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1.
Int J Mol Sci ; 25(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891802

ABSTRACT

Soybean, a major source of oil and protein, has seen an annual increase in consumption when used in soybean-derived products and the broadening of its cultivation range. The demand for soybean necessitates a better understanding of the regulatory networks driving storage protein accumulation and oil biosynthesis to broaden its positive impact on human health. In this study, we selected a chromosome segment substitution line (CSSL) with high protein and low oil contents to investigate the underlying effect of donor introgression on seed storage through multi-omics analysis. In total, 1479 differentially expressed genes (DEGs), 82 differentially expressed proteins (DEPs), and 34 differentially expressed metabolites (DEMs) were identified in the CSSL compared to the recurrent parent. Based on Gene Ontology (GO) term analysis and the Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG), integrated analysis indicated that 31 DEGs, 24 DEPs, and 13 DEMs were related to seed storage functionality. Integrated analysis further showed a significant decrease in the contents of the seed storage lipids LysoPG 16:0 and LysoPC 18:4 as well as an increase in the contents of organic acids such as L-malic acid. Taken together, these results offer new insights into the molecular mechanisms of seed storage and provide guidance for the molecular breeding of new favorable soybean varieties.


Subject(s)
Gene Expression Regulation, Plant , Glycine max , Seeds , Glycine max/genetics , Glycine max/metabolism , Seeds/genetics , Seeds/metabolism , Chromosomes, Plant/genetics , Gene Regulatory Networks , Plant Breeding/methods , Gene Expression Profiling/methods , Gene Ontology , Transcriptome/genetics , Multiomics
2.
J Environ Manage ; 325(Pt B): 116694, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36343400

ABSTRACT

Poor management of crop residues leads to environmental pollution and composting is a sustainable practice for addressing the challenge. However, knowledge about composting with pure crop straw is still limited, which is a novel and feasible composting strategy. In this study, pure corn straw was in-situ composted for better management. Community structure of ß-glucosidase-producing microorganisms during composting was deciphered using high-throughput sequencing. Results showed that the compost was mature with organic matter content of 37.83% and pH value of 7.36 and pure corn straw could be composted successfully. Cooling phase was major period for cellulose degradation with the highest ß-glucosidase activity (476.25 µmol·p-Nitr/kg·dw·min) and microbial diversity (Shannon index, 3.63; Chao1 index, 500.81). Significant compositional succession was observed in the functional communities during composting with Streptomyces (14.32%), Trichoderma (13.85%) and Agromyces (11.68%) as dominant genera. ß-Glucosidase-producing bacteria and fungi worked synergistically as a network to degrade cellulose with Streptomyces (0.3045**) as the key community revealed by multi-interaction analysis. Organic matter (-0.415***) and temperature (-0.327***) were key environmental parameters regulating cellulose degradation via influencing ß-glucosidase-producing communities, and ß-glucosidase played a key role in mediating this process. The above results indicated that responses of ß-glucosidase-producing microorganisms to cellulose degradation were reflected at both network and individual levels and multi-interaction analysis could better explain the relationship between variables concerning composting cellulose degradation. The work is of significance for understanding cellulose degradation microbial communities and process during composting of pure corn straw.


Subject(s)
Composting , Streptomyces , Trichoderma , beta-Glucosidase/metabolism , Zea mays/metabolism , Soil , Cellulose/metabolism , Trichoderma/metabolism , Streptomyces/metabolism , Manure
3.
Arch Microbiol ; 204(4): 236, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35362815

ABSTRACT

Fungi are reputed to play a significant role in the composting matrix as decomposers of recalcitrant organic materials like cellulose and lignin. However, information on the fungi communities' roles in nitrogen transformation under a compost-biochar mixture is scarce. This study investigated shifts in fungal species mediating N transformation and their network patterns in cattle manure-corn straw (CMCS) and CMCS plus biochar (CMCB) composting using high-throughput sequencing data. The results revealed that the addition of biochar altered fungal richness and diversity and significantly influenced their compositions during composting. Biochar also altered the compost fungal network patterns; CMCS had a more complex network with higher positive links than CMCB, suggesting stable niche overlap. The consistent agreement of multivariate analyses (redundancy, network, regression, Mantel and path analyses) indicated that Ciliophora_sp in CMCS and unclassified_norank_Pleosporales in CMCB were the key fungal species mediating total N transformation, whereas Scedosporium_prolificans in CMCS and unclassified_Microascaceae in CMCB were identified as major predictive indices determining NO3--N transformation. Also, Coprinopsis cinerea and Penicillium oxalicum were the predictive factors for NH4+-N transformation in CMCS and CMCB during composting. These results indicated that the effects of biochar on N conversions in composting could be unraveled using multivariate analyses on fungi community evolution, network patterns, and metabolism.


