Irradiation in BCC materials: Defect-induced changes of the effective dislocation mobility and their relation with the dose-dependent fracture response

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block ( n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block ( n = 8) was significantly higher in the region of block (4.53 ± 0.61) compared with that in control preparations (2.23 ± 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 ± 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5–10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.

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Monitoring the side effects with DSC caused by cyclophosphamide treatment

Journal of Thermal Analysis and Calorimetry ◽

10.1007/s10973-019-09064-0 ◽

2019 ◽

Vol 142 (2) ◽

pp. 765-770

Author(s):

Péter Farkas ◽

Franciska Könczöl ◽

Dénes Lőrinczy

Keyword(s):

Side Effects ◽

Red Blood Cells ◽

Blood Cells ◽

Peripheral Nerves ◽

Chemotherapeutic Agents ◽

Cyclophosphamide Treatment ◽

Micro Dsc ◽

Induced Changes ◽

First Time ◽

Dose Dependent

AbstractPolyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a side effect of a cancer therapy (using cyclophosphamide) as well. In the daily use, it is very important to know the kinetics and metabolism of anticancer drugs because this way we can estimate their undesirable consequences to avoid the unwanted complications. Nowadays, the application of DSC in diagnosis of different diseases using blood compounds is increasing; therefore, the purpose of recent study was to introduce at the first time the DSC in the detection of cyclophosphamide-induced changes in plasma and red blood cells in case of an experimental animal model. Guinea pigs (Cavia porcellus, n = 60, in 12 different groups) underwent to cyclophosphamide treatment administrated intraperitoneally with the dose comparable to the human dosage. At the end of treatments, the animals were euthanized, and the experimental samples (plasma end red blood cells) were analyzed by a SETARAM Micro DSC-II calorimeter. The denaturation temperatures and the calorimetric enthalpies were calculated from the heat flow curves. Our results exhibited a dose-dependent difference between thermal parameters of untreated and treated samples, demonstrating that DSC is applicable in this field too. After deconvolution of DSC scans, the changes could be assigned to the attacked compounds. Recently published papers call the attention for this technique more frequently in the medical diagnosis because this way from small amount of sample very quickly and economically possible to detect and predict the expected and unwanted side effects of chemotherapeutic agents.

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Xylazine regulates the release of glycine and aspartic acid in rat brain

Journal of Veterinary Research ◽

10.2478/jvetres-2018-0017 ◽

2018 ◽

Vol 62 (1) ◽

pp. 121-128

Author(s):

Yi-Ming Zhang ◽

Dong-Xu Yu ◽

Bai-Shuang Yin ◽

Xin-Ran Li ◽

Li-Na Li ◽

...

Keyword(s):

Aspartic Acid ◽

Brain Area ◽

Brain Regions ◽

Inhibitory Effect ◽

Test Methods ◽

Control Group ◽

Clinical Anaesthesia ◽

Induced Changes ◽

Dose Dependent

AbstractIntroductionXylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied.Material and MethodsWistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).ResultsDuring anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group.ConclusionThe data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.

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Assessing Competence of Broccoli Consumption on Inflammatory and Antioxidant Pathways in Restraint-Induced Models: Estimation in Rat Hippocampus and Prefrontal Cortex

BioMed Research International ◽

10.1155/2013/590379 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Leila Khalaj ◽

Sara Chavoshi Nejad ◽

Marzieh Mohammadi ◽

Sadaf Sarraf Zadeh ◽

Marieh Hossein Pour ◽

...

Keyword(s):

Prefrontal Cortex ◽

Therapeutic Potential ◽

Apoptotic Cell ◽

Specific Effect ◽

Antioxidant Defense System ◽

Stressful Events ◽

Male Rats ◽

Related Factor ◽

Induced Changes ◽

Dose Dependent

A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA) level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

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Preoptic norepinephrine-induced hypothermia is mediated by alpha 2-adrenoceptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.3.r407 ◽

1992 ◽

Vol 262 (3) ◽

pp. R407-R411 ◽

Cited By ~ 12

Author(s):

N. Quan ◽

L. Xin ◽

A. L. Ungar ◽

C. M. Blatteis

Keyword(s):

