In the last 100 years major depression has increased worldwide. In this study we provided coconut fat (CF, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined lipid brain profile and the possible effect of FO as antidepressant agent in the offspring in adulthood (F1). Rats were submitted to forced swimming test, elevated plus maze, Morris water maze and open field. Peroxidation rate in the cerebral cortex and hippocampus were measured. Docosahexaenoic acid (DHA) concentration in dam's milk, eicosapentaenoic acid (EPA) and DHA concentration in hippocampus and cerebral cortex from F1 rats FO supplemented increased significantly when compared to control (C) and CF rats. Arachidonic acid/EPA ratio in the cerebral cortex and hippocampus decreased in rats submitted to forced swimming test. Peroxidation rate were not different between the groups. Immobility time in the forced swimming test in FO group was reduced (p < 0.01) when compared to C and CF rats. We conclude that lifelong intake of FO was able to induce an antidepressant effect with EPA and DHA concentration increased in the cerebral cortex and hippocampus.

Background and Aims Uremic toxins (UTs) accumulate in the circulation of patients with chronic kidney disease (CKD), contributing to poor outcomes. One of the main objectives of renal replacement therapies is the removal of UTs, and while HD is restricted to the clearance of low molecular weight UTs, hemodiafiltration (HDF) adds efficiency to the removal of medium molecular weight UTs through the association of diffusion and convection methods. Metabolomic analysis from nuclear magnetic resonance (NMR) spectra offers efficient data about metabolites profile, indicating the main features of HDF, and possibly highlighting the positive effects of this modality. Thus, the aim of the present study is to evaluate the profile of metabolites in the circulation of a cohort of patients undergoing HDF. Method From 97 individuals participating in the HDF arm of a randomized control trial (ClinicalTrials.gov Identifier: NCT02787161), we randomly (using Python language; NumPy library) selected 6 patients (mean age 49, 6 males, 44% diabetics, average duration of 245 minutes, blood flow of 400 mL/min, target convective volume of 22 L per treatment). Patient’s serum samples were collected in the beginning of the study (baseline) and 6 months. The samples were prepared with deuterium oxide, sodium trimethylsilylpropanesulfonate as internal standard (ð=0.0 ppm), and further submitted to 1H NMR spectra recorded with Bruker 600 MHz AVANCE III spectrometer in order to identify the patient’s metabolomic profile. Data was evaluated with t-test and results were then compared with the Human Metabolome Database (HMDB) for descending order of the Jaccard similarity score. Results A total of 50 metabolites were investigated. Interestingly, 2 metabolites were significantly (P&lt;0.05) reduced in the serum after 6 months compared to baseline, acetate (3.3 ± 0.1) % and dimethylglyoxal (7.6 ± 0.1) % (Figure 1). In order to confirm the presence of these metabolites in human serum, further studies will be conducted with 2D 1H-13C-HSQCed NMR. Conclusion We observed a reduction of acetate and dimethylglyoxal levels after six months of HDF treatment, in comparison to baseline, most likely as a consequence of the increase in clearance of these molecules. Hypothetically these changes in solute removal could explain the positive effects of HDF on clinical outcomes, and further studies should address this potential benefit of the modality.

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BACKGROUND AND AIMS Patients with chronic kidney disease (CKD) accumulate uraemic toxins (UTs). When compared to other conventional dialysis modalities, high volume haemodiafiltration (HDF) improves the removal of medium and low molecular weight UTs. The present study is a post-hoc analysis comparing the metabolomic profile in serum from patients under high flux HD (hf-HD) and HDF in HDFIT, a multicentric randomized controlled trial (RCT). METHOD Random (pre- and post-dialysis) samples from nine patients in a study arm were selected at baseline and at the end of the follow-up. To compare the samples, 26 possibly matching metabolites were identified by a t-test among the four groups using 1-H nuclear magnetic resonance (NMR). To evaluate the comparison between the modalities in a single treatment session, the clearance rates (CRs) of each metabolite were calculated based on pre- and post-dialysis samples. In addition, to evaluate the effect of UTs removal during the trial follow-up period, the pre-dialysis metabolite concentrations both at the baseline and 6 months were compared with the two arms of the study. RESULTS Evaluating the concentrations of the metabolites during the follow-up period for each study arm, it was possible to assess the effects of UTs removal during the study for each modality. The comparison of the intensity of the peaks identified 26 possible metabolites that differentiated hf-HD and HDF in this timeframe. The correlation (see Figure 1a) then suggested that the peak integrals of 16 of these metabolites increased from baseline to 6 months in the hf-HD, but not in the HDF arm. Amongst the metabolites, several are involved in important metabolic pathways, such as the metabolisms of phenylalanine and the biosynthesis of phenylalanine, tyrosine and tryptophan, which both relate to UTs and the development of cardiovascular diseases. The peak integration relative to glycolic acid was significantly higher (P&lt;.05) at 6 months than at baseline (see Figure 1b) in the hf-HD than in the HDF arm, which has been related to an increased number of renal failure and of renal insufficiency cases [1,2], as well as it related to liver damage [3]. CONCLUSION The concentrations of metabolites related both to CKD and associated pathologies were stable in the HDF arm only during the follow-up period, suggesting enhancement of the long-term stability by this method. In the hf-HD long-term follow-up, the relative increase in the glycolic acid peak integration area, which is related to the metabolite concentration, has also previously been linked to an increased number of renal failures and renal insufficiency cases and to liver damages.