Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023.

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Type IIx muscle fibers are related to poor body composition, glycemic and lipidemic blood profiles in young females: the protective role of type I and IIa muscle fibers.

PURPOSE: The aim of the present study was to investigate the association between muscle fiber composition, body composition, resting glycemic-lipidemic blood profiles, in apparently healthy, young, active females. METHODS: Thirty-four young healthy female volunteers were allocated into two groups, depending on their Vastus Lateralis type IIx muscle fibers percent cross-sectional area (%CSA; H: high type IIx %CSA; L: low type IIx %CSA). Body composition was determined via dual-energy X-ray absorptiometry. Venous blood samples were collected for the determination of resting serum glucose, Insulin, Apo-A1, HOMA-IR, triglycerides (TG), total cholesterol (TC), High-density lipoprotein (HDL-C), and Low-density lipoprotein (LDL-C) concentrations. Nutritional intake was also evaluated. RESULTS: Individuals of the H group have significantly higher body mass, body fat percentage-mass, and resting blood indices of glycemic and lipidemic profiles, compared to those of L group (p < 0.001). Increased type IIx and low type I, IIa muscle fibers %CSAs were linked with poorer body composition, glycemic and lipidemic blood profiles (r: - 0.722 to 0.740, p < 0.001). Linear regression analyses revealed that the impact of muscle fibers %CSA (B coefficients ranged between - 0.700 and 0.835) on the above parameters, was at least, of the same or even of greater magnitude as that of body composition and daily nutritional intake (B: - 0.700 to 0.666). CONCLUSION: Increased type IIx and low Type I, IIa %CSAs are associated with poorer body composition and glycemic-lipidemic profiles in young healthy females. The contribution of the muscle fiber %CSA on health status seems to be comparable to that of nutrition and body composition.

Associations between red blood cells fatty acids, desaturases indices and metabolism of platelet activating factor in healthy volunteers.

INTRODUCTION: Platelet-activating-factor is an inflammatory lipid mediator. Key enzymes of its biosynthesis are CDP-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-CoA:lyso-PAF-acetyltransferases (Lyso-PAF-AT) while PAF-AH/Lp-PLA2 degrade PAF. The interplay between PAF and fatty acids metabolism was explored. MATERIAL AND METHODS: In a healthy population, PAF levels, its metabolic enzymes activity and RBC fatty acids were measured while desaturases indices (D) were estimated. A principal component analysis was also applied to assess patterns of RBC fatty acids. RESULTS: SFA were related to increased PAF biosynthesis and decreased Lp-PLA2 only in women. MUFA were inversely associated with PAF biosynthesis and positively with Lp-PLA2. Omega-6 fatty acids were positively correlated only with PAF-CPT while no significant correlations were observed with n3 fatty acids. D6 index was positively related with PAF biosynthetic enzymes and inversely with Lp-PLA2 while D9 correlated positively with Lp-PLA2. The pattern of high MUFA and low n6 was associated with reduced PAF biosynthesis and/or increased catabolism in both sexes. CONCLUSION: The role of fatty acids in amplifying or reducing inflammation seems to be also reflected in PAF metabolism.

Mining possible associations of faecal A. muciniphila colonisation patterns with host adiposity and cardiometabolic markers in an adult population.

