INNOVATIONS IN FOCUS: MECHANISTIC DISEASE THEORIES, CLIMATE DYNAMICS, AND HOST-PARASITE ADAPTATIONS.

Infectious illnesses are predicted to experience a range of intricate responses from climate change, with some likely to rise, others to fall and many expected to undergo changes in prevalence. The study uses extensive data on global temperature variations and infectious illness transmission in people and animals. We now know a lot more about how the temperature changes across the world and whether or not the spread of infectious diseases impacts people as well as animals. Three primary topics of research are investigated in this paper: improving mechanical disease modelling, investigating the role of environmental variation in sickness dynamics, and understanding the consequences of temperature imbalances between parasites and hosts. By incorporating the latest data stemming from these advancements into weather-disease models and bridging critical knowledge gaps, enhancing our ability to forecast the probable effect of rising temperatures on the prevalence of diseases among both human and animal communities is possible. Through the establishment of important information gaps and the incorporation of new findings into models of climate-disease relationships, it will be possible to predict the effects of changes in climatic averages, variations and extremes on people and wildlife health.

Neonatal immune challenge followed by adult immune challenge induces epigenetic-susceptibility to aggravated visceral hypersensitivity.

BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD. We investigated the hypothesis that neonatal colon immune challenge followed by an adult colon immune challenge upregulates spinal cord BDNF that aggravates visceral sensitivity over and above that induced by adult colon immune challenge alone. METHODS: We induced neonatal and adult colon immune challenges by intraluminal administration of trinitrobenzene sulfonic acid to the rat colon. KEY RESULTS: We found that neonatal immune challenge triggers epigenetic programming that upregulates tyrosine hydroxylase in the locus ceruleus when these rats are subjected to an adult colon immune challenge. The upregulation of locus ceruleus tyrosine hydroxylase, upregulates norepinephrine in the cerebrospinal fluid that acts on adrenergic receptors to enhance pCREB binding to the cAMP response element, which recruits histone acetylene transferase (HAT) to the BDNF gene to enhance its transcription resulting in aggravated visceromotor response to colorectal distension. HAT and adrenergic receptor antagonists block the aggravation of visceral sensitivity. CONCLUSION & INFERENCES: HAT and adrenergic receptor inhibitors may serve as alternates to opioids and NSAIDS in suppressing abdominal pain in IBD.

Costs of diabetes medication among male former elite athletes in later life.

AIMS: Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. METHODS: The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. RESULTS: The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 € [95% CI 33-151 €]) and mixed group athletes (mean 272 € [95% CI 181-388 €]) compared with the controls (mean 376 € [95% CI 284-485 €]), (p < 0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). CONCLUSIONS: A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.

Mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years.

The aim of this cross-sectional study was to compare mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years (n = 150; 50 men in both former elite athlete groups and in their control group). Agility, dynamic balance, walking speed, chair stand, self-rated balance confidence (ABC-scale), jumping height, and handgrip strength were assessed. Former elite power athletes had better agility performance time than the controls (age- and body mass index, BMI-adjusted mean difference -3.6 s; 95% CI -6.3, -0.8). Adjustment for current leisure time physical activity (LTPA) and prevalence of diseases made this difference non-significant (P = 0.214). The subjects in the power sports group jumped higher than the men in the control group (age- and BMI-adjusted mean differences for vertical squat jump, VSJ 4.4 cm; 95% CI 2.0, 6.8; for countermovement jump, CMJ 4.0 cm; 95% CI 1.7, 6.4). Taking current LTPA and chronic diseases for adjusting process did not improve explorative power of the model. No significant differences between the groups were found in the performances evaluating dynamic balance, walking speed, chair stand, ABC-scale, or handgrip strength. In conclusion, power athletes among the aged former elite sportsmen had greater explosive force production in their lower extremities than the men in the control group.

Former male elite athletes have better metabolic health in late life than their controls.

