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Biomedical subjects

C Lundberg

Publications and source records attributed to C Lundberg.

At least 109 records · Page 6Linked to original sources

Anaphylatoxin C5a fails to promote prostacyclin release in cultured endothelial cells from human umbilical veins.

Subcultured endothelial cells from human umbilical veins respond to histamine and melittin with increased prostacyclin production, measured as 6-keto-prostaglandin F1 alpha by radioimmunoassay. However, no response to leukotriene C4 was observed. Primary cultured cells, on the other hand, respond to leukotriene C4 and the histamine response was 7 times more potent for these cells than for subcultured cells. In contrast, neither primary cultures nor subcultures of endothelial cells released prostacyclin following application of either human anaphylatoxin C5a (100 nM) or C3a (1 microM). In addition, these endothelial cells appear to have no specific binding sites for 125I-C5a. However, endothelial cells released prostacyclin in the presence of human polymorphonuclear leukocytes that were activated with C5a. We conclude that involvement of endothelial cells in the haemodynamic response to anaphylatoxin is an indirect function, i.e. C5a activates circulating or tissue cells which in turn stimulate the endothelial cell to produce prostacyclin.

6-Ketoprostaglandin F1 alpha↗

Evidence of tinidazole interference in the oropharyngeal inflammatory process during infectious mononucleosis.

The efficacy of tinidazole was studied in 24 patients with infectious mononucleosis (IM), 13 of whom were randomized for 5 days of tinidazole treatment and 11 for control without placebo. In judging the comparability of the 2 groups not only was the distribution of confounding factors such as age, sex or duration of symptoms before admission considered, but also the distribution of the Epstein-Barr virus (EBV) serological stage at entry. In these respects the groups were well matched. The duration of sore throat and pharyngotonsillitis after admission was significantly shorter for the patients treated with tinidazole than for the controls. Orosomucoid and lactodehydrogenase concentrations normalized more readily in IM patients with a short duration of sore throat after admission and in patients treated with tinidazole compared to those with a long duration of sore throat and to the tinidazole controls. Clinical and laboratory findings were thus parallel and showed a clinical effect of tinidazole, believed to be mediated via the well-known activity of this drug against anaerobic bacteria. The EBV serological stage of each patient at entry could not predict the duration of symptoms. The results showed that the course of the angina was not primarily dependent on the virus host interaction but probably on other factors, still unknown. One such factor could be the balance between the mucosal defence and the normal oropharyngeal microflora.

Adolescent↗

Differences in EBV-specific antibody patterns at onset of infectious mononucleosis.

The EBV-specific antibody patterns of infectious mononucleosis (IM) patients were analyzed in relation to the onset of symptoms and clinical parameters during the acute phase of the disease. The antibody patterns varied considerably on admission. Three groups of patients were identified: one had not yet attained peak antibody titers, the second was at the peak and the third had passed the peak pattern. Patients with a "peak" current pattern had significantly higher lymphocyte counts, ASAT, ALAT, serum IgG and serum IgA concentrations than patients of the third group. Unexpectedly, there was no difference between the groups with regard to duration of sore throat and general malaise before admission. It thus seems that the lymphocyte proliferation during IM closely parallels the course of the EBV-specific antibody responses, whereas the onset of IM does not closely correlate to a specific stage of the antibody pattern.

Adolescent↗

Selective actions of calcium antagonistic drugs on the haemodynamics and regional organ blood flow in rats.

Six substances, all of which influence calcium utilization by smooth muscle, namely nimodipine (50 micrograms/kg), flunarizine (1 mg/kg), verapamil (0.2 mg/kg), lidoflazine (1 mg/kg), magnesium (600 mumol Mg++/kg), and manganese (180 mumol Mn++/kg), were given intravenously to rats and their effects on regional blood flows and on cardiac output were determined by the radioactive microsphere technique. All compounds caused a temporary fall in mean arterial blood pressure. Cardiac output was decreased by manganese, and minute work by nimodipine, manganese and lidoflazine. Nimodipine increased blood flow in the liver, skeletal muscle and heart and decreased that in the stomach, ileum, colon, kidney, spleen and skin; manganese increased flow in the duodenum, jejunum, liver and myocardium and decreased that in the stomach, ileum, colon, spleen and skin; flunarizine increased flow in the liver, heart and brain; and magnesium increased flow in the liver, spleen and brain. Lidoflazine and verapamil, although leading to haemodynamic alterations, had no selective effect on organ blood flow. Selective actions by calcium effector drugs can provide information on mechanisms of calcium flux in various types of vascular smooth muscle, and show that it is possible to tailor combinations of anti-calcium agents with optimal effects on a given organ.

