Biomedical subjects

I Eide

Publications and source records attributed to I Eide.

At least 19 recordsLinked to original sources

PubMed2001

Resolution of GC-MS data of complex PAC mixtures and regression modeling of mutagenicity by PLS.

The present work describes a strategy to predict the mutagenicity of very complex mixtures of polycyclic aromatic compounds (PAC) from gas chromatography-mass spectrometry (GC-MS) patterns of the mixtures, each containing 260 compounds on average. The mixtures, 13 organic extracts of exhaust particles, were characterized by full scan GC-MS. The data were resolved into peaks and spectra for individual compounds by an automated curve resolution procedure. Similarity between spectra was evaluated for peaks that appeared within a time interval of 4 min, using a similarity index of 0.8 to ascertain that the same compound was represented by the same variable name (retention time) in all samples. The resolved chromatograms were integrated, resulting in a predictor matrix of size 13 x 721, which was used as input to a multivariate regression model. Partial least-squares projections to latent structures (PLS) were used to correlate the GC-MS chromatograms to mutagenicity as measured in the Ames Salmonella assay. The best model (high r2 and Q2) was obtained with 52 variables. These variables covary with the observed mutagenicity, and may subsequently be identified chemically. Furthermore, the regression model can be used to predict mutagenicity from GC-MS chromatograms of other organic extracts.

Air Pollutants↗

PubMed2001

Reduced autonomic activity during stepwise exposure to high altitude.

Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in a hypobaric chamber to test the hypothesis of a temporary reduction in autonomic activity. The altitude was increased stepwise to 4500 m over 3 days. Heart rate variability (HRV) was assessed continuously in seven subjects. Baroreceptor reflex sensitivity (BRS) was determined in eight subjects with the 'Transfer Function' method at baseline, at 4500 m and after returning to baseline. Resting plasma catecholamines and cardiovascular- and plasma catecholamine- responses to cold pressor- (CPT) and mental stress-test (MST) were assessed daily in all and 12 subjects, respectively. Data are mean +/- SEM. Compared with baseline at 4500 m there were lower total power (TP) (35 457 +/- 26 302 vs. 15 001 +/- 11 176 ms2), low frequency (LF) power (3112 +/- 809 vs. 1741 +/- 604 ms2), high frequency (HF) power (1466 +/- 520 vs. 459 +/- 189 ms2) and HF normalized units (46 +/- 0.007 vs. 44 +/- 0.006%), P < or = 0.001. Baroreceptor reflex sensitivity decreased (15.6 +/- 2.1 vs. 9.5 +/- 2.6 ms mmHg(-1), P = 0.015). Resting noradrenaline (NA) decreased (522 +/- 98 vs. 357 +/- 60 pmol L(-1), P = 0.027). The increase in systolic blood pressure (SBP) and NA during mental stress was less pronounced (21 +/- 4 vs. 10 +/- 2% and 25 +/- 9 vs. -2 +/- 8%, respectively, P < 0.05). The increase in SBP during cold pressor test decreased (16 +/- 3 vs. 1 +/- 6%, P = 0.03). Diastolic blood pressure, HR and adrenaline displayed similar tendencies. We conclude that a transient reduction in parasympathetic and sympathetic activity was demonstrated during stepwise exposure to high altitude.

Adult↗

PubMed2001

Glucose disposal rates calculated from 60- to 90-minute isoglycemic hyperinsulinemic glucose clamp correlate with cardiovascular risk factors in borderline hypertensive young men.

The hyperinsulinemic glucose clamp is generally performed for at least 120 minutes, due to assumptions of steady-state. We were interested in relationships between glucose disposal rate (GDR) and cardiovascular risk factors, rather than a standard measure of insulin sensitivity per se. Therefore, we analyzed 120-minute clamps performed on borderline hypertensive, but otherwise healthy young men (n = 19). GDR was calculated at different time points and related to baseline cardiovascular risk factors and responses to a mental stress test (MST). The 60-, 90-, and 120-minute GDR correlated significantly with serum high-density lipoprotein (HDL) cholesterol (r=.59, r=.50, and r=.53, respectively), heart rate (HR) during MST (r = -.65, r = -.64, and r = -.58, respectively) and plasma epinephrine (Epi) (r = -.55, r= -.58, and r = -.56, respectively) and norepinephrine (NE) (r = -.52, r = -.49, and r = -.48, respectively) 1 minute after announcement of the MST (all P <.05). Although not statistically significant at all time points, similar relationships were observed between GDR and resting HR, systolic blood pressure (BP) at rest and during mental stress, body mass index (BMI), serum total cholesterol (Chol), serum triglycerides (TG), and blood hemoglobin (HgB), with remarkable consistency from about 40 to 50 minutes onwards. HDL cholesterol and Epi remained independent in stepwise multiple regression analyses with the 60-, 90-, and 120-minute GDR as dependent variables (all P <.05). We suggest that 60- to 90-minute glucose clamps may provide information about the relationship between insulin sensitivity and various cardiovascular risk factors in borderline hypertensive young caucasian men.

