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Impaired intracellular trafficking of sodium-dependent vitamin C transporter 2 contributes to the redox imbalance in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by a glutamine expansion at the first exon of the huntingtin gene. Huntingt … sporter 2 (SVCT2). During synaptic activity, ascorbic acid is released from glial reservoirs to the extracellular space, inducing an increase in SVCT2 localization at the plasma membrane. Here, we studied SVCT2 trafficking and localization in HD. SVCT2 is decreased at synaptic terminals in YAC128 male mice. Using cellular models for HD (STHdhQ7 and STHdhQ111 cells), …

Intragenic CNTNAP2 Deletions: A Bridge Too Far?

Intragenic deletions of the contactin-associated protein-like 2 gene (CNTNAP2) have been found in patients with Gilles de la Tourette syndrome, intellectual disability (ID), obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, stuttering, and attention deficit hyperactivity disorder. A variety of molecular mechanisms, such as loss of transcription factor binding sites and perturbation of penetrance and expressivity, have been proposed to account for the phenotypic variability resulting from CNTNAP2 mutations. Deletions of both

Uptake and metabolism of D-glucose in isolated acinar and ductal cells from rat submandibular glands.

The present study deals with the possible effects of selected environmental agents upon the uptake and metabolism of d-glucose in isolated acinar and ductal cells from the rat submandibular salivary gland. In acinar cells, the uptake of d-[U-(14) C]glucose and its non-metabolised analogue 3-O-[(14) C-methyl]-d-glucose was not affected significantly by phloridzin (0.1 mM) or substitution of extracellular NaCl (115 mM) by an equimolar amount of CsCl, whilst cytochalasin B (20 μM) decreased significantly such an uptake. In ductal cells, both phloridzin and cytochalasin B decreased the uptake of d

Cardiac and renal fibrosis in chronic cardiorenal syndromes.

In recent years, there has been considerable interest in cellular and tissue responses to injury that result in the deposition of extracellu … lasts and myofibroblasts, which produce and secrete procollagen I. Procollagen I cross-links in the extracellular space to form mature collagen, which is a fundamental unit of organ fibrosis. Future research will be concentrating on the pathogenic mechanisms that turn on fibrosis and on therapeutic targets that can either prevent the activation of fibroblasts or limi …

Down-regulation of Na+-coupled glutamate transporter EAAT3 and EAAT4 by AMP-activated protein kinase.

The glutamate transporters EAAT3 and EAAT4 are expressed in neurons. They contribute to the cellular uptake of glutamate and aspartate and thus to the clearance of the excitatory transmitters from the extracellular space. During ischemia, extracellular accumulation of glutamate may trigger excitotoxicity. Energy depletion leads to activation of the AMP-activated protein kinase (AMPK), a kinase enhancing energy production and limiting energy expenditure. The present study thus explored the possibility that AMPK regulates EAAT3 and/or EAAT4. To this end, EAAT3 or EAAT4 were expressed in Xenopus …

Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells.

The effect of melittin on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and viability is largely unknown. This study examined whether me … uced a [Ca(2+)](i) rise by causing Ca(2+) release from endoplasmic reticulum and Ca(2+) influx from extracellular space. Furthermore, melittin can cause Ca(2+)-dependent cytotoxicity in a concentration-dependent manner.

S100B in neuropathologic states: the CRP of the brain?

In recent years there has been a proliferation of interest in the brain-specific protein S100B, its many physiologic roles, and its behaviou … homeostasis. Information about the functional implication of S100B secretion by astrocytes into the extracellular space is scant but there is substantial evidence that secreted glial S100B exerts trophic or toxic effects depending on its concentration. This review summarises the historic development and current knowledge of S100B, including recent interesting finding …

Dinitrosyl-iron triggers apoptosis in Jurkat cells despite overexpression of Bcl-2.

Cells expressing the cytokine-inducible NO synthase are known to trigger apoptosis in neighboring cells. Paramagnetic dinitrosyl nonheme iro … impermeable NO-Fe-MGD complex and to a burst-type release of nitrosonium (NO(+)) equivalents in the extracellular space. These results suggest that in Jurkat cells, DNIC-thiosulfate induces Bcl-2- and caspase-independent apoptosis, which is probably secondary to local nitrosative stress at the cell surface. We hypothesize that the local release of nonheme Fe-NO speci …

Nonylphenol-induced Ca2+ elevation and Ca2+-independent cell death in human osteosarcoma cells.

The effect of the environmental toxicant nonylphenol on cytosolic free Ca2+ concentration ([Ca2+]i) and proliferation has not been explored … phenol induced [Ca2+]i rises by causing Ca2+ release from intracellular stores and Ca2+ influx from extracellular space. Furthermore, nonylphenol can cause Ca2+-unrelated cytotoxicity in a concentration-dependent manner.

Extracellular matrix protein expression in cerebrospinal fluid from patients with tropical spastic paraparesis associated with HTLV-I and Creutzfeldt-Jakob disease.

The cerebrospinal fluid (CSF) is in direct contact with the extracellular space of the CNS, thus biochemical processes in the CNS could potentially be reflected in the CSF. Changes in extracellular matrix (ECM) proteins can be studied through their analysis in the CSF. ECM plays an essential role in CNS homeostasis and several proteins such as laminin (LN), fibronectin (FN), thrombospondin (TS) and heparan sulphate proteoglycan (HS, perlecan) form part of its structure. Possible changes in the levels of these proteins were investigated in two different pathologies--tropical spastic paraparesis…

Elevated extracellular glutamate levels increased the formation of hydroxyl radical in the striatum of anesthetized rat.

