Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)-an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO-control, AIA-untreated adjuvant-induced arthritis, AIA-BIL-adjuvant-induced arthritis administrated UCB, CO-BIL-control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund's adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.

Specific amino acid supplementation rescues the heart from lipid overload-induced insulin resistance and contractile dysfunction by targeting the endosomal mTOR-v-ATPase axis.

OBJECTIVE: The diabetic heart is characterized by extensive lipid accumulation which often leads to cardiac contractile dysfunction. The underlying mechanism involves a pivotal role for vacuolar-type H+-ATPase (v-ATPase, functioning as endosomal/lysosomal proton pump). Specifically, lipid oversupply to the heart causes disassembly of v-ATPase and endosomal deacidification. Endosomes are storage compartments for lipid transporter CD36. However, upon endosomal deacidification, CD36 is expelled to translocate to the sarcolemma, thereby inducing myocardial lipid accumulation, insulin resistance, and contractile dysfunction. Hence, the v-ATPase assembly may be a suitable target for ameliorating diabetic cardiomyopathy. Another function of v-ATPase involves the binding of anabolic master-regulator mTORC1 to endosomes, a prerequisite for the activation of mTORC1 by amino acids (AAs). We examined whether the relationship between v-ATPase and mTORC1 also operates reciprocally; specifically, whether AA induces v-ATPase reassembly in a mTORC1-dependent manner to prevent excess lipids from entering and damaging the heart. METHODS: Lipid overexposed rodent/human cardiomyocytes and high-fat diet-fed rats were treated with a specific cocktail of AAs (lysine/leucine/arginine). Then, v-ATPase assembly status/activity, cell surface CD36 content, myocellular lipid uptake/accumulation, insulin sensitivity, and contractile function were measured. To elucidate underlying mechanisms, specific gene knockdown was employed, followed by subcellular fractionation, and coimmunoprecipitation. RESULTS: In lipid-overexposed cardiomyocytes, lysine/leucine/arginine reinternalized CD36 to the endosomes, prevented/reversed lipid accumulation, preserved/restored insulin sensitivity, and contractile function. These beneficial AA actions required the mTORC1-v-ATPase axis, adaptor protein Ragulator, and endosomal/lysosomal AA transporter SLC38A9, indicating an endosome-centric inside-out AA sensing mechanism. In high-fat diet-fed rats, lysine/leucine/arginine had similar beneficial actions at the myocellular level as in vitro in lipid-overexposed cardiomyocytes and partially reversed cardiac hypertrophy. CONCLUSION: Specific AAs acting through v-ATPase reassembly reduce cardiac lipid uptake raising the possibility for treatment in situations of lipid overload and associated insulin resistance.

Dendrobium officinalis six nostrum ameliorates urate under-excretion and protects renal dysfunction in lipid emulsion-induced hyperuricemic rats.

AIM: Hyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. METHODS: The main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2 g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. RESULTS: DOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24 h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39 mg/g and 0.72 mg/g in DOS, respectively. CONCLUSION: DOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.

Evaluating the appropriate oral lipid tolerance test model for investigating plasma triglyceride elevation in mice.

The oral lipid tolerance test (OLTT) has been known to assess intestinal fat metabolism and whole-body lipid metabolism, but rodent models for OLTT are not yet established. Differences in OLTT methodology preclude the generation of definitive results, which may cause some confusion about the anti-hypertriglyceridemia effects of the test materials. To standardize and generate more appropriate methodology for the OLTT, we examined the effects of mice strain, dietary lipid sources, fasting period, and gender on lipid-induced hypertriglyceridemia in mice. First, lipid-induced hypertriglyceridemia was more strongly observed in male ddY mice than in C57BL/6N or ICR mice. Second, the administration of olive and soybean oils remarkably represented lipid-induced hypertriglyceridemia. Third, fasting period before the OLTT largely affected the plasma triglyceride elevation. Fasting for 12 h, but less than 48 h, provoked lipid-induced hypertriglyceridemia. Fourth, we explored the suppressive effects of epigallocatechin gallate (EGCG), a green tea polyphenol, on lipid-induced hypertriglyceridemia. The administration of 100 mg/kg of EGCG suppressed lipid-induced hypertriglyceridemia and intestinal lipase activity. Fifth, EGCG-induced suppressive effects were observed after lipid-induced hypertriglyceridemia was observed in male mice, but not in female mice. Lastly, lipid-induced hypertriglyceridemia could be more effectively induced in mice fed a high-fat diet for 1 week before the OLTT. These findings indicate that male ddY mice after 12 h fasting displayed marked lipid-induced hypertriglyceridemia in response to soybean oil. Hence, the defined experiment condition may be a more appropriate OLTT model for evaluating lipid-induced hypertriglyceridemia.

