A new technology for the treatment of premature ovarian insufficiency: Cell sheet.

Premature ovarian insufficiency (POI) is defined as the development of hypergonadotropic hypogonadism before the age of 40 with definitive treatment being absent. In the current study, we aim to compare the efficacy of the cell sheet method with an intravenous (IV) application of adipose-derived mesenchymal stem cells (AdMSCs) to the POI with an animal model. In the current prospective study, 6-to-8-week-old Sprague Dawley rats were generated four groups: (i) a control group in which only PBS was administered; (ii) an only-POI group generated by cyclophosphamide; (iii) a POI group treated by way of IV AdMSCs; and (iv) a POI group treated by way of the cell sheet method. Twenty-eight days after an oophorectomy was performed, intracardiac blood was taken. Follicle count, immunohistochemical examination for GDF9, BMP15, and TUNEL were conducted, gene expressions of GDF9 and BMP15 were examined, and E2 was measured in the serum samples. With hematoxylin-eosin, in the third group, multi oocytes follicles were the most remarkable finding. In the fourth group, most of the follicles presented normal morphology. GDF9 involvement was similar between the first and fourth groups. BMP-15 immunoreactivity, in contrast to fourth group, was weak in all stages in the second and third groups. The current attempt represents a pioneer study in the literature in which a cell sheet method is used for the first time in a POI model. These results suggest that the cell sheet method may be a feasible and efficient method for the stem cell treatment of models with POI and could be a new treatment approach in POI.

Do small for gestational age fetuses have placental pathologies?

PURPOSE: Although small for gestational age (SGA) does not cause adverse perinatal outcomes, the placental pathology for fetal growth restricted (FGR) and SGA fetuses is still unknown. The aim of this study is to evaluate the differences between placentas of early onset FGR, late onset FGR, SGA, and appropriate for gestational age (AGA) pregnancies in the manner of microvasculature and expression of anti-angiogenic PEDF factor and CD68. METHODS: The study included four groups (early onset FGR, late onset FGR, SGA and AGA). Placental samples were obtained just after labor in all of the groups. Degenerative criteria were investigated with Hematoxylin-eosin staining. Immunohistochemical evaluation with H score and m RNA levels of Cluster of differentiation 68 (CD68) and pigment epithelium derived factor (PEDF) were performed for each group. RESULTS: The highest levels of degeneration were detected in the early onset FGR group. In means of degeneration SGA placentas were found to be worse than the AGA placentas. The intensity of PEDF and CD68 were significant in early FGR, the late FGR and SGA groups compared to the AGA group (p < 0.001). The mRNA level results of the PEDF and CD68 were also parallel to the immunostaining results. CONCLUSION: Although SGA fetuses are considered constitutionally small, the SGA placentas also demonstrated signs of degeneration similar to the FGR placentas. These degenerative signs were not seen among the AGA placentas.

The histological and biochemical analysis of the effects of radiofrequency radiation on testis tissue of rats and the protective effect of melatonin.

Background/aim: Primarily due to wireless communication devices, especially mobile phones, there has been a steady rise in the intensity of nonionizing radiofrequency radiation (RFR). In recent years, increased human health problems raised concerns about whether there is a positive relationship between intense exposure to RFR and public health. The present study aims to investigate the effects of GSM-like RFR exposure on the male reproductive system and the impact of melatonin treatment (synergistic, antagonist, or additive). Materials and methods: Thirty-six male Wistar Albino rats were used and separated into six groups: i. Control; ii. Sham; iii. RFR exposure; iv. Control-melatonin; v. Sham-melatonin; vi. Melatonin + RFR exposure. Animals were exposed to 2600 MHz RFR with electric (E) field levels of 21.74 V/m for 30 min per day, 5 days per week, for 4 weeks. All testicular tissue samples were evaluated under a light microscope for hematoxylin-eosin staining. Biochemical analyses were performed by measuring malondialdehyde, total nitric oxide, glutathione, and glutathione peroxidase levels. We evaluated the combined effects of prolonged RFR exposure and melatonin treatment on ROS-mediated structural changes in testicular tissues. Results: Results showed that reactive intermediates (malondialdehyde and total nitric oxide) increased significantly with RFR exposure, while the protective effect of melatonin effectively reduced the radical levels of the tissues. Histological evaluation revealed a decrease in cell population and connective tissue elements under RFR exposure, accompanied by marked edema in the testicular tissues. Conclusion: The structural and functional effects of prolonged RFR exposure might be ROS-based. Moreover, these adverse effects might be compensated with externally treated supplements. There is a need for new extensive research.

