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Biomedical subjects

I Gustafsson

Publications and source records attributed to I Gustafsson.

At least 19 recordsLinked to original sources
PubMed2007

Increased plasma levels of asymmetric dimethylarginine in patients with carotid stenosis: no evidence for the role of the common FABP2 A54T gene polymorphism.

OBJECTIVE: Both asymmetric dimethylarginine (ADMA), which is an inhibitor of endothelial nitric oxide synthase and the fatty acid-binding protein 2 (FABP2) A54T gene polymorphism have been associated with cerebrovascular disease. The objective of the present study was to investigate the role of ADMA and the FABP2 A54T polymorphism in carotid atherosclerosis. MATERIAL AND METHODS: 54 patients with severe carotid stenosis and 54 matched controls without significant carotid stenosis were compared. ADMA was analysed with an ELISA method. The FABP2 A54T polymorphism was determined with a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Patients with carotid stenosis had higher ADMA levels (0.76 +/- 0.16 micromol/l) than the controls (0.70 +/- 0.14 micromol/l, P < 0,01). Allele and genotype frequencies of the FABP2 polymorphism did not differ between patients and controls. CONCLUSIONS: ADMA levels in subjects with carotid stenosis are increased which emphasize the role of ADMA as a novel risk factor for atherosclerosis and future cardiovascular risk. The FABP2 A54T polymorphism is not associated with severe carotid stenosis.

Aged↗
PubMed2006

Antibiotics as intermicrobial signaling agents instead of weapons.

It has been widely assumed that the ecological function of antibiotics in nature is fighting against competitors. This made them a good example of the Darwinian struggle-for-life in the microbial world. Based on this idea, it also has been believed that antibiotics, even at subinhibitory concentrations, reduce virulence of bacterial pathogens. Herein, using a combination of genomic and functional assays, we demonstrate that specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunistic bacterial pathogen Pseudomonas aeruginosa. All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of P. aeruginosa type III secretion system and consequently bacterial cytotoxicity. Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial species in natural, nonclinical environments, either by favoring colonization of surfaces (biofilm, motility) or for fighting against eukaryotic predators (cytotoxicity). Our results support the notion that antibiotics are not only bacterial weapons for fighting competitors but also signaling molecules that may regulate the homeostasis of microbial communities. At low concentrations, they can even be beneficial for the behavior of susceptible bacteria in natural environments. This is a complete change on our vision on the ecological function of antibiotics with clear implications both for the treatment of infectious diseases and for the understanding of the microbial relationships in the biosphere.

Biofilms↗
PubMed2004

The influence of protein binding on the antibacterial activity of faropenem against Haemophilus influenzae.

The effects of albumin and human serum on the pharmacodynamics of faropenem were studied. The protein binding of faropenem was 91-95%, corresponding to the increase in MICs for Haemophilus influenzae in broth supplemented with albumin. Time-kill experiments in albumin-containing medium and in inactivated human serum 50% v/v showed that much higher drug concentrations were needed to achieve a bactericidal effect than were needed in broth. Active human serum alone exerted a strain-dependent bactericidal effect. It was concluded that it is the free fraction of faropenem in serum that has antibacterial activity against H. influenzae.

Carbapenems↗
PubMed2001

In vitro pharmacodynamic studies of activities of ketolides HMR 3647 (Telithromycin) and HMR 3004 against extracellular or intracellular Helicobacter pylori.

The pharmacodynamic properties of the ketolides HMR 3647 (telithromycin) and HMR 3004 were studied against Helicobacter pylori. Both ketolides showed a pronounced concentration-dependent killing, a significant postantibiotic effect, a long postantibiotic sub-MIC effect, and a reduction of intracellular H. pylori.

Anti-Bacterial Agents↗
PubMed2001

Pharmacokinetic and pharmacodynamic parameters for antimicrobial effects of cefotaxime and amoxicillin in an in vitro kinetic model.

