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PubMed1981

Circulating and deposited immune complexes in patients with glomerular disease: immunopathologic correlations.

The presence of circulating immune complexes (ICs), and alterations of serum immunoglobulins G, A, and M, properdin factor B, and C3 and C4 levels were correlated with glomerular immune deposits in 50 consecutive renal biopsy patients. Urine from 25 of these patients was also examined for ICs. Agarose gel zone electrophoresis (AGE) was used for IC screening. This method detects greater than or equal to 200 ng of IC per 1.5 microliter sample application (approximately equal to 130 micrograms/ml of serum immune complexes) and gives some indication of antigen or antibody excess in the ICs. Glomerular immune deposits were detected by immunofluorescence and electron microscopy in 72% (36/50) of these patients. Circulating and/or urinary IC were found in 69% (25/36) of patients with positive immunofluorescence and 78% (11/14) of patients with negative immunofluorescence. Five of 11 patients with circulating IC but no renal deposition presented with idiopathic crescentic glomerulonephritis (ICGN). These results indicate that IC that persist in the circulation and/or pass renal glomeruli with minimal deposition may result in tissue injury. Circulating IC in antibody excess were detected in all patients with membranous glomerulonephritis. ICs were also found in 55% of patients with IgA nephropathy. Our observations support the hypothesis of an immune complex pathogenesis for these diseases. Determination of circulating and urinary IC in patients with glomerular disease may help in clinical assessment and provide information concerning the pathogenesis of these diseases in humans.

Adolescent↗
PubMed1981

Salvage of circulating pyrimidine nucleosides in the rat.

A new procedure was developed to measure uridine and cytidine in plasma. These nucleosides are present in micromolar concentrations in the plasma of rats, mice, and humans. Inhibitors of pyrimidine synthesis de novo (pyrazofurin or N-phosphonacetyl-L-aspartate) produce only modest decreases in the concentration of circulating uridine or cytidine in the rat. Since both uridine and cytidine are rapidly cleared from the circulation of the rat, constant infusions of radiolabeled uridine and cytidine were used to establish a steady-state specific activity of circulating nucleoside without altering the normal endogenous concentration. These studies permitted an estimation of the contribution of circulating pyrimidine nucleoside to the nucleotide pools of various rat tissues. Most of the uridine entering the circulation (greater than 70%) is catabolized rather than salvaged by formation of nucleotides. Cytidine in the circulation is much more efficiently utilized and is predominantly salvaged. The implication of these results for chemotherapy based on inhibition of pyrimidine synthesis de novo is discussed.

Amides↗
PubMed1981

Study of circulating immune complex size in systemic lupus erythematosus.

The molecular size of circulating immune complexes in patients with systemic lupus erythematosus was determined by the C1q solid-phase assay after the sera were fractionated by sucrose-gradient ultracentrifugation. Circulating immune complexes in patients with membranous glomerulonephritis were uniformly large, sedimenting exclusively above 19S, whereas the immune complexes in patients with cerebritis were small, at or just above 7S. In lupus patients with diffuse proliferative glomerulonephritis and patients without renal involvement, immune complexes of both large and small sizes were found. Of patients without renal involvement, more circulating immune complexes were associated with active disease (n = 22, prevalence = 82%, mean level = 24 standard deviations) than with inactive disease (n = 17, prevalence = 41%, mean level = 41%, mean level = 6 . 5 standard deviations). In patients with clinical evidence for renal involvement, circulating immune complexes were detected in all of five patients with membranous glomerulonephritis, in 88% of 17 patients with diffuse proliferative glomerulonephritis and in one of four patients with mesangial nephritis. Thus, in addition to the finding of an overall positive correlation between disease activity and circulating immune complex levels, circulating immune complexes of certain general molecular size ranges appear to be associated with different clinical manifestations of systemic lupus erythematosus.

Adult↗
PubMed1995

The coagulation system, but not circulating fibrinogen, contributes to liver injury in rats exposed to lipopolysaccharide from gram-negative bacteria.

