Anionic linear aliphatic surfactants activate TRPV1: a possible endpoint for estimation of detergent induced eye nociception?

The transient receptor potential vanilloid type 1 (TRPV1) has been reported as one of the key components in the pain pathway. Activation of the receptor causes a Ca(2+) influx in sensory C-fibres with secondary effects leading to neurogenic inflammation in the surrounding tissue. We have earlier reported specific activation of TRPV1 by surfactant-containing hygiene products. We have continued this project by investigating activation of the TRPV1 by shampoo and soap ingredients in low concentrations measured as intracellular Ca(2+) influxes in stably TRPV1-expressing neuroblastoma SH-SY5Y cells. As a TRPV1 specific control, the TRPV1 antagonist capsazepine was used. The response was quantified as the product induced Ca(2+) influx during 2 min in relation to the maximum response induced by the TRPV1 agonist capsaicin. The results show that anionic alkyl linear surfactant ingredients such as sodium lauryl sulphate, sodium laureth sulphate, ammonium lauryl sulphate, sodium C12-15 pareth sulphate and N-lauroylsarcosine concentration-dependently induced Ca(2+) influx that could be addressed to TRPV1. The cationic surfactants benzalkonium chloride and cetylpyridinium chloride induced a Ca(2+) influx that was not TRPV1 mediated as well as the zwitterionic surfactant cocamidopropyl betaine, the non-linear anionic surfactant sodium deoxycholate and the non-ionic surfactant Triton-X. These results reveal a new mechanistic pathway for surfactant-induced nociception.

Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4.

Case reports suggest that cranberry juice can increase the anticoagulant effect of warfarin. We investigated the effects of cranberry juice on R-S-warfarin, tizanidine, and midazolam; probes of CYP2C9, CYP1A2, and CYP3A4. Ten healthy volunteers took 200 ml cranberry juice or water t.i.d. for 10 days. On day 5, they ingested 10 mg racemic R-S-warfarin, 1 mg tizanidine, and 0.5 mg midazolam, with juice or water, followed by monitoring of drug concentrations and thromboplastin time. Cranberry juice did not increase the peak plasma concentration or area under concentration-time curve (AUC) of the probe drugs or their metabolites, but slightly decreased (7%; P=0.051) the AUC of S-warfarin. Cranberry juice did not change the anticoagulant effect of warfarin. Daily ingestion of cranberry juice does not inhibit the activities of CYP2C9, CYP1A2, or CYP3A4. A pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely.

Effects of orange juice on the pharmacokinetics of atenolol.

OBJECTIVE: Fruit juices can significantly change the pharmacokinetics of several drugs. Our objective was to investigate the effect of orange juice on the pharmacokinetics of the beta-blocking agent atenolol. METHODS: In a randomized cross-over study with two phases and a washout of 2 weeks, ten healthy volunteers took either 200 ml orange juice or water thrice daily for 3 days and twice on the fourth day. On the morning of day 3, each subject ingested 50 mg atenolol with an additional amount of either 200 ml orange juice or water. The plasma concentrations of atenolol and the cumulative excretion of atenolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 h after. RESULTS: Orange juice decreased the mean peak plasma concentration (C(max)) of atenolol by 49% (range 16-59%, P<0.01), and the mean area under the plasma atenolol concentration-time curve (AUC(0-33 h)) by 40% (range 25-55%, P<0.01). The time of the peak concentration (t(max)) and the elimination half-life (t(1/2)) of atenolol remained unchanged by orange juice. The amount of atenolol excreted into urine was decreased by 38% (range 17-60%, P<0.01), but the renal clearance remained unaltered. The average heart rate was slightly higher during the orange juice+atenolol phase than during the water+atenolol phase. CONCLUSIONS: Orange juice moderately interferes with the gastrointestinal absorption of atenolol. This food-drug interaction can be of clinical significance.

Rifampicin reduces plasma concentrations of celiprolol.

