Ovine (o) and human (h) corticotrophin releasing factor (CRF) in man: CRF-stimulation and CRF-immunoreactivity

1984 ◽  
Vol 106 (3) ◽  
pp. 289-297 ◽  
Author(s):  
G. K. Stalla ◽  
Johanna Hartwimmer ◽  
K. von Werder ◽  
O. A. Müller
Keyword(s):  
Dose Response ◽  
Biological Response ◽  
Cross Reactivity ◽  
Cortisol Secretion ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Sephadex Column ◽  
Corticotrophin Releasing Factor ◽  
Significant Difference ◽  
Human Material

Abstract. The biological activity of ovine (o) and human (h) corticotrophin releasing factor (CRF) in normal volunteers was investigated. Nine subjects received an iv bolus injection of 50, 100 and 200 μg oCRF. There was no dose-response relationship between the injected oCRF dosage and stimulated ACTH, β-endorphin, and cortisol secretion. The addition of glycine as a stabilizer to 50 and 100 μg oCRF had no effect on stimulated ACTH and cortisol secretion. When 50 and 100 μg hCRF were injected into the same subjects no significant difference compared to the oCRF induced ACTH-response was observed. In contrast to the lacking relationship between the CRF dosage and the biological response there was a clearcut dose-response relationship between the amount of oCRF injected and CRF-immunoreactivity 15 min after injection measured with a specific oCRF radioimmunoassay. Though there was only 10% cross-reactivity with synthetic hCRF, endogenous CRF-immunoreactivity could be detected in 53 of 55 pregnant females and in placental extracts. The fact that endogenous CRF immunoreactivity in humans measured by the oCRF-system may be due to the CRF molecule could be supported by identical elution profiles of synthetic and endogenous hCRF which eluted less retarded than oCRF from the Sephadex column. Our data suggest that the already established stimulation-test with oCRF can be replaced in the future by a test using human material in an identical dosage. In addition determination of endogenous CRF seems to be feasible, particularly with the homologous human system and may be of use in evaluation of patients with pituitary adrenal diseases.

Dose-response study of alendronate sodium for the treatment of cancer-associated hypercalcemia.

1993 ◽  
Vol 11 (8) ◽  
pp. 1618-1623 ◽  
Author(s):  
S R Nussbaum ◽  
R P Warrell ◽  
R Rude ◽  
J Glusman ◽  
J P Bilezikian ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Dose Response ◽  
Initial Response ◽  
Complete Response ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Alendronate Sodium ◽  
Double Blind ◽  
Days Of Therapy ◽  
Significant Difference

PURPOSE A randomized, double-blind, dose-ranging study of single-dose intravenous (IV) therapy with alendronate sodium (aminohydroxybutylidene bisphosphonate) was performed in patients with cancer-associated hypercalcemia. PATIENTS AND METHODS Patients with hypercalcemia who had not received antitumor therapy in the preceding 7 days were treated with 48 hours of IV hydration. Patients with persistent hypercalcemia (albumin-corrected serum calcium concentration [CSCC] > or = 11.5 mg/dL) were randomly assigned to receive 2.5, 5, 10, or 15 mg of alendronate infused over 2 hours, or 10 mg of alendronate infused over 24 hours. Fifty-nine patients were treated and 50 patients were assessable for the dose-response relationship. RESULTS Normalization of CSCC (< or = 10.5 mg/dL) was achieved in 22%, 82%, 75%, and 90% of assessable patients in the 2.5-, 5-, 10- (2- and 24-hour groups pooled), and 15-mg dose groups, respectively, within 8 days of therapy. Doses > or = 5 mg were significantly superior to the 2.5-mg dose level (P < .05). There was no significant difference in the minimum CSCC achieved between the 2- and 24-hour infusions of the 10-mg dose. Based on an intent-to-treat analysis of all randomized patients, the overall complete response rate was 74% for dose levels greater than 2.5 mg. For assessable patients who responded to > or = 5 mg of alendronate, the estimated median duration of normocalcemia was 10 days (range, 1 to 25). The estimated median time to relapse (CSCC > 11.5 mg/dL) was 15 days from initial treatment and 12 days from initial response, respectively. Adverse events included a transient febrile response in 34% of patients and eight episodes of reversible elevations in serum transaminase levels among treated patients. CONCLUSION While a statistically significant dose-response relationship was not clearly evident at doses greater than 5 mg, single doses of > or = 5 mg alendronate sodium effectively lowered serum calcium concentrations and were well tolerated in the treatment of cancer-associated hypercalcemia.

scholarly journals Enamel remineralization by fluoride-releasing materials: proposal of a pH-cycling model