Blueberry Polyphenols Ameliorate Visible Light and Lipid-Induced Injury of Retinal Pigment Epithelial Cells.

Although dietary polyphenols are known to be beneficial to vision, the protective distinctions among different types of polyphenols are unclear. In this work, the visual benefits of various blueberry polyphenols were evaluated using an in vitro model of visible light-lipid-induced injury of retinal pigment epithelial cells. Results showed that, at 10.0 µg/mL, the phenolic acid-rich fraction was superior in inhibiting cell death (93.6% ± 2.8% of cell viability). Anthocyanin- and flavonoid-rich fractions shared similar advantages in preventing the expression of senescence-associated ß-galactosidase (34.8% ± 11.1% and 32.2% ± 9.7% of aged cells, respectively) and overexpression of vascular endothelial growth factor (51.8 ± 3.5 and 54.1 ± 6.5 pg/mL, respectively). The flavonoid-rich fraction also showed high activity in ameliorating phagocytosis (70.3% ± 12.6%) and cellular oxidative stress. These results were further confirmed by using the corresponding polyphenol standards. Improved inhibitory effects of polyphenol mixture on cell death and senescence-associated ß-galactosidase expression were also observed. Therefore, various polyphenols play diverse roles and exert synergistic effects in nourishing the retina.

Activities, bioavailability, and metabolism of lipids from structural membranes and oils: Promising research on mild cognitive impairment.

Concomitant with increased lifespan, large segments of the population are experiencing cognitive decline, which might progress to Alzheimer's disease (AD). Currently, there is no cure for AD and, once the neurodegenerative disorders are established, patients use pharmacologic therapy to slow the progression of the symptoms and require appropriate care to manage their condition. The preclinical stage of neural degeneration that progress through mild cognitive impairment (MCI) before the onset of AD is when it might be possible to introduce behavioral changes and pharma-nutritional interventions that modify the risk factors of MCI conversion to AD. Some food components accumulate in brain tissues, where they play essential roles. Among them, polar lipids, omega 3 fatty acids, and carotenoids appear to work additively or synergistically. Therefore, there is an opportunity to formulate nutraceuticals/functional foods to slow the progression of MCI. In this paper, we review the biochemical bases and recent interventions with bioactive lipids-rich formulations. Based on accumulated evidence, we propose that appropriate large-scale trials are warranted.

Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.

Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14days the rats were immunized with 5µg myelin oligodendrocyte glycoprotein (MOG) in incomplete Freund's Adjuvant, which did not cause any clinical signs but animals developed a stable anti-MOG antibody titer. Then the animals received an injection of proinflammatory cytokines through the catheter. This led to a demyelination of cortical and subcortical areas starting from day 1 in a cone-like pattern spreading from the catheter area towards the subarachnoid space. On day 3 cortical demyelination already expanded to the contralateral hemisphere and reached its peak between days 9-15 after cytokine injection with a widespread demyelination of cortical and subcortical areas of both hemispheres. Clinically the animals showed only discrete signs of fatigue and recovered completely after day 15. Even on day 30 we still were able to detect demyelination in subpial and intracortical areas along with areas of partial and complete remyelination. Loss of cortical myelin was accompanied with marked microglia activation. A second injection of cytokines through the catheter on day 30 led to a second demyelination phase with the same symptoms, but again no detectable motor dysfunction. Suffering of the animals appeared minor compared to standard Experimental Autoimmune Encephalomyelitis and therefore, even long-term observation and repeated demyelination phases seem ethically acceptable.

Hypothalamic Lipids: Key Regulators of Whole Body Energy Balance.

Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase and AMP-activated protein kinase, impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues not suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases such as insulin resistance, cardiomyopathy, atherosclerosis, and steatohepatitis. Current data have reported that, similar to what is observed in peripheral tissues, complex lipids such as ceramides and sphingolipids act as lipotoxic species at the hypothalamic level to impact metabolism. Here, we will review what is currently known about hypothalamic lipid metabolism and the modulation of energy homeostasis.

