused with normal saline. This is a simple and specific method of inducing a fall in blood platelet levels and thereby an activation of thrombocytopoiesis and megakaryocytopoiesis. The induced intravascular coagulation is probably counterbalanced by an activated fibrinolysis allowing the animals to survive the infusion and thereby offering the possibility of studying the long-term effects. An increase to about 300% of the normal values in circulating as well as pulmonary megakaryocytes was found 20 and 24 hours after the onset of the infusions respectively. The number of circulating and pulmonary megakaryocytes, showing great individual variations, however, dropped to normal levels within 28 hours after onset of the infusions, which means that megakaryocytes remain detectable for less than eight hours in the lungs. No increase was found in pulmonary megakaryocytes in the control (saline infused) group. In our opinion the entrance of megakaryocytes from the bone marrow into the blood circulation in an incidental event, the number in the circulation reflecting the activity of megakarycocytopoiesis. This experiment supports our suggestion that intravascular coagulation is one of the major pathophysiological mechanisms leading to an increase in pulmonary megakaryocytes.

Animals↗
PubMed2006

Circulating osteoprotegerin affects bone metabolism in dialysis patients with mild secondary hyperparathyroidism.

Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastic formation and activity. Circulating OPG levels are elevated in uremia. The role of elevated circulating OPG levels in uremia remains unknown. Blood samples were obtained from 22 non-diabetic dialysis patients who underwent iliac bone biopsy examination. The serum OPG concentration was assayed by ELISA. The circulating OPG levels showed a negative correlation with the ratio of eroded surface/bone surface (ES/BS) in biopsied iliac bone samples among 15 of those with plasma intact PTH levels less than 300 pg/mL (P < 0.05, r(2) = 0.270). Patients with serum OPG levels less than 2.0 ng/mL showed significantly greater ES/BS values than those with levels > or =3.0 ng/mL, while the intact PTH levels were comparable among those groups. These tendencies disappeared when seven patients with plasma intact PTH levels more than 300 pg/mL were included into the analysis. In conclusion, circulating OPG levels showed a significant negative correlation with a bone resorption parameters in dialysis patients with mild secondary hyperparathyroidism. Circulating OPG might have a suppressive effect on osteoclastic bone resorption in dialysis patients.

Adult↗
PubMed1968

Early effects of abrupt reduction of local pressure on the forearm and its circulation.

1. The pressure at the surface of a segment of forearm enclosed in a plethysmograph was abruptly reduced from atmospheric to -20 to -120 mm Hg.2. Forearm circumference (equivalent to the volume of a small segment of forearm (V(f))) was measured with a strain gauge. Pressure was measured in the plethysmograph (P(p)), in veins exposed (P(ve)) and not exposed (P(vne)) to suction, in the brachial artery not exposed to suction (P(bane)) and in forearm tissue (P(t)).3. Reduction of P(p) caused increase of V(f). This was not due to gas evolution, since bubbles would not be liberated at the pressures employed. Nor was increase of V(f) due to venous backflow since P(ve) fell, but P(vne) did not, even with upper arm circulation occluded or when P(vne) was raised by venous occlusion prior to reduction of P(p).4. Reduction of P(p) temporarily arrested venous outflow since P(ve) < P(vne) < P(bane) for 30 sec. With reduction of P(p) 30 sec after occlusion of the upper-arm circulation, P(ve) < P(vne) for > 1 min, indicating that arterial inflow was then minimal.5. Increase of V(f), following reduction of P(p), was therefore due to inflow of arterial blood, of soft tissue or interstitial fluid. Interstitial fluid could flow from regions external to the plethysmograph, or enter as the result of filtration across capillaries. Occlusion of the upper arm circulation was not expected to interfere with motion of forearm soft tissue or the intratissue flow of interstitial fluid. It appears that capillary filtration is small compared with observed blood flow. Therefore subtraction of V(foccl) measured at intervals after reduction of P(p) (upper arm circulation occluded) from V(f) similarly obtained (but upper arm circulation free) appeared to give change of forearm volume due to inflow of arterial blood (DeltaV(b)). V(b), the volume inflow rate of arterial blood during suction, was then obtained.6. Resting forearm flow was 1.8 ml./min/100 ml. in seven normal subjects (average mean arterial blood pressure 86 mm Hg). With P(p) = -90 mm Hg, V(b) was 10.2 ml./min/100 ml. Suction therefore reduced vascular resistance, measured as (P(bane)-P(ve)) /V(b).

Adult↗
PubMed2005

Circulating levels of nitric oxide and vascular endothelial growth factor throughout ovine pregnancy.

