This corresponds to ∼87% of the total amount injected. Within the first 4 hours the peptide-associated radioactivity in the liver remained constant. It slowly declined to 30.5 %ID/g at 24 hours after injection. At early points in time, minor levels were detectable in the blood (at 10 minutes: 2.8 %ID/g; at 1 hour: 2.0 %ID/g), in the kidneys (at 10 minutes: 2.7 %ID/g; at 1 hour: 2.3 %ID/g) and to a lower extend in heart, lung, and spleen (at 10 minutes:

3.8 %ID/g; at 1 hour: 2.6 %ID/g). No activity was associated with the brain, indicating no crossing of the blood-brain barrier. This confirms the results of noninvasive imaging obtained with genotype D HBVpreS/2-48myr-y-125I (Fig. 2A). Notably, the organ distribution pattern entirely changed when the N-terminal JQ1 cell line fatty acids were removed. At 10 minutes p.i. >50% of the ID/g of HBVpreS/1-48-y-131I was detectable

in the kidneys (Fig. 3B). The signal declined to undetectable levels within the following 4 hours. At early timepoints higher peptide levels were detectable in the blood. No specific accumulation was observed in the liver when compared to other organs. Since a similar distribution was observed for a non-myristoylated scrambled peptide (data not shown), we conclude that myristic acid may mediate binding to a serum factor preventing the 5.4 kDa peptide from filtration in the kidney. In addition, association Alectinib supplier with a serum factor may enhance resistance against serum proteases. To substantiate the sequence-dependence for the hepatotropism of the peptide

we tested the point mutant HBVpreS/2-48stea(G12E)-y-131I. This mutant is defective in HBV infection inhibition.20 Remarkably, the single amino acid substitution completely changed the organ distribution of the peptide in NRMI mice (Fig. 3C). The pronounced association with the liver was lost and the peptide did not retain in the mouse for 24 hours. Thus, selleck inhibitor acylated HBVpreS/2-48-peptides address a homologous target in mouse and human livers with comparable binding specificities for the HBVpreS1-sequence. Finally, we performed organ distribution studies using all peptides depicted in Fig. 3D. To quantify liver association, we calculated a liver enrichment factor and compared it with the inhibitory activity of the same peptide determined in infection inhibition assays (Fig. 3D). Mutants lacking their ability to interfere with HBV infection also lost their potential to accumulate in mouse livers. Inactive peptides (e.g., those with mutations in the essential receptor binding site 9-NPLGFFP-15) behaved like the scrambled mutant, while those with a residual inhibitory activity still retained some hepatotropism. This correlation supports the hypothesis that mice harbor an HBVpreS1-specific receptor which displays the same binding specificity as its human homolog. The unexpected finding that mice harbor an HBVpreS-specific receptor in the liver prompted us to perform in vivo distribution studies in other species.

The Stroop has also been found to be a fairly effective predictor of functional adaptive skills and independent living skills (Boyle, Paul, Moser, & Cohen, 2004). Despite its popularity in clinical practice and research, few studies have examined the influence of effort and malingering on the Stroop. Vickery et al. (2004) administered a battery of neuropsychological tests, including the Stroop, to moderate–severe TBI and healthy participants to determine if head-injured

individuals were better at simulating feigned neuropsychological impairment than healthy individuals. Head-injured and healthy volunteers asked to feign impairment selleckchem had significantly lower scores on the Stroop than control participants (p = .007,

d = 0.80). A study by van Gorp et al. (1999) retrospectively analysed the files of mild-to-moderate TBI patients identified as suspected malingerers and non-malingerers MK-8669 purchase based on improbable symptom history and SVT performance. The patient files included the Color and Interference trials of the Stroop, in addition to other neuropsychological measures. Stroop scores were significantly worse in the malingering group for both the Color (p = .007) and Interference (p = .000) trials, accounting for 10% and 20% of the variance in a discriminant function analysis, respectively. These studies provide evidence that it is possible to distinguish malingering and non-malingering groups on the Stroop. A test or indicator that has the ability to accurately differentiate malingerers