An in vitro kinetic model was used to study the relation between pharmacokinetic and pharmacodynamic (PK-PD) parameters for antimicrobial effect, e.g., the time above MIC (T>MIC), maximum concentration in serum (C(max)), and area under the concentration-time curve (AUC). Streptococcus pyogenes and Escherichia coli were exposed to cefotaxime, and the activity of amoxicillin against four strains of Streptococcus pneumoniae with different susceptibilities to penicillin was studied. The drug elimination rate varied so that the T>MIC ranged from 20 to 100% during 24 h, while the AUC and/or the initial concentration (C(max)) were kept constant. For S. pyogenes and E. coli, the maximal antimicrobial effect (E(max)) at 24 h occurred when the antimicrobial concentration exceeded the MIC for 50 and 80% of the strains tested, respectively. The penicillin-susceptible pneumococci (MIC, 0.03 mg/liter) and the penicillin-intermediate strain (MIC, 0.25 mg/liter) showed maximal killing by amoxicillin at a T>MIC of 50%. For a strain for which the MIC was 2 mg/liter, C(max) needed to be increased to achieve the E(max). Under the condition that C(max) was 10 times the MIC, E(max) was obtained at a T>MIC of 60%, indicating that C(max), in addition to T>MIC, may be an important parameter for antimicrobial effect on moderately penicillin-resistant pneumococci. For the strain for which the MIC was 4 mg/liter, the reduction of bacteria varied from -0.4 to -3.6 log(10) CFU/ml at a T>MIC of 100%, despite an initial antimicrobial concentration of 10 times the MIC. Our studies have shown that the in vitro kinetic model is a useful complement to animal models for studying the PK-PD relationship for antimicrobial effect of antibiotics.

Amoxicillin↗
PubMed2001

Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol.

OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either mibefradil or atenolol for 6 weeks (50 mg once daily for 2 weeks followed by 100 mg once daily for 4 weeks). The ratio between early (E) and late (A) diastolic mitral flow velocities (E/A), the E wave deceleration time (DT) and the left ventricular isovolumetric relaxation time (IRT) were measured by Doppler echocardiography as parameters of left-ventricular diastolic function initially, after 4 and after 6 weeks of treatment. RESULTS: Mibefradil did not change the E/A ratio significantly (+4%, NS), while atenolol treatment resulted in a significant increase in the E/A ratio (+20%, p < 0.001). Mibefradil treatment, on the other hand, resulted in a significant decrease (-8%, p < 0.001) in IRT, while atenolol treatment did not change IRT. Neither mibefradil nor atenolol treatment changed DT significantly. CONCLUSIONS: Both mibefradil and atenolol treatment significantly improves echocardiographic indices of left-ventricular diastolic function in patients with chronic stable angina. However, they affect different parameters and thus apparently act through different mechanisms.

Adrenergic beta-Antagonists↗
PubMed2000

Long-term prognosis of diabetic patients with myocardial infarction: relation to antidiabetic treatment regimen. The TRACE Study Group.

AIMS: The present study was performed to evaluate pre-admission history, presentation, initial treatment and long-term mortality in patients with myocardial infarction and diabetes. METHODS AND RESULTS: Between 1990 and 1992, 6676 patients with acute myocardial infarction were screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. In this cohort 719 (11%) of the patients had a history of diabetes. Among the diabetic patients 19% were treated with insulin, 52% with oral hypoglycaemic agents and 29% with diet only. The diabetic patients were slightly older, more likely to be female and had a higher prevalence of known cardiovascular disease. Even though the diabetic patients had the same frequency of ST-segment elevation on the electrocardiogram and the same admission delay, treatment with thrombolysis and aspirin was less frequently prescribed to the diabetic patients than to patients without diabetes. The mortality rate was significantly increased in the diabetic patients, 7-year mortality being 79% in insulin-treated, 73% in tablet-treated and 62% in diet-treated diabetic patients compared with 46% in patients without diabetes. In a multivariate analysis only diabetic patients treated with oral hypoglycaemic agents or with insulin had an increased mortality compared with non-diabetic patients. CONCLUSIONS: Patients with diabetes mellitus and myocardial infarction are treated with thrombolysis to a lesser extent than non-diabetic patients. Diabetic patients treated with oral hypoglycaemic agents or insulin, but not those treated with diet alone, have a significantly increased mortality following acute myocardial infarction compared with non-diabetic patients.

Aged↗
PubMed2000

In vitro pharmacodynamics of the new ketolides HMR 3004 and HMR 3647 (Telithromycin) against Chlamydia pneumoniae.