Adult↗

PubMed2001

Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure.

We have previously shown correlations between cardiovascular risk factors such as blood pressure (BP), sympathetic nervous system activity, lipids and insulin resistance in young men with elevated screening BP. In the present study we aimed to: (1) compare the genotype distribution and allele frequencies of 11 polymorphisms in seven candidate genes for BP regulation in healthy 21-year-old Caucasian men, between 18 men with normal and 67 men with high screening BP, and (2) evaluate the effect of these polymorphisms in candidate genes on casual BP, BP responses to mental stress or catecholamines and metabolic parameters including insulin sensitivity. There were no differences in genotype distributions or allele frequencies between the subjects with normal and those with high screening BP. Insulin sensitivity was significantly higher in GG homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor (alpha(2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were homozygous both GG in the G-261A polymorphism at the alpha(2A)AR locus and GlyGly in the Arg16Gly polymorphism at the beta2-adrenergic (beta2AR) receptor loci had significantly higher insulin sensitivity and lower catecholamine levels during mental stress than subjects with other genotypes. Subjects who were II homozygous at the angiotensin converting enzyme (ACE) locus and AA homozygous at the angiotensin type I receptor (AT1R) locus had lower BP and a better lipid profile than the rest of the group. Thus, in this explorative study, we report an association between insulin sensitivity and a polymorphism at the alpha(2A)AR locus. We suggest the presence of gene-gene interactions in the renin-angiotensin system and the sympathetic nervous system.

Adult↗

PubMed2001

Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects.

We compared the effects of amlodipine and verapamil slow release on autonomic responses to a 5-min mental arithmetic test (MST) in patients with mild to moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release 240 mg or amlodipine 10 mg in a double-blind crossover design, both after 4 weeks' placebo. Heart rate (HR) and blood pressure (BP) were continuously monitored. Venous plasma catecholamines were analysed by a radioenzymatic assay. Baroreflex sensitivity (BRS) was estimated with the transfer function technique. Calculations of the area under the curve (AUC) were used to estimate average HR, BP and catecholamine concentrations. The reactivity to MST was estimated as percent change from the basal AUC. A paired t-test was performed. Data are means +/-SEM. Compared to verapamil, amlodipine increased average noradrenaline (NA) concentrations (245 +/- 23 vs 191 +/- 17 pg/l, respectively, p = 0.005), NA reactivity (14.0 +/- 5.5% vs -2.9 +/- 3.3, p = 0.004), average HR (65 +/- 2 vs 61 +/- 2 beats/min, p < 0.001) and HR reactivity (2.5 +/- 1.0 vs 0.1 +/- 0.9%, p = 0.056). BP did not differ significantly. BRS correlated with average and baseline HR on both medications (r = -0.53 and -0.63, p < or = 0.03). We conclude that adrenergic responses to MST are blunted on treatment with verapamil compared to amlodipine in hypertensive patients.

Adrenergic Agents↗

PubMed2000

Prediction of in vivo metabolic clearance of 25 different petroleum hydrocarbons by a rat liver head-space technique.

In vitro rates of metabolism and Michaelis-Menten constants were determined for 25 different C6 to C10 hydrocarbons using rat liver slices in a vial head-space equilibration system. The rates of metabolism were compared with steady-state levels obtained in vivo in the same strains of rats after inhalation. Aromates were metabolized at a higher rate than naphthenes n-alkanes, isoalkanes and 1-alkenes. The aromates showed, in contrast to the other hydrocarbons investigated, increased metabolism with increasing number of carbon atoms up to C8 (o-xylene, the most extensively metabolized compound). The in vivo steady-state concentrations of the aromates in blood were inversely related to the in vitro efficiency of their metabolism. This explains the pattern of blood levels observed for the C6 to C10 aromates in the rat after inhalation, with o-xylene demonstrating the lowest concentration. In general, the extent of tissue metabolism of the investigated hydrocarbons might be of greater importance for their body distribution than their lipophilicity, especially for the highly metabolized compounds. The high in vitro intrinsic liver clearances found for the aromates indicate a flow-dependent metabolism of these hydrocarbons in vivo. The head-space liver slice equilibration system seems to work adequately for metabolic studies of hydrocarbons with different volatility and water solubility.