OBJECTIVE: The beta-adrenoceptor-blocking agent celiprolol undergoes negligible metabolism, but is a substrate for P-glycoprotein. Our objective was to investigate the effects of rifampicin on the pharmacokinetics of celiprolol in healthy subjects. METHODS: In a randomized cross-over study with two phases and a washout of 4 weeks, ten healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 200-mg dose of celiprolol was administered orally. The plasma concentrations of celiprolol and the excretion of celiprolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the administration of celiprolol and 2, 4, 6, and 10 h later. MDR1 (P-glycoprotein) genotype was assessed with respect to polymorphisms in exon 21 (G2677T/A) and in exon 26 (C3435T). RESULTS: Rifampicin pretreatment reduced the median area under the plasma celiprolol concentration-time curve AUC(0-33 h) to 0.44-fold [90% confidence interval (CI), 0.27-0.86], relative to the placebo. The median peak plasma concentration, the time of peak concentration, and the elimination half-life of celiprolol were not significantly changed by rifampicin. During the rifampicin phase, the median amount of celiprolol excreted into urine was decreased by 47% ( P<0.05) and celiprolol renal clearance increased by 19% ( P<0.05) compared with the placebo phase. There were great inter-individual differences in the extent of rifampicin-celiprolol interaction. However, no association was found between the MDR1 polymorphisms and the degree of interaction between rifampicin and celiprolol. No significant differences were observed in hemodynamic parameters between the phases. CONCLUSION: Rifampicin pretreatment reduces plasma celiprolol concentrations, possibly by induction of the efflux transporter P-glycoprotein, particularly in the intestinal wall, which leads to decreased absorption of celiprolol.

Introduction: the need for a multidimensional and multidisciplinary approach.

This special issue combines contributions from several disciplines within the social sciences on how to understand long-term use or dependency on various kinds of psychotropics. It emphasizes the need for a multidisciplinary approach in order to understand the complexity of such long-term use. The papers in this issue will base their arguments on psychological, sociological, anthropological, clinical, and social pharmacy perspectives. Different disciplines focus specially on certain topics. For example, psychology can help us to understand what kind of mental processes that are involved in the development of long-term tranquillizer use. Sociology, anthropology and social pharmacy have a particular contribution to make in helping us, in different ways, to understand the social meanings of psychotropic drug use.

Evaluation of programs for the treatment of benzodiazepine dependency.

Programs for the treatment of benzodiazepine dependency differ in a number of ways. Their outcome goals, for example, vary. In some of the programs the reduction or the elimination of benzodiazepine use is the main objective. In others a reduction in anxiety and depression among patients is regarded as much more important than decreasing benzodiazepine use. These differences in goals make comparative evaluations difficult. Further, the type of clients recruited to the programs are often dissimilar. However, it is still possible and valuable to make comparative evaluations of the numerous programs. The aims of published evaluations differ. Most evaluations are directed towards outcome data. Only in a few studies has the aim been to analyze the dynamic treatment process. To achieve more reliable and valid evaluations it is necessary to get data which describe the process and the results from both the clients' and the therapists' perspectives and combining different research strategies.

Identity, cognitive structure, and long-term tranquillizer use: a multidimensional approach.

The article discusses different theoretical perspectives that are relevant in analysing long-term tranquillizer use. The theories mentioned are, e.g., behavioral theory models, cognitive models, humanistic and existential models, transpersonal identity models, psychodynamic reasoning, sociological and anthropological perspectives. A multidimensional model focusing on the connection between identity structure and long-term tranquillizer use is presented. The article argues for the use of mixed methodological strategies, e.g., quantitative and qualitative methods. The implications of the 'actor-spectator paradox" for the analysis of data are also discussed in some detail.

Toward an integrative approach in the analysis of dependency problems.

This article takes some preliminary steps towards an integrated analysis of dependency problems e.g., long-term tranquillizer use, alcohol dependence, problematic use of narcotics. It argues for the need to outline important theoretical, epistemological, and methodological prerequisites in the analysis of the complex dynamic developmental processes involved in dependency problems. The dynamic process leading to dependence can be studied by the aid of an artificial science neural network approach in combination with a mixed method strategy including a clarification of a combination of different epistemological positions. It is intended that the empirical output of this complex strategy will provide a starting point for a new theoretical analysis which, in turn, will lead to new and more relevant input variables in the neural network approach that will help us to extend our knowledge of the dynamic processes leading to dependency.

Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice.

AIMS: To determine whether the pharmacokinetics of cisapride and its interaction with grapefruit juice are stereoselective. METHODS: The study was a randomized, two-phase cross over design with a washout period of 2 weeks. Ten healthy volunteers were pretreated with either water or 200 ml double strength grapefruit juice three times a day for 2 days. On the 3rd each subject ingested a single 10 mg dose of rac-cisapride tablet. Double strength grapefruit juice (200 ml) or water was administered during cisapride dosing and 0.5 and 1.5 h thereafter. Blood samples were collected before and for 32 h after cisapride administration. Plasma concentrations of cisapride enantiomers were measured by a chiral h.p.l.c. method. A standard 12-lead ECG was recorded before cisapride administration (baseline) and 2, 5, 8, and 12 h later. RESULTS: This study showed that cisapride pharmacokinetics are stereoselective. In control (water treated) subjects, the mean Cmax (30 +/- 13.6 ng ml-1; P = 0.0008) and AUC(0, infinity) (201 +/- 161 ng ml-1 h; P = 0.029) of (-)-cisapride were significantly higher than the Cmax (10.5 +/- 3.4 ng ml-1) and AUC(0, infinity) (70 +/- 51.5 ng ml-1 h) of (+)-cisapride. There was no marked difference in elimination half-life between (-)-cisapride (4.7 +/- 2.7 h) and (+)-cisapride (4.8 +/- 3 h). Compared with the water treated group, grapefruit juice significantly increased the mean Cmax of (-)-cisapride from 30 +/- 13.6-55.5 +/- 18 ng ml-1 (95% CI on mean difference, -33, -17; P = 0.00005) and of (+)-cisapride from 10.5 +/- 3.4 to 18.4 +/- 6.2 ng ml-1 (95% CI on mean difference, -11.8, -3.9, P = 0.00015). The mean AUC(0, infinity) of (-)-cisapride was increased from 201 +/- 161 to 521.6 +/- 303 ng ml-1 h (95% CI on mean difference, -439, -202; P = 0.0002) and that of (+)-cisapride from 70 +/- 51.5 to 170 +/- 91 ng ml-1 h (95% CI on mean difference, -143, -53; P = 0.0005). The tmax was also significantly increased for both enantiomers (from 1.35 to 2.8 h for (-)-cisapride and from 1.75 to 2.9 h for (+)-cisapride in the control and grapefruit juice group, respectively; P < 0.05). The t(1/2) of (-)-cisapride was significantly increased by grapefruit juice, while this change did not reach significant level for (+)-cisapride. The proportion of pharmacokinetic changes brought about by grapefruit juice was similar for both enantiomers, suggesting non-stereoselective interaction. We found no significant difference in mean QTc intervals between the water and grapefruit juice treated groups. CONCLUSIONS: The pharmacokinetics of cisapride is stereoselective. Grapefruit juice elevates plasma concentrations of both (-)- and (+)-cisapride, probably through inhibition of CYP3A in the intestine. At present, there are no data on whether the enantiomers exhibit stereoselective pharmacodynamic actions. If they do, determination of plasma concentrations of the individual enantiomers as opposed to those of racemic cisapride may better predict the degree of drug interaction, cardiac safety and prokinetic efficacy of cisapride.

Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.

The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.

Tibia as donor site for alveolar bone grafting in patients with cleft lip and palate: long-term experience.

