Biomedical subjects

T Lyberg

Publications and source records attributed to T Lyberg.

At least 55 records · Page 3Linked to original sources

PubMed2000

Blood platelet activation evaluated by flow cytometry: optimised methods for clinical studies.

A variety of flow cytometry techniques are in use to evaluate in vivo blood platelet activation. We have in this study further developed and optimised these methods to be suitable for use in clinical studies. By preloading the Monovette EDTA vacuum blood sampling tubes with 1/8 vol 4% (w/v) paraformaldehyde (PFA), we were able to assess platelet CD62P (P-selectin) expression in whole blood with less than 0.2% activated platelets. No washing or neutralising steps were required to remove excess fixative. Both basal and agonist-stimulated CD62P expression were stable for at least 48 h after sampling. The standard curve was linear from 1.9 (basal) to 8.1 x 10(3) (TRAP-stimulated) molecules of equivalent soluble fluorochrome units (MESF) in phycoerythrein-conjugated anti-CD62P labelled whole blood samples. These assay conditions were also well suited for assessment of platelet expression of CD41, CD42a, CD61 and CD63. The preanalytic storage period was extended from 10 min to at least 2 h for platelet PAC-1 and fibrinogen binding analysis by preloading Monovette citrate tubes with 8/10 vol buffer. With PFA preloading, blood sampled into citrated tubes could be analysed for fractions of microparticles and platelet-platelet aggregates as well as for aggregate size.

Adult↗

PubMed2000

Evaluation of circulating platelet-leukocyte conjugates: a sensitive flow cytometric assay well suited for clinical studies.

Circulating platelet-leukocyte conjugates are found in patients with a variety of diseases. We have developed a flow cytometry-based assay for monitoring the presence of such conjugates. By preloading the sampling tubes with 1/8 volume of 4% paraformaldehyde, basal levels of platelet-leukocyte conjugates was stable for at least 48 h after blood sampling. The leukocytes were discriminated from the other cells in fixed whole blood by binding of anti-CD45, and no lysing, washing, or centrifugation steps were required. In whole blood from healthy individuals, platelets were found adherent to 3.2% of the lymphocytes, 4.1% of the monocytes and to 2.5% of the granulocytes. The corresponding values for mean number of platelets per leukocyte were 1.3 x 10(-2), 2.5 x 10(-2) and 1.6 x 10(-2), respectively. Upon in vitro agonist (ADP, TRAP) stimulation, the platelet adhesion to monocyte and granulocytes increased several-fold. Microscopy verified the flow cytometry results and revealed that platelet adhered to the leukocytes as platelet-platelet aggregates and not as single platelets as the agonist concentration increased. At high concentrations of TRAP, the strong agonist, large multiconjugates with several granulocytes per platelet-platelet aggregate evolved. Being an assay well suited for clinical studies, the recommended approach may be a valuable tool in establishing the clinical significance of circulating platelet-leukocyte conjugates.

Adenosine Diphosphate↗

PubMed2000

Cardiac endothelin-like immunoreactivity and preproendothelin-1 mRNA expression in human heart failure.

Endothelin (ET) induces hypertrophy of cardiomyocytes and increases synthesis of collagen in vitro. Interestingly, these features are hallmarks of the cardiac remodeling taking place in heart failure. The aim of the present study was to examine cardiac ET peptide and preproET-1 mRNA synthesis in human heart failure. Cardiac tissue was obtained from 11 patients with end-stage heart failure undergoing orthothopic heart transplantation (NYHA III-IV). Cardiac tissue from nine organ donors served as controls. The specimens were examined by immunohistochemistry and mRNA slot blot analyses. Significantly stronger ET-1-like immunoreactivity (ET-1-ir) was seen in the left atrial myocardium of failing hearts compared to the left atrial myocardium of donor hearts. Within each heart, the epicardium showed the strongest ET-1-ir. Left ventricular preproET-1 mRNA expression in the entire group of patients did not differ significantly from that of donor hearts. However, hypertrophic obstructive cardiomyopathy may be associated with a twofold increase in left ventricular preproET-1 mRNA. We report an increase in cardiac ET peptide in human heart failure.

Adolescent↗

PubMed2000

Surgical mandibular advancement and changes in uvuloglossopharyngeal morphology and head posture: a short- and long-term cephalometric study in males.

