Transvascular albumin and IgG flux in skin after a continuous 3-h bradykinin infusion

1992 ◽  
Vol 263 (4) ◽  
pp. H1064-H1070
Author(s):  
J. R. Wallace ◽  
D. R. Bell
Keyword(s):  
Plasma Concentration ◽  
Femoral Artery ◽  
Plasma Clearance ◽  
Initial Response ◽  
Sustained Response ◽  
Distribution Space ◽  
Endothelial Gaps ◽  
Ig G ◽  
Endogenous Albumin ◽  
Sustained Increase

Bradykinin (1 microgram/min) was infused into the femoral artery of one hindleg of anesthetized rabbits for 3 h. Measurements of the initial extravascular uptake for labeled albumin and immunoglobulin (Ig) G were compared with measurements of the lymph protein flux for endogenous albumin and IgG. With bradykinin, the initial extravascular uptake for both albumin and IgG, calculated as the 1-h extravascular distribution space at plasma concentration divided by time and expressed as a plasma clearance, was 12 times the control values. For both proteins, the lymph fluxes were not significantly greater than the values for extravascular uptake, indicating that the sustained increase in lymph protein flux was not due to washout of interstitial protein. The extravascular uptake for IgG was approximately 80% of that for albumin in both control and bradykinin animals, suggesting that the sustained response did not change the selectivity between the two proteins. Changes in the extravascular masses of endogenous albumin and IgG suggest that the initial response to bradykinin was a transient formation of endothelial gaps that did not restrict transvascular IgG transport more than albumin.

scholarly journals POS0461 RESPONSE TO BIOLOGIC THERAPY IN RHEUMATOID ARTHRITIS: RETHINKING OUR CLASSIFICATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 462.1-462
Author(s):  
E. Vallejo-Yagüe ◽  
S. Kandhasamy ◽  
E. Keystone ◽  
A. Finckh ◽  
R. Micheroli ◽  
...  
Keyword(s):  
Treatment Response ◽  
Real World ◽  
Observational Studies ◽  
Initial Response ◽  
Primary Response ◽  
Sustained Response ◽  
Secondary Response ◽  
Real World Data ◽  
World Data ◽  
Secondary Failure

Background:In rheumatoid arthritis (RA), primary failure with biologic treatment may be understood as lack of initial clinical response, while secondary failure would be loss of effectiveness after an initial response. Despite these clinical concepts, there is no unifying operational definition of primary and secondary non-response to RA treatment in observational studies using real-world data. On top of data-driven challenges, when conceptualizing secondary non-responders, it is unclear if the mechanism behind loss of effectiveness after a brief initial response is similar to loss of effectiveness after previous benefit sustained over time.Objectives:This viewpoint aims to motivate discussion on how to define primary and secondary non-response in observational studies. Ultimately, we aim to trigger expert committees to develop standard terminology for these concepts.Methods:We discuss different methodologies for defining primary and secondary non-response in observational studies. To do so, we shortly overview challenges characteristic of performing observational studies in real-world data, and subsequently, we conceptualize whether treatment response should be a dichotomous classification (Primary response/non-response; Secondary response/non-response), or whether one should consider three response categories (Primary response/non-response; Primary sustained/non-sustained response; Secondary response/non-response).Results:RA or biologic registries are a common data source for studying treatment response in real-world data. While registries include disease-specific variables to assess disease progression, missing data, loss of follow-up, and visits restricted to the year or mid-year visit may present a challenge. We believe there is a general agreement to assess primary response within the first 6 month of treatment. However, conceptualizing secondary non-response, one could wonder if a patient with brief initial response and immediate loss of it should belong to the same response category as a patient who relapses after a period of prior benefit that was sustained over time. Until this concern is clarified, we recommend considering a period of sustained response as a pre-requisite for secondary failure. This would result in the following three categories: a) Primary non-response: Lack of response within the first 6 months of treatment; b) Primary sustained response: Maintenance of a positive effectiveness outcome for at least the first 12 months since treatment start; c) Secondary non-response: Loss of effectiveness after achieved primary sustained response. Figure 1 illustrates this classification through a decision tree. Since the underlying mechanisms for treatment failure may differ among the above-mentioned categories, we recommend to use the three-category classification. However, since this may pose additional methodological challenges in real-world data, optionally, a dichotomous 12-month time-point may be used to assess secondary non-response (unfavourable outcome after 12-months) in comparison to primary non-response or non-sustained response (unfavourable outcome within the first 12-months). Similarly, to study primary response, the solely 6-month timepoint may be used.Conclusion:A unified operational definition of treatment response will minimize heterogeneity among observational studies and help improve the ability to draw cross-study comparisons, which we believe would be of particular interest when identifying predictors of treatment failure. Thus, we hope to open the room for discussion and encourage expert committees to work towards a common approach to assess treatment primary and secondary non-response in RA in observational studies.Disclosure of Interests:Enriqueta Vallejo-Yagüe: None declared, Sreemanjari Kandhasamy: None declared, Edward Keystone Speakers bureau: Amgen, AbbVie, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Novartis, Pfizer Pharmaceuticals, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Grant/research support from: Pfizer, BMS, Novartis, Raphael Micheroli Consultant of: Gilead, Eli-Lilly, Pfizer and Abbvie, Andrea Michelle Burden: None declared

scholarly journals The Influence of Sampling Site upon the Distribution Phase Kinetics of Thiopentone

