Effect of cortisol on the plasma and lymphoid tissue distributions of tritiated glucocorticoids in C57BL/6 mice

1988 ◽  
Vol 117 (3) ◽  
pp. 373-378
Author(s):  
S. Durant ◽  
D. Duval ◽  
F. Homo-Delarche
Keyword(s):  
Sex Steroids ◽  
Lymphoid Tissue ◽  
Reticuloendothelial System ◽  
Lymphoid Organs ◽  
Local Concentration ◽  
High Doses ◽  
Tracer Accumulation ◽  
Kinetics Of ◽  
Dose Dependent ◽  
Very High

ABSTRACT The mechanism of action of very high doses of corticosteroids, such as those administered as bolus doses in the treatment of inflammatory and immune diseases or those currently used in rodents to isolate the small proportion of medullary thymocytes considered to be corticoresistant, is still undefined. The possible existence of selective local concentration by some tissues, particularly lymphoid organs, cannot be excluded. Therefore, using C57BL/6 mice, the kinetics of lymphoid tissue and plasma radioactivities after i.p. injection of steroids, either alone or with an excess of non-radioactive cortisol hemisuccinate (up to 10 mg/animal, i.e. 500 mg/kg ) were studied. There was a rapid and dose-dependent retention of [3H]corticosterone and [3H]cortisol in the thymuses of cortisol-treated compared with control animals. The spleen also appeared to be capable of accumulating steroids. However, when the tissue/plasma ratio of [3H]steroid concentration and the change in extracellular space in the presence of an excess of non-radioactive cortisol were taken into consideration, only the thymus was able to concentrate steroids above concentrations in the plasma. Moreover, this effect did not appear to be specific for glucocorticoids, since tracer accumulation was also observed when sex steroids were used as tracers. The cells of the reticuloendothelial system may, in part, be responsible for this phenomenon of steroid concentration in lymphoid organs. J. Endocr. (1988) 117, 373–378

Retinoic acid and pattern formation in the developing chick wing: SEM and quantitative studies of early effects on the apical ectodermal ridge and bud outgrowth

Development ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 139-169
Author(s):  
J. Lee ◽  
C. Tickle
Keyword(s):  
Retinoic Acid ◽  
Local Application ◽  
Local Source ◽  
Local Concentration ◽  
Low Doses ◽  
Response Curves ◽  
Wing Patterns ◽  
Skeletal Pattern ◽  
High Doses ◽  
Dose Dependent

When retinoic acid is locally applied to the anterior margin of developing chick wing buds on ion-exchange beads, dose-dependent changes in the skeletal pattern result. At low doses, additional digits develop. At high doses, there is thinning of the symmetrical wing. Local application of retinoic acid to the apex of the bud also leads to pattern changes, but in contrast normal wing patterns are almost always obtained following application posteriorly. These effects are manifest at 6–7 days after the operation although only a brief exposure (14–20 h) to retinoic acid is required. Therefore the morphology of wing buds was studied at shorter times after the start of treatment. The local application of retinoic acid to the wing bud margin leads to changes in extent of the apical ridge that can be detected at 24 h after application. The behaviour of the apical ridge with varying doses and positions of retinoic acid application has been analysed quantitatively and dose response curves obtained. At low doses of retinoic acid, the length of the apical ridge increases or remains constant, but then progressively decreases with higher doses. The progressive obliteration of the ridge starts first near the bead and then involves more distant parts of the bud. Thus the region of the ridge affected depends on the position at which the retinoic acid is applied. We propose that these effects on the apical ridge reflect dose-dependent responses to the local concentration of retinoic acid that varies with distance from the source. At high doses, the apical ridge disappears but at low doses it is maintained. Since grafts of polarizing region tissue also have a graded effect on ridge morphology, a possible interpretation of the retinoic acid effects is that tissue adjacent to the source is converted into polarizing region tissue. Alternatively, retinoic acid may act directly on the ridge cells. The changes in the extent of the apical ridge produced by retinoic acid lead to different forms of bud outgrowth. The form of the outgrowth depends on the dose of retinoic acid, the position of application and the interaction between the effects of the local source of retinoic acid and those of the polarizing region of the host bud. These considerations give some insights into why anterior application of retinoic acid leads to the development of additional digits whereas posterior application generally gives normal wings.

