SENSITIVITY OF THE RAT TO INCREASING DOSES OF DEXTRAN

1962 ◽  
Vol 40 (1) ◽  
pp. 697-702 ◽  
Author(s):  
Gaetan Jasmin ◽  
Pierre Bois ◽  
Mai-Shian Su
Keyword(s):  
Toxic Effect ◽  
Intravenous Injection ◽  
Dose Response ◽  
Dose Range ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Toxic Dose ◽  
Lower Dose Range ◽  
Higher Doses ◽  
Adrenalectomized Rats

Increasing doses of dextran, a commercial 6% solution, were injected intravenously into both intact and adrenalectomized rats to evaluate the dose–response relationship. The minimum dose capable of producing an edema with 100% incidence was approximately 30 mg/kg in intact and only 4 mg/kg in adrenalectomized rats. Lower doses produced responses of decreasing intensity and incidence with a longer period of onset. Conversely, higher doses resulted in a shorter period of onset and a more intense reaction until a toxic dose was reached, beyond which cyanosis and shock appeared. Adrenalectomized rats reacted similarly to intact ones except that their response occurred at a lower dose range; they could not withstand the toxic effect of higher doses and died of circulatory failure. The fact reported by other workers that the edema is more intense and appears more rapidly after intravenous injection of minute rather than large quantities of dextran was not confirmed; the existence of a "critical dose" that does not produce any edema was not substantiated.

SENSITIVITY OF THE RAT TO INCREASING DOSES OF DEXTRAN

1962 ◽  
Vol 40 (6) ◽  
pp. 697-702 ◽  
Author(s):  
Gaetan Jasmin ◽  
Pierre Bois ◽  
Mai-Shian Su
Keyword(s):  
Toxic Effect ◽  
Intravenous Injection ◽  
Dose Response ◽  
Dose Range ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Toxic Dose ◽  
Lower Dose Range ◽  
Higher Doses ◽  
Adrenalectomized Rats

Increasing doses of dextran, a commercial 6% solution, were injected intravenously into both intact and adrenalectomized rats to evaluate the dose–response relationship. The minimum dose capable of producing an edema with 100% incidence was approximately 30 mg/kg in intact and only 4 mg/kg in adrenalectomized rats. Lower doses produced responses of decreasing intensity and incidence with a longer period of onset. Conversely, higher doses resulted in a shorter period of onset and a more intense reaction until a toxic dose was reached, beyond which cyanosis and shock appeared. Adrenalectomized rats reacted similarly to intact ones except that their response occurred at a lower dose range; they could not withstand the toxic effect of higher doses and died of circulatory failure. The fact reported by other workers that the edema is more intense and appears more rapidly after intravenous injection of minute rather than large quantities of dextran was not confirmed; the existence of a "critical dose" that does not produce any edema was not substantiated.

Fluoxetine seems to widen the nortriptyline antidepressant-like dose range in mice submitted to the tail suspension test (TST)

1992 ◽  
Vol 7 (1) ◽  
pp. 33-37
Author(s):  
IR de Oliveira ◽  
PR Brito ◽  
MF Peres ◽  
R Dardennes ◽  
MA da Rocha-Junior ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Dose Response ◽  
Dose Range ◽  
Tail Suspension Test ◽  
Response Relationship ◽  
Tail Suspension ◽  
Dose Response Relationship ◽  
High Doses ◽  
Higher Doses ◽  
Suspension Test

SummaryThis study was designed to verify whether fluoxetine (FL), a serotonin (5-HT) re-uptake inhibitor, would interfere with nortriptyline (NT), a biphasic U-shaped curvilinear dose-response relationship recently described in our laboratory. We associated 10 mg/kg NT or vehicle to 0, 5, 10, 20 and 40 mg/kg FL, in one group, and 10 mg FL or vehicle to 0, 5, 10, 20 and 40 mg/kg NT, in another group, 30 min before the tail suspension test (TST) in mice. Although we were not able to confirm a synergistic effect between FL and NT, FL-NT association seems to require higher doses of NT to block its own anti-immobility effect at high doses, thus widening NT effective antidepressant-like dose range in mice submitted to TST.

scholarly journals Novel dose–response analyses of treprostinil in pulmonary arterial hypertension and its effects on six-minute walk distance and hospitalizations

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402092395
Author(s):  
Gautam Ramani ◽  
Steven Cassady ◽  
Eric Shen ◽  
Meredith Broderick ◽  
Allie Wasik ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Dose Response ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Higher Doses ◽  
Minute Walk Distance ◽  
Minute Walk

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension. Apart from the inhaled formulation, there is neither a target dose nor a ceiling dose to guide clinicians using treprostinil; doses are individualized for each patient based upon tolerability and clinical improvement. Using combined data from the pivotal subcutaneous and oral treprostinil studies, we evaluated the effect of treprostinil dose on hospitalization and exercise capacity to better define the treprostinil dose–response relationship. Data from the pivotal subcutaneous and oral treprostinil studies were combined by converting oral doses to weight-based continuous doses (ng/kg/min) accounting for patient weight and bioavailability. Patients were divided into dose tertiles (lowest, middle, highest 33%) and retrospectively analyzed. Analysis 1 assessed the effect of dose on pulmonary arterial hypertension-related and all-cause hospitalizations. Analysis 2 evaluated the effects of dose on six-minute walk distance, Borg dyspnea score, and World Health Organization functional class. Results showed that, in Analysis 1, higher doses of treprostinil were associated with significantly longer times to first pulmonary arterial hypertension-related and all-cause hospitalization. In Analysis 2, there was a trend toward improvements in six-minute walk distance with higher doses. In patients with pulmonary arterial hypertension on systemic treprostinil therapy, higher doses were associated with significantly longer time to first pulmonary arterial hypertension-related and all-cause hospitalization. There was a trend toward improvements in six-minute walk distance. Collectively, these results underscore the importance of managing prostacyclin adverse events in order to achieve appropriate dose titration. Further studies are required to confirm these findings and to better characterize the dose–response relationship of treprostinil.

