Biomedical subjects

C Jarstrand

Publications and source records attributed to C Jarstrand.

At least 19 recordsLinked to original sources

PubMed2004

Lipid peroxidation of lung surfactant in experimental neonatal group B streptococcal pneumonia.

Group B streptococcal (GBS) pneumonia, with neutrophilic granulocytes immigrating into the lungs, may occur in neonates. The incidence is particularly high among preterm infants, who often are treated with exogenous surfactant. We have previously demonstrated in vitro that neutrophils stimulated by GBS cause lipid peroxidation (LPO) and functional impairment of lung surfactant. The present study aimed at evaluating LPO of exogenous lung surfactant (Curosurf) and the protective effect of the natural antioxidant, vitamin E in immature ventilated newborn rabbits with experimental neonatal GBS pneumonia. There was a prominent proliferation of GBS in the lungs of animals treated with surfactant and ventilated for 5 h. GBS-infected rabbits had a higher LPO of lung lavage fluid than non-infected ones. The LPO could be diminished using vitamin E, which, however, did not affect bacterial proliferation. During the 5-h incubation period, mean lung-thorax compliance values were significantly lower in GBS-infected than in noninfected animals. We speculate that addition of vitamin E to exogenous surfactant preparations may improve their resistance to LPO and make them more suitable for treatment of neonates with pneumonia.

Animals↗

PubMed2001

Antibodies against a truncated Staphylococcus aureus fibronectin-binding protein protect against dissemination of infection in the rat.

Staphylococcus aureus bacteraemia (SAB) originating from local infections can lead to severe secondary infections such as endocarditis. The protective effect of antibodies against secondary infections was studied in a rat model, where a local joint infection leads to bacteraemia and endocarditis on damaged aortic valves. In this study, immunizations with a truncated D2-domain of the S. aureus fibronectin-binding protein displayed on a cow-pea mosaic virus (CPMV-D) carrier induced protection against endocarditis (P < 0.05). Opsonization of S. aureus with antibodies raised against CPMV-D stimulated both neutrophil activity and macrophage phagocytosis in vitro. Furthermore, intravenous administration of these antibodies protected mice from weight loss due to SAB.

Adhesins, Bacterial↗

PubMed2001

Effect of surfactant and specific antibody on bacterial proliferation and lung function in experimental pneumococcal pneumonia.

OBJECTIVE: To investigate the effect of surfactant and specific antibody on bacterial proliferation in experimental pneumococcal pneumonia. METHODS: Near-term newborn rabbits received a standard dose (10(7)) of type 3 pneumococci via the airways. Control animals were sacrificed 1 minute later. Other animals were ventilated for 5 hours and treated via the tracheal cannula with surfactant (Curosurf 200 mg/kg), a mixture of surfactant and a polyclonal antipneumococcal antibody, the antibody without surfactant, or saline. RESULTS: There was a significant bacterial proliferation in lung tissue in all animals ventilated for 5 hours. Bacterial growth, expressed as log10 colony forming units (CFU) per gram of lung tissue was less prominent in animals treated with a mixture of surfactant and specific antibody than in animals treated with antibody alone (median, 7.51, range, 6.80--7.70 vs. median, 7.92, range, 7.07--8.50; P < 0.05). Dynamic lung-thorax compliance was improved with surfactant or surfactant plus antibody in comparison with saline or antibody alone. CONCLUSIONS: The data suggest that the suppressive effect of the antibody on bacterial proliferation becomes evident only when surfactant is administered together with the antibody.

Animals↗

PubMed2001

Lipid peroxidation caused by oxygen radicals from Fusobacterium-stimulated neutrophils as a possible model for the emergence of periodontitis.

