Biomedical subjects

C Edlund

Publications and source records attributed to C Edlund.

At least 73 records · Page 4Linked to original sources

PubMed1993

Effects of inhibitors of hydroxymethylglutaryl coenzyme A reductase on coenzyme Q and dolichol biosynthesis.

Inhibitors of hydroxymethylglutaryl coenzyme A reductase are used clinically to decrease blood levels of low-density lipoprotein cholesterol in hypercholesterolemic patients. However, little is known about the possible effects of these inhibitors on dolichol and cholesterol synthesis. Oral administration of mevinolin to rats was found here to decrease dolichol, dolichyl-P and coenzyme Q levels in the heart and skeletal muscle and to increase the hepatic dolichol level while decreasing the coenzyme Q content in this same organ. The amounts of dolichyl-P decreased in heart and muscle and increased in brain. Intraperitoneal administration also affected the levels of these lipids. The concentrations of blood lipids were not modified in the same manner as tissue lipids. Analysis of individual enzyme activities and of incorporation of [3H]acetate into various lipids of liver and brain slices demonstrated that both up- and down-regulation of different proteins occur in various tissues, resulting in modifications in lipid synthesis. Hypercholesterolemic patients were found to have high blood coenzyme Q levels, which are decreased upon pravastatin treatment, although they are still above control values. It appears that these HMG-coenzyme A reductase inhibitors do not selectively lower cholesterol levels, but that they also modify the dolichol and coenzyme Q content and synthesis both in the liver and various other tissues.

Animals↗

PubMed1993

Impact of cefpodoxime proxetil and amoxicillin on the normal oral and intestinal microflora.

Ten healthy volunteers were given 200 mg cefpodoxime proxetil tablets every 12 h and ten volunteers received 500 mg amoxicillin tablets every 8 h for seven days and the impact of the agents on the oral and intestinal microflora was studied. In the oral microflora, only minor alterations were observed in both groups. In subjects receiving cefpodoxime proxetil, the numbers of streptococci, enterobacteria and clostridia were strongly reduced in the faecal flora, while there was an overgrowth of enterococci, yeasts and Clostridium difficile. Amoxicillin administration induced somewhat smaller alterations in the faecal microflora, although all subjects had overgrowth of new colonizing amoxicillin resistant microorganisms, mainly Escherichia coli, Klebsiella and Enterobacter. Beta-lactamase activity was detected in the flora of six volunteers from each group.

Adult↗

PubMed1993

A Trypanosoma brucei brucei-derived factor that triggers CD8+ lymphocytes to interferon-gamma secretion: purification, characterization and protective effects in vivo by treatment with a monoclonal antibody against the factor.

A protein factor that stimulates CD8+ lymphocytes to produce and secrete IFN-gamma has been purified from Trypanosoma brucei brucei (T.b. brucei). This was accomplished by raising monoclonal antibodies (MoAbs) against a fraction of T.b. brucei obtained by gel filtration, which contained high levels of material inducing rat mononuclear cells (MNC) to IFN-gamma production. MoAbs from four hybridomas strongly inhibited trypanosome-induced IFN-gamma production. One of them (MO1) was used for purification of the trypanosome-derived lymphocyte triggering factor (TLTF) by affinity chromatography. SDS electrophoresis of the purified TLTF displayed a band of 42-45 kDa MW. Gel filtration of homogenates of whole parasites yielded several peaks of IFN-gamma-inducing activity with a lowest MW of 41-46 kDa. Bioactivity of all peaks was blocked by MO1, suggesting that a single molecule, or a single epitope of additional molecules, is responsible for the different peaks with IFN-gamma-inducing activity. IFN-gamma released from MNC stimulates T.b. brucei growth. Blocking of TLTF in vitro with MO1 inhibited MNC-supported growth of the parasites. To study the in vivo relevance of TLTF in the course of experimental African trypanosomiasis, MO1 was used to treat rats and mice at different times after infection. Treatments instituted at different time-points after infection suppressed parasite growth, abrogated the IFN-gamma production by splenocytes induced by the infection and prolonged survival of the animals. The data support the hypothesis that TLTF and IFN-gamma have a crucial regulatory function in the parasite-host interactions and that these molecules influence the disease course during experimental African trypanosomiasis.

