scholarly journals Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab

2019 ◽  
Vol 41 (5) ◽  
pp. 634-639 ◽  
Author(s):  
Eline De Keyser ◽  
Celine I. Busard ◽  
Sven Lanssens ◽  
Lieve Meuleman ◽  
Barbara A. Hutten ◽  
...  
Keyword(s):  
Antibody Formation ◽  
Serum Concentrations ◽  
Clinical Consequences

scholarly journals Redox imbalance and oxidative DNA damage during isoniazid treatment: A clinical and translational pharmacokinetic study

2020 ◽  
Author(s):  
Isaac Zentner ◽  
Hyun-moon Back ◽  
Leonid Kagan ◽  
Selvakumar Subbian ◽  
Jyothi Nagajyothi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Day Treatment ◽  
Cellular Damage ◽  
Hepatic Tissue ◽  
Serum Concentrations ◽  
Drug Induced ◽  
Dosing Interval ◽  
Redox Imbalance ◽  
Clinical Consequences

ABSTRACTBackgroundThe potential for hepatotoxicity during isoniazid-based tuberculosis (TB) treatment presents a major challenge for TB control programs worldwide. We sought to determine whether pharmacokinetic exposures of isoniazid and its metabolites were related to cellular oxidation/reduction status and downstream markers of oxidative DNA damage.MethodsWe performed intensive pharmacokinetic sampling among isoniazid-treated patients to determine the relative plasma exposures of isoniazid, acetylisoniazid, hydrazine, and acetylhydrazine. Physiologically-based pharmacokinetic modeling was used to estimate liver tissue exposures during a 24-hour dosing interval for each compound. We experimentally treated HepG2 cells with isoniazid and metabolites at equimolar concentrations corresponding to these exposures for 7, 14, and 28 day periods, and performed assays related to redox imbalance and oxidative DNA damage at each timepoint. We related a urine marker of oxidative DNA damage to serum isoniazid pharmacokinetic exposures and pharmacogenetics in a clinical study.ResultsAmong isoniazid-treated patients, serum concentrations of hydrazine and isoniazid concentrations were highly correlated. At equimolar concentrations that approximated hepatic tissue exposures during a 24-hour dosing interval, hydrazine demonstrated the highest levels of redox imbalance, mitochondrial injury, and oxidative DNA damage over a 28-day treatment period. In a clinical validation study of isoniazid-treated TB patients, peak isoniazid serum concentrations were positively associated with a urine biomarker of oxidative DNA damage.ConclusionsIsoniazid and its metabolites share the potential for oxidative cellular damage, with the greatest effects observed for hydrazine. Future studies should investigate the clinical consequences of oxidative stress with regards to clinical episodes of drug induced liver injury during isoniazid treatment.

scholarly journals Interrelationships Between Pituitary Hormones as Assessed From 24-hour Serum Concentrations in Healthy Older Subjects

2019 ◽  
Vol 105 (4) ◽  
pp. e1201-e1214
Author(s):  
Evie van der Spoel ◽  
Ferdinand Roelfsema ◽  
Abimbola A Akintola ◽  
Steffy W Jansen ◽  
P Eline Slagboom ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Serum Concentration ◽  
Correlation Coefficient ◽  
Approximate Entropy ◽  
Pituitary Hormones ◽  
Relative Strength ◽  
Serum Concentrations ◽  
Older Individuals ◽  
Clinical Consequences ◽  
Concentration Series

Abstract Context Hormones of the hypothalamic-pituitary-target gland axes are mostly investigated separately, whereas the interplay between hormones might be as important as each separate hormonal axis. Objective Our aim is to determine the interrelationships between GH, TSH, ACTH, and cortisol in healthy older individuals. Design We made use of 24-hour hormone serum concentrations assessed with intervals of 10 minutes from 38 healthy older individuals with a mean age (SD) of 65.1 (5.1) years from the Leiden Longevity Study. Cross-correlation analyses were performed to assess the relative strength between 2 24-hour hormone serum concentration series for all possible time shifts. Cross-approximate entropy was used to assess pattern synchronicity between 2 24-hour hormone serum concentration series. Results Within an interlinked hormonal axis, ACTH and cortisol were positively correlated with a mean (95% confidence interval) correlation coefficient of 0.78 (0.74–0.81) with cortisol following ACTH concentrations with a delay of 10 minutes. Between different hormonal axes, we observed a negative correlation coefficient between cortisol and TSH of -0.30 (-0.36 to -0.25) with TSH following cortisol concentrations with a delay of 170 minutes. Furthermore, a positive mean (95% confidence interval) correlation coefficient of 0.29 (0.22–0.37) was found between TSH and GH concentrations without any delay. Moreover, cross-approximate entropy analyses showed that GH and cortisol exhibit synchronous serum concentration patterns. Conclusions This study demonstrates that interrelations between hormones from interlinked as well as different hypothalamic-pituitary-target gland axes are observed in healthy older individuals. More research is needed to determine the biological meaning and clinical consequences of these observations.

scholarly journals Extent and Clinical Consequences of Antibody Formation Against Adalimumab in Patients With Plaque Psoriasis