Subject(s)
Composting , Animals , Cattle , Charcoal , Fungi/genetics , Fungi/metabolism , Manure , Nitrogen/metabolism , Zea mays/metabolism
4.
Appl Opt ; 60(13): 3856-3864, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33983323

ABSTRACT

The phase-shifting technique is one of the most important techniques in interferometry. The measurement accuracy of this technique is affected by several kinds of systematic and random errors like miscalibration, nonlinear response and tilt shift of the phase shifter, nonlinear recording, speckles, fringe fluctuation, etc. In this paper, a method for verification of all of these phase measurement error sources is proposed by introducing a grayscale image. This image is composed from the lattice-site representation determined by a four step phase-shifting algorithm, which represents the distribution of phase-shift angle values. The shape of the grayscale image is definitely more expressive and demonstrative for the kinds of measurement error sources than the black dot distribution in lattice-site representation. So, with this technique, we can recognize the existence of various measurement error sources and roughly estimate their magnitudes before proceeding with experiments. Our method is to be rather qualitative than quantitative. The availability of this method is discussed in a phase-shifting Fizeau interferometer and a fringe projection profilometry. This method is useful in all kinds of interferometric measurements based on the phase-shifting technique.

5.
Appl Opt ; 59(3): 687-693, 2020 Jan 20.
Article in English | MEDLINE | ID: mdl-32225204

ABSTRACT

Self-mixing interferometry (SMI) is a reliable method that has been applied to measuring displacements, absolute distances, and velocities of remote targets. Evaluating the optical feedback factor C and the linewidth enhancement factor α is a vital step in calculating laser diode parameters and in processing SMI signals using phase unwrapping. This paper proposes an evaluation method for the optical feedback factor and the linewidth enhancement factor of arbitrary waveforms by investigating the slopes of phase discontinuity distribution in the optical feedback regime of 1

6.
Sci Total Environ ; 883: 163674, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37100152

ABSTRACT

Conventional composting is a viable method treating agricultural solid waste, and microorganisms and nitrogen transformation are the two major components of this proces. Unfortunately, conventional composting is time-consuming and laborious, and limited efforts have been made to mitigate these problems. Herein, a novel static aerobic composting technology (NSACT) was developed and employed for the composting of cow manure and rice straw mixtures. During the composting process, physicochemical parameters were analyzed to evaluate the quality of compost products, and microbial abundance dynamics were determined using high-throughput sequencing technique. The results showed that NSACT achieved compost maturity within 17 days as the thermophilic stage (≥55 °C) lasted for 11 days. GI, pH, and C/N were 98.71 %, 8.38, and 19.67 in the top layer, 92.32 %, 8.24, and 22.38 in the middle layer, 102.08 %, 8.33, and 19.95 in the bottom layer. These observations indicate compost products maturated and met the requirements of current legislation. Compared with fungi, bacterial communities dominated NSACT composting system. Based on the stepwise verification interaction analysis (SVIA), the novel combination utilization of multiple statistical analyses (Spearman, RDA/CCA, Network modularity, and Path analyses), bacterial genera Norank Anaerolineaceae (-0.9279*), norank Gemmatimonadetes (1.1959*), norank Acidobacteria (0.6137**) and unclassified Proteobacteria (-0.7998*), and fungi genera Myriococcum thermophilum (-0.0445), unclassified Sordariales (-0.0828*), unclassified Lasiosphaeriaceae (-0.4174**), and Coprinopsis calospora (-0.3453*) were the identified key microbial taxa affecting NH4+-N, NO3--N, TKN and C/N transformation in the NSACT composting matrix respectively. This work revealed that NSACT successfully managed cow manure-rice straw wastes and significantly shorten the composting period. Interestingly, most microorganisms observed in this composting matrix acted in a synergistic manner, promoting nitrogen transformation.