Results from various in vitro experiments have indicated that excitotoxicity and oxidative stress are two interrelated major mechanisms in c … usion, we have obtained direct evidence showing that the elevated glutamate concentrations in brain extracellular space would increase the formation of hydroxyl radical, and these results implied that oxidative stress occurring in brain disorders might be induced by excitotoxicity.

Osmotic-hypertensive opening of the blood-brain barrier in rats does not necessarily provide access for potassium to cerebral interstitial fluid.

The blood-brain barrier was breached in urethane anaesthetized rats by infusing hypertonic mannitol or NaCl at high rate under high pressure into one internal carotid artery. Opening of the blood-brain barrier was confirmed by staining of the perfused hemisphere by intravenous Evans Blue dye. Orthodromic-evoked potentials in CA1 region of hippocampus were transiently extinguished, and the extracellular potential in hippocampus and neocortex shifted in the positive direction during hypertonic infusion. After the hypertonic infusion, the permeability of the barrier to K+ was tested by infusing i

Colloid and crystalloid fluid resuscitation.

The choice of colloid or crystalloid solutions for fluid resuscitation of critically ill patients remains controversial. Marked reduction of extracellular water is considered an important defect in shock by proponents of crystalloid fluid therapy. Large volumes of crystalloid replenish this extracellular deficit. Hypovolemia is regarded as the primary defect in shock by those favoring colloid fluid therapy. Colloidal fluids promptly restore plasma volume and reestablish hemodynamic stability with substantially lesser volumes of fluid. However, only 8% of infused water and less than 25% of infu

Gadolinium modulates gentamicin uptake via an endocytosis-independent pathway in HK-2 human renal proximal tubular cell line.

The aim of this study was to characterize the uptake mechanism of gentamicin, an aminoglycoside antibiotic, in human renal proximal tubular cell line HK-2. Sodium-dependent uptake of D-[(3)H]glucose and L-[(3)H]alanine was observed in HK-2 cells, indicating that the cells employed in this study retain functional characteristics of the renal proximal tubular cells. On the other hand, mRNA and protein expression of megalin, an endocytic receptor which is responsible for the internalization of gentamicin into the renal proximal tubular cells, was very faint in HK-2 cells. Various aminoglycoside a

Adipokine Metabolic Drivers, Gut Dysbiosis, and the Prostate Microbiome: Novel Pathway Enrichment Analysis of the Adiposity-Based Chronic Disease-Prostate Cancer Network.

Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment … e results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular spac …

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Совпадение в аннотации оригинала
Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's … can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances; these can be pathology-associated abnormal structures, such as amyloid β proteins, or damage-associated molecular patterns released from injured cells, including their mitochondria. Once in the extracellular space, dama …

Measuring myocardial blood flow with 82rubidium using Gjedde-Patlak-Rutland graphical analysis.

OBJECTIVE: Myocardial blood flow (MBF) is measured with 82Rb using non-linear, least-squares computerised modelling. The study aim was to ex … s of K1 and Z are, respectively, ml/min/ml intracellular space and ml/min/ml total tissue including extracellular space, myocardial extracellular fluid volume (ECV) is 1 - [Z/K1]. Using Z/K1 (see Results) to modify its index, the Lortie equation was changed to Z = (1-0.77 × [Formula: see text]e-BZ/MBFZ)*MBFZ, following which MBFZ was calculated from Z. In GPR analysi …

Prostate cancer detection on dynamic contrast-enhanced MRI: computer-aided diagnosis versus single perfusion parameter maps.

OBJECTIVE: The purpose of this article is to assess the value of computer-aided diagnosis (CAD) for prostate cancer detection on dynamic con … ncement, percentage enhancement ratio, time of arrival, efflux rate constant from the extravascular extracellular space to the blood plasma (k(ep)), first-order rate constant for eliminating gadopentetate dimeglumine from the blood plasma (k(el)), and constant depending on the properties of the tissue and represented by the size of the extravascular extracellular spa …

Cardiac sympathetic activity in myocardial ischemia: release and effects of noradrenaline.

Sympathetic overactivity in myocardial ischemia is closely associated with the progression of myocyte injury and the incidence of malignant arrhythmias. Adrenergic stimulation of the ischemic myocardium is predominantly due to increased local noradrenaline concentrations in the heart, whereas plasma catecholamine levels are of minor relevance. During the first few minutes of ischemia, efferent sympathetic nerves are activated. Excessive accumulation of noradrenaline, however, is prevented since adenosine, formed in the ischemic myocardium, suppresses exocytotic noradrenaline release, and relea

Diagnostic Value of Extracellular Volume Quantification and Myocardial Perfusion Analysis at CT in Cardiac Amyloidosis.

Background CT can provide information regarding myocardial perfusion and expansion of the extracellular space, which is relevant to patients with cardiac amyloidosis (CA). Purpose To evaluate the role of CT in the diagnosis and prognosis of CA. Materials and Methods In this prospective study (Commission National de l'Informatique et des Libertés registration no. 1431858), participants with CA, participants with nonamyloid cardiac hypertrophy (NACH), and participants without hypertrophy were included between April 2017 and December 2018. The confirmed diagnosis of CA was determined according to…