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Biomedical subjects

C Edlund

Publications and source records attributed to C Edlund.

At least 55 records · Page 3Linked to original sources

Effect of vancomycin on intestinal flora of patients who previously received antimicrobial therapy.

To evaluate the ecological disturbances of peroral vancomycin administration following cephalosporin administration, 20 healthy volunteers received cefuroxime axetil tablets (250 mg) perorally twice a day for 1 week, and 10 of these volunteers subsequently received vancomycin capsules (125 mg) perorally four times daily for 7 days. The concentration of vancomycin in feces after 1 week of vancomycin administration was high (mean +/- SD, 520 +/- 197 mg/kg), which correlated with the ecological disturbances noted in the vancomycin recipients. Vancomycin administration resulted in a rapid decrease in the numbers of intestinal Enterococcus faecium, Enterococcus faecalis, and Enterococcus durans (P < or = .05), while there was a significant emergence of motile enterococci with decreased susceptibility to vancomycin (Enterococcus gallinarum and Enterococcus casseliflavus; minimum inhibitory concentration, 4-16 mg/L) (P < or = .01). Because of vancomycin administration, there was also a significant overgrowth of vancomycin-resistant Pediococcus species and lactobacilli as well as of Klebsiella species, Citrobacter species, and Enterobacter species (P < or = .01). The numbers of bifidobacteria and Bacteroides species were significantly reduced during vancomycin administration. None of the enterococcal strains carried vanA or vanB. Twenty-two of the 27 motile enterococci carried the vanC-1 gene specific for E. gallinarum, whereas five strains carried the vanC-2(C-3) gene, thus implicating that they were E. casseliflavus or Enterococcus flavescens.

Administration, Oral↗

An effective methodology for surveying a Medicaid population: the 1996 Oregon Health Plan client satisfaction survey.

There are many barriers to measuring client satisfaction for a Medicaid population. This vulnerable group is poor, often undereducated, and highly mobile, making both telephone surveys and mail-return surveys difficult to administer successfully. The Oregon Health Plan (OHP), a Medicaid managed care delivery system, has developed a client satisfaction survey and approach that yielded a 63% response rate. Readability, satisfaction indicators reflective of a Medicaid population, and survey administration are all identified as essential to an adequate response rate. The data from the 1996 Oregon Health Plan Client Satisfaction Survey are being used in the OHP's analysis and evaluation program and its ongoing quality improvement process.

Chronic Disease↗

Comparative effects of levofloxacin and ofloxacin on the normal oral and intestinal microflora.

The aim of the study was to study the ecological effects of levofloxacin, compared to that of ofloxacin, on the oral and intestinal human microflora. 10 healthy volunteers received levofloxacin (500 mg) and 10 subjects were given ofloxacin (400 mg) perorally, once daily for 7 days. Saliva and stool samples were obtained prior to drug administration, during administration (days 2, 4 and 7), and after withdrawal of the agents (days 9, 11, 14 and 21). The concentrations of levofloxacin and ofloxacin in the saliva and faecal samples, respectively, were assayed, and quantitative and qualitative microbiological analyses were performed. Oral administration of levofloxacin and ofloxacin led to low drug concentrations in the saliva, which corresponded with mild disturbances in the oral microflora. High drug levels were obtained in the intestinal tract, and both agents caused a selective reduction in the normal microflora, mainly directed towards aerobic Gram-negative bacteria. There was no significant difference between levofloxacin and ofloxacin, regarding ecological effects on the normal oral and intestinal microflora. From an ecological point of view, these agents acted favourably, since no major selection of resistant strains occurred in the normal microflora during administration.

Administration, Oral↗

Resistance of the normal human microflora to mercury and antimicrobials after exposure to mercury from dental amalgam fillings.

The concentrations of mercury in saliva and feces and the resistance pattern of the gastrointestinal microflora were investigated for 20 subjects. Ten patients, with a mean number of 19 amalgam surfaces, had all amalgam fillings removed during one dental session. Ten subjects without amalgam fillings served as a control group. Saliva and fecal samples were collected before amalgam removal and 2, 7, 14, and 60 days afterward. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. No differences in the resistance pattern of the oral microflora were detected between the two groups. In the amalgam group there was an increase in the relative number of intestinal microorganisms resistant to mercury, ampicillin, cefoxitin, erythromycin, and clindamycin on days 7-14. This was not statistically significant in light of the normal variations of the control group. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed.

Adolescent↗

Effects of omeprazole and amoxycillin on the human oral and gastrointestinal microflora in patients with Helicobacter pylori infection.

