The role of omega-3 fatty acids in developmental psychopathology : A systematic review on early psychosis, autism, and ADHD

In this systematic review, we will consider and debate studies that have explored the effects of omega-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of omega-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far

CYP3A5 ALLELE A IS ASSOCIATED WITH HIGHER BLOOD PRESSURE VALUES IN YOUNG PATIENTS WITH KIDNEY TRANSPLANT ON CALCINEURIN INHIBITORS

The second part of this in-depth clinical review focuses on drugs used in the prevention of AKI in the patient at risk and/or in the management of the patient with incipient AKI. Among the drugs used to maintain a normal renal perfusion pressure, norepinephrine and vasopressin are most commonly used in hypotensive critically ill patients. The most recent RCT did not find a difference between low-dose vasopressin plus norepinephrine and norepinephrine alone in patients with septic shock, suggesting that either approach is reasonable. However, vasopressin may be beneficial in the less severe septic shock subgroup. Loop diuretics may convert an oliguric into a non-oliguric form of AKI that may allow easier fluid and/or nutritional support of the patient. Volume overload in AKI patients is common and diuretics may provide symptomatic benefit in that situation. However, loop diuretics are neither associated with improved survival, nor with better recovery of renal function in AKI. Among the renal vasodilating drugs, the routine administration of dopamine to patients for the prevention of AKI or incipient AKI is no longer justified. On the other hand, although additional studies may be warranted, fenoldopam may appear to be a likely candidate for the prevention of AKI, particularly in critically ill patients, if the positive results obtained in some recent studies are confirmed. Trials with natriuretic peptides were in general inconclusive but despite the fact that nesiritide is currently approved by the FDA only for the treatment of heart failure, this vasodilator may in the future play a role in the prevention of AKI, particularly in association with heart failure and cardiac surgery. The most recent trials seem to confirm a potential positive preventive effect of N-acetylcysteine (NAC), particularly in contrast-induced nephropathy (CIN), NAC alone should never take the place of IV hydration in patients at risk for CIN; fluids likely have a more substantiated benefit. At present, initiation of statin therapy for the prevention of CIN cannot be recommended, but these drugs should not be stopped before a radiological intervention in patients on chronic statin therapy. Rasburicase is very effective in the prevention of acute tumour lysis syndrome. Erythropoietin (EPO) has tissue-protective effects and prevents tissue damage during ischaemia and inflammation, and currently trials are performed with EPO in the prevention of AKI post-cardiac surgery, CIN and post-kidney transplantation. From this review it becomes clear that single-drug therapy will probably never be effective in the prevention of AKI and that multiple agents may be needed to improve outcomes. In addition, drugs should be administered early during the course of the disease

The polyunsaturated fatty acid balance in kidney health and disease : A review

Epidemiological studies show that circulating polyunsaturated fatty acids contribute to preserve renal function. In renal disease states there is generally a lack of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) as measured in biological samples, but despite intense research for more than 30 years, it is still unclear how and to what extent their supplementation would benefit kidney disorders. Studies evaluating the n-6 series and the kidney are less frequent. The last compilation of clinical trials with n-3 LCPUFA supplements focusing on renal function and damage dates back to 2012. We here discuss n-3 and n-6 fatty acids in relation to the kidney summarizing single- and double blind randomized controlled trials performed between 2012 and 2016. Nine were sub-studies/post-hoc analyses of previous parent trials. Twelve out of the twenty trials reported on fatty acid profile or fatty acid species. Factors that may explain inconsistent results obtained after supplementation with the n-3 LCPUFA EPA and DHA in kidney disease are discussed such as baseline levels determining response, drug interaction. The need of evaluating fatty acid status before and after intervention is emphasized, to match changes in outcome measure with changes of any fatty acid potentially involved

Relationship between mRNA expression levels of CYP3A4, CYP3A5 and SXR in peripheral mononuclear blood cells and aging in young kidney transplant recipients under tacrolimus treatment

Aim: The activity of several key enzymes involved in the metabolism of many drugs is subject to change closely related to the age of patients. This possibility must also be considered in the case of tacrolimus, the most important calcineurins inhibitor, which is widely used in pediatric kidney transplantation. As well as in the liver and intestine, some of the enzymes involved in the metabolism of tacrolimus were also isolated in the peripheral blood mononuclear cells (PBMCs), where also appear to play an important regulatory action. Therefore, the influence of some external factors on the expression of specific mRNA can be determined noninvasively. Patients & methods: The correlation between the levels of mRNA specific for key enzymes SXR, CYP3A and ABCB1 involved in the metabolism of tacrolimus was evaluated in PBMCs obtained from a selected population of 29 young kidney transplant recipients. A possible correlation between the expression of these specific mRNAs and tacrolimus pharmacokinetics was also investigated. Results: The patients' age and their blood concentrations of SXR mRNA were directly correlated with the expression of CYP3A4, CYP3A5 mRNAs, but not of ABCB1 mRNA in the PBMCs. tacrolimus-normalized daily dose was strongly correlated with patient's age and multivariable regression indicates the CYP3A4-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio. Conclusion: Aging and SXR mRNA significantly affect the expression of CYP3A4- and CYP3A5-specific mRNA as measured by their concentration in PBMC

Fatty acids in nephrotic syndrome and chronic kidney disease

The role of fatty acids (FAs) in inflammation and in the related chronic diseases has been demonstrated. However, there is a lack of consistent and agreed knowledge about the role of FA profile and renal physiology and pathology, most articles focusing on the effect of polyunsaturated FAs supplementation, without considering the impact of basal FA metabolism on the efficacy of the supplementation. Here, we have summarized the specific literature concerning the assessment of circulating FA in 2 renal diseases, namely nephrotic syndrome and chronic kidney disease, also under hemodialytic treatment, and have received the most significant contributions in the last years. The effects of changes of FA profile and metabolism and the possible involvement of polyunsaturated FA metabolites in raising and modulating inflammation are discussed