Search

• long-term exposure to fluoride during the development leads to the decrease in the expression of COX1 and COX2 in the brain. • a statistically significant increase in PGE2 concentration and COX2 immunexpression was observed in hippocampus. • exposure to fluoride in the prenatal and neonatal period may result in the development of inflammation in the brain. • Neurotoxic mechanism of fluoride may be associated with an increase in COX2 activity and in PGE2 concentration in the hippocampus. : Sixty percent of the mammalian brain is composed of lipids including arachidonic acid (AA). AA released from cell membranes is metabolised in the cyclooxygenase (COX) pathway to prostanoids – biologically active substances involved in the regulation of many processes including inflammation. It has been shown that long-term exposure to fluoride in pre and neonatal period is dangerous because this element is able to penetrate through the placenta and to cross the blood-brain barrier. Exposure to fluoride during the development affects metabolism and physiology of neurons and glia which results in the impairment of cognitive functions but the exact mechanisms of fluoride neurotoxicity are not clearly defined. : The aim of this study was to determine whether exposure to fluoride during the development affects COXes activity and the synthesis of prostanoids. : Pre- and postnatal toxicity model in Wistar rats was used. Experimental animals received 50 mg/L of NaF in drinking water ad libitum , while control animals received tap water. In cerebral cortex, hippocampus, cerebellum and striatum were measured fluoride concentration, COX1 and COX2 genes expression, immunolocalization of the enzymatic proteins and concentration of PGE2 and TXB2. : of this study showed statistically significant changes in the concentration of fluoride in brain structures between study group and control animals. Moreover, significant changes in the expression level of COX1 and COX2, and in the concentration of PGE2 and TXB2 were observed. : Exposure to fluoride in the prenatal and neonatal period result in the increase in COX2 activity and increase in PGE2 concentration in rats brain, which may lead to disturbances in central nervous system homeostasis.‬‬ [ABSTRACT FROM AUTHOR]

One very promising hypothesis of Major Depressive Disorder (MDD) pathogenesis is the gut-brain axis (GBA) dysfunction, which can lead to subclinical inflammation, hypothalamic–pituitary (HPA) axis dysregulation, and altered neural, metabolic and endocrine pathways. One of the most important parts of GBA is gut microbiota, which was shown to regulate different functions in the central nervous system (CNS). The purpose of this scoping review was to present the current state of research on the relationship between MDD and gut microbiota and extract causal relationships. Further, we presented the relationship between the use of probiotics and antidepressants, and the microbiota changes. We evaluated the data from 27 studies aimed to investigate microbial fingerprints associated with depression phenotype. We abstracted data from 16 and 11 observational and clinical studies, respectively; the latter was divided into trials evaluating the effects of psychiatric treatment (n = 3) and probiotic intervention (n = 9) on the microbiome composition and function. In total, the data of 1187 individuals from observational studies were assessed. In clinical studies, there were 490 individuals analysed. In probiotic studies, 220 and 218 patients with MDD received the intervention and non-active study comparator, respectively. It was concluded that in MDD, the microbiota is altered. Although the mechanism of this relationship is unknown, we hypothesise that the taxonomic changes observed in patients with MDD are associated with bacterial proinflammatory activity, reduced Schort Chain Fatty Acids (SCFAs) production, impaired intestinal barrier integrity and neurotransmitter production, impaired carbohydrates, tryptophane and glutamate metabolic pathways. However, only in few publications this effect was confirmed by metagenomic, metabolomic analysis, or by assessment of immunological parameters or intestinal permeability markers. Future research requires standardisation process starting from patient selection, material collection, DNA sequencing, and bioinformatic analysis. We did not observe whether antidepressive medications influence on gut microbiota, but the use of psychobiotics in patients with MDD has great prospects; however, this procedure requires also standardisation and thorough mechanistic research. The microbiota should be treated as an environmental element, which considers the aetiopathogenesis of the disease and provides new possibilities for monitoring and treating patients with MDD. • The gut microbiota is altered in patients with MDD. • The microbial taxonomic changes are associated with MDD pathomechanism. • Causative role of gut microbiota in MDD has not been proven. • Antidepression medications did not affect gut microbiota. • Psychobiotics use in patients with MDD has great prospects. [ABSTRACT FROM AUTHOR]

For decades, metformin has been the drug of first choice in the management of type 2 diabetes. However, approximately 2–13% of patients do not tolerate metformin due to gastrointestinal (GI) side effects. Since metformin influences the gut microbiota, we hypothesized that a multi-strain probiotics supplementation would mitigate the gastrointestinal symptoms associated with metformin usage. This randomized, double-blind, placebo-controlled, single-center, cross-over trial (ProGasMet study) assessed the efficacy of a multi-strain probiotic in 37 patients with metformin intolerance. Patients were randomly allocated (1:1) to receive probiotic (PRO-PLA) or placebo (PLA-PRO) at baseline and, after 12 weeks (period 1), they crossed-over to the other treatment arm (period 2). The primary outcome was the reduction of GI adverse events of metformin. 37 out of 82 eligible patients were enrolled in the final analysis of whom 35 completed the 32 weeks study period and 2 patients resigned at visit 5. Regardless of the treatment arm allocation, while on probiotic supplementation, there was a significant reduction of incidence (for the probiotic period in PRO-PLA/PLA-PRO: P = 0.017/P = 0.054), quantity and severity of nausea (P = 0.016/P = 0.024), frequency (P = 0.009/P = 0.015) and severity (P = 0.019/P = 0.005) of abdominal bloating/pain as well as significant improvement in self-assessed tolerability of metformin (P < 0.01/P = 0.005). Moreover, there was significant reduction of incidence of diarrhea while on probiotic supplementation in PRO-PLA treatment arm (P = 0.036). A multi-strain probiotic diminishes the incidence of gastrointestinal adverse effects in patients with type 2 diabetes and metformin intolerance. [ABSTRACT FROM AUTHOR]