Nitric oxide (NO) production has been shown to increase uterine blood flow and be elevated in ewes carrying multiple fetuses during late gestation. Vascular endothelial growth factor (VEGF) has been reported to increase eNOS expression and NO production in endothelial cell cultures. As angiogenesis and vasodilatation of the uterine and placental vascular beds are important at all stages of pregnancy, it is important to understand how VEGF and NO change throughout gestation in circulation. Therefore the objectives of the current study were to evaluate the systemic levels of VEGF and NO metabolite (NOx) throughout ovine gestation and to determine if there was an effect of sheep carrying singletons versus multiple fetuses. NOx and VEGF concentrations were analysed in systemic blood from pregnant ewes starting on day 27 of pregnancy and at multiple intermittent intervals throughout pregnancy until term. Blood samples from non-pregnant and postpartum ewes were also analysed. NOx concentrations in maternal blood expressed a biphasic pattern with NOx concentrations increasing (P < 0.05) over non-pregnant values on days 40-69 of gestation, returning to non-pregnant concentrations from days 70-100, and again increasing (P < 0.05) until term. Postpartum NOx concentrations were similar to non-pregnant values. While ewes carrying multiple fetuses had increased (P < 0.05) concentrations of NOx on days 60-69, there were no differences in NOx concentrations in ewes carrying singletons or multiples from day 70-99 of gestation. Starting on day 100 and continuing throughout the duration of pregnancy, ewes carrying multiple fetuses had increased (P < 0.05) concentrations of NOx compared to ewes carrying singletons. Concentrations of VEGF showed a different pattern from NOx with VEGF decreasing (P < 0.05) from day 20-69 of pregnancy compared to non-pregnant ewes. Concentrations of VEGF returned to non-pregnant levels by day 70 and remained constant throughout the duration of pregnancy. On days 20-39, ewes carrying singleton fetuses had an increased VEGF concentration (P < 0.05), whereas ewes carrying multiple fetuses demonstrated elevated VEGF concentrations from day 90-109 of gestation. Concentrations from non-pregnant and postpartum ewes did not differ (P > 0.1). While there was no effect of fetal number on circulating VEGF concentrations, circulating levels of NOx were substantially increased (P < 0.05) in ewes carrying multiple fetuses, compared to ewes carrying singletons. The pattern of the rise in NOx in circulating plasma was not directly associated with changes in VEGF regardless of the number of fetuses present. However, circulating concentrations of NOx and VEGF appear to, respectively, follow patterns of uterine blood flow and angiogenesis of the uterus. An understanding of these circulatory patterns may have important implications for fetal size, birth weight and fetal/developmental origins of adult disease.

Animals↗
PubMed1981

Reduction of circulating granulocytes induced by type 1 pneumococcal cell walls in New Zealand white rabbits.

Granulocytopenia seen during human pneumococcal disease is associated with a worsened prognosis. Streptococcus pneumoniae type 1 reduces circulating granulocytes and induces pulmonary leukostasis in rabbits. We studied which type 1 pneumococcal fraction(s) might be responsible for the reduction in circulating granulocytes. Rabbits were challenged intravenously with nonpyrogenic sterile saline, sonicated type 1 pneumococci, capsular polysaccharide from type 1 pneumococci, or cell walls from type 1 pneumococci. Nonviable pneumococci caused a mean decrease in blood granulocytes of 64% as compared with a mean increase of 124% in saline-injected controls, a difference significant at P less than 0.001. Pneumococcal cell walls induced significant decreases in circulating granulocytes at all doses tested when compared with saline-injected controls, whereas capsular polysaccharide induced no reduction in granulocytes. On a weight-for-weight basis, cell wall induced significantly more granulocyte reduction than did capsular polysaccharide at doses of either 10 mg (P less than 0.01) or 20 mg (P less than 0.005). A nonencapsulated pneumococcus also induced a profound granulocyte reduction (mean decrease in blood granulocytes, 88%) in the absence of detectable circulating polysaccharide. The cell wall fraction of S. pneumoniae type 1 was a more effective constituent in promoting the reduction in circulating granulocytes in rabbits.

Agranulocytosis↗
PubMed2003

Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993.

From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. Complete genomic sequences of an early (1988) and a late (1993) cVDPV isolate revealed that their 5' untranslated region (5' UTR) and noncapsid- 3' UTR sequences were derived from other species C enteroviruses. Circulation of type 2 cVDPVs occurred at a time of low OPV coverage in the affected communities and ceased when OPV coverage rates increased. The potential for cVDPVs to circulate in populations with low immunity to poliovirus has important implications for current and future strategies to eradicate polio worldwide.