The aim of the present study was to investigate, by means of an extensive cephalometric examination, the alterations which took place in hyoid bone position, head posture, position and morphology of the soft palate, and tongue and sagittal dimensions of the pharyngeal airway after mandibular advancement osteotomy for the correction of mandibular retrognathism. The sample consisted only of adult males who underwent mandibular advancement by bilateral sagittal ramus split osteotomy (BSRO) with rigid fixation. Profile cephalograms were obtained 1-3 days before surgery (20 subjects), and 6 months (20 subjects) and 3 years (19 subjects) after the surgery. Statistical evaluation was performed by paired Student's t-test and Pearson product moment correlation analysis. At the short-term follow-up, hyoid bone and vallecula assumed a more superior (AH perpendicular FH, AH perpendicular ML, AH perpendicular S, V perpendicular FH) and anterior position (AH-C3 Hor, V-C3), which was maintained at the long-term follow-up. The soft palate (NL/PM-U) became more upright at the short-term follow-up. The tongue demonstrated a transient increase in height (H perpendicular VT) and a less upright position (VT/FH) at the long-term observation. In addition, a more upright cervical spine (OPT/HOR, CVT/HOR) was recorded at the long-term follow-up. The pharyngeal airway space at the level of the oropharynx (U-MPW) and the retroglossal space at the base of the tongue (PASmin) showed an increase in the sagittal dimension at the short-term follow-up. Significant widening at the PASmin level was sustained at the long-term follow-up, indicating that mandibular advancement osteotomy could increase airway patency and be a treatment approach for sleep apnoea in selected patients.

Adult↗

PubMed2000

Surgical mandibular setback and changes in uvuloglossopharyngeal morphology and head posture: a short- and long-term cephalometric study in males.

A detailed cephalometric analysis was conducted on a sample of 31 adult males who underwent correction of mandibular prognathism by mandibular setback osteotomy (BSRO) with rigid fixation to evaluate the changes in uvuloglossopharyngeal morphology, hyoid bone position and head posture. Lateral cephalograms were obtained 1-3 days prior to the operation and at standardized 6 months and 3 years post-operative follow-up. Statistical evaluation was performed by paired Student's t-test and Pearson product moment correlation analysis. Inferior position of the hyoid bone (AH perpendicular FH, AH perpendicular ML, AH perpendicular S) and valeculla (V perpendicular FH) was recorded at the 6-month follow-up, a transient finding as at 3 years almost complete recovery to their pre-surgical position was noted. No posterior displacement of the above structures (AH-C3 Hor, V-C3) was recorded. Soft palate length (pm-U) was increased and maintained at the long-term follow-up while its posture (NL/pm-U) became less upright. The tongue showed increased length (V-T) and sagittal area (TA) and a more upright posture (VT/FH) at the late follow-up. Increased contact length between tongue and the soft palate (CL) and less residual oropharyngeal area [area not occupied by soft tissues, (TA + SPA)/OPA] was found at the long-term follow-up. Craniocervical agulation (NSL/OPT, NSL/CVT) was increased indicating cervical hyperflexion at the 3-year follow-up. Reduction of the sagittal dimension of the oropharyngeal airway space (U-MPW) appeared at the first follow-up and was sustained at the longest follow-up which, in conjunction with the decrease in residual oropharyngeal area, could raise questions regarding airway patency after mandibular setback osteotomy.

Adult↗

PubMed2000

Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock.

In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to evaluate the effect of a continuous infusion of live serogroup A streptococci (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony-forming units/kg per h] caused early signs of severe septicaemia in the pigs, with pulmonary hypertension, systemic hypotension, reduced cardiac output and liver hypoperfusion, ultimately leading to shock with a high mortality. There was a sequential and ordered activation of the coagulation, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold increase at 4 h). These findings are similar to changes observed during endotoxin infusion. This procoagulant state favours disseminated intravascular coagulation and microthrombus formation, ultimately threatening tissue viability.

Animals↗

PubMed2000

Aminoethyl-isothiourea, a nitric oxide synthase inhibitor and oxygen radical scavenger, improves survival and counteracts hemodynamic deterioration in a porcine model of streptococcal shock.