Tibial bone grafts were studied in 137 patients with clefts of the lip and palate. Twenty-one had clefts of the lip and primary palate and 116 had complete unilateral clefts of the lip and palate. Bone grafting was performed secondarily or late secondarily. Bone was harvested from the proximal part of the tibia distal to the tuberosity through an incision about 15 mm long. The mean follow-up time after bone grafting was 5.5 years (range 2-11). There were no operative, or early or late postoperative complications reported (such as haematoma, fracture, or shortening of the limb). Harvesting time was about 15 minutes. The possibility of operating with two teams makes the total operating time shorter. Bleeding was negligible (less than 15 ml) and the amount of bone obtained was always sufficient. Patients were mobilised the next day and were back to full physical activity by one month. Indications for tibial bone grafting included facilitation of tooth eruption into the graft, giving bony support to the neighbouring teeth, making it possible to insert a titanium fixture, raising the alar base of the nose, and closing an oronasal fistula. Compared with iliac, cranial, mandibular, and costal donor sites, using the tibia took less time, gave less bleeding, made it possible for two teams to operate simultaneously, gave a smaller scar, and there were minimal complications and satisfactory quantity and quality of bone in all cases. The results suggested that the tibia is an excellent choice of graft for residual alveolar clefts in patients with cleft lip and palate.

Maxillary development and dental occlusion in patients with unilateral cleft lip and palate after combined velar closure and lip-nose repair at different ages.

Maxillary morphology and occlusal development were studied after simultaneous velar closure and lip/nose reconstruction in patients with unilateral cleft lip and palate. Fifty-two Brazilian patients were divided into three groups according to the age at which they had had the one-stage operation (mean ages: 8, 18, and 77.5 months). They were compared with 30 similar white patients who had been operated on with a corresponding method, but where surgery had been carried out in three different stages. In general, differences in outcome between the groups were attributed to racial differences in facial morphology. The combined operation did not affect the transverse development or the overall occlusion and only slightly influenced the morphology of the maxillary incisor region. The palatal cleft width reduced significantly (p < 0.001) after the combined procedure. However, the potential for this reduction seemed to be less when patients were operated on after their first year of life.

Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin.

BACKGROUND: Grapefruit juice is a potent inhibitor of CYP3A4-mediated drug metabolism. We wanted to investigate how long the inhibitory effect of grapefruit juice lasts, with the CYP3A4 substrate simvastatin used as a model drug. METHODS: This crossover study consisted of 5 study days, during which 10 healthy volunteers ingested 40 mg simvastatin with water (control), with "high-dose" grapefruit juice (200 mL double-strength grapefruit juice three times a day for 3 days), or 1, 3, and 7 days after ingestion of "high-dose" grapefruit juice. For safety reasons, the study was performed in three parts to allow simvastatin-free days between the study days. Serum concentrations of simvastatin and simvastatin acid were measured by liquid chromatography-tandem mass spectrometry up to 12 hours. RESULTS: When simvastatin was taken with grapefruit juice, the mean peak serum concentration (Cmax) and the mean area under the serum concentration-time curve [AUC(0-infinity)] of simvastatin were increased 12.0-fold (P < .001) and 13.5-fold (P < .001), respectively, compared with control. When simvastatin was administered 24 hours after ingestion of the last dose of grapefruit juice, the Cmax and AUC(0-infinity) were increased 2.4-fold (P < .01) and 2.1-fold (P < .001), respectively, compared with control. When simvastatin was given 3 days after ingestion of grapefruit juice, the Cmax and AUC(0-infinity) were increased 1.5-fold (P = .12) and 1.4-fold (P = .09), respectively, compared with control. Seven days after ingestion of grapefruit juice, no differences in the Cmax or AUC(0-infinity) of simvastatin were seen. The mean Cmax and AUC(0-infinity) of simvastatin acid were increased 5.0-fold and 4.5-fold, respectively (P < .001), compared with control when simvastatin was taken with grapefruit juice and 1.7-fold (P < .01) when it was taken 24 hours after ingestion of grapefruit juice. After an interval of 3 or 7 days between ingestion of grapefruit juice and simvastatin, the pharmacokinetic variables of simvastatin acid did not differ significantly from those in the control phase. CONCLUSIONS: When simvastatin is taken 24 hours after ingestion of "high-dose" grapefruit juice, the effect of grapefruit juice on the AUC of simvastatin is only about 10% of the effect observed during concomitant intake of grapefruit juice and simvastatin. The interaction potential of even high amounts of grapefruit juice with CYP3A4 substrates dissipates within 3 to 7 days after ingestion of the last dose of grapefruit juice.

Effect of grapefruit juice dose on grapefruit juice-triazolam interaction: repeated consumption prolongs triazolam half-life.

