Klotho, BDNF, NGF, GDNF Levels and Related Factors in Withdrawal Period in Chronic Cannabinoid Users.

Klotho and neurotropic factors have recently been shown to be related to some psychiatric disorders and neurocognitive disorders, but there is no study on this issue within substance users. In this study, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) and klotho serum levels of a patient group consisting of 27 chronic cannabis users according to the DSM-V and 27 healthy volunteers were compared, and their relationships with other the clinical features of other patients were evaluated. Clinical scales, the Buss-Perry Aggression Scale, and the Substance Craving Scale were repeated on the first day of hospitalisation and on the seventh day of withdrawal. BDNF, GDNF, NGF and klotho levels were analysed using the ELISA method. There was no differences between the cannabinoid use disorder group and the control group regarding their klotho and other neurotrophic levels, but initiation age of cannabis use was negatively correlated with these levels. In addition, there was a relationship between verbal aggression scores and BDNF and NGF levels. There was a positive correlation between klotho and neurotrophic factors in all groups (patient group Day 1, patient group Day 7, control group) (p < 0.01). When comparing the difference between the correlations using the cocor (a comprehensive solution for the statistical comparison of correlations), the klotho-GDNF and klotho-NGF correlations for the first day of the patient group and the control group were different. In this study, rather than a difference in klotho levels and neurotropic factors, a significant relationship between these markers and each other and clinical parameters was demonstrated; further studies are needed to understand the exact mechanism.

Klotho, vitamin D and homocysteine levels during acute episode and remission periods in schizophrenia patients.

AIM: Neurodegenerative processes are effective in schizophrenia. However, the underlying causes of the symptoms and associated factors have not yet been fully elucidated. Recent research has focused on the relationship between neurodegeneration and vitamin D, Klotho and homocysteine levels. In this study, we aimed to investigate this relationship in schizophrenia. METHOD: This study included 30 schizophrenic inpatients, 30 schizophrenic outpatients in remission and 28 healthy volunteers as the control group. The psychiatric diagnoses of our patients were evaluated according to DSM-IV criteria. The Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Clinical Global Impression (CGI) scale were used for clinical measurements. Serum Klotho, homocysteine, vitamin D, vitamin B12 and folic acid levels were analyzed using ELISA and compared with clinical properties. RESULTS: The PANSS scores and CGI scores were higher in schizophrenic inpatients than outpatients, and the GAF scores were lower (p < 0.05). Three groups were compared for Klotho, homocysteine and vitamin D serum levels; Klotho levels were elevated but the difference was not statistically significant (p > 0.05). However, vitamin B12, folic acid and homocysteine levels were higher in schizophrenic patients than the control group (p < 0.05). CONCLUSIONS: Higher levels of homocysteine with concomitant higher levels of vitamin B12 and folic acid suggest a relationship of this pathway with schizophrenia. Differences in Klotho levels were elevated but it was not significant. Replication studies to investigate probable associations with larger samples are needed.

Effect of the Oxidant-Antioxidant System in Seminal Plasma on Varicocele and Idiopathic Infertility in Male Humans.

BACKGROUND: The aim of this study was to investigate seminal oxidant-antioxidant activity in idiopathic and varicocele infertility in men. METHODS: Total anti-oxidant capacity (TAC), total oxidant status (TOS), paraoxonase (PON1), aryl esterase (ARE), and total thiol levels (TTL) were measured in seminal plasma with an autoanalyzer. The TOS/TAC ratio was determined as the oxidative stress index (OSI). A histopathological evaluation of the sperm was performed in the andrology laboratory of the hospital. Number, motility, morphology, volume, pH, and leukocytes were evaluated in all samples according to World Health Organization criteria. The three study groups were as follows: G1, males with idiopathic infertility; G2, males with varicocele infertility; and G3, normal healthy males (had fathered a child in the last 2 years). Each group was composed of 36 men (age, 25 - 40 years). The Rel Assay Diagnostics kit was used to determine the levels of the parameters. The study was conducted according to the principles of the declaration of Helsinki and was approved by Sakarya University Medicine Faculty Ethic Committee (e.n: 16214662/050.01.04/07). Statistical significance was assumed if p < 0.05. All statistical evaluations were performed using SPSS (version 20.0 for Windows; SPSS, Inc., Chicago, IL, USA). RESULTS: No differences were detected between the mean values of antioxidant parameters among the three groups (Kruskal-Wallis test). The p-values of the test parameters (TAC, TOS, PON1, ARE, TTL, OSI) are respectively: 0.494, 0.548, 0.068, 0.151, 0.202, 0.873. The antioxidant parameters of all subjects were compared using the MannWhitney U-test in both groups as fertile (G3) and infertile (G1 + G2). The PON1 levels in infertile subjects were significantly higher than those in fertile subjects. There was a statistically significant difference (p = 0.042). The other antioxidant parameters had no statistically significant difference (p > 0.05). The ARE was not performed in group 3 (control) due to a methodological problem. CONCLUSIONS: PON1 levels in infertile subjects were significantly higher than those of fertile subjects.

