Vortioxetine improved schizophrenia-like behavioral deficits in a Poly I:C-induced maternal immune activation model of schizophrenia in rats.

BACKGROUND: Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic-polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring. OBJECTIVES: The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C-induced schizophrenia-like model in rats. METHODS: For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL-6 levels after 2 h. At postnatal days 83-86, behavioral tests were performed. RESULTS: Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open-field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69-83) caused significant improvements in these deficits. CONCLUSION: Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.

Is There an Association Between Dietary Antioxidant Levels and Sperm Parameters in Male Infertility?

INTRODUCTION: Oxidative stress is known as a mechanism underlying male infertility; it is defined as an imbalance between pro-oxidants and antioxidants leading to DNA damage, peroxidation of plasma membrane lipids, and protein oxidation. This study was conducted to investigate the relationship between total antioxidant capacity and sperm parameters in male infertility. METHODS: A total of 187 men with infertility (asthenospermia group (n=51), oligospermia group (n=40), and control group (n=96) were included in the current study. The following risk factors were recorded: age, sperm volume, sperm motility, hormone levels, and dietary antioxidant content. RESULTS: Demographic parameters and hormone levels of cases showed no statistically significant difference between groups (p > 0.05). Semen volume, motility, vitamin A, retinol, vitamin D, and vitamin C levels were statistically significantly lower in the asthenospermia and oligospermia groups (p < 0.05). According to the logistic regression model, lower vitamin A, retinol, vitamin D, and vitamin C levels were risk factors for poor sperm outcomes (p < 0.001). Conclusion: Male infertility with poor sperm outcomes should have an assessment of antioxidant capacity and nutritional specialization including food high in antioxidants could improve sperm parameters in asthenospermia and oligospermia and it could be used for therapeutic opportunities.

Therapeutic effect of thymoquinone on brain damage caused by nonylphenol exposure in rats.

Nonylphenol (NP), causes various harmful effects such as cognitive impairment and neurotoxicity. Thymoquinone (TQ), has antioxidant, anti-inflammatory, and neuroprotective properties. In this study, our aim is to investigate the effects of TQ on the brain damage caused by NP. Corn oil was applied to the control group. NP (100 mg/kg/day) was administered to the NP and NP + TQ groups for 21 days. TQ (5 mg/kg/day) was administered to the NP + TQ and TQ groups for 7 after 21 days. At the end of the experiment, the new object recognition test was applied to the rats and the rats were killed and their brain tissues were removed. Sections taken from brain tissues were stained with hematoxylin-eosin for histopathological evaluation. In addition, neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), Cas-3, and nerve growth factor (NGF) immunoreactivities were evaluated in brain tissue sections. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were determined. Comet assay was applied to determine DNA damage in cells. The results of our study showed that NP, caused behavioral disorders and damage to the cerebral cortex in rats. This damage in the form of neuron degeneration seen in the cortex was associated with apoptosis involving Cas-3 activation, increased DNA damage, and free oxygen radicals. NP, SOD, and CAT caused a decrease in enzyme activities. In addition, the cellular protein NeuN was decreased, astrocytosis-associated GFAP was increased, and growth factor NGF was decreased. When all our evaluations are taken together, treatment with TQ showed an ameliorative effect on the behavioral impairment and brain damage caused by NP exposure.

The long-lasting effects of aceclofenac, a COX-2 inhibitor, in a Poly I:C-Induced maternal immune activation model of schizophrenia in rats.

