Search PubMed⌕ Search

Biomedical subjects

L Johansson

Publications and source records attributed to L Johansson.

At least 19 recordsLinked to original sources
PubMed2000

A novel phantom design for emission tomography enabling scatter- and attenuation-"free" single-photon emission tomography imaging.

A newly designed technique for experimental single-photon emission tomography (SPET) and positron emission tomography (PET) data acquisition with minor disturbing effects from scatter and attenuation has been developed. In principle, the method is based on discrete sampling of the radioactivity distribution in 3D objects by means of equidistant 2D planes. The starting point is a set of digitised 2D sections representing the radioactivity distribution of the 3D object. Having a radioactivity-related grey scale, the 2D images are printed on paper sheets using radioactive ink. The radioactive sheets can be shaped to the outline of the object and stacked into a 3D structure with air or some arbitrary dense material in between. For this work, equidistantly spaced transverse images of a uniform cylindrical phantom and of the digitised Hoffman rCBF phantom were selected and printed out on paper sheets. The uniform radioactivity sheets were imaged on the surface of a low-energy ultra-high-resolution collimator (4 mm full-width at half-maximum) of a three-headed SPET camera. The reproducibility was 0.7% and the uniformity was 1.2%. Each rCBF sheet, containing between 8.3 and 80 MBq of 99mTcO4- depending on size, was first imaged on the collimator and then stacked into a 3D structure with constant 12 mm air spacing between the slices. SPET was performed with the sheets perpendicular to the central axis of the camera. The total weight of the stacked rCBF phantom in air was 63 g, giving a scatter contribution comparable to that of a point source in air. The overall attenuation losses were <20%. A second SPET study was performed with 12-mm polystyrene plates in between the radioactive sheets. With polystyrene plates, the total phantom weight was 2300 g, giving a scatter and attenuation magnitude similar to that of a patient study. With the proposed technique, it is possible to obtain "ideal" experimental images (essentially built up by primary photons) for comparison with "real" images degraded by photon scattering and attenuation losses. The method can serve as a tool for experimental validation and intercomparison of attenuation and scatter correction methods. Moreover, the large flexibility of this phantom design will allow investigations of arbitrary activity distributions and autoradiography or other imaging techniques such as PET, x-ray computed tomography or magnetic resonance imaging.

Brain↗
PubMed2000

A peptidyl derivative structurally based on the inhibitory center of cystatin C inhibits bone resorption in vitro.

Human cystatin C is a cysteine proteinase inhibitor belonging to the cystatin superfamily, which previously has been shown to inhibit bone resorption in bone organ culture. The aminoterminal segment, Arg(8)-Leu(9)-Val(10)-Gly(11) (RLVG), of the single polypeptide chain of cystatin C constitutes an essential part of its inhibitory center. In the present study, the effect of benzyloxycarbonyl-Arg(8)-Leu(9)-Val(10)-Gly(11)-diazomethane (Z-RLVG-CHN(2)) on bone resorption in vitro was compared with the effects of cystatin C and calcitonin. Bone resorption was assessed by the release of (45)Ca and (3)H from mouse calvarial bones prelabeled with [(45)Ca]CaCl(2) and [(3)H]-proline, respectively. Z-RLVG-CHN(2) concentration-dependently inhibited the release of (45)Ca and (3)H in bones stimulated by parathyroid hormone (PTH), with half-maximal inhibition obtained at 1 micromol/L. The inhibitory actions of Z-RLVG-CHN(2) and cystatin C were persistent, whereas action induced initially by calcitonin was lost with time. The inhibition caused by Z-RLVG-CHN(2) and cystatin C on PTH-stimulated (45)Ca release was observed after 6 h, whereas inhibition by calcitonin was seen already after 2 h. In contrast, the inhibitory effects of Z-RLVG-CHN(2) and cystatin C, as well as that of calcitonin, on (3)H release was seen already after 2 h. Z-RLVG-CHN(2), in which the reactive carboxyterminal diazomethane was substituted by nonreactive groups [-OH, -NH(2), or -N(CH(3))(2)], resulted in peptidyl derivatives, which, in contrast to Z-RLVG-CHN(2) and cystatin C, inhibited neither cysteine proteinases nor bone resorption. In contrast to wild-type cystatin C, recombinant human cystatin C with Gly substitutions for residues Arg(8), Leu(9), Val(10), and Trp(106), and with low or nonexistent affinity for cysteine proteinases, did not display any inhibitory effect on bone resorption. These data strongly indicate that Z-RLVG-CHN(2) inhibits bone resorption in vitro by a mechanism that seems primarily to be due to an inhibition of bone matrix degradation via cysteine proteinases. The data also corroborate the hypothesis that cystatin C inhibits bone resorption by virtue of its cysteine proteinase inhibitory capacity.