Alterations of the hematologic cells in synthetic cannabinoid users.

BACKGROUND: Functions, morphology, distributions, and index of the circulating cells are the most useful parameters that indicate various inflammatory and toxic conditions. The aim of this study was to investigate the clinical significance of these parameters in patients diagnosed with (synthetic) cannabis use disorder. METHODS: This study included a total of 40 patients in the study group (SG) with synthetic cannabis use; and 40 healthy individuals as the control group (CG). Participants, who had hematological disorders and other chronic diseases, were excluded from the study. All hematological parameters of SG were compared with CG. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) values were calculated and compared between groups. RESULTS: There were statistically significant differences between the groups in terms of WBC, MCH, RDW, MCV, MPV, and NEU, LYM%, MONO% parameters (P<.05). MPW and LYM% were significantly lower in SG compared to CG. WBC, MCH, RDW, MCV, MPV, MONO, and NEU parameters were significantly higher in SG compared to CG (P<.05). UIBC and TIBC levels were significantly higher in SG compared to CG (P<.001). Although there was statistically significant difference between groups in terms of NLR, there was no significant difference for PLR values. CONCLUSION: Our data suggested that chronic use of cannabinoids can lead to deterioration of hematopoietic cells. Chronic use of cannabinoids was consistent with subthreshold/subclinical megaloblastic anemia with iron deficiency. Inflammatory cells, especially neutrophil and monocyte counts were higher in SG compared to CG. Thus, recovery of subclinical hematological parameters should be considered in cannabis use disorder patients.

Altered Plasma MicroRNA Expression in Patients with Mitral Chordae Tendineae Rupture.

BACKGROUND: Mitral chordae tendineae rupture (MCTR) is a progressive disorder which leads to severe mitral regurgitation. Despite its importance, the precise pathogenetic mechanism of MCTR remains unclear. The study aim was to investigate the expression profile of circulating microRNAs (miRNAs) as being potentially involved in the development of MCTR. METHODS: Twenty-one patients with 'primary' MCTR, and 30 age- and gender-matched controls, were enrolled in the study. Comparisons were made between the expression levels of circulating miRNAs in MCTR patients and controls. Four target gene databases were used to predict target genes and pathways of differentially expressed miRNAs. RESULTS: Compared to controls, the expression of 22 miRNAs (hsa-miR-106b-5p, hsa-miR-126-3p, hsa-miR-150-5p, hsa-miR-17-5p, hsa-miR-195-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-222-3p, hsa-miR-223-3p, hsa-miR-23a-3p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-93-5p, hsa-miR-26b-5p, hsa-miR-30e-5p, hsa-miR-373-3p, hsa-miR-15b-5p, hsa-miR-16-5p, hsa-miR-191-5p, hsa-miR-26a-5p) were significantly down-regulated in the MCTR group. Bioinformatic analysis indicated that the following potential miRNA targets and pathways are commonly related to the development of MCTR: MMPs, TIMP-2,TGFBR2, VEGFA, PIK3R2, NRAS, PPP3CA, PPP3R1, PTGS 2 were predicted as putative targets of 13 of these miRNAs. CONCLUSIONS: The present study is the first to describe altered miRNA expression in patients with MCTR. Bioinformatic analysis has revealed that target genes involved in MCTR development were regulated by miRNAs.

Investigating associations between appetite-regulating hormones, aggression and craving in males with cannabis use disorder.