Effects of quercetin on hepatic fibroblast growth factor-21 (FGF-21) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) levels in rats fed with high fructose.

BACKGROUND: Available studies show that quercetin reduces Metabolic Syndrome (MetS) and its complications, increases insulin sensitivity and improves glucose levels. It has been reported that the increase in hepatic gene expressions of fibroblast growth factor-21 (FGF-21), an important metabolic regulator of insulin sensitivity, glucose and energy homeostasis, and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which plays a central role in the regulation of cellular energy metabolism, eliminate the negative effects of fructose in fructose-fed rats. The main purpose of our study is to examine the effects of quercetin on hepatic FGF-21 and PGC-1α expressions and levels, as well as its protective and therapeutic role on MetS components in rats fed with fructose. METHODS AND RESULTS: In our study, 24 Sprague Dawley male rats were divided into 4 groups: control, fructose, quercetin, fructose+quercetin (n = 6). During the 10-week experiment, quercetin was administered at a daily dose of 15 mg/kg body weight and fructose at a rate of 20%. Blood pressure and weights of all groups were measured and recorded. At the end of week 10, blood and liver tissue samples were taken. Serum insulin, glucose and triglyceride, total, HDL and VLDL cholesterol levels were determined from the samples. Insulin resistance was calculated using the HOMA-IR formula. Hepatic PGC-1α and FGF-21 protein levels and their mRNA expressions were determined. Criteria for metabolic syndrome were successfully established with fructose. It was observed that the administration of quercetin alone and in combination with fructose exerted positive effects and improved MetS criteria. It was determined that the administration of quercetin increased hepatic FGF-21 and PGC-1α protein levels and Messenger RNA (mRNA) expressions of them, which were decreased by fructose application. CONCLUSIONS: The results of our study showed that 10-week administration of quercetin at 15 mg/kg exerted beneficial effects on lipid and carbohydrate metabolism in the fructose-mediated MetS model; therefore, quercetin may have great potential in the prevention and treatment of metabolic disorders.

The relationship between good quality embryo rates and IVF outcomes/embryo transfer policies in extended embryo culture.

This study aims to investigate which parameters affect the change in good quality embryo rates during the cleavage stage and whether they have any effect on embryo transfer policies and IVF results. We analysed changes in good quality embryo (grades 1 and 2) rates during the period on days 2, 3 and 5; patients with five or fewer embryos (group 1), 6-10 embryos (group 2) and more than 10 embryos (group 3). The good quality embryo rates decreased in all groups on day 5. When the infertility reasons are studied among all of the groups, ovulatory dysfunction is found to be significantly higher in group 2 compared to group 1 and unexplained infertility was found to be significantly higher in group 2 compared to group 1 and group 3. Total antral follicle, mature oocyte and total oocyte counts were found to be significantly lower in group 1. However, there is no significant difference found among all of the groups for ß-HCG levels and clinical pregnancies. Changes in good quality embryo rates at the cleavage stage in extended embryo culture do not have an impact on IVF results.IMPACT STATEMENTWhat is already known on this subject? The number and quality of embryos in the cleavage stage are important parameters affecting the embryo transfer decision on day 5. There is still insufficient knowledge concerning changes in the percentage of increased good quality embryo transfers associated with IVF outcomes during the second to the third day, and the third to the fifth day.What do the results of this study add? Day 5 embryo transfer is possible in patients with a low number of embryos, according to our results. The good quality embryo rates of patients with a low number of embryos at the cleavage stage are more promising compared to patients having more than five embryos.What are the implications of these findings for clinical practice and/or further research? An extended embryo culture option can be used on patients with a low number of embryos for clinical practice.

The other side of COVID-19 pandemic: Effects on male fertility.

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a major pandemic threat worldwide. According to the existing clinical data, this virus not only causes respiratory diseases and affects the lungs but also induces histopathological or functional changes in various organs like the testis and also the male genital tract. The renin-angiotensin system (RAS), also ACE 2 and TMPRSS2 play an important role in the cellular entry for SARS-CoV-2. Because the male genital system presents high ACE 2 expression, the importance of this pathway increases in COVID-19 cases. As the COVID-19 pandemic has affected the male genital system in direct or indirect ways and showed a negative impact on male reproduction, this paper focuses on the possible mechanisms underlying the damage caused by COVID-19 to the testis and also other components of the male genital tract.