1984 ◽  
Vol 12 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Robin Barrett ◽  
G. G. Graham ◽  
T. A. Torda
Keyword(s):  
Plasma Concentration ◽  
Intravenous Administration ◽  
Femoral Artery ◽  
Time Course ◽  
Sampling Site ◽  
Acute Tolerance ◽  
Hplc Assay ◽  
Distribution Phase ◽  
Kinetics Of

In six sheep anaesthetised with ketamine blood was sampled from the jugular and femoral veins and the femoral artery at frequent intervals for 12 minutes following the intravenous administration of 5 or 10 mg/kg sodium thiopentone. Samples were also taken from cubital veins and radial arteries of five patients who received 5 mg/kg thiopentone. The plasma concentration of thiopentone was determined by an HPLC assay. The time course of plasma concentration of thiopentone showed considerable variation according to sampling site as well as variation between individuals. Such sampling site-dependent variation may result in the appearance of acute tolerance.

Plasmatic diatrizoate-I131 disappearance and glomerular filtration in the dog

1963 ◽  
Vol 204 (4) ◽  
pp. 536-540 ◽  
Author(s):  
M. Donald Blaufox ◽  
David R. Sanderson ◽  
W. Newlon Tauxe ◽  
Khalil G. Wakim ◽  
Alan L. Orvis ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Urinary Excretion ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Biliary Excretion ◽  
Plasma Clearance ◽  
Compartment System ◽  
Intravenous Injections

A study was made of the disappearance of sodium diatrizoate-I131 from the plasma of ten dogs after single intravenous injections. The plasma disappearance curves suggested a two-compartment system. The renal plasma clearance of diatrizoate-I131 calculated from these curves and the conventional renal plasma clearance of creatinine were not statistically different. Clearances calculated from the urinary excretion and midperiod plasma concentration of radioactivity in four experiments yielded values averaging 10% less than the creatinine clearance. Chromatographic studies of commercially available diatrizoate-I131 revealed the presence of about 5% free iodide and of about 5% of unidentified impurities. These impurities seem to account, partly at least, for the differences found between diatrizoate clearance and creatinine clearance. Biliary excretion and erythrocytic uptake of diatrizoate were minimal and did not appear to influence the analysis.

scholarly journals Antidepressant medicationsv.cognitive therapy in people with depression with or without personality disorder

2008 ◽  
Vol 192 (2) ◽  
pp. 124-129 ◽  
Author(s):  
Jay C. Fournier ◽  
Robert J. DeRubeis ◽  
Richard C. Shelton ◽  
Robert Gallop ◽  
Jay D. Amsterdam ◽  
...  
Keyword(s):  
Personality Disorder ◽  
Cognitive Therapy ◽  
Antidepressant Drugs ◽  
Antidepressant Medication ◽  
Poor Response ◽  
Initial Response ◽  
Response Rates ◽  
Sustained Response ◽  
Random Assignment ◽  
Sustained Response Rate

BackgroundThere is conflicting evidence about comorbid personality pathology in depression treatments.AimsTo test the effects of antidepressant drugs and cognitive therapy in people with depression distinguished by the presence or absence of personality disorder.MethodRandom assignment of 180 out-patients with depression to 16 weeks of antidepressant medication or cognitive therapy. Random assignment of medication responders to continued medication or placebo, and comparison with cognitive therapy responders over a 12-month period.ResultsPersonality disorder status led to differential response at 16 weeks; 66%v.44% (antidepressantsv.cognitive therapy respectively) for people with personality disorder, and 49%v.70% (antidepressantsv.cognitive therapy respectively) for people without personality disorder. For people with personality disorder, sustained response rates over the 12-month follow-up were nearly identical (38%) in the prior cognitive therapy and continuation-medication treatment arms. People with personality disorder withdrawn from medication evidenced the lowest sustained response rate (6%). Despite the poor response of people with personality disorder to cognitive therapy, nearly all those who did respond sustained their response.ConclusionsComorbid personality disorder was associated with differential initial response rates and sustained response rates for two well-validated treatments for depression.

scholarly journals Investigations on the Influence of Zidovudine in the Pharmacokinetics of Isoniazid and Its Hepatotoxic Metabolites in Rats

