scholarly journals Quality Assurance in Drug Assaying and Pharmacokinetics-Blood Protein Evaluation in Calibration Curves

2020 ◽  
Vol 11 (01) ◽  
pp. 45-52
Author(s):  
S. Vallie ◽  
S. Naidoo

In bioanalytical drug assays, plasma protein/albumin content can challenge the biomatrix and reduce drug recovery through the albumin-binding affinity (ABA) of drug molecules. Global quality assurance in sample preparation for analyte quantification during bioavailability assessments has evolved extensively, and the quality standards of the strictly regulated current global quality controlled drug manufacturing processes (cGQMP) now apply in pharmacokinetics (PK) studies. Previous analyses in large clinical trials had found that laboratory-prepared calibrator plasma/serum protein levels differed significantly from those of patients with occasional hyperproteinemia/hypoproteinemia and disease-related hyperalbuminemia/hypoalbuminemia. We, therefore, investigated improving assay accuracy by including adjustments for patient plasma/serum protein levels in protein evaluation calibrations curves (PROTEC). Using a combined PROTEC of two calibrators (with 1.6 ± 0.5 g/dL and 4.3g/dL albumin, respectively) to test rifampicin recovery from patients with hypoalbuminemia (1.6 ± 0.5 g/dL), we found that relative accuracy of drug recovery differed by minimum 0.1% for low ABA drugs and maximum >20% for moderate ABA drugs. Assay accuracy improved after accommodating for varying patient plasma/serum protein levels. We, therefore, propose using patient-calibrator PROTEC-PK in validation assay development/therapeutic drug monitoring to ensure that patient albumin levels are within acceptable validation accuracy ranges.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. Zamani ◽  
H. Mohammadi ◽  
S. Z. Mirhoseini

AbstractSerum protein levels are related to physiological and pathological status of animals and could be affected by both genetic and environmental factors. This study aimed to evaluate genetic variation of serum protein profile in sheep. Blood samples were randomly collected from 96 Lori-Bakhtiari ewes, a heavy meat-type breed. Total protein, albumin, globulin, α1, α2, β and γ globulins and IgG levels were measured in blood serum. The samples were genotyped using the Illumina OvineSNP50 BeadChip. The studied traits adjusted for age, birth type, birth season and estimate of breeding value for body weight were considered as pseudo-phenotypes in genome-wide association analysis. In the GWAS model, the first five principal components were fitted as covariates to correct the biases due to possible population stratification. The Plink, R and GCTA software were used for genome-wide association analysis, construction of Q-Q and Manhattan plots and estimation of genetic variances, respectively. Noticeable genomic heritabilities ± SE were estimated for total and γ globulins (0.868 ± 0.262 and 0.831 ± 0.364, respectively), but other protein fractions had zero or close to zero estimates. Based on the Bonferroni adjusted p values, four QTLs located on 181.7 Mbp of OAR3, 107.7 Mbp of OAR4, 86.3 Mbp of OAR7 and 83.0 Mbp of OAR8 were significantly associated with α1, β, β and γ globulins, respectively. The results showed that the PKP2, IGF2R, SLC22A1 and SLC22A2 genes could be considered as candidate genes for blood serum proteins. The present study showed significant genetic variations of some blood protein fractions.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 577-P
Author(s):  
AMIR BASHKIN ◽  
AKRAM SAFADI ◽  
BELLA GROSS ◽  
NETANEL A. HOROWITZ ◽  
RIVKA SHARON ◽  
...  

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sandeep Kumar ◽  
M. Ajmal Khan ◽  
Emma Beijer ◽  
Jinxin Liu ◽  
Katherine K. Lowe ◽  
...  

