Effects of dietary Antrodia cinnamomea fermented product supplementation on metabolism pathways of antioxidant, inflammatory, and lipid metabolism pathways-a potential crosstalk.

OBJECTIVE: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. METHODS: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. RESULTS: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. CONCLUSION: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Effects of dietary Antrodia cinnamomea fermented product supplementation on antioxidation, anti-inflammation, and lipid metabolism in broiler chickens.

OBJECTIVE: This study was investigated the effects of dietary supplementation of Antrodia cinnamomea fermented product on modulation of antioxidation, anti-inflammation, and lipid metabolism in broilers. METHODS: Functional compounds and in vitro antioxidant capacity were detected in wheat bran (WB) solid-state fermented by Antrodia cinnamomea for 16 days (FAC). In animal experiment, 400 d-old broiler chickens were allotted into 5 groups fed control diet, and control diet replaced with 5% WB, 10% WB, 5% FAC, and 10% FAC respectively. Growth performance, intestinal microflora, serum antioxidant enzymes and fatty acid profiles in pectoral superficial muscle were measured. RESULTS: Pretreatment with hot water extracted fermented product significantly reduced chicken peripheral blood mononuclear cells death induced by lipopolysaccharide and 2,2'-Azobis(2-amidinopropane) dihydrochloride. Birds received 5% and 10% FAC had higher weight gain than WB groups. Cecal coliform and lactic acid bacteria were diminished and increased respectively while diet replaced with FAC. For FAC supplemented groups, superoxide dismutase (SOD) activity increased at 35 days only, with catalase elevated at 21 and 35 day. Regarding serum lipid parameters, 10% FAC replacement significantly reduced triglyceride and low-density lipoprotein level in chickens. For fatty acid composition in pectoral superficial muscle of 35-d-old chickens, 5% and 10% FAC inclusion had birds with significantly lower saturated fatty acids as compared with 10% WB group. Birds on the 5% FAC diet had a higher degree of unsaturation, followed by 10% FAC, control, 5% WB, and 10% WB. CONCLUSION: In conclusion, desirable intestinal microflora in chickens obtaining FAC may be attributed to the functional metabolites detected in final fermented product. Moreover, antioxidant effects observed in FAC were plausibly exerted in terms of improved antioxidant enzymes activities, increased unsaturated degree of fatty acids in chicken muscle and better weight gain in FAC inclusion groups, indicating that FAC possesses promising favorable mechanisms worthy to be developed.

Potential crosstalk of oxidative stress and immune response in poultry through phytochemicals - A review.

Phytochemicals which exist in various plants and fungi are non-nutritive compounds that exert numerous beneficial bioactive actions for animals. In recent years following the restriction of antibiotics, phytochemicals have been regarded as a primal selection when dealing with the challenges during the producing process in the poultry industry. The selected fast-growing broiler breed was more fragile when confronting the stressors in their growing environments. The disruption of oxidative balance that impairs the production performance in birds may somehow be linked to the immune system since oxidative stress and inflammatory damage are multi-stage processes. This review firstly discusses the individual influence of oxidative stress and inflammation on the poultry industry. Next, studies related to the application of phytochemicals or botanical compounds with the significance of their antioxidant and immunomodulatory abilities are reviewed. Furthermore, we bring up nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor kappa B (NF-κB) for they are respectively the key transcription factors involved in oxidative stress and inflammation for elucidating the underlying signal transduction pathways. Finally, by the discussion about several reports using phytochemicals to regulate these transcription factors leading to the improvement of oxidative status, heme oxygenase-1 gene is found crucial for Nrf2-mediated NF-κB inhibition.

Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms.

Using population pharmacokinetic analysis (PPK), we attempted to identify predictors of S-warfarin clearance (CL(S)) and to clarify population differences in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and white patients. Significant predictors of CL(S) included clinical (age, body weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African American ethnicity, the median CL(S) being 30% lower in the latter than in Asians and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. These results indicate warfarin dosing algorithms should be evaluated in each respective ethnic population. Further study of a large African American cohort will be necessary to confirm the present findings.

Antioxidant molecular targets of wheat bran fermented by white rot fungi and its potential modulation of antioxidative status in broiler chickens.