It is well established that rats exposed to inflammation during pregnancy or the perinatal period have an increased chance of developing schizophrenia-like symptoms and behaviors, and people with schizophrenia also have raised levels of inflammatory markers. Therefore, there is evidence supporting the idea that anti-inflammatory drugs may have therapeutic benefits. Aceclofenac is a nonsteroidal anti-inflammatory drug that has anti-inflammatory properties and is used clinically to treat inflammatory and painful processes such as osteoarthritis and rheumatoid arthritis, making it a potential candidate for preventive or adjunctive therapy in schizophrenia. This study therefore examined the effect of aceclofenac in a maternal immune activation model of schizophrenia, in which polyinosinic-polycytidylic acid (Poly I:C) (8 mg/kg, i.p.) was administered to pregnant rat dams. Young female rat pups received daily aceclofenac (5, 10, and 20 mg/kg, i.p., n = 10) between postnatal day 56 and 76. The effects of aceclofenac were compared with assessment of behavioral tests and ELISA results. During the postnatal days (PNDs) 73-76, behavioral tests were conducted in rats, and on PND 76, ELISA tests were performed to examine the changes in Tumor necrosis factor alpha (TNF-α), Interleukin-1ß (IL-1ß), Brain-derived neurotrophic factor (BDNF), and nestin levels. Aceclofenac treatment reversed deficits in prepulse inhibition, novel object recognition, social interaction, and locomotor activity tests. In addition, aceclofenac administration decreased TNF-α and IL-1ß expression in the prefrontal cortex and hippocampus. In contrast, BDNF and nestin levels did not change significantly during treatment with aceclofenac. Taken together, these results suggest that aceclofenac may be an alternative therapeutic adjunctive strategy to improve the clinical expression of schizophrenia in the further studies.

Group I mGluRs positive allosteric modulators improved schizophrenia-related behavioral and molecular deficits in the Poly I:C rat model.

RATIONALE: Maternal polyinosinic-polycytidylic acid (Poly I:C) exposure leads to an increase in various proinflammatory cytokines and causes schizophrenia-like symptoms in offspring. In recent years, group I metabotropic glutamate receptors (mGluRs) have emerged as a potential target in the pathophysiology of schizophrenia. OBJECTIVES: The aim of our study was to investigate the behavioral and molecular changes by using the mGlu1 receptor positive allosteric modulator (PAM) agent RO 67-7476, and the negative allosteric modulator (NAM) agent JNJ 16259685 and the mGlu5 receptor PAM agent VU-29, and NAM agent fenobam in the Poly I:C-induced schizophrenia model in rats. METHODS: Female Wistar albino rats were treated with Poly I:C on day 14 of gestation after mating. On the postnatal day (PND) 34-35, 56-57 and 83-84, behavioral tests were performed in the male offspring. On the PND84, brain tissue was collected and the level of proinflammatory cytokines was determined by ELISA method. RESULTS: Poly I:C caused impairments in all behavioral tests and increased the levels of proinflammatory cytokines. While PAM agents caused significant improvements in prepulse inhibition (PPI), novel object recognition (NOR), spontaneous alternation and reference memory tests, they brought the levels of proinflammatory cytokines closer to the control group. NAM agents were ineffective on behavioral tests. It was observed that PAM agents significantly improved Poly I:C-induced disruption in behavioral and molecular analyses. CONCLUSIONS: These results suggest that PAM agents, particularly the mGlu5 receptor VU-29, are also promising and could be a potential target in schizophrenia.

The efficacy of systemic inflammatory response and oxidative stress in erectile dysfunction through multi-inflammatory index: a prospective cross-sectional analysis.

BACKGROUND: Systemic inflammation and oxidative stress increase the possibility of erectile dysfunction (ED) through a coordinated response to vascular endothelial damage. AIM: The study aimed to evaluate the status of oxidative stress and systemic inflammation in ED. METHODS: The analysis was a prospective, cross-sectional, single-center study. The study included non-ED (n = 54) and ED (n = 104) groups. The study analyzed demographics, clinical outputs, oxidative stress (total antioxidant status [TAS], total oxidant status [TOS], oxidative stress index [OSI]), and an inflammatory condition (multi-inflammatory index 1 [MII-1], MII-2). OUTCOMES: Oxidative stress and systemic inflammation were evaluated together in ED, which was evaluated with the help of the International Erectile Function Index (IIEF) scale. RESULTS: TAS significantly decreased in the ED group compared with the non-ED group (2.25 ± 0.83 mmol Trolox equivalents/L vs 1.45 ± 0.65 mmol Trolox equivalents/L; P = .001). TOS increased in the ED group (14.1 ± 6.2 µmol H2O2 equivalents/L) compared with non-ED group (11.05 ± 6.8 µmol H2O2 equivalents/L) (P = .002). OSI was as low as 0.74 ± 0.33 in the non-ED group and as high as 2.38 ± 0.85 in the ED group (P = .001). Both MII-1 (273 ± 398 vs 745 ± 1311; P = .012) and MII-2 (4.66 ± 5.02 vs 19.7 ± 29.4; P = .031) increased in the ED group compared with the non-ED group. IIEF was negatively correlated with MII-1 (r = -0.298; P = .009), MII-2 (r = -0.341; P = .006), and OSI (r = -0.387; P < .0001), while TAS had a strong positive correlation with the IIEF (r = 0.549; P = .0001). OSI was correlated with MII-1 (r = 0.304; P = .001) and MII-2 (r = 0.334; P = .001). OSI was the strongest parameter in predicting ED (P = .0001; area under the curve, 0.795; 95% confidence interval, 0.696-0.855). The cutoff was 0.71 at 80.5% sensitivity and 67.2% specificity. CLINICAL IMPLICATIONS: OSI showed diagnostic potential for ED as an oxidative stress indicator, while MII-1 and MII-2 showed the effectiveness. STRENGTHS AND LIMITATIONS: MIIs, a novel indicator of systemic inflammatory condition, were analyzed for the first time in patients with ED. The long-term diagnostic efficacy of these indices was lacking, as all patient data did not include long-term follow-up. CONCLUSION: Considering their low cost and easy applicability compared with OSI, MIIs could be essential parameters in the follow-up for ED for physicians.