OBJECTIVE: To test the effect of a continuous infusion of the nitric oxide (NO) synthase (S) inhibitor aminoethyl-isothiourea (AE-ITU) on survival time, hemodynamics, and oxygen transport in a porcine model of live group A streptococcal (GAS) sepsis. Furthermore, to examine the role of endothelin-1, histamine, and reactive oxygen species (ROS) in streptococcal shock. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-eight pigs with an average weight of 25 kg. INTERVENTIONS: Sixteen animals received a continuous infusion of live Streptococcus pyogenes 1.3 x 10(10) colony forming units/hr: eight received fluids only, and the other eight received an intravenous infusion of AE-ITU 10 mg/kg/hr starting 30 mins before the GAS challenge. Six control pigs received AE-ITU 10 mg/kg/hr iv for 5 hrs. Another six animals received half the dose of GAS over 5 hrs. MEASUREMENTS AND MAIN RESULTS: GAS infusion caused a rapid increase in pulmonary, hepatic, and systemic vascular resistance, followed by hypotension with a 90% lethality at 4 hrs. Treatment with AE-ITU increased 4-hr survival in septic animals from 1/8 to 8/8 and 5-hr survival from 0/8 to 5/8, prevented hypotension, and increased urine output. AE-ITU attenuated the decrease in cardiac output, liver blood flow, and oxygen delivery, and hepatic arterial blood flow as a fraction of cardiac output increased (all p < .05). Plasma nitrate/nitrite levels decreased in all animals. Inducible NOS and endothelial constitutive NOS activities in liver, gut, and lung were not increased during sepsis, nor were they decreased after AE-ITU. Plasma levels of endothelin-1 and methylhistamine increased in all septic animals and were not modified by AE-ITU. AE-ITU prevented the increase in monocyte ROS production caused by GAS. In control animals, AE-ITU caused an increase in mean arterial pressure, liver blood flow, and oxygen delivery. CONCLUSIONS: In this model of porcine GAS-induced septic shock, which was not associated with enhanced NO production, infusion of the NOS inhibitor AE-ITU prolonged survival, prevented hypotension, and improved cardiac contractility, organ perfusion, and tissue oxygenation. These beneficial effects of AE-ITU might be a result of the combined effect of ROS scavenging and modulation of local NO production, thus improving the balance of vasodilator and vasoconstrictor forces and reducing oxidative stress.

Animals↗

PubMed2000

Obstructive sleep apnea (OSA): a cephalometric analysis of severe and non-severe OSA patients. Part II: A predictive discriminant function analysis.

One hundred male obstructive sleep apnea (OSA) patients were classified into 2 groups on the basis of apnea-hypopnea index (AHI) as severe (AHI > or = 50) and non-severe (AHI < 50). A comprehensive cephalometric analysis of cervicocraniofacial skeletal and upper airway soft tissue morphology was performed in 51 non-severe and 49 severe OSA patients. In addition, a multivariate statistical method (principal component, analysis and predictive discriminant analysis) was performed to identify the components that could correctly differentiate the severe from the non-severe OSA patients. Eight principal components (PCs) of cervicocraniofacial skeletal morphology, 4 PCs of hyoid bone position and head posture, and 7 PCs of upper airway soft tissue morphology, together with the selected demographic variables, were deduced to formulate a linear canonical discriminant function. The equation of a 9-variable model was generated as follows: PDF score = 4.127 - 0.144 (Body Mass Index) - 0.376 (PC1.1) + 0.311 (PC1.4) + 0.214 (PC1.5) + 0.075 (PC 2.1) - 1.309 (PC2.3) + 0.708 (PC3.2) - 0.059 (PC3.3) + 0.609 (PC3.6). The cutoff score was -0.03899. The overall rate of correct classification was 83%. The results showed that Body Mass Index and 8 other PCs contributed significantly to the OSA severity. These analyses are proven to be a useful adjunctive diagnostic tool to select optimal treatment regimens for OSA patients with varying degrees of severity.

Aged↗

PubMed2000

Obstructive sleep apnea (OSA): a cephalometric analysis of severe and non-severe OSA patients. Part I: Multiple comparison of cephalometric variables.

One hundred male obstructive sleep apnea (OSA) patients were classified into 2 groups, on the basis of Apnea-Hypopnea Index (AHI), as severe (AHI > or = 50) and non-severe (AHI < 50). A comprehensive cephalometric analysis of cervicocraniofacial skeletal morphology and upper airway soft tissue morphology was performed in 51 non-severe OSA patients, 49 severe OSA patients, and 36 controls with the purpose of examining the different features among these 3 groups. Sixty-eight cephalometric variables were compared among these 3 groups by 1-way analysis of variance with post hoc Bonferroni test. The results showed that both OSA groups had aberrations of cervicocraniofacial skeletal morphology and upper airway soft tissue morphology versus the controls. Severe OSA patients demonstrated increased maxillo-mandibular retrognathism, with a high mandibular plane angle resulting from increased anterior lower facial height and decreased posterior lower facial height, versus the non-severe OSA group. The craniocervical extension, forward head posture, inferiorly positioned hyoid bone, and the enlarged and elongated soft palate and upright tongue posture were more exaggerated as well. These findings imply that there should be different treatment regimens for the 2 subgroups of OSA patients to achieve treatment success. Cephalometric analysis is therefore highly recommended to verify the aberrant cervicocraniofacial morphology in severe and non-severe OSA patients.