Animals↗

PubMed1993

Antimicrobial resistance in human oral and intestinal anaerobic microfloras.

In the present study we determined the resistance patterns of anaerobic bacteria from human saliva and stool specimens and investigated whether there were significant differences in resistance between outpatients and hospitalized patients, regardless of whether they had received antimicrobial agents. No bacterial strains resistant to ampicillin, piperacillin, cefoxitin, cefuroxime, imipenem, clindamycin, doxycycline, chloramphenicol, or metronidazole were isolated from the saliva samples. However, resistance to ampicillin, cefoxitin, and cefuroxime was found in strains from 70% of the fecal samples (mainly Bacteroides thetaiotaomicron, Clostridium innocuum, and Bacteroides ovatus). Resistance to both ampicillin and cefuroxime was frequently found in 19% of the isolated strains (mainly B. thetaiotaomicron, B. ovatus, and Bacteroides vulgatus). No strains that were resistant to imipenem, chloramphenicol, or metronidazole were found. Hospitalization and/or intake of antimicrobial agents was associated with an increase in the relative number of resistant anaerobic intestinal bacteria. The percentage of resistant anaerobic strains encountered, compared with the total number of anaerobic bacteria in the normal fecal microflora, was between 5.2 and 14.8%, with the lower value associated with the outpatient group. Two-thirds of the resistant strains from this group had a relative frequency of less than 1% of the total anaerobic flora, while one-third of the strains were present at a level of greater than 1%; for the hospitalized patients, two-thirds of the strains were present at a level of greater than 1%, and one-third of the strains were present at a level of less than 1% (P < 0.001). Patients who had received antimicrobial agents for 6 days or more (n=20) had an average of 1.6 resistant anaerobic strains each, while patients treated for 3 to 5 days (n = 30) had a mean number of 0.87 resistant strains each ( P < 0.05).

Adult↗

PubMed1992

Effects of mevinolin treatment on tissue dolichol and ubiquinone levels in the rat.

Rats were treated with mevinolin by intraperitoneal injection (15 days) or dietary administration (30 days). The cholesterol, dolichol, dolichyl phosphate and ubiquinone contents of the liver, brain, heart, muscle and blood were then investigated. The cholesterol contents of these organs did not change significantly, with the exception of muscle. Intraperitoneal administration of the drug increases the amount of dolichol in liver, muscle and blood and decreases the dolichyl-P amount in muscle. The same treatment increases the level of ubiquinone in muscle and blood and decreases this value in liver and heart. Oral administration decreases dolichol, dolichyl-P and ubiquinone levels in heart and muscle, while in liver the dolichol level is elevated and ubiquinone level lowered. In brain the amount of dolichyl-P is increased. Intraperitoneal injection of mevinolin also modifies the liver dolichol and dolichyl-P isoprenoid pattern, with an increase in shorter chain polyisoprenes. The levels of dolichol and ubiquinone in the blood do not follow the changes observed in other tissues. Incorporation of [3H]acetate into cholesterol by liver slices prepared from mevinolin-treated rats exhibited an increase, whereas in brain no change was seen. Labeling of dolichol and ubiquinone was increased in both liver and brain, but incorporation into dolichyl phosphate remained relatively stable. The results indicate that mevinolin affects not only HMG-CoA reductase but, to some extent, also affects certain of the peripheral enzymes, resulting in considerable effects on the various mevalonate pathway lipids.

Acetates↗

PubMed1992

Nonmembrane associated dolichol in rat liver.

