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.

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.

[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.