Animals↗
PubMed2000

Gadolinium-enhanced magnetic resonance angiography, digital subtraction angiography and duplex of the iliac arteries compared with intra-arterial pressure gradient measurements.

PURPOSE: to compare gadolinium-enhanced magnetic resonance angiography (Gd-MRA), digital subtraction angiography (DSA) and duplex of the iliac arteries with intra-arterial pressure gradient measurement as the reference method. MATERIALS AND METHODS: Gd-MRA, DSA and duplex examinations of the iliac arteries were performed in 30 patients (60 arteries) with lower-limb arterial occlusive disease. In 29 arteries, pressure measurements were made (n=25) or the artery was found to be occluded on catheterisation (n=4). An aortofemoral peak systolic pressure gradient of 20 mmHg or more was regarded as haemodynamically significant. Stenoses with a diameter reduction of 50% or more on MRA or DSA, or an increase in peak systolic velocity greater than 150% (duplex) were considered significant. MRA examinations were evaluated by means of maximum intensity projections (MRA-MIP) and using source images and curved multiplanar reconstruction (MRA-MPR). RESULTS: the sensitivity (specificity) for a significant iliac artery stenosis were 81% (75%) for MRA-MIP, 76% (75%) for MRA-MPR, 86% (88%) for DSA, and 72% (88%) for duplex. CONCLUSION: with intra-arterial pressure measurements as the reference method, similar results were achieved with Gd-MRA, DSA and duplex concerning the detection of haemodynamically significant iliac artery stenoses. The use of source images and multiplanar reconstructions resulted in higher accuracy for the detection of occlusions.

Aged↗
PubMed2000

Evaluation of methods for endoscopic staging of nasal polyposis.

Endoscopy is needed for reliable evaluation of the treatment of nasal polyposis. In this study, we compared the reproducibility of various score systems for staging nasal polyposis and the inter-individual variations between investigators. The mass of the polyps was assessed by five methods, three new techniques (numbers 1, 2 and 3) and two established ones (numbers 4 and 5). These were: 1, lateral imaging projecting the extension of the polyps by drawing on a schematic picture of the lateral wall of each nasal cavity; 2, assessment of polyp obstruction estimating the proportion of the total nasal cavity volume occupied by polyps; 3, nasal airway patency--determining the relationship between the patient's patent airway lumen and an imaginary maximal nasal airway lumen; 4, a score system with four steps ad modum Lildholdt et al.--determining their relationship to fixed anatomical landmarks; and 5, a score system with three steps ad modum Lund and Mackay--determining their relationship to the middle meatus. High correlations were found between the first and the second assessments by a given investigator with all five methods used to score nasal polyposis. High correlations were also shown between the various methods. When three investigators examined a given patient, there were no significant differences between the investigators using score systems 1, 3 and 4. However, with score systems 2 and 5, there was insufficient agreement between the investigators. The patient's symptom of nasal blockage was not a good indicator of the size of the polyps, especially as regards small polyps. Two of the best methods tested (1 and 4) were selected for further clinical studies regarding evaluation of the sensitivity of score systems to detect changes in polyp size during treatment.

Adult↗
PubMed2000

Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.

PURPOSE: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). MATERIAL AND METHODS: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). RESULTS: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. CONCLUSION: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.

Aged↗
PubMed2000

Reproducibility and repeatability of 99Tcm-HMPAO rCBF SPET in normal subjects at rest using brain atlas matching.