Evidence suggests that components of the coagulation system contribute to the pathogenesis of liver injury after exposure to lipopolysaccharide (LPS) from gram-negative bacteria. Although the mechanism by which the coagulation system mediates liver injury remains unknown, it has been proposed that the conversion of fibrinogen to insoluble fibrin and consequent deposition in liver microvasculature may contribute to the development of liver injury. The purpose of this study was to test the hypothesis that the coagulation system contributes to LPS hepatotoxicity by a mechanism which is dependent on circulating fibrinogen. A marked reduction in plasma fibrinogen concentration occurred in rats after LPS exposure. The decrease in circulating fibrinogen, which marked activation of the coagulation cascade: 1) occurred at doses of LPS that caused liver injury; 2) was temporally associated with the onset of liver injury; and 3) was attenuated by pretreatment with heparin or warfarin under conditions which afforded protection against liver injury. Pretreatment with either pentoxifylline or antiserum to tumor necrosis factor-alpha, both of which protect against LPS hepatotoxicity, also attenuated the LPS-induced decrease in circulating fibrinogen. Polymorphonuclear leukocyte (neutrophil) depletion protected against liver injury after administration of either a small (2 mg/kg) or a large (8 mg/kg) dose of LPS and attenuated the decrease in circulating fibrinogen albeit to a lesser degree after the larger LPS dose. Depletion of circulating fibrinogen with ancrod did not afford protection against LPS hepatotoxicity. These results suggest that the coagulation system contributes to the pathogenesis of LPS-induced liver injury, but it does so by a mechanism which is independent of circulating fibrinogen.

Ancrod↗
PubMed1993

Antibodies chaperone circulating IL-6. Paradoxical effects of anti-IL-6 "neutralizing" antibodies in vivo.

In the baboon or the mouse, a stimulus such as LPS, TNF, or IL-1 typically led to a rapid induction of circulating IL-6, the levels peaked by 2 to 3 h and then declined to near-baseline values by 6 to 8 h. Administration to baboons or mice of "neutralizing" anti-IL-6 mAb followed by an IL-6 inducer led to a marked and sustained increase in circulating IL-6 levels. IL-6 Ag, IL-6 biologic activity, neutralizing anti-IL-6 mAb, and IL-6/anti-IL-6-mAb complexes could all be observed for an extended period of time (beyond 8 h) in the circulation of such animals. Nevertheless, in mice, if the anti-IL-6 mAb had been administered before the IL-6 inducer, there was a reduction in the in vivo IL-6-induced stimulation of fibrinogen levels, indicating that most of the intravascular IL-6 was not readily available for eliciting hepatocyte effects under these experimental conditions. Intraperitoneal administration into mice of mixtures of murine rIL-6 or human rIL-6 together with their respective anti-IL-6 mAb led to a marked increase in the appearance and longevity in the peripheral circulation of the exogenously administered murine or human rIL-6 species in a biologically active form. Varying the ratio of human rIL-6 to anti-human IL-6 mAb indicated that a molar ratio of 1:1 was sufficient for the ability of mAb to chaperone IL-6 in the murine circulation. Human rIL-6 mixed with "neutralizing" mAb in the approximate ratio 1:1 elicited an enhanced fibrinogen response in vivo in the mouse; an IL-6:mAb ratio of 1:125 led to a reduction in the fibrinogen response even though the levels of circulating B9 bioactivity and of human rIL-6-Ag were maximal under these conditions. Gel-filtration chromatographic and Western blotting analyses of IL-6 present in vivo in the mAb-free baboon revealed that although the IL-6 Ag was largely present in high molecular mass complexes of size 400 kDa in association with soluble IL-6 receptor, the B9 bioactivity was largely of low molecular mass (20 kDa). In contrast, in the anti-IL-6 mAb-treated baboon or mouse, the IL-6 Ag and bioactivity were both largely in complexes of 200 kDa. Thus, the binding of IL-6 in the intravascular compartment to other proteins, anti-IL-6 mAb in the present studies, gives IL-6 unexpected biochemical and pharmacologic properties in vivo.

