Protective effects of E-CG-01 (3,4-lacto cycloastragenol) against bleomycin-induced lung fibrosis in C57BL/6 mice.

Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-ß expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.

Exercise Improves Physical Capacity, Cognition, Quality of Life and Promotes Neurotrophic Factors in Patients with Multiple Sclerosis.

Introduction: We aimed to determine the effect of regular exercise on aerobic capacity, strength values, and plasma levels of Nerve Growth Factor (NGF) and Neurotrophin-3 (NT-3) in patients with multiple sclerosis (MS) and investigate its effects on MS symptoms including cognitive impairment, fatigue, balance disorders, and quality of life (QOL). Methods: Forty-three relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score of 4 or less participated in the study. Participants were divided into three groups: aerobic group, strength group, and control group. The patients in the exercise groups had exercise programs three days a week for three months. Aerobic capacity (maximum VO2 value), strength measurements, and balance tests were done, and NGF and NT-3 plasma levels were analyzed in all participants at the beginning and end of the study. Multiple Sclerosis Quality of Life-54 (MSQoL-54), fatigue impact scale, Pittsburgh Sleep Quality Index (PSQI) and, to evaluate cognitive functions, BICAMS scale were applied. Results: Aerobic exercise and strength exercise groups had significant increases in VO2 max, back and leg strength values, and NGF and NT-3 plasma levels (p<0.01). Cognitive functions, fatigue, sleep quality, and QOL significantly improved in the exercise groups (p<0.01). The balance values were also significantly improved in the aerobic group (p<0.01), and althoughimprovement although improvement was observed in the strength group, it was not statistically significant (p>0.05). Conclusions: Our study provides evidence that regular exercise improves quality of life, cognitive functions, fatigue, and sleep quality in MS patients. The levels of NGF and NT-3, which are important factors in neural regeneration and remyelination, were increased post exercise. It can be suggested that exercise may have a potential effect on MS and slow down the disease process with these results.

The Effects of Different Pressure Pneumoperitoneum Models Created By Standard or Heated-Humidified CO2 Insufflation on Ovary and Peritoneum: an Experimental Study in Rats.

There is still controversy over whether structural and morphological changes can be observed in tissues depending on the carbon dioxide (CO2) nature or the applied intra-abdominal pressures (IAP). This study aimed to investigate the effects of different pressure or CO2 nature used for pneumoperitoneum in gynecological laparoscopic surgery on inflammation, DNA damage, oxidative stress, and histopathological changes in ovarian and peritoneal tissue. For this purpose, forty female rats were randomly divided into 6 groups and different pneumoperitoneum models were created in these groups. Rats in group other than control and sham groups received standard (CD) or heated-humidified CO2 (HH) insufflations at low (4 mmHg) or high pressure (8 mmHg). The ovary and peritoneum sections were evaluated microscopically for apoptotic index (API) and API scoring was calculated. Tissue and plasma interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-α), anti-Mullerian hormone (AMH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). The most severe changes occurred in the 8CD group microscopically, while the least severe changes occurred in the 4HH group. All histopathological parameters except for ovarian apoptotic index and peritoneal PCNA at low pressure were higher in the CD group. TNF-α and 8-OHdG levels were higher in the CD group at both low and high pressures. Standard CO2 caused more prominent histopathological changes at high pressures and systemic inflammation in both pressure groups. The least change between the experimental study groups in terms of histopathological and biochemical was observed in the low-pressure heated-humidified group.

Neuroprotective effects of dexpanthenol on streptozotocin-induced neuronal damage in rats.

AIM: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. DESIGN AND METHODS: In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n = 6), STZ + Saline (n = 6) and STZ + Dexpanthenol (n = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3). RESULTS: It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-α in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects. CONCLUSION: Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.

Retinal Nerve Fiber Layer Thickness Correlates with Serum and Cerebrospinal Fluid Neurofilament Levels and is Associated with Current Disability in Multiple Sclerosis.