from non-malingerers also provides direct evidence regarding whether performance on that particular test is an accurate reflection of the individual’s actually cognitive capacity. One limitation of these studies is that scores that effectively differentiated the performances were not reported. To be of clinical utility, it is necessary to determine cut-off scores that best characterize performance validity. Therefore, the purpose of this study was to examine the accuracy of select Stroop variables (Word, Color, Color–Word, and Interference residual scores) in discriminating performance validity. A criterion-groups Ribose-5-phosphate isomerase validation design was employed, comparing mild TBI patients who met published criteria for malingering (Slick et al., 1999) with mild TBI patients who showed no indication of malingering. Groups of moderate–severe TBI patients and patients with different neurological and psychiatric diagnoses were included for comparison. Results of the study are presented in frequency tables that can easily be referenced in clinical practice. Participants in this group were drawn from a cohort of 165 consecutive cases referred to a south-eastern clinical practice for a neuropsychological evaluation after suffering an apparent TBI.

Our review of the HCV-HLA literature identified only three studies of HLA alleles and HCV serostatus in high-risk populations16–18 and there were no consistent findings or strong associations. We therefore treated all of the analysis of HCV serostatus LY2157299 concentration and HLA alleles as exploratory, and all significant P-values were adjusted for multiple comparisons. Of the 64 HLA class I and II alleles with >5% prevalence in the 838 IDUs studied, B*5703 (P = 0.03), Cw*0304 (P = 0.04), and Cw*0701 (P = 0.01), were significantly associated with HCV infection (see Supporting Table 2), but these associations did not retain significance after adjustment for multiple comparisons

(P = 0.99, 1.0, and 0.64, respectively). There were no significant interactions by race/ethnicity or HIV serostatus/CD4+ T-cell count. We studied the relation of high-resolution HLA class I and II genotype with HCV viremia and with HCV serostatus in IDUs. Although there have been a number of prior studies of HLA alleles and HCV viremia, many of the findings to date have been conflicting. Part of this variability may relate to aspects of study design, including differences in sample size Palbociclib datasheet and whether an appropriate control group was used. Furthermore,

few studies examined HLA class I alleles, with only one having conducted high-resolution class I genotyping.12 There have also been very little data regarding HLA and the prevalence of HCV infection (i.e., seropositivity) in high-risk populations.16–18 To build on the existing data, therefore, we conducted high-resolution HLA class I and II genotyping in a large multiracial cohort of U.S. women with high prevalence of HCV and HIV Baricitinib infection. Several significant associations between HLA class I and II alleles and HCV viremia were observed. These included 6 of the 12 HLA alleles that we identified as having a high prior probability of association with HCV viremia based on a critical review of the literature. Because each of these associations represented discrete a priori hypotheses it is unlikely that they occurred by chance. Both B*5701 and B*5703, for example, were

significantly associated with an absence of HCV RNA. Two earlier studies of HLA class I had reported similar associations with the B*57 allele group; the first was conducted in a large multiracial, majority male population in the United States,12 whereas the second was conducted in a small, majority male population in West Africa.13 A third study conducted in Ireland also found an association between the B*57 allele group and HCV viremia, although the results did not attain statistical significance.14 In the current study the relation of the B*57 allele group with HCV viremia mainly reflected the combined effects of B*5701 and B*5703, but we caution that our dataset included too few women with other B*57 alleles (e.g., B*5702, B*5704) to study in detail.

To analyze protein-bound DNA, primers for real-time quantitative polymerase chain reaction (PCR) were used (Supporting Table). The percentage of the input that was bound was calculated using the ΔCt method and averaged for at least three biological replicates. Primers and reverse-transcription PCR determinations of RNA expression were see more performed as described.15 Briefly, total RNA from homogenized mouse liver was extracted with

TRIzol reagent (Invitrogen) according to the manufacturer’s instructions. Complementary DNA was obtained by reverse transcription of 2 μg of RNA using the SuperScript system (Invitrogen). Real-time PCR was performed using primers for the indicated genes (Supporting Table). Collected liver samples were fixed in 10% neutral

buffered formalin (Fisher), embedded in wax paraffin, and sectioned at 5-6 mm by the University selleck chemical of Texas MD Anderson Cancer Center Department of Veterinary Medicine and Surgery. Sections were rehydrated and stained with hematoxylin and eosin or with anti-Ki67 (Abcam) marker and then counterstained with hematoxylin following the manufacturers’ recommended protocols. Antigen retrieval and immunodetection was performed using solutions from Vector Labs according to the manufacturer’s instructions (Vector Laboratories). Endogenous peroxidase activity was quenched by incubating slides in a methanol/H2O2 solution. Immunoblotting was performed using standard sodium dodecyl sulfate–polyacrylamide gel electrophoresis and western blot methodology.15 Protein extracts from liver ADP ribosylation factor tissue collected at 0, 12, 24, 48, 72, 84, 96, and 168 hours following PH and 12 hours following sham surgery were prepared using T-PER buffer

