scholarly journals Corticosterone Upregulates Gene and Protein Expression of Catecholamine Markers in Organotypic Brainstem Cultures

2019 ◽  
Vol 20 (12) ◽  
pp. 2901 ◽  
Author(s):  
Carla L. Busceti ◽  
Rosangela Ferese ◽  
Domenico Bucci ◽  
Larisa Ryskalin ◽  
Stefano Gambardella ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Cell Metabolism ◽  
Internal Organs ◽  
Dopamine Beta Hydroxylase ◽  
Expression Of Genes ◽  
Gene And Protein Expression ◽  
Specific Receptors ◽  
Catecholamine Neurons ◽  
High Doses ◽  
Very High

Glucocorticoids are produced by the adrenal cortex and regulate cell metabolism in a variety of organs. This occurs either directly, by acting on specific receptors in a variety of cells, or by stimulating catecholamine expression within neighbor cells of the adrenal medulla. In this way, the whole adrenal gland may support specific metabolic requirements to cope with stressful conditions from external environment or internal organs. In addition, glucocorticoid levels may increase significantly in the presence of inappropriate secretion from adrenal cortex or may be administered at high doses to treat inflammatory disorders. In these conditions, metabolic alterations and increased blood pressure may occur, although altered sleep-waking cycle, anxiety, and mood disorders are frequent. These latter symptoms remain unexplained at the molecular level, although they overlap remarkably with disorders affecting catecholamine nuclei of the brainstem reticular formation. In fact, the present study indicates that various doses of glucocorticoids alter the expression of genes and proteins, which are specific for reticular catecholamine neurons. In detail, corticosterone administration to organotypic mouse brainstem cultures significantly increases Tyrosine hydroxylase (TH) and Dopamine transporter (DAT), while Phenylethanolamine N-methyltransferase (PNMT) is not affected. On the other hand, Dopamine Beta-Hydroxylase (DBH) increases only after very high doses of corticosterone.

Daunorubicin and Platelet Function

1981 ◽  
Vol 45 (01) ◽  
pp. 038-042 ◽  
Author(s):  
M E Pogliani ◽  
R Fantasia ◽  
G Lambertenghi-Deliliers ◽  
E Cofrancesco
Keyword(s):  
Electron Microscope ◽  
Cellular Membrane ◽  
Hemorrhagic Diathesis ◽  
Clot Retraction ◽  
Freezing And Thawing ◽  
Platelet Factor ◽  
High Doses ◽  
Very High ◽  
Platelet Functions

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.

scholarly journals Quantifying prescribed high dose opioids in the community and risk of overdose

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joe Schofield ◽  
Deborah Steven ◽  
Rebecca Foster ◽  
Catriona Matheson ◽  
Alexander Baldacchino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Service Improvement ◽  
High Dose ◽  
Opioid Overdose ◽  
Opioid Prescribing ◽  
Patient Level ◽  
Strong Opioid ◽  
High Doses ◽  
Strong Opioids ◽  
Very High

Abstract Background Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise. Methods Participating practices ran searches to identify patients prescribed strong opioids and their characteristics, polypharmacy, and other overdose risk factors. Data were anonymised before being analysed at practice and patient-level. Morphine Equivalent Doses were calculated for patients based on drug/dose information and classed as Low/Medium/High/Very High. Descriptive statistics were generated on the strong opioid patient population and overdose risk factors. The relationship between the prescribing of strong opioids and practice/patient-level factors was investigated using linear and logistic regression models. Results Eighty-five percent (46/54) of GP practices participated. 12.4% (42,382/341,240) of individuals in participating practices were prescribed opioids and, of these, one third (14,079/42,382) were prescribed strong opioids. The most common comorbidities and overdose risk factors among strong opioid recipients were pain (67.2%), cardiovascular disease (43.2%), and mental health problems (39.3%). There was a positive significant relationship between level of social deprivation among practice caseload and level of strong opioid prescribing (p < 0.001). People prescribed strong opioids tended to be older (mean 59.7 years) and female (8638, 61.4%) and, among a subset of patients, age, gender and opioid drug class were significantly associated with prescribing of High/Very High doses. Conclusions Our findings have identified a large population at potential risk of prescription opioid overdose. There is a need to explore pragmatic models of tailored interventions which may reduce the risk of overdose within this group and clinical practice may need to be tightened to minimise overdose risk for individuals prescribed high dose opioids.