OBJECTIVE: The possible contribution of bacteria and polymorphonuclear neutrophils (PMN) to the disease process of periodontitis was evaluated. DESIGN: Fusobacterium nucleatum has been associated with chronic adult periodontitis. Intracellular production and extracellular release of reactive oxygen species (ROS) by PMN stimulated by fusobacteria were evaluated. To estimate the potential extracellular damage that might be caused by the ROS, the lipid peroxidation (LPO) of an exogenous phospholipid, Intralipid, was assayed. METHODS: The ROS production of PMN was studied by the nitroblue tetrazolium and chemiluminescence tests. The levels of malonaldehyde (MDA) and 4-hydroxyalkenals were used to indicate LPO. RESULTS: Fusobacterium nucleatum strains stimulated neutrophils to produce a large amount of ROS, independently of plasma complement factors. The two strains tested induced considerable intracellular, but no extracellular chemiluminescence responses during the first hour, indicating that ROS were released into phagosomes. However an incubation period of 4 h, in the presence of the extracellular lipid resulted in a high degree of LPO, presumably caused by ROS release from the Fusobacterium-stimulated PMN. ROS production and lipid peroxidation could be counteracted by vitamin E. CONCLUSION: In periodontitis local bacteria might stimulate PMN to release ROS, which cause inflammation and destruction.

Adult↗

PubMed2000

Interaction between lung surfactant and nitric oxide production by alveolar macrophages stimulated by group B streptococci.

The major etiologic agent in neonatal pneumonia and meningitis is group B streptococci (GBS). Nitric oxide (NO) production by alveolar macrophages (AM) in response to Gram-positive bacteria such as GBS and the effect of surfactant on this production have received little attention. We studied production of NO by GBS-stimulated AM using the Griess reaction, the effect of lung surfactant on this NO production, and the possible lipid peroxidation (LPO) of surfactant caused by NO. The LPO test was used to measure surfactant peroxidation. Heat-killed and live GBS were found to stimulate NO production by rat alveolar macrophages, and the presence of interferon gamma (IFN-gamma) increased this stimulation in a synergistic manner. Curosurf(R), the natural surfactant used in our study, significantly reduced NO production in various sets of experiments. Lipid peroxidation of surfactant was noted when NO was produced by stimulated AM, a phenomenon that could be suppressed by NG-monomethyl L-arginine (L-NMMA), the inhibitor of NO synthase. In the lung of GBS-infected neonates, nitric oxide produced by AM might contribute to the destruction of surfactant caused by inflammatory cells. Pediatr Pulmonol. 2000; 30:106- 113.

Animals↗

PubMed2000

Mercury intolerance in relation to superoxide dismutase, glutathione peroxidase, catalase, and the nitroblue tetrazolium responses.

Through percutaneous provocation with metallic mercury and phenyl mercuric acetate in patients stating the presence of subjective psychosomatic symptoms following dental amalgam treatment, it has been possible to categorize and score two extreme groups of patients, mercury-intolerant and mercury-tolerant patients reacting and not reacting, respectively, to low doses of mercury. The intolerant patients had a high psychosomatic score and the tolerant patients had a low or null score when exposed to low doses of the two mercury compounds. Determination of the scavenger enzymes superoxide dismutase, glutathione peroxidase, and catalase showed no significant differences between the mercury-intolerant and the mercury-tolerant patients and the controls. The activity of superoxide dismutase and the quantitative psychosomatic score elicited by either metallic mercury or phenyl mercuric acetate showed a positive correlation. On the other hand, analyses of the psychosomatic score and the areas under the curves of the nitroblue tetrazolium test response showed negative correlations. The results indicate that the oxidative metabolism and, in particular, superoxide dismutase may be perturbed in mercury-intolerant patients.

Aged↗

PubMed2000

Direct and phagocyte-mediated lipid peroxidation of lung surfactant by group B streptococci.