Animals↗
PubMedDate not supplied

Circulating soluble intercellular adhesion molecule-1 in type C viral hepatitis.

BACKGROUND/AIMS: Intercellular adhesion molecule-1 (ICAM-1) is one of the members of the immunoglobulin supergene family; it expresses in response to inflammatory mediators and activation. Circulating soluble ICAM-1 (sICAM-1) levels in acute and chronic viral hepatitis C virus infection were studied. MATERIALS AND METHODS: Thirty blood samples from 10 patients with acute hepatitis C, and 36 blood samples from 25 patients with chronic hepatitis C were compared with those from 10 healthy volunteers, using the enzyme immunoassay method. RESULTS: The mean circulating sICAM-1 activities in healthy volunteers was 339 +/- 93 ng/ml. Maximum values of sICAM-1 activities in acute (1394 +/- 502 ng/ml, P = 0.004) and chronic (662 +/- 477 ng/ml, P = 0.047) hepatitis C were increased. Acute hepatitis had a higher maximum circulating sICAM-1 activity than chronic hepatitis (P = 0.009). Longitudinal circulating sICAM-1 activities roughly correlated with the serum aminotransferase (ALT) activities. In acute viral hepatitis C, three patients developed an increase in circulating sICAM-1 activities before the manifestation of abnormal ALT activity. Circulating sICAM-1 activities showed a positive correlation with serum ALT activities (P < 0.001) and serum total bilirubin levels (P = 0.001) and a negative correlation with serum albumin levels (P = 0.01). CONCLUSIONS: The present study suggested that ICAM-1 plays a role in the hepatocellular injury during viral hepatitis C infection.

Acute Disease↗
PubMed1997

[Trend of circulating eosinophils in healthy children and children suffering from infectious diseases. A retrospective study].

INTRODUCTION: Acute bacterial and viral infections are accompanied by a marked diminution in circulating eosinophils in the blood. This forms part of the host's physiological response to acute infection and was first studied in adults early this century. The aims of this study were to check whether eosinopenia during acute phlogosis is a phenomenon present in pediatric patients, and whether the trend is comparable to the experimental models reported; to describe the trend of circulating eosinophils in the remission process. METHODS: A retrospective study was performed in 34 children hospitalised in the Pediatric Hospital of AUSL 2-Lucca (Italy) for bacterial or viral infective diseases documented by cell culture or presumed diagnosed. Children with the following characteristics were excluded from the study: 1) blood samples collected for hemochrome analysis at times other than normal (7-8 a.m.); 2) cortisone treatment administered up to 5 days prior to blood sample and/or during hospitalisation; 3) positive personal anamnesis for manifest allergic diseases. On admittance (children during acute phase) and at the start of remission, an absolute count of circulating eosinophils was performed in these children using an automatic globule counter. Sixty-six children with non evident infective and/or inflammatory diseases were included in the study as a control group. This group was also selected in the same way as infective subjects. RESULTS: The mean number of circulating eosinophils was 288 (+/- 248) in the control group, 46 (+/- 58) in subjects at the acute phase of infective pathology and 252 (+/- 162) in infective patient during the remission phase. The difference between the two means was statistically significant. This characteristic falling and rising trend of circulating eosinophils was found in 33 of the 34 infective subjects examined. CONCLUSIONS: Eosinophil values found in control subjects are broadly in line with those reported in the literature. Eosinopenia during the course of acute infection and the early rise during remission represent a characteristic phenomenon indicating the body's "normal" response to a non-parasitic infection. Both eosinophil levels, namely in the control group (288/mm3) and in acute-phase subjects (46/mm3), should be regarded as "normal" provided they refer to the appropriate situation. The precocity and precision with which the eosinophil trend follows the phases of the infection underlines the value of the assay of these cells as a reliable parameter for monitoring acute infection. There are also indications that, in an inflammatory situation, the behaviour of circulating eosinophils may provide a practical clinical marker of the predominant lymphocyte pattern (Th1 or Th2), as well as the phase of phlogosis, active or remission.