Subject(s)
Composting , Oryza , Animals , Cattle , Female , Manure/microbiology , Nitrogen , Soil , Bacteria , Oryza/microbiology
7.
Waste Manag ; 142: 132-142, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35219063

ABSTRACT

Composting is the mainstream technology for the treatment of agricultural solid waste, but limited efforts were made to investigate fungal composition and its contributions to nitrogen transformation in different depths of compost. In this study, spatial distributions of fungi were analyzed using high throughput sequencing by multi-angle analyses, and the key fungal communities determining nitrogen transformation were quantified and identified by multi-aspect analyses during cow manure composting. Multi-angle analyses showed that fungal structure, biomarkers and trophic mode composition varied in different layers, revealing that spatial heterogeneity is the distinctive attribute of composting system. Ascomycota and Basidiomycota were dominant phyla during composting, the two phyla peaked in top and bottom layer respectively. At mesophilic stage, Tremellales, and unclassified Ascomycota (order) were biomarkers in top and middle layer respectively, and so were Remersonia, Pyrenochaetopsis, and Wallemia in bottom layer by LEfSe analysis. Based on multi-aspect analyses, Unclassified Dothideomycetes mainly affected NH4+-N transformation both in top (1.2816***) and middle layers (1.1726*). Trichocladium asperum (0.9536***) and Zopfiella (-0.9484***) mainly affected TN transformation in top layer. Guehomyces pullulans (-0.9684**) and Preussia (-1.0508**) regulated NO3--N transformation in middle layer. Thermomyces lanuginosus (0.7127***) and Typhula sp. UW973129 (0.7298***) were the key species promoting TN and C/N transformation in bottom layer, respectively. Interestingly, different fungal communities showed a complex network interaction driving nitrogen transformation, and the abundance of microbial community could be conducive to characterizing nitrogen transformation in the vertical space of composting.


Subject(s)
Composting , Mycobiome , Animals , Cattle , Female , Fungal Structures , Manure/microbiology , Nitrogen , Soil
8.
J Immunol ; 182(4): 2502-10, 2009 Feb 15.
Article in English | MEDLINE | ID: mdl-19201906

ABSTRACT

Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4(+) T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.


Subject(s)
Allergens/immunology , Alternaria/immunology , Asthma/immunology , Asthma/microbiology , Dendritic Cells/immunology , Th2 Cells/immunology , Adoptive Transfer , Ambrosia/immunology , Animals , Cytokines/biosynthesis , Cytokines/immunology , Mice , Mice, Transgenic , Ovalbumin/immunology , Pollen/immunology
9.
J Mol Model ; 27(6): 156, 2021 May 07.
Article in English | MEDLINE | ID: mdl-33961100

ABSTRACT

The modified embedded atom method (MEAM) potentials improved by Jin et al. (Appl. Phys. A120 (2015), p. 189) were applied to calculate the mono- and bi-vacancy properties as well as the phonon dispersions for hexagonal close-packed (HCP) metals Be, Co, Hf, Mg, and Re. We expressed the formulas for calculating the mono- and bi-vacancy properties by the molecular static (MS) method based on the MEAM potentials for HCP metals. The lattice dynamics (LD) method and the MEAM potentials were adopted to calculate the phonon dispersion properties. The calculation results show better agreement with the experimental data than the previous calculations by using the unimproved embedded atom model.

10.
Bioresour Technol ; 323: 124572, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33370679

ABSTRACT

This study investigated nitrification process during cattle manure-maize straw (CM) and biochar (CMB) composting in terms of multi-variable interaction (MVI) among environmental parameters, ammonia-oxidizing archaea (AOA) and bacteria (AOB) community structure, nitrogen-related enzymes as well as substrates using structural equation model (SEM). Results showed that adding biochar significantly reduced potential ammonia oxidation rates. SEM analysis revealed that AOB was affected by temperature and pH, which stimulated the release of urease, increased NH4+-N concentration and finally exerted influence on nitrification in CM. Temperature (0.755) and NO2--N (-0.994) were identified as the main factors mediating nitrification in CM and CMB, respectively. Moreover, MVI analysis indicated that nitrification and denitrification occurred simultaneously. Mutual verification of SEM and quantitative analyses (RNA level) confirmed that AOB predominated nitrification. The above results indicated that nitrification could be better explained by MVI using SEM during composting.