Thermal Effects ◽

Preoptic Area ◽

Adrenergic Agonists ◽

Metabolic Heat ◽

Adrenoceptor Agonist ◽

Per Se ◽

Induced Changes ◽

Dose Dependent ◽

Skin Temperatures ◽

Alpha Antagonist

We have shown previously that norepinephrine (NE) microdialyzed into the preoptic area of conscious guinea pigs evokes a fall in core temperature (Tco) that is mediated by a reduction in metabolic rate. To identify the adrenoceptor subtype(s) involved in this effect, we microdialyzed intrapreoptically various adrenergic agonists or antagonists singly or in combinations. Tco and ear skin temperatures of the animals were monitored throughout the experiments. alpha 1-, beta-, beta 1-, and beta 2-agonists and antagonists did not induce significant Tco changes. Although the alpha 2-antagonists yohimbine (Yoh) and rauwolscine (Rau) did not have thermal effects per se, the alpha 2-agonist clonidine evoked dose-dependent Tco falls that were abolished by codialyzed Yoh and Rau. The microdialysis of NE evoked, as before, a 0.7 +/- 0.2 degrees C Tco fall; it was abolished by the codialyzed alpha-antagonist phentolamine, Yoh, and Rau but not by the beta-antagonist propranolol. No adrenoceptor agonist induced changes in ear skin temperature. These results indicate that the hypothermizing effect of intrapreoptically microdialyzed NE is achieved by a reduction in metabolic heat production, mediated by alpha 2-adrenoceptors.

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Confirmation of Fenfluramine Effect on 5-HT1B Receptor Binding of [11C]AZ10419369 using an Equilibrium Approach

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.172 ◽

2011 ◽

Vol 32 (4) ◽

pp. 685-695 ◽

Cited By ~ 27

Author(s):

Sjoerd J Finnema ◽

Andrea Varrone ◽

Tzung-Jeng Hwang ◽

Christer Halldin ◽

Lars Farde

Keyword(s):

Specific Binding ◽

Occipital Cortex ◽

Serotonin Release ◽

Binding Potential ◽

Bolus Administration ◽

Positron Emission ◽

Equilibrium Approach ◽

Induced Changes ◽

Dose Dependent

Assessment of serotonin release in the living brain with positron emission tomography (PET) may have been hampered by the lack of suitable radioligands. We previously reported that fenfluramine caused a dose-dependent reduction in specific binding in monkeys using a classical displacement paradigm with bolus administration of [11C]AZ10419369. The aim of this study was to confirm our previous findings using an equilibrium approach in monkey. A total of 24 PET measurements were conducted using a bolus infusion protocol of [11C]AZ10419369 in three cynomolgus monkeys. Initial PET measurements were performed to assess suitable Kbol values. The fenfluramine effect on [11C]AZ10419369 binding was evaluated in a displacement and pretreatment paradigm. The effect of fenfluramine on [11C]AZ10419369 binding potential ( BPND) was dose-dependent in the displacement paradigm and confirmed in the pretreatment paradigm. After pretreatment administration of fenfluramine (5.0 mg/kg), the mean BPND of the occipital cortex decreased by 39%, from 1.38 ± 0.04 to 0.84 ± 0.09. This study confirms that the new 5-HT1B receptor radioligand [11C]AZ10419369 is sensitive to fenfluramine-induced changes in endogenous serotonin levels in vivo. The more advanced methodology is suitable for exploring the sensitivity limit to serotonin release as measured using [11C]AZ10419369 and PET.

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Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00666.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. R380-R393 ◽

Cited By ~ 8

Author(s):

Dan Li ◽

Jin Fu Wen ◽

Jing Yu Jin ◽

Hua Jin ◽

Hai Sun Ann ◽

...

Keyword(s):

Protein Kinase ◽

Selective Inhibitor ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Camp Analog ◽

Induced Changes ◽

Protein Kinase Signaling ◽

Dose Dependent ◽

Rabbit Atria

Changes in cyclic nucleotide production and atrial dynamics have been known to modulate atrial natriuretic peptide (ANP) release. Although cardiac atrium expresses histamine receptors and contains histamine, the role of histamine in the regulation of ANP release has to be defined. The purpose of the present study was to define the effect of histamine on the regulation of ANP release in perfused beating rabbit atria. Histamine decreased ANP release concomitantly with increases in cAMP efflux and atrial dynamics in a concentration-dependent manner. Histamine-induced decrease in ANP release was a function of an increase in cAMP production. Blockade of histamine H2 receptor with cimetidine but not of H1 receptor with triprolidine abolished the responses of histamine. Cell-permeable cAMP analog, 8-Br-cAMP, mimicked the effects of histamine, and the responses were dose-dependent and blocked by a protein kinase A (PKA)-selective inhibitor, KT5720. Nifedipine failed to modulate histamine-induced decrease in ANP release. Protein kinase nonselective inhibitor staurosporine blocked histamine-induced changes in a concentration-dependent manner. KT5720 and RP-adenosine 3′,5′-cyclic monophosphorothioate, another PKA-selective inhibitor, attenuated histamine-induced changes. These results suggest that histamine decreases atrial ANP release by H2 receptor-cAMP signaling via PKA-dependent and -independent pathways.