1. The study focused on antioxidant molecular targets of wheat bran fermented by white rot fungi (WRF) in poultry. After solid-state fermentation of wheat bran by WRF for 12 d, scanning electron microscopy found that the lignocellulose structure showed degradation and fragmentation. 2. A total of 300 1-d-old broilers were evenly divided by gender and randomly allocated into the following treatments: (1) maize-soybean meal (control group), (2) 10% of wheat bran replacing maize (10% WB group) or (3) 10% of fermented wheat bran replacing maize (10% FWB group). 3. The results indicated that the antioxidant gene expression, such as haem oxygenase-1 and glutathione-S-transferase of chicken peripheral blood mononuclear cells, of the 10% FWB group was significantly higher than that of the control group at d 35. For genes of Nicotinamide adenine dinucleotide phosphate oxygenase 1 and reactive oxygen species modulator protein 1, the expression of the 10% FWB group was lower than that of the control group at d 21 and 35. 4. In conclusion, wheat bran fermented by WRF could increase lignocellulolytic enzyme activities and the levels of active components that further regulate the expression of antioxidant molecular targets in poultry.

Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals - A review.

Oxidative stress suppresses animal health, performance, and production, subsequently impacting economic feasibility; hence, maintaining and improving oxidative status especially through natural nutrition strategy are essential for normal physiological process in animals. Phytochemicals are naturally occurring antioxidants that could be considered as one of the most promising materials used in animal diets in various forms. In this review, their antioxidant effects on animals are discussed as reflected by improved apparent performance, productivity, and the internal physiological changes. Moreover, the antioxidant actions toward animals further describe a molecular basis to elucidate their underlying mechanisms targeting signal transduction pathways, especially through the antioxidant response element/nuclear factor (erythroid-derived 2)-like 2 transcription system.

Genome-wide DNA methylation profile implicates potential cartilage regeneration at the late stage of knee osteoarthritis.

OBJECTIVE: The aim of this work was to characterize the genome-wide DNA methylation profile of cartilage from three regions of tibial plateau isolated from patients with primary knee osteoarthritis (OA), providing the first DNA methylation study that reflects OA progression. METHODS: The unique model system was used to section three regions of tibial plateau: the outer lateral tibial plateau (oLT), the inner lateral tibial plateau (iLT) and the inner medial tibial plateau (iMT) regions which represented the early, intermediate and late stages of OA, respectively. Genome-wide DNA methylation profile was examined using Illumina Infinium HumanMethylation450 BeadChip array. Comparisons of the iLT/oLT and iMT/oLT groups were carried out to identify differentially methylated (DM) probes (DMPs) associated with OA progression. DM genes were analyzed to identify the gene ontologies (GO), pathways, upstream regulators and networks. RESULTS: No significant DMPs were identified in iLT/oLT group, while 519 DMPs were identified in iMT/oLT group. Over half of them (68.2%) were hypo-methylated and enriched in enhancers and OpenSea. Upstream regulator analysis identified many microRNAs. DM genes were enriched in transcription factors, especially homeobox genes and in Wnt/ß-catenin signaling pathway. These genes also showed changes in expression when analyzed with expression profiles generated from previous studies. CONCLUSION: Our data suggested the changes in DNA methylation occurred at the late stage of OA. Pathways and networks enriched in identified DM genes highlighted potential etiologic mechanism and implicated the potential cartilage regeneration in the late stage of knee OA.

Insights into osteoarthritis progression revealed by analyses of both knee tibiofemoral compartments.

OBJECTIVE: To identify disease relevant genes and pathways associated with knee Osteoarthritis (OA) progression in human subjects using medial and lateral compartment dominant OA knee tissue. DESIGN: Gene expression of knee cartilage was comprehensively assessed for three regions of interest from human medial dominant OA (n = 10) and non-OA (n = 6) specimens. Histology and gene expression were compared for the regions with minimal degeneration, moderate degeneration and significant degeneration. Agilent whole-genome microarray was performed and data were analyzed using Agilent GeneSpring GX11.5. Significant differentially regulated genes were further investigated by Ingenuity Pathway Analysis (IPA) to identify functional categories. To confirm their association with disease severity as opposed to site within the knee, 30 differentially expressed genes, identified by microarray, were analyzed by quantitative reverse-transcription polymerase chain reaction on additional medial (n = 16) and lateral (n = 10) compartment dominant knee OA samples. RESULTS: A total of 767 genes were differentially expressed ≥ two-fold (P ≤ 0.05) in lesion compared to relatively intact regions. Analysis of these data by IPA predicted biological functions related to an imbalance of anabolism and catabolism of cartilage matrix components. Up-regulated expression of IL11, POSTN, TNFAIP6, and down-regulated expression of CHRDL2, MATN4, SPOCK3, VIT, PDE3B were significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples. CONCLUSIONS: Our study provides a strategy for identifying targets whose modification may have the potential to ameliorate pathological alternations and progression of disease in cartilage and to serve as biomarkers for identifying individuals susceptible to progression.