We aimed to evaluate colonisation patterns of Akkermansia muciniphila in a Greek adult population and to investigate model-adjusted associations of A. muciniphila with host adiposity and cardiometabolic markers. Participants (n=125) underwent anthropometric, dietary, physical activity and lifestyle evaluation. Blood sampling for determination of blood lipid indices, glucose metabolism, adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), inflammation and oxidative stress parameters was also performed. Stool A. muciniphila presence and levels were determined by quantitative PCR and subjects were grouped based on bimodal distribution of levels (Low vs High). A. muciniphila was detected in 88.6% of participants. Overweight/obese (OW/OB) subjects were more prone in low bimodal levels of A. muciniphila compared to normal-weight (NW) individuals (58.75 vs 27.59%, P=0.004), with a 4-time greater likelihood after multi-adjusted logistic regression analysis (P=0.016). Levels of A. muciniphila were negatively associated with total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio (log10:-0.009±0.004, P=0.033), whereas detection of this bacterium was negatively associated with both TC/HDL-C ratio (log10: -0.049±0.023, P=0.036) and low-density lipoprotein cholesterol/HDL-C ratio (-0.407±0.176, P=0.023). Furthermore, low bimodal levels of A. muciniphila were positively associated with fasting blood glucose (log10: 0.018±0.009, P=0.037). In terms of inflammation markers, levels of A. muciniphila were positively associated with soluble cluster of differentiation-14 (sCD14) (log10: 0.012±0.004, P=0.003) and faecal detection of this bacterium had a positive association with anti-inflammatory interleukin 10 levels (log10: 0.325±0.131, P=0.015). In addition, A. muciniphila levels were positively associated with total adiponectin (log10: 0.046±0.015, P=0.002), whereas low bimodal levels of A. muciniphila had an inverse relationship with this blood marker (log10: -0.131±0.053, P=0.016). In conclusion, we confirmed the previously reported association of A. muciniphila with metabolic health for the first time in a Greek urban population; furthermore, we shed some light to novel atherosclerotic risk markers with rather unexplored connections with A. muciniphila colonisation patterns in human subjects.

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial.

BACKGROUND/OBJECTIVES: The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). SUBJECTS/METHODS: In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m2), IGT-B (n=20, BMI: 32.5±5kg/m2) or T2D (n=12, BMI: 32.2±5.2kg/m2) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. RESULTS: Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P<0.001 vs P=0.02, respectively). The 6-meal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P<0.05). There were no differences in HOMA-IR or plasma lipids between interventions. CONCLUSION: Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects.

Amino acid profile and metabolic syndrome in a male Mediterranean population: A cross-sectional study.

BACKGROUND AND AIMS: The metabolic syndrome (MetS) refers to a cluster of clinically relevant factors that increases the risk of cardiovascular diseases and all-cause mortality. Circulating levels of several amino acids and metabolites related to one-carbon metabolism have been associated with cardiometabolic risk factors and MetS. We aimed to identify the amino acid profile that is significantly associated with MetS among an all male Mediterranean population. METHODS AND RESULTS: One hundred middle-aged men (54.6 ± 8.9 years) participated in a cross-sectional study carried out during 2011-2012. The International Diabetes Federation (IDF) criteria were used to define MetS. Fasting plasma levels of 20 common amino acids and 15 metabolites related to amino acid and one-carbon metabolism were measured using gas chromatography (GC-MS/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Principal components analysis was applied. Fifty-six participants fulfilled the IDF criteria for defining MetS. Five factors were extracted from the 35 measured metabolites. The branched-chain amino acids/aromatic amino acids (BCAA/AAA) related pattern and the glutamine/glycine/serine/asparagine (Gln/Gly/Ser/Asn) related pattern were significantly associated with MetS (odds ratio, 95% confidence interval; 6.41, 2.43-16.91, and 0.47, 0.23-0.96, respectively) after adjustment for age, current smoking status, physical activity level and medical treatment for hypertension, dyslipidaemia, type 2 diabetes mellitus. Further adjustment for liver function markers (i.e. glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and γ-glutamyltransferase), and plasma adiponectin levels did not significantly affect the associations. CONCLUSION: The BCAA/AAA pattern was positively associated, while the Gln/Gly/Ser/Asn pattern was inversely associated with established cardiometabolic risk factors and MetS. Plasma adiponectin levels or markers of liver function did not significantly affect these associations.

The relation of diet with PAF and its metabolic enzymes in healthy volunteers.

