Novel immediate/sustained-release formulation of acetaminophen-ibuprofen combination (Paxerol®) for severe nocturia associated with overactive bladder: A multi-center, randomized, double blinded, placebo-controlled, 4-arm trial.

AIM: To determine short-term efficacy and safety of Paxerol®, novel immediate:sustained (50%:50%) release tablets containing 325 mg acetaminophen and 150 mg ibuprofen per tablet. METHODS: One of three dose levels, corresponding to the amounts in 1, 2, and 3 tablets, of Paxerol and placebo were administered for 14 consecutive days to patients with severe nocturia (defined in this study as an average nocturnal voids [NV] ≥2.5) associated with overactive bladder (OAB). Changes in NV, as well as Nocturia Quality of Life (NQOL), duration of first uninterrupted sleep (DFUS), and total hours of nightly sleep (THNS) associated with treatment were assessed. Short-term safety/tolerability was assessed throughout the study and for at least 30 days post-treatment. RESULTS: Paxerol at all three doses reduced NV to a greater degree than placebo (average NV -1.1, -1.4, -1.3 voids for low, mid, and high doses, respectively, vs -0.3 void for placebo). NQOL and THNS were similar between baseline and treatment values in all four groups. There were also no between-group differences. Paxerol at high dose tended to (although not statistical significantly) increase DFUS to a greater degree than placebo (1.2 vs 0.4 h, P = 0.057). There were no treatment related adverse events in any of the four groups. CONCLUSIONS: This study demonstrates short-term efficacy and short-term safety of Paxerol in patients with severe nocturia associated with OAB. The results warrant further investigation of the long-term efficacy and safety of Paxerol in larger patient populations.

Decreasing recurrent bowel obstructions, improving quality of life with physiotherapy: Controlled study.

AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy vs no treatment. METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, which is the normal course for patients with recurring SBO. Comparison of the groups allowed us to assess changes when the physiotherapy was added as an adjunct treatment for patients with recurring SBO. RESULTS: Despite histories of more prior hospitalizations, obstructions, surgeries, and years impacted by bowel issues, the 103 CPA-treated subjects reported a significantly lower rate of repeat SBO than 136 untreated controls (total obstructions P = 0.0003; partial obstructions P = 0.0076). Subjects treated with the therapy demonstrated significant improvements in five of six total domains in the validated Small Bowel Obstruction Questionnaire (SBO-Q). Domains of diet, pain, gastrointestinal symptoms, quality of life (QOL) and pain severity when compared to post CPA treatment were significantly improved (P < 0.0001). The medication domain was not changed in the CPA treated group (P = 0.176). CONCLUSION: CPA physical therapy was effective for patients with adhesive SBO with significantly lower recurrence rate, improvement in reported symptoms and overall quality of life of subjects.

Effects of fat supplementation on plasma glucose, insulin and fatty acid analysis in ponies maintained on a forage-based diet.

The objective of this study was to observe how fat incorporated into an equine forage-based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14-day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14-day period before a five-day trial period. Each pony received all four diets by the end of the study. Each trial was a five-day period with a three-day sample collection. Blood samples for each collection week were taken 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270 min and at 5, 6, 7, 8, 9 and 10 hr post-feeding. Excess fat did not impact plasma glucose (p > .1), nor did it affect blood plasma insulin concentration. While there was no time alteration found for plasma fatty acid concentration (p > .1), C14:0 increased when ponies were fed 0% fat and C18:2 decreased when ponies were fed 0% fat. Plasma fatty acids (% of total FA) were higher in C18:0, C18:1, C18:2 and C20:1 in the added fat diets (p < .1). These findings suggest the amounts reported in this study of fat supplementation on a forage-based diet did influence the fatty acid analysis within the pony, but did not negatively impact blood glucose and insulin concentrations.

Comparative electrocardiographic, autonomic and systemic inflammatory responses to soy biodiesel and petroleum diesel emissions in rats.