(Pierce/Thermoscientific) according to the manufacturer’s instructions. Hepatocytes were isolated from adult 129 p53+/+, p53+/−, and p53−/− littermates via collagenase perfusion.16 Live hepatocytes were loaded with Hoechst33342 (Invitrogen) and DNA content was determined with an InFlux flow cytometer (Beckton Dickinson) using a 150-μm nozzle as described.3 The Institutional Animal Care and Use Committee of Oregon Health & Science University approved the experiments. To quantify DNA content (ploidy profiling), hepatocytes were isolated from livers after PH and sham surgery via collagenase perfusion.16 Cells were fixed by gentle vortexing in ice-cold 80% (vol/vol) ethanol and stained with 50 μg/mL propidium iodide in 0.2% Tween in phosphate-buffered saline supplemented with 1 μg/mL (wt/vol) RNAse A (Molecular Probes). Cytofluorometric acquisitions were performed on a FACSCalibur flow cytometer (BD Biosciences). Statistical analysis was performed with CellQuest software (BD Biosciences), upon gating on the events characterized by normal forward scatter and side scatter parameters. Results are expressed as the mean ± SEM. Statistical analyses were performed by Student t test; P < 0.05 was considered significant.

To analyze protein-bound DNA, primers for real-time quantitative polymerase chain reaction (PCR) were used (Supporting Table). The percentage of the input that was bound was calculated using the ΔCt method and averaged for at least three biological replicates. Primers and reverse-transcription PCR determinations of RNA expression were PLX3397 clinical trial performed as described.15 Briefly, total RNA from homogenized mouse liver was extracted with

TRIzol reagent (Invitrogen) according to the manufacturer’s instructions. Complementary DNA was obtained by reverse transcription of 2 μg of RNA using the SuperScript system (Invitrogen). Real-time PCR was performed using primers for the indicated genes (Supporting Table). Collected liver samples were fixed in 10% neutral

buffered formalin (Fisher), embedded in wax paraffin, and sectioned at 5-6 mm by the University VX-809 mouse of Texas MD Anderson Cancer Center Department of Veterinary Medicine and Surgery. Sections were rehydrated and stained with hematoxylin and eosin or with anti-Ki67 (Abcam) marker and then counterstained with hematoxylin following the manufacturers’ recommended protocols. Antigen retrieval and immunodetection was performed using solutions from Vector Labs according to the manufacturer’s instructions (Vector Laboratories). Endogenous peroxidase activity was quenched by incubating slides in a methanol/H2O2 solution. Immunoblotting was performed using standard sodium dodecyl sulfate–polyacrylamide gel electrophoresis and western blot methodology.15 Protein extracts from liver FER tissue collected at 0, 12, 24, 48, 72, 84, 96, and 168 hours following PH and 12 hours following sham surgery were prepared using T-PER buffer

(Pierce/Thermoscientific) according to the manufacturer’s instructions. Hepatocytes were isolated from adult 129 p53+/+, p53+/−, and p53−/− littermates via collagenase perfusion.16 Live hepatocytes were loaded with Hoechst33342 (Invitrogen) and DNA content was determined with an InFlux flow cytometer (Beckton Dickinson) using a 150-μm nozzle as described.3 The Institutional Animal Care and Use Committee of Oregon Health & Science University approved the experiments. To quantify DNA content (ploidy profiling), hepatocytes were isolated from livers after PH and sham surgery via collagenase perfusion.16 Cells were fixed by gentle vortexing in ice-cold 80% (vol/vol) ethanol and stained with 50 μg/mL propidium iodide in 0.2% Tween in phosphate-buffered saline supplemented with 1 μg/mL (wt/vol) RNAse A (Molecular Probes). Cytofluorometric acquisitions were performed on a FACSCalibur flow cytometer (BD Biosciences). Statistical analysis was performed with CellQuest software (BD Biosciences), upon gating on the events characterized by normal forward scatter and side scatter parameters. Results are expressed as the mean ± SEM. Statistical analyses were performed by Student t test; P < 0.05 was considered significant.