Animals↗

PubMed1999

Endogenous and background DNA adducts by methylating and 2-hydroxyethylating agents.

Detection of 7-alkylguanine DNA adducts is useful to assess human exposure to and the resulting DNA damage caused by simple alkylating agents. The background 7-methylguanine (7-MG) and 7-hydroxyethylguanine (7-HEG) adduct levels were determined in human and rat tissues, using thin-layer chromatography (TLC) combined with high pressure liquid chromatography (HPLC). In addition, these two adduct levels were also compared in various tissues between smokers and non-smokers. The results demonstrated that the background level of 7-alkylguanine adducts in WBC and lung tissues of non-smokers was 2.9 and 4.0 adducts/107 nucleotides, respectively. In smokers with lung cancers 7-MG adduct level in lung samples (6.3+/-1.9 adducts/107 nucleotides) and in bronchus samples (6.1+/-1.5 adducts/107 nucleotides) was significantly higher than that in WBC samples (3.3+/-0.9 adducts/107 nucleotides). 7-HEG adduct levels obtained from the same individuals were 0.8+/-0.3 in lung, 1.0+/-0.8 in bronchus and 0.6+/-0.2 adducts/107 nucleotides in WBC, respectively. Animal studies showed that background levels of 7-MG (2.1-2.5 adducts/107 nucleotides) in control rats were approximately 2-4-fold higher than 7-HEG levels (0.6-0.9 adducts/107 nucleotides). After a 3-day exposure to 300 ppm ethene, 7-HEG adducts accumulated to a similar extent in different tissues of rats, with the mean adduct level of 5.6-7.0 in liver, 7.4 in lymphocytes and 5.5 adducts/107 nucleotides in kidney.

Animals↗

PubMed1999

Comparison of (32)P-postlabeling and high-resolution GC/MS in quantifying N7-(2-Hydroxyethyl)guanine adducts.

This study compares (32)P-postlabeling and high-resolution gas chromatography/mass spectrometry (GC/MS) in the quantification of N7-(2-hydroxyethyl)guanine adducts (7-HEG) in DNA obtained from the same tissue samples of control rats and rats exposed to ethene. The samples were obtained from two independent studies. In one study, male Sprague-Dawley rats were exposed to 300 ppm ethene for 12 h/day for 3 days ("Euro samples"). In the other study, male F-344 rats were exposed to 3000 ppm ethene for 6 h/day for 5 days ("U.S. samples"). DNA from liver and kidney from the European study was isolated in the European laboratory, and DNA from liver and spleen from the U.S. study was isolated in the U.S. laboratory. The DNA samples were coded, divided into two portions, and exchanged between the two laboratories. All DNA samples from both laboratories were analyzed with respect to 7-HEG adducts by (32)P-postlabeling and high-resolution GC/MS in the European and U.S. laboratories, respectively. However, the U.S. samples were repurified in the European laboratory before the postlabeling analysis. The data from the Euro and the U.S. samples were therefore treated separately in the regression analysis of the (32)P-postlabeling versus GC/MS data. The slope of the regression line for the Euro samples was 1.19 (r = 0.97), implying that the GC/MS data were slightly lower than the postlabeling data (one possible outlier was excluded). The slope of the regression line for the U.S. samples was 0.61 (r = 0.94), implying that the GC/MS data were somewhat higher than the postlabeling data. The main conclusion from this study is that there is very good agreement between the (32)P-postlabeling and high-resolution GC/MS methods in quantifying 7-HEG adducts to DNA, particularly when identical DNA samples are analyzed and the RNA content is <2%. The paper also discusses the background levels of adducts, the interorgan distribution, comparison between different strains, and exposure conditions.

Animals↗

PubMed1999

Vagal stimulation augments maximal (penta) gastrin-stimulated acid secretion in humans.