An involvement of COX and 5-LOX pathways in the penicillin- and pentylenetetrazole (PTZ)-induced epilepsy models.

This study aimed to examine the relationship between epilepsy and COX/5-LOX inflammation pathways in the penicillin and pentylenetetrazole (PTZ)-induced epilepsy models. For this purpose, 42 albino male Wistar rats were used in this study. In the penicillin and PTZ-induced epilepsy models, epileptiform activity was induced by injection of penicillin (500 IU, i.c.) and PTZ (35 mg/kg, i.p., three times a week), respectively. Licofelone (20 mg/kg, i.p.), a dual inhibitor of COX/5-LOX, and esculetin (20 mg/kg, i.p.), a 5-LOX inhibitor, were given. In the penicillin-induced epilepsy model, ECoG activity was recorded for 180 min. In the PTZ-induced epilepsy model, both ECoG activity was recorded, and behavioral parameters were performed. In the penicillin groups, both licofelone and esculetin decreased the mean spike frequency and amplitude during the experiments. In the PTZ groups, licofelone (20 mg/kg, i.p.) was more effective than esculetin (20 mg/kg, i.p.). Licofelone showed its protective effects both in ECoG activity and in behavioral parameters. Esculetin was less effective when compared to licofelone. The electrophysiological and behavioral data from the present study indicated that inflammation pathways might have a crucial role in controlling epileptiform activity in rats. Licofelone might be a valuable candidate in advanced studies.

Vortioxetine suppresses epileptiform activity and cognition deficits in a chronic PTZ-induced kindling rat model.

This study aimed to examine the effects of vortioxetine, a novel antidepressant, on epileptiform activity in pentylenetetrazole (PTZ)-induced kindling model in rats. For this purpose, 20 male Wistar Albino rats were used, and epileptiform activity was induced by injection of PTZ (35 mg/kg, i.p., three times a week). In the vortioxetine groups, vortioxetine (5 mg/kg and 10 mg/kg) was administered before the kindling process. During the kindling process, the Fisher and Kittner seizure scales were used to score seizure severity. After kindling, novel object recognition (NOR) tests were performed to evaluate the cognitive performance of rats. Electrodes were implanted into the fully kindled animals for ECoG recordings. In the PTZ group, the number of total spikes was 1367±136 spikes/20 minutes. First myoclonic jerks decreased while seizure severity and total spike count increased in the PTZ group. On the other hand, the total spike number and seizure severity significantly decreased and first myoclonic jerks increased in the vortioxetine groups compared to the PTZ group. Based on the NOR test, vortioxetine administration markedly raised the discrimination index compared to the PTZ group. Electrophysiological and behavioural data from the present study suggest that vortioxetine, a novel drug, plays a critical role in controlling PTZ-induced epileptiform activity in rats. Vortioxetine may therefore be a valuable candidate to prevent seizure activity and treat cognitive deficits associated with epilepsy.

The Effect of Intravesical Prostatic Protrusion in Patients with Benign Prostatic Hyperplasia: Controlled, Clinical Study.