Hepatic endoplasmic reticulum stress Selleckchem AZD3965 signals including glucose-regulated protein-78 (GRP78), activating transcription factor 4, growth arrest and DNA damage-inducible gene 153 (GADD153), caspase 12, and transcription

factor sterol response element binding protein-1c (SREBP-1c) were up-regulated in ethanol-fed mice with genotype interactions and negative correlations with the SAM/SAH ratio. Immunohistochemical staining showed reduction in trimethylated histone H3 lysine-9 (3meH3K9) protein levels in centrilobular regions in both ethanol groups, with no changes in trimethylated histone H3 lysine-4 levels. The chromatin immunoprecipitation assay revealed a decrease in levels of suppressor chromatin marker 3meH3K9 in the promoter regions of GRP78, SREBP-1c, and GADD153 in ethanol-treated heterozygous cystathionine beta synthase selleck mice. The messenger RNA expression of the histone H3K9 methyltransferase EHMT2 (G9a) was selectively decreased in ethanol-fed mice. Conclusion: The pathogenesis of alcoholic steatohepatitis is mediated in part through the effects of altered methionine metabolism on epigenetic regulation of pathways of endoplasmic reticulum stress relating

to apoptosis and lipogenesis. (HEPATOLOGY 2009.) Previous studies established associations of abnormal hepatic methionine Interleukin-3 receptor metabolism with the development and clinical expression of alcoholic steatohepatitis (ASH).1, 2 In transmethylation reactions, homocysteine is methylated to methionine and then S-adenosylmethionine (SAM), which is a substrate and principal methyl donor in methylation reactions, whereas S-adenosylhomocysteine (SAH) is both a product and potent inhibitor of methylation reactions.3 Therefore, the SAM/SAH ratio is considered a useful expression of methylation capacity.2 SAH is also the substrate for SAH hydrolase, a reversible reaction that generates homocysteine in the forward direction, but increases SAH when homocysteine

is in excess. In transsulfuration reactions, homocysteine is a substrate for the cystathionine beta synthase (CβS) reaction, which is facilitated by SAM to generate cystathionine and ultimately glutathione (GSH), the principal antioxidant in the liver.4 Our prior studies in ethanol-fed micropigs linked elevated liver homocysteine and SAH levels to endoplasmic reticulum (ER) stress.5 In mice fed intragastric ethanol, betaine prevented hepatic lipid accumulation and hepatocellular apoptosis by lowering homocysteine and SAH levels.6 Feeding ethanol to micropigs with a folate-deficient diet accelerated the onset and severity of ASH while increasing liver homocysteine and SAH and reducing SAM and the SAM/SAH ratio.

Hepatic endoplasmic reticulum stress Gefitinib signals including glucose-regulated protein-78 (GRP78), activating transcription factor 4, growth arrest and DNA damage-inducible gene 153 (GADD153), caspase 12, and transcription

factor sterol response element binding protein-1c (SREBP-1c) were up-regulated in ethanol-fed mice with genotype interactions and negative correlations with the SAM/SAH ratio. Immunohistochemical staining showed reduction in trimethylated histone H3 lysine-9 (3meH3K9) protein levels in centrilobular regions in both ethanol groups, with no changes in trimethylated histone H3 lysine-4 levels. The chromatin immunoprecipitation assay revealed a decrease in levels of suppressor chromatin marker 3meH3K9 in the promoter regions of GRP78, SREBP-1c, and GADD153 in ethanol-treated heterozygous cystathionine beta synthase Erlotinib cell line mice. The messenger RNA expression of the histone H3K9 methyltransferase EHMT2 (G9a) was selectively decreased in ethanol-fed mice. Conclusion: The pathogenesis of alcoholic steatohepatitis is mediated in part through the effects of altered methionine metabolism on epigenetic regulation of pathways of endoplasmic reticulum stress relating

to apoptosis and lipogenesis. (HEPATOLOGY 2009.) Previous studies established associations of abnormal hepatic methionine Resveratrol metabolism with the development and clinical expression of alcoholic steatohepatitis (ASH).1, 2 In transmethylation reactions, homocysteine is methylated to methionine and then S-adenosylmethionine (SAM), which is a substrate and principal methyl donor in methylation reactions, whereas S-adenosylhomocysteine (SAH) is both a product and potent inhibitor of methylation reactions.3 Therefore, the SAM/SAH ratio is considered a useful expression of methylation capacity.2 SAH is also the substrate for SAH hydrolase, a reversible reaction that generates homocysteine in the forward direction, but increases SAH when homocysteine