The aim of this study was to assess regional cerebral blood flow (rCBF) in normal subjects at rest using 99Tcm-HMPAO single photon emission tomography (SPET). Analysis of reproducibility and repeatability was performed both before and after normalization of flow data. Six healthy volunteers were examined, three times each, according to a routine rCBF protocol. A computerized brain atlas was used to evaluate flow data in eight selected regions. The overall reproducibility of rCBF was evaluated from two scans performed at an average interval of 3 months. Repeatability was evaluated from two scans, 3 h apart and without re-injection of 99Tcm-HMPAO. For the normalized (relative) flow data, the reproducibility was +/- 1.3% and the repeatability +/- 2.2% (i.e. methodological errors dominate). For the non-normalized flow data, the corresponding values were +/- 14.8% and +/- 5.9%. rCBF SPET with 99Tcm-HMPAO is highly reproducible provided that the flow data are normalized. The variation in flow between individuals at one point in time and 3 months later was less than +/- 5% for all brain regions.

Adult↗
PubMed2000

A comparison of 99Tcm-MDP and 99Tcm-MIBI in the detection of breast cancer.

In this study, we made an intra-individual comparison of the uptake of 99Tcm-MDP and 99Tcm-MIBI in breast cancer. Twenty women with large breast masses (one dimension > or = 3 cm on mammography) underwent SPET in the supine position with both agents. All transverse sections demonstrating tumour activity were added together and the net (total) tumour uptake in a region of interest was compared to that of surrounding tissue activity (background). We also evaluated maximum tumour uptake versus background activity. Tumour uptake was observed in all examinations. In contrast to MIBI, eight MDP examinations showed increased uptake in normal breast parenchyma in addition to tumour uptake. There was no significant difference in net tumour uptake between the two tracers and non-parenchymal (indifferent) background activity, but the maximum tumour activity of MIBI was significantly higher than that of MDP. In the eight MDP examinations with parenchymal activity, mammograms were required to identify tumour uptake correctly. In conclusion, MDP may provide similar images to MIBI in postmenopausal women not receiving hormone replacement therapy. For other patients, MIBI gives better tumour depiction.

Adult↗
PubMed2000

The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors.

SHP (short heterodimer partner) is an unusual orphan nuclear receptor consisting only of a ligand-binding domain, and it exhibits unique features of interaction with conventional nuclear receptors. While the mechanistic basis of these interactions has remained enigmatic, SHP has been suggested to inhibit nuclear receptor activation by at least three alternatives; inhibition of DNA binding via dimerization, direct antagonism of coactivator function via competition, and possibly transrepression via recruitment of putative corepressors. We now show that SHP binds directly to estrogen receptors via LXXLL-related motifs. Similar motifs, referred to as NR (nuclear receptor) boxes, are usually critical for the binding of coactivators to the ligand-regulated activation domain AF-2 within nuclear receptors. In concordance with the NR box dependency, SHP requires the intact AF-2 domain of agonist-bound estrogen receptors for interaction. Mutations within the ligand-binding domain helix 12, or binding of antagonistic ligands, which are known to result in an incomplete AF-2 surface, abolish interactions with SHP. Supporting the idea that SHP directly antagonizes receptor activation via AF-2 binding, we demonstrate that SHP variants, carrying either interaction-defective NR box mutations or a deletion of the repressor domain, have lost the capacity to inhibit agonist-dependent transcriptional estrogen receptor activation. Furthermore, our studies indicate that SHP may function as a cofactor via the formation of ternary complexes with dimeric receptors on DNA. These novel insights provide a mechanistic explanation for the inhibitory role of SHP in nuclear receptor signaling, and they may explain how SHP functions as a negative coregulator or corepressor for ligand-activated receptors, a novel and unique function for an orphan nuclear receptor.

Amino Acid Motifs↗
PubMed2000

Tissue plasminogen activator, plasminogen activator inhibitor-1, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex as risk factors for the development of a first stroke.