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Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK−/− and GLUT5−/− mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00188.2015 ◽

2015 ◽

Vol 309 (9) ◽

pp. G779-G790 ◽

Cited By ~ 33

Author(s):

Chirag Patel ◽

Keiichiro Sugimoto ◽

Veronique Douard ◽

Ami Shah ◽

Hiroshi Inui ◽

...

Keyword(s):

Metabolic Syndrome ◽

Organ Dysfunction ◽

Elevated Blood ◽

Wild Type ◽

Dietary Fructose ◽

Ad Libitum ◽

Induced Changes ◽

Dose Dependent ◽

Ad Libitum Feeding ◽

Endogenous Synthesis

Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were <0.07 mM, were independent of time after feeding, were similar to those of GLUT5−/−, and did not lead to hyperglycemia. Postprandial fructose levels, however, increased markedly in those fed isocaloric 20% fructose, causing significant hyperglycemia. Deletion of KHK prevented fructose-induced hyperglycemia, but caused dramatic hyperfructosemia (>1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK−/− mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK−/−, mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK−/− mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK−/− and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome.

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Regulation of pyruvate dehydrogenase activity in rat epididymal fat-pads and isolated adipocytes by adrenaline

Biochemical Journal ◽

10.1042/bj1740119 ◽

1978 ◽

Vol 174 (1) ◽

pp. 119-130 ◽

Cited By ~ 10

Author(s):

S J Smith ◽

E D Saggerson

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Acid Synthesis ◽

Maximum Decrease ◽

Isolated Adipocytes ◽

Induced Changes ◽

Relationship Of ◽

The Relationship ◽

Dose Dependent ◽

Fat Pads

1. Dose-dependent effects of adrenaline on PDHa activity were investigated with both incubated rat epidiymal fat-pads and isolated adipocytes. 2. Adrenaline (10nM- 5 micrometer) decreased PDHa activity in fat-pads incubated with 5 mM-[U-14C]glucose + insulin (20 munits/ml). Changes in [U-14C]glucose incorporation into fatty acids in these tissues correlated only loosely with changes in PDHa activity. There was a good inverse relationship between adrenaline-induced changes in PDHa activity and increases in lipolysis (glycerol release). 3. Adrenaline (10nM - 0.5 micrometer) decreased PDHa activity in fat-pads incubated with 5 mM-[U-14C]pyruvate + insulin (20 munits/ml), whereas 1 micrometer- and 5 micrometer-adrenaline slightly increased PDHa activity. All concentrations of adrenaline tested decreased [U-14C]pyruvate incorporation into fatty acids. Between 10nM- and 0.5 micrometer-adrenaline percentage decreases in PDHa activity paralleled decreases in faty acid synthesis. 4. Effects of adrenaline on PDHa activity and fatty acid synthesis in fat-pads incubated with 5mM-[U-14C]pyruvate + insulin (20 munits/ml) could not be mimicked by addition of albumin-bound palmitate. 5. The response of PDHa activity to adrenaline (0.1 nM - 1 micrometer) in isolated adipocytes differed with the carbohydrate substrate used in the incubations. With 5 mM-glucose + insulin (20 munits/ml), PDHa activity was significantly increased by 10 nM-adrenaline, but not by 1 micrometer-adrenaline, the response to adrenaline being biphasic. There was some correlation between PDHa activity and accumulation of non-esterified fatty acids. With 5 mM-glucose alone adrenaline (0.1 nM - 1 micrometer) had no effect on PDHa activity even though lipolysis was increased by adrenaline (0.1 micrometer - 1 micrometer). With 5mM-fructose in the presence and absence of insulin, lipolytic doses of adrenaline decreased PDHa activity. No tested concentrations of adrenaline increased PDHa with this substrate. 6. In the presence of 5 mM-fructose, palmitate was significantly more effective than adrenaline with respect to the maximum decrease in PDHa activity that could be elicited. 4. The relationship of changes in PDHa activity to changes in lipogenesis and the likelihood of adrenaline-induced changes in PDHa activity being secondary to changes in non-esterified fatty acid metabolism are discussed.

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