Fourteen patients with Helicobacter pylori infection were treated with omeprazole capsules 20 mg and amoxycillin capsules 1000 mg twice daily for 14 days and 14 patients with omeprazole capsules 20 mg and placebo twice daily for 14 days. Samples from saliva, dental plaque and faeces and biopsies from antrum and corpus were analysed in order to determine the ecological changes in the normal microflora. Several microorganisms were affected by both treatment regimens. Two patients were colonised with enterobacteria in the oral cavity and stomach during the omeprazole plus amoxycillin treatment. A general increase in the number of microorganisms from gastric mucosa was observed in both treatment groups. A selection of resistant enterobacteria and an increase in beta-lactamase production was observed in the faecal samples during the omeprazole plus amoxycillin treatment. Eradication of H. pylori in the omeprazole-amoxycillin group was 50% and in the omeprazole placebo group 0% four weeks after treatment. No viable H. pylori were cultivated in the saliva, dental plaque or faecal samples. Treatment with omeprazole 20 mg and amoxycillin 1000 mg twice daily for 14 days altered the normal microflora in the oral, gastric and intestinal tract and antibiotic resistant microorganisms increased in numbers in the intestinal microflora.

Adult↗

Antimicrobial treatment of periodontal diseases disturbs the human ecology: a review.

Periodontal diseases are associated with specific pathogenic microorganisms and therefore antimicrobial agents are often used in the treatment of patients with periodontitis refractory to conventional mechanical therapy. Perorally administered antimicrobial agents often lead to ecological disturbances in the normal oral and intestinal microflora with overgrowth of potentially pathogenic microorganisms, which may spread within the host or from patient to patient, causing infections. The use of antimicrobial agents also promotes the emergence of bacterial drug resistance, both in the periodontal pocket and in the normal oral and intestinal microflora. Topical administration of antimicrobial agents in the periodontal pockets causes restricted disturbances in the intestinal microflora, although there is a substantial risk of development of resistance at the site of application. A number of clinical studies imply that correct use of antimicrobial agents might be beneficial for a subset of patients with adult or juvenile periodontitis. The choice of antimicrobial agent should always be based on accurate microbial analyses of the subgingival microflora and in vitro antimicrobial susceptibility tests of the most important periodontal pathogens. Preferably, agents with low potential of causing ecological disturbances should be used.

Anti-Bacterial Agents↗

Age-dependent modifications in the metabolism of mevalonate pathway lipids in rat brain.

The levels and rates of biosynthesis of mevalonate pathway lipids in rat brain were investigated during development and aging. Between birth and 18 months of age there are only moderate decreases in the phospholipid and cholesterol contents but an increase in the levels of dolichyl-P and, particularly of dolichol. The amount of ubiquinone is unchanged. The rate of incorporation of [3H]leucine into protein decreases by 10% during the first year, while the incorporation of [3H]glycerol into phospholipids decreases by 20%. The high rates of [3H]mevalonate incorporation into cholesterol and dolichol after birth decreases rapidly. In contrast, the rate of incorporation into ubiquinone is constant. Squalene synthase activity decreases rapidly in the early postnatal period and at 18 months of age this activity is 10-fold lower than immediately after birth. cis-Prenyltransferase activity is also high during the first postnatal month and reaches a constant level at 4 months of age. Significantly, nonaprenyl 4-hydroxybenzoate transferase activity is high during the entire period investigated. The rate of lipid peroxidation does not change during aging. These results demonstrate that brain cholesterol and dolichol exhibit a low rate of turnover during aging, whereas ubiquinone is synthesized at a high rate and exhibits rapid turnover throughout the entire lifespan.

Aging↗

Induction of beta-lactamase by cefoxitin in anaerobic intestinal microflora.

Beta-lactamases produced by two anaerobic bacterial strains, Bacteroides ovatus Ax34:1 and Clostridium butyricum NBL3, were shown to be significantly inducible under anaerobic conditions in subinhibitory concentrations of cefoxitin. The induction ratio of beta-lactamase production for Bacteroides ovatus was 2.6 and for Clostridium butyricum 1.6. Incubation of faecal samples with different concentrations of cefoxitin did not result in any induction of beta-lactamase production. When adding a highly inducible aerobic strain (Citrobacter freundii F72:6, induction ratio of 26.5 in broth culture) to faecal samples, an induction ratio of 4.5 was reached. Faeces seem to inhibit beta-lactamase induction in aerobic and anaerobic bacteria. The inducible enzymes produced by the anaerobic strains did not have the same properties as beta-lactamases from aerobic inducible strains, according to substrate profiles and inhibition studies. The results of the present study indicate that increased levels of beta-lactamases in the normal intestinal microflora, which often are observed after administration of beta-lactam agents, are probably due to selection of stably derepressed mutants rather than to induction of beta-lactamase production.