CONTEXT: Biodiesel fuel represents an alternative to high particulate matter (PM)-emitting petroleum-based diesel fuels, yet uncertainty remains regarding potential biodiesel combustion emission health impacts. OBJECTIVE: The purpose of this study was to compare cardiovascular responses to pure and blended biodiesel fuel emissions relative to petroleum diesel exhaust (DE). MATERIALS AND METHODS: Spontaneously hypertensive rats were exposed for 4 h per day for four days via whole body inhalation to combustion emissions (based on PM concentrations 50, 150 or 500 µg/m(3) or filtered air) from pure (B100) or blended (B20) soy biodiesel, or to pure petroleum DE (B0). Electrocardiogram (ECG) and heart rate variability (HRV, an index of autonomic balance) were monitored before, during and after exposure while pulmonary and systemic inflammation were assessed one day after the final exposure. ECG and HRV data and inflammatory data were statistically analyzed using a linear mixed model for repeated measures and an analysis of variance, respectively. RESULTS: B100 and B0, but not B20, increased HRV during all exposure days at the highest concentration indicating increased parasympathetic tone. Electrocardiographic data were mixed. B100 and B0, but not B20, caused significant changes in one or more of the following: serum C-reactive protein, total protein, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, and blood urea nitrogen (BUN) and plasma angiotensin converting enzyme (ACE) and fibrinogen. DISCUSSION AND CONCLUSIONS: Although responses to emissions from all fuels were mixed and relatively mild, some findings point to a reduced cardiovascular impact of blended biodiesel fuel emissions.

Association Mapping of Total Carotenoids in Diverse Soybean Genotypes Based on Leaf Extracts and High-Throughput Canopy Spectral Reflectance Measurements.

Carotenoids are organic pigments that are produced predominantly by photosynthetic organisms and provide antioxidant activity to a wide variety of plants, animals, bacteria, and fungi. The carotenoid biosynthetic pathway is highly conserved in plants and occurs mostly in chromoplasts and chloroplasts. Leaf carotenoids play important photoprotective roles and targeted selection for leaf carotenoids may offer avenues to improve abiotic stress tolerance. A collection of 332 soybean [Glycine max (L.) Merr.] genotypes was grown in two years and total leaf carotenoid content was determined using three different methods. The first method was based on extraction and spectrophotometric determination of carotenoid content (eCaro) in leaf tissue, whereas the other two methods were derived from high-throughput canopy spectral reflectance measurements using wavelet transformed reflectance spectra (tCaro) and a spectral reflectance index (iCaro). An association mapping approach was employed using 31,253 single nucleotide polymorphisms (SNPs) to identify SNPs associated with total carotenoid content using a mixed linear model based on data from two growing seasons. A total of 28 SNPs showed a significant association with total carotenoid content in at least one of the three approaches. These 28 SNPs likely tagged 14 putative loci for carotenoid content. Six putative loci were identified using eCaro, five loci with tCaro, and nine loci with iCaro. Three of these putative loci were detected by all three carotenoid determination methods. All but four putative loci were located near a known carotenoid-related gene. These results showed that carotenoid markers can be identified in soybean using extract-based as well as by high-throughput canopy spectral reflectance-based approaches, demonstrating the utility of field-based canopy spectral reflectance phenotypes for association mapping.

Cup introduction, drink type and vitamin supplementation in preterm babies at 11-25 months.

