Search PubMed⌕ Search

Biomedical subjects

A Forsgren

Publications and source records attributed to A Forsgren.

208 records · Page 12Linked to original sources

Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin.

The fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) in stimulated human peripheral blood lymphocytes. In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated (T cell mitogens or alloantigens) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin (5-80 micrograms/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro (20 micrograms/ml). EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction. In addition, EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells (NFAT-1) as compared to control cells without antibiotics. Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A. Taken together, cipro inhibited IFN-gamma synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription.

Animals↗

Experimental recurrent otitis media induced by Haemophilus influenzae: protection and serum antibodies.

PURPOSE: To study whether acute otitis media caused by encapsulated or nontypeable Haemophilus influenzae confers cross-reactive protective immunity in an animal model system and to explore the possible involvement of various humoral specific antibodies in protection. MATERIALS AND METHODS: Rats were intrabullarly challenged with H influenzae type b and two different nontypeable H influenzae strains. One month after the initial infection, the animals were rechallenged ipsilaterally or contralaterally with either a homologous or heterologous strain, and the susceptibility to reinfection was investigated by otomicroscopy. RESULTS: The animals challenged and rechallenged with the type b strain were well-protected ipsilaterally and contralaterally, while the protection after homologous rechallenge with a nontypeable strain was partial in the ipsilateral ear and very poor in the contralateral ear. Middle ears previously infected with a nontypeable strain remained fully susceptible to infections with heterologous strains, but there was an indication of cross-protection in the animal groups where the first episode of acute otitis media was caused by type b and the second by a nontypeable strain. Using the Western blot technique and an enzyme linked immunosorbant assay, the serological response to different outer membrane proteins, especially protein D, of H influenzae during and after middle ear infection were investigated. The serological response from the type b infected animals were generally more distinct, while the antibody levels against protein D were lower in these groups compared with the groups infected with nontypeable strains. CONCLUSIONS: These data indicate that H influenzae type-b-induced experimental otitis media results in a better protection than a nontypeable-induced, and H influenzae b confers a cross protection.

Animals↗

New quinolones: in vitro effects as a potential source of clinical toxicity.

4-Quinolones affect mammalian cellular functions in vitro in several ways. High concentrations inhibit DNA replication, but individual genes are perhaps sensitive to lower concentrations of drug. Inhibition of cell proliferation differs widely among 4-quinolones. Ciprofloxacin and norfloxacin are the most antiproliferative, inhibiting cell growth by approximately 30% at 20 mg/L. Genotoxicity tests with 4-quinolones are probably "false-positive" as a result of increased [3H]thymidine uptake that is not related to DNA damage. Ciprofloxacin at greater than or equal to 10 mg/L causes significant strand breaks in DNA, which seemingly are quickly repaired and do not cause mutations or cancer. Production of immunoglobulin is inhibited by ciprofloxacin at a concentration of 5 mg/L, but production of the growth factor interleukin 2 (IL-2) is increased by 4-quinolones at the same concentration and is hyperinduced at higher concentrations. Thus the effects are very contradictory. Increased production of IL-2 may contribute to central nervous system adverse effects. 4-Quinolones in combination with theophylline or antiinflammatory drugs may inhibit gamma-aminobutyric acid receptor binding and thereby have adverse effects on the central nervous system. Some 4-quinolones induce crystalluria, which may be nephropathic.

4-Quinolones↗

Acute otitis media in older children and adults treated with phenoxymethyl penicillin or erythromycin stearate. Bacteriological and immunological aspects.

Seventy-eight patients, all over 10 years of age, with clinical signs of acute otitis media, received either phenoxymethyl penicillin or erythromycin stearate, in a randomized manner, and the clinical, bacteriological and immunological effects were studied. Haemophilus influenzae and Streptococcus pneumoniae were the major pathogens isolated from the nasopharynx in 30 and 28 patients, respectively. Increased levels of C-reactive protein (CRP) were detected in 53 (68%) of the patients. There was no statistical difference in the CRP-levels depending on species of bacteria isolated. The highest incidence was observed in cases with Branhamella catarrhalis and H. influenzae. Persistence of H. influenzae during antibiotic therapy was demonstrated in 70% and after therapy in 63% compared to 4% and 11% persistence of S. pneumoniae. The type of antibiotic treatment did not influence persistence. An immune response to H. influenzae and S. pneumoniae was detected significantly more often in patients treated with erythromycin stearate than with phenoxymethyl penicillin.

Acute Disease↗

Effect of LTB4 and its isomers on human leucocyte migration into skin chambers.