Animals↗

Permeability-increasing ability of PAF-acether in rat skin.

Platelet-activating factor (PAF-acether), a phospholipid compound with effects on several cells, e.g., platelets and polymorphonuclear leukocytes (PMNs), was examined for its effect on microvascular permeability in rat skin. It was found to increase microvascular permeability, measured as exudation of [125I]human serum albumin, in amounts exceeding 1 pmol, and was more than 1000 times as potent as histamine. The effect was independent of cell infiltration, as no accumulation of PMNs, measured as the amount of myeloperoxidase in the skin, occurred and as the response was unaltered in animals rendered neutropenic due to treatment with an antiserum against PMNs.

Animals↗

Hemorrhagic shock in the dog. II. Studies on central hemodynamics and regional blood flow.

Oxygen consumption, hemodynamics, and regional blood flow (with the radioactive microspheres technique) were determined in 12 anesthetized dogs subjected to hemorrhagic shock. The animals were kept in hypotension at 40 mmHg, until 15% of the maximum shed blood had been infused to keep arterial pressure stable, whereafter all the shed blood was retransfused. Cardiac output (CO) decreased to 33% and 25% of preshock values in survivors (S) and nonsurvivors (NS), respectively, and after retransfusion it was significantly higher in S. After retransfusion, NS showed a higher arterial pCO2 than S adding a respiratory component to the metabolic acidosis that occurred during and after hemorrhage. Blood flow to the brain was not impeded during shock, but as CO decreased the fraction delivered to the brain was increased 2.6-3.3-fold. Myocardial blood flow decreased to about 28% of preshock values immediately after hemorrhage, and increased to about 54% at the end of hemorrhage. After retransfusion S had a higher myocardial flow than NS. The flow to the gut paralleled the decrease in CO during hemorrhage and immediately after retransfusion NS exhibited an overperfusion in ileum and colon compared to the preshock values. Kidney blood flow fell progressively during the course of hypotension, similarly in S and NS. After retransfusion it was normalized in S but not in NS. The preshock flow to pancreas was significantly higher in S than in NS, but during and after shock the blood flow did not differ between S and NS.

Animals↗

Comparison of the Fick principle and the radioactive microsphere method in measuring cardiac output during haemorrhagic shock.

The applicability of radioactive microspheres in measuring cardiac output (CO) during haemorrhagic shock in the dog was studied. The COs thus determined were compared with CO values obtained simultaneously by the Fick method. In 13 animals simultaneous CO measurements by the two methods were performed prior to and after initial bleeding (down to a mean arterial pressure of 40 mmHg), at the termination of the hypotension period, and 5 and 60 min following blood reinfusion. An excellent correlation (r = 0.97) between the two methods was found for all determinations combined. Furthermore, during each of the five phases of the shock procedure no difference was observed between the two methods of measuring CO and the correlation varied from moderate to excellent (r = 0.61-0.94). The results suggest that the microsphere method has a precision and validity comparable to those of conventional methods in measuring CO in situations when it is extremely low, as in haemorrhagic shock, in addition to having high accuracy in normal conditions.

Animals↗

Inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A comparison between gauze and Debrisan treatment.