UNLABELLED: BACKGROUND NAD PURPOSE: Abnormalities in the fibrinolytic system have been associated with an increased risk for stroke in a few studies. This study was designed to test whether plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and tPA/PAI-1 complex could predict a first-ever stroke. METHODS: The study was an incident case-control study nested within the Västerbotten Intervention Program and the Northern Sweden Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) cohorts. In this study 108 first-ever stroke cases were defined according to the MONICA classification, and 216 controls from the same cohort were randomly selected and matched for age, sex, sampling time, and geographic region. RESULTS: Stroke occurred on average 30 months after the blood sampling date. The mean plasma concentration of tPA/PAI-1 complex was higher for the stroke cases than for the controls (3.9 versus 3.0 microgram/L). In univariate regression analysis, significantly higher odds ratios were found for the tPA/PAI-1 complex as continuous variable. When divided into quartiles, the odds ratio was 2.74 for the highest quartile compared with the lowest. In the multivariate model, the tPA/PAI-1 complex remained an independent predictor for stroke. Additionally, tPA mass concentration quartiles 3 and 4 showed a significant association with all stroke as outcome. No association was found, however, for PAI-1. In subgroup analysis of cerebral hemorrhage (n=18), the mean tPA/PAI-1 complex level was higher for the cases than for the controls (4.8 versus 3.0 microgram/L), and in multivariate analysis including all controls (n=216), only tPA/PAI-1 complex remained significant. CONCLUSIONS: This prospective study shows that tPA/PAI-1 complex, a novel fibrinolytic marker, is independently associated with the development of a first-ever stroke, especially hemorrhagic stroke. This finding supports the hypothesis that disturbances in fibrinolysis precede a cerebrovascular event.

Case-Control Studies↗
PubMed1999

Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes.

Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.

Animals↗
PubMed1999

The orphan nuclear receptor SHP inhibits agonist-dependent transcriptional activity of estrogen receptors ERalpha and ERbeta.

SHP (short heterodimer partner) is an unusual orphan nuclear receptor that contains a putative ligand-binding domain but lacks a conserved DNA-binding domain. Although no conventional receptor function has yet been identified, SHP has been proposed to act as a negative regulator of nuclear receptor signaling pathways, because it interacts with and inhibits DNA binding and transcriptional activity of various nonsteroid receptors, including thyroid hormone and retinoid receptors. We show here that SHP interacts directly with agonist-bound estrogen receptors, ERalpha and ERbeta, and inhibits ER-mediated transcriptional activation. SHP specifically targets the ligand-regulated activation domain AF-2 and competes for binding of coactivators such as TIF2. Thus, SHP may represent a new category of negative coregulators for ligand-activated nuclear receptors. SHP mRNA is widely expressed in rat tissues including certain estrogen target tissues, and subcellular localization studies demonstrate that SHP is a nuclear protein, suggesting a biological significance of the SHP interactions with ERs. Taken together, these results identify ERs as novel SHP targets and suggest that competition for coactivator-binding is a novel mechanism by which SHP may inhibit nuclear receptor activation.

Animals↗
PubMed1999

Sequence optimization in mangafodipir trisodium-enhanced liver and pancreas MRI.

To find an optimal magnetic resonance (MR) sequence for mangafodipir trisodium-enhanced liver and pancreas imaging, six healthy volunteers were studied using a 1.5 T MR system with different T1-weighted abdominal imaging sequences. These were turbo field (gradient)-echo (TFE), fast field (gradient)-echo (FFE), and spin-echo sequences before and after mangafodipir trisodium administration. Various parameter combinations were investigated within each sequence type, and then the best combination was found and compared with those of the other sequences. Signal intensity (SI) measurements were made in regions of interest in the liver, pancreas, and a reference marker with a known T1 value. Contrast index (CI, SItissue/SImarker) and contrast-to-noise ratio (CNR, [SItissue/SImarker]/SDbackground) were calculated, and percentage CI increase and CNR in the postcontrast images were used for the best sequence evaluation. Regarding CI, the TFE sequence with a TR/TE/flip angle of 15 msec/4.6 msec/20 degrees and inversion time of 300 msec had the largest pre- to postcontrast percentage increase. The FFE sequence with a TR/TE/flip angle of 140 msec/4.6 msec/90 degrees had the highest postcontrast CNR and is considered to be the optimal sequence for mangafodipir trisodium-enhanced MR imaging of the liver and pancreas.

Adult↗
PubMed1999

Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test.

The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of 14C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq 14C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%+/-3.9% (mean of adults and children +/- standard error of the mean) of the administered 14C activity was recovered. The majority of the administered activity, 88.3%+/-6.2% in adults and 87.7%+/-5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%+/-0.6% of the activity was exhaled within 20 days and in children 2.6%+/-0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO2 production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO2. The urinary bladder received the highest absorbed dose: in adults, 0.15+/-0.01 mGy/MBq and in children of various ages (7-14 years), 0.14-0.36 mGy/MBq. The findings indicate that an investigation with 14C-urea gives an effective dose to adults of 2.1+/-0.1 microSv (for 110 kBq) and to children of 0.9-2.5 microSv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with 14C-urea in whole families, including children.