Risk of skin ulcerations associated with oral nicorandil therapy: a population-based study.

BACKGROUND: Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. OBJECTIVES: To determine the relationship between use of nicorandil and skin ulceration. METHODS: We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). RESULTS: The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. CONCLUSIONS: Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil.

Effects of co-fermented Pleurotus eryngii stalk residues and soybean hulls by Aureobasidium pullulans on performance and intestinal morphology in broiler chickens.

Soybean hulls are a by-product of soybean processing for oil and meal production; Pleurotus eryngii stalk residues (PESR) are by-products of the edible portion of the fruiting body enriched in bioactive metabolites. This study evaluated the effects of co-fermented PESR and soybean hulls with Aureobasidium pullulans on performance and intestinal morphology in broiler chickens. The in vitro experimental results showed that xylananse and mannanase activity of solid-state fermented soybean hulls (100% SBH) and soybean hulls partially replaced with PESR (75:25, SHP) reached peak at day 12; solid-state fermentation (SSF) enhanced the total phenolic content and trolox equivalency in both products as well. Additionally, FSHP had higher xylotriose and mannobiose levels than fermented FSBH did. A total of 400 broilers (Ross 308) were assigned randomly into four groups receiving the basal diet (control) or the basal diet supplemented with 0.5% fermented SBH (0.5% FSBH), 0.5% fermented SBHP (0.5% FSHP) and 1.0% fermented SBHP (1.0% FSHP) until 35 d of age, respectively. Results demonstrated that 0.5% FSHP addition increased body weight gain as compared with corresponding normal diet fed control in birds during entire experimental period. Compared with the control group, 0.5% FSHP group significantly increased the ratio of lactic acid bacteria to Clostridium perfringens in ceca as well as ileum villus height and jejunum villus height/crypt depth ratio of 35 d old birds. In conclusion, 0.5% FSHP supplementation in the diet could obtain not only improved body weight gain, but optimal intestinal morphology by exerting its bioactive metabolite properties when fed to broilers.

Direct assessment of articular cartilage and underlying subchondral bone reveals a progressive gene expression change in human osteoarthritic knees.

OBJECTIVE: To evaluate the interaction of articular cartilage (AC) and subchondral bone (SB) through analysis of osteoarthritis (OA)-related genes of site-matched tissue. DESIGN: We developed a novel method for isolating site-matched overlying AC and underlying SB from three and four regions of interest respectively from the human knee tibial plateau (n = 50). For each site, the severity of cartilage changes of OA were assessed histologically, and the severity of bone abnormalities were assessed by microcomputed tomography. An RNA isolation procedure was optimized that yielded high quality RNA from site-matched AC and SB tibial regions. Quantitative polymerase chain reaction (Q-PCR) analysis was performed to evaluate gene expression of 61 OA-associated genes for correlation with cartilage integrity and bone structure parameters. RESULTS: A total of 27 (44%) genes were coordinately up- or down-regulated in both tissues. The expression levels of 19 genes were statistically significantly correlated with the severity of AC degeneration and changes of SB structure; these included: ADAMTS1, ASPN, BMP6, BMPER, CCL2, CCL8, COL5A1, COL6A3, COL7A1, COL16A1, FRZB, GDF10, MMP3, OGN, OMD, POSTN, PTGES, TNFSF11 and WNT1. CONCLUSIONS: These results provide a strategy for identifying targets whose modification may have the potential to ameliorate pathological alterations and progression of disease in both AC and SB simultaneously. In addition, this is the first study, to our knowledge, to overcome the major difficulties related to isolation of high quality RNA from site-matched joint tissues. We expect this method to facilitate advances in our understanding of the coordinated molecular responses of the whole joint organ.

Estimation of the warfarin dose with clinical and pharmacogenetic data.

BACKGROUND: Genetic variability among patients plays an important role in determining the dose of warfarin that should be used when oral anticoagulation is initiated, but practical methods of using genetic information have not been evaluated in a diverse and large population. We developed and used an algorithm for estimating the appropriate warfarin dose that is based on both clinical and genetic data from a broad population base. METHODS: Clinical and genetic data from 4043 patients were used to create a dose algorithm that was based on clinical variables only and an algorithm in which genetic information was added to the clinical variables. In a validation cohort of 1009 subjects, we evaluated the potential clinical value of each algorithm by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable therapeutic dose; we also evaluated other clinically relevant indicators. RESULTS: In the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring < or = 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring > or = 49 mg per week). CONCLUSIONS: The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.