PURPOSE: Platelet-activating factor (PAF), a potent inflammatory mediator, is implicated in atherosclerosis. Its key biosynthetic enzymes are lyso-PAF acetyltransferases (lyso-PAF-AT), responsible for PAF synthesis through the remodeling route and a specific CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), responsible for its de novo biosynthesis. PAF acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase A2 catabolize PAF. The impact of diet on PAF metabolism is ill-defined. The aim was to investigate associations between PAF, its enzymes and dietary factors. METHODS: One-hundred and six (n = 106) healthy volunteers were recruited. Food-frequency questionnaires, dietary recalls, lifestyle and biochemical variables were collected. Food groups, macronutrient intake, a priori (MedDietScore) and a posteriori defined food patterns with PCA analysis, dietary antioxidant capacity (DAC), glycemic index (GI) and glycemic load were assessed. RESULTS: PAF was inversely correlated with antioxidant-rich foods (herbal drinks and coffee), the DAC as well as a dietary pattern characterized by legumes, vegetables, poultry and fish (all Ps < 0.05). PAF was positively correlated to % fat intake. Lyso-PAF-AT was also negatively associated with healthy patterns (fruits, nuts and herbal drinks, and a pattern rich in olive oil and whole-wheat products), as well as the DAC and % monounsaturated fatty acids. PAF-CPT was negatively associated with GI and coffee intake and positively with dietary cholesterol. PAF-AH was negatively associated with coffee and positively associated with alcohol consumption (all Ps < 0.05). CONCLUSIONS: In conclusion, the DAC and healthy dietary patterns were inversely associated with PAF or its biosynthetic enzymes, suggesting potential new mechanisms of the diet-disease associations.

Gender-specific distribution of selenium to serum selenoproteins: associations with total selenium levels, age, smoking, body mass index, and physical activity.

The epidemiology of selenium (Se) is mainly based on the determination of total serum selenium levels (TSe) which by many aspects is an inadequate marker of Se status. In this study we applied a recently developed LC-ICP-MS method, for the determination of the selenium content of the three main serum selenium-containing proteins, in a subcohort of the ATTICA study. This enables us to investigate whether the selenium distribution to selenoproteins may correlate with demographic (age, gender) and lifestyle variables (smoking, physical activity) that are crucial for the development of chronic diseases. A sub-sample from the ATTICA Study, consisted of 236 males (40 ± 11 years) and 163 females (38 ± 12 years), was selected. The selenium content of glutathione peroxidase (GPx-3), selenoprotein P (SelP) and selenoalbumin (SeAlb) was determined in serum by LC-ICP/MS method. We found that 26% of TSe is found in GPx-3, 61% in SelP and 13% in SeAlb. We have assessed the different ratios of selenoproteins' selenium content (Se-GPX-3/Se-SelP, Se-GPX-3/Se-SeAlb, Se-SelP/Se-SeAlb), showing that people with similar TSe may have different distribution of this selenium to selenoproteins. Total selenium levels and gender are the variables that mostly affect selenium distribution to selenoproteins while age, smoking, physical activity and BMI do not significantly influence selenium distribution. In conclusion, the simultaneous determination of the selenium content of serum selenium-containing selenoproteins is necessary for a thorough estimation of selenium status. The ratio of the Se content between selenoproteins may be proven a novel, valid marker of selenium status.

Pretreatment with sevoflurane attenuates direct lung injury.

BACKGROUND: Sevoflurane exerts effects on pulmonary cells that could protect against lung injury. We evaluated the potential of pretreatment with sevoflurane to attenuate lipopolysaccharide (LPS)-induced lung injury. METHODS: LPS was administered intratracheally in Wistar rats to induce lung injury. Sevoflurane was administered for 30 min at 0.25, 0.5 or 1.0 MAC 15 min before LPS or for 30 min at 0.5 MAC 24 hours before LPS. After initial analysis of bronchoalveolar lavage fluid (BALF) cells and total protein, the group of 0.5 MAC 15 min before LPS was further analyzed for surfactant aggregates subfractions, plasma malondialdehyde levels and lung histology. RESULTS: LPS instillation resulted in neutrophils sequestration in the lungs, loss of alveolar macrophages, increased BALF total protein and decreased large surfactant aggregates. Only inhalation of sevoflurane for 30 min at 0.5 MAC 15 min before LPS installation effectively reduced neutrophil accumulation, preserved alveolar epithelial cells and reduced total protein content in BALF. This regimen also reduced plasma malondialdehyde levels and increased large surfactant aggregates, despite the application of mechanical ventilation. This effect was preserved after LPS instillation and the favorable composition of surfactant was maintained. CONCLUSION: Pretreatment with sevoflurane effectively attenuates direct severe lung injury, possibly by inhibition of neutrophil accumulation and alteration of the surfactant composition.