BACKGROUND: Although prostate cancer releases more prostate-specific antigen (PSA) per unit of prostate volume (PV), data are limited regarding the association between intravesical prostatic protrusion (IPP) and the PSA level. OBJECTIVES: The study aim was to evaluate the IPP effect in patients with benign prostatic hyperplasia. METHOD: This study included patients with (n = 119) and without (n = 121) IPP. The age, International Prostate Symptom Score (IPSS), PSA level, maximum and average flow rates, PV, hematuria, urinary retention, and post-void residual (PVR) volume were compared between the 2 groups. RESULTS: The mean ages were similar between the 2 groups (66.56 ± 8.67 and 66.92 ± 8.7 years, respectively, p = 0.747), and there were no statistically significant differences in the IPSS, maximum and average flow rates, hematuria, PVR volume, and urinary retention means (p > 0.05). However, the IPP patients had lower total PSA (tPSA) and free PSA (fPSA) levels than those without IPP (3.55 [4.18] vs. 5.26 [5.24] ng/mL, p = 0.013 and 0.7 [1.09] vs. 1.05 [1.23] ng/mL, p = 0.029, respectively). Moreover, there were strong positive correlations between the IPP grade and the tPSA and fPSA levels (r = 0.262, p = 0.001 and r = 0.254, p = 0.002 respectively). CONCLUSIONS: This study demonstrated that IPP results in a decreased PSA level, even with a higher PV.

The effect of serotonin on penicillin-induced epileptiform activity.

OBJECTIVE: This study was aimed at examining the epileptiform activity of the 5-HT2 serotonin receptor agonist and antagonist, and 5-hydroxytryptophan (5-HTP) in penicillin-induced epilepsy in albino Wistar rats. METHODS: For this purpose, 90 albino male Wistar rats were used in this study. Epileptiform activity was induced by an injection of penicillin, an agonist of GABAA receptor, (500 IU, i.c.) into the somatomotor cortex. Thirty minutes after the injection of penicillin, 2,5-dimethoxy-4-iodoamphetamine (DOI, an agonist of 5-HT2 receptor) (0.5, 1, 2 and 4 mg/kg, i.p.), methysergide, an antagonist of 5-HT2 receptor, (1, 10, 20, 50 and 100 µM, i.c.v.) and 5-HTP, precursor of 5-HT, (25, 50, 75 and 100 mg/kg, i.p.) were administered, respectively. RESULTS: DOI, at the doses of 1 and 2 mg/kg, significantly decreased penicillin-induced epileptiform activity (p < 0.05). Methysergide, at the doses of 20, 50 and 100 µM, significantly increased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The doses of 50, 75 and 100 mg/kg of 5-HTP decreased the mean spike frequency of penicillin-induced epileptiform activity (p < 0.05). The mean of amplitude of penicillin-induced epileptiform activity did not significantly change in any of the groups (p > 0.05). CONCLUSION: The electrophysiological data from the present study suggest that serotonin 5-HT2 receptors have an important role in controlling penicillin-induced epileptiform activity in the rat.

Effects of low and high doses of acetylsalicylic acid on penicillin-induced epileptiform activity.

BACKGROUND: The most common headache associated with epilepsy occurs after seizure activity and is called a postictal headache. Therefore, the objective of this study was to investigate the effects of low and high doses acetylsalicylic acid (aspirin) on a penicillin-induced experimental epilepsy model. METHODS: Adult male Wistar rats (n = 28, weighing 220 ±â€¯40 g) were used in the experiments. The rats were divided into four groups as Control, Penicillin, Aspirin 150 mg/kg, Aspirin 500 mg/kg. Seizure activity was triggered by an intracortical injection of penicillin G potassium (500 IU/2.5 µl) into the sensory motor cortex. An electrocorticogram was recorded by using conductive screw electrodes. Aspirin at the doses of 500 mg/kg and 150 mg/kg was given intraperitoneally (ip) 30 min after penicillin administration. RESULTS: Anticonvulsant activity appeared at the 30th and 40th min after an intracortically administered injection of penicillin in the groups given aspirin doses of 500 mg/kg (ip) and 150 mg/kg (ip) respectively. The amplitude of epileptiform activity at both doses of aspirin decreased but the difference was not statistically significant. CONCLUSIONS: The results of the present study suggest that low and high doses of aspirin may decrease epileptiform activity in penicillin-induced epilepsy. Aspirin might be suggested for headache associated with epilepsy.