BACKGROUND: To avoid adverse effects of prolonged bottle use, the recommendations are that full-term babies are introduced to cups from 6 months and discouraged bottles from 12 months old. There are no recommendations for preterm babies. In the UK, the Department of Heath recommends the introduction of vitamin supplements, alongside the transition from formula to cow's milk. The present study aimed to determine age of cup introduction in a group of preterm babies, identify drinks offered from bottles versus cups and the types of cups used, and establish the prevalence and appropriateness of vitamin supplementation. METHODS: A validated postal questionnaire was sent to the parents of 369 babies born <34 weeks of gestation at Queen Charlottes Neonatal Unit; 104 sent in 2003 and 265 sent in 2004-2005. The questionnaire was sent when the babies were calculated to be between 12 and 18 months (all ages stated are uncorrected). A separate questionnaire was sent for each baby from multiple pregnancies. RESULTS: The questionnaire return rate was 46% (n = 169). Length of gestation (P < 0.001), hospital stay (P = 0.009), birth weight (P = 0.002) and maternal age (P < 0.001) were significantly greater and more mothers were of European origin (P = 0.036) for those babies for whom questionnaires were returned compared to nonresponders. Infant gender did not differ. Fifty-seven percent had been introduced to a cup before 12 months, distribution was: 58% (n = 53) of singletons, 54% (n = 37) of twins and 67% (n = 6) of triplets. This rose to 80% before 13 months. Thirteen percent (n = 22) had not started drinking from a cup and 17% (n = 29) only used cups at the time of the questionnaire. Cow's milk had been introduced to 69% (n = 117) of all babies and 32% (n = 54) were still on formula (10 on both and eight were on neither; hence, the figures do not sum to 100%). Cow's milk was drunk from bottles by 56% (n = 95) and formula by 31% (n = 52). A significantly greater proportion of twins and triplets were drinking cow's milk compared to singletons [80% (n = 62) versus 60% (n = 55) P = 0.005] and significantly fewer were drinking formula [22% (n = 17) versus 40% (n = 37) P = 0.012]. Water was the drink most commonly given from a cup (80%) (n = 135) followed by juice, which was given to 64% (n = 108). Juice drinks were given by bottle in 16% (n = 27). Fifty-two percent (n = 88) used a 'spill-proof' cup some of the time. Vitamins were given as recommended in 18% (n = 31), given even though not recommended in 12% (n = 20), not given but recommended in 49% (n = 83) and appropriately not given in 21% (n = 35). A greater percentage of twins and triplets, compared to singletons, were not commenced on vitamins, even though they were no longer drinking formula. CONCLUSIONS: The present study reports baseline data on cup introduction in preterm babies both from singleton and multiple births. The data suggest that education about appropriate bottle drinks, timing of cup introduction, suitable cups and the correct use of vitamin drops is required. However, because the profile of responders differed from nonresponders, these results may not be applicable to all preterm babies.

Nanomedicine-nanoemulsion formulation improves safety and efficacy of the anti-cancer drug paclitaxel according to preclinical assessment.

Paclitaxel is an important anticancer drug and is currently used to treat a variety of cancers, including ovarian carcinomas, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma. The objectives of the studies were to assess and compare the safety and efficacy of EmPAC (a newly developed nanoemulsion formulation of paclitaxel) versus Taxol (the injectable formulation of paclitaxel involving the use of polyethylated or polyoxyl castor oil currently used in the clinic). The objectives were also to investigate the mechanism for the improved safety and efficacy of EmPAC over Taxol. These results showed that EmPAC had better anti-tumor efficacy than Taxol, according to in vitro cell culture studies and studies in animal tumor models. EmPAC had improved anti-tumor efficacy even in tumor cell lines that are known to be multi-drug resistant. Part of the mechanism of action for the improved efficacy may be related to EmPAC inducing greater cellular uptake of paclitaxel into tumor cells than Taxol did, according to the in vitro cell culture radioactive-labeled studies and in vitro cell culture antibody studies. It may also partly be because EmPAC delivered more paclitaxel to the tumor mass than Taxol, while the delivery of paclitaxel to other tissues (e.g., blood, muscle, liver, spleen, kidney and lung) were similar between the two formulations of paclitaxel, according to studies in animals with tumor xenograft. EmPAC also had better safety than Taxol according to toxicology studies in rabbits. This may be because EmPAC does not contain the toxic ingredients used in formulating Taxol (such as polyethylated or polyoxyl castor oil). These results support the clinical development of the nanoemulsion formulation of paclitaxel.

Augmentation of targeted delivery with pulsed high intensity focused ultrasound.