Child↗
PubMed1997

Simulation of human circulation at cardiopulmonary bypass.

This article describes a simulation model of the human circulatory system under extracorporeal circulation. The model is supposed to enable the design of a controller for heart-lung-machines, and to perform simulations of the controllers' behaviour. The controller should be able to control extracorporeal circulation based on the oxygen supply to individual organs. The model contains all important control mechanisms in the human circulation that maintain hemodynamics, and the influences of extracorporeal circulation to them. We considered the renin-angiotensin-system, the arterial local autoregulation and the autonomic nervous system. The behaviour of the most important hormone levels is reproduced. Furthermore, hemodynamics in the arterial tree is modeled with locally distributed pressure and flow parameters in 128 vessel segments to gain knowledge about the oxygen supply position of single internal organs. The influences of the special circumstances of an operation under extracorporeal circulation such as anesthesia or hypothermia are implemented in the model. Simulation results show that our model describes the behaviour of human circulation detailed enough to validate the designed controllers.

Arteries↗
PubMed1999

Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating red cell substitute.

A major obstacle in the development of red cell substitutes has been overcoming their short circulation persistence. In this study, distearoyl phosphoethanolamine polyethylene glycol 5000 (PEG-PE) (10 mol%) was added to the formulation of liposome-encapsulated hemoglobin (LEH) to decrease reticuloendothelial system uptake and prolong LEH circulation persistence. PEG-LEH was radiolabeled with technetium-99m, infused into rabbits (25% of blood pool at 1 ml/min) (n = 5), and monitored by scintigraphic imaging at various times out to 48 h. At 48 h, animals were sacrificed, and tissue samples were collected for counting in a scintillation well counter. Tissue distribution data at 48 h revealed that 51.3 +/- 3.4% of the technetium-99m-PEG-LEH remained in circulation, a greater than 3-fold increase in the circulation half-life compared with circulation half-lives previously reported for non-PEG-containing LEH formulations. The liver had the greatest accumulation at 48 h (12.7 +/- 0.7%), followed by bone marrow (6.2 +/- 0.1%), whereas the spleen had only 1.4 +/- 0.2%. The addition of PEG-PE to the LEH formulation greatly prolongs the circulation persistence of LEH and represents a significant step in the development of red cell substitutes with prolonged oxygen delivery.

Animals↗
PubMed1987

Improvement of cerebral circulation by extracorporal collateral between the femoral and the external carotid artery in experimentally induced ischaemia.

The purpose of this study was to examine the effect of extracorporal collateral circulation (ECCC) between the femoral and the external artery (ECA) on the cerebral circulation, in experimentally induced ischaemia, in rabbits. The animals were divided in four groups. Seven animals (Group A) were used to determine the injection pressure (150-160 mmHg) at the ECA, necessary to achieve collateral circulation between ECA and internal carotid artery (ICA), after occlusion of ICA. Group B (8 rabbits) was the control group for establishing cerebral ischaemia (CI) by a) ligating the common carotid artery bilaterally, b) coagulating the right vertebral artery and c) exsanguinating the animal (removing 28-30 ml of blood). The induced ischaemia was studied by BP and PCO2 monitoring, CBF measurement, videomicroscopy of surface cerebral vessels, and finally macroscopic and microscopic examination of brain sections. In group C (8 animals)-moderate degree of CI-brain circulation improved in all animals after the application of the ECCC, installed at 135 min after the onset of CI. In 10 animals (group D) with severe and prolonged (225 min) CI, ECCC enhanced the brain circulation in eight animals to a variable degree.

Animals↗
PubMed1991

Coronary collateral circulation in coronary artery disease and systemic hypertension.