Adult↗

PubMed2000

Long-term stability of mandibular setback surgery: a follow-up of 80 bilateral sagittal split osteotomy patients.

The objective of this cephalometric study was to evaluate skeletal stability and time course of postoperative changes in 80 consecutive mandibular prognathism patients operated with bilateral sagittal split osteotomy (BSSO) and rigid fixation. Lateral cephalograms were taken on 6 occasions: immediately preoperative, immediately postoperative, 2 and 6 months postoperative, and 1 and 3 years postoperative. The results indicate that BSSO with rigid fixation for mandibular setback is a fairly stable clinical procedure. Three years after surgery, mean relapse at pogonion represented 26% of the surgical setback (19% at point B). Most of the relapse (72%) took place during the first 6 months after surgery. Clockwise rotation of the ascending ramus at surgery with lengthening of the elevator muscles, though evident in this study and apparently responsible for the early horizontal postoperative changes, does not seem to be associated with marked relapse. Changes occurring in some of the younger patients between 1 and 3 years postoperatively are likely to be manifestations of late mandibular growth.

Adolescent↗

PubMed2000

Stability of extraoral vertical ramus osteotomy: plate fixation versus maxillomandibular/skeletal suspension wire fixation.

The objective of this cephalometric study was to evaluate skeletal stability and time course of postoperative changes in 2 groups of mandibular prognathism patients following extraoral oblique vertical ramus osteotomy (VRO). One group (n = 22) received maxillomandibular fixation and skeletal suspension wires (MMF group) for a period of 8 weeks. In the other group (n = 22), the segments were rigidly fixed with plates and the patients were allowed to function immediately after surgery. Lateral cephalograms were taken on 5 occasions: immediately presurgical, immediately postsurgical, 8 weeks postsurgical, 6 months postsurgical, and 1 year postsurgical. During the first 8 weeks after surgery, the MMF group demonstrated posterior movement of the mandible, with an increase in mandibular plane angle, shortening of the rami, and dental compensations. Upon release of MMF and skeletal suspension wiring, a small anterior relapse tendency was observed, but the net setback 1 year after surgery was still greater than the actual surgical setback. In the plate fixation group, postoperative changes were mainly in the form of a small anterior relapse tendency in the range of 10% of the surgical setback. The results indicate that the use of plate fixation with VRO, while eliminating the inconvenience for the patient of several weeks of MMF and preventing the early side effects observed in the MMF group, also resulted in a more predictable surgical procedure, with excellent stability 1 year after surgery.

Adult↗

PubMed1999

Heterogeneity of procoagulant activity and cytokine release in subpopulations of alveolar macrophages and monocytes.

We have studied the expression of tissue factor (TF) and fibrinopeptide A (FPA) generation as well as the release capacity of TNF-alpha, IL-1beta, and IL-6 in density-defined subpopulations of alveolar macrophages (AM) and monocytes (Mo). TF was equally expressed on all AM subpopulations and Mo, while the FPA-forming capacity was at the same level in low density AM as in Mo and was significantly (P < 0.05) higher in low density AM than in high density AM. The lipopolysaccharide (LPS)-induced release of TNF-alpha was higher (P < 0.05) in high density AM than in low density AM and in Mo. IL-1beta release was undetectable in unstimulated AM and in LPS-stimulated low density AM, while the LPS-induced IL-1beta release in high density AM was low compared to the levels demonstrated in Mo. LPS-stimulated IL-6 release was not distinctively different in the AM subpopulations and Mo. The presented study showed that FPA generation and LPS-stimulated TNF-alpha release were dependent on the density (i.e., maturity) of AM. This implies that a skewed distribution of AM subpopulations induced by disease processes may profoundly influence the inflammatory reactions, including extravascular activation of coagulation.

Adult↗

PubMed1999

Allergen-stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide.

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.

Adult↗

PubMed1999

LPS from Actinobacillus actinomycetemcomitans and the expression of beta2 integrins and L-selectin in an ex vivo human whole blood system.

Actinobacillus actinomycetemcomitans is assumed to be an important etiological agent in localized juvenile periodontitis (LJP) and to have the ability to invade periodontal tissues. This bacterium has also been noted for its potential to cause serious extraoral infections. In this study, the effect of lipopolysaccharides (LPS) extracted from A. actinomycetemcomitans on the expression of the leukocyte adhesion molecules CD11a/CD18, CD11b/CD18, CD11c/CD18 and L-selectin (CD 62L) were measured in an ex vivo whole blood system by use of fluorescent antibodies followed by flow cytometry. LPS from Escherichia coli, which is known to elicit a strong inflammatory response was used as a reference. The expression of the beta2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 were significantly upregulated in granulocytes and monocytes. This expression was dose-dependent. The baseline levels of L-selectin was high on all three types of leukocytes, but on granulocytes and monocytes it decreased dramatically after stimulation with LPS. The LPS from A. actinomycetemcomitans was equally potent as LPS from E. coli in its ability to affect the expression of the leukocyte integrins and L-selectin.

