Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways.

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine-phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment.

Complete mitochondrial genome sequence and gene organization of Chinese indigenous chickens with phylogenetic considerations.

In this study, we sequenced the complete mitochondrial DNA of Chinese indigenous Jinhu Black-bone and Rugao chickens. The two chicken mitochondrial genomes were deposited in GenBank under accession Nos. KP742951 and KR347464, respectively. The complete mitochondrial genomes of Jinhu Black-bone and Rugao chickens were sequenced and found to span 16,785 and 16,786 bp, respectively, and consisted of 22 tRNA genes, two rRNA genes (12S rRNA and 16S rRNA), 13 protein-coding genes, and one control region (D-loop). The majority of genes were positioned on the H-strand, and the ND6 and eight tRNA genes were found to be encoded on the L-strand. The mitogenomes showed a similar gene order to that of the published Gallus gallus genome, as neither included a control region. The overall base composition of the genome of the two chickens was A = 30.22/30.28%, G = 13.57/13.49%, T = 23.74/23.76%, and C = 32.48/32.48%. Nucleotide skewness of the coding strands of the two chicken genomes (AT-skew = 0.12, GC-skew = -0.41) was biased towards T and G. Phylogenetic analysis revealed 29 subspecies, and the molecular genetic relationship among the 29 subspecies was identical to that of traditional taxonomy.

Practices and thinking of laboratory detection in the aid to West Africa to fight against Ebola.

BACKGROUND: The outbreak of Ebola virus disease in West Africa has brought great disaster to the people's health in affected countries. China dispatched first group of public health experts and medical staff to Sierra Leone in September 2014 to fight Ebola. METHODS: To systematically collect huge amount of primary data, and to make analysis, draw conclusions and lessons in terms of six aspects, respectively as training before departure, local disease information, track of epidemic situation, transformation of temporary laboratory, detection of Ebola virus samples as well as assessment through single blind test. RESULTS: 1) Our team has launched preparatory works in advance before going to Sierra Leone. 2) Malaria is the country's severest infectious disease. 3) Observation centers were overcrowded with large number of suspected cases being inspected, implying high risk of nosocomial infection. 4) A BSL-II laboratory with 3 work areas and 2 buffer areas was built, achieving several major functions within 6 days. 5) Confirmed by South African Raqqa laboratory, our detection accuracy reached 100%. 6) At one week before return, the daily average sample amount of our team reached 66 cases and our detection capability was equivalent to that of USA. CONCLUSIONS: Successful experience from fighting against Ebola in Sierra Leone could be summarized as: 1) Optimized processes and scientific security measures are prerequisite to improving the detection ability. 2) The close collaboration between laboratory and observation center has created a new model of China's foreign aid. 3) Comprehensive information investigation and training lay a solid foundation for the successful completion of tasks.

Conjugated linoleic acids alleviate the immunosuppression of peripheral blood T lymphocytes in broiler chickens exposed to cyclosporin A.

The immunoregulatory actions of conjugated linoleic acids (CLA) of relevance immunosuppression were investigated. To test the hypothesis that CLA ameliorate immunosuppression, we developed the immunosuppressive model of peripheral blood T lymphocytes in broiler chickens induced by cyclosporin A. Peripheral blood T lymphocytes of broiler chickens were cultured with media containing various concentrations (25, 50, 100, and 200 µmol/L) of c9, t11-CLA and t10, c12-CLA to investigate the effects of CLA isomers on peripheral blood T lymphocyte proliferation, interleukin-2, the activity of phospholipase C, and protein kinase C production. Results suggested that CLA alleviated the immunosuppression of T lymphocytes in broiler chickens exposed to cyclosporin A through increasing of peripheral blood T lymphocyte proliferation and interleukin-2. The 2 CLA isomers enhanced T lymphocyte proliferation at low concentration and inhibited T lymphocyte proliferation at high concentration. In addition, the effect of c9, t11-CLA was better than that of t10, c12-CLA. At the cellular level, the effects of CLA on the alleviation of immunosuppression in T lymphocytes are mainly attributable to increasing the signaling molecules, such as phospholipase C and protein kinase C.

Melamine residues in eggs of quails fed on diets containing different levels of melamine.