Genome-wide association study of bipolar I disorder in the Han Chinese population.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, ß-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Electron scattering by methanol and ethanol: a joint theoretical-experimental investigation.

We present a joint theoretical-experimental study on electron scattering by methanol (CH(3)OH) and ethanol (C(2)H(5)OH) in a wide energy range. Experimental differential, integral and momentum-transfer cross sections for elastic electron scattering by ethanol are reported in the 100-1000 eV energy range. The experimental angular distributions of the energy-selected electrons are measured and converted to absolute cross sections using the relative flow technique. Moreover, elastic, total, and total absorption cross sections for both alcohols are calculated in the 1-500 eV energy range. A complex optical potential is used to represent the dynamics of the electron-alcohol interaction, whereas the scattering equations are solved iteratively using the Padé's approximant technique. Our calculated data agree well with those obtained using the Schwinger multichannel method at energies up to 20 eV. Discrepancies at high energies indicate the importance of absorption effects, included in our calculations. In general, the comparison between our theoretical and experimental results, as well as with other experimental data available in the literature, also show good agreement. Nevertheless, the discrepancy between the theoretical and experimental total cross sections at low incident energies suggests that the experimental cross sections measured using the transmission technique for polar targets should be reviewed.

Experimental and theoretical investigations on photoabsorption and photoionization of trimethylphosphate in the vacuum-ultraviolet energy range.

In this work, we report a joint experimental-theoretical investigation on interaction of vacuum-ultraviolet radiation with trimethylphosphate (TMP) molecule (C(3)H(9)O(4)P) in gas phase. This species together with tetrahydrofuran (THF) are model compounds of deoxyribose nucleic acids (DNA)/ribose nucleic acids (RNA) backbone. Absolute photoabsorption cross sections (σ(a)) and ionization yields (η) are measured using the double-ion-chamber technique in the 11.0-21.45 eV energy range. Photoionization (σ(i)) and neutral-decay (σ(n)) cross sections in absolute scale are also derived. Moreover, theoretical photoabsorption cross sections are calculated using the time-dependent density functional theory from the excitation threshold up to 16 eV. Good agreement between the present calculated and experimental photoabsorption cross sections in the 11.0-14.5 eV range is encouraging. Also, the present measured data of σ(a) and σ(i) for TMP are about 1.3 and 1.5 times of those of THF, respectively. Thus, the experimental evidences that the majority of strand breaks being located at sugar rings in the irradiated DNA/RNA backbone moiety may be induced by a possible migration of the hole, initially created at phosphate group, to the linked sugar groups. Finally, absolute partial photoionization cross sections are derived from the experimental time-of-flight mass spectra.

Development and preliminary validation of a patient-reported outcome measure for swallowing after total laryngectomy (SOAL questionnaire).

OBJECTIVES: To develop and validate a laryngectomee-specific questionnaire to investigate swallowing function. This paper describes the generation of questionnaire items, pretesting with laryngectomees and a preliminary validation. DESIGN: This study employed 2 phases: questionnaire development and questionnaire validation. Items were developed from patient (n = 10) and clinician (n = 6) focus groups. Content checking, acceptability and face validity were determined through pretesting with 10 laryngectomees and via consensus feedback from 35 speech and language therapists. During preliminary validation, the 17-item final questionnaire was administered to 3 different groups. Discrimination amongst groups was established by comparing questionnaire responses of a laryngectomee group (n = 19) with known dysphagic (n = 19) and non-dysphagic groups (n = 20). Questionnaire responses from the reference dysphagic group were compared with an instrumental assessment of swallowing, the modified barium swallow (MBS). SETTING: Large urban teaching hospital. PARTICIPANTS: Speech and language therapists, laryngectomees, non-dysphagic volunteers, post-radiotherapy dysphagic patients. MAIN OUTCOME MEASURE: Preliminary validation of SOAL questionnaire. RESULTS: Normal, laryngectomee and dysphagic groups had significantly different SOAL scores, as did laryngectomees with different degrees of swallowing impairment (Kruskall Wallis, P << 0.001). The subjective SOAL score had a strong positive correlation with the reference measure of ratings on the MBS (r = 0.5; P = 0.03). CONCLUSIONS: The swallowing outcome after laryngectomy (SOAL) questionnaire is a simple, self-administered tool to assess swallowing function post-total laryngectomy. Further specific testing with a laryngectomy cohort is necessary for full validation. Its potential value lies in screening for dysphagia in clinics or during long-term follow-up of laryngectomees.

Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1).

