Randomized controlled trial assessing two commercial weight loss programs in adults with overweight or obesity.

Objective: Lifestyle interventions remain the cornerstone for obesity treatment. Commercial programs offer one weight loss approach, yet the efficacy of few such programs have been rigorously investigated. The purpose of this study was to evaluate the efficacy of two commercial weight-loss programs, both utilizing pre-portioned meal replacements (MRs) and different levels of behavioural support, compared to a self-directed control diet in adults with overweight and obesity.

Effect of an Energy-Restricted, Nutritionally Complete, Higher Protein Meal Plan on Body Composition and Mobility in Older Adults With Obesity: A Randomized Controlled Trial.

Background: Increasing protein content of the diet might be an effective strategy to preserve muscle mass in older adults undergoing caloric restriction, thereby preserving muscle function.

Methods: Ninety-six older adults (70.3 ± 3.

Comparative effectiveness of a portion-controlled meal replacement program for weight loss in adults with and without diabetes/high blood sugar.

Background: Individuals with type 2 diabetes (DM2) may be less successful at achieving therapeutic weight loss than their counterparts without diabetes. This study compares weight loss in a cohort of adults with DM2 or high blood sugar (D/HBS) to a cohort of adults without D/HBS. All were overweight/obese and following a reduced or low-calorie commercial weight-loss program incorporating meal replacements (MRs) and one-on-one behavioral support.

Effectiveness of a Medifast meal replacement program on weight, body composition and cardiometabolic risk factors in overweight and obese adults: a multicenter systematic retrospective chart review study.

Background: Recent medical guidelines emphasize the importance of actively treating overweight and obesity with diet and lifestyle intervention to achieve ≥ 5% weight loss in a 6-month period. Commercial programs offer one approach provided there is evidence of their efficacy and safety. This study was conducted to evaluate the effectiveness of the Medifast® 4 & 2 & 1 Plan™ on weight loss, body composition and cardiometabolic risk factors in overweight and obese adults.

Developing regulatory strategy for microbicides.

Ever since the discovery that a virus was responsible for AIDS, prevention of HIV infection has been a drug/vaccine development target in therapeutic research. Microbicide products are a viable, globally applicable option; however, to date, no product has been approved anywhere in the world. Development of such a product will need to account for the changing disease landscape and will need to leverage available regulatory pathways to gain approvals in the developed world and emerging markets.

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.

Background: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae.

Aim: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge.

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.

Objectives: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1-mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions.

Docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-6) algal oils reduce inflammatory mediators in human peripheral mononuclear cells in vitro and paw edema in vivo.

The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA.

Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6).

17S-HDPAn-6 (17S-hydroxydocosa-4Z,7Z,10Z,13Z,15E-pentaenoic acid) and 10S,17S-HDPAn-6 (10S,17S-dihydroxydocosa-4Z,7Z,11E,13Z,15E-pentaenoic acid) are potent anti-inflammatory resolvins derived from DPAn-6 (docosapentaenoic acid n-6) and are analogous in structure and action to DHA (docosahexaenoic acid)-derived resolvins. These resolvins have proven to be potential drug candidates, albeit with therapeutic profiles that need optimization. The main objectives of this study were to evaluate key features of DPAn-6 derived resolvins that are important for therapeutic efficacy, demonstrate that these DPAn-6 resolvins could be produced naturally, and could therefore have physiological significance.

Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6).

Enzymatically oxygenated derivatives of the omega-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C.

Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid.

Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests.

Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food.

Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food.

Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide.

Concentrations of the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) in human breast milk are important indicators of infant formula DHA and AA concentrations, and recent evidence suggests that neural maturation of breastfed infants is linked to breast-milk LCPUFA concentrations. We report a descriptive meta-analysis that considered 106 studies of human breast milk culled to include only studies that used modern analysis methods capable of making accurate estimates of fatty acid (FA) profiles and criteria related to the completeness of reporting. The final analysis included 65 studies of 2474 women.