Adolescent↗
PubMed1999

Healthy dietary habits in relation to social determinants and lifestyle factors.

The aim of the present study was to evaluate the importance of social status and lifestyle for dietary habits, since these factors may influence life expectancy. We studied the association of four indicators for healthy dietary habits (fruits and vegetables, fibre, fat and Hegsted score) with sex, age, socio-economic status, education, physical leisure exercise, smoking and personal attention paid to keeping a healthy diet. Data were gathered with a self-administered quantitative food-frequency questionnaire distributed to a representative sample of Norwegian men and women aged 16-79 years in a national dietary survey, of whom 3144 subjects (63%) responded. Age and female sex were positively associated with indicators for healthy dietary habits. By separate evaluation length of education, regular physical leisure exercise and degree of attention paid to keeping a healthy diet were positively associated with all four indicators for healthy dietary habits in both sexes. Socio-economic status, location of residence and smoking habits were associated with from one to three indicators for healthy dietary habits. In a multiple regression model, age, education and location of residence together explained from 1 to 9% of the variation (R2) in the four dietary indicators. Length of education was significantly associated with three of four dietary indicators both among men and women. By including the variable 'attention paid to keeping a healthy diet' in the model, R2 increased to between 4 and 15% for the four dietary indicators. Length of education remained correlated to three dietary indicators among women, and one indicator among men, after adjusting for attention to healthy diet, age and location of residence. Residence in cities remained correlated to two indicators among men, but none among women, after adjusting for age, education and attention to healthy diet. In conclusion, education was associated with indicators of a healthy diet. Attention to healthy diet showed the strongest and most consistent association with all four indicators for healthy dietary habits in both sexes. This suggests that personal preferences may be just as important for having a healthy diet as social status determinants.

Adolescent↗
PubMed1999

Neu5Acalpha3Gal is part of the Helicobacter pylori binding epitope in polyglycosylceramides of human erythrocytes.

The sialic acid dependent binding by the human pathogen Helicobacter pylori to polyglycosylceramides of human erythrocytes was investigated. Polyglycosylceramides, complex glycosphingolipids with a branched N-acetyllactosamine core, were isolated from human erythrocytes, blood group O, and subfractionated after peracetylation by anion-exchange chromatography. Three subfractions were deacetylated, analysed by matrix-assisted laser desorption ionization-time of flight MS and 2D 1H NMR spectroscopy. The observed mass ranges were m/z = 3093-7622, 3968-7255 and 3459-7987 in the mass spectra of the first, second and third fractions, respectively. The observed ions agreed with the general formula Hex(x+2)HexNAcxFucyNeu5AczCer. Two-dimensional 1H total correlation spectra of the mixtures showed that the first fraction contained 3-linked sialic acid and the second and third fractions contained both 3-linked and 6-linked sialic acid. Thin-layer chromatogram binding assays using the lectins from Maackia amurensis, specific for Neu5Acalpha3Galbeta4GlcNAc, and Sambucus nigra, specific for Neu5Acalpha6Gal/GalNAc, were used to confirm this distribution. H. pylori recognized all three fractions in the binding assay, indicating that the 3-linked, rather than 6-linked, sialic acid is essential for binding.

Ceramides↗
PubMed1999

Perception of surface pressure applied to the hand.

The study aimed to determine the relationship between the physical magnitude and the subjective perception of applied pressure, and to determine discomfort and pain thresholds. Free modulus magnitude estimation of the subjective pressure level was made on three points: on the finger, the palm and the thenar area. The pressure was judged to be higher at the thenar point than at the finger and palm points. The slopes of the linear functions (log magnitude estimates as a function of log pressure) were 0.66, 0.78 and 0.76 for the finger, palm and thenar points respectively. The discomfort threshold was 38% of the pain pressure threshold at the finger point, 40% at the palm and 22% at the thenar point. The results are probably of importance in the performance of hand-intensive work, in particular in the design of hand tools.

Adolescent↗
PubMed1999

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat.

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.

Animals↗