Animals↗
PubMed2026

Genomic surveillance of enterovirus D68 circulating in 2025 reveals the emergence of a novel A2/B3 recombinant lineage.

Enterovirus D68 (EV-D68) has re-emerged over the past decade as a significant respiratory pathogen associated with severe respiratory disease and acute flaccid myelitis. Its circulation has typically followed a biennial pattern, with predominance in late summer and early fall, a pattern that was temporarily disrupted during the COVID-19 pandemic. Surveillance in 2025 revealed off-season circulation of EV-D68. This study describes the genomic characteristics of the 2025 EV-D68 viruses and the clinical features of affected patients. Between May and December 2025, remnant respiratory specimens positive for rhinovirus/enterovirus were screened for EV-D68 and subjected to whole-genome sequencing. Phylogenetic analyses were performed using maximum-likelihood methods. Recombination was assessed using subgenomic phylogenies, SimPlot similarity and BootScan analyses, and read-level inspection. Among 1,321 patients tested, 147 (11.1%) were EV-D68-positive, and 119 (81.0%) yielded complete genomes. EV-D68 positivity increased in July 2025, peaked in August (~21%), and remained elevated through September and October, exceeding levels observed in 2024. Patients had a median age of 36 years, with infections disproportionately affecting older adults. Phylogenetic analysis demonstrated exclusive circulation of subclade A2. Five genomes formed a distinct recombinant lineage (A2-Re). Subgenomic phylogenies showed clustering with A2 viruses in the P1 region and with B3 viruses in the P2-P3 regions. SimPlot and BootScan analyses identified a recombination breakpoint near the 2A/2B junction (~nt 3,700). The recombinant lineage was associated with temporally clustered cases in September-October. These findings demonstrate recombination between distinct EV-D68 subclades and underscore the importance of whole-genome surveillance for accurate viral characterization. Continued genomic monitoring is essential for detecting emerging variants with potential implications for transmissibility, pathogenicity, and public health preparedness.IMPORTANCEThis study highlights an increased off-season circulation of Enterovirus D68 (EV-D68) and a higher burden of disease in adults in 2025. The identification of a novel A2-B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses. Detection of this lineage in temporally clustered cases suggests local transmission and underscores the potential for rapid spread of newly emerged variants. These findings emphasize the limitations of partial genomic approaches and the critical role of whole-genome sequencing in accurately characterizing circulating strains and identifying recombination events. Enhanced genomic surveillance is essential to detect emerging variants in real time, inform diagnostic assay performance, and support public health responses. Continued monitoring of EV-D68 evolution will be important for anticipating changes in disease burden, guiding clinical awareness, and strengthening preparedness for future outbreaks.

Humans↗
PubMed1976

Circulating immunoblasts in polymyalgia rheumatica.

The percentage of immunoblasts circulating in the peripheral blood has been examined in a group of 29 patients with polymyalgia rheumatica (PMR). Less than 0.5% of immunoblasts were found in healthy young controls, but 18 of 29 unselected patients with PMR were positive when first tested, a similar proportion to that found in rheumatoid arthritis. Raised immunoblasts were found in only one of 12 elderly controls. The presence of circulating immunoblasts correlated with the activity of polymyalgia both as assessed by the erythrocyte sedimentation rate (ESR) and as assessed by an independent clinical observer. This was true in the group overall and in those patients where serial studies were made. Patients studied from the time of disease presentation showed a concurrent fall in ESR and in immunoblasts on starting steroid therapy. Detection of circulating immunoblasts can be a useful additional test in the assessment of disease activity in PMR, especially in cases with a low ESR. The presence of circulating immunoblasts supports the concept of an immunological aetiology for PMR. This is strengthened by the finding that raised immunoglobulins were more common in patients with circulating immunoblasts.

Arthritis, Rheumatoid↗
PubMed1982

Circulating immune complexes in cutaneous and systemic vasculitis: clinicopathological correlations.

A high incidence of raised levels of circulating immune complexes has found in a group of patients with idiopathic vasculitis. Serial measurements in 8 patients with systemic vasculitis showed a good correlation between clinical status and circulating immune complex levels. Some correlation existed between the constituents of circulating and tissue-bound complexes in 6 patients so studied. However, there was no correlation between apparent organ involvement and hypocomplementaemia and the levels of size of circulating immune complexes. It is concluded that the measurement of circulating immune complexes may be clinically useful in vasculitis, but that no direct evidence is yet available that they are pathogenetically related to those which are tissue-bound.