2010 ◽  
Vol 146 (2) ◽  
Author(s):  
Lidian L. A. Lecluse ◽  
Rieke J. B. Driessen ◽  
Phyllis I. Spuls ◽  
Elke M. G. J. de Jong ◽  
Steven O. Stapel ◽  
...  
Keyword(s):  
Plaque Psoriasis ◽  
Antibody Formation ◽  
Clinical Consequences

Immunogenicity of bone morphogenetic proteins

2009 ◽  
Vol 10 (5) ◽  
pp. 443-451 ◽  
Author(s):  
Chang Ju Hwang ◽  
Alexander R. Vaccaro ◽  
James P. Lawrence ◽  
Joseph Hong ◽  
Huub Schellekens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bone Morphogenetic Proteins ◽  
Antibody Formation ◽  
Binding Assay ◽  
Antibody Detection ◽  
Clinical Effects ◽  
Human Proteins ◽  
Clinical Consequences ◽  
Safety Parameter ◽  
Osteogenic Protein

Object The object of this paper is to review the immunogenicity of bone morphogenetic proteins (BMPs) and to compare the results of the immunogenicity characterization and clinical consequences between recombinant human (rh)BMP-2 and recombinant human osteogenic protein-1 (rhOP-1/BMP-7). Methods The immunogenicity of therapeutic proteins and its clinical effects were reviewed. The characteristics of BMPs were also described in terms of immunogenicity. The methods and results of antibody detection in various clinical trials of rhBMP-2 and rhOP-1 were compared, including the most recent studies using a systematic characterization strategy with both a binding assay and bioassay. Results Similar to all recombinant human proteins, rhBMPs induce immune responses in a select subgroup of patients. Adverse effects from this response in these patients, however, have not been reported with antibody formation to either rhBMP-2 or rhOP-1. Overall, the incidence of antibody formation was slightly higher in rhOP-1 trials than in rhBMP-2 trials. Conclusions Although they occur in a subgroup of patients, the immune responses against rhBMPs have no correlation with any clinical outcome or safety parameter. Clinicians, however, must be aware of the potential complications caused by the immunogenicity of BMPs until more studies clearly elucidate their safety.

scholarly journals CELLS AS ANTIGEN CARRIERS AND AS IMMUNOGLOBULIN PRODUCERS

1967 ◽  
Vol 126 (2) ◽  
pp. 305-330 ◽  
Author(s):  
Chi-Tao Chou ◽  
S. Dubiski ◽  
Bernhard Cinader
Keyword(s):  
Antibody Response ◽  
Antibody Formation ◽  
Human Albumin ◽  
Peritoneal Exudate ◽  
Serum Concentrations ◽  
Peritoneal Exudate Cells ◽  
Donor Cells ◽  
Synthetic Capacity ◽  
Thymus Cells ◽  
Stimulate Antibody

The injection into newborn rabbits of a small quantity of human albumin, associated with red blood corpuscles or nucleated rabbit cells, induces an antibody response in the majority of animals, whereas the same quantity of antigen in solution fails to stimulate antibody formation or induces tolerance. The promoting capacity of the cells depends on attachment of antigen to them. The antibody produced after the injection of albumin, associated with nucleated cells, is of recipient origin. However, immunoglobulin carrying the marker of donor cells can be demonstrated in the recipient animals, and may reach serum concentrations similar to those normally present in animals which are heterozygous with respect to the marker. It appears that the antibody-promoting function and the synthetic capacity for allotype are quite distinct and that the period required for allotype formation is very short with mononuclear peritoneal exudate cells and is very much longer with cells from the thymus. The capacity of cells from lymph nodes for sustained allotype formation is less than that of thymus cells but greater than that of mononuclear peritoneal exudate cells.

scholarly journals Postnatal Development of Blood Serum Concentrations of Immunoglobulin IgG, IgA and IgM Isotypes in Suckling Foal

2006 ◽  
Vol 75 (2) ◽  
pp. 175-182 ◽  
Author(s):  
M. Sedlinská ◽  
J. Krejčí ◽  
M. Vyskočil ◽  
H. Kudláčková
Keyword(s):  
Blood Serum ◽  
Postnatal Development ◽  
Antibody Formation ◽  
Serum Concentrations ◽  
Elisa Method ◽  
Thoroughbred Foals

Postnatal changes in concentrations of immunoglobulin IgG, IgM and IgA isotypes from birth until the age of five months were monitored by the ELISA method. The experiment was performed in a group of 52 thoroughbred foals and their mothers. Among the investigated animals, failure of colostral immunity transfer was recorded in only four foals (7.7 percent). The concentrations of immunoglobulin IgG and IgA isotypes primarily decreased during the first weeks of life and then gradually increased until the end of the investigated period. The concentrations of immunoglobulin IgG isotype reached the values of adult animals by the end of the investigated period. However, immunoglobulin IgA isotype did not reach those values during the entire investigated period. The concentrations of immunoglobulin IgM isotype were quite rapidly increasing from the birth on. The beginning of active antibody formation was inversely proportional to the level of colostral immunoglobulins.

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