2017 ◽  
Vol 32 (1) ◽  
pp. 9-18
Author(s):  
Raghu Ramanathan ◽  
Karthikeyan Sivanesan
Keyword(s):  
Plasma Concentration ◽  
Drug Interactions ◽  
Bacterial Infections ◽  
Plasma Clearance ◽  
Combined Therapy ◽  
Maximum Plasma Concentration ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Group I ◽  
Pharmacokinetic Drug

The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites. Seventy two rats were randomly divided into two major groups with their sub-groups each comprising 6 animals. The Group I received INH alone at a dose of 25 mg/kg; b.w and Group II received AZT (50 mg/kg; b.w) along with INH orally. Pharmacokinetic studies of INH and its metabolites i.e., acetyl hydrazine (ACHY) and hydrazine (HYD) shows that INH and ACHY attains maximum plasma concentration ( Cmax) within 30 minutes and HYD attains Cmax at 1 hour after INH administration and all these analytes disappear from plasma within 4 hours. Pharmacokinetic studies also revealed that AZT treatment did not showed any drug-drug interactions and have no effect on the T1/2, plasma clearance, AUC, Cmax and Tmax of INH and its hepatotoxic metabolites.

Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance

1989 ◽  
Vol 257 (5) ◽  
pp. E743-E750 ◽  
Author(s):  
J. H. Henriksen ◽  
N. J. Christensen
Keyword(s):  
Plasma Concentration ◽  
Infusion Rate ◽  
Plasma Clearance ◽  
Whole Body ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance ◽  
Infusion Time ◽  
Total Plasma ◽  
Straight Line ◽  
Body Clearance

To investigate catecholamine residence in plasma, constant intravenous infusions of increasing duration (20, 40, and 80 min) of [3H]norepinephrine [( 3H]NE), [3H]isoproterenol [( 3H]IP) IP) and a reference substance: 131I-labeled hippurate were performed in six normal volunteers. In contrast to [3H]IP and 131I-hippurate, whole body clearance from plasma of [3H]NE, as obtained from infusion rate divided by plasma concentration of tracer [1.74 +/- 0.64 (SD) 1/min] was significantly higher than the value obtained by total tracer infusion divided by total plasma area of tracer (1.27 +/- 0.51, P less than 0.01). Mean residence time in plasma (theta) after stopping the infusion of [3H]NE increased along an almost straight line with progressive infusion time, theta of 131I-hippurate increased less, and constant values were recorded after 40 min infusion of [3H]IP. Our results suggest the presence of a very large (cellular) pool from which a reversible transport of [3H]NE back into plasma takes place. The plasma clearance of tracer NE, as determined from infusion rate and plasma concentration of tracer, includes transport to and accumulation in this large store. Thus the "final metabolic clearance," reflecting irreversible removal of NE, is smaller than previously estimated due to recycling through the plasma space. Attention has been drawn to limitations of [3H]NE kinetics.

World Wrestling Entertainment Responds to the Chris Benoit Tragedy: A Case Study

2011 ◽  
Vol 4 (1) ◽  
pp. 99-114 ◽  
Author(s):  
Laura Richardson Walton ◽  
Kevin D. Williams
Keyword(s):  
Qualitative Analysis ◽  
Initial Response ◽  
Sustained Response ◽  
Response Strategies ◽  
World Wrestling Entertainment ◽  
Immediate Response

An organization’s initial response to a crisis can dictate the tone of its sustained response throughout the crisis, as well as stakeholders’ reactions to the incident. When news of the deaths of professional wrestler Chris Benoit, his wife, and their 7-yr-old son broke, World Wrestling Entertainment (WWE) immediately paid tribute to the superstar. A memorial show to Benoit’s career aired as investigators searched the family’s home. The investigation revealed that Benoit murdered his wife and son before taking his own life, resulting in WWE’s retraction of its earlier tributes. Furthermore, the organization had to respond to the swarm of speculation that steroids—and WWE’s lax policy on their use—were to blame. This case study analyzes WWE’s immediate response strategies to their employee’s family’s deaths and the subsequent strategies used on learning that the employee was implicated. Qualitative analysis of corporate documents and official statements seeks to provide direction regarding how similar organizations should respond in the days immediately after tragic events when employees may be implicated.

