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OBJECTIVES: Depression during pregnancy negatively affects fetal development. Fluoxetine as a selective serotonin reuptake inhibitor (SSRIs) is used for treatment of gestational depression. This study is trying to determine the effects of fluoxetine on the renal, heart and lung development. MATERIALS AND METHODS: Fifteen pregnant rats were treated with fluoxetine at 7 mg/kg from days 0 to 21 of gestation. Immediately after born, heart and kidney samples were evaluated for genes expression and histological assessment. Lung sample were fixed for immunohistochemical study. RESULTS: The gene expression of BMP7 and WNT4 were reduced in the kidney of fluoxetine-treated group (P-value<0.05), but in the heart of both groups no significant difference was found in gene expression (P-value>0.05). Histological assessment showed that the glomeruli of the kidneys in treated group are more primordial compared to control. There was a developmental deficiency in Bowman's capsule, and the capsular space was not clear. The arrangements of the filaments, the position of the nucleus and cells morphology were normal in the hearts of both groups. Immunohistochemical analysis demonstrated that in the fluoxetine-exposed group HoxB5 is more expressed in the mesenchymal cells, but in the control group the expression is limited to alveolar cells. CONCLUSION: According to developmental changes in kidney, heart and lung, fluoxetine affects neonatal growth during pregnancy, which may lead to delay of some organs growth. So, it is essential to survey the roles of antidepressant drugs on fatal and neonatal development during pregnancy.
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OBJECTIVES: Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. RESULTS: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. CONCLUSION: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.
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Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke.
Asunto(s)
Acrilamidas/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Interleucina-10/sangre , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/sangre , Canales Catiónicos TRPV/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Acrilamidas/farmacología , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Modelos Animales de Enfermedad , Masculino , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar , Accidente Cerebrovascular/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Inflammation and infectious agents such as Chlamydia pneumoniae have been associated with cardiovascular disease. OBJECTIVE: To evaluate the serum high sensitivity C-reactive protein (hs-CRP) and antibodies against Chlamydia pneumoniae and Chlamydial heat shock protein-60 (Cp-HSP-60) in patients with ischemic heart disease (IHD). METHODS: 62 patients with IHD having either acute myocardial infarction (AMI; n=31) or unstable angina (UA; n=31) and 31 sex- and age- matched healthy subjects as a control group were enrolled in this study. Serum samples of participants were tested for the presence of hs-CRP and antibodies against C. pneumoniae and Cp-HSP-60 using ELISA method. RESULTS: The seroprevalence of anti-C. pneumoniae antibody in AMI group (93.5%) or UA group (90.3%) was significantly higher than the control group (61.3%; p<0.001). The seroprevalence of anti-Cp-HSP60 IgG was 22.6% in healthy subjects with mean end titer of 43.1+/-6.32. The seropositive rates of anti-Cp-HSP60 were 48.4%, 54.8% and 51.6% in AMI, UA and the overall IHD groups with mean end titers of 94+/-22.86, 113.8+/-24.25 and 103.9+/-16.57, respectively. Both the seroprevalence and the mean titer of anti-Cp-HSP60 in patients groups were significantly higher than those observed in the control group (p<0.04 and p<0.03, respectively). Moreover, the mean serum hs-CRP levels was significantly higher in the IHD group as compared to the control group (21.6 microg/ml+/-3.73 vs 2.5 microg/ml+/-0.52; p<0.00001). The mean serum hs-CRP levels of AMI (30.3 microg/ml+/-6.07) or UA (12.9 microg/ml+/-3.85) groups were also significantly higher than those observed in the control group (p<0.00001 and p<0.001, respectively). Furthermore, the difference of the mean serum hs-CRP levels between AMI and UA groups was also significant (p<0.02). CONCLUSIONS: These results showed that the seroprevalence of antibodies against C. pneumoniae and Cp-HSP-60 and the serum levels of hs-CRP and anti-Cp-HSP60 IgG were higher in patients with IHD.