BACKGROUND: Aggression and craving are common and important withdrawal symptoms in cannabis use disorder. The present study investigated the association between appetite-regulating hormones, aggression, and craving during cannabis withdrawal syndrome (CWS). METHODS: Fifty-six male subjects diagnosed with cannabis withdrawal and 45 healthy males were included in the study. The Substance Craving Scale, the Buss-Perry Aggression Questionnaire, and the State-Trait Anxiety Inventory were implemented at baseline. Blood samples were drawn to measure ghrelin, leptin, adiponectin, and resistin levels in the serum. Then, the Point Subtraction Aggression Paradigm (PSAP) was applied. Bloodwork and psychometric assessment procedures were re-implemented after the PSAP. At the 7-day follow-up, psychometric assessments and hormone measurements were repeated in the CWS group. RESULTS: Baseline serum ghrelin and adiponectin levels were lower in the CWS group than controls at baseline. After PSAP, there was a significant increase in ghrelin levels of patients with CWS compared to controls. Patients yielded higher aggression scores, while there was no significant correlation between hormonal changes and PSAP findings. At 7-day follow, ghrelin and resistin levels significantly increased, while serum leptin decreased in patients with CWS. Finally, there was a positive association between craving and resistin levels. CONCLUSIONS: Our results present the changes in appetite-regulating hormones. Long-term follow-up studies are needed to shed light on neuroendocrinological aspects of cannabis withdrawal.

Effects of Iodixanol on Respiratory Functions during Coronary Angiography and the Role of Body Composition.

PURPOSE: The purposes of this study are to assess the acute effects of iodixanol, an iso-osmolar contrast media, on pulmonary functions and to evaluate the body composition in order to find out its role in causing this deterioration. METHODS: 35 male and 25 female patients undergoing diagnostic coronary angiography (CA) were enrolled in the study. Before CA, all patients' body compositions were evaluated by measuring their body mass indexes (BMIs) and waist-to-hip ratios (WHRs). Total body waters (TBWs), fat masses (FMs), fat-free masses (FFMs), and basal metabolism rates (BMRs) were measured via bioimpedance analysis. The CA was performed via radial artery route using iodixanol in every patient. The pulmonary function tests of these patients were performed before, during, and 2 hours after the CA. FEV1∆, FEF25-75%∆, and FVC∆ parameters were calculated by subtracting the measured baseline value from the measurement after the CA. RESULTS: Angiography caused significant reduction in forced expiratory volume in 1 sec (FEV1, from 94.17 ± 18.83 to 84.45 ± 18.31, p < 0.0001), forced vital capacity (FVC, from 96.57 ± 15.82 to 88.31 ± 17.96, p < 0.0001), and forced expiratory flow at 25-75% (FEF25-75% from 82.54 ± 24.26 to 72.11 ± 25.41, p=0.001) and remained lower after 2 h after CA in male patients, respectively. FEV1 values were 103.40 ± 17.79 to 94.96 ± 17.063 (p=0.004); FVC values were 107.20 ± 19.03 to 99.08 ± 20.56 (p=0.009); and FEF25-75% values were 83.92 ± 24.30 to 73.24 ± 20.45 (p=0.005) before and after CA and remained lower after 2 h after CA in female patients, respectively. FEV1/FVC ratio remained unchanged. FEF25-75%∆ was statistically correlated with FFM, TBW, and WHR (p < 0.05; r=-0.344, r=-0.347, and r=0.357, resp.), and FVC∆ was correlated with WHR in male patients (p=0.018, r=397). CONCLUSIONS: Our data suggested that diagnostic CA using iodixanol, an iso-osmolar contrast media, leads significant impairment in respiratory functions. Due to the persistence of these reductions even 2 hours after CA, ventilatory functions should be considered especially in patients whose body compositions or hydration levels are not within the desired physiological range.

Evaluation of Immunomodulatory and Hematologic Cell Outcome in Heroin/Opioid Addicts.