Abstract Background The nutrition of calves from birth until weaning is predominantly from liquid (milk or milk-based) feeds. Liquid feed allowances are often restricted during artificial rearing to accelerate the development of the rumen by promoting solid feed intake. Liquid feeds bypass the rumen and are digested in the lower digestive tract, however, the influence of different types of milk feeds, and their allowances, on the calf hindgut microbiota is not well understood. In this study, faecal samples from 199 calves raised on three different allowances of milk replacer: 10% of initial bodyweight (LA), 20% of initial bodyweight (HA), and ad libitum (ADLIB), were collected just prior to weaning. Bacterial community structures and fermentation products were analysed, and their relationships with calf growth and health parameters were examined to identify potential interactions between diet, gut microbiota and calf performance. Results Differences in the total concentrations of short-chain fatty acids were not observed, but higher milk replacer allowances increased the concentrations of branched short-chain fatty acids and decreased acetate to propionate ratios. The bacterial communities were dominated by Ruminococcaceae, Lachnospiraceae and Bacteroides, and the bacterial diversity of the ADLIB diet group was greater than that of the other diet groups. Faecalibacterium was over three times more abundant in the ADLIB compared to the LA group, and its abundance correlated strongly with girth and body weight gains. Milk replacer intake correlated strongly with Peptococcus and Blautia, which also correlated with body weight gain. Bifidobacterium averaged less than 1% abundance, however its levels, and those of Clostridium sensu stricto 1, correlated strongly with initial serum protein levels, which are an indicator of colostrum intake and passive transfer of immunoglobulins in early life. Conclusions Higher milk replacer intakes in calves increased hindgut bacterial diversity and resulted in bacterial communities and short chain fatty acid profiles associated with greater protein fermentation. Increased abundances of beneficial bacteria such as Faecalibacterium, were also observed, which may contribute to development and growth. Moreover, correlations between microbial taxa and initial serum protein levels suggest that colostrum intake in the first days of life may influence microbiota composition at pre-weaning.


1976 ◽  
Vol 13 (4) ◽  
pp. 207-214
Author(s):  
Hiroshi Yamanouchi ◽  
Hideo Tohgi ◽  
Masakuni Kameyama ◽  
Mototaka Murakami ◽  
Tamotsu Matsuda

1971 ◽  
Vol 40 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Berenice Abrams

1. Serum proteins were studied in 106 children ranging from 3 to 14 years using a modification of Laurell's method of quantitative immunoelectrophoresis. 2. Quantitative values are given for eleven proteins, viz.: α1 lipoprotein, α1 antitrypsin, α1 easily precipitable glycoprotein, α1 group specific component, α2 macroglobulin, caeruloplasmin, haptoglobin, transferrin, haemopexin, β lipoprotein, and β1AC(C3). 3. There were no significant differences in protein levels between the sexes, and no correlation between age and protein level within the age range studied. 4. The values were also compared with those of infants aged 6–12 months, young adults of 16–25 years, and adults of 16–65 years.


1967 ◽  
Vol 45 (4) ◽  
pp. 571-575 ◽  
Author(s):  
W. F. Blatt ◽  
J. Kerkay

Total protein, serum protein, and lipoprotein electrophoretic distribution and hematocrit values were determined in two groups of men during acclimatization to 6 weeks of cold and 11 days of heat respectively. After 3 weeks of cold exposure total serum protein and albumin content decreased, while the globulin fractions increased; thus, the calculated albumin/globulin ratio was significantly depressed. During the last 2 weeks, these parameters gradually returned to control values. Overall, the protein changes during heat acclimatization were minimal, although the globulins decreased slightly, yielding a small increase in the albumin/globulin ratio. The hematocrit levels were significantly lowered during both environmental exposures, whereas the lipoprotein distribution remained essentially unchanged.


1986 ◽  
Vol 32 (3) ◽  
pp. 523-526 ◽  
Author(s):  
M Landt ◽  
L L Norling ◽  
M Steelman ◽  
C H Smith

Abstract The Monoject Samplette (Sherwood) capillary serum-separator tube was evaluated for use in pediatric capillary blood collection. When patients' values for eight common clinical-chemical tests and five therapeutic drugs were compared with values from specimens concomitantly collected in plain Caraway tubes, only chloride and total CO2 were significantly different. The chloride differences (range 0-2 mmol/L) were considered to be clinically insignificant. Higher CO2 values in Samplette specimens were apparently ascribable to decreased loss to the atmosphere. Samplette values for therapeutic drugs were higher than corresponding Caraway values, but only the differences for digoxin were judged to be clinically significant. Both recoverable serum and the incidence of hemolysis were lower in Samplette specimens than in Caraway specimens. Storage of serum over the clots (with separator material interposed) in Samplettes for 24 h had no clinically significant effect on results for glucose or potassium. Storage of specimens for as long as 24 h had no effect on theophylline, phenytoin, and gentamicin concentrations, but phenobarbital reproducibly decreased after 24 h. We conclude that the Samplette serum-separator tube is suitable for the collection of capillary blood for many of the chemical tests commonly ordered for pediatric patients.


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