This paper reviews the enhanced delivery of genes, drugs and therapeutics using ultrasound. It begins with a general overview of the field and the various techniques associated with it, including sonophoresis, hyperthermia (with ultrasound), sonoporation, and microbubble assisted transvascular and targeted delivery. Particular attention is then paid to pulsed high intensity focused ultrasound drug delivery without the use of ultrasound contrast agents. Feasibility and mechanistic studies of this technique are described in some detail. Conclusions are then drawn regarding possible mechanisms of this treatment, and to contrast with the better known treatments relying on injection of ultrasound contrast agents.

Treating fallopian tube occlusion with a manual pelvic physical therapy.

OBJECTIVE: To determine the efficacy of a non-invasive, manual soft-tissue physical therapy in opening completely blocked fallopian tubes in infertile women with confirmed bilateral occlusion and a history indicative of abdominopelvic adhesions. DESIGN: Retrospective analysis. SETTING: Clear Passage Therapies, Inc, clinic, Gainesville, Florida. PATIENTS: 28 infertile women (mean age = 35.2) with diagnosed complete tubal occlusion (proximal, midtubal, distal, or combination). The patients were being treated for various types of abdominopelvic pain and dysfunction (eg, intercourse and/or pelvic pain, menstrual cramps, endometriosis pain). INTERVENTION: A 20-hour series of manual physical therapy treatments (mean duration = 1 week) designed to address pain and restricted soft tissue mobility due to adhesions and micro-adhesions. The therapists accessed some of the deeper structures (such as the fallopian tubes) indirectly by manipulating the peritoneum, uterine and ovarian ligaments, and neighboring structures. MAIN OUTCOME MEASURES: (1) Unilateral or bilateral tubal patency confirmed by diagnostic test or natural intrauterine pregnancy; (2) natural intrauterine pregnancy rate achieved by patent patients within the 2-year follow-up period. RESULTS: Of the 28 patients, 17 (61%, 95% exact CI 41%-78%) demonstrated post-treatment unilateral or bilateral patency, as measured by hysterosalpingography or natural intrauterine pregnancy. The median interval between the last treatment date and patency confirmation was 1 month. Nine of the 17 (53%) patent patients reported a subsequent natural intrauterine pregnancy. CONCLUSION: Since truly occluded tubes are not known to reopen spontaneously, the results suggest this non-invasive therapy might be considered as an adjuvant to standard gynecological procedures in treating tubal occlusion.

Effects of light on microalgae concentrations and selenium uptake in bivalves exposed to selenium-amended sediments.

The purpose of the current study was to evaluate the role of visible light during trophic transfer of the essential metalloid, selenium (Se) from sediments by way of the microalgae Phaeodactylum tricornutum to bivalves. Initial experiments compared uptake of Se with algal cell number after deposit-feeding (Tellina deltoidalis) and filter-feeding (Soletellina alba) bivalves were exposed for 12 days under 16:8 h light:dark and 24-hour dark regimes to sediments amended with Se (17 mg/kg dry weight). Comparisons of filter-feeding with deposit-feeding organisms indicated >2-fold higher body burdens in the deposit-feeding organisms after 12 days. Darkness failed to significantly and consistently diminish algal cell densities. However, general trends indicated a decrease of pelagic algal numbers in +Se/dark treatments during the 12-day exposure. To determine whether time-dependent patterns were present in the uptake of Se by the deposit-feeding species, a second experiment was conducted using Se-laden sediments under light and dark conditions. Algal cell counts were measured and Se concentrations determined in animals sampled at days 0, 3, 6, 9, and 12. Deposit-feeding animals maintained in the dark accumulated, Se more rapidly than animals on light to dark cycles until 12 days at which time no significant differences were observed between treatments. Concentrations of Se in tissues of deposit-feeding bivalves were not directly related to algal cell density in lighted or dark chambers. These results indicate that pelagic microalgae may only play a key role in Se uptake during early hours of exposure, and feeding behavior may be a more important factor in deposite-feeding bivalves.