The extent and functional capacity of coronary collateral circulation in patients with systemic hypertension has not been elucidated. In the present study, 313 patients with coronary artery disease were studied to evaluate coronary collateral circulation in relation to the presence of systemic hypertension and left ventricular hypertrophy. Patients had greater than or equal to 95% diameter luminal obstruction of either the left anterior descending or the right coronary artery. Patients were classified into 2 groups: The hypertensive group consisted of 61 patients, mean age 55 +/- 9 years, with systemic hypertension, and the normotensive group consisted of 252 patients, mean age 53 +/- 8 years, without hypertension. The hypertensive group had more severe angina pectoris and less history of healed myocardial infarction than the normotensive group (p less than 0.001). Left ventricular wall thickness was 1.26 +/- 0.1 cm in the hypertensive and 1.03 +/- 0.06 cm in the normotensive group (p less than 0.001). The hypertensive group had more extensive coronary collateral circulation than the normotensive group (p less than 0.01). There was a positive relation between coronary collateral circulation and left ventricular wall thickness (p less than 0.001). These results indicate that patients with systemic hypertension and coronary artery disease have an increase in coronary collateral circulation corresponding to the degree of left ventricular wall thickness.

Cardiomegaly↗
PubMed1997

Pulmonary AV malformations after superior cavopulmonary connection: resolution after inclusion of hepatic veins in the pulmonary circulation.

BACKGROUND: A high incidence of pulmonary arteriovenous malformations (PAVMs) has been reported in patients who have polysplenia and congenital heart disease after superior cavopulmonary anastomosis. Interruption of hepatic venous return to the pulmonary circulation is believed to potentiate the development of PAVMs. Surgical inclusion of hepatic flow in the pulmonary circulation may result in their resolution. METHODS: We reviewed 3 patients with congenital heart disease and polysplenia in whom PAVMs developed and who had subsequent hepatic vein inclusion in the pulmonary circulation. RESULTS: Patients underwent superior cavopulmonary connection at a median age of 8 months. The PAVMs were diagnosed at a median duration of 8 months after operation (arterial saturation <75% in room air). Hepatic venous flow was included in the pulmonary circulation at operation. Resolution of PAVMs occurred at a median duration of 7 months after operation (arterial saturation >90% in room air). CONCLUSIONS: Surgical inclusion of hepatic venous blood in the pulmonary circulation results in the resolution of PAVMs. Electively associating the hepatic veins with the pulmonary vasculature may prevent the development of PAVMs in patients who are at risk.

Arteriovenous Malformations↗
PubMed2002

Pravastatin promotes coronary collateral circulation in patients with coronary artery disease.

BACKGROUND: Previous studies suggested that hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) promotes collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with pravastatin and the development of coronary collateral circulation as assessed by the Rentrop Score in patients with coronary artery disease (CAD) in a case-control study. DESIGN: The study included patients who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels. Patients who did and did not receive pravastatin were defined as case participants (n = 42) and control participants (n = 100), respectively. RESULTS: The case participants included a higher percentage of 3-V patients with a Rentrop Score 1 compared to the control participants but there was no difference among 1-V and 2-V patients, suggesting that pravastatin was associated with coronary collateral circulation independent of the number of stenosed vessels. Patients with 3-V disease who were treated with pravastatin were most likely [odds ratio (confidence interval), 17.4 (4.4-115)] to develop collateral circulation, as assessed by multiple logistic regression analysis. CONCLUSIONS: Treatment with pravastatin was associated with the development of collateral circulation in patients with CAD, suggesting that such action constitutes part of the pleiotropic effects of statin.

Aged↗
PubMed1991

Urethral blood circulation during cardiopulmonary bypass.

The haemodynamic changes induced by extracorporeal circulation (ECC) are thought to be important in the induction of urethral strictures in open heart surgery when indwelling latex catheters are used. In the present study, 6 piglets were cannulated and connected to extracorporeal perfusion apparatus. Pump flows correlated with human ECC values with non-haemic prime were used. The mucosal and submucosal blood circulation in the urethra reduced by 66% during ECC (P less than 0.05). The brain and hepatic arterial flows increased. A significant reduction was seen in renal blood circulation. The changes in the urethral blood circulation during ECC correlated with previous findings. The reduced wash out levels of chemicals leaching from the indwelling latex catheters as a result of reduced local blood circulation are the main trigger for the induction of urethral strictures during ECC and in other shock-like circulatory disturbances in the human body.