The long-term use of opioids leads alternations in both innate-adaptive immune systems and other diagnostic hematologic cells. The purpose of this study is to evaluate the alterations of these parameters in patients with heroin/opioid addictions. Adults, meeting the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria of the American Psychiatric Association regarding opioid use disorder (Heroin Group or HG, n = 51) and healthy controls (Control Group or CG, n = 50), were included in the study. All hematological parameters, inflammation indexes (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio), and iron panel were compared with the controls. Mean corpuscular volume, red blood cell distribution width, mean corpuscular hemoglobin content, unsaturated iron-binding capacity, and total iron-binding capacity were significantly higher in HG compared to CG, while red blood cell count, hemoglobin, hematocrit, and serum iron levels were significantly lower. Additionally, platelet and platelet distribution width were significantly high while mean platelet volume was low in HG. Regarding the parameters related to immunity, white blood cell, neutrophil count, and neutrophil percentage were significantly high while lymphocyte percentage and basophils count were significantly low. Besides, inflammatory indexes were significantly higher in HG compared to CG. Intravenous administration of heroin resulted in lower levels of hemoglobin, hematocrit, and mean corpuscular volume than inhalation and intranasal administration. Our data demonstrated that chronic use of opioids is related to all of the hematologic series. The chronic use of opioid alters the immunologic balance in favor of innate immunity cells and changes the hematometric/morphometric characteristics of erythrocytes. What is more, the route of heroin administration should be taken into consideration as well. This study may lead to a better understanding of the hematological effects of heroin/opioid use in patients with relevant addictions.

Atrial natriuretic peptide and posterior pituitary neurohormone changes in patients with acute schizophrenia.

OBJECTIVES: Interactions between neuropeptides and psychiatric disorders have been investigated for many years. The aim of this study was to evaluate oxytocin (OXT), arginine-vasopressin (AVP), and atrial natriuretic peptide (ANP) and assess their interactions with each other, as well as investigate these changes with the manifestations of schizophrenia. PARTICIPANTS AND METHODS: Thirty-four individuals having acute schizophrenia and 24 healthy individuals as the control group were included in the study. Positive and Negative Syndrome Scales, Global Assessment of Functionality score, and Clinical Global Impression (CGI) scores were measured. Serum hormone levels were analyzed using enzyme-linked immunosorbent assay and were compared with the clinical findings. RESULTS: OXT levels were significantly lower and AVP levels were significantly higher in patients having acute schizophrenia than the control group. OXT was negatively correlated with Positive and Negative Syndrome Scales positive score and CGI score, while it was positively correlated with Global Assessment of Functionality score. AVP was negatively correlated with CGI score. ANP levels of the patients having schizophrenia were lower than the control group; however, there was no significant correlation with clinical findings. CONCLUSION: The obtained data indicate that the AVP level was higher, but OXT and ANP levels were lower in the patients having acute schizophrenia. Specifically OXT is related with reduced disease severity and increased functionality.

Effect of intermittent hypoxia on the cardiac HIF-1/VEGF pathway in experimental type 1 diabetes mellitus.

OBJECTIVE: High altitude and hypoxic preconditioning have cardioprotective effects by increasing coronary vascularity, reducing post-ischemic injury, and improving cardiac function. Our purpose was to examine if intermittent hypoxia treatment has any restoring effects related to the possible role of the HIF-1/VEGF pathway on diabetic cardiomyopathy. METHODS: Wistar Albino male rats (n=34) were divided into four groups: control (C), intermittent hypoxia (IH), diabetes mellitus (DM), and diabetes mellitus plus intermittent hypoxia (DM+IH). Following a streptozotocin (STZ) injection (50 mg/kg, i.p.), blood glucose levels of 250 mg/dL and above were considered as DM. IH and DM+IH groups were exposed to hypoxia 6 h/day for 42 days at a pressure corresponding to 3000 m altitude. Twenty-four hours after the IH protocol, hearts were excised. Hematoxylin and eosin-stained apical parts of the left ventricles were evaluated. Hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor 164 (VEGF164), and VEGF188 polymerase chain reaction products were run in agarose gel electrophoresis. Band density analysis of UV camera images was performed using Image J. The data were compared by one-way ANOVA, repeated measures two-way ANOVA, and the Kruskal-Wallis test. RESULTS: The percent weight change was lower in the DM group than in the controls (p=0.004). The tissue injury was the highest in the DM group and the least in the IH group. Diabetes decreased, whereas the IH treatment increased the vascularity. A decrease was observed in the VEGF188 mRNA levels in the DM+IH group compared with the C group, but there were no difference in HIF-1α and VEGF164 mRNA levels between the groups. CONCLUSION: The IH treatment restored the diabetic effects on the heart by reducing tissue injury and increasing the capillarity without transcriptional changes in HIF-1/VEGF correspondingly.