Low nephron number has been recognised as an important cardiovascular risk factor and recently a strong correlation between renal mass and nephron number has been demonstrated in newborns. The aim of this study was to investigate individual, as well as combined, effects of common variants of genes which encode for major components of the renin–angiotensin system ( REN G10601A, AGT G(− 6)A, ACE I/D, AGTR1 A1166C) on kidney size in healthy, full-term newborns. A significant additive main effect of the ACE I/D polymorphism, as well as an additive-by-additive interaction between AGT G(− 6)A and AGTR1 A1166C variants, were found. The variance attributed to the epistatic effect was 27.9 ml 2 /m 4 , which accounted for 73.8% of the interaction variance (37.8 ml 2 /m 4 ), 66.4% of the genetic variance (42.0 ml 2 /m 4 ) and 4.4% to the total phenotypic variance (628 ml 2 /m 4 ). No other statistically significant main or epistatic effects were detected. Our results highlight the importance of considering gene–gene interactions as part of the genetic architecture of congenital nephron number, even when the loci do not show significant single locus effects. Unravelling the genetic determinants of low nephron number, along with early molecular screening, may well help to identify children at risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Glucocorticoids and their receptors are involved in inflammation and many cardiovascular risk factors. We examined associations of Tth111I, N363S and ER22/23EK NR3C1 gene polymorphisms and haplotypes, with coronary artery disease (CAD), severity of CAD (single-vessel vs. multivessel disease) and risk factors. Methods: Three hundred ten individuals were submitted to coronary angiography. Selected genotypes were determined by PCR-RFLP. Results: Carriers of the Tth111I allele T were found significantly less often in the CAD compared with the non-CAD group (49.7 vs. 64.6%, p = 0.013); this association was similar for TGA haplotype carriers (49.2 vs. 62.8%, p = 0.024); the T allele was more frequent in females (66.3 vs. 51.1%, p = 0.020) and its presence was associated with higher levels of HDL-cholesterol (46.6 ± 12.7 vs. 43.5 ± 10.1 mg/dL for T-carriers vs. noncarriers, p = 0.045). The TT genotype proved to be less common in MVD than SVD (5.9 vs. 14.1%, p = 0.075). The 363S allele was significantly associated with diabetes mellitus (DM) (24.4 vs. 10.9%; carriers in DM and non-DM subjects, respectively, p = 0.027), the TT genotype or TGA/TGA diplotype (in which the 363S allele was absent) were less frequent in DM than in non-DM subjects (p = 0.012 for Tth111I-TT and p = 0.020 for TGA/TGA diplotype). No significant associations between CAD and N363S or ER22/23EK polymorphisms were found. Conclusions: Our results suggest that the Tth111I NR3C1 polymorphism may play a protective role in the development of CAD, and homozygous TT in development of MVD. The N363S polymorphisms may contribute to the development of diabetes in the Polish population. [Copyright &y& Elsevier]

Chronic inflammatory conditions resulting from elevated levels of circulating proinflammatory mediators are common in the elderly. The aim of the paper was to analyze the balance between proinflammatory and anti-inflammatory markers in longevous individuals. The study was conducted in persons aged >90 years old, residents of Poland living either at home or staying at residential care facilities. The study included 90 persons (69 women and 21 men) aged between 90 and 103 years. Persons with abnormal CRP presented with a statistical tendency toward higher fibrinogen and lower IL10 and IL-1α levels compared to patients in whom CRP level was within the normal range. IL-6 concentration predicted abnormality within CRP. Inflammation in persons above the age of 90 years old might be linked to abnormal fibrinogen and IL-6 levels. • Fibrinogen level decline with age. • Persons with abnormal CRP (>5) have tendency toward higher fibrinogen and lower IL-10 and IL-1α levels. • CRP abnormality might be predicted by IL-6 concentration. [ABSTRACT FROM AUTHOR]

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5–20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = −0.70, q = 0.016), Clostridia (r = −0.71, q = 0.026), Firmicutes (r = −0.67. q = 0.032), and the RF32 order (r = −0.70, p = 0.016) in the Alphaproteobacteria (r = −0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings. • Gut microbiota is associated with a severity of depressive symptoms. • Microbiota changes are not predictive of clinical improvement in patients with MDD. • Gut integrity and inflammatory markers are associated with symptom severity and response to treatment of patients with depressive episodes. [ABSTRACT FROM AUTHOR]