Distribution, interconversion, and dose response of n-3 fatty acids in humans.

n-3 Fatty acids have important visual, mental, and cardiovascular health benefits throughout the life cycle. Biodistribution, interconversion, and dose response data are reviewed herein to provide a basis for more rational n-3 dose selections. Docosahexaenoic acid (DHA) is the principal n-3 fatty acid in tissues and is particularly abundant in neural and retinal tissue.

The interaction between cytoplasmic prion protein and the hydrophobic lipid core of membrane correlates with neurotoxicity.

Prion protein (PrP), normally a cell surface protein, has been detected in the cytosol of a subset of neurons. The appearance of PrP in the cytosol could result from either retro-translocation of misfolded PrP from the endoplasmic reticulum (ER) or impaired import of PrP into the ER. Transgenic mice expressing cytoplasmic PrP (cyPrP) developed neurodegeneration in cerebellar granular neurons, although no detectable pathology was observed in other brain regions.

Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress.

Quinones permeate our biotic environment, contributing to both homeostasis and cytotoxicity. All quinones generate reactive oxygen species through redox cycling, while partially substituted quinones also undergo arylation (Michael adduct formation) yielding covalent bonds with nucleophiles such as cysteinyl thiols. In contrast to reactive oxygen species, the role of arylation in quinone cytotoxicity is not well understood.

Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients: a randomized, controlled study.

Objective: Several studies have reported omega-3 and omega-6 fatty acid imbalances in patients with cystic fibrosis (CF). Whether these imbalances contribute to or are manifestations of the pathophysiology of CF is unknown. The study objective was to determine bioavailability, tissue accretion, and safety of a large dose of an algal source of docosahexaenoic acid (DHA) triacylglycerol and to observe effects on lung function in patients with CF.

Maintenance of liver functions in rat hepatocytes cultured as spheroids in a rotating wall vessel.

Rat hepatocytes were cultured initially as spheroids on culture plates and then transferred into a rotating wall vessel (high-aspect ratio vessel [HARV]) for further culturing. Morphological evaluation based on electron microscopy showed that hepatocyte spheroids cultured for 30 d in the HARV had a compact structure with tight cell-cell junctions, numerous smooth and rough endoplasmic reticulum, intact mitochondria, and bile canaliculi lined with microvilli. The viability and differentiated properties of the hepatocytes cultured in the HARV were further substantiated by the presence of both phase I oxidation and phase II conjugation drug-metabolizing enzyme activities, as well as albumin synthesis.

In vitro genotoxicity testing of ARASCO and DHASCO oils.

ARASCO and DHASCO oils are microbially-derived triglycerides rich in arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids, respectively. Both oils were tested for mutagenic activity in three different in vitro mutagenesis assays. All assays were conducted with and without metabolic activation.

A developmental safety study in rats using DHA- and ARA-rich single-cell oils.

The long-chain omega-3 and omega-6 fatty acids, docosahexaenoic and arachidonic acids, are important in fetal development, but may be depleted from the mother during pregnancy as she transfers reserves to the developing fetus in utero and later to the infant through her breast milk. Pregnant women can increase their dietary intake of these nutrients to maintain adequate maternal reserves and ensure an optimal infant supply. DHASCO(R) and ARASCO(R) oils, concentrated sources of docosahexaenoic and arachidonic acids, respectively, have been tested in acute and subchronic studies without toxic effects.

A combined subchronic (90-day) toxicity and neurotoxicity study of a single-cell source of docosahexaenoic acid triglyceride (DHASCO oil).

Docosahexaenoic acid (DHA), a 22-carbon long-chain polyunsaturated fatty acid of the omega-3 family, is a major structural component of neural membranes and is a particularly important nutrient during infant development. New safe and well-defined sources of DHA are required for infant formula fortification and dietary supplementation. DHASCO oil is an algal-derived triglyceride containing 40-50% DHA.

Characterization of a primary hepatocyte culture system for toxicological studies.

An hepatocyte culture system was developed for potential use in toxicological studies in vitro. Rat hepatocytes were isolated by two-step collagenase perfusion and cultured on Vitrogen-coated Permanox dishes in a modified Chee's medium containing 1 microM dexamethasone and 1% dimethylsulfoxide. The cells remained highly viable for at least 10 d as determined by lactate dehydrogenase release and total protein levels.