[Lipoid Pneumonia Associated with Lipid-Containing Nasal Sprays and Nose Drops]. / Lipidpneumonie durch Lipid-haltige Nasensprays und -tropfen.

BACKGROUND: Regularly updating the German pharmacopoeia on contemporary preparations DAC/NRF, chapter "Nasal Applications" and the recommendations on "Nasal Oils" as well as "Nasal Ointments and Emulsions", the issue of the risk of lipoid pneumonia associated with the use of plant oils and when compared to mineral oils arose. MATERIAL AND METHODS: We searched different databases: the "Grosse Deutsche Arzneimittelspezialitäten-Taxe" containing all products available in German pharmacies, the Cochrane Library, the pharmacovigilance-database of the BfArM, and Medline to evaluate the benefit/risk-ratio of plant oils in nasal drops and sprays. RESULTS: In German pharmacies, a number of both, mineral oil-containing drugs for nasal application and plant oil-containing medical devices are available. The risk of lipoid pneumonia described for mineral oil-containing nasal products can not entirely be transferred to plant oil-containing products. However, evidence from the literature suggests a risk for lipoid pneumonia, which needs to be considered given the non-proven efficacy of such medical devices in the majority of proposed indications. To minimize risks, recommendations are made for patient groups that should not use lipid-containing nasal products. CONCLUSIONS: Acknowledging the potential lethal outcome of lipoid pneumonia, a demanding diagnosis, and absence of a specific therapy, lipid-containing nasal products should be used only with great caution. Based on the current knowledge, the statements regarding the risk of lipoid pneumonia for lipid-containing nasal products in the DAC/NRF should not be modified.

Development and Evaluation of Lipid Nanoparticles for Drug Delivery: Study of Toxicity In, Vitro and In Vivo.

Lipid nanoparticles have received considerable attention in the field of drug delivery, due their ability to incorporate lipophilic drugs and to allow controlled drug release. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) are three different lipid nanostructured systems presenting intrinsically physical properties, which have been widely studied in recent years. Despite the extensive applicability of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated thus far. It is generally believed that lipids are biocompatible. However, it is known that materials structured in nanoscale might have their intrinsic physicochemical properties modified. Thus, the aim of this study was to evaluate the cytotoxicity of these three nanoparticle systems. To this end, in vitro and in vivo toxicity studies were carried out. Our results indicate that nanoparticles containing the solid lipid GMS (SLN and NLC) induced an important cytotoxicity in vitro, but showed minimal toxicity in vivo--evidenced by the body weight analysis. The NE did not induce in vitro toxicity and did not induce body weight alteration. On the contrary, the SLN and NLC possibly induce an inflammatory process in vivo. All nanoparticle systems induced lipid peroxidation in the animals' livers, but only SLN and NLC induced a decrease of antioxidant defences indicating that the main mechanism of toxicity is the induction of oxidative stress in liver. The higher toxicity induced by SLN and NLC indicates that the solid lipid GMS could be the responsible for this effect. Nevertheless, this study provides important insights for toxicological studies of different lipid nanoparticles systems.

Extra virgin olive oil phenolic extracts counteract the pro-oxidant effect of dietary oxidized lipids in human intestinal cells.

The phenolic fraction of extra virgin olive oil (EVOO) concentrates before absorption in the intestinal lumen, where it may contribute to the modulation of enterocytes response to oxidative and inflammatory stimuli. We evaluated the ability of two monovarietal EVOOs phenolic extracts, Bosana and Nera di Gonnos/Tonda di Cagliari, typical and widespread varieties in Sardinia (Italy), to counteract in enterocytes like Caco-2 cells the pro-oxidant action of oxidized lipids, tert-butyl hydroperoxide (TBH) or a mixture of oxysterols of dietary origin. We confirmed that TBH treatment causes a significant increase of ROS production, GSH depletion, increase of MDA, fatty acids hydroperoxides and 7-ketocholesterol, and showed first evidence of oxidative imbalance and cell damage due to oxysterols exposure. Preincubation of cells with the phenolic extracts significantly attenuated oxidative modifications. Bosana extract showed the highest concentration of total phenols, mainly hydroxytyrosol and tyrosol, and was the most active in presence of TBH, where the free radical scavenging activity of these simple phenols seems to be a determining factor. The two extracts were equally effective, in spite of the different composition, in presence of oxysterols, where ROS production probably occurs according to different and more complex mechanisms.