is in excess. In transsulfuration reactions, homocysteine is a substrate for the cystathionine beta synthase (CβS) reaction, which is facilitated by SAM to generate cystathionine and ultimately glutathione (GSH), the principal antioxidant in the liver.4 Our prior studies in ethanol-fed micropigs linked elevated liver homocysteine and SAH levels to endoplasmic reticulum (ER) stress.5 In mice fed intragastric ethanol, betaine prevented hepatic lipid accumulation and hepatocellular apoptosis by lowering homocysteine and SAH levels.6 Feeding ethanol to micropigs with a folate-deficient diet accelerated the onset and severity of ASH while increasing liver homocysteine and SAH and reducing SAM and the SAM/SAH ratio.

8 UCP2 (and Doxorubicin UCP3) contain reactive cysteines that can be modified by GSH. The deglutathionylation/glutathionylation regulates UCP2 and UCP3 activity. In the presence of elevated ROS, GSH is depleted and the

proteins lose the conjugated glutathione, thereby rendering them active and able to neutralized ROS. Under the conditions of APAP-induced hepatotoxicity, elevated ROS levels likely mediate similar activation of UCP2, however, only following activation by PPARα. In conclusion, this study adds to our understanding of how toxic doses of APAP mediate hepatotoxicity and provides new insight into the importance of PPARα activation in maintaining proper mitochondrial function, most likely through UCP2 under normal and pathologic conditions. Further, this study lends even greater support for how repression of PPARα activation can lead to deleterious effects. Using Ucp2-null mice and mice transiently expressing UCP2 (from adenovirus), a convincing role for UPC2 in protecting against APAP-induced hepatotoxicity through preservation of mitochondrial function was demonstrated. Further studies to determine the mechanisms by which UCP2 facilitates this protection are warranted and will provide

greater understanding by which ROS elevating hepatoxicants, such as APAP, mediate their effects. We thank Jared Correll and Jessica Montanez for technical assistance and Dr. Chi Chen for insightful discussions. Additional Supporting Information may be found in the online version of this article. “
“BACKGROUND and AIM: Hepatitis C virus either (HCV) causes mitochondrial injury Ulixertinib order and oxidative stress, and impaired mitochondria are selectively eliminated through autophagy-dependent degradation (mitophagy). However, whether HCV infection affects mitophagy in terms of

mitochondrial quality control remains unknown. METHODS: The effect of HCV on mitophagy was examined using HCV-JFH1-infected cells, genome-length HCV RNA-replicating cells (OR6 cells), HCV core-expressing cells and the uncoupling reagent carbonyl cyanide mchlorophenylhydrazone as a mitophagy inducer in addition to liver cells from HCV-infected human hepatocyte chimeric mice and. transgenic mice expressing the HCV polyprotein. RESULTS : The results indicated that translocation of the E3 ubiquitin ligase Parkin to the mitochondria was impaired without reduction of PTEN-induced putative kinase 1activity in the presence of HCV infection both in vitro and in vivo. Co-immunoprecipitation revealed that Parkin was associated with the HCV core protein but not other HCV proteins, such as NS3, NS4A and NS5A. Furthermore, a yeast two-hybrid assay identified a specific interaction between the HCV core protein and an N-terminal Parkin fragment that contains one of the amino acids that is essential for its mitochondrial localization.

8 UCP2 (and this website UCP3) contain reactive cysteines that can be modified by GSH. The deglutathionylation/glutathionylation regulates UCP2 and UCP3 activity. In the presence of elevated ROS, GSH is depleted and the

proteins lose the conjugated glutathione, thereby rendering them active and able to neutralized ROS. Under the conditions of APAP-induced hepatotoxicity, elevated ROS levels likely mediate similar activation of UCP2, however, only following activation by PPARα. In conclusion, this study adds to our understanding of how toxic doses of APAP mediate hepatotoxicity and provides new insight into the importance of PPARα activation in maintaining proper mitochondrial function, most likely through UCP2 under normal and pathologic conditions. Further, this study lends even greater support for how repression of PPARα activation can lead to deleterious effects. Using Ucp2-null mice and mice transiently expressing UCP2 (from adenovirus), a convincing role for UPC2 in protecting against APAP-induced hepatotoxicity through preservation of mitochondrial function was demonstrated. Further studies to determine the mechanisms by which UCP2 facilitates this protection are warranted and will provide

