Lymphatic absorption of α-linolenic acid in rats fed flaxseed oil-based emulsion

The bioavailability of α-linolenic acid (ALA) from flaxseed oil in an emulsified form v. a non-emulsified form was investigated by using two complementary approaches: the first one dealt with the characterisation of the flaxseed oil emulsion in in vitro gastrointestinal-like conditions; the second one compared the intestinal absorption of ALA in rats fed the two forms of the oil. The in vitro study on emulsified flaxseed oil showed that decreasing the pH from 7·3 to 1·5 at the physiological temperature (37°C) induced instantaneous oil globule coalescence. Some phase separation was observed under acidic conditions that vanished after further neutralisation. The lecithin used to stabilise the emulsions inhibited TAG hydrolysis by pancreatic lipase. In contrast, lipid solubilisation by bile salts (after lipase and phospholipase hydrolysis) was favoured by preliminary oil emulsification. The in vivo absorption of ALA in thoracic lymph duct-cannulated rats fed flaxseed oil, emulsified or non-emulsified, was quantified. Oil emulsification significantly favoured the rate and extent of ALA recovery as measured by the maximum ALA concentration in the lymph (Cmax?=?14?mg/ml at 3?h in the emulsion group v. 9?mg/ml at 5?h in the oil group; P?相似文献   

Alternative payment and care‐delivery models in oncology: A systematic review

Rising US health care costs have led to the creation of alternative payment and care‐delivery models designed to maximize outcomes and/or minimize costs through changes in reimbursement and care delivery. The impact of these interventions in cancer care is unclear. This review was undertaken to describe the landscape of new alternative payment and care‐delivery models in cancer care. In this systematic review, 22 alternative payment and/or care‐delivery models in cancer care were identified. These included 6 bundled payments, 4 accountable care organizations, 9 patient‐centered medical homes, and 3 other interventions. Only 12 interventions reported outcomes; the majority (n = 7; 58%) improved value, 4 had no impact, and 1 reduced value, but only initially. Heterogeneity of outcomes precluded a meta‐analysis. Despite the growth in alternative payment and delivery models in cancer, there is limited evidence to evaluate their efficacy. Cancer 2018. © 2018 American Cancer Society.     

Fast cerebellar oscillation associated with ataxia in a mouse model of Angelman syndrome

Ataxia may result from various cerebellar cortex dysfunctions. It is included in the diagnostic criteria of Angelman syndrome, a human neurogenetic condition. In order to better understand the cerebellar dysfunction in this condition, we recorded in vivo cerebellar activity in a mouse model of Angelman syndrome produced by null mutation of the maternal Ube3a gene. We found fast oscillation (approximately 160 Hz) in the cerebellar cortex sustained by abnormally increased Purkinje cell firing rate and rhythmicity. This oscillation is inhibited by sensory stimulation and gap junction or GABA(A) receptor blockers. A physiologically similar oscillation was previously found in mice lacking calcium-binding proteins that also present ataxia, but never in wild-type mice. We propose that fast oscillation in the cerebellar cortex is implicated in the cerebellar symptomatology of Angelman syndrome.     

3,4-Methylenedioxy-N-methamphetamine (ecstasy) promotes the survival of fetal dopamine neurons in culture

The current study examined whether modest concentrations of MDMA could increase the survival and/or neurite outgrowth of fetal midbrain dopamine (DA) neurons in vitro since increased DA neurite outgrowth has been previously observed in vivo from prenatal exposure. MDMA concentrations in fetal brain were quantified to determine relevant in vivo concentrations to employ in vitro. A dose response study in vitro demonstrated that MDMA, at concentrations observed in vivo, resulted in increased, DA-specific, neuron survival. Higher doses resulted in non-specific neurotoxicity. MDMA application immediately after culture establishment resulted in greater survival than delayed application, however both were superior to control. MDMA significantly increased the expression of the slc6a3 gene (dopamine transporter; DAT) in culture. Co-application of the DAT reuptake inhibitor methylphenidate (MPH) with MDMA attenuated this effect. Progressive reductions in MPH concentrations restored the MDMA-induced survival effect. This suggests that MDMA's action at DAT mediates the survival effect. Neurite density per neuron was unaffected by MDMA in vitro suggesting that MDMA promotes DA neuron survival but not neurite outgrowth in culture. Finally, animals prenatally exposed to MDMA and examined on postnatal day 35 showed an increase in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra but not in the ventral tegmental area. These data suggest that during development, MDMA can increase the survival of DA neurons through its action at its transporter. Understanding how MDMA increases DA neuron survival may provide insight into normal DA neuron loss during development.     

Evidence for a New Crystalline Phase of Racemic Ibuprofen

Purpose  The aim of this work is to search for the existence of crystalline polymorphism for racemic Ibuprofen. Methods  The pharmaceutical material was studied by X-ray diffraction to identify crystalline phases, and by Differential Scanning Calorimetry to follow the thermodynamic evolution of these forms versus temperature. Results  Results presented here show that, in addition to the already known conventional crystalline phase, whose nucleation domain extends between 233 K and 263 K and which melts at 349 K, racemic Ibuprofen can crystallize in another polymorphic phase. The nucleation of this new polymorphic variety is triggered by a stay at least 60 degrees below the glass transition temperature Tg of Ibuprofen (Tg = 228 K). This nucleation is probably of heterogeneous type. The new phase melts well below the conventional one, i.e. at 290 K. A schematic free energy diagram is provided allowing establishing the relative thermodynamic stability of the two polymorphs. Conclusions  These results establish, for the first time, that Ibuprofen can exist under two different crystalline phases which constitute a monotropic system, the new form being metastable.     

Role of 3D volume growth rate for drug activity evaluation in meningioma clinical trials: the example of the CEVOREM study

BackgroundWe aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome.MethodsWe performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment.ResultsClass 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = −18.7%/month within 3 first months and −0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = −0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones.ConclusionsTumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.