2010 ◽  
Vol 21 (5) ◽  
pp. 446-451 ◽  
Author(s):  
Eliana Rodrigues ◽  
Alberto Carlos Botazzo Delbem ◽  
Denise Pedrini ◽  
Luciana Cavassan
Keyword(s):  
Dose Response ◽  
Response Relationship ◽  
Surface Microhardness ◽  
Dose Response Relationship ◽  
Cross Sectional ◽  
Microhardness Test ◽  
Significant Difference ◽  
Ph Cycling ◽  
And Control

This study proposes a pH-cycling model for verifying the dose-response relationship in fluoride-releasing materials on remineralization in vitro. Sixty bovine enamel blocks were selected for the surface microhardness test (SMH1). Artificial caries lesions were induced and surface microhardness test (SMH2) was performed. Forty-eight specimens were prepared with Z 100, Fluroshield, Vitremer and Vitremer ¼ diluted - powder/liquid, and subjected to a pH-cycling model to promote remineralization. After pH-cycling, final surface microhardness (SMH3) was assessed to calculate percent recovery of surface microhardness (%SMHR). Fluoride present in enamel (μg F/mm3) and in the pH-cycling solutions (μg F) was measured. Cross-sectional microhardness was used to calculate mineral content (∆Z). There was no significant difference between Z 100 and control groups on analysis performed on - %SMHR, ∆Z, μg F and mg F/mm3 (p>0.05). Results showed a positive correlation between %SMHR and μg F/mm3 (r=0.9770; p=0.004), %SMHR and μg F (r=0.9939; p=0.0000001), ∆ and μg F/mm3 (r=0.9853; p=0.0002), ∆ and μg F (r=0.9975; p=0.0000001) and between μg F/mm3 and μg F (r=0.9819; p=0.001). The pH-cycling model proposed was able to verify in vitro dose-response relationship of fluoride-releasing materials on remineralization.

Dose–response relationship of mannitol and intracranial pressure: a metaanalysis

2008 ◽  
Vol 108 (1) ◽  
pp. 80-87 ◽  
Author(s):  
Marco D. Sorani ◽  
Geoffrey T. Manley
Keyword(s):  
Intracranial Pressure ◽  
Dose Response ◽  
Statistical Significance ◽  
Clinical Importance ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Treatment Protocols ◽  
Important Relationship ◽  
Significant Difference ◽  
Relationship Of

Object Brain edema can increase intracranial pressure (ICP), potentially leading to ischemia, herniation, and death. Edema and elevated ICP are often treated with osmotic agents to remove water from brain tissue. Mannitol is the osmotic diuretic most commonly used in the intensive care unit; however, despite its clinical importance, treatment protocols vary from center to center, and the dose–response relationship is not understood. The goal of this metaanalysis was to aggregate and analyze data from studies in which authors have described the dose–response relationship between mannitol and ICP. Methods The authors identified 18 studies that quantitatively characterized the dose–response relationship of mannitol and ICP. We also examined study designs and mannitol administration protocols. Results Meta-regression found a weak linear relationship between change in ICP (ΔICP) and dose (ΔICP = 6.6 × dose − 1.1; p = 0.27, R2 = 0.05). The lack of statistical significance could reflect the variation in protocols among studies and the variation in patients both within and among studies. However, the authors found a highly significant difference (p < 0.001) in decrease in ICP when the initial ICP was higher or lower than 30 mm Hg. Nonlinear regression suggested that ICP decrease is greatest shortly after mannitol is given (R2 = 0.63). Finally, the authors found that recent studies tend to include fewer patients and set a lower ICP threshold for mannitol administration but report more parameters of interest; the duration of mannitol's effect was the most frequently unreported parameter. Conclusions Despite its clinical importance, the determination of the mannitol dose–response curve continues to be challenging for many reasons. This metaanalysis highlights the need for a consensus of methods and results required to determine this important relationship.

scholarly journals Effect of a Pedometer-based Walking Intervention on Body Composition in Patients with ESRD: A Randomized Controlled Trial

2019 ◽  
Author(s):  
Anoop Sheshadri ◽  
Piyawan Kittiskulnam ◽  
Jennifer C. Lai ◽  
Kirsten L. Johansen
Keyword(s):  
Body Composition ◽  
Muscle Mass ◽  
Fat Mass ◽  
Dose Response ◽  
Intervention Group ◽  
Step Count ◽  
Response Relationship ◽  
Dialysis Patients ◽  
Dose Response Relationship ◽  
Significant Difference