Antigen-Antibody Complex↗
PubMed1989

In vivo binding of circulating immune complexes by C3b receptors (CR1) of transfused erythrocytes.

The effects of packed erythrocyte transfusion with high CR1 activity on circulating immune complex concentrations were studied in 14 transfusion experiments involving 12 patients with immune complex related diseases. Before erythrocyte transfusion circulating immune complex concentrations ranged from 8 to 128 micrograms/ml. After transfusion (2-3 units) immune complex concentrations decreased depending on the levels of CH50 titres in the recipients. In 11 experiments, in which the patients' CH50 titres ranged from 21 to 44, immune complex concentrations decreased by 75-100% within five days. The CH50 titres were also decreased after erythrocyte transfusion but subsequently increased to initial ranges within 6-35 days. In three patients with low CH50 titres (1.0-10.0) decreases in immune complexes were not observed. Direct Coombs' tests for IgG and C3 were performed before and after erythrocyte transfusion to determine potential in vivo binding of circulating immune complexes. Thus in eight of 14 experiments, in which erythrocytes carried no IgG before packed erythrocyte transfusion, seven became Coombs' positive for IgG after the transfusion. In seven of 14 experiments, in which erythrocytes were negative for complement before transfusion, five became positive afterwards. Moreover, in 12 instances slight increases of CR1 activity of patients' erythrocytes were observed within eight days, which improved further within 35 days after erythrocyte transfusion. These studies suggest that transfusion of erythrocytes with high CR1 activity results in the removal of circulating immune complexes and that this process is dependent on complement consumption. These experiments support the hypothesis that erythrocyte-CR1 has a functional role in the removal of circulating immune complexes and may thereby inhibit the deposition of immune complexes within body tissue constituents.

Antigen-Antibody Complex↗
PubMed2001

Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma).

OBJECTIVE: To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features. METHODS: Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren). RESULTS: Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diffuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR. NGF levels increased progressively as the disease worsened. Similarly, VIP circulating levels were significantly increased in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach statistical significance. However, both neuropeptides, following the same trend as NGF, increased as the disease worsened (skin score and lung disease). CONCLUSIONS: The increase of NGF and VIP in patients with SSc, the former in the diffuse subset of the disease, and in patients with prominent articular disease, may suggest a link between neurotransmitters and the disease pathogenesis. Neuropeptide circulating levels seem to increase only in patients with the most severe disease.

Biomarkers↗
PubMed2006

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. OBJECTIVES: To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. METHODS: Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma. CONCLUSIONS: Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.

Adolescent↗
PubMed2006

Circulating endothelial progenitor cells in patients with cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) encompasses the constellation of anginal chest pain in the presence of a pathological functional test and a normal coronary angiogram. Endothelial progenitor cells (EPCs) in the peripheral circulation contribute to tissue vascularisation. OBJECTIVE: To investigate the number and functional properties of circulating EPCs in patients with CSX. METHODS: 17 patients with CSX and a referent population (n = 20) were matched for age, atherosclerotic risk factors and use of drugs. Numbers of EPCs were studied by FACS, and their functional properties, including their proliferative capacity, adherence to matrix and mature endothelial cells as well as their ability to support in vitro tube formation, were investigated. Levels of soluble markers that associate with peripheral mobilisation and homing were studied in the serum samples of all subjects. RESULTS: Patients with CSX had significantly increased numbers of circulating EPCs as compared with the referent population (both CD34+/KDR and CD34+/CD133+). The proliferative capacity of EPCs and their ability to support in vitro tube formation were significantly impaired in patients with CSX as compared with the referent population. However, adhesiveness of EPCs from patients with CSX to fibronectin and cultured mature endothelial cells was enhanced as compared with the referent population. Serum vascular endothelial growth factor correlated with peripheral CD34+/KDR cell numbers, whereas serum concentration of erythropoietin correlated with the number of circulating CD34+/CD133+ cells CONCLUSION: Patients with CSX have a significantly altered circulating EPC phenotype that could potentially aid in understanding the complex pathogenesis of the syndrome.

Adiponectin↗
PubMed1981

Serial measurement of circulating immune complexes in myocardial infarction.