Recent findings regarding calcium and phytase in poultry nutrition

2017 ◽  
Vol 57 (11) ◽  
pp. 2311 ◽  
Author(s):  
M. Bedford ◽  
X. Rousseau
Keyword(s):  
Low Cost ◽  
Essential Element ◽  
Dependent Manner ◽  
Maximum Value ◽  
Mild Deficiency ◽  
High Doses ◽  
And Performance ◽  
Dose Dependent ◽  
Hydrolysis Of ◽  
Very High

Calcium (Ca) is an essential element for poultry and even a mild deficiency can lead to significant welfare and performance issues. As a result, it is often fed at levels in excess of requirement, partly as an insurance policy and, to some degree, because of its relatively low cost compared with other feed ingredients. However, when diets meet but do not exceed the phosphorus (P) requirements of the bird, a marginal Ca excess can interfere with P digestibility. This problem is exacerbated when phytases are used to provide some of the required P because Ca decreases the efficiency of phytate (IP6) hydrolysis in a dose-dependent manner. More recently, phytases have been used at very high doses (1500 FyTase units (FTU); ‘superdosing’) in commercial diets, to improve bird performance by removing as much of the dietary IP6 and lower esters of phytate (IP5, IP4, IP3 and IP2) as possible, all of which are considered anti-nutrients, and concomitantly producing as much inositol, a nutrient, as possible. In such a regimen, the ability of the phytase to degrade the lower phytate esters, namely IP4, IP3 and IP2, takes on greater importance than does simply releasing phytate P. Calcium has recently been shown to reduce the efficacy of hydrolysis of the lower phytate esters to a greater degree than the extent to which it decreases IP6 hydrolysis. As a result, Ca concentrations in the diet should be monitored frequently if the maximum value of a phytase is to be realised.

Cannabinoids Reveal Separate Controls for Whisking Amplitude and Timing in Rats

2010 ◽  
Vol 104 (5) ◽  
pp. 2532-2542 ◽  
Author(s):  
Maciej Dominik Pietr ◽  
Per Magne Knutsen ◽  
David I. Shore ◽  
Ehud Ahissar ◽  
Zvi Vogel
Keyword(s):  
Cannabinoid Receptor ◽  
Spectral Power ◽  
Cycle Duration ◽  
Dependent Manner ◽  
Timing Channels ◽  
Amplitude Control ◽  
High Doses ◽  
Dose Dependent ◽  
Very High

Whisking is controlled by multiple, possibly functionally segregated, motor sensory-motor loops. While testing for effects of endocannabinoids on whisking, we uncovered the first known functional segregation of channels controlling whisking amplitude and timing. Channels controlling amplitude, but not timing, were modulated by cannabinoid receptor type 1 (CB1R). Systemic administration of CB1R agonist Δ9-tetrahydrocannabinol (Δ9-THC) reduced whisking spectral power across all tested doses (1.25–5 mg/kg), whereas whisking frequency was affected at only very high doses (5 mg/kg). Concomitantly, whisking amplitude and velocity were significantly reduced in a dose-dependent manner (25–43 and 26–50%, respectively), whereas cycle duration and bilateral synchrony were hardly affected (3–16 and 3–9%, respectively). Preadministration of CB1R antagonist SR141716A blocked Δ9-THC–induced kinematic alterations of whisking, and when administered alone, increased whisking amplitude and velocity but affected neither cycle duration nor synchrony. These findings indicate that whisking amplitude and timing are controlled by separate channels and that endocannabinoids modulate amplitude control channels.