INTRODUCTION: The main purpose of the present study is to confirm Peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness is a biomarker of axonal degeneration in patients with Multiple Sclerosis (MS) and to evaluate its relationship with Neurofilament heavy chain (NfH) and Nitrotyrosine (NT). METHOD: We quantified serum (s) and/or cerebrospinal fluid (CSF) NfH and NT levels in 30 relapsing-remitting MS patients (RRMS), 16 secondary progressive MS (SPMS) patients and in 29 control subjects matched for age and gender. Optical coherence tomography (OCT) measurements of pRNFL were performed in all subjects. Clinical outcomes were tested by Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS). RESULTS: RRMS patients exhibited significantly higher NfH/NT levels (99 pg/mL, 107.52 nM respectively) than controls (74 pg/mL, 48.72 nM) in CSF (p<0.0001), but not in sera. SPMS patients had significantly higher s NfH/NT values (111.25 pg/mL, 1251.77 nM respectively) and lower mean pRNFL thickness (79 µm) than patients with RRMS (98.50 µm) and controls (108 µm) (p<0.0001). pRNFL thickness was significantly correlated with all clinical disability measurements (EDSS, Trail Making test, 9-Hole Peg Test, and PASAT) in both RRMS and SPMS (p<0.001, p=0.02, p=0.03, p=0.02 respectively). A positive correlation was also found between serum and/or CSF NfH levels and EDSS scores in RRMS and SPMS (p<0.001, p=0.02 respectively). The pRNFL thickness was also correlated significantly with serum and/or CSF NfH levels but not with s/CSF NT levels in both clinical forms of MS (p<0.01, p<0.001 respectively). CONCLUSION: The current study demonstrated that both pRNFL and s/CSF NfH are reliable and quantitative biomarkers that correlate with current disease course and cross-sectional measure of disability in patients with MS.

The Prophylactic Effects of Metoprolol, Diltiazem, and Pilocarpine on Hypoglycemia-Induced Prolongation of QT Interval.

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose <40 mg/dl was defined as hypoglycemia. Electrocardiograms (ECG) were taken in lead I (DI), and QTc was calculated by using Bazett's formula. Results Group 2 (insulin + saline) showed that it had a significantly prolonged QTc interval as compared to the control group (p<0.0001). However, treatments of the rats with metoprolol, pilocarpine, and diltiazem significantly prevented prolongation of the QTc interval as compared to the insulin + saline group (p<0.005, p<0.005, and p<0.01, respectively). Conclusion The findings of the present study demonstrated the efficacy of metoprolol, pilocarpine, and diltiazem in the prevention of hypoglycemia-induced QTc prolongation in male rats.

Comparison of the Effects of Extracorporeal Irradiation and Liquid Nitrogen on Nerve Recovery in a Rat Model.

AIM OF THE STUDY: Biologic reconstruction using tumor-bearing bone autografts devitalized by liquid nitrogen or extracorporeal irradiation (oncological sterilization) is a safe and effective method in musculoskeletal surgery. The purpose of this study was to examine the effects of these two oncological sterilization methods on nerve recovery. METHODS: A total of 48 rats were randomly divided into 3 groups as autograft, irradiation and liquid nitrogen groups. A nerve defect created in the right sciatic nerve was reconstructed with an autograft obtained from the nerve itself. Group I underwent reconstruction with standard nerve autograft. Group II and Group III underwent reconstruction with devitalized nerve autograft treated through extracorporeal irradiation and liquid nitrogen, respectively. The left sciatic nerves of the rats served as control. Electromyography, motor function test and histomorphological analysis were performed to assess the nerve recovery on the 3rd (early stage) and 4th months (late stage). RESULTS: Electrophysiological assessment revealed better results in irradiation group compared with liquid nitrogen group in terms of myelinization and axonal regeneration. Motor performance of the autograft group was slightly better than the other groups. Histologically, autograft group demonstrated better results compared with other groups. Late-stage assessments revealed high rates of myelinization in the graft segment in liquid nitrogen group and in the segment distal to the graft in irradiation group. CONCLUSIONS: This study has demonstrated that nerve autografts treated by oncological sterilization methods may be used for nerve reconstruction in limb salvage surgery. However, further studies are needed to clarify the applicability of these methods.

