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The role of acetyl-L-carnitine (LAC) in the treatment of mental disorders


Introduction: Currently, there are no fully reliable biomarkers to identify individuals suffering from depression, and conventional antidepressant treatment has its limitations. The potential influence of acetyl-L-carnitine (LAC) on the treatment of mental disorders, including depressive disorders, was noted already in the 1980s.

Goal and method: The literature on the role of LAC in the treatment of mental disorders, in particular depressive disorders, was reviewed using the Google Scholar and Pub Med databases. Two lines of research were considered:

1. the role of LAC in the therapy of various mental disorders and

2. the role of LAC in the treatment of depression and dysthymia

Conclusions: Because LAC is safe to use and has a very good tolerance profile, authors have explored its role in the treatment of many neurological and psychiatric diseases. There are studies showing that LAC supplementation has a positive effect on ADHD treatment outcomes in boys diagnosed with fragile X syndrome and plays a role in the treatment of dementia. Research has also been conducted on the impact of LAC on the treatment of depressive and dysthymic disorders. Positive outcomes of such therapy have been reported. An important correlation has been observed between LAC concentrations and the severity and onset of depressive symptoms. For instance, reduced levels of LAC have been found in people with treatment-refractory depression. It has also been proposed that LAC could decrease vulnerability to depression.

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Self-image and selected clinical variables in the context of childhood abuse in subjects with alcohol dependence


Objective: The objective of the study was to determine the differences in selected clinical variables and self-image in people with alcohol dependence differing in severity of physical, emotional and sexual abuse experienced before age 18.

Method: The study included 90 people with alcohol dependence. The following research tools were used: Early Trauma Inventory (ETI), Adjective Check List (ACL), MAST, SAAD, and a questionnaire designed by the authors. In order to identify groups with varying indices of physical, emotional and sexual childhood abuse, a cluster analysis method was used.

Results: Two groups of subjects with alcohol dependence were identified: Group 1 with high indices of physical, emotional and sexual childhood abuse and Group 2 with low indices. In terms of self-image the subjects in Group 1 compared to subjects in Group 2 were characterized by a lower self-esteem, self-acceptance, resistance to stress, less intense needs for achievement, endurance, order, nurturing others, interaction with opposite-sex partners, subordinations but more intense need for change. The age of alcohol use initiation and the onset of regular alcohol drinking was statistically significantly lower in Group 1. The severity of alcohol dependence was significantly lower in Group 2. The subjects in Group 1 significantly more frequently confirmed the history of a hereditary predisposition to alcohol dependence, suicidal ideation, suicide attempts and self-harm.

Discussion: The obtained results closely correspond to the data available in the literature.

Conclusions: An assessment of exposure to various forms of childhood abuse appears to be an indispensable element of collecting medical history of people with alcohol dependence.

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c-Fos and FosB/ΔFosB colocalizations in selected forebrain structures after olanzapine, amisulpride, aripiprazole, and quetiapine single administration in rats preconditioned by two different mild stressors sequences


Objective. Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell).

Methods. The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor – handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles.

Results. The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated.

Conclusion. The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.

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Chronic exposure of adult male Wistar rats to bisphenol A causes testicular oxidative stress: Role of gallic acid


Objectives. Bisphenol A (BPA) has been reported that among other male reproductive dys-functions, it can cause marked estrogenic effects including alteration in serum hormones as well as testicular lesions in exposed animals. This work sought to study the role of gallic acid (GA), a known antioxidant, on the BPA-induced testicular oxidative stress in adult male Wistar rats using serum hormone analysis, histopathology, and biochemical assays.

Methods. Adult male rats were divided into four groups (n=10) including control (0.2 ml of corn oil), GA (20 mg/kg/day), BPA (10 mg/kg/day), BPA+GA (BPA, 10 mg/kg/day + GA, 20 mg/kg/day). All medications were given by oral gavage for 45 consecutive days. The body and testicular weights were measured. Blood and organ samples were collected for the serum hormonal assay: testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL), and tissue biochemistry analysis: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA), hydrogen peroxide (H2O2), respectively.

Results. The BPA-treated rats showed significant reduction in the gonadosomatic index. BPA also caused significant decrease in the levels of the serum testosterone and prolactin. Furthermore, BPA induced testicular oxidative stress by decreasing the activities of antioxidant enzymes and increasing reactive oxygen species. However, co-treatment with GA protected against these alterations.

Conclusion. Findings from the present study confirmed the previously reported data and show that the ability of GA, as a potent antioxidant, may protect against BPA-induced alterations in the male reproductive function. Hence, GA protects against testicular oxidative stress in adult male Wistar rats following chronic exposure to BPA.

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May C-peptide index be a new marker to predict proteinuria in anemic patients with type 2 diabetes mellitus?