Osteoprotegerin and nuclear factor-kappaB ligand are associated with leptin and adiponectin levels, in apparently healthy women.

OBJECTIVES: We investigated the relationship between the major bone turnover markers, i.e., Osteoprotegerin (OPG) and Receptor activator of nuclear factor-kappaB ligand (RANKL) and serum adipokines (leptin, adiponectin) levels in a sample of apparently healthy women. METHODS: A random sample which consisted of 80 females (18-71 years) was studied. Elisa method was used to measure the OPG, RANKL and the leptin, adiponectin levels in females' serum. RESULTS: OPG values were inversely correlated with leptin (rho = -0.38, p = 0.002) and positively correlated with age (rho = 0.27, p=0.01) and body mass index (rho = 0.29, p=0.009). RANKL values were inversely correlated with adiponectin (rho = -0.23, p = 0.06) and age (rho = -0.30, p=0.01). Additionally, OPG was higher in post- as compared to pre-menopausal women. Further data analysis adjusting for potential confounders revealed that the OPG/RANKL ratio was positively associated with adiponectin and inversely associated with leptin levels independent of the effect of age, body mass index and menopausal status. CONCLUSIONS: These results reveal that leptin circulating levels are inversely associated with serum OPG/RANKL ratio among healthy women.

Dietary habits of Greek adults and serum total selenium concentration: the ATTICA study.

PURPOSE: The trace element selenium is an essential micronutrient for human health, and its low levels in serum are implicated in the pathogenesis of several chronic diseases. The determination of total serum selenium levels may contribute to the assessment of the health status of all populations. Since the serum selenium levels are highly affected by diet, we assessed its association with the dietary habits of Greek adults. METHODS: Serum selenium levels were determined with inductively coupled plasma mass spectrometry in a cohort of 506 participants (men: 296, women: 210) aged 18-75 from the ATTICA study. Food consumption was evaluated with a validated food-frequency questionnaire. RESULTS: Evaluation of the relationship between serum total selenium with major food groups and beverages by multi-adjusted analysis revealed that serum selenium was positively correlated with the consumption of red meat (2.37 ± 0.91, p = 0.01) while the consumption of other selenium-containing foods (i.e., fish, cereals, dairy products, vegetables) did not demonstrate such a relationship. Moreover, principal component analysis revealed that the adoption of a vegetarian type of diet is inversely correlated with total selenium (-3.94 ± 2.28, p = 0.08). CONCLUSIONS: Among the dietary habits that were examined, red meat seems to be the major determinant of serum selenium in Greek adults.

Dietary antioxidant capacity and concentration of adiponectin in apparently healthy adults: the ATTICA study.

BACKGROUND/OBJECTIVES: This study aimed at evaluating the relationship of adiponectin concentration with total dietary antioxidant capacity in free-living, apparently healthy adults from the ATTICA study. SUBJECTS/METHODS: A random subsample from the ATTICA study, consisting of 310 men (40+/-11 years) and 222 women (38+/-12 years), was selected. Adiponectin, along with other inflammatory markers, was measured in fasting participants. Dietary habits were evaluated using a food frequency questionnaire and the dietary antioxidant capacity was based on published values of Italian foods measured by three different assays: ferric-reducing antioxidant power (FRAP), total radical-trapping antioxidant parameters (TRAP) and trolox-equivalent antioxidant capacity (TEAC). RESULTS: Positive associations were observed between dietary antioxidant capacity and adiponectin concentration, as assessed with FRAP (b+/-s.e.=0.012+/-0.005, P=0.018 per 1 mmol Fe (II)/day), TRAP (b+/-s.e.=0.030+/-0.013, P=0.017 per 1 mmol trolox equivalent/day) and TEAC (b+/-s.e.=0.025+/-0.012, P=0.042, per 1 mmol trolox equivalent/day) in multiadjusted analysis. Moreover, a negative relation of dietary antioxidant indices with inflammatory markers was revealed. CONCLUSIONS: Diets with high antioxidant capacity are related to increased adiponectin levels. An adiponectin-mediated route through which antioxidant-rich foods exert beneficial effects against inflammation and cardiovascular diseases can be thus hypothesized.