greater understanding by which ROS elevating hepatoxicants, such as APAP, mediate their effects. We thank Jared Correll and Jessica Montanez for technical assistance and Dr. Chi Chen for insightful discussions. Additional Supporting Information may be found in the online version of this article. “
“BACKGROUND and AIM: Hepatitis C virus Sclareol (HCV) causes mitochondrial injury buy Rucaparib and oxidative stress, and impaired mitochondria are selectively eliminated through autophagy-dependent degradation (mitophagy). However, whether HCV infection affects mitophagy in terms of

mitochondrial quality control remains unknown. METHODS: The effect of HCV on mitophagy was examined using HCV-JFH1-infected cells, genome-length HCV RNA-replicating cells (OR6 cells), HCV core-expressing cells and the uncoupling reagent carbonyl cyanide mchlorophenylhydrazone as a mitophagy inducer in addition to liver cells from HCV-infected human hepatocyte chimeric mice and. transgenic mice expressing the HCV polyprotein. RESULTS : The results indicated that translocation of the E3 ubiquitin ligase Parkin to the mitochondria was impaired without reduction of PTEN-induced putative kinase 1activity in the presence of HCV infection both in vitro and in vivo. Co-immunoprecipitation revealed that Parkin was associated with the HCV core protein but not other HCV proteins, such as NS3, NS4A and NS5A. Furthermore, a yeast two-hybrid assay identified a specific interaction between the HCV core protein and an N-terminal Parkin fragment that contains one of the amino acids that is essential for its mitochondrial localization.

Most patients suffer a severe bleeding diathesis that includes postnatal umbilical cord bleeding, cutaneous bruising and haematomas, intramuscular and joint haemorrhage, postoperative haemorrhage, impaired wound healing, spontaneous abortions in early pregnancy and intracranial haemorrhage, which is the major cause

of death [40]. Typically, bleeding Pexidartinib mw symptoms occur hours or days after trauma as the initially formed uncrosslinked fibrin clot is not stable. The possible diagnosis of congenital FXIII deficiency should not be delayed in any child with an unidentified bleeding disorder. Prolonged umbilical bleeding with a normal coagulation profile mandates FXIII analysis. Congenital FXIII deficiency can be caused by mutations in both FXIII genes. More than 70 causative mutations in the FXIII-A gene have been published, but only five mutations in the FXIII-B gene (see online databases www.f13-database.de, and those held by the ISTH at www.isth.org/and www.hgmd.cf.ac.uk). Most mutations code for a single amino acid exchange resulting in defective folding and instability of the mutant protein [40]. Acquired FXIII deficiency has been

reported in several conditions. FXIII A-subunit levels fall to 20–70% from decreased synthesis or consumption. Over 30 cases of severe FXIII deficiency caused by autoantibodies against FXIII-A have also been reported (∼30% in association with systemic lupus erythematosus [SLE]). These may inhibit FXIII activation or FXIIIa activity [41]. Clinical symptoms in congenital CB-839 solubility dmso ADAMTS5 FXIII deficiency may be suggestive, but the diagnosis must be based on appropriate laboratory tests. Unless there is another concomitant coagulation disorder, typical coagulation screening tests are normal. Traditionally, solubility of fibrin clots in urea, acetic acid or monochloroacetic acid solution (clot solubility test)

has been used for screening. This qualitative method detects only very severe FXIII deficiency, is not standardized, and its sensitivity depends on the fibrinogen level, the clotting reagent (thrombin and/or Ca2+) and the solubilizing agent and its concentration. The detection limit varies between <0.5% and 5% FXIII activity. The high number of undiagnosed or late-diagnosed FXIII deficiencies is partly attributable to the use of this test and it is therefore no longer recommended. Diagnosis and classification of FXIII deficiencies require a quantitative functional FXIII activity assay that detects all forms of FXIII deficiency as a first-line screening test. Quantitative FXIII activity assays are based on two assay principles: (i) Measurement of ammonia released during the transglutaminase reaction and (ii) measurement of labelled amine incorporated into a protein substrate.