Maturational changes in the LH response of domestic fowl to synthetic chicken LHRH-I and -II

1989 ◽  
Vol 123 (2) ◽  
pp. 311-318 ◽  
Author(s):  
S. C. Wilson ◽  
F. J. Cunningham ◽  
R. A. Chairil ◽  
R. T. Gladwell
Keyword(s):  
Plasma Concentration ◽  
Sexual Development ◽  
Plasma Concentrations ◽  
Egg Laying ◽  
Prolonged Action ◽  
Initial Rise ◽  
Lh Release ◽  
Higher Doses ◽  
Type Response ◽  
Sustained Increase

ABSTRACT Treatment of chickens at different stages of sexual development with a single i.v. injection of synthetic chicken LHRH (cLHRH)-I or -II stimulated a rise in the plasma concentration of LH within 1 min. The activity of cLHRH-II was 1·3- to 2·7-fold greater than that of cLHRH-I in sexually immature cockerels and hens as determined by the changes in the plasma concentration of LH during the 5 or 10 min after injection. This could be attributed to both a greater effectiveness of cLHRH-II to stimulate LH release and to a more prolonged action. Thus, LH concentrations in plasma were maximal within 1–2 min of injection of all doses of cLHRH-I but within 2–5 min of injection at the higher doses of cLHRH-II. The responsiveness of the pituitary gland to cLHRH-I and -II was substantially greater in the sexually immature cockerel than in the hen and diminished during sexual development of the hen. Coincident with the onset of egg laying, the characteristics of the LH response to cLHRH-II changed to consist of an initial rise during the first 2 min, followed by a more sustained increase with LH concentrations still rising 10 min after injection. In contrast, after injection with cLHRH-I, plasma concentrations of LH rose to a peak at 2 min and thereafter declined gradually. Treatment of the sexually immature hen with oestradiol, progesterone or a combination of both steroids did not enable the expression of a laying hen-type response to the injection of cLHRH-II. It would appear, therefore, that unidentified events associated with the final stages of sexual maturation bring about changes in the mechanism of action of cLHRH-II which differ from those of cLHRH-I. Journal of Endocrinology (1989) 123, 311–318

Latency of pancreatic enzyme response to intraduodenal stimulants

1980 ◽  
Vol 238 (1) ◽  
pp. G23-G29 ◽  
Author(s):  
M. V. Singer ◽  
T. E. Solomon ◽  
J. Wood ◽  
M. I. Grossman
Keyword(s):  
Response Time ◽  
Pancreatic Juice ◽  
Sodium Oleate ◽  
Pancreatic Enzyme ◽  
Initial Response ◽  
Truncal Vagotomy ◽  
Before And After ◽  
Pancreatic Fistulas ◽  
The Mean ◽  
Sustained Increase

In six dogs with pancreatic fistulas, secretin (500 ng . kg-1 . h-1) was given to provide a flow of pancreatic juice of about 1 drop/s. Amylase concentration was measured in each drop before and after rapid intraduodenal injection of L-tryptophan, sodium oleate, and NaCl or after rapid intraportal injection of cholecystokinin (CCK). Latency of response (time between injection and a sustained increase in amylase output greater than the mean + 3 SD of prestimulation output) was 0.30 min to tryptophan and 0.33 min to oleate. These were significantly (P less than 0.01) less than the latency to intraportal CCK (0.53 min). Atropine and truncal vagotomy increased the latency to tryptophan and oleate 10-fold but had no effect on the latency to intraportal CCK. We conclude that, since the latency of amylase response to intraduodenal stimulants was shorter than to intraportal CCK, the initial response is probably not due to release of hormones. The finding that atropine and vagotomy increased latency of response to intraduodenal stimulants indicates that a vagovagal cholinergic reflex mediates the early pancreatic enzyme response to intestinal stimulants.

Plasma Concentrations of Radiocalcium after Oral Administration, and Their Relationship to Absorption

1970 ◽  
Vol 38 (1) ◽  
pp. 27-39 ◽  
Author(s):  
P. Tothill ◽  
A. W. Dellipiani ◽  
J. Calvert
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Plasma Clearance ◽  
Calcium Absorption ◽  
Plasma Concentrations ◽  
Total Absorption ◽  
Isotope Method ◽  
Exchange Processes ◽  
Disappearance Curve ◽  
Double Isotope

1. Different radioisotopes of calcium were administered orally and intravenously to a series of patients, some normal and others with diseases that might affect calcium absorption or metabolism. Concentrations of the two isotopes in plasma were determined at intervals. A mathematical procedure was developed for deriving from these measurements the total absorption of the oral dose and also the absorption/time relationship. 2. The correlation between absorption and plasma concentration of the oral dose at various times after administration was studied and found to be very good, the 2 hr plasma level giving the best correlation, particularly when account was taken of the patient's weight. 3. The effect of variations in the disappearance curve of the injected isotope upon the shape of the plasma appearance curve of the oral isotope was examined. It is concluded that for the majority of cases, when absorption is not greatly delayed, and the exchange processes determining the shape of the disappearance curve are not markedly abnormal, 2 hr plasma concentration gives a good indication of absorption. When abnormalities in these processes are present, only the double isotope method gives accurate results. 4. The results were applied to examine the validity of other published methods of analysis. It was found that plasma concentrations of orally administered radiocalcium alone can give useful information about absorption, but not about plasma clearance.

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