The ketolides HMR 3004 and HMR 3647 (telithromycin) are a new class of macrolides that have a potential clinical efficacy against intracellular pathogens. The objectives of this study were to investigate the MIC, minimum bactericidal concentration, and time-dependent killing of two Chlamydia pneumoniae strains of the two ketolides. The killing effect was also studied with a newly developed intracellular in vitro kinetic model. Furthermore, HMR 3647 was studied for the effect of a subinhibitory concentration of 0.5 times the MIC after a preexposure of 10 times the MIC during 12 h. The MICs for both strains were 0.0039 and 0.0156 mg/liter for HMR 3004 and HMR 3647, respectively. Killing with 10 times the MIC was time dependent, increasing from a 1-log-unit decrease in the number of inclusions per well at 48 h to a maximal effect of 2.8-log-unit decrease after 96 h. A preexposure of 10 times the MIC of HMR 3647 for 12 h followed by a subinhibitory concentration of 0.5 times the MIC increased the killing effect to a 1.2-log-unit reduction in inclusions per well. An exposure for 12 h gave poor reduction of inclusions, while a static dose of 10 times the MIC for 72 h showed a 2.2-log-unit reduction in inclusions per well. In the kinetic model, a small number of inclusions were detected after 72 h by one exposure of 10 times the MIC. Regrowth could not be detected after 120 h. The ketolides HMR 3004 and HMR 3647 have bactericidal activity and show a significant sub-MIC effect on the intracellular pathogen C. pneumoniae.

Anti-Bacterial Agents↗
PubMed1999

Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group.

OBJECTIVES: This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND: Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS: The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of trandolapril in 1,749 patients with AMI and ejection fraction < or =35%. The mean follow-up time was 26 months. RESULTS: A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS: The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Analysis of odour and taste problems in high-density polyethene.

The compounds that cause off-flavours in plastics, have been recognized mainly as carbonyl compounds (aldehydes, ketones and esters). They occur in low concentrations, and due to their low-threshold odour concentrations, their typical odours were identified. Most of these off-flavour compounds are volatile. Chemical analysis of smelling compounds requires a very sensitive method with a high-resolution capability. The analysis of volatile organic compounds (VOCs) in high density polyethene (HD-PE) granules and waters in which the granules have been shaken for 4 h, were carried out by gas chromatography-mass spectrometry-sniffing system (GC-MS-SNIFF) and by gas chromatography-fourier transform infrared spectroscopy-sniffing system (GC-FTIR-SNIFF). A purge-and-trap technique was used to introduce the VOCs from samples into the gas chromatograph. Leaching waters of HD-PE granules were also evaluated by panel. This panel agreed upon six descriptive attributes for odour: sweet, chemical, stale, dusty, foul and floor-cloth. The attributes for taste were: sweet, metallic, stony, pungent, dusty, plastic, foul, stink bug and candle grease.

Chromatography, Gas↗
PubMed1997

Report from the HLA class II typing by PCR-SSP Multicentre Study.

Results from 360 HLA-DR and -DQ 'low-resolution' typings with polymerase chain reaction sequence-specific primers (PCR-SSP), performed by nine laboratories, were analysed for their overall utility in routinely defining the HLA-DR1-DR18, DR51-DR53 and DQ1-DQ9 specificities in less than 2.5 h. Thirty EDTA blood samples and 10 DNA samples were distributed and analysed by each laboratory. DNA was extracted using a rapid bromide salt extraction protocol. Complete HLA-DR and -DQ typings were performed, three by three, on pre-aliquoted 96-tube PCR trays. When compared with reference typing, 351/360 (98%) correct DR typings were obtained, whereas 320/360 (89%) of the DQ phenotypes were correctly assigned. The time for three complete HLA-DR and -DQ 'low-resolution' typings, including DNA extraction, ranged from 2.0 h to 2.3 h. Unfortunately, an unusually high level of PCR amplification failures was observed (3%), probably due to diffusion and a significant volume loss from some of the pre-aliquoted primer mixes. Consequently, only 52% of the typings were without any amplification failure, and 0-2 amplification failures where found in 88% of the PCR-SSP typings performed. The number of HLA-DR-DQ retypings needed was 7 and 8%, respectively, reflecting the low number of typings where allelic identification was directly affected by the relatively high level of amplification failures in this study. Thus, a 91-98% success rate of correctly identified HLA-DR and -DQ alleles could be maintained, even under suboptimal typing conditions.

Alleles↗
PubMed1997

Assay of antibiotic susceptibility of Chlamydia pneumoniae.

It is well known that treatment of Chlamydia pneumoniae infections is difficult. High doses and prolonged treatment is often needed to achieve clinical cure despite good in vitro effect of the drugs used. We here discuss different methodological problems in the determination of MIC and MBC values of C. pneumoniae. The length of the preincubation time and the lack of fluctuation of the antibiotic concentrations may affect the outcome of the currently used assay.