Effects of baseline serum levels of Se on markers of eccentric exercise-induced muscle injury.

Inflammation and oxidative stress have been implicated in the mechanism of eccentric exercise-induced muscle injury. This study examined whether baseline serum levels of selenium (Se), a trace element that participates in both antioxidant and anti-inflammatory systems, affects the overall response to injury. Thirteen males performed 36 maximal eccentric actions with the elbow flexors of the non-dominant arm on a motorized dynamometer. Venous blood samples were collected immediately before and after exercise at 2, 24, 48, 72 and 96 hours. Established indicators of muscle damage such as maximum isometric torque (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG), arm circumference (CIRC), muscle soreness and serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined at the same time points. Baseline serum levels of Se were also measured. Complementary data regarding assessment of Se status were retrieved by the use of a semi-quantitative food frequency questionnaire. All measures changed significantly (p<0.05) after exercise. The main finding of this study was that baseline Se serum levels were associated inversely with CK, LDH and FANG and positively with MIT and ROM (p<0.05). These data suggest that beyond overt Se deficiency, suboptimal Se status possibly worsens muscle functional decrements subsequent to eccentric muscle contractions.

Biological activity of total lipids from red and white wine/must.

Wine is an essential component of the Mediterranean diet, and it is thought to exert a protective effect against coronary heart disease. Although many efforts have been made to determine the protective compounds in wines, their exact nature and how they are involved in the protection mechanisms are still unclear. In this study, total lipids, total polar lipids, and total neutral lipids of five wines and three musts were tested in vitro for their ability to induce washed rabbit platelet aggregation and/or to inhibit platelet activating factor (PAF) induced aggregation. The results showed that the biological activity of wine/must total lipids can be attributed mainly to total polar lipids. In the red wine Cabernet Sauvignon, we fractionated total neutral lipids, total polar lipids, and pigments by HPLC. Each fraction was tested in vitro for its biological activity. Structural data of the most active fractions, based on biological, chemical, and spectral methods, are also presented.

Simultaneous quantitation of topoisomerase II alpha and beta isoform mRNAs in lung tumor cells and normal and malignant lung tissue.

Certain drugs used in the treatment of lung cancer and other human malignancies are cytotoxic because of their ability to interact with the two isoforms of topoisomerase II (topo II), topo IIalpha and topo IIbeta. As part of an effort to evaluate the contribution of topo II alterations to drug sensitivity and resistance in lung cancer, we have developed a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay to measure levels of topo II alpha and beta mRNAs simultaneously using a single pair of primers with sequences common to both isoforms. The PCR products derived from the topo II alpha and beta mRNAs are both 446 bp but have different electrophoretic mobilities in a nondenaturing polyacrylamide gel, allowing sensitive, rapid quantitation when the products are radiolabeled with [35S]-dATP. Using this RT-PCR method, poly(A+) RNA from 13 non-small cell lung cancer (NSCLC) cell lines was analyzed. The results obtained indicated that the cell lines express a wide range of topo II alpha mRNA levels (12-fold) and topo IIbeta mRNA levels (5.5-fold). Tumor and normal lung tissues from 25 patients with NSCLC were also examined. In the tumor samples, the levels of the topo II alpha and beta mRNAs were similar. However, mean topo IIalpha mRNA levels in the tumors were approximately 7-fold higher than those of the paired normal lung tissues. In contrast, topo IIbeta mRNA levels were similar in both tumor and normal lung. Topo II alpha and beta mRNA levels were both significantly lower in the squamous cell tumors than in the adenocarcinoma samples. Topo IIbeta mRNA levels in the squamous cell tumors were also significantly lower than those in paired normal lung tissue. The RT-PCR method described is reliable and convenient, and for the first time, makes the rapid simultaneous direct comparison of topo IIalpha and topo IIbeta mRNA levels feasible in large numbers of clinical samples.