OBJECTIVE: Grapefruit juice inhibits CYP3A4-mediated metabolism of several drugs during first pass. In this study, the effect of grapefruit juice dose on the extent of grapefruit juice-triazolam interaction was investigated. METHODS: In a randomised, four-phase, crossover study, 12 healthy volunteers received 0.25 mg triazolam with water, with 200 ml normal-strength or double-strength grapefruit juice or, on the third day of multiple-dose [three times daily (t.i.d.)] administration of double-strength grapefruit juice. Timed blood samples were collected up to 23 h after dosing, and the effects of triazolam were measured with four psychomotor tests up to 10 h after dosing. RESULTS: The area under the plasma triazolam concentration time curve (AUC(0-infinity)) was increased by 53% (P < 0.01), 49% (P < 0.01) and 143% (P < 0.001) by a single dose of normal-strength, a single dose of double-strength and multiple-dose administration of double-strength grapefruit juice, respectively. The peak plasma concentration (Cmax) of triazolam was increased by about 40% by a single dose of normal-strength grapefruit juice (P < 0.01) and multiple-dose grapefruit juice (P < 0.01) and by 25% by a single dose of double-strength grapefruit juice (P < 0.05). The elimination half-life (t(1/2)) of triazolam was prolonged by 54% during the multiple-dose grapefruit juice phase (P < 0.001). A significant increase in the pharmacodynamic effects of triazolam was seen during the multiple-dose grapefruit juice phase in the digit symbol substitution test (DSST, P < 0.05), in subjective overall drug effect (P < 0.05) and in subjective drowsiness (P < 0.05). CONCLUSIONS: Even one glass of grapefruit juice increases plasma triazolam concentrations, but repeated consumption of grapefruit juice produces a significantly greater increase in triazolam concentrations than one glass of juice. The t(1/2) of triazolam is prolonged by repeated consumption of grapefruit juice, probably due to inhibition of hepatic CYP3A4 activity.

Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells.

We examined whether the persistent activation of AKT or Stat3 oncogene product is present in prostate, breast, and cervical cancer cells. We found that some prostate and breast cancer cell lines express high levels of phosphorylated AKT. Interestingly, the cancer cells, which only express low levels of phosphorylated AKT express high levels of phosphorylated Stat3. AKT or Stat3 is also highly phosphorylated in human papilloma virus-negative cervical cancer cells. Therefore, these results indicate that AKT and Stat3 are highly phosphorylated in some breast, prostate and cervical cancer cells, which may play a role in tumorigenesis of these cancers.

Combined bone grafting and delayed closure of the hard palate in patients with unilateral cleft lip and palate: facilitation of lateral incisor eruption and evaluation of indicators for timing of the procedure.

OBJECTIVE: To compare outcomes of bone grafting performed before eruption of the lateral incisor to outcomes of grafting performed before eruption of the canine and to evaluate the long-term results of bone grafting combined with delayed closure of the hard palate during mixed dentition. DESIGN: Seventy consecutive patients (52 men and 18 women) with complete unilateral cleft lip and palate were studied. All patients underwent bone grafting with simultaneous closure of the cleft in the hard palate at the stage of mixed dentition. The velum had been repaired in infancy. Mean age for the bone grafting procedure was 8.4 years. Bone grafting was performed to facilitate eruption of the lateral incisor in 43 (61%) of the patients and to facilitate eruption of the canine in the remaining 27 (39%) patients. Intraoral radiographs were used to evaluate the morphologic characteristics of the cleft and the stage of eruption of the permanent lateral incisor and canine before bone grafting. Mean follow-up time was 4.0 years (range, 1-10.1 years). RESULTS: The mean time for the surgery, which included bone grafting and repair of the residual cleft in the hard palate, was 109 minutes, and the mean amount of bleeding was 121 ml. The rate of dehiscence in the flap covering the alveolar bone graft was 14%, and the rate of total failure of bone grafting was 3%. An oronasal fistula developed in the hard palate of 13% of patients, but the fistula was of sufficient size to serve as an indication for reoperation in only 6%. The postoperative alveolar bony height in the cleft area was more than 75% of the normal height in 94% of patients. Closure of the cleft space in the dental arch was performed or planned to be achieved orthodontically in 91% of patients. When bone grafting was performed to facilitate eruption of the lateral incisor, the cleft space was closed orthodontically in 100% of patients. The optimal indicator for timing of the bone grafting procedure from an orthodontic point of view was when the permanent lateral incisor or the canine close to the cleft was covered by a thin shell of bone (i.e., 7-9 years of age).

Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride.

BACKGROUND: Grapefruit juice increases the bioavailability of several drugs that are metabolized during first pass by CYP3A4. In this study, the effect of grapefruit juice on the pharmacokinetics of orally administered cisapride was investigated. METHODS: In a randomized, two-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water three times a day for 2 days. On day 3, each subject ingested 10 mg cisapride with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours after cisapride administration. Timed blood samples were collected for 32 hours after cisapride intake, and a standard 12-lead ECG was recorded before the administration of cisapride and 2, 5, 8, and 12 hours later. RESULTS: The mean peak plasma concentration of cisapride was increased by 81% (range, 38% to 138%; P < .01) and the total area under the plasma cisapride concentration-time curve by 144% (range, 65% to 244%; P < .01) by grapefruit juice. The time of the peak concentration of cisapride was prolonged from 1.5 to 2.5 hours (P < .05) and the elimination half-life from 6.8 to 8.4 hours (P < .05) by grapefruit juice. ECG tracings did not show any significant differences in the QTc interval between the grapefruit juice and control phases. CONCLUSIONS: Grapefruit juice significantly increases plasma concentrations of cisapride, probably by inhibition of the CYP3A4-mediated first-pass metabolism of cisapride in the small intestine. Concomitant use of high amounts of grapefruit juice and cisapride should be avoided, at least in patients with risk factors for cardiac arrhythmia.

Dietary habits affect the susceptibility of low-density lipoprotein to oxidation.

OBJECTIVE: To study, if there are differences in the fatty acid composition of low-density lipoprotein (LDL) in people eating three different long-standing habitual diets: vegetarian, high fish intake, or high saturated fat (milk fat) diet as a control group, and to study if these differences influence the oxidation susceptibility of LDL. DESIGN: Cross-sectional study using blood samples and a validated dietary frequency questionnaire with illustrations. SETTING: Helsinki University Central Hospital, Finland. SUBJECTS: The effect of three different types of long-standing diets of different fatty acid content (a strict vegetarian diet, n=11; a high fish intake diet, n=9; and a high saturated fat (milk fat) diet, controls, n=7) on the serum and LDL fatty acid content, and on the susceptibility of LDL to oxidation in vitro, was studied in healthy normocholesterolemic volunteers who had been on these diets for years. Oxidation of LDL was carried out by using CuSO4 as a pro-oxidant. RESULTS: There were no statistically significant differences in the serum lipids or lipoproteins, though the vegetarian group exhibited lowest mean values of total, high-density lipoprotein (HDL) and LDL cholesterol levels. Both the serum and LDL eicosapentaenoic, docosapentaenoic and docosahexaenoic acid proportions were highest in the fish and lowest in the vegetarian groups. Linoleic acid was highest among the vegetarians. In the fish group, the vitamin A concentration in serum was higher than in vegetarians and controls and beta-carotene lower than in controls, but in alpha-tocopherol, or lycopene concentrations there were no statistically significant differences. The lag phase of LDL oxidation was shortest (116 min) in the fish group and longest (165 min) in the vegetarian group, and the control group was between them (129 min). The mean oxidation percentage after 2.5 h of copper-induced oxidation was highest (44%) in the fish group and lowest (22%) in the vegetarian group and intermediate (31%) in the control group. CONCLUSION: Long-term dietary habits predict the fatty acid composition of serum and LDL, and influence the susceptibility of LDL to oxidation. In the fish group with the highest content of omega-3 fatty acids in LDL, the oxidation susceptibility of LDL was highest. In the vegetarian group with less omega-3 fatty acids in LDL, the LDL was more resistant to oxidation. SPONSORSHIP: Helsinki University Central Hospital.