Anti-Bacterial Agents↗
PubMed1996

New pharmacokinetic in vitro model for studies of antibiotic activity against intracellular microorganisms.

The capacity for intracellular growth is an important survival strategy for a large group of common pathogens. Helicobacter pylori, the etiological agent for gastritis and duodenal ulcer, has been shown by both in vivo and in vitro studies to have the capacity to invade epithelial cells. In vitro models are used to study the effect of antibiotics on microoganisms. Most investigations are performed in broth culture or on agar plates, but kinetic models for bacteria in broth have been described. We present a new, kinetic model adapted for intracellular pathogens. A glass chamber, with a metal rack fitting Falcon cell culture inserts, was connected to a pump by rubber tubes. Different tube diameters and pump speeds were evaluated, and the assay was designed to mimic the half-lives of the antibiotics in vivo, i.e., 11.5 h for azithromycin, 5 h for clarithromycin, and 1 h for amoxicillin. Monolayers of HEp-2 cells were grown in the inserts for 2 days, after which H. pylori (clinical strain 88-23), was added to the system. Internalization was allowed for 12 h, and extracellular H. pylori cells were eradicated with gentamicin. The inserts were moved to the glass chamber, containing medium with 12.5 mg of either amoxicillin or azithromycin per liter or 2.4 mg of clarithromycin per liter. This represents 12.5, 50, and 80 times the extracellular minimum bactericidal concentration value, respectively. Samples were taken at 0, 2, 4, 6, 8, and 24 h. The HEp-2 cells were lysed, and intracellular bacteria were counted by plating. Inserts with infected cells grown in drug-free medium were included as controls for each time interval. A 3-log10 reduction of H. pylori was achieved in the experiments with azithromycin, and a 4-log10 reduction was achieved in the clarithromycin experiments, while no intracellular effect was seen when amoxicillin was used. The antibiotic concentrations at the sampling intervals were 12.5, 3.1, 0.8, 0.2, 0.05, and 0 mg/liter for amoxicillin; 12.5, 11.5, 10, 9, 8, and 3 mg/liter for azithromycin; and 2.4, 1.8, 1.4, 1, 0.8, and 0 mg/liter for clarithromycin. This new model for pharmacokinetic studies provides a useful tool, with applications for a broad range of microorganisms.

Amoxicillin↗
PubMed1994

Complement killing of Yersinia enterocolitica and retention of the bacteria by leucocyte removal filters.

We report studies on the complement sensitivity of four strains of Yersinia enterocolitica, serotypes O:3, O:9, O:5.27, and O:20, isolated from blood units involved in transfusion fatalities. Complement in fresh CPD plasma killed Y. enterocolitica within 4 h at 22 degrees C in 100% of the experiments. The bactericidal action was serotype and complement activation pathway dependent. Both classic and alternate pathways seemed to be active, but the latter to a lesser degree. When the classic pathway was blocked by chelation of Ca2+ no complete killing was obtained. Complement did not enhance or condition Yersinia for leucocyte filter retention. Direct removal of Yersinia by filtration was also related to serotype; all strains were reduced by filtration in heat-inactivated plasma, and all except serotype O:5.27 were reduced in Ca(2+)-chelated plasma. Our findings may explain why plasma products and platelet concentrates are rarely involved in Yersinia sepsis related to transfusion.

Adsorption↗
PubMed1994

Novel automated microbial screening of platelet concentrates.

The recovery of bacteria and the speed of detection of microbial growth in platelet concentrates (PC) were studied, comparing a novel automated blood culture system (BacT/Alert) with two traditional methods. Full-scale experiments were performed with a total of 33 units of PC (average content 320 x 10(9) platelets per unit) obtained from pooled buffy coats. Six strains known as possible PC contaminants were tested: S. epidermidis, S. aureus, P. aeruginosa, B. cereus, E. aerogenes, and S. sanguis. Using an inoculum of 50-98 bacteria/ml, bacterial contamination was detected in all of 11 PCs on 132 sampling occasions. With a small inoculum (0.3-9 bacteria/ml), the bacterial contamination was detected in all PCs in which abundant growth appeared, but failed to be detected in some instances where the bacterial content was very small. All of 11 uninoculated PC controls were negative. With the automated method the time for detection of a culture-positive PC was 6-16 h, clearly shorter than with the two manual-visual systems. The new system provides a rapid, reliable, and labour-saving method for screening of bacterial contamination in PCs. This would increase safety particularly if the present 5-day shelf life were extended.

Bacillus cereus↗