CYCLIC AMP AND CYCLIC GMP ACCUMULATION BY ISOLATED HAMSTER GRANULOSA CELLS STIMULATED BY LH AND FSH

1978 ◽  
Vol 89 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Anastasia Makris ◽  
Kenneth J. Ryan
Keyword(s):  
Cyclic Amp ◽  
Granulosa Cells ◽  
Dose Response ◽  
Cyclic Gmp ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Cyclic Amp Accumulation ◽  
Relationship Of ◽  
Higher Doses ◽  
Cyclic Amp Synthesis

ABSTRACT Cyclic AMP and cyclic GMP accumulation in hamster granulosa cells as a function of gonadotrophin dose (LH or FSH) and time (0–30 min) was determined. The pattern of acute cyclic AMP accumulation was similar in LH and FSH stimulated granulosa cells, except that the cells were more sensitive to FSH than LH. There was a positive dose response relationship of cyclic AMP accumulation in LH and FSH stimulated cells. LH appeared to partially inhibit FSH stimulated cyclic AMP synthesis. Cyclic GMP accumulation was distinctly different in LH and FSH stimulated cells. An inverse dose response relationship of cyclic GMP to dose LH was observed, with only the lowest dose of LH (0.005 IU/ml) stimulating cyclic GMP synthesis. FSH at 0.005 IU/ml did not stimulate cyclic GMP synthesis, but at higher doses generated cyclic GMP in a positive dose-related manner. The results suggest that specificity of hormone action in granulosa cells may be governed in part by differential on cyclic AMP and cyclic GMP in these cells.

Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

2021 ◽  
pp. 1-10
Author(s):  
Lena Rink ◽  
Anne Adams ◽  
Cora Braun ◽  
Tom Bschor ◽  
Kathrin Kuhr ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Major Depressive ◽  
Meta Analyses ◽  
Higher Doses ◽  
Norepinephrine Reuptake

<b><i>Introduction:</i></b> Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. <b><i>Objective:</i></b> This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. <b><i>Methods:</i></b> A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). <b><i>Results:</i></b> From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. <b><i>Conclusion:</i></b> Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

Histopathologic Effects of Cidofovir on Cartilage

2005 ◽  
Vol 133 (5) ◽  
pp. 666-671 ◽  
Author(s):  
Jeffrey H. Spiegel ◽  
Jennifer G. Andrus ◽  
Catherine M. Stefanato ◽  
Timothy Heeren
Keyword(s):  
Dose Response ◽  
Rabbit Model ◽  
Recurrent Respiratory Papillomatosis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Local Effects ◽  
Skin Changes ◽  
New Zealand White Rabbits ◽  
Higher Doses

OBJECTIVE: To evaluate the effects of subcutaneously injected cidofovir on cartilage in a rabbit model. STUDY DESIGN: Prospective study. The ears of 6 New Zealand White rabbits received perichondrial injection at 2 sites each of 0.1 mL of cidofovir in concentrations of 75 mg/mL, 25 mg/mL, 5 mg/mL, and 0 mg/mL. Animals were monitored for 6 weeks, and then injection sites excised and evaluated for histopathologic changes in epithelium, perichondrium, and cartilage. RESULTS: A positive dose–response relationship existed for gross skin changes; however, there was no dose–response relationship for severity of change in the epithelium. There was a temporal component to gross changes, demonstrating peak incidence and severity between 2 and 3 weeks after injection, with resolution of most changes within the 6-week study period. There was an increased likelihood of cartilage change when injecting cidofovir, but no clear relationship with injected dose. CONCLUSION: We report the first evaluation of the local effects of cidofovir injection on cartilage. The results of this study using a rabbit model suggest that delayed skin changes or histopathologic change in the cartilage may be expected in approximately one third of sites injected. Although there was a statistical likelihood for increased local change after cidofovir injection, there was no correlation of severity with injected dose. SIGNIFICANCE: Higher doses of cidofovir than commonly are used in the treatment of recurrent respiratory papillomatosis may be safe to use, although the effects of repeat application and long-term complications are not yet evident.

Dose-Response Relationship of Inhaled Metaproterenol Sulfate in Preschool Children With Mild Asthma

PEDIATRICS ◽  
1990 ◽  
Vol 85 (6) ◽  
pp. 1072-1075
Author(s):  
Eliezer Nussbaum ◽  
Mario Eyzaguirre ◽  
Stanley P. Galant
Keyword(s):  
Preschool Children ◽  
Dose Response ◽  
Area Under The Curve ◽  
Mild Asthma ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Parallel Group ◽  
Relationship Of ◽  
Primary Variable ◽  
Higher Doses

The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P &lt; .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma.

A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Subcutaneous Injection ◽  
Response Relationship ◽  
Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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