The distribution of dolichol in rat liver was studied. Upon high-speed centrifugation, 9% of the total tissue dolichol was recovered in the supernatant. Dolichol was enclosed in vesicles and in lipidic particles which were isolated by gel filtration and density gradient centrifugation. The particles had a diameter of 20 nm and contained dolichol, ubiquinone, cholesterol, phospholipid and some protein. Similar particles were recovered upon incubation of isolated hepatocytes with liposomes containing dolichol. From the lysosomal lumen, lipid particles containing dolichol, ubiquinone, cholesterol and phospholipid, but no protein, were isolated. The diameter of the particles was 20-40 nm with a molecular weight of 130 kDa. Puromycin treatment inhibited protein synthesis, but did not affect dolichol transfer from the endoplasmic reticulum to lysosomes, suggesting that the transfer is not mediated by newly synthesized apoprotein. The results indicate that a sizeable portion of the total cellular dolichol is present in cytoplasm and in lysosomal lumen. Furthermore, dolichol probably participates in the translocation process.

Animals↗

PubMed1992

Purification and characterization of an imipenem hydrolysing metallo-beta-lactamase from Bacteroides fragilis.

An imipenem resistant beta-lactamase producing strain of Bacteroides fragilis was isolated from a clinical specimen. The specific activity of the unpurified beta-lactamase was 5.5 U/mg protein. The beta-lactamase was purified 60-fold by Q Sepharose, Sephacryl S-300 and Mono Q column passages. The strain was able to inactivate imipenem and cefoxitin in broth cultures. The enzyme hydrolysed imipenem more rapidly than ampicillin, benzylpenicillin, cephalothin and cefoxitin. The activity of the enzyme was Zn2+ dependent and was completely inhibited by EDTA. The inhibition was reversed by ZnSO4. Preincubation with the common beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam did not reduce the enzyme activity. The molecular weight was determined by sodium dodecyl sulfate gradient gel electrophoresis to be 31,000 Daltons and the isoelectric point was 4.5.

Bacteroides fragilis↗

PubMed1992

Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type.

The lipid compositions of 10 different brain regions from patients affected by Alzheimer's disease/senile dementia of Alzheimer's type were analyzed. The total phospholipid amount decreased somewhat in nucleus caudatus and in white matter. The cortical areas that are morphologically affected by Alzheimer's disease, i.e., frontal and temporal cortex and the hippocampus, showed elevated contents of lipid solvent-extractable phosphatidylinositol. Sphingomyelin content was decreased in regions rich in myelin. There was a 20-50% decrease in dolichol amount in all investigated parts of the brain, but no change was seen in the polyisoprenoid pattern. Levels of alpha-unsaturated polyprenes were decreased in Alzheimer brains. Dolichyl-phosphate content increased in most regions, up to 100%. In both control and Alzheimer tissue almost all of the dolichyl-phosphate was covalently bound, apparently through glycosylation. Cholesterol amounts were highly variable but mostly unchanged, whereas ubiquinone concentrations increased by 30-100% in most regions in brains affected by Alzheimer's disease. These results demonstrate that both phospholipids and neutral lipids are modified in brains affected by Alzheimer's disease/senile dementia of Alzheimer's type.

Aged↗

PubMed1992

Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease.

The lipid compositions of various regions of the human brain were investigated during aging and in Alzheimer's disease. The phospholipid amounts and compositions remained unchanged during aging. There were, however, considerable differences both in phospholipid composition and amount when the various regions were compared. The level of dolichol increased severalfold in all regions up to the age of 70, but there was no further elevation thereafter. The ubiquinone level decreased significantly in all parts of the brain upon aging. In Alzheimer's disease, the dolichol level was decreased in all regions, and particularly, in those affected by the disease. In contrast, the dolichyl-P concentration increased in those regions that exhibited morphological changes. There was no modification in cholesterol distribution, but a significant elevation in ubiquinone content was observed in most regions. The only phospholipid whose level was elevated was phosphatidylinositol, and only in those parts of the brain that were affected. The content of polyunsaturated fatty acids in phosphatidylethanolamine was greatly decreased in connection with the disease, with a parallel increase in the saturated portion. The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain.