Elite-class athletes have longer life expectancy and lower risk for chronic noncommunicable diseases possibly because of physically active and healthier lifestyle. In this study, we assessed former male Finnish elite-class athletes' (n = 392) and their matched controls' (n = 207) body composition, and risk for the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later life. Compared with the controls, the former athletes had lower body fat percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88). High volume of current leisure-time physical activity (LTPA) was associated with lower body fat percentage (P for trend < 0.001). When current volume of LTPA increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98-0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite-class athlete during young adulthood may help to protect from developing metabolic syndrome, present exercise levels and volume of LTPA seem equally important as well.

Cardiovascular health in former elite male athletes.

To increase our knowledge on the effects of previous and current physical activity on cardiovascular health, we studied a group of Finnish male former elite athletes (endurance, n = 49; power, n = 50) and their 49 age and area-matched controls, aged 64-89 years. Body mass index (BMI), fasting serum glucose, lipids, blood pressure, and ultrasonography of cardiac and carotid artery structure and function were measured. Former endurance athletes smoked less, had lower prevalence of hypertension, and had higher intensity and volume of leisure time physical activity (LTPA) than the controls. No difference was detected in cardiac or carotid artery structure and function between these groups. Former athletes performing high-intensity LTPA were slightly younger (possible selection bias), had lower BMI and waist circumference, lower use of antihypertensives, lower prevalence of diabetes, lower pulse wave velocity, and higher carotid artery elasticity than former athletes not performing high-intensity LTPA. In conclusion, former athletes had a higher intensity and volume of LTPA than the controls. Athletes performing vigorous LTPA had more elastic arteries than athletes performing moderately or no LTPA. Vigorous LTPA through the whole lifetime associates with good cardiovascular health, although the previous medical history may play an important role.

Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex-specific visceral hypersensitivity in offspring.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdominal pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life experiences. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. METHODS: We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. KEY RESULTS: Chronic prenatal stress induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. Chronic prenatal stress upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation, and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. CONCLUSIONS & INFERENCES: The development of VHS, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients.

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation.

Cumulative incidence of shoulder region tendon injuries in male former elite athletes.

Some types of sports are thought to include a high risk for shoulder region tendon injuries but little data exist on long-term cumulative incidence of these injuries. The aim of our study was to investigate shoulder region tendon injuries diagnosed by physicians in former elite male athletes participating in sports including maximal overhead manoeuvres (overhead athletes) and also other athletes before the age of 45 years and within the subjects' lifetime, compared to control subjects. A postal questionnaire was sent in 2002 to male former elite athletes (n=785; mean age 68 years when responding to the questionnaire; overhead athletes n=111, others n=674) and control subjects (n=416; mean age 67 years). Overhead athletes had a higher risk for shoulder region tendinopathy before the age of 45 (adjusted odds ratio (OR) 4.1, 95% confidence interval (CI) 2.0-8.4, p<0.001) and within lifetime (OR 1.8, 95% CI 1.1-3.0, p=0.027) compared to control subjects. Compared to controls the risk for tendon rupture before the age of 45 (adjusted OR 4.4, 95% CI 1.3-14.8, p=0.016) and within lifetime (OR 2.0, 95% CI 1.0-6.9, p=0.041) was also high in overhead athletes. There was no difference in the risks of shoulder region tendon injuries between the other athletes and the control subjects. Our data indicate that shoulder region injuries are common in athletes participating in sports including maximal overhead manoeuvres and the long-term consequences of these injuries for athletes' daily life and functional ability should be determined.

Former athletes' health-related lifestyle behaviours and self-rated health in late adulthood.