Since the late sixties, the pentagastrin test has been the standard method to examine maximal gastric acid secretion in humans. However, studies on rats and dogs have shown that maximal pentagastrin-stimulated acid secretion can be augmented by concomitant cholinergic stimulation. The aim of this study was to examine whether the combined stimulation of the vagal nerves and pentagastrin infusion could increase maximal gastric acid secretion compared with pentagastrin alone. Eight healthy medical students (seven males) were included in the study. Gastric acid secretion was determined thrice in each subject. On day one, pentagastrin (6 microg kg(-1) h(-1)) was infused. On day two, insulin-induced hypoglycaemia (plasma glucose approximately 2.3 mM during 30 min) was obtained by applying the glucose clamp technique. On day three, pentagastrin infusion and insulin induced-hypoglycaemia were combined. The combination of insulin-induced hypoglycaemia and pentagastrin infusion increased peak acid output about 20% (P = 0.018) compared with pentagastrin alone. The hypoglycaemia did not cause significant release of gastrin. It is concluded that vagal stimulation of gastric acid secretion may be safely obtained by insulin-induced hypoglycaemia when applying the glucose clamp technique. In addition, maximal pentagastrin-stimulated acid secretion does not represent the maximal acid secretory capacity in humans.

Adult↗

PubMed1998

Mutagenicity testing of organic extracts of diesel exhaust particles after spiking with polycyclic aromatic hydrocarbons (PAH).

In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After replacing DCM with dimethylsulphoxide (DMSO), the extract was spiked with four individual PAH: benzo(a)pyrene, benzo(a)anthracene, pyrene and fluoroanthene. The PAH were added separately and in various combinations to the extract to determine the effects of each variable and to identify possible interactions between the individual PAH and between the PAH and the extract. The study was designed as a fractional factorial experiment with the five variables (the DEP extract and the four PAH), giving 16 (instead of 32) mixtures plus a triplicate centrepoint and background, i.e. a total of 20. The fractionated factorial design used in the present work supports a model with linear and interaction terms. The mixtures were tested for mutagenicity in the Ames assay using four strains of Salmonella typhimurium in the presence of rat liver xenobiotic enzymes (S9-mix). Projections to Latent Structures (PLS) was used to quantify the mutagenicity of each compound and possible interactions. The four individual PAH and the DEP extract acted additively in the Ames test with 10% S9-mix.

Anthracenes↗

PubMed1998

Arterial and venous plasma catecholamines during submaximal steady-state exercise.

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0.81, 95% CI 0.71-0.87), as were systolic blood pressure and heart rate (r = 0.78, 95% CI 0.71-0.87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.

Adult↗

PubMed1998

In vitro screening for metabolic interactions among frequently occurring binary mixtures of volatile organic chemicals in Norwegian occupational atmosphere.

Surveys of Norwegian industrial occupational atmosphere between 1983 to 1996, have identified the 12 most frequent occurring binary combinations of volatile organic chemicals. These combinations were tested in vitro for mutual inhibition or enhancement of metabolism by the head space vial equilibration technique with liver S9 obtained from in vivo untreated or pretreated (with the binary mixture) rats. The in vitro system responded to in vivo pretreatment by increasing the metabolic rate of several potentially toxic organic chemicals such as toluene, xylene, styrene, and dichloromethane. In untreated liver S9, the metabolism of several of the tested binary pairs was inhibited when coexposed in vitro to their most prevalent follower as shown for instance for ethanol (with ethyl acetate), dichloromethane (with styrene) and mutually between toluene and xylene. This inhibitory effect disappeared, however, for several of the solvents when combined with the in vivo induced liver S9, a situation which may be the most relevant for occupational exposure. It is concluded that several metabolic interactions occur between low-molecular weight volatile chemicals found in occupational air. These are both inductive and inhibitory in nature and a further mechanistic evaluation including a higher number of differentiated dosage levels, must be performed before a possible health hazard can be confirmed or rejected for the investigated combinations.

Air Pollutants, Occupational↗

PubMed1998

Mixture design and multivariate analysis in mixture research.