Anti-Bacterial Agents↗

Bioavailability and bacterial degradation of rectally administered 2-chloro-2'-deoxyadenosine.

2-Chloro-2'-deoxyadenosine (CdA) is a new drug for the treatment of hairy cell leukemia and other lymphoproliferative diseases. It is generally administered as a continuous intravenous infusion during 5-7 days. The oral bioavailability is only 50%. The bioavailability after rectal administration was investigated in two patients with chronic lymphocytic leukemia. Five milligrams per square metre was given i.v. as a 2-h infusion and 24 h later the same dose was administered rectally in a gel formulation. The mean bioavailability was only 21% due to deglycosylation of CdA to 2-chloroadenine (CAde). To further elucidate the factors which are important for the rectal availability of CdA, the in vitro stability of CdA in bacterial cultures was tested. Clostridium perfringens and Escherichia coli as well as whole feces rapidly deglycosylated CdA to CAde while Bacteroides fragilis, Enterococcus faecalis as well as saliva only degraded CdA slowly or not at all. It is concluded that, due to bacterial degradation, rectal administration of CdA has no advantage over oral administration.

Administration, Rectal↗

Interferon-gamma and a factor derived from trypanosomes cause behavioural changes in the rat.

A newly isolated interferon-gamma (IFN-gamma) immunoreactive molecule, "neuronal IFN-gamma", and recombinant lymphocyte-derived IFN-gamma were injected intracerebroventricularly (i.c.v.) through a previously implanted cannula into adult male rats during both the light and the dark phases of the light/dark cycle. The two molecules caused a reduction in both frequency and duration of rearing and locomotion during the dark, but not the light, phase. A molecule isolated from Trypanosoma brucei brucei, a parasite of the same subspecies of trypanosomes which causes African sleeping sickness, can induce production and release of IFN-gamma and "neuronal IFN-gamma" from lymphocytes and neurons, respectively. I.c.v. injection of this factor also reduced rearing during the dark period, but to a less extent. Thus, "neuronal IFN-gamma" appears to have effects on animal behaviour in common with lymphocyte-derived IFN-gamma. This study highlights the potential role of these cytokines in behaviour disturbances.

Animals↗

Trypanosomes cause dysregulation of c-fos expression in the rat suprachiasmatic nucleus.

Rats infected with the parasite Trypanosoma brucei brucei showed selective changes of c-fos expression in the suprachiasmatic nucleus of the hypothalamus (SCN) during spontaneous sleep (S) and wakefulness (W) under a basal 12 h/12 h light-dark (L-D) cycle. In the vast majority of W (D phase) control animals the SCN was devoid of cells displaying Fos-related immunopositivity, while Fos-like-immunoreactive (ir) neurones were detected in most S (L phase) control rats. In most infected animals, on the other hand, Fos-ir neurones were detected in the SCN during W, but not during the S period, with a significant difference between control and infected S rats. Thus, these data indicate that the basal c-fos expression in the SCN during the L-D and S-W cycles is considerably altered in experimental trypanosomiasis. This is the first observation of a selective change in the SCN in trypanosome-infected rat brains. Since the SCN plays an important role as a pace-maker for biological rhythms, this finding may provide a basis for understanding the pathogenesis behind endogenous rhythm dyregulation and changes in sleeping pattern in human trypanosomiasis (African sleeping sickness).

Animals↗

Neuronal interferon-gamma immunoreactive molecule: bioactivities and purification.

An interferon (IFN)-gamma immunoreactive molecule, localized to small neurons in peripheral sensory ganglia (N-IFN-gamma), has been detected with two mouse monoclonal antibodies (DB1 and DB16) directed against different epitopes of rat IFN-gamma. To define N-IFN-gamma with regard to its protein characteristics and bioactivities, DB1 and DB16 were used to purify N-IFN-gamma from rat trigeminal ganglia in a two-step sequential antibody-affinity procedure. Sodium dodecylsulfate polyacrylamide gel electrophoresis (PAGE) and silver staining of purified N-IFN-gamma displayed three bands with an approximate molecular mass of 66, 62 and 54 kDa. The N-IFN-gamma bioactivity was confined to the protein stained on gel when native material was run on PAGE. Biological effects of pure N-IFN-gamma were examined and compared with those of lymphocyte-derived recombinant IFN-gamma. N-IFN-gamma had antiviral effects in vitro and induced major histocompatibility complex class I and II antigens on macrophages and in cells in skeletal muscle cell cultures. N-IFN-gamma also stimulated myoblast proliferation and affected cholinergic receptor distribution on myotubes similar to recombinant IFN-gamma. Both molecules potently stimulated Trypanosoma brucei brucei growth. These data suggest that, although N-IFN-gamma is a protein distinct from lymphocyte-derived IFN-gamma, the two molecules have enough structural similarities to allow for antibody recognition of at least two epitopes, and action on similar target structures on both parasite and mammalian cells.