In newborn infants, group B streptococci (GBS) often cause pneumonia, with polymorphonuclear leukocytes (PMN) migrating into the lungs. Because surfactant therapy may be needed in such patients, we evaluated the interaction between GBS or GBS-stimulated PMN and a surfactant preparation (Curosurf) in vitro. The superoxide production of GBS strains or GBS-activated PMN was measured, using the nitroblue tetrazolium (NBT) test and the subsequent lipid peroxidation (LPO) as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The growth of GBS in surfactant was determined and related to the LPO. Finally, the effect of LPO on surfactant activity, caused by GBS-stimulated PMN, was assessed by measuring dynamic surface tension in a pulsating bubble surfactometer. Curosurf diminished the NBT reduction by both live GBS and GBS-stimulated PMN. Surfactant was peroxidized by reactive oxygen species (ROS) from both GBS and GBS-stimulated PMN in a time-dependent manner. Vitamin E significantly reduced the peroxidation level of surfactant in both cases. Surfactant peroxidation was associated with a reduction in the number of live bacteria. The biophysical activity of Curosurf was impaired by GBS-stimulated PMN, as reflected by increased minimum surface tension during cyclic compression. These findings indicate that Curosurf undergoes LPO by ROS produced by GBS and/or PMN. We speculate that exogenous surfactant preparations should be supplemented with vitamin E or another antioxidant, when given to infants with GBS pneumonia.

Adult↗

PubMed2000

Cytokine, elastase and oxygen radical release by Fusobacterium nucleatum-activated leukocytes: a possible pathogenic factor in periodontitis.

Periodontitis is characterised by tissue destruction caused by reactive oxygen species (ROS) and proteolytic enzymes, which are released by the interaction between bacteria and phagocytes. We estimated the ability of Fusobacterium species to induce release of tissue destructive and proinflammatory mediators from in vitro activated peripheral leukocytes. ROS was measured with the nitroblue tetrazolium (NBT) method, elastase with a specific chromogenic substrate and cytokines, including interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) with a sandwich ELISA method. Various clinical isolates of unopsonized Fusobacterium species stimulated the neutrophils to an increased NBT- reduction. IL-1beta, TNFalpha, IL-8 and elastase were released in significantly higher levels from neutrophils stimulated by Fusobacterium species. In conclusion, unopsonized Fusobacterium species can induce increased production of oxygen radicals, cytokines and elastase from leukocytes activated in vitro.

Analysis of Variance↗

PubMed2000

Treatment of experimental Cryptococcus neoformans infection in newborn rabbits by airway instillation of specific antibody and surfactant.

Cryptococcosis in AIDS patients has a slow response to antifungal chemotherapy, and passive antibody treatment has thus been considered as an adjunct. Polyclonal anticryptococcal IgG dissolved in a suspension of modified natural surfactant was given intratracheally to near-term rabbits. Killing of Cryptococcus neoformans within the lungs was determined by counting the colony forming units (cfu). After 5 h a significant decrease in cfu was observed in rabbits treated with the IgG-surfactant mixture compared with control animals receiving saline. In conjunction with conventional therapy, the combined treatment of IgG-surfactant given by bronchoscopy might be used in high-risk patients to enhance killing of the yeast within the lungs.

Animals↗

PubMed2000

Lipid peroxidation by alveolar macrophages challenged with Cryptococcus neoformans, Candida albicans or Aspergillus fumigatus.

Increased formation of oxygen radicals has previously been shown for alveolar macrophages (AM) challenged with Cryptococcus neoformans cells opsonized with fresh serum or polyclonal immunoglobulin G. AM show similar responses to Candida albicans or Aspergillus fumigatus. Oxygen radicals are capable of damaging various macromolecules, including lipids. In the present study, lipid peroxidation (LPO) caused by AM incubated with the fungi was examined in the presence and absence of lung surfactant. The level of malonaldehyde was used as an indicator of LPO. AM damage was examined by electron microscopy (EM), by trypan blue exclusion and by counting the AM loss from culture dish to supernatant. Stimulation of AM by each fungus increased cellular LPO but did not affect AM viability. A slight surfactant LPO induced by AM alone was shown with significantly increased values after addition of each fungus. EM studies showed that dense lipid droplets, presumably consisting of oxidized lipids, were ingested in high amounts together with C. neoformans cells that had been opsonized in fresh serum, and in low amounts in combination with C. albicans. These processes were accompanied by increased numbers of AM in the supernatants. LPO and detachment of AM were counteracted by vitamin E. In the lungs, AM exposed to one of these fungal pathogens might promote peroxidation of surfactant lipids.