Evaluation of toxicity of gadolinium-based contrast agents on neuronal cells.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI). Recently, increased signal intensity has been reported in specific brain areas after repeated administrations of GBCAs. PURPOSE: To investigate the toxic effects of GBCAs on neuronal cells by using SH-SY5Y neuroblastoma cell cultures. MATERIAL AND METHODS: For toxicity assays, SH-SY5Y cells were incubated with different doses (0-1000 µM) of several macrocyclic (gadoterate meglumine and gadobutrol) and linear GBCAs (gadoversetamide, gadopentetate dimeglumine, gadodiamide, and gadoxetate disodium) for 48 h. Cell viability and proliferation capacity were evaluated by using MTS assay, LDH assay, and colony-forming assay. In addition, Western blotting of Bcl-2 and Bax proteins and nuclear Hoechst 33258 staining were performed to evaluate apoptotic cell death. The results were expressed as mean ± SEM. The data were analyzed using Student's t-test. A P value < 0.05 was accepted as statistically significant. RESULTS: Both macrocyclic and linear GBCAs significantly and dose-dependently reduced cell viability in neuronal cells compared to control. Cell viability was measured between 89.5% ± 4% and 61% ± 0.7% in GBCA-treated groups. In addition, neurotoxicity was more prominent in linear GBCA-treated cultures (P < 0.0005). Bax protein levels were increased in GBCA-treated cells particularly with linear agents whereas Bcl-2 expression was decreased concomitantly. CONCLUSION: The results of the present study indicated that exposure to specific GBCAs, even at low micro-molar concentrations, may have detrimental effects on neuronal survival. Further investigations are required to clarify the molecular mechanism underlying GBCA-induced cell death.

The potential effects of anticonvulsant drugs on neuropeptides and neurotrophins in pentylenetetrazol kindled seizures in the rat.

Purpose: Neuropeptides and neurotrophic factors are thought to be involved in epileptogenesis. This study aims to investigate the potential effects of anticonvulsant drugs on neuropeptides (galanin and neuropeptide Y) and neurotrophic factors (BDNF and NGF) in pentylenetetrazol (PTZ)-kindled seizures in the rat.Methods: Forty-eight adult male Sprague-Dawley rats were included in the study. The animals were divided into 8 groups of six rats. Group 1 was defined as naïve control, and received no medication. Group 2 (PTZ + saline) was treated with sub-convulsive doses of PTZ (35 mg/kg) and saline i.p. for 14 days. For anticonvulsant treatments, Groups 3-8 were treated with 200 mg/kg levetiracetam (PTZ + LEV), 1 mg/kg midazolam (PTZ + MDZ), 80 mg/kg phenytoin (PTZ + PHT), 80 mg/kg topiramate (PTZ + TPR), 40 mg/kg lamotrigine (PTZ + LMT) and 50 mg/kg sodium valproate (PTZ + SV), respectively. All anticonvulsant drugs were injected 30 min prior to PTZ injection throughout 14 days. Following treatment period, behavioral, biochemical and immunohistochemical studies were performed.Results: PTZ + saline group revealed significantly decreased galanin, NPY, BDNF and NGF levels compared to control. PTZ + MDZ group had significantly increased galanin, BDNF and NGF levels compared to saline group. Also, PTZ + LEV group showed increased BDNF levels. PTZ + saline group revealed significantly lower neuron count and higher GFAP (+) cells in hippocampal CA1-CA3 regions. All anticonvulsants significantly reduced hippocampal astrogliosis whereas only midazolam, levetiracetam, sodium valproate and lamotrigine prevented neuronal loss.Conclusion: Our results suggested that anticonvulsant drugs may reduce the severity of seizures, and exert neuroprotective effects by altering the expression of neuropeptides and neurotrophins in the epileptogenic hippocampus.

The investigation of therapeutic potential of oxytocin and liraglutide on vincristine-induced neuropathy in rats.

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP-1 analogue, in a rat model of vincristine-induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR-administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR-induced neuropathy.