EFFECTS OF ECDYSONES, JUVENILE HORMONE ANALOGS, AND 6-OXOOCTANOIC ACID ON THE DEVELOPMENT OF THE MOSQUITO, CULEX TARSALIS (DIPTERA: CULICIDAE)

1974 ◽  
Vol 106 (1) ◽  
pp. 79-85 ◽  
Author(s):  
P. I. Ittycheriah ◽  
M. S. Quraishi ◽  
E. P. Marks
Keyword(s):  
Juvenile Hormone ◽  
Topical Treatment ◽  
Adult Emergence ◽  
Fourth Instar ◽  
Culex Tarsalis ◽  
Juvenile Hormone Analog ◽  
Hormone Analog ◽  
High Doses ◽  
Hormone Analogs ◽  
Very High

AbstractEggs, larvae, and pupae of Culex tarsalis Coquillett were treated with ecdysones, juvenile hormone analogs, and 6-oxooctanoic acid. Effects of these agents on mortality, induction of supernumerary stages, and adult emergence were determined. Topical treatment of eggs with CRD9499 (a juvenile hormone analog), β-ecdysone, and 22-isoecdysone caused a reduction in adult emergence. Treatment of fourth-instar larvae with these chemicals not only induced mortality but also caused the formation of supernumerary intermediate stages. Larvae of C. tarsalis were very susceptible to CRD9499, but pupae were resistant. The ecdysones caused some mortality but only at very high doses and would thus be of little use as larvicides. 6-Oxooctanoic acid caused high rates of mortality at 0.001 M concentrations.

scholarly journals Vitamin B12 transport in blood. I. Congenital deficiency of transcobalamin II

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 71-82 ◽  
Author(s):  
E Gimpert ◽  
M Jakob ◽  
WH Hitzig
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Congenital Deficiency ◽  
Complete Clinical Remission ◽  
High Concentrations ◽  
High Doses ◽  
Vitamin B12 Binder ◽  
Very High ◽  
Transcobalamin Ii

Abstract Some characteristics of vitamin B12 binding and transport in the serum of an infant with congenital hereditary transcobalamin II (TC II) deficiency were studied using the following parameters and methods: vitamin B12 level and binding capacity; electrophoretic mobility in polyacrylamide gel electrophoresis; various immunodiffusion and absorption experiments, using a specific anti-TC II antiserum and the patient's serum as antigen. The results of these studies point to a deficient synthesis of TC II. Parenteral administration of high doses of vitamin B12 was followed by rapid and complete clinical remission and the appearance of vitamin B12 binder in the alpha 2 region which is similar to “fetal binder.” Thus, very high concentrations of vitamin B12, either carrier free or bound to this alpha 2 binder, were able to correct the disturbed physiology of TC II deficiency, presumably by normalization of DNA-thymine synthesis.

scholarly journals GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high doses

2009 ◽  
Vol 325 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Ariel J. Levine ◽  
Zachary J. Levine ◽  
Ali H. Brivanlou
Keyword(s):  
Nodal Signaling ◽  
High Doses ◽  
Very High

Facilitation in Sea Anemones

1952 ◽  
Vol 29 (2) ◽  
pp. 235-254
Author(s):  
D. M. ROSS
Keyword(s):  
Bile Salt ◽  
Standardized Tests ◽  
Single Stimulus ◽  
Living Animal ◽  
Sea Anemones ◽  
Nerve Net ◽  
Reported Effect ◽  
High Doses ◽  
Electrical Stimuli ◽  
Very High

1. The previously reported effect of anemone extracts, the occurrence of quick closing responses to single electrical stimuli in Metridium, has been re-investigated. In standardized tests it was found that whereas hundreds of stimuli are required for each response to a single stimulus in untreated animals, after anemone extract the incidence of such responses is one per nine stimuli. 2. The incidence of these responses falls off with decreasing doses of extract and the effect disappears when less than 1/500th of the material from a single large Metridium is administered. There is no evidence that extracts from ‘stimulated’ and ‘unstimulated’ (i.e. anaesthetized or quick-frozen) anemones differ in potency. Extracts from divided animals show greater activity in the ‘sphincter-disk’ fraction. 3. The incidence of the responses also falls off in time and is highest from 15 to 30 sec. after beginning the treatment. The effect is sporadic and short-lived and responses to two or more successive stimuli are exceptional. 4. A number of treatments, such as drastic changes in pH, KCl(K+ x 8), tetramethylammonium hydroxide (1 : 100), NH4C1 (1 : 340) and especially bile salt and saponin, have similar effects. Drugs with neuro-muscular effects elsewhere (acetylcholine, adrenaline, tyramine, histamine, etc.) were generally ineffective except at very high doses. Food stimulants too were ineffective. 5. From the time relations and other aspects of the responses to single stimuli it is concluded that the effect should not be attributed to a substance with the function of a ‘facilitator’ in the living animal. 6. While the effects are consistent with the passage of occasional adventitious impulses in the nerve net, there is a singular absence of spontaneous or post-stimulus contractions. Certain implications of this feature of the results are discussed.

scholarly journals Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 209 ◽  
Author(s):  
Klaudia Skrzypek ◽  
Marcin Majka
Keyword(s):  
Transcription Factor ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Metabolism ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Non Coding Rnas ◽  
Tumor Growth And Metastasis ◽  
Novel Therapeutic Strategies

SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs.