Animals↗

PubMed1999

Phagocyte-induced lipid peroxidation of lung surfactant.

Surfactant therapy is given routinely to premature newborns with respiratory failure. However, alterations in surfactants have been shown to be a significant factor in some forms of respiratory failure in newborns in animal models of lung injury. To investigate whether antioxidant supplementation might help to protect exogenous surfactant from damage by oxygen free radicals, we examined the influence of vitamin E in combination with surfactant on superoxide production as estimated by the nitroblue tetrazolium reduction test, and measured surfactant peroxidation with a new colorimetric method with or without addition of superoxide dismutase (SOD) or vitamin E. Our results showed that surfactant interacts with free radicals; surfactant reduced superoxide production by neutrophils and was peroxidized when incubated with resting and with stimulated cells. Vitamin E supplementation decreased superoxide radical production and in a dose-dependent manner decreased surfactant peroxidation. The decrease in lipid peroxidation by SOD was not significant. These findings suggest that phagocytes induce lipid peroxidation of lung surfactant, a reaction that might be prevented by antioxidants.

Humans↗

PubMed1999

Characterization of beta-lactam-resistant Bacteroides fragilis isolates by use of PCR fingerprinting.

PCR fingerprinting was used for characterization of 35 beta-lactam-resistant Bacteroides fragilis strains isolated in Sweden and Hungary. Ten B. fragilis strains showed unique PCR fingerprints by use of the M13 core primer. Their main product was a DNA fragment with a length of 2000-bp which was absent in the other 25 strains and the reference strain B. fragilis ATCC 25285. The 2000-bp fragment from four imipenem-resistant strains gave rise to positive reactions in a specific PCR for detection of ccrA. Printed by the T3B primer, five B. fragilis strains, including the imipenem-resistant strains showed unique PCR fingerprints. The investigated imipenem-resistant strains produced carbapenem-hydrolysing metallo-beta-lactamases. The study indicates that the unique PCR fingerprinting profiles shown in highly beta-lactam resistant B. fragilis strains are correlated to antimicrobial resistance. The PCR fingerprinting technique is a useful tool for differentiation of Bacteroides fragilis strains with high-level beta-lactam resistance.

Journal Article↗

PubMed1999

Lipid peroxidation of lung surfactant by bacteria.

The epithelium of the lung is lined with extracellular pulmonary surfactant. This is the surface that invading bacteria first come into contact with when they enter the alveoli. As bacteria become established and interact with this layer, various characteristics of surfactant may become altered. We studied free radical production by three bacterial species, group B streptococci, Escherichia coli, and Pseudomonas aeruginosa, as well as the effect of two concentrations of lung surfactant (Curosurf at 0.04 and 0.4 mg/ml) on this production estimated by the nitro blue tetrazolium reduction test. We also measured the lipid peroxidation of surfactant at various incubation times (0-20 h), using a LPO-586 test kit. In addition, the effect of vitamin E as an antioxidant in a concentration of 0.5 microM was determined by the lipid peroxidation test. We found that the nitro blue tetrazolium reduction by the three bacterial species and lipid peroxidation of lung surfactant increased with time. Vitamin E reduced the lipid peroxidation of this surfactant. By measuring bacterial growth at various incubation times we showed that lung surfactant was bactericidal to group B streptococcal and E. coli strains and that P. aeruginosa strains were resistant to surfactant. We conclude that bacteria, probably by their production of reactive oxygen species, cause lipid peroxidation of lung surfactant.