Arterial Occlusion After Hyaluronic Acid Injection: Treatment With Hyaluronidase and Streptokinase.

ABSTRACT: The most feared complication of the hyaluronic acid injections in the periorbital region is embolism of the central retinal artery. The present study aimed to compare the effectiveness of hyaluronidase administered intravenously (systemically) alone or in combination with streptokinase with that of intra-arterial revascularization. Thirty rats were divided into 5 groups. The bilateral oblique groin flap of the rats was raised; the right side was the experiment group, and the left side was the sham control. The right superficial epigastric artery was occluded with a hyaluronic acid injection. After occlusion, no additional procedures were performed in group 1, whereas group 2 received systemic hyaluronidase, group 3 received intra-arterial hyaluronidase, group 4 received systemic hyaluronidase and streptokinase, and group 5 received intra-arterial hyaluronidase and streptokinase. On the seventh day, the rats were killed, flap necrosis rate was calculated, and histological examination was performed. There was no significant difference in the necrosis rates of the rats in groups 2, 3, 4, and 5 (P > 0.05). In histological evaluation, the histological view closest to normal arterial structure was observed in group 4. Immunohistochemical analysis revealed that the ischemia scores of systemic therapy were significantly lower than those of intra-arterial therapy. These results have shown that hyaluronidase and streptokinase administered systemically is as effective as intra-arterial revascularization and does not cause arterial wall degeneration. It has been shown that systemic administration of hyaluronidase and streptokinase is as successful as intra-arterial revascularization in the treatment of arterial embolism with hyaluronic acid.

Is leptin receptor expression triggered in the case of embryo transfer to endometrium coculture?

Background/aim: A synchronized dialogue between maternal and embryonic tissues is required for successful implantation. Low uterine receptivity is responsible for two-thirds of implantation failures and leptin is effective in the physiology of reproduction by binding to specific receptors. In this study, we investigateleptin receptor expression in cases of embryo transfer to endometrial coculture. Materials and methods: Biopsy materials were taken from 20 females with indication for coculture application and were cultured in an appropriate medium after the epithelial cells were isolated. The grown cells were cultured in chamber slides as the first group. For the second group, day 3 embryo was added to chamber slides and the development was observed. The embryo was transferred 1 or 2 days later and other cells (after the transfer process) were used to form the second group. After fixation, immunohistochemical staining was performed with anti-leptin primary antibody. Results: Regarding the coculture without embryo transfer, moderate leptin receptor immunoreactivity was seen in the perinuclear region and the cell membrane. Also, regarding the coculture with embryo transfer, moderate leptin receptor immunoreactivity was seen in the cytoplasm and strong leptin receptor immunoreactivity was seen in the cell membrane. Conclusion: Embryo transfer to endometrium coculture triggers leptin receptor expression

Effects of Low-Level Laser Therapy With a Herbal Extract on Alveolar Bone Healing.

PURPOSE: This study investigated the effect of a gallium-aluminum-arsenide (GaAlAs) diode laser used in low-level laser therapy (LLLT) with the application of Mecsina Hemostopper on mandibular alveolar bone healing. MATERIALS AND METHODS: Standard semispherical bone defects were created in left mandibular diastema sites of 32 female Long-Evans rats. Experimental animals were allocated to 1 of 4 groups: control group (no treatment), laser group (GaAlAs LLLT), Mecsina group, and laser-Mecsina combination group. Liquid Mecsina 0.01 mL was applied to the bone defects. Laser treatment was performed for 7 days after surgery at an energy dose of 10 J/cm2. All animals were sacrificed to observe hard tissue healing histologically, immunohistochemically, and radiologically at 30 days after surgery. RESULTS: Histologic assessment showed significantly more calcified tissue areas and significantly more osteoblast cells in the laser and laser-Mecsina groups than in the other groups (P < .01). Qualitative morphologic assessment showed that more bone tissue was present in the laser-Mecsina group than in the other groups. CONCLUSION: This study showed that LLLT, Mecsina application, and combined treatments were effective in healing alveolar bone among all tested treatment modalities.

Sutureless approach with vein grafts and mesenchymal stem cells in primary nerve repair: Functional and immunohistological results.