Debrisan treatment was compared with the use of gauze in an experimental model of open wounds in the rat. The amounts of exudate absorbed by the gauze and by Debrisan were measured daily during the post-wounding period and the myeloperoxidase (MPO) activity in the exudate was determined. Blood flow, water content and accumulation of the collagen amino acid hydroxyproline in the granulation tissue were measured on days 3, 5, 7 and 10 post-wounding. The amount of exudate absorbed both by gauze and by Debrisan reached a peak on post-wounding days 4-5 and was greater in Debrisan-treated wounds. MPO activity in the Debrisan-absorbed exudate, on the other hand, was lower throughout the study period than in the exudate absorbed by gauze. Granulation tissue blood flow and water content reached maximum values on day 7 post-wounding, irrespective of treatment. Blood flows were 39% and 40% lower in the Debrisan-treated wounds on post-wound days 3 and 7, respectively, than in the gauze-treated wounds, whereas the water contents of the former wounds were 23% and 15% lower on days 3 and 10, respectively. The hydroxyproline content of the granulation tissue increased continuously from day 3 to day 10 and was similar in the two wounds. These results suggest that Debrisan is more effective than gauze for absorbing wound exudate, when applied on an openly secreting wound. In addition, the inflammatory reaction taking place in Debrisan-treated wounds seems to be less severe than in wounds treated with gauze.

Animals↗

Toxicological studies on omeprazole.

As part of the safety evaluation of the gastric antisecretory drug, omeprazole, toxicological studies have been performed in several species of animals. The acute toxicity after oral administration to rodents was low. The oral LD50 value was above 4 g/kg. The general toxicity after repeated administration has been studied in rats and dogs. No clinical signs of adverse reactions were seen. Some minor changes in hematology parameters were observed. In rats and mice decreases in the erythrocyte count, hematocrit and hemoglobin have occasionally been found at doses of 125 mumol/kg/day and more. Hyperplasia of oxyntic mucosal cells, concomitant with increases in stomach weight, oxyntic mucosal thickness and folding, has been observed in the species investigated, the dog, rat and mouse. In addition, slight chief cell atrophy and eosinophilia of the chief cell granules were observed in rats. The oxyntic mucosal effects were reversible upon treatment being discontinued. In the oncogenicity studies, gastric carcinoids occurred in the rat but not in the mouse. Investigations of the carcinoids showed that the vast majority of the endocrine cells could be characterised as ECL-cells. The hyperplasia of oxyntic mucosal cells, including hyperplasia of endocrine ECL-cells and development of gastric carcinoids in rats, is attributable to the pronounced hypergastrinemia produced as a secondary effect of almost complete inhibition of acid secretion by the large doses of omeprazole used in the toxicity studies. In agreement with this hypothesis, the hyperplasia of the oxyntic cells was prevented by antrectomy. The reproduction studies performed in rats and rabbits showed no sign of fetal toxicity or teratogenic effect. The results of the short-term mutagenicity tests, Ames test, the micronucleus test in mice and the mouse lymphoma test were all negative.

Administration, Oral↗

Human nasal mucosa reaction during chilling of the feet.

As rhinostereometry, an optical measurement method, allows meticulous studies of changes in nasal mucosa congestion, the mucosal reaction in eight healthy volunteers was studied with this technique before, during and after 20 minutes' chilling of the feet in cold water. In five volunteers there were no observable mucosal reactions. In three volunteers the mucosal congestion changed but not uniformly, and not in such a way that the change could be explained as an effect of chilling of the feet. In four volunteers there was a clearly observable increased nasal secretion. This gives a possible explanation of the increased nasal breathing resistance observed in similar studies using rhinomanometry as the measuring method.

Adult↗

Selective tissue accumulation of manganese and its effect on regional blood flow and haemodynamics after intravenous infusion of its chloride salt in the rat.

Manganese chloride (MnCl2), with or without the addition of trace amounts of 54Mn2+, was administered as a 7-min i.v. infusion in rats. Tissue accumulation of 54Mn2+ was determined 0-15 min after the infusion, and cardiac output, regional blood flows and vascular resistances were measured 5 and 60 min after the infusion by the microsphere technique. The plasma half-life of 54Mn2+ was found to be 4.7 min. Mn2+ accumulated in several organs, the highest relative concentrations being seen in the liver, duodenum, jejunum, kidney and heart, and intermediate concentrations in the ileum, colon, stomach and spleen. There was no uptake in the lung, skeletal muscle or brain. During the infusion of 180 mumol/kg b.w. of Mn2+, the arterial blood pressure fell from a mean of 123 +/- 5 mm Hg to a minimum of 85 +/- 7 mm Hg, and thereafter returned to normal. Five minutes after termination of the infusion, there was a decrease in cardiac output and minute work but not in total peripheral resistance, a finding interpreted as a negative inotropic effect of Mn2+. At this time blood flow was decreased in the stomach, ileum, colon, spleen and skin, and increased in duodenum, jejunum and liver. The blood flows were normalized 60 min after termination of the infusion in all organs except the liver and heart. The effects are probably due to the calcium-antagonistic properties of Mn2+ and the tissue accumulation is most probably a result of intracellular accumulation through calcium channels. The relation between tissue accumulation and tissue selectivity of blood-flow alterations is unexplained.