Mixture design has been used to identify possible interactions between mutagens in a mixture. In this paper the use of mixture design in multidimensional isobolographic studies is introduced. Mutagenicity of individual nitro-polycyclic aromatic hydrocarbons (PAH) was evaluated is an organic extract of diesel exhaust particles (DEPs). The particles were extracted with dichloromethane (DCM). After replacing DCM with dimethyl sulfoxide, the extract was spiked with three individual nitro-PAH: 1-nitropyrene, 2-nitrofluorene, and 1,8-dinitropyrene. The nitro-PAH were added separately and in various combinations to the extract to determine the effects of each variable and to identify possible interactions between the individual nitro-PAH and between the nitro-PAH and the extract. The composition of the mixtures was determined by mixture design (linear axial normal) with four variables (the DEP extract and the three nitro-PAH, giving 8 different mixtures plus a triplicate centerpoint, i.e., a total of 11. The design supports a model with linear and interaction (product) terms. Two different approaches were used: traditional mixture design within a well-defined range on the linear part of the dose-response curves and an isobolographic mixture design with equipotent doses of each variable. The mixtures were tested for mutagenicity in the Ames assay using the TA98 strain of Salmonella typhimurium. The data were analyzed with projections to latent structures (PLS). The three individual nitro-PAH and the DEP extract acted additively in the Ames test. The use of mixture design either within a well-defined range of the linear part on the dose-response curve or with equipotent doses saves experiments and reduces the possibility of false interaction terms in situations with dose additivity or response additivity.

Animals↗

PubMed1997

The adjuvant activity of diesel exhaust particles and carbon black on systemic IgE production to ovalbumin in mice after intranasal instillation.

The adjuvant activity of diesel exhaust particles (DEP) on systemic IgE production to ovalbumin (OA) was studied in mice after intranasal administration. The main purpose was to elucidate which part of the particles was responsible for the effect, the carbon core and/or the adsorbed organic substances. Female Balb/cA mice were immunized with OA either alone or in combination with DEP or carbon black particles (CB), the latter used as a surrogate for the non-extractable carbon core of DEP. Controls were given DEP, CB or buffer alone. The animals were immunized four times. 1 and 2 weeks after the last immunization anti OA IgE antibody in serum was analysed by enzyme linked immunosorbent assay (ELISA). An increased response to the antigen was observed in animals receiving OA together with DEP or CB, compared with animals receiving OA alone. The increased response was seen as both increased number of responding animals and increased serum anti OA IgE antibody. For OA + DEP 37% of the animals showed a serum anti OA IgE response, whereas 22% of the OA + CB animals and 10% of the OA animals responded. In conclusion, this work shows that not only DEP, but also CB have an adjuvant activity for specific IgE production after intranasal instillation. However, the activity of DEP may be more pronounced than that of CB. The results imply that both the organic matter adsorbed to DEP and the non-extractable carbon core are responsible for the observed adjuvant effect.

Adjuvants, Immunologic↗

PubMed1997

Diesel exhaust particles and carbon black have adjuvant activity on the local lymph node response and systemic IgE production to ovalbumin.

The possible adjuvant effect of diesel exhaust particles (DEP) on the response to the model allergen ovalbumin (OA) was studied in BALB/c mice using the popliteal lymph node (PLN) assay. In addition to changes in PLN weight, cell numbers and cell proliferation, specific serum IgE anti-OA antibody levels were measured. OA inoculated together with DEP into one hind footpad gave a significantly augmented response (increase in weight, cell numbers and cell proliferation) in the draining popliteal lymph node as compared to DEP or OA alone. Also, the local lymph node response was of longer duration when DEP were given with the allergen. Experiments in thymus-deficient nu/nu mice indicated that the lymph node response observed in BALB/c mice was of a specific immunologic character and not an unspecific inflammatory reaction. The OA-specific IgE response was increased in mice receiving OA together with DEP as compared to the response in mice receiving OA without DEP. Carbon black (CB) was given with and without OA in some experiments, as a surrogate for the non-extractable core of DEP. CB was found to resemble DEP in its capacity to increase the local lymph node response and serum specific IgE response to OA, but CB appeared to be slightly less potent than DEP. Thus, both DEP and CB had a significant adjuvant effect on the local immune-mediated inflammatory response and on the systemic specific IgE response to allergen. The results indicate that the non-extractable particle core contributes substantially to the adjuvant activity of DEP.

Adjuvants, Immunologic↗

PubMed1997

Mutagenicity testing of organic extracts of diesel exhaust particles after fractionation and recombination.