The Safety and Efficacy of a Sustainable Marine Extract for the Treatment of Thinning Hair: A Summary of New Clinical Research and Results from a Panel Discussion on the Problem of Thinning Hair and Current Treatments.

Alopecia and thinning hair are highly prevalent conditions affecting a large proportion of men and women. Diffused hair loss is often more difficult to diagnose in women, mostly due to over-reliance on the assumption of hormonal influences, and it is commonly treated with a multi-therapy approach. Clinical studies have demonstrated the effectiveness of a nutraceutical supplement to provide essential nutrients that aid in stimulating existing hair growth and reducing hair shedding. The supplement Viviscal® contains a proprietary blend of proteins, lipids, and glycosaminoglycans derived from sustainable marine sources. We present here a summary of studies that have examined the safety and efficacy of this nutraceutical; as well as discussions on hair loss and current therapies from a recently convened expert panel in dermatology and plastic surgery.

Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo.

Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1) L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by (1)H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo.

Submicron complex lipid carriers for curcumin delivery to intestinal epithelial cells: Effect of different emulsifiers on bioaccessibility and cell uptake.

Submicrometric lipid-based carriers were developed to encapsulate curcumin and deliver it to intestinal epithelial cells. A lipid matrix comprising monoolein, sunflower oil and water at weight ratio 1:1:1 was selected, upon screening of different combinations of amphiphilic molecules, vegetable oils and water, because of its high encapsulations efficiency of curcumin, retained over time and relatively lower content of amphiphilic molecules. Upon dispersion in aqueous phase, the carriers were stabilized by: (a) whey protein isolates (WPI), alone and (b) in combination with modified starch (WPI-MS), or by (c) polysorbate 20 (T20). Whereas T20-stabilized systems exhibited extremely fine particles (120 nm), WPI and WPI-MS stabilized carriers were characterized by a significantly larger mean particle size (270 nm). The thicker macromolecular layer of WPI and WPI-MS enabled better (a) physical stability, (b) controlled shell degradation during simulated digestion, and (c) curcumin bioaccessibility targeted at the intestinal digestion phase than T20-systems. However, uptake studies in HT29 cell lines, simulating intestinal epithelial cells, showed that WPI and WPI-MS carriers exhibited after 24h a lower relative uptake than T20-stabilized systems (about 60% and 80%, respectively), as a consequence of smaller size and higher cell adherence of T20 carriers to the cell membrane.

Perna canaliculus lipid complex PCSO-524™ demonstrated pain relief for osteoarthritis patients benchmarked against fish oil, a randomized trial, without placebo control.

Osteoarthritis (OA) typically generates pain, reduced mobility and reduced quality of life. Most conventional treatments for osteoarthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesics, have side effects. PCSO-524™, a non polar lipid extract from the New Zealand Green Lipped Mussel, is rich in omega-3 fatty acids and has been shown to reduce inflammation in both animal studies and patient trials. This OA trial examined pain relief changes in relation to quality of life and safety of use for OA patients who took PCSO-524™ compared with patients who took fish oil (containing an industry standard EPA-18% and DHA-12% blend). PCSO-524™ patients showed a statistically significant improvement compared with patients who took fish oil. There was an 89% decrease in their pain symptoms and 91% reported an improved quality of life. Patients treated with fish oil showed significantly less improvement and a greater level of physical discomfort during the study. These results suggest that PCSO-524™ might offer a potential alternative complementary therapy with no side effects for OA patients.

The acceptability, feasibility, and efficacy (phase I/II study) of the OVERcome (Olive Oil, Vaginal Exercise, and MoisturizeR) intervention to improve dyspareunia and alleviate sexual problems in women with breast cancer.