Animals↗

The inflammatory reaction in an experimental model of open wounds in the rat. The effect of arachidonic acid metabolites.

The study concerned the effect of arachidonic acid metabolites on the inflammatory reaction in granulation tissue of open wounds in rats. Metabolites or inhibitors were applied in a wound chamber attached to circular, open, full-thickness skin wounds 5 days post-wounding. The adjacent wound served as control. Blood flow, albumin extravasation and accumulation of polymorphonuclear leucocytes (PMNLs) were measured in the granulation tissue. Prostaglandin E2 (PGE2 5.7 microM) increased blood flow and albumin extravasation by 95 and 16%, respectively, without affecting PMNLs. Leukotriene B4 (LTB4 2.7 microM) increased PMNL accumulation by 142% without altering albumin extravasation. Indomethacin (28 microM, repeatedly) did not affect blood flow or albumin extravasation, but increased PMNL accumulation by 21%. Methylprednisolone (3.3 mM, repeatedly) reduced blood flow and albumin extravasation by 29 and 31%, respectively, without influencing PMNLs. The granulation tissue obviously responds to exogenous PGE2 and LTB4. Endogenous arachidonic acid metabolites seem to play only a minor role in the inflammatory process in this model.

Animals↗

Bacteria and inflammatory cells in maxillary sinusitis.

A series of maxillary sinus mucosal specimens and a series of smears of retained maxillary sinus secretions were studied with regard to the relationship between bacteria and inflammatory cells in order to illustrate aspects of the inflammatory process and to investigate the cause of mucosal damage in maxillary sinusitis. The results show that the granulocytes in the retained secretions are actively phagocytizing organisms if conditions are favourable for the granulocytes. Such situations are present in mucopurulent secretions but mostly not in strictly purulent secretions. A correlation was found between the presence of large numbers of inflammatory cells and tissue destruction, whereas bacterial invasion of the mucosa was a rare phenomenon and seen only in areas where the epithelial lining was destroyed. This indicates strongly that the mucosal damage in sinusitis is caused by inflammatory cells and not primarily by bacteria.

Granulocytes↗

The effect of tinidazole on primary EBV infection and immunocompetence.

Tinidazole and metronidazole have been reported beneficial in the treatment of acute anginose infectious mononucleosis. As this disease is caused by the Epstein-Barr virus (EBV), the effect of tinidazole on EBV infection of human B-lymphocytes was investigated. Tinidazole had no effect on induction of EBV determined nuclear antigen (EBNA) or DNA synthesis, while immunoglobulin synthesis was increased in the presence of the drug. Cytotoxicity directed against EBV positive cell lines and long term T-lymphocyte mediated anti-EBV memory, were not affected by tinidazole. In view of these findings we suggest that tinidazole does not act directly on the primary EBV infection in vitro. Nor do our findings indicate any adverse effects of tinidazole on the virus-host relation.

Antigens, Viral↗

Low secretory IgA concentrations in oral secretions during the acute phase of infectious mononucleosis.

Although the Epstein-Barr virus (EBV) relation to infectious mononucleosis (IM) has been well established, the question why IM is not compulsory during a primary EBV infection has yet to be solved. Assuming a possible oropharyngeal secretory immunoincompetence as an etiological component of IM, the secretory IgA concentrations in oral secretions during the acute phase of IM was investigated. Low concentrations of secretory IgA in IM patients (n = 18) were found, mean value 0.180 g/l as compared to those in healthy controls (n = 10), mean value 0.680 g/l. Furthermore, diminishing concentrations of secretory IgA were found during the acute phase of IM. There was no corresponding serum IgA decrease. The investigation also revealed that tinidazole, claimed to be beneficial in the treatment of anginous IM, did not affect the concentrations of spit secretory IgA.

Adolescent↗