To study the changes in the quantity of circulating immune complexes in myocardial infarction two serial investigations were performed in 45 and 63 patients, respectively. For the detection of circulating immune complexes in the first series, two methods, a complement consumption test and a Clq-solubility test were used. In the second series, a polyethylene glycol (PEG)-precipitation assay was added to these methods. The incidence of circulating immune complexes was studied on the first, third, seventh, 14th, and 21st day. On the first day the complexes were detected in 59% of the patients. Their occurrence increased in the further samplings to 77%, but from the seventh day their concentration decreased and on the 21st day they were detected in 63%. Three types of changes in the level of circulating immune complexes could be shown. In type I immune complexes were detected in the first days after the onset of the infarction, then, after a gradual decrease, the results became negative. In type II immune complexes appeared in the second to third week and their quantity did not alter during the entire observation period. In type III the circulating immune complexes could be detected throughout the whole period of the study. These changes in their concentration were frequently associated with the clinical course of the disease.

Adult↗
PubMed1977

Increased circulating plasma catecholamines and plasma renin activity in dogs after chemical sympathectomy with 6-hydroxydopamine.

Circulating plasma catecholamines, plasma renin activity, and other variables were measured in unanesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 50 mg/kg). Chemical sympathectomy resulted in an immediate fall in mean arterial blood pressure and a delayed reduction in heart rate. Significant increases in plasma glucose and lactate concentrations, circulating plasma catecholamines, and plasma renin activity were found 24 h after 6-OHDA treatment. Circulating catecholamine levels decreased rapidly as time elapsed after sympathectomy and were half the initial values after 2 weeks. Plasma renin activity remained elevated during the 1st week after 6-OHDA treatment and returned to control levels during the 2nd week. Significant correlations were found between circulating catecholamines and heart rate mean arterial pressure, and plasma glucose and lactate concentrations. A significant correlation was also found between plasma renin activity and the mean arterial blood pressure. These results confirm that the adrenal medulla increases its catecholamine secretion rate into the circulation to compensate for the loss of adrenergic innervation after 6-OHDA treatment. They also indicate that the renin-angiotensin system represents another important compensatory mechanism for circulatory homeostasis in sympathectomized animals.

Animals↗
PubMed2004

Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia.

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-alpha-/- mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an alpha-melanocyte-stimulating hormone analog, or CNTF(Ax15), a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-alpha-/- and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-alpha-/-, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTF(Ax15) treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTF(Ax15) treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.

Adipose Tissue↗
PubMed1981

Source and fate of circulating citrulline.

Previous work has demonstrated a continuous release of citrulline from the small intestine into the circulation. To evaluate the physiologic significance of this process, we have now measured citrulline uptake and release by isolated, perfused livers and, through surgical means and arteriovenous difference measurements, by various organs of the rat in vivo. Intestinally derived citrulline, an end product of glutamine nitrogen metabolism, passes through the liver without appreciable uptake. No significant extraintestinal source of circulating citrulline was found. Contrary to earlier suggestions, the liver releases no citrulline normally, but only when supplied with unphysiological high levels of ornithine and ammonia. Renal citrulline uptake was equivalent to approximately 83% the rate of intestinal release; kidneys, in turn, released arginine equivalent to approximately 75% of the citrulline taken up. Acute experiments in which the intestine, intestine plus liver, or kidneys were excluded from the circulation indicate that additional organs may also participate in citrulline exchange, at least when the circulating citrulline level is abnormal. The intestinal-renal pathway seems to account for a large though still unmeasured portion of the citrulline turnover in the circulation.

Amino Acids↗
PubMed1991

Vascular responses of umbilical-placental circulation to vasodilators in fetal lambs.

It has been suggested that the umbilical-placental circulation is maximally vasodilated under normal conditions. To test this hypothesis, we investigated the effect of vasodilators on umbilical-placental vascular resistance. In nine chronically instrumented fetal lambs, catheters were placed in the descending aorta, umbilical artery, umbilical vein, and inferior vena cava. Umbilical-placental blood flow was measured by an electromagnetic flow probe placed around the common umbilical artery. Forskolin and nitroglycerin both dilated the umbilical-placental circulation, causing a dose-dependent decrease in umbilical-placental resistance to approximately 80% of baseline, indicating that the umbilical-placental circulation has some dilatory reserve. Both the adenosine 3',5'-cyclic monophosphate and the guanosine 3',5'-cyclic monophosphate mechanisms, which are directly stimulated by forskolin and nitroglycerin, respectively, are functional in the umbilical-placental circulation. However, the vasodilators prostacyclin and adenosine, which act through specific cell membrane receptors, have no effect on the umbilical-placental resistance. The inability of these agents to dilate the umbilical-placental circulation could be due to a lack of the appropriate receptors in the umbilical-placental vasculature.

Adenosine↗