The Preventive Effect of Oxytocin on Retinopathy in Streptozotocin-Induced Diabetic Rats

Objectives: The aim of this study was to investigate the impact of intravitreal and intraperitoneal use of oxytocin (OT) on retinopathy in streptozotocin-induced diabetic rats. Materials and Methods: Twenty-four 6­8-week-old adult male and female Sprague Dawley rats were used in the study. Diabetes was induced in the rats with a single injection of intraperitoneal streptozotocin. Diabetes was verified after 48 hours by measuring blood glucose levels of 260 mg/dl (14.4 mmol/L) or higher in diabetic rats. The rats were divided into 4 groups and treated as follows: intravitreal physiological saline group (0.01 mL saline weekly), intravitreal OT group (10 µU/µL OT weekly), intraperitoneal physiological saline group (1 mL daily), and intraperitoneal OT group (100 IU/kg OT daily). Hamilton syringes fitted with 27-gauge needles were used for intraperitoneal injections while 31-gauge needles were used for intravitreal injection. After 4 weeks of treatment the rats were euthanized to evaluate outer nuclear layer (ONL) thickness, vascular endothelial growth factor (VEGF) immunoexpression, and plasma VEGF levels from blood samples obtained by cardiac puncture. Results: Morphometric analysis of retinal cross-sections showed that intravitreal and intraperitoneal OT significantly increased ONL thickness compared to physiological saline-treated groups. Also, OT treatment significantly decreased VEGF protein expression compared with the physiological saline groups. Plasma VEGF level was significantly higher in the physiological saline treatment group compared to the OT treatment group. Conclusion: OT reduces diabetic retinopathy progression, particularly when administered intravitreally. To our knowledge, this is the first attempt to investigate the impact of OT on diabetic retinopathy and may provide a new area for further research.

The investigation of protective effects of glucagon-like peptide-1 (GLP-1) analogue exenatide against glucose and fructose-induced neurotoxicity.

Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by hyperglycemia due to insufficiency of insulin and/or insulin resistance. Clinical studies have revealed a higher risk of neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease in diabetic patients. Recently, glucagon-like peptide-1 (GLP-1) is an attractive potential treatment modality for various neurodegenerative diseases. In our study, we aimed to investigate whether exenatide, a GLP-1 analogue, has neuroprotective effects against glucose and fructose-induced toxicity in human SH-SY5Y neuroblastoma cell line. Neurotoxicity was induced by incubating SH-SY5Y cells with different doses (25-100 mM) of glucose and fructose for 24, 48 and 72 hours. Following determination of the significant toxic doses of glucose and fructose, the cells were treated with various doses of exenatide (10-250 nM) in the presence or absence of glucose and fructose. Neurotoxicity was evaluated by MTT assay and Hoechst 33258 staining. Caspase-3 activity and the levels of advanced glycation end products (AGEs) were determined in the cytosolic fractions of treated cells. Our results demonstrated that both glucose and fructose treatments decreased cell viability in neuronal cells dose and time-dependently. Glucose and fructose-treated groups showed increased numbers of apoptotic cells, caspase-3 activity and AGEs levels. Treatment of the cells with exenatide significantly prevented cell death. The most prominent effect was observed at 100 nM exenatide-treated cultures. Our results suggest that high doses of glucose and fructose may lead to neurotoxicity, and exenatide may have protective effects against neuronal damage through its anti-apoptotic feature.

The Investigation of the Antitumor Agent Toxicity and Capsaicin Effect on the Electron Transport Chain Enzymes, Catalase Activities and Lipid Peroxidation Levels in Lung, Heart and Brain Tissues of Rats.