Animals↗

Isoprenoids in aging and neurodegeneration.

During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In a neurodegenerative disease, Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. This study shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation.

Adult↗

Content and fatty acid composition of cardiolipin in the brain of patients with Alzheimer's disease.

The frontal, temporal and occipital cortex from human brains affected by Alzheimer's disease were analyzed for their contents and fatty acid compositions of cardiolipin. Phospholipids were purified using an HPLC system and cardiolipin was found to be present in the same amount (on a protein basis) as in age-matched controls. One-third of the total fatty acyl moieties of this phospholipid were saturated, one-third monounsaturated and one-third polyunsaturated. In affected brain regions the levels of certain polyunsaturated fatty acids displayed moderate decreases, not exceeding 10-15%. However, the total amount of polyunsaturated fatty acids decreased by only 9%. These results demonstrate that the amount and structure of brain cardiolipin are not modified to any great extent in connection with Alzheimer's disease.

Aged↗

Ubiquinone-10 protects neurons from virus-induced degeneration.

Cultured neurons from rat dorsal root ganglia and cerebral cortex were infected with Sendai virus, which gives a productive replication with lysis of most neurons, and with the RW strain of mumps virus, which undergoes defective replication causing degeneration of only 30-40% of the neurons within 5 days after initial infection. In Sendai virus-infected cells the amount of polyisoprenoid lipids was enhanced. In mumps virus-infected cultures there were transient reductions in the contents of cholesterol, dolichol, and ubiquinone-9 in the cultures, whereas the reduction in the ubiquinone-10 level was progressive, reaching 20% of its original value 21 days after infection. Treatment of mumps virus-infected cultures with ubiquinone-10 protected the neurons from degeneration, whereas no effects were observed on exposure to ubiquinone-9. Linolenic acid (18:3) and arachidonic acid (20:4), but not myristic acid (14:0) and palmitic acid (16:0), also had significant neuroprotective effects.

Animals↗

The relationship between an increase in beta-lactamase activity after oral administration of three new cephalosporins and protection against intestinal ecological disturbances.

Forty-four healthy volunteers were given either amoxycillin (ten subjects), cefpodoxime proxetil (ten subjects), ceftibuten (14 subjects) or cefuroxime axetil (ten subjects) orally for 7-10 days, in order to study the ecological effects on the intestinal microflora. In all three groups receiving oral cephalosporins there was a significant increase in beta-lactamase activity during administration (P < 0.05). There was also an inverse correlation between enzyme activity in faeces during administration compared with the concentration of drug in the intestines and the level of ecological disturbance in the normal intestinal microflora. In volunteers given amoxycillin, only small alterations in the faecal microflora were observed although overgrowth by new amoxycillin resistant enterobacteria occurred in all volunteers. There was an overgrowth of enterococci and yeasts during treatment with cefpodoxime proxetil, ceftibuten or cefuroxime axetil, whereas the numbers of enterobacteria were reduced. Colonization with resistant enterobacteria did not occur, but 14 of 34 subjects receiving oral cephalosporins were colonized by Clostridium difficile. Side-effects were mild and not associated with the ecological alterations in the intestinal microflora.

Administration, Oral↗

CD8 is critically involved in lymphocyte activation by a T. brucei brucei-released molecule.

T. brucei brucei released a lymphocyte triggering factor (TLTF), which triggered purified CD8+, but not CD4+, T cells to interferon gamma (IFN-gamma) mRNA expression and secretion and to [3H]thymidine incorporation. TLTF also induced mRNA for transforming growth factor beta, but not for interleukin-4. The action of this TLTF on mononuclear cell (MNC) cultures was blocked by anti-CD8 antibodies and by soluble CD8. MNCs from a mutant mouse strain lacking CD8 expression were not triggered by TLTF. IFN-gamma provides a growth stimulus for T. brucei brucei, and infected CD8- mice had much lower parasitemia and survived longer than CD8+ mice. The host-parasite interaction in experimental African trypanosomiasis thus involves parasite release of TLTF, which by binding to CD8 triggers CD8+ cells to produce the parasite growth-promoting cytokine IFN-gamma.

Animals↗