PURPOSE: The aim of this study was to define a sutureless peripheral nerve repair technique with a vein graft and bone marrow-derived stem cells (BMSC) and compare it to epineural repair. MATERIALS AND METHODS: Thirty Wistar Albino rats were divided into five groups evenly. In the control group (C), epineural repair was performed. In the SV (suture + vein) and MSV (BMSC + suture + vein) groups, epineural repair was wrapped with a vein graft. In the V (vein) and MV (vein + BMSC) groups, sutureless repair using a vein graft was performed by taking sutures away from the regeneration site. Rats were evaluated with pinprick, toe spread tests and sciatic nerve index (SFI) at 4th, 8th, and 12th weeks. They were sacrificed at 12th week, repair sites were harvested and evaluated immunohistochemically. RESULTS: There was no difference in pinprick and toe spread tests between the groups at 12th week. The mean SFI was -76.5 ± 3.7, -65.2 ± 11.7, -46.2 ± 19.4, -68.8 ± 9.8, -56 ± 8.8 in the C, SV, MSV, V, MV groups, respectively. The MSV group showed significantly the best SFI results (P < .05). NF-H immunostaining scores were as C; 1 ± 0.18, SV; 2.5 ± 0.36, MSV; 4 ± 0.49, V; 1.56 ± 0.54, MV; 3 ± 0.39, whereas GAP-43 scores were as C; 1 ± 0.31, SV; 2.66 ± 0.56, MSV; 4.50 ± 0.23, V; 2 ± 0.23, MV; 3 ± 0.6. The best nerve regeneration according to immunostaining results was observed in the MSV group (P < .05). The mean fibrosis area was 221.5 ± 25.9, 101.6 ± 7.1, 121.3 ± 18.8, 150.3 ± 12.1, 152.4 ± 11.8 µm2 in the above groups, respectively. SV and MSV groups showed the significantly less fibrosis area (P < .05). CONCLUSION: Epineural suture repair combined with vein wrapping and BMSCs (MSV) showed the best SFI, GAP-43, and NF-H immunostaining results.

Botulinum Toxin Type A: Assessing The Effects on The Brain Stem.

BACKGROUND: In this study, our aim is to investigate the possible effects of Botulinum toxin type A administrations in the early and late periods on the brain stem. METHODS: Eighteen white New Zealand rabbits were used in this study with the subjects being divided into three groups. Group I received 0.05 mL sterile saline to the left anterior auricular muscles. Group II and III were injected with Botulinum toxin type A (Botox, Allergan) to the left anterior auricular muscles. Group II was sacrificed 5 days after application and Group III was sacrificed 12 weeks after application; brain stem tissues were then taken. The samples were examined with Caspase 3, 8, and 9 immunohistochemical stainings. RESULTS: In the control group with Caspase-3 immune staining, moderate-to-strong immune reactivity was seen in a small number of neurons. In the Caspase-8 and 9 immune stainings, the immune reactive neurons were seen in greater numbers when compared with the Caspase-3 immune reactive neurons. In the early and late period, groups with Caspase-8 and 9 immune stainings, the immune reactive neurons were seen in greater numbers and in the wider area when compared with the Caspase-3 immune reactive neurons. No significant differences were recognized in the Caspase immune stainings between the early and late period groups. The results were statistically supported. CONCLUSION: It was concluded that Botulinum toxin type A application did not trigger apoptosis in stem cell tissues. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Effect of Hyaluronic Acid Application on the Perisilicon Capsule Structure.

BACKGROUND: Silicon implants constitute a major part of plastic surgery practice. Although materials with high biocompatibility have been used around the implants, capsule formation still develops and progressive nature of this process results in capsule contraction. The aim of this study is to evaluate the effects of hyaluronic acid injected around the silicon block on the capsule structure. METHODS: Twenty Wistar albino rats were used in the study. Rats were divided into two main groups (group 1 and group 2) and two subgroups. Rats in group 1 were sacrificed in week 4 and rats in group 2 were sacrificed in week 8. A subcutaneous pouch was created in the dorsum of the rats and a silicon block was placed into the pouch in groups 1A and 2A. 0.2 ml of hyaluronic acid was injected around the silicon block in group 1B and group 2B. Rats were sacrificed and capsule structure and thickness were analyzed following macroscopic evaluation. Concentrations of transforming growth factor-ß1 (TGF-ß1) and heat shock protein-47 (HSP-47) were evaluated immunohistochemically, and statistical comparisons were made. RESULT: Capsule structure consisted of three layers in all the groups. A more intense collagen structure was observed in the middle layer. The capsule was thinnest in group 1A and thickest in group 2B; the difference between the groups was statistically significant. TGF-ß1 was most intense in group 2B and it was correlated with the amount of collagen. Involvement of HSP-47 was observed mainly in collagen and also in fibroblasts and vascular structures, and its concentration was found to be lower in groups 2A and 2B. CONCLUSION: Exogenously added cross-linked hyaluronic acid increased the capsular thickness and may increase the risk of developing capsular contracture around silicone implants. LEVEL OF EVIDENCE II: Evidence was obtained from the well-designed controlled trials without randomization.