Comparative effects of arginine vasopressin and oxytocin in cell culture systems

1992 ◽  
Vol 263 (2) ◽  
pp. F222-F227
Author(s):  
V. A. Briner ◽  
P. Tsai ◽  
H. L. Choong ◽  
R. W. Schrier
Keyword(s):  
Arginine Vasopressin ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Cell Culture Systems ◽  
Antagonist Binding ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent ◽  
Very High

Arginine vasopressin (AVP) and oxytocin (OXT) induced contraction in cultured vascular smooth muscle cells (VSMC) and glomerular mesangial cells (GMC). The contractile response of AVP and OXT was paralleled by Ca2+ mobilization as assessed by 45Ca2+ efflux in a dose-dependent manner. The effects of AVP were blocked by pretreating VSMC and GMC with a V1 antagonist. OXT-stimulated effects, however, were not affected by preexposure of VSMC and GMC to an OXT antagonist but were inhibited by the V1 antagonist. Competition studies demonstrated displacement of [3H]AVP from its receptors by unlabeled AVP, the V1 antagonist, and high doses of OXT. The OXT antagonist was the least effective in displacing [3H]AVP. Thus occupancy of the V1 receptor by OXT may initiate signal transduction and contraction in VSMC and GMC in a manner qualitatively similar to that of the AVP agonist. Cultured myometrium cells (MMC) also contracted in response to AVP and OXT. Moreover, 45Ca2+ efflux increased in response to both hormones in a dose-dependent manner. AVP-stimulated contraction and 45Ca2+ efflux were blocked in MMC by pretreatment with V1 antagonist. OXT-induced effects were inhibited by the OXT antagonist but not by the V1 antagonist. Binding experiments showed that [3H]AVP was displaced equally by unlabeled AVP and V1 antagonist. Very high concentrations of OXT antagonist also demonstrated displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

The effect of heterotrophic yield on the assessment of the correction factor for anoxic growth

1996 ◽  
Vol 34 (5-6) ◽  
pp. 67-74 ◽  
Author(s):  
D. Orhon ◽  
S. Sözen ◽  
N. Artan
Keyword(s):  
Correction Factor ◽  
Domestic Sewage ◽  
Yield Coefficient ◽  
Heterotrophic Growth ◽  
Metabolic Processes ◽  
Anoxic Conditions ◽  
Industrial Wastewaters ◽  
Systems Modelling ◽  
Kinetics Of ◽  
Very High

For single-sludge denitrification systems, modelling of anoxic reactors currently uses the kinetics of aerobic heterotrophic growth together with a correction factor for anoxic conditions. This coefficient is computed on the basis of respirometric measurements with the assumption that the heterotrophic yield remains the same under aerobic and anoxic coditions. The paper provides the conceptual proof that the yield coefficient is significantly lower for the anoxic growth on the basis of the energetics of the related metabolic processes. This is used for the interpretation of the very high values for the correction factor experimentally determined for a number of industrial wastewaters. A default value for the anoxic heterotrophic yield coefficient is calculated for domestic sewage and compatible wastewaters and proposed for similar evaluations.

Polymer structure and catalytic activity of ion exchangers

1981 ◽  
Vol 46 (7) ◽  
pp. 1577-1587 ◽  
Author(s):  
Karel Jeřábek
Keyword(s):  
Catalytic Activity ◽  
Ethyl Acetate ◽  
Active Sites ◽  
Crosslinking Agent ◽  
Reaction Medium ◽  
Polymer Structure ◽  
Local Concentration ◽  
Ion Exchangers ◽  
Styrene Divinylbenzene ◽  
Kinetics Of

Catalytic activity of ion exchangers prepared by partial sulphonation of styrene-divinylbenzene copolymers in reesterifications of ethyl acetate by methanol and propanol, hydrolysis of ethyl acetate and in synthesis of bisphenol A has been compared with data on polymer structure of these catalysts and with distribution of the crosslinking agent, divinylbenzene, calculated from literature data on kinetics of copolymerisation of styrene with divinylbenzene. It was found that the polymer structure of ion exchangers influences catalytic activity predominantly by changing the local concentration of acid active sites. The results obtained indicated that the effect of transport phenomena on the rate of catalytic reactions does not depend on the degree of swelling of the ion exchangers in reaction medium but it is mainly dependent on the relative affinity of reaction components to the acid groups or to the polymer skeleton.

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.

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