Pulsed-high intensity focused ultrasound and low temperature-sensitive liposomes for enhanced targeted drug delivery and antitumor effect.

PURPOSE: To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. EXPERIMENTAL DESIGN: Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature-sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. RESULTS: In vitro incubations simulating the pulsed-HIFU thermal dose (42 degrees C for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. CONCLUSIONS: Combining low-temperature heat-sensitive liposomes with noninvasive and nondestructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women.

BACKGROUND: Seasonal Affective Disorder (SAD) is a sub-type of depression that only occurs during the winter months. A reduction in vitamin D may be linked to SAD. Since vitamin D deficiency has been reported to be common in older people, vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group. OBJECTIVE: To assess the effect of vitamin D supplementation on the mental health of older women. SETTING: Primary care in three areas of the UK (Herts, Newcastle, York). SUBJECTS: Women aged 70 years or more recruited to the trial in the months May-October. INTERVENTION: Eligible women were randomised to receive calcium and vitamin D supplementation or no supplementation. OUTCOME MEASURE: At baseline and the six monthly assessment the mental component score (MCS), calculated from the SF-12 questionnaire was used to assess participants' subjective psychological well-being. RESULTS: A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October (1205 woman in the control group and 912 women in the intervention group). Of these women, 1621 had a MCS score at baseline and six months. Comparison of the six month mean MCS scores, adjusting for baseline MCS score and age, showed there was no significant difference between the two scores (p = 0.262). CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

Combined chemical and enzymatic stable isotope labeling for quantitative profiling of detergent-insoluble membrane proteins isolated using Triton X-100 and Brij-96.

Effective quantitative profiling of detergent-insoluble membrane proteins using high-throughput mass spectrometry (MS)-based proteomics would allow a better understanding of physiological and pathological processes that take place at the cell surface. To increase the coverage of proteins present in detergent-resistant membrane microdomains (DRMMs), a combination of 16O/18O and isotope coded affinity tags (ICAT) labeling was used in a comparative analysis of detergent-insoluble membrane proteins isolated from rat basophilic leukemia cells (RBL-2H3), with either Triton X-100 or Brij-96. The analysis resulted in the quantification of 738 unique proteins from Triton X-100 and Brij-96 isolated DRMMs, significantly exceeding the number of proteins quantified from either single labeling technique. Twenty-five noncysteine-containing proteins were quantified, as well as 32 cysteine-containing proteins that would have been missed if either 16O/18O or ICAT labeling had been used exclusively, which illustrate better proteome coverage and enhanced ability to quantitate. The comparative analysis revealed that proteins were more readily extracted using Triton X-100 than Brij-96; however, Triton X-100 also extracted larger quantities of non-DRMMs-associated proteins. This result confirms previous, targeted studies suggesting that DRMMs isolated using Triton X-100 and Brij-96 differ in their protein content.

Increased osmolality of breast milk with therapeutic additives.

AIM: To evaluate the changes in the osmolality of expressed breast milk (EBM) after the addition of seven additives and four proprietary fortifiers commonly used during neonatal intensive care. METHODS: The osmolality of 5 ml EBM was measured with increasing doses of 6% NaCl, caffeine, sodium ironedetate, folic acid, and multivitamin drops. Sodium acid phosphate and chloral hydrate were added to 8 ml EBM, and the fortifiers were added to standard volumes of EBM. Dose-effect curves were plotted, and the volume of milk that must be added to the above additives to maintain osmolality below 400 mOsm/kg was calculated. RESULTS: The osmolality of the pure additives ranged from 242 to 951 mOsm/kg. There was a significant increase in the osmolality of EBM with increasing doses of all additives except caffeine. The osmolality of EBM with many additives in clinically used dosages potentially exceeded 400 mOsm/kg. The greatest increase occurred with sodium ironedetate syrup, where the osmolality of EBM increased to 951.57 (25.36) mOsm/kg. Proprietary fortifiers increased the osmolality of EBM to a maximum of 395 mOsm/kg. CONCLUSION: Routine additives can significantly increase the osmolality of EBM to levels that exceed current guidelines for premature infant feeding. A simple guide for clinical use is presented, which indicates the amount of milk required as diluent if hyperosmolality is to be avoided.