A new strategy for the evaluation of mixtures is presented. The mixture used was the organic extract of diesel exhaust particles (DEP). After extraction with dichloromethane (DCM), the crude extract was fractionated according to polarity into five fractions: aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, dinitro-PAHs, and polar compounds. After dissolving in dimethylsulphoxide (DMSO), the three fractions containing the primary mutagens (fractions 3-5) were recombined in different combinations to create new extracts. The blend matrix was obtained using a mixture design at three dose levels to support an empirical model with linear, interaction, and quadratic terms (Taylor polynome). The recombined extracts were tested in the Ames Salmonella assay using strain TA100. Multivariate data analysis was performed with projections to latent structures (PLS). The best model describing the relation between the mutagenicity (response) and the three fractions (variables) contained two interaction terms. The model showed high correlation (r2) and prediction properties (Q2), the latter obtained after cross validation. Interaction terms are only indications of possible synergism or antagonism and have to be evaluated with respect to dose-additivity and response-additivity. The incorporation of dose in the design reduced the number of samples (recombined extracts) significantly, compared to determining dose-response curves on each sample (i.e. the recombined extracts in different dilutions). Furthermore, instead of running two independent experiments as required in the standard procedure for the Ames test, predictions and verifications of a few new samples were used. The principle of fractionation and recombination, and the use of mixture design may in principle be extended to an unlimited number of variables. An adaptation of mixture design to the isobole method is discussed.

Hydrocarbons↗

PubMed1996

Inhalation experiments with mixtures of hydrocarbons. Experimental design, statistics and interpretation of kinetics and possible interactions.

The paper describes experimental and statistical methods for toxicokinetic evaluation of mixtures in inhalation experiments. Synthetic mixtures of three C9 n-paraffinic, naphthenic and aromatic hydrocarbons (n-nonane, trimethylcyclohexane and trimethylbenzene, respectively) were studied in the rat after inhalation for 12h. The hydrocarbons were mixed according to principles for statistical experimental design using mixture design at four vapour levels (75, 150, 300 and 450 ppm) to support an empirical model with linear, interaction and quadratic terms (Taylor polynome). Immediately after exposure, concentrations of hydrocarbons were measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat. Multivariate data analysis and modelling were performed with PLS (projections to latent structures). The best models were obtained after removing all interaction terms, suggesting that there were no interactions between the hydrocarbons with respect to absorption and distribution. Uptake of paraffins and particularly aromatics is best described by quadratic models, whereas the uptake of the naphthenic hydrocarbons is nearly linear. All models are good, with high correlation (r2) and prediction properties (Q2), the latter after cross validation. The concentrations of aromates in blood were high compared to the other hydrocarbons. At concentrations below 250 ppm, the naphthene reached higher concentrations in the brain compared to the paraffin and the aromate. Statistical experimental design, multivariate data analysis and modelling have proved useful for the evaluation of synthetic mixtures. The principles may also be used in the design of liquid mixtures, which may be evaporated partially or completely.

Adipose Tissue↗

PubMed1996

Marked increase in gastric acid secretory capacity after omeprazole treatment.

BACKGROUND: In contrast with the histamine2 (H2) blockers, proton pump inhibitors have not been shown to give rebound hypersecretion of acid. Taking into consideration the hyperplasia of the enterochromaffin-like (ECL) cell provoked by hypergastrinaemia secondary to profound acid inhibition and the central role of histamine from ECL cells in the regulation of acid secretion, the lack of any rebound acid hypersecretion after treatment with proton pump inhibitors has been questioned. AIMS: To reassess the effect of treatment with omeprazole on post-treatment acid secretion. METHODS AND PATIENTS: Basal and pentagastrin stimulated acid secretion were determined in nine patients with reflux oesophagitis before and 14 days after termination of a 90 day treatment period with the proton pump inhibitor omeprazole (40 mg daily). Basal gastrin release were determined before and during omeprazole treatment. Furthermore, biopsy samples from the oxyntic mucosa were taken before and at the end of the treatment period for chemical (histamine and chromogranin A (CgA)) evaluation of the ECL cell mass. RESULTS: A substantial increase in meal stimulated gastrin release during omeprazole treatment resulted in an increased ECL cell mass. Furthermore, CgA in serum increased during omeprazole treatment suggesting that serum CgA may be used as a test to evaluate ECL cell hyperplasia. A significant increase in basal and a marked (50%) and significant increase in pentagastrin stimulated acid secretion were found after treatment with omeprazole. CONCLUSIONS: Increased acid secretion after a conventional treatment period with a proton pump inhibitor is probably due to ECL cell hyperplasia and may have negative consequences for acid related diseases.

Adult↗