91 research outputs found
Serum adiponectin and transient elastography as non-invasive markers for postoperative biliary atresia
<p>Abstract</p> <p>Background</p> <p>Biliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores.</p> <p>Methods</p> <p>Sixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ≥ 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan).</p> <p>Results</p> <p>BA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 μg/ml, <it>P </it>= 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, <it>P </it>< 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 μg/ml, <it>P </it>< 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 μg/ml, <it>P </it>< 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (<it>r </it>= 0.58, <it>r </it>= 0.46, and <it>r </it>= 0.60, <it>P </it>< 0.001, respectively).</p> <p>Conclusions</p> <p>Serum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA.</p
Characterisation of Dermanyssus gallinae glutathione S-transferases and their potential as acaricide detoxification proteins
BACKGROUND: Glutathione S-transferases (GSTs) facilitate detoxification of drugs by catalysing the conjugation of the reduced glutathione (GSH) to electrophilic xenobiotic substrates and therefore have a function in multi-drug resistance. As a result, knowledge of GSTs can inform both drug resistance in, and novel interventions for, the control of endo- and ectoparasite species. Acaricide resistance and the need for novel control methods are both pressing needs for Dermanyssus gallinae, a highly economically important haematophagous ectoparasite of poultry. METHODS: A transcriptomic database representing D. gallinae was examined and 11 contig sequences were identified with GST BlastX identities. The transcripts represented by 3 contigs, designated Deg-GST-1, −2 and −3, were fully sequenced and further characterized by phylogenetic analysis. Recombinant versions of Deg-GST-1, −2 and −3 (rDeg-GST) were enzymically active and acaricide-binding properties of the rDeg-GSTs were established by evaluating the ability of selected acaricides to inhibit the enzymatic activity of rDeg-GSTs. RESULTS: 6 of the identified GSTs belonged to the mu class, followed by 3 kappa, 1 omega and 1 delta class molecules. Deg-GST-1 and −3 clearly partitioned with orthologous mu class GSTs and Deg-GST-2 partitioned with delta class GSTs. Phoxim, permethrin and abamectin significantly inhibited rDeg-GST-1 activity by 56, 35 and 17 % respectively. Phoxim also inhibited rDeg-2-GST (14.8 %) and rDeg-GST-3 (20.6 %) activities. CONCLUSIONS: Deg-GSTs may have important roles in the detoxification of pesticides and, with the increased occurrence of acaricide resistance in this species worldwide, Deg-GSTs are attractive targets for novel interventions
Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia
Elevated serum periostin is associated with liver stiffness and clinical outcome in biliary atresia
The Effects of Andrographolide on the Enhancement of Chondrogenesis and Osteogenesis in Human Suprapatellar Fat Pad Derived Mesenchymal Stem Cells
Andrographolide is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculata, and widely used for its potential medical properties. However, there are no reports on the effects of andrographolide on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of andrographolide on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. The results revealed that andrographolide had no cytotoxic effects when the concentration was less than 12.5 µM. Interestingly, andrographolide had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, andrographolide can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, andrographolide suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. These findings confirm that andrographolide can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine
Economic evaluation of prenatal screening for fetal aneuploidies in Thailand.
Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context
Interleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritis
Economic evaluation of multiple-pharmacogenes testing for the prevention of adverse drug reactions in people living with HIV
Purpose: Pharmacogenetics (PGx) testing is one of the methods for determining whether individuals are at risk of adverse drug reactions (ADRs). It has been reported that multiple-PGx testing, a sequencing technology, has a higher predictive value than single-PGx testing. Therefore, this study aimed to determine the most cost-effective PGx testing strategies for preventing drug-induced serious ADRs in human immunodeficiency virus (HIV)-infected patients.
Patients and Methods: Potential strategies, including 1) single-PGx esting (ie, HLA-B*57:01 testing before prescribing abacavir, HLA-B*13:01 testing before prescribing co-trimoxazole and dapsone, and NAT2 testing before prescribing isoniazid) and 2) multiple-PGx testing as a combination of four single-gene PGx tests in one panel, were all compared to no PGx testing (current practice). To evaluate total cost in Thai baht (THB) and quality-adjusted life years (QALYs) for each strategy-based approach to a societal perspective, a hybrid decision tree and Markov model was constructed. Incremental cost-effectiveness ratios (ICERs) were estimated. Uncertainty, threshold, and scenario analyses were all performed.
Results: Before prescribing HIV therapy, providing single or multiple-PGx testing might save roughly 68 serious ADRs per year, and the number needed to screen (NNS) to avoid one serious ADR was 40. Consequently, approximately 35% and 40% of the cost of ADR treatment could be avoided by the implementation of single- and multiple-PGx testing, respectively. Compared with no PGx testing strategy, the ICERs were 146,319 THB/QALY gained for single-PGx testing and 152,014 THB/QALY gained for multiple-PGx testing. Moreover, the probability of multiple-PGx testing being cost-effective was 45% at the Thai willingness to pay threshold of 160,000 THB per QALY. Threshold analyses showed that multiple-PGx testing remained cost-effective under the range of cost, sensitivity at 0.95– 1.00 and specificity at 0.98– 1.00.
Conclusion: Single and multiple-PGx testing might be cost-effective options for reducing the incidence of drug-induced serious ADRs in people living with HIV
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