Aged↗

PubMed1992

Efficacy of tosufloxacin in the treatment of experimentally induced intra-abdominal infections in rats.

A reproducible experimental model of intra-abdominal infections in rats has been devised in order to simulate intra-abdominal sepsis in patients. Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was reestablished by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of tosufloxacin alone and in combination with metronidazole, with the combination gentamicin and metronidazole in the treatment of intra-abdominal infections. Eighty per cent of the untreated animals died within three days. Within three days 20% of the animals receiving tosufloxacin died. Animals treated with tosufloxacin plus metronidazole or gentamicin plus metronidazole had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination of tosufloxacin and metronidazole seems to be as successful as gentamicin plus metronidazole in the treatment of intra-abdominal infections.

4-Quinolones↗

PubMed1991

Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth.

The hemoflagellate Trypanosoma brucei (T.b.) is the cause of African sleeping sickness. T. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (MNC). Co-cultivation in vitro of rat or human MNC and T.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (IFN-gamma) which was dependent on CD8+ lymphoid cells. The parasites triggered MNC proliferation if IFN-gamma was blocked by a specific antibody in vitro. Separate cultures of parasites and MNC in a two-chamber system allowing exchange of soluble mediators showed CD8+ cell-dependent MNC triggering, indicating that a diffusable factor released by trypanosomes acts on the MNC. Gel filtration according to molecular mass of disrupted parasites and assay of the fractions revealed a peak activity at an approximate molecular mass of 185 kDa for the trypanosome-derived lymphocyte-triggering factor (TLTF). Conversely, there was a CD8+ cell-dependent action of MNC on the trypanosomes. MNC released a diffusable factor that in short-term experiments caused a striking increase in number of parasites. This effect was inhibited by antibodies against rat IFN-gamma. The increase in number of trypanosomes was promoted by rat MNC or rat IFN-gamma but not human MNC or human IFN-gamma suggesting a species-restricted recognition of IFN-gamma. An in vivo uptake of IFN-gamma by the parasites was suggested by immunohistochemical staining of T.b. brucei with an mAb against rat IFN-gamma and Western blot of the parasites showing a band with a molecular mass corresponding to IFN-gamma. The bidirectional signals we define here may explain certain features of trypanosomiasis, i.e. T cell activation, immunosuppression and host-range restriction. The seemingly important role of the TLTF indicates that it should be purified and explored as target for immune-specific intervention.

Animals↗

PubMed1991

Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease.

The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain, i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18:1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer's disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18:1, is not significantly altered in Alzheimer's disease, but there is a substantial increase in the relative amounts of the saturated components 14:0, 16:0 and 18:0. This is paralleled by a decrease in the polyunsaturated FA 20:4, 22:4 and 22:6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process.

Adult↗

PubMed1991

Comparative effects of clarithromycin and erythromycin on the normal intestinal microflora.

10 healthy volunteers received 250 mg of clarithromycin orally q 12 h for 7 days and 10 other volunteers 1000 mg of erythromycin ethylsuccinate orally q 12 h for 7 days. Stool specimens were collected before, during and after antibiotic administration. In the clarithromycin group, the numbers of streptococci and enterobacteria decreased among aerobic microorganisms while in the erythromycin group streptococci, enterococci and enterobacteria decreased and staphylococci increased during antibiotic administration. The anaerobic intestinal microflora was also affected. The alterations were more pronounced in the volunteers receiving erythromycin than in those having clarithromycin.

Administration, Oral↗

PubMed1991

A model of bacterial-antimicrobial interactions: the case of oropharyngeal and gastrointestinal microflora.