Ciliary body toxicities of systemic oxcarbazepine and valproic acid treatments: electron microscopic study.

Ciliary body is responsible for humour aqueous production in posterior chamber. Valproic acid (VPA) has been widely used for the treatment of epilepsy and other neuropsychiatric diseases such as bipolar disease and major depression. Oxcarbazepine (OXC) is a new anti-epileptic agent that has been used recently for childhood epilepsies such as VPA. In this study, we aimed to investigate the effects of VPA and OXC treatments used as antiepileptic in ciliary body by electron microscopy. In our study, 40 Wistar rats (21 days old) were divided equally into four groups which were applied saline (group 1), VPA (group 2), OXC (group 3) and VPA + OXC (group 4). The as-prepared ocular tissues were characterized by transmission electron microscopy (TEM) technique in scanning and transmission electron microscopy (SEM-TEM) (Carl Zeiss EVO LS10). The results confirmed that VPA caused dense ciliary body degeneration. Additionally, ciliary body degeneration in group 4 was supposed to be due to VPA treatment. Ciliary body damage and secondary outcomes should be considered in patients with long-term VPA therapy.

The Effect of Maternal High-Fat Diet on Adipose Tissue Histology and Lipid Metabolism-Related Genes Expression in Offspring Rats.

The developing fetus is dependent on the maternal nutritional environment. This study was conducted to determine the effects of a maternal high-fat diet (HFD) applied during pregnancy and/or lactation on the expression levels of some lipid-related genes in rat models. Half of the pregnant rats (n: 6) were fed an HFD (energy from fat: 45%), while the other half (n: 6) were fed a control diet (CD) (energy from fat, 7.7%) during the pregnancy period. During lactation, dams in both groups were divided into two subgroups, with half fed the CD and the other half fed the HFD. Thus, four groups were obtained: CD-CD, CD-HFD, HFD-CD, and HFD-HFD. At the end of lactation, all mothers and half of the offspring were sacrificed. The remaining offspring were fed a CD for five weeks. The average birth weight of the CD group offspring was found to be lower than that of the HFD group (p < 0.05). The amount of adipose tissue was highest in CD-HFD (p < 0.05), while gene expression levels were similar between groups (p > 0.05), and the most degenerative histological changes were observed in the eight-week HFD-HFD (p < 0.05). This study suggests that maternal HFD during pregnancy and lactation may increase adiposity in offspring rats, especially during the weaning period.

Acyl ghrelin, desacyl ghrelin and their ratio affect hepatic steatosis via PPARγ signaling pathway.

BACKGROUND AND STUDY AIMS: Ghrelin is an appetite hormone-containing 28-amino acid and has 4 different forms in the body. Ghrelin forms have different physiological functions in the body. This study aims to analyze the effect of acyl and desacyl ghrelin hormone on hepatic steatosis and biochemical findings in 36 male Wistar rats. MATERIALS AND METHODS: Rats were split into 6 equal groups, consisting of control, acyl ghrelin, desacyl ghrelin, acyl/desacyl 3:1, acyl/desacyl 1:1, and acyl/desacyl 1:3 groups, and administered placebo or 200 ng/kg hormone subcutaneous twice a day for 14 days. Oral Glucose Tolerance Test (OGTT) was performed on Day 15, Insulin Tolerance Test (ITT) on Day 16, and scarification procedure on Day 17. Certain biochemical data and liver diacylglycerol (DAG), glycogen, protein kinase C and PPAR-γ levels were detected in the blood. Histological analyses were also conducted on the liver tissues. RESULTS: The highest plasma total cholesterol and VLDL-K levels were found in the acyl/desacyl 1:3 group, and lower insulin, and HOMA-IR levels were found in groups where acyl and desacyl were administered together (p < 0.05). PPAR-γ gene expression level increased in acyl ghrelin and acyl/desacyl 1:3 groups compared to the control group. Protein kinase C gene expression was highest in the acyl/desacyl 1:3 group. The most severe degenerative findings compliant with steatosis in the liver were observed in the acyl ghrelin group (p < 0.05). CONCLUSION: It was determined that administering rats acyl alone and acyl/desacyl by 1:3 caused the highest PPAR-γ gene expression, serum total cholesterol, HDL-K, and VLDL-K levels in the body. Besides, it is shown that desacyl ghrelin effectively regulates the blood glucose level when administered alone.