Separation of biologically active lipids from red wine.

A number of lines of evidence suggest that red wine exerts a protective effect against coronary heart disease, but the nature of the protective compounds is unclear and the mechanism is incompletely understood. In this study, total lipids of a Greek red wine were separated into neutral and polar lipids. Polar lipids were further separated into glyco- and phospholipids, which were fractionated by HPLC. Each lipid fraction was tested in vitro for its ability to inhibit platelet-activating factor (PAF) and thrombin-induced washed rabbit platelet aggregation and/or to cause platelet aggregation. A significant number of glyco- and phospholipids that exerted the above biological activities were detected. Structural data of an active phosphoglycolipid are also provided. trans-Resveratrol demonstrated also a dose-dependent inhibition of PAF-induced platelet aggregation along with the already reported inhibitory activity against thrombin and adenosine-5'-diphosphate. Because it has already been reported that PAF is involved in atheromatosis generation, the existence of PAF inhibitors in red wine may contribute to the protective role of red wine against atherosclerosis.

Lipid fractions with aggregatory and antiaggregatory activity toward platelets in fresh and fried cod (Gadus morhua): correlation with platelet-activating factor and atherogenesis.

Cod (Gadus morhua) is a popular part of the diet in many countries on both sides of the North Atlantic; in most cases it is consumed fried. In this study, total lipids of cod muscle were separated into neutral and polar lipids, which were further fractionated by HPLC. The lipid fractions were tested in vitro, against washed rabbit platelets, for the probable existence of lipid compounds that either exhibit an action similar to that of platelet-activating factor (PAF) or inhibit the action of PAF. The platelet bioassay was used to evaluate total lipids, total polar lipids, and total neutral lipids, before any further separation. Detection of these compounds in fresh and fried cod could be used to evaluate the nutritional value of this important fish. The in vitro biological study of lipids showed that in fresh cod lipid fractions, ranges of PAF-like and anti-PAF-like activities were present, whereas in fried cod lipid fractions, both neutral and polar, anti-PAF activities were mainly observed. Because it has already been reported that PAF is involved in atheromatosis generation, the existence of PAF inhibitors in cod may contribute to the possible protective role of fish, in this case cod, against atherosclerosis.

Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response.

Recently, cDNAs have been identified that encode four human proteins (MRP2-5) with structural similarity to the multidrug resistance protein (MRP). Preliminary studies have shown that levels of mRNAs encoding MRP2, MRP3, and MRP5, are increased in some drug-selected cell lines, but the correlation of MRP2-5 mRNA levels with drug resistance has not been examined. Using a collection of small cell lung cancer (SCLC) and non-SCLC patient samples and unselected cell lines established from patients at various stages of treatment, we examined the expression of MRP2, MRP3, MRP4, and MRP5, as well as MDR1 and MRP, by PCR. The levels of individual mRNAs were correlated with the sensitivity of these cell lines to doxorubicin (DOX), vincristine, VP-16, and cis-diamminedichloroplatinum(II), as determined by a modified MTT assay. Using both SCLC and non-SCLC cell lines, we confirmed the previously observed correlation of MRP mRNA levels with resistance to DOX (B. G. Campling et al., Clin. Cancer Res., 3:115-122, 1997) and found a strong correlation of MRP3 mRNA levels with resistance of the cell lines to DOX. In addition, the mRNA levels of both MRP and MRP3 correlated with resistance of the cell lines to vincristine, VP-16, and cis-diamminedichloroplatinum(II). These findings are consistent with the suggestion that MRP3, like MRP, may contribute to the drug resistance phenotype of lung cancer cells.