The aim of this study was to examine the associations between self-rated health (SRH), physical activity and other lifestyle habits among former athletes and referents in late adulthood. Male athletes (N=514) who represented Finland from 1920 through 1965 and referents (N=368) who were classified healthy at the age of 20 years participated in this population-based cohort study. The present analysis was based on a questionnaire study in 2001. SRH was assessed by a single question. Univariate binary and multivariate logistic regression analyses were used to examine the associations of health-related behaviours with SRH. The majority of former athletes (64%) rated their health better than referents (48%). A higher percentage of the athletes (54%) compared to the referents (44%) belonged to the most physically active groups (MET quintiles IV-V). A high percentage of the athletes (77%) and referents (79%) were occasional or moderate alcohol users. The proportion of never smokers among athletes was 59% and among referents 37%. Among current smokers there were no differences in nicotine dependence between athletes and referents (p=0.07). In the univariate analysis the odds of reporting good SRH was 2 times higher for athletes (OR 2.01, 95% CI 1.53-2.64, p<0.001) than for referents. In multivariate logistic regression analysis, former participation in team and power athletic groups had significantly higher SRH than the referents even after adjusting for age, level of physical activity, alcohol and smoking habit, and occupation. People who participated in very active physical exercise in their youth, as indexed by participation in competitive sports by elite athletes, continue a physically active lifestyle, and maintained healthier lifestyle. They had significantly higher SRH than the referents in their senior years, which was not totally explained by their physically active and healthier lifestyles.

Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults.

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.

Patient-reported complications associated with Campylobacter jejuni infection.

This study aimed to investigate the occurrence of complications, especially musculoskeletal symptoms, after sporadic Campylobacter jejuni enteritis of domestic origin in Finland. This multi-centre cross-sectional study was conducted during a seasonal peak in 2002. Questionnaires were sent to Campylobacter-positive patients, representing different geographical areas, 2 months after collection of positive stool samples. Medical records were viewed in several cases. Besides antimicrobial susceptibility testing C. jejuni isolates were serotyped. A total of 235 patients (58%) returned the questionnaire and 201 C. jejuni-positive patients were finally included in the study. Musculoskeletal symptoms associated with C. jejuni enteritis were frequent (39%); joint pain was most commonly reported (81%). The incidence of reactive arthritis was 4% and that of Achilles enthesopathy and/or heel pain was 9%. Stomach ache during enteritis was associated with the later development of joint pain. Antimicrobial treatment was common but did not prevent complications.

Brain magnetic resonance imaging of siblings from families with two or more children with learning or intellectual disabilities and need for full-time special education.

BACKGROUND: Several factors are involved in determining a child's need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. PURPOSE: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. MATERIAL AND METHODS: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. RESULTS: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). CONCLUSION: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE.

Budesonide improves decreased airway conductance in infants with respiratory symptoms.

OBJECTIVE: Inhaled corticosteroids (ICS) are commonly used to treat wheezing disorders in children, but few studies have investigated the effect of ICS on lung function in infants. We evaluated the efficacy of inhaled budesonide for decreased specific airway conductance (sGaw) as an indication of bronchial obstruction in very young children with recurrent cough and/or wheeze. PATIENTS, DESIGN AND INTERVENTIONS: Functional residual capacity (FRC) and sGaw of steroid-naive children aged 3-26 months with respiratory symptoms were measured using an infant whole-body plethysmograph. Clinically indicated bronchoscopy was performed in 79% of the patients to exclude anatomical abnormalities before randomisation. Children with abnormal lung function and respiratory symptoms were randomised into two treatment groups, receiving either inhaled budesonide (400 microg/day) or placebo with NebuChamber for 6 weeks. Inhaled terbutaline 0.25 mg/dose was used as a rescue medication. Lung function measurements were repeated after 6 weeks. MAIN OUTCOME MEASURE: Lung function. RESULTS: 44 children with a median age of 11.3 months (range 3.7-25.9) completed the study. Median sGaw improved from a z score of -3.6 to -1.2 (p<0.001) in the budesonide group and from -3.2 to -2.6 (p = 0.033) in the placebo group; between group difference p = 0.014. Improvement in sGaw was more pronounced in children with atopy (p = 0.017). Symptom-free days increased in both the budesonide and placebo groups with no difference between groups. CONCLUSION: Treatment with inhaled budesonide for 6 weeks improved sGaw in young children with chronic cough or wheeze and bronchial obstruction.

Severe diarrhoea caused by highly ciprofloxacin-susceptible Campylobacter isolates.

