Occurrence of birefringent retinal inclusions in cynomolgus monkeys after high doses of canthaxanthin

urpose. To reproduce and investigate in a primate animal model the phenomenon of the red carotenoid canthaxanthin (/?,/5-carotene-4'4'-dione) to induce crystal-like retinal deposits as they have been observed in the ocular fundus of humans after high canthaxanthin intake (i.e., more than 30 mg/day). Methods. Groups of four cynomolgus monkeys (Macaco, fascicularis) per gender and dose were administered 5.4, 16.2, or 48.6 mg candiaxanthin/kg body weight daily by oral gavage for 2.5 years. Eight control animals received placebo. In vivo ophthalmoscopy was performed at intervals of 3 months along with electroretinography after 12 and 24 months and retinal biomicroscopy just before the monkeys were killed. Retinal wholemounts or frozen sections were investigated postmortem by polarization, bright field, and differential interference contrast microscopy. Retinal and preterminal plasma canthaxanthin concentrations were determined by high-performance liquid chromatography (HPLC). Results. By ophthalmoscopy and retinal biomicroscopy in vivo, no crystals or other lightreflecting particles were observed in the central paramacular retina. However, postmortem polarization microscopy of all 24 canthaxanthin-treated animals showed a circular zone in the peripheral retina containing birefringent, polymorphous red, orange, or white inclusions. The density of these inclusions was diminished within 1 to 8 mm posterior to the ora serrata. These inclusions were located mainly in the inner retinal layers, that is, the nerve fiber layer and ganglion cell layer, inner plexiform layer, and inner nuclear layer. Twelve of the 24 canthaxanthin-treated animals showed yellow, golden birefringent inclusions in die macula. Retinas of placebo-treated monkeys were free of birefringent, crystal-like inclusions. The HPLC confirmed the presence of all-trans canthaxanthin, and 4-OH-echinenone and isozeaxanthin as well, in the retinas of all can thaxan dim-treated animals. Neither electroretinography nor histopathology indicated any adverse effects of the canthaxanthin-induced retinal inclusions seen in this study. Conclusions. A high intake of canthaxanthin for 2.5 years led to the deposition of crystal-like birefringent inclusions in the inner layers of the peripheral retina and, to some extent, the central retina of cynomolgus monkeys. The presence of these deposits did not interfere with morphology nor with retinal function. Invest Ophthalmol Vis Sci. 1997;38:741-752. A he carotenoid canthaxanthin (/?,/3-carotene-4'4'-dione) is synthesized in nature by the mushroom Cantharellus cinnabarinus. It also occurs in a variety of other plants and animals (e.g., in algae, Crustacea, birds, o

ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs

Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced ‘browning’ in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow

Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in human

Saying without Knowing What or How

In response to Stephen Neale (2016), I argue that aphonic expressions, such as PRO, are intentionally uttered by normal speakers of natural language, either by acts of omitting to say something explicitly, or by acts of giving phonetic realization to aphonics. I argue, also, that Gricean intention-based semantics should seek divorce from Cartesian assumptions of transparent access to propositional attitudes and, consequently, that Stephen Schiffer’s so-called meaning-intention problem is not powerful enough to banish alleged cases of over-intellectualization in contemporary philosophy of language and mind

Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations.

The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

<p>Abstract</p> <p>Background</p> <p>Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications.</p> <p>Case presentation</p> <p>Here we describe a case of hepatic artery thrombosis after living-donor liver transplantation which was not preceded by signs of liver failure but rather by an episode of acute psychosis. After re-transplantation the patient recovered without sequelae.</p> <p>Conclusion</p> <p>This case highlights the need to remain cautious when psychiatric disorders occur in patients after liver transplantation. The diagnostic procedures should not be restricted to medical or neurological causes of psychosis alone but should also focus vascular complications related to orthotopic liver transplantation.</p

The distribution, ecology and predicted habitat use of the Critically Endangered angelshark (Squatina squatina) in coastal waters of Wales and the central Irish Sea

The angelshark (Squatina squatina) has the northernmost range of any angel shark species, but there is limited information on its distribution, habitat use and ecology at higher latitudes. To address this, Angel Shark Project: Wales gathered 2231 S. squatina records and 142 anecdotal resources from fishers, coastal communities and archives. These spanned the coastal waters of Wales and the central Irish Sea and were dated from 1812 to 2020, with 97.62% of records within 11.1 km (6 nm) of the coast. Commercial, recreational and charter boat fishers provided the majority of S. squatina records (97.18%), with significantly more sightings from three decades (1970s, 1980s and 1990s) and in the months of September, June, August and July (in descending order). The coastal area between Bardsey Island and Strumble Head had the most S. squatina records (n = 1279), with notable concentrations also found in Carmarthen Bay, Conwy Bay and the Outer Severn Estuary. Species distribution models (SDM) identified four environmental variables that had significant influence on S. squatina distribution, depth, chlorophyll-a concentration, sea surface temperature (SST) and salinity, and these varied between the quarters (Q) of the year. SDM model outputs predicted a larger congruous area of suitable habitat in Q3 (3176 km2) compared to Q2 (2051 km2), with suitability along the three glacial moraines (Sarn Badrig, Sarn-y-Bwch and Sarn Cynfelyn) strongly presented. Comparison of modelled environmental variables at the location of S. squatina records for each Q identified reductions in depth and salinity, and increases in chlorophyll-a and SST when comparing Q2 or Q3 with Q1 or Q4. This shift may suggest S. squatina are making seasonal movements to shallow coastal waters in Q2 and Q3. This is supported by 23 anecdotal resources and may be driven by reproductive behaviour, as there were 85 records of S. squatina individuals ≤60 cm in the dataset, inferred as recently born or juvenile life-history stages. The results have helped fill significant evidence gaps identified in the Wales Angelshark Action Plan and immediate next research steps are suggested