Escherichia coli↗

PubMed1999

Phagocyte-induced lipid peroxidation of different intravenous fat emulsions and counteractive effect of vitamin E.

Unsaturated fatty acids, a major component of fat emulsions used in parenteral nutrition, are prone to peroxidation which is an important feature of oxygen-associated tissue damage. We used the nitroblue tetrazolium (NBT) reduction test to measure the production of superoxide radicals by stimulated polymorphonuclear neutrophils (PMN) in the presence of different fat emulsions: Intralipid (containing 100% long-chain triacylglycerols, LCT), Vasolipid (a physical mixture of 50% LCT and 50% medium-chain triacylglycerols, MCT) and Structolipid (structured triacylglycerols containing 63% LCT and 37% MCT). We measured the amount of malonaldehyde (MDA) and 4-hydroxyalkenal to determine the lipid peroxidation of the three fat emulsions in the presence of stimulated neutrophils. Further, we investigated the role of vitamin E (alpha-tocopherol) in preventing lipid peroxidation in vitro. The results showed that the values of NBT reduction of PMN were significantly decreased in each of the three fat emulsions and that increasing concentrations of fat emulsions were associated with decreased values of NBT reductions, in a dose-dependent way (P<0.001). There were, however, no statistically significant differences between the values of the three different types of fat emulsions (P>0.05). Lipid peroxidation increased significantly in the presence of all three types of fat emulsions, and was more pronounced for Intralipid than for Vasolipid and Structolipid after 1 and 2 h of incubation with resting as well as with stimulated phagocytes. The increased lipid peroxidation of the fat emulsions was markedly reduced by vitamin E, and the inhibition was concentration dependent. In conclusion, lipid peroxidation in vitro is more pronounced when PMNs are incubated with fat emulsions. This increase in lipid peroxidation can be reduced by adding vitamin E to the fat emulsions.

Adolescent↗

PubMed1999

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients.

Candida overgrowth and invasion constitute a serious threat with a high mortality in BMT recipients. Currently available topical antifungal prophylaxis is largely ineffective, and as resistance to existing, absorbable drugs for systemic use is rapidly developing, new forms of therapy are needed. We investigated the effect of oral treatment of BMT recipients with a bovine immunoglobulin product derived from animals immunized against several Candida species. The natural Candida colonization was first followed in 19 patients to establish the colonization pattern. Half of the patients were found to be colonized prior to transplantation and altogether 72% were colonized at some point during follow-up. Those with a high pre-transplant concentration of Candida in saliva (>100 CFU/ml) remained colonized throughout the BMT treatment period. The therapeutic effect was monitored in two other patient groups. The first group consisted of nine patients, where, due to a low number of primary colonized patients, response in colonized patients was suggestive of a therapeutic effect. In the second group, 10 patients with a high level of colonization (>100 CFU/ml) were given 10 g daily of the product in three divided doses. The results suggest a treatment-related reduction in Candida colonization in a majority (7/10) of patients and one patient became completely negative. As no adverse effects were noted, our findings encourage additional studies in immunocompromised, transplant patients.

Administration, Oral↗

PubMed1999

Coagulase-negative staphylococci are the most common bacteria found in cultures from the deep portions of hidradenitis suppurativa lesions, as obtained by carbon dioxide laser surgery.