Cisplatin is one of the most active cytotoxic agents in cancer treatment. To clarify the interaction with mitochondria, we hypothesize that the activities of mitochondrial electron transport chain (ETC) enzymes succinate dehydrogenase (SDH) and cytochrome c oxidase (COX), nucleotide levels, as well as levels of catalase (CAT) enzyme and membrane lipid peroxidation (LPO) can be affected by cisplatin. There was a significant decrease of both SDH and COX activities in the lung, heart, and brain tissues at the 1st day after cisplatin exposure, and the observed decreased levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in comparison with the control could be because of cisplatin-induced mitochondrial dysfunction. The investigations suggested that cisplatin inhibits SDH, COX, and ATP synthase. The higher LPO level in the studied tissues after 1 and 4 days post-exposure to cisplatin compared to control can be inferred to be a result of elevated electron leakage from the ETC, and reactive oxygen species (ROS) can lead to wide-ranging tissue damage such as membrane lipid damage. Consequently, it was observed that capsaicin may have a possible protective effect on ETC impairment caused by cisplatin. The activities of SDH and COX were higher in heart and brain exposed to cisplatin + capsaicin compared to cisplatin groups, while LPO levels were lower. The investigated results in the cisplatin + capsaicin groups suggested that the antioxidant capacity of capsaicin scavenges ROS and prevents membrane destruction.

Neurobehavioral effects of long-term maternal fructose intake in rat offspring.

BACKGROUND: Previous studies have indicated an association between maternal metabolic conditions and general developmental disturbances of the offspring. OBJECTIVE: We aimed to investigate the influence of long-term maternal fructose intake during gestation and lactation on neurobehavioral development of rat offspring. METHODS: Twelve female Sprague Dawley rats were received either 30% fructose enriched water (n = 6) or regular tap water (control, n = 6) for 12 weeks. Then, control and fructose-received females were caged with a fertile male, and received 30% fructose and regular chow throughout pregnancy, delivery and until offspring's weaning. On P21, forty littermates (10 male control, 10 female control, 10 male fructose and 10 female fructose) were separated and housed with ad libitum access to standard food and tap water. Following behavioral evaluations at P50, brain levels of TNF-α, neuregulin 1 (NRG1), glutamic acid decarboxylase 67 (GAD67), nerve growth factor (NGF), insulin-like growth factor 1 (IGF-1), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed. RESULTS: Analysis of the behavioral tests (three-chamber social test, open field test, passive avoidance learning test and stereotypy test) revealed significant differences among the groups. Histologically, hippocampal CA1 and CA3 regions displayed significant alterations such as gliosis and neuronal cell death in fructose-exposed groups compare to controls. Biochemical measurements of the brain levels of TNF-α and neurodevelopmental markers showed significant differences between controls and fructose-exposed groups. CONCLUSION: These results suggest a possible link between the chronic maternal metabolic stress, such as long-term fructose intake, and neurodevelopmental disturbances in the offspring.

Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study.

The aim of the present study was to compare the effects of artificial sweeteners (aspartame, saccharin, and sucralose) on rat brain. Twenty-four adult male Sprague-Dawley rats were included in the study. The control group (n = 6) received regular tap water, whereas other groups received aspartame (3 mg/kg/day, n = 6,) or saccharin (3 mg/kg/day, n = 6) or sucralose (1.5 mg/kg/day, n = 6) in the drinking water. Following 6 weeks, the passive avoidance learning (PAL) test was performed to evaluate the neurobehavioral effects of sweeteners. The brains were assessed for lipid peroxides, neuron count, and Glial fibrillary acidic protein (GFAP) immunohistochemistry. Our results demonstrated that chronic intake of sweeteners significantly impaired PAL performance in all groups. Hippocampal CA1-CA3 areas revealed significantly lower neuronal count in aspartame and increased GFAP expression in all groups. Brain lipid peroxides were significantly higher in all groups. Our findings suggest that long-term consumption of artificial sweeteners may have harmful effects on cognition and hippocampal integrity in rats.

Neuroprotective effects of octreotide on diabetic neuropathy in rats.

The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

Accumulation of α-Synuclein in Cerebellar Purkinje Cells of Diabetic Rats and Its Potential Relationship with Inflammation and Oxidative Stress Markers.