Radiation-induced tumour necrosis factor-alpha expression: clinical application of transcriptional and physical targeting of gene therapy.

Promising data are emerging on a new anticancer agent, Ad.EGR-TNF, an adenoviral vector, which contains radio-inducible DNA sequences from the early growth response (EGR1) gene promoter and cDNA for the gene encoding human tumour necrosis factor-alpha. Ad.EGR-TNF combines the well-documented broad-spectrum anticancer activity of TNFalpha with the proven clinical usefulness of radiotherapy. Systemic delivery of the TNFalpha protein has had limited success clinically because of severe dose-limiting toxic effects. This limitation has been overcome by the use of a gene delivery approach, combined with a radiation-inducible promoter to express the TNFalpha protein in the irradiated tumour tissue. Preclinical and early phase I clinical testing indicates that effective concentrations of TNFalpha can be delivered to the tumour site without significant systemic exposure or toxic effects. The combination of radiation and TNFalpha gene delivery has produced striking antitumour effects in model systems in animals. In the clinical setting, potent anticancer activity has been observed with a high rate of complete and partial objective tumour responses. A novel mechanism of destruction of the tumour vasculature seems to be central to this distinct antitumour activity. This review summarises the rationale, mechanistic basis, preclinical data, and preliminary clinical findings for this new treatment model.

External beam radiotherapy for synchronous rectal and prostatic tumors.

Two patients were diagnosed with large rectal tumors and localized prostate cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0 ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close proximity allowed creation of a modified three-dimensional conformal radiotherapy plan to treat both tumors. The patients had no evidence of rectal tumor recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL at 1 and 2 years after therapy, respectively. We conclude that efficient, effective pelvic irradiation can be designed for synchronous rectal and prostate malignancies.

Serum and liver lipids in rats fed diets containing corn oil, cottonseed oil, or a mixture of corn and cottonseed oils.

Previous research has demonstrated that the total replacement of corn oil (CO) with cottonseed oil (CSO) in the diets of growing male rats results in a lowering of the total cholesterol (TC) concentration in the serum. It is not, however, known if a partial replacement of dietary CO with CSO would be sufficient to lower TC levels, nor is the effect of replacing dietary CO with CSO on other indices of cholesterol status (e.g., the levels of high-density lipoprotein cholesterol [HDL-C], non-HDL-C [i.e., very-low and low-density lipoprotein-cholesterol], or the TC/HDL-C ratio). Growing male rats were fed diets having CO, CSO, or a CO/CSO (1:1, w/w) oil mixture (OM) as the source of dietary oil (diet groups CO, CSO, and OM, respectively). There were no differences between CO and OM groups for TC, HDL-C, non-HDL-C, or the TC/HDL-C ratio. However, TC was significantly lower (p < or = 0.05) for the CSO group than the CO group (2.85 vs. 3.23 mmol/l, or 110 vs. 125 mg/dl, respectively) as was HDL-C (1.83 vs. 2.13 mmol/l, or 71 vs. 82 mg/dl, respectively), but there were no differences between these groups for non-HDL-C or the TC/HDL-C ratio. Diet had no effect on serum triglycerides (TGs) or on total liver content of either cholesterol or TGs. Thus, partial (50%) replacement of CO with CSO was without effect on any of these serum indices of cholesterol status, but total replacement resulted in lower TC and HDL-C, without affecting non-HDL-C or the TC/HDL-C ratio. Because, relative to CO, CSO has higher levels of saturated fatty acids but lower levels of monounsaturated and polyunsaturated fatty acids, the cholesterol-lowering effect of CSO appears to be unrelated to its fatty acid composition, and may be caused by a component of its nonsaponifiable fraction.