Abstract Background: A randomized trial of a pedometer-based intervention with weekly activity goals led to a modest increase in step count among dialysis patients. In a secondary analysis, we investigated the effect of this intervention on body composition.Methods: 60 dialysis patients were randomized to standard care or a 6-month program consisting of 3 months of pedometers and weekly step count targets and 3 months of post-intervention follow-up. We obtained bioelectrical impedance spectroscopy (BIS) data on 54 of these patients (28 control, 26 intervention) and used linear mixed-modeling (adjusted for sex and dialysis modality) to estimate differences in change in total-body muscle mass (TBMM) adjusted for height2, fat mass (kg), and body mass index (BMI) (kg/m2) between control and intervention groups.Results: The median age of participants was 57.5 years (53 – 66), and 76% were men. At baseline, there was no significant difference between groups in age, BMI, race, or body composition, but there were more men in the intervention group. After 3 months, patients in the intervention group increased their average daily steps by 2,414 (95% CI 1047, 3782) more than controls (p<0.001), but there were no significant differences in body composition. However, at 6 months, participants in the intervention had a significantly greater increase from baseline in TBMM of 0.7 kg/m2 (95% CI 0.3, 1.13), decrease in fat mass (‑4.3 kg [95% CI ‑7.1, ‑1.5]) and decrease in BMI (-1.0 kg/m2 [95% CI -1.8, -0.2]) relative to controls. In post-hoc analysis, each increase of 1,000 steps from 0 to 3 months was associated with a 0.3 kg decrease in fat mass (95% CI 0.05, 0.5) from 0 to 6 months, but there was no dose-response relationship with TBMM/ht2 or BMI.Conclusion: A pedometer-based intervention resulted in greater decreases in fat mass with relative preservation of muscle mass, leading to a greater decrease in BMI over time compared with patients not in the intervention. These differences were driven as much by worsening in the control group as by improvement in the intervention group. Step counts had a dose-response relationship with decrease in fat mass.Trial Registration: ClinicalTrials.gov (NCT02623348). 02 December 2015. https://clinicaltrials.gov/ct2/show/NCT02623348

scholarly journals Effect of a Pedometer-based Walking Intervention on Body Composition in Patients with ESRD: A Randomized Controlled Trial

2020 ◽  
Author(s):  
Anoop Sheshadri ◽  
Piyawan Kittiskulnam ◽  
Jennifer C. Lai ◽  
Kirsten L. Johansen
Keyword(s):  
Body Composition ◽  
Muscle Mass ◽  
Fat Mass ◽  
Dose Response ◽  
Intervention Group ◽  
Step Count ◽  
Response Relationship ◽  
Dialysis Patients ◽  
Dose Response Relationship ◽  
Significant Difference

Abstract Background: A randomized trial of a pedometer-based intervention with weekly activity goals led to a modest increase in step count among dialysis patients. In a secondary analysis, we investigated the effect of this intervention on body composition.Methods: 60 dialysis patients were randomized to standard care or a 6-month program consisting of 3 months of pedometers and weekly step count targets and 3 months of post-intervention follow-up. We obtained bioelectrical impedance spectroscopy (BIS) data on 54 of these patients (28 control, 26 intervention) and used linear mixed-modeling (adjusted for sex and dialysis modality) to estimate differences in change in total-body muscle mass (TBMM) adjusted for height2, fat mass (kg), and body mass index (BMI) (kg/m2) between control and intervention groups.Results: The median age of participants was 57.5 years (53 – 66), and 76% were men. At baseline, there was no significant difference between groups in age, BMI, race, or body composition, but there were more men in the intervention group. After 3 months, patients in the intervention group increased their average daily steps by 2,414 (95% CI 1047, 3782) more than controls (p<0.001), but there were no significant differences in body composition. However, at 6 months, participants in the intervention had a significantly greater increase from baseline in TBMM of 0.7 kg/m2 (95% CI 0.3, 1.13), decrease in fat mass (‑4.3 kg [95% CI ‑7.1, ‑1.5]) and decrease in BMI (-1.0 kg/m2 [95% CI -1.8, -0.2]) relative to controls. In post-hoc analysis, each increase of 1,000 steps from 0 to 3 months was associated with a 0.3 kg decrease in fat mass (95% CI 0.05, 0.5) from 0 to 6 months, but there was no dose-response relationship with TBMM/ht2 or BMI.Conclusion: A pedometer-based intervention resulted in greater decreases in fat mass with relative preservation of muscle mass, leading to a greater decrease in BMI over time compared with patients not in the intervention. These differences were driven as much by worsening in the control group as by improvement in the intervention group. Step counts had a dose-response relationship with decrease in fat mass. Trial Registration: ClinicalTrials.gov (NCT02623348). 02 December 2015. https://clinicaltrials.gov/ct2/show/NCT02623348

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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