Objective. The present study was conducted to evaluate the relationship between plasma oxidative stress markers such as malondialdehyde (MDA) and glutathione (GSH), inflammatory marker pentraxin-3 (PTX3), and cerebellar accumulation of α-synuclein in streptozotocin- (STZ-) induced diabetes model in rats. Methods. Twelve rats were included in the study. Diabetes (n = 6) was induced with a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Diabetes was verified after 48 h by measuring blood glucose levels. Six rats served as controls. Following 8 weeks, rats were sacrificed for biochemical and immunohistochemical evaluation. Results. Plasma MDA levels were significantly higher in diabetic rats when compared with the control rats (p < 0.01), while plasma GSH levels were lower in the diabetic group than in the control group (p < 0.01). Also, plasma pentraxin-3 levels were statistically higher in diabetic rats than in the control rats (p < 0.01). The analysis of cerebellar α-synuclein immunohistochemistry showed a significant increase in α-synuclein immunoexpression in the diabetic group compared to the control group (p < 0.01). Conclusion. Due to increased inflammation and oxidative stress in the chronic period of hyperglycemia linked to diabetes, there may be α-synuclein accumulation in the cerebellum and the plasma PTX3 levels may be assessed as an important biomarker of this situation.

Which Should Be the Preferred Technique During Laparoscopic Ovarian Cystectomy.

The aim of the present study was to determine the long-term effects of different laparoscopic hemostatic techniques on ovarian reserve after ovarian cystectomy. Ninety patients with unilateral ovarian cysts were recruited and randomly distributed into 2 groups. Laparoscopic stripping cystectomy was performed in all patients. Afterward, cystectomy hemostasis was achieved via hemostatic suture or bipolar electrocoagulation. Serum levels of anti-Müllerian hormone (AMH) were determined preoperatively and postoperatively at 1, 3, and 12 months, and patients were evaluated for residual ovarian volume, antral follicle count, and pregnancy. The statistical difference was determined between the 2 groups in terms of AMH levels at 3 months (hemostatic suture group = 3.17 ± 3.40 vs bipolar electrocoagulation group = 2.38 ± 2.57, P = .006) and 12 months (hemostatic suture group = 3.71 ± 3.09 vs bipolar electrocoagulation group = 2.78 ± 2.85, P = .005). In addition, in the hemostatic suture group, there was no statistically significant difference between preoperative and postoperative AMH levels ( P = .165) and between the postoperative antral follicle count ( P = .779) and the residual ovarian volume ( P = .248), whereas in the bipolar electrocoagulation group, postoperative AMH levels were lower than preoperative levels ( P = .028) and postoperative residual ovarian volumes at 3 and 12 months were lower than those at 1 month ( P = .001). Nonetheless, pregnancy rates were not significantly different ( P = .546). Bipolar electrocoagulation is more destructive compared with hemostatic suture. However, the ovarian reserve does not decrease further during the follow-up period.

Oxytocin provides protection against diabetic polyneuropathy in rats.

PURPOSE: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats. MATERIALS AND METHODS: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 µg/kg OT or 160 µg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed. RESULTS: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 µg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group. CONCLUSION: Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.

The impact of salpingectomy and single-dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy.

OBJECTIVE: To investigate the effects of salpingectomy and methotrexate treatments on ovarian reserve in ectopic pregnancy. STUDY DESIGN: In this prospective study, a total of 131 patients with ectopic pregnancy were divided into 3 groups of methotrexate (MTX) only (Group-1, n: 55), salpingectomy only (Group-2, n: 61), and salpingectomy following MTX (Group-3, n: 15). Pretreatment and post-treatment anti-Müllerian hormone (AMH) levels were evaluated. RESULTS: Significant differences in AMH levels were detected between group 1 and group 2 (2.52±1.28 vs. 1.96±1.66, p=0.043), and group 1 and group 3 (2.52±1.28 vs. 1.77±0.76, p=0.035) at one month postoperative. However, these differences disappeared at the 3rd postoperative month. When AMH levels were compared within the same group, postoperative one month AMH levels were significantly lower than the preoperative AMH levels only in group 3 (p=0.03). However, this difference also disappeared at the 3rd postoperative month. CONCLUSION: Systemic single-dose methotrexate treatment, unilateral salpingectomy, and salpingectomy following methotrexate administration in ectopic pregnancy were reassuring based on pretreatment and post-treatment AMH levels. Current medical and surgical treatment approaches do not have an obvious negative effect on ovarian reserve.