Complementary DNA (cDNA) clones encoding human macrophage-specific specific colony-stimulating factor (CSF-1) were isolated. One cDNA clone codes for a mature polypeptide of 224 amino acids and a putative leader of 32 amino acids. This cDNA, which was cloned in the Okayama-Berg expression vector, specifies the synthesis of biologically active CSF-1 in COS cells, as determined by a specific radioreceptor assay, macrophage bone marrow colony formation, and antibody neutralization. Most of the cDNA isolates contain part of an intron sequence that changes the reading frame, resulting in an abrupt termination of translation; these cDNA's were inactive in COS cells. The CSF-1 appears to be encoded by a single-copy gene, but its expression results in the synthesis of several messenger RNA species, ranging in size from about 1.5 to 4.5 kilobases.

Rapidly involuting congenital haemangioma associated with transient thrombocytopenia and coagulopathy: a case series.

Rapidly involuting congenital haemangioma (RICH) may present with thrombocytopenia, low fibrinogen and elevated fibrin degradation products and D-dimers. Such complications have rarely been reported. We wished to define the clinical characteristics of the thrombocytopenia and coagulopathy associated with RICH, to emphasize the transient nature of this haematological complication and to distinguish these abnormalities from true Kasabach-Merritt phenomenon (KMP). We present a case series of seven patients with large RICH who presented with thrombocytopenia and coagulopathy during the first week of life. Clinical and haematological characteristics were recorded retrospectively. Two of the patients were treated with embolization due to early signs of high-output cardiac failure; four patients received oral corticosteroids in the range of 2 mg kg(-1) daily; one patient did not receive any treatment in the neonatal period, although the tumour was excised at 6 months of age. Two patients with platelet counts lower than 10 x 10(9) L(-1) received a platelet transfusion. There were no bleeding complications and only one patient presented with petechiae. In all seven patients, platelet counts started to increase at > 2 weeks of age and the coagulopathy resolved. We conclude that RICH may present with thrombocytopenia and coagulopathy similar to mild KMP early in the neonatal period. However, in contrast to true KMP, these abnormal laboratory findings are self-limited and are usually not complicated by bleeding problems.

Evaluation of potential antioxidant and anti-inflammatory effects of Antrodia cinnamomea powder and the underlying molecular mechanisms via Nrf2- and NF-κB-dominated pathways in broiler chickens.

Antrodia cinnamomea, a precious and unique medical fungus existing exclusively in Taiwan, exhibits antioxidant and immunomodulatory properties. This study was conducted to evaluate the beneficial effects of A. cinnamomea powder (ACP) and to further illuminate its underlying antioxidant and immunomodulation molecular mechanisms in broilers. The functional compounds of ACP-crude triterpenoids, crude polysaccharides, and total phenolic content-were assayed, respectively. Two-hundred-forty one-day-old broilers (Ross 308) were assigned to 4 treatment groups receiving dietary supplementation with ACP at 0, 0.1, 0.2, and 0.4% for 35 days. Each group had 4 replicate pens, with 15 birds per pen. During 1 to 21- and 22 to 35-day periods, chickens on ACP-supplemented diet demonstrated increased body weight gain, compared to those on the control diet, resulting in increased weight gain throughout the entire experimental period with an increased tendency in feed consumption yet no significant difference in FCR. Blood antioxidant potentiality, superoxide dismutase (SOD), increased in birds fed the supplemented diet at both 21 and 35 d, accompanied by higher catalase (CAT) activity at 21 days. In vivo peripheral blood mononuclear cells (PBMC) exposed to lipopolysaccharide (LPS) and 2,2΄-Azobis(2-amidinopropane) dihydrochloride (AAPH) capability showed that the diminished cell viability caused by both challenge factors was improved in ACP-supplemented groups. Antioxidant genes dominated by Nrf2 genes, such as HO-1 and GCLC, were up-regulated in 35-day-old birds. Inflammatory-related genes, such as IL-1ß and IL-6, ruled mainly by NF-κB, were rather down-regulated by 0.2% ACP addition at 21 and 35 days. Protein expression of Nrf2 and NF-κB in the liver supported the mRNA results, demonstrating that all ACP-supplemented groups showed significantly higher Nrf2 expression, whereas the NF-κB was inhibited. In conclusion, preferable microbial balance may putatively indicate the improvement of immunomodulatory-related capacity by ACP. Furthermore, ACP could induce the Nrf2-dependent pathway and decrease the NF-κB-dominated inflammatory signaling pathway. Antioxidant and immune capacity in terms of antioxidant enzymes and cell tolerance also was elevated by ACP. Concomitantly, body weight increasing with ACP supplementation as compared to the corresponding control group further implied the promising effects exerted by ACP.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.