Objective. C-peptide is a reliable marker of beta cell reserve and is associated with diabetic complications. Furthermore, HbA1c level is associated with micro- and macro-vascular complications in diabetic patients. HbA1c measurement of diabetic patients with anemia may be misleading because HbA1c is calculated in percent by taking reference to hemoglobin measurements. We hypothesized that there may be a relationship between C-peptide index (CPI) and proteinuria in anemic patients with type 2 diabetes mellitus (T2DM). Therefore, the aim of the present study was to investigate the association between C-peptide levels and CPI in anemic patients with T2DM and proteinuria.

Methods. The patients over 18 years of age with T2DM whose C-peptide levels were analyzed in Endocrinology and Internal medicine clinics between 2014 and 2018 with normal kidney functions (GFR>60 ml/min) and who do not use any insulin secretagogue oral antidiabetic agent (i.e. sulfonylurea) were enrolled into the study.

Results. Hemoglobin levels were present in 342 patients with T2DM. Among these 342 cases, 258 (75.4%) were non-anemic whereas 84 (24.6%) were anemic. The median DM duration of the anemic group was statistically significantly higher in T2DM (p=0.003). There was no statistically significant difference found in proteinuria prevalence between non-anemic and anemic patient groups (p=0.690 and p=0.748, respectively). Anemic T2DM cases were corrected according to the age, gender, and duration of DM. C-peptide and CPI levels were not statistically significant to predict proteinuria (p=0.449 and p=0.465, respectively).

Conclusion. The present study sheds light to the association between C-peptide, CPI, and anemic diabetic nephropathy in T2DM patients and indicates that further prospective studies are needed to clarify this issue.

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Possible ameliorating effects of Glycyrrhiza Glabra (Licorice) on the sperm parameters in rats under high fat diet


Objectives. Adverse effects of obesity, which is caused by an imbalance between the energy intake and expenditure, on the male reproductive system have been reported. Considering the anti-obesity effect of Glycyrrhiza Glabra (GC), we conducted this study to elucidate whether it can ameliorate the sperm parameters.

Methods. In this experimental study, male Wistar rats of 6–8 weeks old were divided into four groups: control, high fat diet (HFD), GC50 (HFD plus 50 mg/kg GC extract), and GC100 (HFD plus 100 mg/kg GC extract). During the 16 weeks of the study course, the rats consumed the extract through gavage, daily. Body mass index (BMI), body weight gain, serum lipid profile, leptin concentration, and sperm parameters were investigated. Data were analyzed by one-way analysis of variance (ANOVA) (post hoc Tukey) to express the significance of mean differences of variables between groups, and linear regression test was used to express the correlation model of variables. Both tests were performed by SPSS software; p≤0.05 was considered significant.

Results. BMI was significantly decreased by the GC50 and GC100 groups compared to HFD group. GC50 group considerably decreased leptin level compared to HFD group. A significant positive correlation between leptin and triglyceride levels was evident. GC50 and GC100 extensively increased the total sperm motility and ameliorated the sperm abnormal morphology and count compared to HFD group.

Conclusion. Glycyrrhiza Glabra extract may exert its ameliorating effects on the sperm parameters through its anti-obesity impact. Both doses of the extract were effective, however, the GC100 was more effective in improving the sperm parameters.

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Relationship between the night shift work and thyroid disorders: A systematic review and meta-analysis


Objectives. The night shift workers were reported to have health consequences, ranging from mild, as cluster headache, to severe, as heart attacks and hormonal irregularities. This study is aimed to perform a systematic review and meta-analyze of the association between the night shift work and the thyroid disorders.

Methods. We comprehensively searched eight databases, including PubMed and Google Scholar for the relevant articles. This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement.

Results. We finally included six papers involving 4074 participants. Four papers were eligible for meta-analysis involving 1864 night shift workers and 2017 day shift workers. We against found that thyroid stimulating hormone (TSH) is significantly higher in the night shift group compared to the day shift group.

Conclusions. The higher TSH among the night shift workers is attributed to disruption of the circadian rhythm and sleep/wake cycle, with subsequent eating disorders. We proposed that more attention should be paid to the working pattern and the related health consequences.

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The role of adipose tissue secretion in the creation and pain level in osteoarthritis


Objectives. With increasing evidence regarding the metabolic basis of osteoarthritis (OA), we studied the relationship between adipose tissue and OA.

Methods. This study is part of an OA registry in the eastern part of Fars Province, Iran. Overall, 150 patients with OA and 300 sex matched individuals were selected as a control group. They were compared regarding adipokine concentration (leptin, adiponectin, resistin and visfatin), anthropo-metric indices, the Western Ontario and McMaster universities arthritis index score (WOMAC).

Results. All adipokine levels were higher among OA patients (p<0.001). After adjusting for age, sex, and body mass index (BMI), adipokines showed a significant and positive association with OA (B: 14.12, B: 9.92, B: 24.71 and B: 12.29 for leptin, adiponectin, visfatin, and resistin, respectively; p<0.001). Except the adiponectin that had a negative relationship with BMI in the OA group (r=–0.570, p<0.001), other adipokines had positive relationships with BMI (r=0.781, p<0.001; r=0.530, p<0.001; r=0.549, p<0.001 for leptin, visfatin, and resistin, respectively). Only leptin and adiponectin levels were correlated with pain (B: 0.045, –0.079 and p<0.05).