The in vivo chemotactic effect of LTB4 and of its isomers, 6-trans-LTB4, 12 epi-6-trans-LTB4 and 5S, 12S-DHETE, was tested with a skin chamber technique in healthy volunteers and in parallel in vitro with an under-agarose technique. LTB4 had an in vivo chemotactic effect at 10(-7) mol/l in 24-hour experiments, while its isomers had no in vivo chemotactic effect at this concentration. LTB4 was also in vitro a more effective attractant than its isomers. In addition, C5ades Arg was tested using zymosan-activated serum, and was found to have an in vivo chemotactic effect at 1.5 X 10(-10) mol/l. However, when LTB4 and C5ades Arg were studied in 6-hour experiments in skin chambers there was an alteration in relative potency, LTB4 being relatively more potent at shorter test durations. This is most likely due to metabolisation of LTB4 in the presence of PMN:s and precludes a strict comparison of the in vivo chemotactic effects of LTB4 and C5ades Arg. When zymosan-activated serum or LTB4 was replaced by PBS after six hours in skin chamber experiments more leukocytes accumulated in the chambers at 24 hours than in chambers containing PBS for the whole 24 hour period. The reason for the increased migration even after the removal of the chemo-attractants as well as the relevance of LTB4 and C5a as chemo-attractants in the inflammatory process is discussed.

Chemotaxis, Leukocyte↗

Reduced in vivo leucocyte migration and elastase and lysozyme concentrations in skin chamber experiments with piroxicam in healthy volunteers.

Leucocyte migration in vivo, studied with a skin chamber technique was inhibited in eight healthy volunteers after six days' medication with piroxicam, 20 mg a day, but not after only one day's medication. The inhibition was not correlated to the serum content of the drug. The median trough values of piroxicam in serum were 2.5 mg/l and in blister fluid 1.2 mg/l after six days' medication. Leucocyte migration in vitro under agarose was not inhibited after six days' medication with piroxicam. When normal polymorphonuclear leucocytes were incubated with piroxicam in vitro migration under agarose was inhibited but only at piroxicam concentrations higher than those attainable in clinical therapy. The concentrations of elastase and lysozyme in the skin chamber decreased after six days' medication with piroxicam.

Adult↗

Kinetics of enzymes released from polymorphonuclear leucocytes in a skin chamber.

Ten healthy volunteers were investigated with a skin chamber technique developed for leucocyte migration studies. Chambers, filled with autologous serum, were harvested at 4, 8, 12, 22, and 30 hours. A marked increase was found both in the concentration of elastase in chamber serum as measured by RIA, and of lysozyme as measured both with lysoplate and electroimmuno assays. The immuno-reactive elastase was shown to consist exclusively of elastase-alpha 1-proteinase-inhibitor complexes. During the first 22 hours the concentrations of elastase and lysozyme were roughly proportional to the number of cells in the skin chamber (r = 0.92 and 0.85). At longer incubation times there was a decrease of relative concentration of elastase but not of lysozyme. Lactate dehydrogenase (LDH) was measured as a marker of the lysis of chamber leucocytes. Lysis was less than 1.5% at all incubation times. The present study shows a release of elastase from primary granules and of lysozyme when polymorphonuclear leucocytes migrate into a skin chamber.

Adult↗

Long-term effects on bacterial sensitivity patterns of preoperative antibiotic prophylaxis in colorectal surgery.

Since 1973, when doxycycline was introduced as peroperative prophylaxis in elective colorectal surgery at Malmö General Hospital, Sweden, there has been an unchanged and low rate (8-12%) of septic complications in colonic surgery. For treating postoperative infections ampicillin, cefuroxime and piperacillin have been used since 1973, 1980 and 1982 respectively. The sensitivity pattern of E. coli and Klebsiella against these four antibiotics used for prophylaxis and treatment has been followed for the past five years and only minor changes have occurred through the period. However, a lower frequency of antibiotic resistance was recorded for bacteria isolated peroperatively than postoperatively after colorectal surgery or from infection sites from other patients presumably mostly due to selection caused by antibiotics used within the hospital. Due to the good clinical outcome and seemingly lack of development of antibiotic resistance in peroperative isolates, doxycycline still remains a choice for prophylaxis in bowel surgery.

Adolescent↗

Inhibition of in vivo leucocyte migration by NSAIDs.

Leucocyte migration was studied in vivo using a skin window technique, and in vitro by migration under agarose. No difference was found between 28 patients with rheumatoid arthritis (RA), 10 patients with psoriatic arthritis (PA) and 30 healthy controls. Most patients were under treatment with anti-rheumatic drugs. Patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) had significantly lower values (p less than 0.01) than untreated patients. In vivo but not in vitro migration decreased during short-term treatment with diclofenac and naproxen, an effect observed both in patients and in healthy individuals. After pre-incubation of normal polymorphonuclear leucocytes with diclofenac, in vitro migration was diminished only at concentrations of 50 micrograms/ml and above, which are at least 10 times higher than those attained clinically. The in vivo effect of NSAIDs on leucocyte migration may imply a long-term disease modifying influence in chronic arthritides.

Adult↗