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Objectives : A diverse range of adverse effects has been linked to the application of antidepressants for the treatment of depressive disorder. Recently, evidence has been emerging of the adverse metabolic effects of antidepressants. This study investigated the effects of antidepressants on plasma glucose and other factors in the fat and muscle tissue relating to metabolism. METHODS : Long-Evans-Tokushima-Ostuka (LETO) rats were used to evaluate the effects of different antidepressants. Amitriptyline, fluoxetine, and mirtazapine were administered to each of three subgroups for 4 weeks, between 11 and 15 weeks old, while a fourth subgroup was administered no antidepressant during the same period. Changes of weight and daily intake were monitored. Tissues and blood were collected at 15 weeks. RESULTS : The fluoxetine subgroup showed lower weight gain and lower food efficacy ratio than did the other subgroups. Blood glucose and other circulating factors showed no significant differences among groups, except for the leptin levels of the fluoxetine subgroup. However, the amitriptyline and mirtazapine subgroups showed similar patterns in the response of mRNA expression of peroxisome proliferator-activated receptors gamma cofactor-1 and uncoupling protein-1, 2, 3. CONCLUSION : These results could indicate possible differences in metabolic response based on the kind of antidepressant used.
Тема - темы
Animals , Rats , Amitriptyline , Antidepressive Agents , Blood Glucose , Depressive Disorder , Energy Metabolism , Fluoxetine , Glucose , Leptin , Mianserin , Muscles , Peroxisome Proliferator-Activated Receptors , Plasma , RNA, Messenger , Weight GainРеферат
PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Тема - темы
Humans , Alleles , Aspirin , Asthma , Cytokines , Eosinophils , Haplotypes , Hypersensitivity , Inflammation , Ligands , Logistic Models , Peroxisome Proliferator-Activated Receptors , Peroxisomes , Polymorphism, Single Nucleotide , PPAR gammaРеферат
PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Тема - темы
Humans , Alleles , Aspirin , Asthma , Cytokines , Eosinophils , Haplotypes , Hypersensitivity , Inflammation , Ligands , Logistic Models , Peroxisome Proliferator-Activated Receptors , Peroxisomes , Polymorphism, Single Nucleotide , PPAR gammaРеферат
@#The inflammatory reaction after acute cerebral infarction can aggravate the cerebral ischemic reperfusion injury.Activation of peroxisome proliferator-activated receptors-γ(PPAR-γ) has neuroprotective effects by which induces anti-inflammatory actions in cerebral ischaemia,thus as a potential novel pharmacological target for ischemic stroke was regarded.Acupuncture can improve cerebral ischemia injury by inhibiting synthesis of inflammatory cytokines,downregulating expressions of inflammatory mediators and adhesion molecule,suppressing the functions of inflammatory cells.Therefore,it will be a promising orientation to sift the effective acupuncture for that can stimulate the activation of PPAR-γ,and the research of mechanism of acupuncture on anti-inflammatory reaction after cerebral ischemic by activating PPAR-γ dependent pathways.
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@#The inflammatory reaction after acute cerebral infarction can aggravate the cerebral ischemic reperfusion injury.Activation of peroxisome proliferator-activated receptors-γ(PPAR-γ) has neuroprotective effects by which induces anti-inflammatory actions in cerebral ischaemia,thus as a potential novel pharmacological target for ischemic stroke was regarded.Acupuncture can improve cerebral ischemia injury by inhibiting synthesis of inflammatory cytokines,downregulating expressions of inflammatory mediators and adhesion molecule,suppressing the functions of inflammatory cells.Therefore,it will be a promising orientation to sift the effective acupuncture for that can stimulate the activation of PPAR-γ,and the research of mechanism of acupuncture on anti-inflammatory reaction after cerebral ischemic by activating PPAR-γ dependent pathways.
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Objective To study the genotype frequencies of peroxisome proliferator-activated- receptors- gamma (PPAR?) C161→T gene and its possible association with serum lipid levels and dietary intakes. Methods PCR-PFLP method was used to detect the polymorphism of PPAR?C161→T gene of 800 adults in Shanghai. Their physical examinations,dietary survey and the levels of serum lipid profile , including TG、TC ,HDL and LDL were analyzed. Results (1) The genotype frequencies of PPAR?C161→T CC,CT and TT were 35.1 %, 47.0 % and 17.9 % respectively , which were in agreement with Hardy- Weinberg equilibrium. There was no significant difference in distribution of genotypes or allele between the hyperlipidemia group and the control group and the result was same between male and female subjects. (2)After adjusting age,gender and body mass index, the levels of TG were significantly different among three genotypes groups,the highest in CC genotype. (3) After adjusting age and gender, the intakes of protein were significantly different among three genotype groups. (4) There was significant difference in the negative correlation between energy,protein and carbohydrate and serum TG levels in hyperlipidemia group.Conclusion PPAR? C161→T gene polymorphism influenced serum TG level, while associated with protein intakes. It might contribute to the heterogeneity in TG response to dietiary intervention.