Conclusion. The present study shows that aside to the well-known role of mechanical stress in OA pathogenesis (weight load), leptin, adiponectin, visfatin, and resistin, which represent the adi-pose tissue independent on the weight, may play a chemical role in OA pathogenesis. In addition, leptin and adiponectin may be involved in the pain levels among patients with OA.

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Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells


Objective. The aim of the present study was to investigate the effect of adipokine NAMPT (nicotinamide phosphoribosyltransferase) silencing on the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other proliferation related proteins in U87 glioma cells for evaluation of the possible significance of this adipokine in intergenic interactions.

Methods. The silencing of NAMPT mRNA was introduced by NAMPT specific siRNA. The expression level of NAMPT, IGFBP3, IRS1, HK2, PER2, CLU, BNIP3, TPD52, GADD45A, and MKI67 genes was studied in U87 glioma cells by quantitative polymerase chain reaction. Anti-visfatin antibody was used for detection of NAMPT protein by Western-blot analysis.

Results. It was shown that the silencing of NAMPT mRNA led to a strong down-regulation of NAMPT protein and significant modification of the expression of IRS1, IGFBP3, CLU, HK2, BNIP3, and MKI67 genes in glioma cells and a strong up-regulation of IGFBP3 and IRS1 and down-regulation of CLU, BNIP3, HK2, and MKI67 gene expressions. At the same time, no significant changes were detected in the expression of GADD45A, PER2, and TPD52 genes in glioma cells treated by siRNA specific to NAMPT. Furthermore, the silencing of NAMPT mRNA suppressed the glioma cell proliferation.

Conclusions. Results of this investigation demonstrated that silencing of NAMPT mRNA with corresponding down-regulation of NAMPT protein and suppression of the glioma cell proliferation affected the expression of IRS1 gene as well as many other genes encoding the proliferation related proteins. It is possible that dysregulation of most of the studied genes in glioma cells after silencing of NAMPT is reflected by a complex of intergenic interactions and that NAMPT is an important factor for genome stability and regulatory mechanisms contributing to the control of glioma cell metabolism and proliferation.

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The use of ex vivo ovary culture for assessment of alterations in steroidogenesis following neonatal exposure to poly(ethylene glycol)-block-polylactide methyl ether or titanium dioxide nanoparticles in Wistar rats


Objectives. Rapid development and widespread application of different types of nanoparticles (NPs) may result in increased exposure of humans and animals to NPs. Recently, reproductive toxicity due to NP exposure has become a major component of risk assessment. Current data have suggested that NPs may pose adverse effects on male and female reproductive health by altering normal testis and ovarian structure, and sex hormone levels. To detect possible alterations in steroidogenesis in adult and infantile rats following neonatal exposure to polymeric poly(ethylene glycol)-block-polylactide methyl ether (PEG-b-PLA) or titanium dioxide (TiO2) NPs, whole ovary cultures were used.

Methods. Newborn female Wistar rats were intraperitoneally (i.p.) injected daily with two different doses of PEG-b-PLA NPs (20 and 40 mg/kg body weight, b.w.) or TiO2 NPs (1% LD50 TiO2=59.2 µg/kg b.w. and 10% LD50 TiO2=592 µg/kg b.w.) from postnatal day 4 (PND 4) to PND 7. The ovaries were collected on PND73 and PND15 of PEG-b-PLA- and TiO2 NP-treated rats, respectively, and their corresponding control animals. Minced ovaries were cultured in vitro in the absence (basal conditions) or presence of gonadotropins (follicle-stimulating hormone, FSH and luteinizing hormone, LH) and insulin-like growth factor-1 (IGF-1) (stimulated conditions) for 6 days. At indicated time intervals, culture media were collected for steroid hormone (progesterone, estradiol) analysis by specific radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) kits.

Results. Basal progesterone and estradiol secretion by ovaries from adult rats (PND73) were significantly decreased (p<0.01) in both PEG-b-PLA-treated groups after 3 days and 1 day of ex vivo ovary culture, respectively, compared with control group. With the presence of FSH/LH and IGF-1 in the culture medium, progesterone and estradiol production significantly increased (p<0.001) compared to basal levels. Stimulated progesterone production was significantly decreased (p<0.05) in PEG-b-PLA40-treated group after 3 days of culture compared with controls. After ex vivo culture of rat ovaries collected on PND15, basal progesterone and estradiol levels measured in the culture media did not differ between control and both TiO2 NP-treated groups. The ovaries from rats neonatally exposed to both doses of TiO2 NPs failed to respond to FSH/IGF stimulation in progesterone secretion at all time intervals.

Conclusions. The obtained results indicate that neonatal exposure to NPs in female rats may alter ovarian steroidogenic output (steroid hormone secretion) and thereby might subsequently induce perturbation of mammalian reproductive functions. Possible mechanisms (induction of oxidative stress, inflammation) of adverse effects of NPs on ovarian function should be further elucidated.

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