1. An experiment was conducted to determine residual melamine concentrations in eggs of quail given diets containing different concentrations of melamine, and to estimate the time at which withdrawing melamine from the diet would result in undetectable concentrations in eggs. A total of 600 Japanese quails (Coturnix coturnix japonica) were randomly divided into 5 treatments, and given melamine at concentrations of 0, 2, 10, 50, and 100 mg/kg diet respectively for 30 d. From d 31 to 41, all quails were given a diet without melamine. Each diet was offered to 4 replicates (cages) of 30 quails each. On d 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, and 41, eggs were collected for the determination of melamine and cyanuric acid levels. 2. Throughout the 41 d experimental period, inclusion levels of melamine in the diets of quails had no significant effect on daily feed intake, egg production percentage, and feed efficiency. No detectable amount of cyanuric acid was found in all eggs. When the diets contained melamine at 2 mg/kg, the amounts of melamine in eggs were below the detection limit. During the entire 30 d exposure, the maximum melamine concentrations in eggs were 0·162, 0·998 and 1·784 mg/kg for the 10, 50 and 100 mg/kg treatment groups, respectively, which demonstrated a linear dose-response relationship. 3. Upon feeding a diet without melamine, the melamine concentration in eggs decreased rapidly. The time taken for the amounts of melamine to decline below the detection limit were 1, 5, and 5 d for quails fed on the diets containing melamine at 10, 50, and 100 mg/kg respectively. 4. Melamine is not metabolised into cyanuric acid in quails, and a positive relationship exists between the concentrations in feed and in eggs.

Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-ß-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

Conjugated linoleic acids alleviate infectious bursal disease virus-induced immunosuppression in broiler chickens.

The immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to viral disease pathogenesis and immune responses were investigated. To test the hypothesis that CLA ameliorates immunosuppression, we developed a viral challenge model by infecting chickens with infectious bursal disease virus (IBDV). After 14 d of dietary supplementation with either soybean oil or CLA, half of the chickens in each group were challenged with IBDV. We examined the effect of CLA on the development of lesions (i.e., lymphoid depletion and necrosis) and observed the immune responses against IBDV. The IBDV infection depleted lymphocytes in the medullary area and significantly stimulated interferon (IFN)-γ and IL-6 mRNA relative expression of bursa (P < 0.05) compared with the uninfected bursa. Compared with the CLA diet, lymphocytes depletion was more accentuated in chickens fed the control diet, whereas IFN-γ and IL-6 mRNA relative expression were upregulated (P < 0.05). Additionally, histopathological examination of the bursa revealed that the pathological changes tended to be more severe in infected chickens fed the control diet, which also significantly decreased (P < 0.05) on lymphocyte proliferation. Significant interactions were found between infection and diets for lymphocyte proliferation, antibody titers, and IFN-γ mRNA relative expression (P < 0.05). The results of this study indicate that dietary CLA enhanced immune function in chickens, particularly those of the IBDV-immunosuppressive status. Furthermore, at the molecular level, the immunoregulatory functions of CLA on chickens are attributable mainly to the antiinflammatory properties of CLA and are mediated, at least in part, through suppressing IBDV-specific proinflammatory cytokines mRNA relative expression.

Sodium alginate oligosaccharides from brown algae inhibit Salmonella Enteritidis colonization in broiler chickens.

The effects of sodium alginate oligosaccharides (sAO) on growth performance, cecal microbiota, Salmonella translocation to internal organs, and mucosal immune responses to challenge with Salmonella enterica serovar Enteritidis in broiler chickens were investigated. We designed an experiment with a 2 × 3 factorial arrangement, in which 3 feed treatments with supplementation of sAO at 0 (controls), 0.04, or 0.2% were provided in the diet for birds not challenged or challenged with Salmonella Enteritidis. There were 5 randomly placed replicate pens for each treatment. At 8 to 12 d of age, one-half the poults were orally gavaged with 10(8) cfu of Salmonella Enteritidis and the nonchallenged groups were inoculated with sterile PBS. Body weight loss and mortality resulting from Salmonella infection were mitigated by the addition of sAO. Supplementation of sAO at 0.2% was the most effective concentration for reducing Salmonella colonization and increasing the number of lactic acid bacteria in the cecum of chickens challenged with Salmonella Enteritidis. Cecal Salmonella Enteritidis-specific IgA production was significantly increased by sAO at 0.2% at 5 d postchallenge compared with the other treatments and was maintained at higher levels at the 2 dosages of sAO at 10 d postchallenge. With Salmonella Enteritidis challenge, sAO at 0.04% showed an anti-inflammatory effect through upregulation of interleukin (IL)-10 expression in the cecal tonsils. The supplementation level of 0.2% showed dramatic immunostimulatory activity by inducing interferon-γ, IL-10, and IL-1ß mRNA expression in cecal tonsils of nonchallenged birds. However, the high level of sAO induced a robust mucosal immune response in the absence of a challenge, and this may have led to a decline in BW. These findings suggest that dietary sAO can decrease Salmonella colonization and improve intestinal barrier function and performance of chickens.

High-performance liquid chromatographic analysis of resveratrol analog 3,5,4'-trimethoxystilbene in rat plasma.

(E)-3,5,4'-Trimethoxystilbene (BTM-0512), the analog of resveratrol, is potentially useful for the treatment of human diseases. This is the first study to use high-performance liquid chromatography (HPLC) for the determination of the resveratrol analog in rat plasma. Plasma proteins (0.1 mL) were precipitated with acetonitrile after the addition of the internal standard chlorzoxazone. The analysis used a BDS HYPERSIL C(18) analytical column (5 microm, 4.6 x 250 mm) with acetonitrile/water as the mobile phase. The UV-detection wavelength was 303 nm. The calibration curve was linear over the range of 0.025-10 microg/mL with a correlation coefficient of 0.9958. This concentration range corresponds well with the plasma concentrations of BTM-0512 in pharmacokinetic studies. There was a recovery of 102.2%, 95.3% and 103.7% from 0.05, 5 and 10 microg/mL plasma samples, respectively. The relative standard deviation of intra- and interday assay variations was all less than 13%. This HPLC assay is a quick, precise and reliable method for the analysis of BTM-0512 in pharmacokinetic studies.

Pharmacokinetics and tolerability of modafinil tablets in Chinese subjects.

OBJECTIVE: To investigate the pharmacokinetics and tolerability of modafinil in Chinese subjects. METHODS: Twelve healthy volunteers were given an escalating single dose of modafinil (100, 200 and 400 mg) in a three-period study (study 1). Another 12 volunteers received 100 mg twice daily for 7 days in multiple-dose study (study 2). Blood samples were taken from 0 to 60 h for study 1. And samples for study 2 were collected before administration on three consecutive morning and then from 0 to 60 h after the last dose. Pharmacokinetic parameters were calculated and compared with results from published data. RESULTS: In study 1, C(max) and area under the concentration-time curve of modafinil and modafinil acid were increased proportionally with dose levels; t(1/2) was independent on the dose levels. In study 2, the steady state was reached on day 4, and mean trough plasma concentration of modafinil was 1.36 +/- 0.34 mug/mL. Apparent plasma clearance and apparent volume of distribution were lower in 100 mg twice-daily group than those in 100 mg single group. The adverse events were mild and moderate in study 1 and 2. CONCLUSIONS: In this pharmacokinetic study, modafinil was safe and well tolerated by young healthy Chinese subjects. The major pharmacokinetic parameters of modafinil in Chinese subjects are similar to those reported in Caucasians although the half-life seems to be longer in the former than in the latter. This apparent difference requires investigation.

[HPLC determination of PAHs from electric power plant by UVD-FLD connected in series].

An HPLC method of UVD-FLD connected in series was used to detect naphthalene, biphenyl, fluorene, phenanthrene, anthracene, fluoranthene, 2-methyl-anthracene, chrysene, benzanthracene, benzfluoranthene [b], benzfluoranthene[k], benzopyrene PAH compounds in electricity plant environment. A CLC-ODS column (150 mm x 6.0 mm i.d.) with acetonitrile-water(85:15, V/V) as mobile phase and UV detector set at 250 nm and fluorescent detector set at lambda ex295 nm and lambda em427 nm were used. These 12 PAHs can be separated completely by this method. The earlier eluted eight PAHs were detected by UVD and the rest were detected by FLD. The minimum detectable concentrations of the 12 PAHs were 0.002 mg/L-0.1 mg/L. Satisfactory results were obtained in the analysis of PAH compounds in waste water, flue gas and flyash from several electric power plant in Hunan Province.

[Clinical study on zhengan xifeng decoction in preventing and treating hypertensive nephropathy].

Seventeen cases of hypertensive nephropathy with azotemia (test group) treated with Zhengan Xifeng Decoction (ZGXFI) and routine regimen of Western Medicine were observed. The result was compared with that of 15 cases treated with routine regimen alone (control group). After 3 months of treatment, the blood pressure, sodium excretion, blood urea nitrogen and creatinine were all reduced, while creatinine clearance rate (CCr) and residual renal function index (RRFI) were improved significantly in both groups. Compared with control group, the treatment on test group showed a more prominent effect on lowering of diastolic blood pressure, elevating the hemoglobin, reducing the blood level of triglyceride and creatinine as well as improving on CCr and RRFI, suggesting the deterioration of residual renal function could be restrained by ZGXFD, through improve the disorder of lipid metabolism, osmolality gradient and creatinine kinetics.