Acute effects of aceclofenac, COX-2 inhibitor, on penicillin-induced epileptiform activity.

PURPOSE: The effects of COX-2 inhibitors on seizure activity are controversial. The aim of the current study was to determine the post-treatment effect of aceclofenac on penicillin-induced experimental epilepsy. METHODS: Male Wistar rats were used in all experiments (n=18). The seizure activity was triggered by penicillin (i.c.). Aceclofenac was injected intraperitoneally at doses of 10mg/kg and 20mg/kg. RESULTS: Intraperitoneal administration of 10 and 20mg/kg aceclofenac doses, exhibited proconvulsant properties on seizure activity on rats. The mean spike frequency and amplitude of aceclofenac 10mg/kg were 41.89±2.12 spike/min and 0.619±0.094mV, respectively. The mean spike frequency and amplitude of aceclofenac 20mg/kg were 35.26±2.72 spike/min and 0.843±0.089mV, respectively. CONCLUSION: The results indicated that not all of the COX-2 inhibitors may have anticonvulsant or proconvulsant features on patients with epilepsy susceptibility and must be used with great care. It was also suggested that not only cyclooxygenase metabolic pathway but also lipoxygenase pathway should be considered together in further detailed studies.

Comparison of laparoscopic and open ureterolithotomy in impacted and very large ureteral stones.

PURPOSE: To compare the efficacy of laparoscopic and open ureterolithotomy in patients with ureteral stones. MATERIALS AND METHODS: Patients who had undergone open or laparoscopic ureterolithotomy between 2001 and 2013 in our clinic were enrolled in the study.Ureterolithotomy was performed due to the following reasons: failure to position the patient for ureteroscopy, unreachable stone with ureteroscopy also use of balloon dilatation, high stone volume, and the need for removal of kidney stones at the same session.. The patients' demographic data, the volume of the stones, the duration of the operation and the hospital stay, the amount of analgesics administered after the operation, and the need for another procedure were compared. RESULTS: Of study subjects 32 patients had undergone open and 20 patients had undergone laparoscopic ureterolithotomy. When the two groups were compared, there was no statistically significant difference with regard to the mean age (44.5-44 years), the body mass index (26-24.7 kg/m²), the stone volume (420-580 mm³), the duration of operation (122-123 min), the need for another procedure and complications. The mean amount of analgesics administered after the operation (3.6 and 1.81 doses, P = .02) and the mean hospital stay (6.1 and 2.9 days, P = .01) were significantly lower in the laparoscopic ureterolithotomy group. CONCLUSION: Laparoscopic ureterolithotomy is a good alternative with less need for analgesia and a shorter hospital stay when compared with open ureterolithotomy.

Preoperative evaluation of pediatric kidney stone prior to percutaneous nephrolithotomy: is computed tomography really necessary?

The objective of the study was to investigate the precise role of computed tomography (CT) in preoperative radiologic evaluation and surgical planning of kidney stone in children prior to percutaneous nephrolithotomy (PNL). A total of 113 pediatric patients (aged ≤18 years) undergoing PNL for renal stone(s) in three referral hospitals between March 2010 and August 2012 were retrospectively evaluated. Depending on the preoperative radiologic evaluation, patients were divided into two groups. Those evaluated with CT were classified as group-1 (n = 50) and the remaining cases undergoing intravenous urography (IVU) examination were classified as group-2 (n = 63). Patient- and procedure-related variables and perioperative measures were compared between the groups. The mean age, stone size and localization were similar in both groups (p = 0.07, p = 0.57, p = 0.6, respectively). Although the postoperative hemoglobin drop was found to be significantly higher in group-2 (1.5 ± 1.3 vs. 0.9 ± 0.6 g/dL, p = 0.005), the mean operation time, fluoroscopic screening time, access number, overall success and complication rates were comparable (p = 0.06, p = 0.94, p = 0.75, p = 041, and p = 0.41, respectively). However, the mean hospitalization time was significantly prolonged in group-2 than in group-1 (p = 0.03). Our findings clearly demonstrate that, despite the key role of preoperative CT in particular patients with anatomically abnormal kidneys, IVU is a valuable alternative imaging modality with comparable radiation doses in children.