The impact of fluoroquinolone resistance of Campylobacter jejuni and Campylobacter coli isolates on the outcome of the disease in sporadic Campylobacter infections of Finnish individuals was studied. Questionnaires were sent, during a 6-month study period, to patients who were stool culture-positive for Campylobacter spp. In total, 192 returned questionnaires were analysed and assessed, together with the susceptibility data of the respective bacterial isolates. Only one (2%) of the domestic, but half of the imported, Campylobacter isolates were resistant to ciprofloxacin. Ciprofloxacin resistance was not associated with particularly severe infection. Instead, ciprofloxacin-susceptible Campylobacter isolates, as compared to ciprofloxacin-resistant isolates, showed a tendency to cause more severe infections, characterized by bloody stools and hospitalization.

Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours.

AIMS: The polycomb factor BMI-1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI-1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a) and MDM2 in both high- and low-grade human glioma. METHODS: Tumour samples were collected from 305 adult patients treated for primary grades 2-4 gliomas between 1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin-embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models. RESULTS: BMI-1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI-1 immunoreactive tumour cells and poor survival in World Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki-67 mitotic index was also observed. CONCLUSIONS: BMI-1 is found in all histological types of gliomas and the relative protein expression of BMI-1 is a novel independent prognostic marker in oligodendroglial tumours.

Beneficial effect of resin salve in treatment of severe pressure ulcers: a prospective, randomized and controlled multicentre trial.

BACKGROUND: Resin salve of the Norway spruce (Picea abies) has been used in folk medicine to heal wounds and infections. OBJECTIVES: To study its clinical effectiveness in the treatment of pressure ulcers of the skin. METHODS: A prospective, randomized, controlled multicentre trial involving 37 patients with grade II-IV pressure ulcers in 11 primary care hospitals was carried out between 2005 and 2007. The ulcers were randomly allocated to receive either resin salve or sodium carboxymethylcellulose hydrocolloid polymer treatment. The inclusion criterion was grade II-IV pressure ulcer. Exclusion criteria were a life expectancy of less than 6 months or a malignant disease. The primary outcome measure was complete healing of the ulcer within 6 months. Secondary outcome measures were partial healing of the ulcer, and successful eradication of bacterial strains cultured from the ulcers at study entry. RESULTS: Thirteen patients of the resin group and nine patients of the control group completed the 6-month trial. All ulcers healed in 12 of the 13 patients (92%) in the resin group and in four of the nine patients (44%) in the control group (P=0.003; power 73%). Complete healing of the ulcers over time was significantly more common in the resin group than in the control group (P=0.013). Bacterial cultures from the ulcer area more often became negative within 1 month in the resin group. CONCLUSIONS: Traditional resin salve is significantly more effective in the treatment of infected and noninfected severe pressure ulcers than cellulose polymer gauzes.

Female fertility and childbirth after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: The aim of this study was to calculate the probability of becoming pregnant after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, and to evaluate complications during pregnancy and childbirth. METHODS: A questionnaire was posted to 160 women with an IPAA and to 160 controls. The probability of becoming pregnant after IPAA was calculated by the Kaplan-Meier method. RESULTS: Of 54 women who had undergone IPAA surgery, 36 (67 per cent) succeeded in becoming pregnant naturally, compared with 49 (82 per cent) of 60 controls. The probability of pregnancy after 2 years of trying was 56 per cent in the IPAA group and 91 per cent in the control group (P < 0.001). Women in the IPAA group needed infertility investigations more often (24 versus 10 per cent; P = 0.044). In all, 39 (72 per cent) women in the IPAA group and 53 (88 per cent) in the control group bore a child. Twenty-one of 39 women in the IPAA group and 13 of 53 in the control group had a caesarean section (P = 0.005). Anal incontinence after delivery occurred more often in the control group. CONCLUSION: Women with an IPAA mostly suffer a reduction in the probability of conception rather than complete infertility. Because complications during pregnancy and delivery were rare, caesarean section should be based mainly on obstetric indications.

Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease.

BACKGROUND: Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). MATERIALS AND METHODS: Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. RESULTS: Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf > 400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = -0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of severity and extent of CAD. CONCLUSION: Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis.