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Dopamine is an important hormone and neurotransmitter, and its levels in human fluids can indicate stress, depression, and various mental disorders. Food products, as well as medications, affect its level in the human body greatly. Therefore, dopamine monitoring is crucial, and necessary for improving the quality of life. The priority is to search for simple and environmentally friendly sensor systems for the in vitro detection of dopamine, enabling mass utilization.In this study, we explored the use of o-phthalaldehyde (OPA) as an indicator for the detection of dopamine, with fluorescence in the visible range (λex/λem = 390/455 nm), while direct dopamine fluorescence measurement was in the UV range (λex/λem = 280/320 nm). The longer excitation/emission wavelengths of dopamine-OPA complex, as well as lower detection limits, are useful for developing a simple detection method using LEDs. Three types of poloxamers were tested as additives to improve the fluorescence signal from the reaction between dopamine and OPA. Pluronic F127 led to a 16-fold increase in the fluorescence. Utilizing 4% Pluronic F127 with OPA at pH 7 resulted in a linear response within concentration ranges of dopamine (0.5–3 µM), achieving a limit of detection of 0.015 µM. In contrast, a direct detection of dopamine within the same range exhibited a detection limit of 0.13 µM.

Purpose: Current eating disorder treatment approaches for youth were developed for use with cisgender girls, which limits the understanding of effectiveness for cisgender boys and transgender and gender expansive (TGE) youth. Here, we compare treatment outcomes for cisgender boys and TGE youth with cisgender girls receiving family-based treatment for an eating disorder., Methods: Patients were aged 6-24 and either active in treatment or discharged from September 1, 2020, to November 1, 2022 (N = 1,235). Patient exposure to treatment varied given individualized length of treatment. Outcomes include eating disorder symptoms, depression, anxiety, suicidality, caregiver burden, and parental confidence in supervising treatment. Treatment outcomes for cisgender boys and TGE youth were compared with cisgender girls., Results: Patients included n = 975 cisgender girls, n = 152 cisgender boys, and n = 108 TGE youth. Anorexia nervosa was the most common diagnosis. Cisgender boys reported significantly lower eating disorder (b = -2.7 [-4.1, -1.3]), anxiety (b = -1.6 [-2.2, -0.9]), and depression (b = -1.7 [-2.4, -0.9]) symptoms at admission compared with cisgender girls. TGE patients had significantly higher anxiety (b = 1.08 [0.28, 1.91]) and depression (b = 1.72 [0.78, 2.65]) symptoms compared with cisgender girls. Cisgender boys started with significantly lower suicidal ideation (b = -1.28 [-2.19, -0.43]) and TGE patients with significantly higher suicidal ideation (b = 1.63 [0.76, 2.51]) than cisgender girls. All symptoms improved during treatment and improved at similar rates over time in treatment regardless of gender identity., Discussion: Early evidence from this study supports the use of family-based treatment for cisgender boys and TGE youth with eating disorders. Further research is needed on the long-term outcomes of this approach for youth of all genders., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Herein we describe an interfacial local drug delivery system for bone morphogenetic protein 2 (BMP-2) based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP). The application horizon is the functionalization of bone substituting materials (BSM) used for the therapy of systemic bone diseases. Nanoparticular ternary complexes of cationic and anionic polysaccharides and BMP-2 or two further model proteins, respectively, were prepared in dependence of the molar mixing ratio, pH value and of the cationic polysaccharide. As further proteins chymotrypsin (CHY) and papain (PAP) were selected, which served as model proteins for BMP-2 due to similar isoelectric points and molecular weights. As charged polysaccharides ethylenediamine modified cellulose (EDAC) and trimethylammonium modified cellulose (PQ10) were combined with cellulose sulphatesulfate (CS). Mixing diluted cationic and anionic polysaccharide and protein solutions according to a slight either anionic or cationic excess charge colloidal ternary dispersions formed, which were cast onto germanium model substrates by water evaporation. Dynamic light scattering (DLS) demonstrated, that these dispersions were colloidally stable for at least one week. Fourier Transform Infrared (FTIR) showed, that the cast protein loaded PEC NP coatings were irreversibly adhesive at the model substrate in contact to HEPES buffer and solely CHY, PAP and BMP-2 were released within long-term time scale. Advantageously, out of the three proteins BMP-2 showed the smallest initial burst and the slowest release kinetics and around 25% of the initial BMP-2 content were released within 14days. Released BMP-2 showed significant activity in the myoblast cells indicating the ability to regulate the formation of new bone. Therefore, BMP-2 loaded PEC NP are suggested as novel promising tool for the functionalization of BSM used for the therapy of systemic bone diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Platelets have been shown to migrate and thus to invade the vascular wall. Platelet migration is stimulated by SDF-1. In other cell types, migration is dependent on Ca(2+) entry via Ca(2+) channels. Ca(2+) influx is sensitive to cell membrane potential which is maintained by K(+) channel activity and/or Cl(-) channel activity. The present study explored the role of ion channels in the regulation of SDF-1 induced migration. Platelets were isolated from human volunteers as well as from gene targeted mice lacking the Ca(2+) activated K(+) channel SK4 (sk4(-/-)) and their wild type littermates (sk4(+/+)). According to confocal microscopy human platelets expressed the Ca(2+) channel Orai1 and the Ca(2+)-activated K(+) channel K(Ca)3.1 (SK4). SDF-1 (100 ng/ml) stimulated migration in human platelets, an effect blunted by Orai1 inhibitors 2-aminoethoxydiphenyl borate 2-APB (10 μM) and SKF-96365 (10 μM), by unspecific K(+) channel inhibitor TEA (30 mM), by SK4 specific K(+) channel blocker clotrimazole (10 μM), but not by Cl(-) channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid NPPB (100 μM). Significant stimulation of migration by SDF-1 was further observed in sk4(+/+) platelets but was virtually absent in sk4(-/-) platelets. In conclusion, platelet migration requires activity of the Ca(2+) channel Orai1 and of the Ca(2+) activated K(+) channel SK4, but not of NPPB-sensitive Cl(-) channels., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Automated indices derived from mid-latency auditory evoked potentials (MLAEP) have been proposed for monitoring the state of anaesthesia. The A-Line ARX index (AAI) has been implemented in the A-Line monitor (Danmeter, V1.4). Several studies have reported variable and, in awake patients, sometimes surprisingly low AAI values. The purpose of this study was to reproduce these findings under steady-state conditions and to investigate their causes., Methods: Ten awake unmedicated volunteers were studied under steady-state conditions. For each subject, the raw EEG and the AAI were recorded with an A-Line monitor (V1.4) during three separate sessions of 45.0 (1.6) min duration each. MATLAB (Mathworks) routines were used to derive MLAEP responses from EEG data and to calculate maximal MLAEP amplitudes., Results: The AAI values ranged from 15 to 99, while 11.4% fell below levels which, according to the manufacturer, indicate an anaesthetic depth suitable for surgery. Inter-individual and intra-individual variation was observed despite stable recording conditions. The amplitudes of the MLAEP varied from 0.8 to 42.0 microV. The MLAEP amplitude exceeded 2 microV in 75.3% of readings. The Spearman's rank correlation coefficient between the MLAEP amplitude and the AAI value was r=0.89 (P<0.0001)., Conclusions: The version of the A-Line monitor used in this study does not exclude contaminated MLAEP signals. Previous publications involving this version of the A-Line monitor (as opposed to the newer A-Line/2 monitor series) should be reassessed in the light of these findings. Before exclusively MLAEP-based monitors can be evaluated as suitable monitors of depth of anaesthesia, it is essential to ensure that inbuilt validity tests eliminate contaminated MLAEP signals.

Background: Information on molecular targets that may be involved in the neurotoxicity of bupivacaine is limited. Suppression of Kv3 channels has been demonstrated to result in abnormal patterns in the electroencephalogram and in seizures. Inhibition of Kv3 channels by bupivacaine may consequently contribute to its neuroexcitatory side-effects. Data on the effects of bupivacaine on these potassium channels are lacking. We therefore characterized the effects of bupivacaine on human Kv3 channels natively expressed in SH-SY5Y cells., Methods: Kv3 channels natively expressed in human SH-SY5Y cells were studied using a standard whole-cell patch-clamp protocol., Results: Bupivacaine reversibly inhibited Kv3 channels in a concentration-dependent manner. The half-maximal inhibitory concentration (IC50) for conductance block was 57 microM and the Hill coefficient was close to unity. Bupivacaine accelerated macroscopic current decline by inducing inactivation-like behaviour. The midpoint of current activation was shifted to depolarized potentials in a concentration-dependent and reversible manner by a maximum of 26 mV. The IC50 was 47 microM and the Hill coefficient was 2.4. The free arterial plasma concentrations of bupivacaine that have been estimated to occur during convulsions in man would inhibit the Kv3 channels by at least 40% and would shift the midpoint of current activation by a minimum of 9 mV., Conclusions: Both inhibition of potassium channels and a depolarizing shift of their activation midpoint would increase neuronal excitability. The effects of bupivacaine on human Kv3 channels are thus compatible with a contributory role of Kv channel alteration in bupivacaine-induced neuronal excitation.

Abnormal isoforms of the prion protein (PrP(Sc)) that cause prion diseases are propagated and spread within the body by "carrier" cell(s). Cells of the immune system have been strongly implicated in this process. In particular, PrP(Sc) is known to accumulate on follicular dendritic cells (FDCs) in individuals affected by variant Creutzfeld-Jakob disease. However, FDCs do not migrate widely and the natural history of prion disorders suggests other cells may be required for the transport of PrP(Sc) from the site of ingestion to lymphoid organs and the central nervous system. Substantial evidence suggests that the spread of PrP(Sc) requires bone marrow-derived cells that express normal cellular prion protein (PrP(C)). This study examined the expression of PrP(C) on bone marrow-derived cells that interact with lymphoid follicles. High levels of PrP(C) are present on myeloid dendritic cells (DCs) that surround the splenic white pulp. These myeloid DCs are ontologically and functionally distinct from the FDCs. Consistent with these observations, expression of PrP(C) was strongly induced during the generation of mature myeloid DCs in vitro. In these cells PrP(C) colocalized with major histocompatibility complex class II molecules at the level of light microscopy. Furthermore, given the close anatomic and functional connection of myeloid DCs with lymphoid follicles, these results raise the possibility that myeloid DCs may play a role in the propagation of PrP(Sc) in humans.

The importance of dendritic cells (DCs) for the initiation and regulation of immune responses not only to foreign organisms but also to the self has raised considerable interest in the qualitative and quantitative analysis of these cells in various human diseases. Plasmodium falciparum malaria is characterized by the poor induction of long-lasting protective immune responses. This study, therefore, investigated the percentage of peripheral blood DCs as lineage marker-negative and HLA-DR(+) or CD83(+) cells in healthy children and in children suffering from acute malaria in Kilifi, Kenya. Comparable percentages of CD83(+) DCs were found in peripheral blood of healthy children and children with malaria. However, the percentage of HLA-DR(+) peripheral blood DCs was significantly reduced in children with malaria. The results suggest that a proportion of peripheral blood DCs may be functionally impaired due to the low expression of HLA-DR on their surface.

Computed tomography, magnetic resonance imaging, and transesophageal echocardiography represent the relatively noninvasive techniques available for imaging thoracic aortic disease, especially in the evaluation of aneurysms and dissections. The article discusses the technique and application of these modalities in the evaluation of thoracic aorta. Imaging appearances of the commonly encountered pathologies of the thoracic aorta are presented and discussed, and potential pitfalls of technique and diagnosis are addressed.

Fast inactivation of sodium channel function is modified by anaesthetics. Its quantitative contribution to the overall anaesthetic effect is assessed by removing the fast inactivation mechanism enzymatically. Sodium channels from human brain cortex were incorporated into planar lipid bilayers. After incorporation, channels were exposed to increasing concentrations of pentobarbital (pentobarbitone), either before or after fast inactivation had been enzymatically removed using trypsin. Anaesthetic suppression of these channels with or without the fast inactivation site was compared by analysing single channel currents. Treatment with cytoplasmic trypsin alleviated two-thirds of the pentobarbital block on open channel probability (fractional channel open time). The hyperpolarizing shift in steady-state activation caused by pentobarbital was not affected by treatment with trypsin. Extracellular trypsin was ineffective. These results support a model of general anaesthetic action on sodium channels in which anaesthetics produce a concentration-dependent shift in the distribution between activated and inactivated states towards fast inactivation. Some pentobarbital effects remained after removal of inactivation. The results support a multi-mechanistic model of anaesthetic action on brain sodium channels.

1. There is no generally accepted and quantifiable definition of general anesthesia. 2. Ion channels are discussed as examples of in-vitro systems used to investigate anesthetic mechanisms. Experimental evidence has accumulated demonstrating that voltage-gated ion channels and ligand-gated ion channels may be affected by clinically relevant concentrations of general anesthetics. 3. There are many factors modulating the anesthetic sensitivity of ion channels, including membrane lipid, electrolyte environment, ion channel subtype, and the functional state of the network. 4. Neuronal networks relevant to human general anesthesia have to be identified before criteria can be formulated as to which component of any particular ion channel function has to be altered to what extent in order to make a contribution to clinical anesthesia.

The molecular mechanisms by which anaesthetics interfere with neuronal function are controversial. We have examined the effects of pentobarbitone on muscle-derived (eel electroplax) sodium channels incorporated into planar bilayers under exactly the same experimental conditions that we used previously to study the anaesthetic modification of human brain channels. This technique allows examination of protein-mediated similarities and differences. Sodium channels from the electroplax (muscle-derived) of the electric eel were purified and reconstituted into planar lipid bilayers containing 4:1 phosphatidylethanolamine:phosphatidylcholine in the presence of batrachotoxin, a sodium channel activator. Pentobarbitone had similar voltage-independent blocking effects on sodium channels from eel electroplax and human brain, as demonstrated by similar dose-response curves (IC50 = 613 mumol litre-1). However, activation of sodium channels from eel electroplax, in contrast with human brain, was relatively insensitive to the concentration of pentobarbitone. The only significant effect was a -5.8-mV shift in the activation midpoint with pentobarbitone 680 mumol litre-1. Therefore, differences in primary structures played no role in the observed voltage-independent block of channels by pentobarbitone, whereas subunits or other structural differences between sodium channels from eel electroplax and human brain must be responsible for the minimal effect of pentobarbitone on activation of muscle-derived sodium channels.

A rare case of focal primary amyloidosis is presented with CT and MR correlation. Imaging findings demonstrate an expansile, mixed sclerotic and lytic lesion in the sternum, with MR signal characteristics similar to those previously described for diffuse primary amyloidosis and hemodialysis-related amyloidosis.

In search of a molecular site and mechanism of action for anaesthetics, we have examined the effects of racemic ketamine on single human CNS sodium channels with the new planar lipid bilayer technique. In the dose range studied (0.05-9.2 mmol litre-1) ketamine depressed in a dose-dependent manner two major functions of the sodium channel, by reducing the fractional open time in a voltage-independent manner (ED50 1.1 mmol litre-1; maximal conductance block 71%) and by interfering with the voltage-dependent, steady-state activation. These actions occurred at concentrations which were greater than those used clinically in general anaesthesia (up to 0.02 mmol litre-1), therefore they reflect local rather than general anaesthetic effects which may be related to the hydrophobic properties of ketamine. In comparison with two other i.v. anaesthetic agents, pentobarbitone and propofol, racemic ketamine behaves differently at both the molecular and the clinical level.

Cerebrospinal fluid (CSF) beta-endorphin concentrations were determined before and after treatment in 28 patients suffering chronic neuralgic low back pain/sciatica. Nine patients carried the additional diagnosis of major depressive disorder. Pain treatment was multimodal and resulted in variable pain reduction. CSF beta-endorphin concentrations spanned a wide range with no association to age, gender, pain ratings, depressive symptomatology, and drug intake. CSF beta-endorphin concentrations were not influenced by the presence of major depressive disorder and did not change with successful treatment of pain and resolution of depression.