Subject(s)
Composting , Manure , Ammonia , Animals , Archaea , Cattle , Charcoal , Nitrification , Oxidation-Reduction , Soil , Soil Microbiology , Zea mays
11.
Gan To Kagaku Ryoho ; 35(12): 2262-4, 2008 Nov.
Article in Japanese | MEDLINE | ID: mdl-19106590

ABSTRACT

INTRODUCTION: Granulysin is a cytotoxic granule protein of cytotoxic T-lymphocytes and natural killer cells. Gastric cancer patients of stage II and stage III were reported to have pre-operative serum granulysin, which is a good prognostic factor. Activated T lymphocytes produce a lot of granulysin in the cell. We hypothesized that activated T lymphocytes transfer therapy may increase in serum granulysin leveles of stage IV and relapsed patients. METHOD: Between April 2002 and December 2007, the patients received a standard therapy with activated lymphocytes transfer therapy. Peripheral blood samples were taken from the patients. Serum granulysin concentrations were measured using a granulysin-specific ELISA kit. RESULT: The average serum granulysin level for Stage IV (n=29) and relapsed patients (n=13) was 3.3 ng/mL. The gastric cancer patients were classified into two groups based on their concentration of serum granulysin level: high group (> or = 3.3 ng/mL); low group (< 3.3 ng/mL). There were no significant differences between these two groups in gender and age. The stage IV high group had a longer survival time than the stage IV low group. After 60 days from the activated T lymphocytes transfer therapy, the average pre-treatment serum granulysin had increased. However, there was no significant difference to note. It is noteworthy that serum granulysin is a novel parameter of patients cancer immunity.


Subject(s)
Antigens, Differentiation, T-Lymphocyte/blood , Immunotherapy , Lymphocyte Activation/immunology , Lymphocyte Transfusion , Lymphocytes/immunology , Stomach Neoplasms/immunology , Stomach Neoplasms/therapy , Biomarkers/blood , Humans , Liver Neoplasms/blood , Liver Neoplasms/immunology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Neoplasm Staging , Stomach Neoplasms/blood , Stomach Neoplasms/pathology , Survival Rate
12.
J Hazard Mater ; 147(1-2): 8-14, 2007 Aug 17.
Article in English | MEDLINE | ID: mdl-17239533

ABSTRACT

A new design of supercritical water oxidation (SCWO) bench-scale reactor has been developed to handle high-risk wastes resulting from munitions demilitarization. The reactor consists of a concentric vertical double wall in which SCWO reaction takes place inside an inner tube (titanium grade 2, non-porous) whereas pressure resistance is ensured by a Hastelloy C-276 external vessel. The performances of this reactor were investigated with two different kinds of chemical warfare agent simulants: OPA (a mixture of isopropyl amine and isopropyl alcohol) as the binary precursor for nerve agent of sarin and thiodiglycol [TDG, (HOC(2)H(4))2S] as the model organic sulfur heteroatom. High destruction rates based on total organic carbon (TOC) were achieved (>99.99%) without production of chars or undesired gases such as carbon monoxide and methane. The carbon-containing product was carbon dioxide whereas the nitrogen-containing products were nitrogen and nitrous oxide. Sulfur was totally recovered in the aqueous effluent as sulfuric acid. No corrosion was noticed in the reactor after a cumulative operation time of more than 250 h. The titanium tube shielded successfully the pressure vessel from corrosion.


Subject(s)
Chemical Warfare Agents/chemistry , Hazardous Waste/prevention & control , Pressure , Carbon Dioxide , Nitrogen , Nitrous Oxide , Oxygen/chemistry , Sulfuric Acids , Titanium , Water/chemistry
13.
J Hazard Mater ; 124(1-3): 119-24, 2005 Sep 30.
Article in English | MEDLINE | ID: mdl-15941618

ABSTRACT

Supercritical water oxidation can effectively destroy a large variety of high-risk wastes resulting from munitions demilitarization and complex industrial chemical. An important design consideration in the development of supercritical water oxidation is the information on the oxidation rate. In this paper, the oxidation rate of isopropyl amine (OPA), one of high-risk wastes resulting from munitions demilitarization, was investigated under supercritical water oxidation (SCWO) conditions in an isothermal tubular reactor. H2O2 was used as the oxidant. The reaction temperatures were ranged from 684 to 891 K and the residence times varied from 9 to 18s at a fixed pressure of 25 MPa. The conversion of OPA was monitored by analyzing total organic carbon (TOC) on the liquid effluent samples. The initial TOC concentrations of OPA varied from 7.21 to 143.78 mmol/l at the conversion efficiencies from 88.94 to 99.98%. By taking into account the dependence of reaction rate on oxidant and TOC concentration, a global power-law rate expression was regressed from 38 OPA experimental data. The resulting pre-exponential factor was 2.46(+/-0.65)x10(3)l(1.37)mmol(-0.37)s(-1); the activation energy was 64.12+/-1.94 kJ/mol; and the reaction orders for OPA (based on TOC) and oxidant were 1.13+/-0.02 and 0.24+/-0.01, respectively.


