Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ12,14PGJ2 a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ12,14PGJ2 production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ2 and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment. 相似文献
Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.
Methods
Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.
Results
In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.
Conclusions
Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection. 相似文献
Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies. 相似文献
Context The root of Helicteres angustifolia L. (Sterculiaceae) has been used as folk herbal drug to treat cancer, bacterial infections, inflammatory, and flu in China. However, there is no report on its antidiabetic activity.Objective This study evaluates the antidiabetic activity of ethanol extract from H. angustifolia root.Materials and methods The promoting effect of H. angustifolia root ethanol extract (25, 50, and 100 μg/mL) on glucose uptake was evaluated using HepG2 cell, differentiated C2C12 myotubes, and differentiated 3T3-L1 adipocytes. The antidiabetic activity of the extract was assessed in vivo using STZ-induced diabetic rats by orally administration of the extract (200 and 400?mg/kg b.w.) once per day for 28 d. Blood glucose, TG, TC, TP, HDL-C, UA, BUN, AST, ALT, insulin, and HOMA-IR were analyzed.Results The results showed that the extract increased glucose uptake in C2C12 myotubes and 3T3-L1 adipocytes with an IC50 value of 79.95 and 135.96 μg/mL, respectively. And about 12%, 19%, and 10% (p < 0.05) in HepG2 cells when compared with the control at the concentration of 25, 50, and 100 μg/mL, respectively. After 28 days’ treatment with the extract, significant reduction was observed in blood glucose, HOMA-IR, TC, TG, UA, BUN, AST, and ALT levels, while the levels of TP and HDL cholesterol increased.Discussion and conclusion These results suggest that H. angustifolia root ethanol extract possess potent antidiabetic activity, which is the first report on antidiabetic activity of this plant. 相似文献
Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.
Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.
Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk. 相似文献
Interneurons immunoreactive for vasoactive intestinal polypeptide (VIP) are integral elements of columnar organization patterns in the rat cerebral cortex. By application of the sensitive mirror technique, the co-localization of VIP with the classical inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT), was investigated in neocortical neurons. Furthermore, the frequency of co-localization of ChAT with GABA was determined. In a sample of 118 VIP-immunoreactive neurons, mostly from the primary somatosensory cortex, it was demonstrated that virtually all of them reveal immunoreactivity for GABA and, therefore, are to be GABAergic. Moreover, 34% of mostly bipolar, VIP-positive neurons contained ChAT and are, thus, supposedly cholinergic as well. Co-localization of VIP and ChAT varied according to cortical laminae. Finally, 88% of a total of 60 ChAT-immunoreactive neurons were also immunostained for GABA. It is concluded that almost all VIP-immunoreactive neurons and most of the cholinergic neurons in rat neocortex represent partly overlapping subpopulations of inhibitory interneurons utilizing GABA. 相似文献
While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiatedIGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onIGABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onIGABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA. 相似文献