Platelet-rich plasma (PRP) is a fraction of plasma that contains high levels of multiple growth factors. The purpose of this study was to examine the effects of PRP on cell proliferation and matrix ...synthesis by porcine chondrocytes cultured in alginate beads, conditions that promote the retention of the chondrocytic phenotype, in order to determine the plausibility of using this plasma-derived material for engineering cartilage.
PRP and platelet-poor plasma (PPP) were prepared from adult porcine blood. Adult porcine chondrocytes were cultured in the presence of 10% PRP, 10% PPP or 10% fetal bovine serum (FBS) for 3 days. Cell proliferation, proteoglycan (PG) and collagen synthesis were quantified, and the structure of newly synthesized PG and collagen was characterized.
Treatment with 10% PRP resulted in a small but significant increase in DNA content (+11%, vs FBS;
P
<
0.01; vs PPP;
P
<
0.001). PG and collagen syntheses by the PRP-treated chondrocytes were markedly higher than those by chondrocytes treated by FBS or PPP (PG; PRP: +115% vs FBS; +151% vs PPP, both
P
<
0.0001, collagen; PRP: +163% vs FBS; +163% vs PPP, both
P
<
0.0001). Biochemical analyses revealed that treatment with PRP growth factors did not markedly affect the types of PGs and collagens produced by porcine chondrocytes, suggesting that the cells remained phenotypically stable in the presence of PRP.
PRP isolated from autologous blood may be useful as a source of anabolic growth factors for stimulating chondrocytes to engineer cartilage tissue.
Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic ...acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.
In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.
Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.
Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.
A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity ...both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. We propose here that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular and ventral attention networks as well as decreased functioning of the fronto-parietal and default mode networks. This functional network model can be used to differentiate the pathology of anxiety disorders from other psychiatric illnesses such as major depression and provides targets for novel treatment strategies.
Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to ...investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (P<0.05, family-wise error). Notably, there was a significant negative correlation between LSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (P<0.05). These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing.
MDMA ("ecstasy") is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have investigated subjects with heavy use ...patterns, and the effects of transient MDMA use are unclear. In this review, we therefore focus on subjects with moderate use patterns, in order to assess the evidence for harmful effects. We searched for studies applying neuroimaging techniques in man. Studies were included if they provided at least one group with an average of <50 lifetime episodes of ecstasy use or an average lifetime consumption of <100 ecstasy tablets. All studies published before July 2015 were included. Of the 250 studies identified in the database search, 19 were included. There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures. The lack of significant results was associated with high methodological heterogeneity in terms of dosages and co-consumption of other drugs, low quality of studies and small sample sizes.
A variable compliance, soft gripper Giannaccini, M. E.; Georgilas, I.; Horsfield, I. ...
Autonomous robots,
2014/1, Letnik:
36, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
Autonomous grasping is an important but challenging task and has therefore been intensively addressed by the robotics community. One of the important issues is the ability of the grasping device to ...accommodate varying object shapes in order to form a stable, multi-point grasp. Particularly in the human environment, where robots are faced with a vast set of objects varying in shape and size, a versatile grasping device is highly desirable. Solutions to this problem have often involved discrete continuum structures that typically comprise of compliant sections interconnected with mechanically rigid parts. Such devices require a more complex control and planning of the grasping action than intrinsically compliant structures which passively adapt to complex shapes objects. In this paper, we present a low-cost, soft cable-driven gripper, featuring no stiff sections, which is able to adapt to a wide range of objects due to its entirely soft structure. Its versatility is demonstrated in several experiments. In addition, we also show how its compliance can be passively varied to ensure a compliant but also stable and safe grasp.
HPLC–MS-based metabonomic analysis was used to investigate urinary metabolic perturbations associated with
d-serine-induced nephrotoxicity.
d-Serine causes selective necrosis of the proximal straight ...tubules in the rat kidney accompanied by aminoaciduria, proteinuria and glucosuria. Alderely Park (Wistar-derived) rats were dosed with either
d-serine (250
mg/kg ip) or vehicle (deionised water) and urine was collected at 0–12, 12–24, 24–36 and 36–48
h post-dosing. Samples were analysed using a Waters Alliance
® HT 2795 HPLC system coupled to a Waters Micromass Q-ToF-micro™ equipped with an electrospray source operating in either positive or negative ion mode. Changes to the urinary profile were detected at all time points compared to control. In negative ion mode, increases were observed in serine (
m/
z
=
103.0077),
m/
z
=
104.0376 (proposed to be hydroxypyruvate) and glycerate (
m/
z
=
105.0215), the latter being metabolites of
d-serine. Furthermore, an increase in tryptophan, phenylalanine and lactate and decreases in methylsuccinic acid and sebacic acid were observed. Positive ion analysis revealed a decrease in xanthurenic acid, which has previously been assigned and reported using HPLC–MS following exposure to mercuric chloride and cyclosporine A. A general aminoaciduria, including proline, methionine, leucine, tyrosine and valine was also observed as well as an increase in acetyl carnitine. Investigation of additional metabolites altered as a result of exposure to
d-serine is on-going. Thus, HPLC–MS-based metabonomic analysis has provided information concerning the mechanism of
d-serine-induced renal injury.
An integrated metabonomics study using high-resolution 1H NMR spectroscopy has been applied to investigate the biochemical composition of intact liver tissue (using magic angle spinning), liver ...tissue extracts, and blood plasma samples obtained from control and acetaminophen-treated mice. Principal components analysis was used to visualize similarities and differences in biochemical profiles. The time- and dose-dependent biochemical effects of acetaminophen were related to the drug toxicity, as determined using histopathology. Metabolic effects in intact liver tissue and lipid soluble liver tissue extracts from animals treated with the high dose level of acetaminophen included an increase in lipid triglycerides and monounsaturated fatty acids together with a decrease in polyunsaturated fatty acids, indicating mitochondrial malfunction with concomitant compensatory increase of peroxisomal activity. In addition, a depletion of phospholipids was observed in treated liver tissue, which suggested an inhibition of enzymes involved in phospholipid synthesis. There was also a depletion in the levels of liver glucose and glycogen. In addition, the aqueous soluble liver tissue extracts from high dose animals also revealed an increase in lactate, alanine, and other amino acids, together with a decrease in glucose. Plasma spectra showed increases in glucose, acetate, pyruvate, and lactate. These observations all provide evidence for an increased rate of glycolysis. These findings could indicate a mitochondrial inability to use pyruvate in the citric acid cycle and also reveal the impairment of fatty acid β-oxidation in liver mitochondria of such treated mice.
Highlights • Pazopanib with cyclophosphamide had a MTD of 600 mg per day. • Main side effects were elevation of the liver enzymes, diarrhea, leukopenia. • Quality of life was not reduced during ...treatment. • One patient experienced durable benefit from therapy for more than two years.
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