Therapeutic effects of melatonin in long-term exposure to 2100MHz radiofrequency radiation on rat sperm characteristics.

INTRODUCTION: Radiofrequency electromagnetic fields (RF-EMFs) are one of the risk factors for male reproductive health and melatonin can be an ideal candidate for therapeutic development against RF-induced male fertility problems due to its antioxidant properties. The possible therapeutic role of melatonin in the destructive effects of 2100MHz RF radiation on rat sperm characteristics is investigated in the present study. METHODS: Wistar albino rats were divided into four groups and the experiment continued for ninety consecutive days; Control, Melatonin (10mg/kg, subcutaneously), RF (2100MHz, thirty minutes per day, whole-body), and RF+Melatonin groups. Left caudal epididymis and ductus deferens tissues were placed in sperm wash solution (at 37°C) and dissected. The sperms were counted and stained. Measurements of the perinuclear ring of the manchette and posterior portion of the nucleus (ARC) were performed and the sperms were examined at an ultrastructural level. All of the parameters were evaluated statistically. RESULTS: The percentages of abnormal sperm morphology were significantly increased with RF exposure, while the total sperm count was significantly decreased. RF exposure also showed harmful effects on acrosome, axoneme, mitochondrial sheath, and outer dense fibers at the ultrastructural level. The number of total sperms, sperms with normal morphology increased, and ultrastructural appearance returned to normal by melatonin administration. DISCUSSION: The data showed that melatonin may be a beneficial therapeutic agent for long-term exposure of 2100MHz RF radiation-related reproductive impairments.

Melatonin effective to reduce the microscopic symptoms of polycystic ovary syndrome-related infertility: An experimental study.

Polycystic ovary syndrome (PCOS) is an endocrine disorder seen in women of reproductive age and has been gradually increasing over the years. The mechanism of the syndrome has still not been clearly understood. In this study, the possible effects of exogenously administrated melatonin on melatonin (MT1) receptor, Growth Differentiation Factor-9 (GDF9), and Bone Morphogenetic Protein-15 (BMP15) in experimental PCOS were investigated. Thirty-two 6-8-week-old Sprague-Dawley rats were randomly divided into four groups (n = 8 in each) as Sham control (Group 1), Melatonin (Group 2), PCOS (Group 3), and PCOS + Melatonin (Group 4) groups. At the end of the 21st day, the experiment was terminated, the ovary tissues were taken, and Hematoxylin-Eosin staining, MT1, GDF9, BMP15 immunohistochemical labeling, western blot, and quantitative real-time polymerase chain reaction (qPCR) analyses were performed. Serum Luteinizing Hormone (LH)/Follicle Stimulating Hormone (FSH) levels and colpo-cytological examinations were also carried out. The results revealed that melatonin administration increased the expression levels of the MT1 receptor, GDF9, and BMP15 in PCOS at protein and mRNA levels. It was determined that melatonin administration reduced the microscopic symptoms of PCOS. Melatonin was found to be effective via the MT1 receptor in the pathogenesis of PCOS, and it suppressed the transport pathways of GDF9 to granulosa cells in antral follicles.

Analysis of potential protective effects of caffeic acid phenethyl ester against gentamicin ototoxicity: An experimental study.