Animals↗
PubMed1996

Differential role of endothelium-derived nitric oxide in the modulation of the systemic and pulmonary circulation in lambs.

We have studied the differential role of endothelium-derived nitric oxide (EDNO) in the regulation of the systemic and pulmonary circulations of the lamb. Hemodynamic effects of NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg i.v.), an inhibitor of NO synthesis, were determined in juvenile (6 +/- 1 weeks old) lambs, under conditions of basal and elevated vasomotor tone. Under basal conditions, L-NAME raised both systemic (SVR) and pulmonary vascular resistances (PVR) by 20-30% (increasing SVR from 0.318 +/- 0.013 to 0.385 +/- 0.015 mm Hg.min.ml-1.kg and PVR from 0.050 +/- 0.003 to 0.067 +/- 0.010 mm Hg.min.ml-1.kg). When tone was elevated in the pulmonary circulation with hypoxia (PVR was elevated by 60%, from 0.059 +/- 0.010 to 0.094 +/- 0.019 mm Hg.min.ml-1.kg), L-NAME treatment resulted in an augmented increase in PVR (PVR increased by greater than 50% to 0.140 +/- 0.024 mm Hg.min.ml-1.kg). However, when tone was elevated to a comparable degree in the systemic circulation with angiotensin infusion (SVR was elevated by 60%, from 0.432 +/- 0.065 to 0.065 to 0.634 +/- 0.113 mm Hg.min.ml-1.kg), the response to L-NAME was not augmented. Our data suggest that the role of EDNO in the modulation of the pulmonary circulation is dependent on the level of vasomotor tone, whereas its role in the systemic circulation is small and is independent of the level of vasomotor tone.

Animals↗
PubMed1998

Effect of coronary collateral circulation on exercise stress test.

In this study, patients who have recovery-only ST segment depression in exercise stress test were chosen. It is proposed that coronary collateral circulation could improve with stress-increased coronary perfusion, and accordingly, patients with recovery-only ST segment depression were evaluated by coronary angiography for grading the coronary collateral circulation. Twenty-one men and five women were assigned to the study group. Sixteen men and two women who had exercise-induced ST segment depression were assigned to the control group. Age and gender of both groups were not statistically different (p>0.05). The reason for terminating the exercise stress test was chest pain in two of 26 patients in the study group versus 15 of 18 in the control group (p<0.001). In both groups coronary collateral frequency and grade were directly correlated with the severity of the coronary artery disease (p<0.001 in the study group, and p<0.05 in the control group). When both groups were compared for the frequency of significant coronary collateral circulation, 14 of 26 patients in the study group versus 4 of 18 patients in the control group had significant coronary collateral circulation (p=0.035). The authors conclude that recovery-only ST segment depression correlates well with the frequency of significant coronary collateral circulation, and coronary collaterals may prevent myocardial ischemia during exercise.

Case-Control Studies↗
PubMed2003

Angiotensin-converting enzyme inhibitor promotes coronary collateral circulation in patients with coronary artery disease.

Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI.

Aged↗
PubMed2006

The role of collateral circulation in preserving myocardial function.

The coronary collateral circulation is an alternative source of blood supply to the myocardium jeopardized by the failure of the original stenotic or occluded vessel to provide adequate blood flow to this region. One hundred coronary angiograms and left ventriculograms of patients with coronary artery disease from the Cardiology Department of University Clinics Centre in Sarajevo were reviewed. The role of collateral circulation in preserving myocardial function was assessed by comparing regional left ventricular contractility in 34 instances of total arterial occlusion and adequate colateral circulation with that in 34 instances of total arterial occlusion and inadequate collateral circulation. Among the group with adequate collaterals, regional left ventricular contraction was normal in 41%, hypokinetic in 53% and akinetic or dyskinetic in only 5%. Among the group with inadequate collaterals, regional contraction was normal in 9%, hypokinetic in 20 % and akinetic or dyskinetic in 70%. These data indicate that collateral circulation plays an important role in preserving myocardial contractility in patients with coronary artery disease.

Collateral Circulation↗