Subject(s)
Industrial Waste/prevention & control , Propylamines/metabolism , Water Pollutants, Chemical/analysis , Water Pollution, Chemical/prevention & control , Water/chemistry , Kinetics , Osmolar Concentration , Oxidants/chemistry , Oxidation-Reduction , Temperature
14.
Am J Chin Med ; 33(2): 167-80, 2005.
Article in English | MEDLINE | ID: mdl-15974476

ABSTRACT

The pathogenic mechanism and effective treatment of inflammatory bowel disease (IBD) are still unknown. In the present study, we examined the protective effect of hawthorn fruit (Crataegifructus) on two murine colitis models: dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding and weight loss within 10 days. However, hawthorn fruit (2 g/kg body weight) restored the body weight and colon length and increased hemoglobin count in these animals. Hawthorn fruit not only decreased signs of inflammation such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions, but also showed improvement of leukotriene B4 (LTB4), a biochemical parameter of inflammation mass. TNBS colitis mice had significantly lower rates of survival than normal control animals; however, treatment with hawthorn fruit significantly improved survival in TNBS colitis mice. The results suggest that hawthorn fruit and the Kampo formula that contains this ingredient may have potential therapeutic utility in patients with IBD.


Subject(s)
Colitis/drug therapy , Crataegus/chemistry , Phytotherapy , Plant Preparations/therapeutic use , Acute Disease , Animals , Anticoagulants/toxicity , Colitis/veterinary , Dextran Sulfate/toxicity , Disease Models, Animal , Female , Fruit , Mice , Mice, Inbred BALB C , Trinitrobenzenesulfonic Acid/toxicity
15.
Am J Chin Med ; 33(1): 87-94, 2005.
Article in English | MEDLINE | ID: mdl-15844836

ABSTRACT

We investigated the effects of water and ethyl acetate extracts of Citrus unshiu peel (Aurantii Nobilis pericarpium) on hepatitis C virus (HCV) absorption in MOLT-4 cells (a human lymphoblastoid leukemia cell line). By reverse transcription polymerase chain reaction (RT-PCR), we showed that both the ethyl acetate layer of Citrus unshiu peel extract and fraction 7 decreased HCV absorption in MOLT-4 cells. Furthermore, we demonstrated that 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) is the active ingredient that markedly inhibited HCV infection in MOLT-4 cells.


Subject(s)
Antioxidants/pharmacology , Citrus/chemistry , Drugs, Chinese Herbal/pharmacology , Flavones/pharmacology , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Antioxidants/chemistry , Cell Line, Tumor , Flavones/chemistry , Humans , Leukemia, T-Cell
16.
J Am Geriatr Soc ; 52(9): 1518-21, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15341554

ABSTRACT

OBJECTIVES: To evaluate whether a traditional Chinese herbal medicine, ba wei di huang wan (BDW), improves cognitive and physical functioning in dementia patients. DESIGN: An 8-week randomized, double-blind, placebo-controlled trial. SETTING: Long-term-care facility in Japan. PARTICIPANTS: Thirty-three patients with mild to severe dementia (7 men and 26 women; mean age +/- standard deviation=84.4 +/- 7.8) were recruited and enrolled from May 2002 through September 2002. INTERVENTION: Participants were randomly assigned to the active drug (BDW) group (n=16) or the placebo group (n=17) and treated for 8 weeks. MEASUREMENT: Cognitive function and activities of daily living (ADLs); palsatility index. RESULTS: After the trial, cognitive function as assessed using the Mini-Mental State Examination (MMSE) significantly improved from 13.5 +/- 8.5 to 16.3 +/- 7.7 (P<.01, 95% confidence interval (CI)=-4.1 to -1.4) in the BDW group. The ADL score in the Barthel Index also significantly changed, from 61.8 +/- 34.6 to 78.9 +/- 21.1 (P<.01, 95% CI=-26.2 to -7.9). In contrast, MMSE and Barthel Index scores of the placebo group showed no significant change. Eight weeks after the end of the administration, MMSE and Barthel Index scores of the BDW group declined to the baseline level. The pulsatility index in the internal carotid artery as measured using Doppler sonography significantly decreased in the BDW group (2.5 +/- 1.7 to 1.9 +/- 0.5, P<.05) but not in the placebo group. CONCLUSION: These results argue the benefits of BDW in the treatment of dementia.


Subject(s)
Dementia/drug therapy , Drugs, Chinese Herbal/therapeutic use , Activities of Daily Living , Aged , Aged, 80 and over , Analysis of Variance , Blood Pressure/drug effects , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/drug effects , Carotid Artery, Internal/physiopathology , Cognition/drug effects , Dementia/diagnosis , Dementia/physiopathology , Double-Blind Method , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Female , Humans , Japan , Male , Medicine, Chinese Traditional , Mental Status Schedule , Neuropsychological Tests , Pilot Projects , Pulsatile Flow/drug effects , Sample Size , Treatment Outcome , Ultrasonography, Doppler
17.
J Clin Pharmacol ; 44(5): 520-31, 2004 May.
Article in English | MEDLINE | ID: mdl-15102873

ABSTRACT

Palonosetron (Aloxi, Onicit) is a selective 5-HT(3) receptor antagonist recently approved by the Food and Drug Administration for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. This study was performed to determine the pharmacokinetics and assess the safety and tolerability of intravenous (IV) palonosetron in healthy U.S. and Japanese subjects. Subjects were administered a single IV dose of palonosetron, ranging from 0.3 to 90 microg/kg in either of two randomized, double-blind, placebo-controlled, ascending-dose studies (n = 80 and n = 32, respectively). Serial blood samples were obtained in both studies to evaluate the pharmacokinetics of palonosetron and its N-oxide metabolite, M9. Intravenous palonosetron was well tolerated across a wide range of doses in both studies. The incidence and severity of adverse events (AEs) were similar between subjects receiving palonosetron and those receiving placebo, with no dose-dependent incidences. The most frequently reported AEs were headache, transient elevation of liver enzymes, and constipation. Systemic exposure (AUC and C(max)) for palonosetron generally increased with increasing dose. Mean total body clearance, elimination half-life, and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg, 33.7 to 54.1 hours, and 3.85 to 12.6 L/kg, respectively, in U.S. subjects and from 2.58 to 3.50 mL/min/kg, 30.8 to 36.8 hours, and 6.96 to 9.85 L/kg, respectively, in Japanese subjects. The pharmacokinetics of palonosetron appeared to be independent of dose, with no dose adjustment required in Japanese subjects. The plasma concentration profile of palonosetron, as represented by a half-life of approximately 40 hours, may provide a clinical advantage over other 5-HT(3) antagonists.


Subject(s)
Asian People , Isoquinolines/pharmacokinetics , Quinuclidines/pharmacokinetics , Receptors, Serotonin, 5-HT3/administration & dosage , Serotonin 5-HT3 Receptor Antagonists , Adult , Area Under Curve , Constipation/chemically induced , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Headache/chemically induced , Humans , Inactivation, Metabolic/physiology , Infusions, Intravenous , Injections, Intravenous , Isoquinolines/adverse effects , Isoquinolines/metabolism , Liver/drug effects , Liver/enzymology , Men , Palonosetron , Quinuclidines/adverse effects , Quinuclidines/metabolism , Time Factors , United States
18.
J Ethnopharmacol ; 79(3): 341-6, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11849839

ABSTRACT

In this study, the protective effect of Polygalae root was evaluated in a murine model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days, could recover the lost body weight and decrease the gross rectal bleeding. Polygalae root also reduced the degree of inflammation and improved significantly the histological changes such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions. Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed. The results showed that IFN-gamma was increased, but IL-4 was decreased in TNBS-induced colitis, when those were compared with the sham controls. But the administration of Polygalae root to TNBS-induced colitis mice showed lower production of IFN-gamma and higher production of IL-4 than the TNBS-induced colitis. These results suggest that the protective effects of Polygalae root against the TNBS colitis may be associated with the regulation of cytokine production of intraepithelial lymphocytes.