INTRODUCTION: Almost half of breast cancer survivors experience chronic sexual problems. Despite the negative effects of dyspareunia on physical and overall quality of life, sexual dysfunction remains underreported and undertreated in clinical practice. This is likely due to the paucity of evidence-based interventions to improve sexual functioning. AIM: The study aims to prospectively evaluate the acceptability, feasibility, and efficacy of a novel intervention (Olive Oil, Vaginal Exercise, and MoisturizeR [OVERcome]) to improve sexual problems following breast cancer treatment. MAIN OUTCOME MEASURES: Dyspareunia, sexual functioning, quality of life, distress, and pelvic floor muscles (PFMs) functioning were evaluated. METHODS: Twenty-five women with dyspareunia were instructed to perform pelvic floor muscle (PFM) relaxation exercises twice/day to prevent/manage PFM overactivity, apply a polycarbophil-based vaginal moisturizer three times/week to alleviate vaginal dryness, use olive oil as a lubricant during intercourse, and complete a weekly compliance diary. PFM relaxation training was administered by a physiotherapist at weeks 0 and 4, with follow-up at weeks 12 and 26. At each visit, women completed validated self-report questionnaires and the physiotherapist recorded objective measures of PFM functioning. RESULTS: OVERcome resulted in significant improvements in dyspareunia, sexual function, and quality of life over time (all P<0.001). PFM relaxation training was reported to be effective (P≤0.001). Maximum benefits were observed at week 12. Most women rated PFM relaxation exercises (92%), vaginal moisturizer (88%), and olive oil (73%) as helpful, indicating that the intervention was acceptable. Unexpectedly, six cases (11%) of vaginal stenosis were noted during initial screening. CONCLUSIONS: This novel intervention is acceptable to patients with demonstrated efficacy in improving dyspareunia and sexual function following breast cancer. Delivery of the OVERcome intervention appears feasible in a clinical setting, providing a potential treatment for this important clinical issue. The unexpected number of observed cases of stenosis further highlights the underreporting of sexual problems in this population, deserving further exploration.

Role of disease and macronutrient dose in the randomized controlled EPaNIC trial: a post hoc analysis.

RATIONALE: Early parenteral nutrition to supplement insufficient enteral feeding during intensive care (early PN) delays recovery as compared with withholding parenteral nutrition for 1 week (late PN). OBJECTIVES: To assess whether deleterious effects of early PN relate to severity of illness or to the dose or type of macronutrients. METHODS: Secondary analyses of a randomized controlled trial (EPaNIC; n = 4,640) performed in seven intensive care units from three departments in two Belgian hospitals. In part 1, all patients were included to assess the effect of the randomized allocation to early PN or late PN in subgroups of patients with increasing-on-admission severity of illness. In part 2, observationally, the association of the amount and type of macronutrients with recovery was documented in those patient cohorts still present in intensive care on Days 3, 5, 7, 10, and 14. MEASUREMENTS AND MAIN RESULTS: The primary end point was time to live discharge from the intensive care unit. For part 1, a secondary end point, acquisition of new infections, was also analyzed. All statistical analyses were performed by univariable and adjusted multivariable methods. In none of the subgroups defined by type or severity of illness was a beneficial effect of early PN observed. The lowest dose of macronutrients was associated with the fastest recovery and any higher dose, administered parenterally or enterally, was associated with progressively more delayed recovery. The amount of proteins/amino acids rather than of glucose appeared to explain delayed recovery with early feeding. CONCLUSIONS: Early combined parenteral/enteral nutrition delayed recovery irrespective of severity of critical illness. No dose or type of macronutrient was found to be associated with improved outcome. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions.

The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.

Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts.

BACKGROUND: To scientifically test a traditionally belief of some Asian countries residents that opium may prevent or have ameliorating effects on cardiovascular diseases (CVD) we investigated the effect of passive opium smoking (POS) on plasma lipids and some cardiovascular parameters in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. METHODS: 40 rabbits were fed for 2 weeks with cholesterol-enriched diet and divided to control (CTL), short-term opium (SO) and long-term opium (LO) groups. SO and LO groups were exposed to POS for 3 days and 4 weeks respectively. ECG, blood pressure (BP) and left ventricular pressure recorded and serum lipid and cardiac troponin I levels were measured. Isoproterenol (ISO) injected for induction of cardiac ischemia and after 4h the above variables were measured along with cardiac histopathology assessment. RESULTS: HDL cholesterol decreased significantly in LO compared to CTL group (35+/-5 vs 53+/-5mg/dl). Groups treated with ISO showed significantly higher increments in troponin I level (P<0.05) except for LO group and reduction of BP was higher in ISO and SO+ISO groups compared to CTL and SO groups respectively (-38+/-6 vs -23+/-4 and -37+/-11 vs -11+/-3 percent respectively, P<0.05). Reduction in BP was significantly lower in LO+ISO compared to ISO group. Opium exposure caused a trend of increase in blood pressure, LDL cholesterol and ECG disturbances, attenuated ISO induced myonecrosis but augmented tissue congestion and hemorrhage. CONCLUSION: POS can be considered as a CVD risk factor. Opium does not reduce BP or cholesterol level, as is anticipated by its users.