The significance of bacterial findings in hidradenitis suppurativa (HS) is controversial. Interpretation of the results of bacteriological examinations from the surface of HS lesions is obscured by the possible contamination of resident skin bacteria. Bacteriological analysis of aspirates from deeper parts of HS is liable to show low sensitivity. We used a carbon dioxide (CO2) laser method to evaporate the diseased tissue level by level from the surface downwards, allowing concurrent sampling of bacteriological cultures from each level and thereby minimizing contamination with bacteria from the level above. In this study, 22 women and three men with a mean age of 35.3 years and a mean HS duration of 10.6 years were treated with this CO2 laser surgical method. Aerobic and anaerobic cultures from superficial and deep levels were taken during surgery. The regions treated were axillary in eight and perineal in 17 cases. Bacterial cultures were positive for one or more specimens from at least one level in all cases and from deep levels in all but three cases. Sixteen different species or sub-species were found. Staphylococcus aureus and coagulase-negative staphylococci (CNS) were the species most frequently found. Peptostreptococcus species and Propionibacterium acnes were not uncommon. S. aureus was detected in a total of 14 cases, six of which were from the deep levels. S. aureus was the sole bacterium isolated in two deep cultures. CNS were found in 21 patients and 16 of these isolates were from the deep levels. In nine of the 16 deep samples CNS were the only bacteria detected. These findings motivate a re-evaluation of the significance of bacteria in the progress of HS and in particular they suggest that CNS are true pathogens. It is known that foreign bodies aggravate the virulence of the CNS in surgical implants, and an environment which resembles that produced by a foreign body, as found in chronic HS tissue, serves to intensify the pathogenic properties of CNS in HS.

Adult↗

PubMed1999

Combined treatment with surfactant and specific immunoglobulin reduces bacterial proliferation in experimental neonatal group B streptococcal pneumonia.

Neonates suffering from group B streptococcal (GBS) pneumonia often lack type-specific opsonizing antibodies. We studied the influence of combined intratracheal treatment with surfactant and a specific antibacterial polyclonal antibody (IgG fraction) on bacterial proliferation and lung function in an animal model of GBS pneumonia. Near-term newborn rabbits received an intratracheal injection of either the specific IgG antibody, nonspecific IgG, surfactant, a mixture of surfactant and the antibody, or 0.9% saline. At 30 min the rabbits were infected with a standard dose (10(8)) of the encapsulated GBS strain 090 Ia. After 5 h of mechanical ventilation the mean estimated increase in bacterial number in lung homogenate (log10 colonies/g) was 0.76 in the antibody group, 0.92 in the nonspecific IgG group, 0.55 in the surfactant group, and 1.29 in the saline group. A mean decrease in bacterial number (-0.05) was observed in the group that received combined treatment with surfactant and antibody (p < 0.05 versus all other groups). Lung-thorax compliance was significantly higher in both groups of surfactant-treated animals compared with saline or IgG treatment. We conclude that in experimental neonatal GBS pneumonia combined treatment with surfactant and a specific immunoglobulin against GBS reduced bacterial proliferation more effectively than either treatment alone.

Animals↗

PubMed1999

Production of nitric oxide by rat alveolar macrophages stimulated by Cryptococcus neoformans or Aspergillus fumigatus.

Cryptococcus neoformans and Aspergillus fumigatus are airborne fungi and the alveolar macrophages (AM) constitute a first line of host defence against both pathogens. We investigated the ability of rat AM to produce nitric oxide (NO) when challenged in vitro with C. neoformans, A. fumigatus conidia or inert silica particles alone and together with interferon gamma (IFN-Gamma). The role of NO in the killing of C. neoformans as well as the relationship between phagocytosis of the yeast or A. fumigatus conidia and NO production by AM were studied. Both fungi, but not the inert particles induced a small but significant increase in NO production by AM. A synergistically enhanced NO production by AM was observed when each fungus, but not silica particles, were incubated together with IFN-Gamma. AM treated with IFN-Gamma and challenged with C. neoformans showed higher killing activity than untreated AM, a finding that correlated with increased NO production by AM. Both effects were reduced by an inhibitor of NO synthesis. Increased NO production by IFN-Gamma activated AM was found together with an increased accumulated attachment of A. fumigatus conidia and serum opsonized, but not unopsonized C. neoformans. The IFN-Gamma dependent increase in accumulated attachment of the fungi might be responsible for the synergistic effect of the fungi and IFN-Gamma on the NO production. Our data suggest that activated rat AM might efficiently use the antimicrobial nitric oxide system in the defence against these pathogens in the normal host.

Animals↗