Microencapsulated Tuna Oil Results in Higher Absorption of DHA in Toddlers.

: Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving the stability and bioavailability of DHA at levels akin to human breast milk. The aims of this study were (a) to investigate the bioavailability of microencapsulated omega-3 DHA formulations in healthy toddlers compared with high DHA fish oil for a one-month period and (b) to assess the effect of DHA supplementation on children's sleep and cry patterns. Sixty toddlers were randomly allocated to four groups: 1. unfortified formula, 2. unfortified formula plus high DHA tuna oil, 3. fortified formula with dairy-based microencapsulated high DHA tuna oil powder, and 4. fortified formula with allergenic-free microencapsulated high DHA tuna oil powder. Bioavailability was assessed from both blood and faecal fatty acid levels. The results showed an enhanced bioavailability with significantly greater concentrations of blood DHA levels in formulas with microencapsulated powders. There were no significant effects of treatment on sleep and cry patterns. Application and delivery of microencapsulated DHA tuna oil powder in toddlers' formula provided better bioavailability of the active DHA.

How does high DHA fish oil affect health? A systematic review of evidence.

The health benefits of fish oil, and its omega-3 long chain polyunsaturated fatty acid content, have attracted much scientific attention in the last four decades. Fish oils that contain higher amounts of eicosapentaenoic acid (EPA; 20:5n-3) than docosahexaenoic acid (DHA; 22:6n-3), in a distinctive ratio of 18/12, are typically the most abundantly available and are commonly studied. Although the two fatty acids have traditionally been considered together, as though they were one entity, different physiological effects of EPA and DHA have recently been reported. New oils containing a higher quantity of DHA compared with EPA, such as fractionated and concentrated fish oil, tuna oil, calamari oil and microalgae oil, are increasingly becoming available on the market, and other oils, including those extracted from genetically modified oilseed crops, soon to come. This systematic review focuses on the effects of high DHA fish oils on various human health conditions, such as the heart and cardiovascular system, the brain and visual function, inflammation and immune function and growth/Body Mass Index. Although inconclusive results were reported in several instances, and inconsistent outcomes observed in others, current data provides substantiated evidence in support of DHA being a beneficial bioactive compound for heart, cardiovascular and brain function, with different, and at times complementary, effects compared with EPA. DHA has also been reported to be effective in slowing the rate of cognitive decline, while its possible effects on depression disorders are still unclear. Interestingly, gender- and age- specific divergent roles for DHA have also been reported. This review provides a comprehensive collection of evidence and a critical summary of the documented physiological effects of high DHA fish oils for human health.

Reproductive toxicity of denosumab in cynomolgus monkeys.

Denosumab is a monoclonal antibody that inhibits bone resorption by targeting RANKL, an essential mediator of osteoclast formation, function, and survival. Reproductive toxicity of denosumab was assessed in cynomolgus monkeys in an embryofetal development study (dosing GD20-50) and a pre-postnatal toxicity study (dosing GD20-parturition). In the embryofetal toxicity study, denosumab did not elicit maternal toxicity, fetal harm or teratogenicity. In the pre-postnatal toxicity study, there were increased stillbirths, and one maternal death due to dystocia. There was no effect on maternal mammary gland histomorphology, lactation, or fetal growth. In infants exposed in utero, there was increased postnatal mortality, decreased body weight gain, and decreased growth/development. Denosumab-related effects in infants were present in bones and lymph nodes. There was full recovery at 6 months of age from most bone-related changes observed earlier postpartum. The effects observed in mothers and infants were consistent with the pharmacological action of denosumab.

Medication adherence in the MTA: saliva methylphenidate samples versus parent report and mediating effect of concomitant behavioral treatment.

OBJECTIVE: Although research supports the use of appropriately administered stimulant medication to treat children with ADHD, poor adherence and early termination undermine the efficacy of this treatment in real-world settings. Moreover, adherence measures often rely on parent report of medication use, and their validity and reliability are unknown. METHOD: Drawing on data from 254 participants in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder, we examine the discrepancy between parents' verbal reports of medication adherence and physiological adherence measures determined via methylphenidate saliva assays collected at four time points during the 14-month treatment period. In addition, we examine the impact of physiologically documented medication adherence on parent- and teacher-reported outcomes through 14 months. RESULTS: Overall, nearly one fourth (24.5%) of the saliva samples indicated nonadherence. Among subjects, 63 (24.8%) of the 254 participants were nonadherent on 50% or more of their repeated saliva assays. Only 136 (53.5%) of the subjects were adherent at every time point at which saliva assays were taken, indicating that some degree of nonadherence characterized nearly half of all other NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder-treated children. Findings also indicated that nonadherence produced greater deleterious effects in children in the medication-only condition compared with those receiving both medication and behavioral treatment. CONCLUSIONS: Same-day saliva methylphenidate assays suggest that nearly half of the parents are inaccurate informants of their child's ADHD medication adherence and that parents may overestimate actual (physiological) adherence. This finding suggests the need for interventions to improve accuracy of parental report. Clinicians need to focus on adherence enhancement strategies to improve outcomes of children being treated with medication, particularly when benefits are suboptimal.

Preclinical safety and pharmacokinetics of recombinant human factor XIII.

Factor XIII (FXIII) is a thrombin-activated protransglutaminase responsible for fibrin clot stabilization and longevity. Deficiency in FXIII is associated with diffuse bleeding and wound-healing disorders in humans. This report summarizes results from several studies conducted in adult cynomolgus monkeys (M. fascicularis) to evaluate the safety and pharmacokinetics of recombinant human factor XIII A(2) dimer (rFXIII). Intravenous slow bolus injection of rFXIII resulted in the expected formation of the heterotetramer rA(2)cnB(2), prolonged circulating half-life (5-7 days), and increased plasma transglutaminase activity. Recombinant FXIII was well tolerated as a single dose up to 20 mg/kg rFXIII (2840 U/kg), as repeated daily doses up to 6 mg/kg (852 U/kg) for 14 days, and as 3 repeated doses of 8 mg/kg (1136 U/kg) separated by 14 days. Overt toxicity occurred after a single intravenous injection of = 22.5 mg/kg rFXIII (3150 U/kg), or with 2 doses of = 12.5 mg/kg (1775 U/kg) administered within 72 hours. The rFXIII-mediated toxicity was expressed as an acute systemic occlusive coagulopathy. Evaluation of plasma samples from dosed animals demonstrated formation of cross-linked fibrin/fibrinogen oligomers and higher-order protein aggregates, which are hypothesized to be responsible for the observed vessel occlusion and associated embolic sequelae. These results demonstrate that rFXIII-mediated toxicity results from exaggerated pharmacological activity of the molecule at supraphysiological concentrations. The absence of observed toxicological effect with repeated intravenous doses up to 8 mg/kg (1136 U/kg) was used to support an initial clinical dose range of 0.014 to 0.35 mg/kg (2-50 U/kg).

Society of Toxicologic Pathology position on histopathology data collection and audit trail: compliance with 21 CFR parts 58 and 11.

The purpose of this paper is to discuss the requirement of the audit trail to track changes made to the histopathology data, in order to be compliant with the Code of Federal Regulations (CFR), Volume 21, for both Part 58 (Good Laboratory Practices [GLP]) and Part 11 (Electronic Records/Signatures).