Subject(s)
Colitis/chemically induced , Colitis/prevention & control , Polygalaceae , Trinitrobenzenesulfonic Acid , Animals , Colitis/pathology , Colon/drug effects , Colon/pathology , Cytokines/biosynthesis , Dose-Response Relationship, Drug , Female , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lymphocytes/immunology , Lymphocytes/metabolism , Mice , Mice, Inbred BALB C , Organ Size/drug effects , Phytotherapy/methods , Phytotherapy/statistics & numerical data , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Roots/chemistry , Spleen/drug effects , Thymus Gland/drug effects
19.
J Ethnopharmacol ; 81(3): 365-72, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12127238

ABSTRACT

In this study, we investigated the effect of Rauwolfia radix on heat shock protein (HSP) 70 expression and cytotoxicity against tumor cells in activated human T cells. When activated T cells were cultured with Rauwolfia radix for 18 h, HSP70 expression after heat shock was remarkably increased, and cytotoxicity against T98G tumor cells was augmented. Moreover, Rauwolfia radix also enhanced the cytotoxicity of heat shocked activated T cells against Molt-4 and T98G tumor cells. Secretions of interferon-gamma (IFN-gamma) and tumor necrosis alpha (TNF-alpha), due to Concanavalin A (Con A) stimulation, were increased by Rauwolfia radix in activated T cells. To investigate the antitumor effect in vivo, EL-4 tumor-bearing mice were administered with Rauwolfia radix in drinking water. The survival period of the Rauwolfia radix treatment group was significantly prolonged compared with that of the control group. Reserpine, the major active ingredient of Rauwolfia radix, also enhanced the cytotoxicity of activated T cells against Molt-4 and T98G tumor cells, and prolonged the survival period of EL-4 tumor-bearing mice. Taken together, our results suggest that Rauwolfia radix can enhance the activity of immune cells against tumor cells.


Subject(s)
Cytotoxicity, Immunologic/drug effects , Lymphocyte Activation/drug effects , Neoplasms/immunology , Plant Extracts/pharmacology , Rauwolfia/chemistry , T-Lymphocytes/drug effects , Animals , Blotting, Western , Cell Survival/drug effects , Concanavalin A/immunology , Female , Gene Expression Regulation/drug effects , HSP70 Heat-Shock Proteins/biosynthesis , Heat-Shock Response , Humans , Interferon-gamma/biosynthesis , Mice , Mice, Inbred C57BL , Neoplasms/pathology , Plant Roots/chemistry , Reserpine/pharmacology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Time Factors , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/biosynthesis
20.
J Altern Complement Med ; 10(5): 841-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15650474

ABSTRACT

OBJECTIVE: The phagocytic activity of macrophages as a novel approach to scientific elucidation of the effects of Chinese medicines was studied through administration of a kampo preparation, by measuring the rise in body temperature, which is thought to stimulate innate defensive functions of organisms and enhance the immune systems. DESIGN: Using dogs as experimental models, a rise in body temperature following administration of Kakkon-to was observed, and the average number and average rate of phagocytosis of macrophages in blood using latex micro-particles was investigated. RESULTS: The body temperature of the treated animals significantly increased 30 minutes after administration (p<0.01), and remained elevated for more than 5 hours. A comparison of body temperatures before and after administration showed significant increases over controls from 1 to 11 hours, p<0.01; and at 12 hours, p<0.05 after administration. The average number and the average rate of phagocytosis were significantly increased 1 (p<0.05) and 2 (p<0.01) hours after administration. The mean number of phagocytized cells significantly increased (p<0.05) at 1 hour after administration compared with that before administration, and the mean phagocytic rate also increased significantly (p<0.01) 2 hours after administration. Increases (p<0.01) in both the rate of phagocytosis and the number of cells phagocytized were found at every measurement point from 2 to 24 hours after administration. Significant increases (p<0.01) were also observed in both the rate of phagocytosis and the number of cells phagocytized 3 hours after administration, when compared with the control group. CONCLUSION: This paper demonstrates that ingestion of Kakkon-to not only increases the body temperature but also enhances the phagocytic activity of macrophages, an in vivo defense mechanism, suggesting that Kakkon-to contributes to the suppression of multiplication of common cold viruses and influenza viruses, which consequently results in improvement of various symptoms during infection with common cold viruses.


Subject(s)
Body Temperature/drug effects , Drugs, Chinese Herbal/pharmacology , Macrophage Activation/drug effects , Phagocytosis/drug effects , Animals , Common Cold/immunology , Dogs , Female
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