Gene expression analysis in burn wounds of rats

2002 ◽  
Vol 283 (4) ◽  
pp. R918-R930 ◽  
Author(s):  
Marcus Spies ◽  
Mohan R. K. Dasu ◽  
Nenad Svrakic ◽  
Olivera Nesic ◽  
Robert E. Barrow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Regulation ◽  
Cell Metabolism ◽  
Expression Patterns ◽  
Burn Wound ◽  
Oligonucleotide Arrays ◽  
Burn Wound Healing ◽  
Expression Of Genes ◽  
Systemic Responses

The events occurring early in the burn wound trigger a sequence of local and systemic responses that influence cell and tissue survival and, consequently, wound healing and recovery. Using high-density oligonucleotide arrays we identified gene expression patterns in skin samples taken from a region of injury in the burn rat model. The associated genomic events include the differential expression of genes involved in cell survival and death, cell growth regulation, cell metabolism, inflammation, and immune response. The functional gene cluster detected and their time appearance matched the time sequence known to occur in burn wound healing.

Tools for risk assessment in radiation therapy

2012 ◽  
Vol 41 (3-4) ◽  
pp. 197-207 ◽  
Author(s):  
P. Ortiz López
Keyword(s):  
Radiation Therapy ◽  
Radiological Protection ◽  
Quality And Safety ◽  
Energy Agency ◽  
Safety Issues ◽  
Safety Programme ◽  
Specific Safety ◽  
High Doses ◽  
Very High ◽  
Icrp Publication

Radiotherapy has unquestionable benefits, but it is also associated with unique and specific safety issues. It is the only application of radiation in which humans are intentionally delivered very high doses. Safety in radiotherapy remains heavily dependent on human actions. A step-by-step approach is suggested for the prevention of accidental exposures in radiation therapy: (1) allocation of responsibilities to qualified professionals, and design of a quality and safety programme - no radiotherapy practice should be operated without these key elements; (2) use of the lessons from accidental exposures to test whether the quality and safety programme is sufficiently robust against these types of events –publications by the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency provide a collection of lessons to facilitate this step; and (3) find other latent risks by posing the questions ‘What else could go wrong?’ or ‘What other potential hazards might be present?’ in a systematic, anticipative manner - methods to do so are described briefly in ICRP Publication 112.

scholarly journals Central leptin regulates heart lipid content by selectively increasing PPAR β/δ expression

2018 ◽  
Vol 236 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Cristina Mora ◽  
Cristina Pintado ◽  
Blanca Rubio ◽  
Lorena Mazuecos ◽  
Virginia López ◽  
...  
Keyword(s):  
Target Genes ◽  
Cardiac Tissue ◽  
Cardiac Metabolism ◽  
Pyruvate Dehydrogenase Kinase ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Of Genes ◽  
Gene And Protein Expression ◽  
Tag Accumulation

The role of central leptin in regulating the heart from lipid accumulation in lean leptin-sensitive animals has not been fully elucidated. Herein, we investigated the effects of central leptin infusion on the expression of genes involved in cardiac metabolism and its role in the control of myocardial triacylglyceride (TAG) accumulation in adult Wistar rats. Intracerebroventricular (icv) leptin infusion (0.2 µg/day) for 7 days markedly decreased TAG levels in cardiac tissue. Remarkably, the cardiac anti-steatotic effects of central leptin were associated with the selective upregulation of gene and protein expression of peroxisome proliferator-activated receptor β/δ (PPARβ/δ, encoded by Pparb/d) and their target genes, adipose triglyceride lipase (encoded by Pnpla2, herefater referred to as Atgl), hormone sensitive lipase (encoded by Lipe, herefater referred to as Hsl), pyruvate dehydrogenase kinase 4 (Pdk4) and acyl CoA oxidase 1 (Acox1), involved in myocardial intracellular lipolysis and mitochondrial/peroxisomal fatty acid utilization. Besides, central leptin decreased the expression of stearoyl-CoA deaturase 1 (Scd1) and diacylglycerol acyltransferase 1 (Dgat1) involved in TAG synthesis and increased the CPT-1 independent palmitate oxidation, as an index of peroxisomal β-oxidation. Finally, the pharmacological inhibition of PPARβ/δ decreased the effects on gene expression and cardiac TAG content induced by leptin. These results indicate that leptin, acting at central level, regulates selectively the cardiac expression of PPARβ/δ, contributing in this way to regulate the cardiac TAG accumulation in rats, independently of its effects on body weight.

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