Objectives: In this study, it is aimed to investigate the potential protective effect of caffeic acid phenethyl ester (CAPE) on ototoxicity caused by gentamicin in a rat model. Materials and Methods: Thirty Wistar albino rats were divided into 3 groups. Group I was selected as the control group. Gentamicin was administered intraperitoneally in group II, gentamicin and CAPE in group III. Audiological assessment was performed by the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) measurements before and after treatment of each group. At the end of the study all rats were decapitated, cochlea was removed and electron microscopic examination was performed. Results: In group II post-treatment DPOAE levels were found to be lower than pretreatment DPOAE levels (P<0.05). However, in group III, there is no significant difference between pre- and post-treatment DPOAE levels (P>0.05). Except for Group I, ABR thresholds increased after the procedure and this increase was statistically significant (P<0.0001). According to histological examination by transmission electron microscopy, CAPE has a cellular protective effect against gentamicin ototoxicity. Conclusion: CAPE may ameliorate hearing deterioration caused by gentamicin ototoxicity and protect the cochlear cells from apoptosis due to the strong antioxidant effect.

Involvement of endometrial IGF-1R/IGF-1/Bcl-2 pathways in experimental polycystic ovary syndrome: Identification of the regulatory effect of melatonin.

The involvement of endometrial IGF-1R/IGF-1/Bcl-2 pathways and the potential regulatory effects of exogenously administrated melatonin on this expression is investigated in the experimental PCOS model in the present study. Thirty-two 6-8 week old Sprague Dawley rats were divided into four groups: the Sham Control Group (1% CMC/day by oral gavage [o.g.]); the Melatonin Group (2 mg/kg/day melatonin by subcutaneous administration [s.c.]); the Experimental PCOS Group (1 mg/kg/day Letrozole by o.g.); and the Experimental PCOS + Melatonin Group (1 mg/kg/day Letrozole by o.g. and 2 mg/kg/day melatonin by s.c. administration). Vaginal smear samples were taken from the 14th day to the end of the experiment for colpocytological measurements. At the end of the 21 day experimental period, uterine tissues were taken; Hematoxylin-Eosin histochemical, IGF-1R/IGF-1/Bcl-2, PCNA immuno-histochemical stainings and western blot analyses were performed for related antibodies. All of the data was supported statistically. The epithelium of endometrium lost its single-layer structure in some parts, separation was observed between the epithelium and the basal membrane junction, intracellular edema was found in the uterine glands by the polycystic ovary-induction. Also this induction increased the expression of IGF-1R/IGF-1, Bcl-2, and PCNA proteins. Morphological degenerations returned to its normal appearance generally by the melatonin administrations and melatonin also regulated the increased expression of endometrial IGF-1R/IGF-1/Bcl-2 and PCNA pathways. It is concluded that additional studies are needed, using melatonin as a supporting agent may be appropriate in cases of PCOS.

The effect of antiepileptic drugs on re-myelinization of axons: Phenytoin, levetiracetam, carbamazepine, and valproic acid, used following traumatic brain injury.

OBJECTIVE: Traumatic brain injury is a major health and socioeconomic problem and the first cause of young death worldwide. For this reason, the prevention of post-traumatic brain injury and the research of new methods for it are important today. In this study, we aimed to determine whether the use of antiepileptic drugs contributed to axonal healing after traumatic brain injury. METHODS: Thirty-six Long-Evans rats, each weighing 300-350 g, were used in this study. A total of 6 groups, including the sham, control, and 4 study groups, were determined. A 1.5 mm-sized trauma was created in the biparietal area with a blunt-tipped dissector. Carbamazepine phenytoin valproic acid and levetiracetam (phenytoin: 30 mg/kg, valproic acid: 60 mg/kg, levetiracetam: 80 mg/kg, and carbamazepine: 36 mg/kg) were intraperitoneally administered to the study groups, and the control group intraperitoneally received a physiological saline solution (15 ml/kg) twice daily for 3 days. After 72 h, hemispheres of the sacrificed subjects were taken for examination in biochemistry and histology. Glutathione, malondialdehyde, and NG2 levels in the samples were determined. RESULTS: No significant difference was found in biochemical measurements. Histopathological examination revealed that the NG2 expression was more intense in the group treated with phenytoin and levetiracetam (phenytoin was partly higher) and the amount of edema decreased. The NG2 expression increased and the edema decreased, though lower in the group treated with carbamazepine and valproic acid, compared with phenytoin and levetiracetam. An increase in the NG2 expression and edema intensity were determined in the control and sham groups. CONCLUSION: Antiepileptic drug selection after traumatic brain injury is an important medical matter. Although the patient-oriented selection is essential, the study suggests that the choice of phenytoin, levetiracetam carbamazepine, and valproic acid will, respectively, have an accelerating effect for axonal healing.