The normal human oropharyngeal and gastrointestinal microflora is a complex ecosystem in a symbiotic relationship with the host. The microflora helps to prevent invasion of pathogens and participates in several metabolic processes. On the other hand, under certain conditions members of the normal microflora can cause serious infections. Administration of antimicrobial agents may cause severe alterations in the normal microflora. Suppression of the anaerobic flora has been associated with decreased colonization resistance, i.e. the resistance of the normal host to the implantation of exogenous microorganisms.

Bacteria, Anaerobic↗

PubMed1990

Rates of cholesterol, ubiquinone, dolichol and dolichyl-P biosynthesis in rat brain slices.

Slices from the brain and liver of rats were prepared and upon incubation exhibited a continuous and high capacity for incorporation of radioactive precursors into proteins and lipids. Using [3H]mevalonate as precursor, the rates of biosynthesis of cholesterol, ubiquinone, dolichol and dolichyl-P in brain slices were determined and found to be 5.5, 0.25, 0.0093 and 0.0091 nmol/h/g, respectively. Dolichol and dolichyl-P accumulate to a limited extent, but almost all of these lipids in the brain originate from de novo synthesis. The calculated half-lives for cholesterol, ubiquinone, dolichol and dolichyl-P were 4076, 90, 1006 and 171 h, respectively. The results indicate that lipids formed via the mevalonate pathway in the brain have an active and independently regulated biosynthesis.

Animals↗

PubMed1990

Effect of lomefloxacin on the normal oral and intestinal microflora.

Ten healthy volunteers received 400 mg of lomefloxacin orally once daily for seven days. Saliva and faecal samples were collected on days 0, 2, 4, 7, 9, 11, 14 and 21 to investigate the effect of lomefloxacin on the normal oral and intestinal microflora. The mean concentration of lomefloxacin in faeces on day 7 was 203 mg/kg, while saliva levels were low, less than 0.6 mg/l in nine of ten volunteers. Aerobic gram-negative microorganisms were almost completely eradicated, while aerobic gram-positive and anaerobic microorganisms were virtually unaffected by the lomefloxacin administration. Two weeks after lomefloxacin was discontinued, the oral and intestinal microflora had returned to normal levels.

4-Quinolones↗

PubMed1990

Impact of antimicrobial agents on human intestinal microflora.

The most common and significant cause of disturbances in the normal intestinal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent in the bile, or secretion from the intestinal mucosa. In most cases, the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, stomatitis, diarrhea, or colitis. Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains. During the last fifteen years, the impact of different antimicrobial agents on the human microflora has been studied by several investigators. In this article published data on the impact of beta-lactam antibiotics, macrolides, tetracyclines, nitroimidazoles, clindamycin and quinolones on the human intestinal microflora are reviewed.

4-Quinolones↗

PubMed1990

Lipid compositions of different regions of the human brain during aging.

The neutral and phospholipid compositions of various regions of the human brain were analyzed using autopsy material covering the life period between 33 and 92 years of age. The protein content was also measured and, on a weight basis, this content is unchanged in the cerebellum, pons, and medulla oblongata, whereas in the 90-year-old group it decreases in the hippocampus, gray matter, and nucleus caudatus. In white matter, the protein content decreases continuously with age. The phospholipid composition is characteristic of the region investigated, but remains unchanged during aging. The total phospholipid content exhibits only a 5-10% decrease in the oldest age group. The content of dolichol and its polyisoprenoid pattern are also characteristic of the region analyzed. Between 33 and 92 years of age, the amount of dolichol in all portions of the brain increases three- to fourfold, but the isoprenoid pattern remains constant. The level of dolichyl-P varies between different regions, but only a moderate increase is seen with age. Ubiquinone content is highest in the nucleus caudatus, gray matter, and hippocampus, and in all areas this content is decreased to a great extent in the oldest age groups. All regions of the human brain are rich in cholesterol, but alterations in the amount of this lipid are highly variable during aging, ranging from no change to a 40% decrease.

Adult↗