Aggregatibacter actinomycetemcomitans↗

PubMed1999

Effect of intravenous bilirubin infusion on biliary phospholipid secretion, hepatic P-glycoprotein expression, and biliary cytotoxicity in pigs.

BACKGROUND: Infusion of large intravenous bilirubin loads in bile acid-depleted pigs reduces P-glycoprotein-dependent biliary phospholipid secretion and increases the cytotoxicity of bile. The reasons for the diminution of biliary phospholipid secretion and the increase in biliary cytotoxicity are not known. This study was undertaken to determine whether the bilirubin-induced lowering of biliary phospholipid secretion is associated with alterations in hepatic P-glycoprotein (P-gp) expression and to determine why bilirubin infusions increase biliary cytotoxicity. METHODS: Hepatic bile was collected from bile acid-depleted pigs before and during intravenous bilirubin infusion. Hepatic P-gp expression was measured with protein blot analysis, using the P-gp-specific antibody C219. Biliary cytotoxicity was assayed against erythrocytes. The biliary phospholipid fatty acid profile was determined by means of gas chromatography. RESULTS: Bilirubin infusions lowered biliary phospholipid secretion by 69% without changing hepatic P-gp expression, suggesting that bilirubin infusions have an inhibitory effect on hepatic P-gp activity. Bilirubin infusions did not cause P-gp losses into bile. An unequivocal, proportional relationship (r2 = 0.80) pertained between cytotoxicity and the bile acid to phospholipid ratio in bile secreted before and during bilirubin infusion and in phosphatidylcholine-supplemented bile. Unconjugated bilirubin in bile did not contribute to biliary cytotoxicity. Biliary phospholipids were always phosphatidylcholine >> phosphatidylethanolamine, mainly of C16:0, 18:2 and C16:0, 18:1 fatty acid configuration. CONCLUSIONS: Intravenous bilirubin loads reduce biliary phospholipid secretion without changing hepatic P-gp expression. Bilirubin infusions increase biliary cytotoxicity by augmenting the biliary bile acid to phospholipid ratio.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed1999

Inhalation of nitric oxide inhibits ADP-induced platelet aggregation and alpha-granule release.

To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear.

Journal Article↗

PubMed1999

Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-1 receptor antagonist in human whole blood.

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) is supposed to be an important etiological agent in localized juvenile periodontitis (LJP). We have studied the effect of lipopolysaccharide (LPS) extracted from these periodontopathogenic bacteria on synthesis of the proinflammatory cytokines, interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) in human whole blood. LPS from A. actinomycetemcomitans in concentrations > or =1 ng/ml induced a significant production of all these proinflammatory cytokines, whereas LPS from Escherichia coli (E. coli), strain 026:B6 had to be added in concentrations > or =1 microg/ml to obtain a similar effect. Similarly, LPS from A. actinomycetemcomitans > or =0.1 ng/ml resulted in production of IL-1ra, while LPS from E. coli 026:B6 had to be added at > or =10 ng/ml to obtain similar effects. It has been suggested that the ratio between production of proinflammatory and anti-inflammatory cytokines may influence the outcome of periodontal diseases. Other in vitro and in vivo studies have, however, indicated that very large excesses (100-1000 times) of IL-1ra compared to IL-1beta are required to shift the IL-1ra:IL-1beta ratio in favor of an inhibition of IL-1 bioactivity. In our ex vivo system, we found that stimulation with extremely low doses of A. actinomycetemcomitans LPS (0.1-1 ng/ml) resulted in IL-1ra production solely, without concomitant production of IL-1beta, the excess of IL-1ra over IL-1beta peaking at 1 ng/ml, which accordingly should suggest that LPS from A. actinomycetemcomitans primarily has proinflammatory effects.

Aggregatibacter actinomycetemcomitans↗

PubMed1999

Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance.

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 x 10(6), 15 micrometer in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 +/- 1.5 (SE) + (5.8 +/- 0.7 x 10(-7) x number of injected microspheres). Because injection of 40 x 10(6) microspheres induced a long-lasting hyperemic response, which could be blocked by 8-p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 x 10(6) microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 +/- 3% of area at risk in control animals to 84 +/- 6% (P < 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.

Animals↗