Effect of aripiprazole on neural tube development in early chick embryos.

INTRODUCTION: Aripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information regarding ARI, which has been classified as pregnant use category C by the FDA. METHODS: 125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed. RESULTS: According to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001). CONCLUSION: Morphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.

Effect of post-gastrulation exposure to acrylamide on chick embryonic development.

The critical developmental stages of the embryo are strongly influenced by the dietary composition of the mother. Acrylamide is a food contaminant that can form in carbohydrate-rich foods that are heat-treated. The aim of this study was to investigate the toxicity of a relatively low dose of acrylamide on the development of the neural tube in the early stage chick embryos. Specific pathogen-free fertilized eggs (n = 100) were treated with acrylamide (0.1, 0.5, 2.5, 12.5 mg/kg) between 28-30th hours of incubation and dissected at 48th hours. In addition to morphological and histopathological examinations, proliferating cell nuclear antigen (PCNA) and caspase 3 were analyzed immunohistochemically. The brain and reproductive expression gene (BRE) was analyzed by RT-PCR. Acrylamide exposure had a negative effect on neural tube status even at a very low dose (0.1 mg/kg) (p < 0.05). Doses of 0.5 mg/kg and above caused a delay in neural tube development (p < 0.05). Crown-rump length and somite count decreased dose-dependently, while this decrease was not significant in the very low dose group (p > 0.05), which was most pronounced at doses of 2.5 and 12.5 mg/kg (p < 0.001). Acrylamide exposure dose-dependently decreased PCNA and increased caspase 3, with this change being significant at doses of 0.5 mg/kg and above (p < 0.001). BRE was downregulated at all acrylamide exposures except in the very low dose group (0.1 mg/kg). In conclusion, we find that acrylamide exposure (at 0.5 mg/kg and above) in post-gastrulation delays neural tube closure in chicken embryos by suppressing proliferation and apoptosis induction and downregulating BRE gene expression.

Subcortical Volume Changes in Schizophrenia and Bipolar Disorder: A Quantitative MRI Study

SUMMARY: Volume abnormalities in subcortical structures, including the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus have been observed in schizophrenia (SZ) and bipolar disorder (BD), not all individuals with these disorders exhibit such changes. In addition, the specific patterns and severity of volume changes may vary between individuals and at different stages of the disease. The study aims to compare the volumes of these subcortical structures between healthy subjects and individuals diagnosed with SZ or BD. Volumetric measurements of lateral ventricle, globus palllidus, caudate, putamen, hippocampus, and amygdale were made by MRI in 52 healthy subjects (HS), 33 patients with SZ, and 46 patients with BD. Automatic segmentation methods were used to analyze the MR images with VolBrain and MRICloud. Hippocampus, amygdala and lateral ventricle increased in schizophrenia and bipolar disorder patients in comparison with control subjects using MRIcloud. Globus pallidus and caudate volume increased in patients with schizophrenia and bipolar disorder compared control subjects using Volbrain. We suggested that our results will contribute in schizophrenia and bipolar disorder patients that assessment of the sub-cortical progression, pathology, and anomalies of subcortical brain compositions. In patients with psychiatric disorders, VolBrain and MRICloud can detect subtle structural differences in the brain.

Se han observado anomalías de volumen en las estructuras subcorticales, incluidos el hipocampo, la amígdala, el tálamo, el núcleo caudado, el putamen y el globo pálido, en la esquizofrenia (SZ) y el trastorno bipolar (BD); no todos los individuos con estos trastornos presentan tales cambios. Además, los patrones específicos y la gravedad de los cambios de volumen pueden variar entre individuos y en diferentes etapas de la enfermedad. El estudio tuvo como objetivo comparar los volúmenes de estas estructuras subcorticales entre sujetos sanos e individuos diagnosticados con SZ o BD. Se realizaron mediciones volumétricas del ventrículo lateral, globo pálido, núcleo caudado, putamen, hipocampo y amígdala mediante resonancia magnética en 52 sujetos sanos (HS), 33 pacientes con SZ y 46 pacientes con BD. Se utilizaron métodos de segmentación automática para analizar las imágenes de resonancia magnética con VolBrain y MRICloud. El hipocampo, la amígdala y el ventrículo lateral aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con sujetos de control que utilizaron MRIcloud. El globo pálido y el núcleo caudado aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con los sujetos control que utilizaron Volbrain. Sugerimos que en pacientes con esquizofrenia y trastorno bipolar, nuestros resultados contribuirán a la evaluación de la progresión subcortical, la patología y las anomalías de las composiciones cerebrales subcorticales. En pacientes con trastornos psiquiátricos, VolBrain y MRICloud pueden detectar diferencias estructurales sutiles en el cerebro.

Effect of sugammadex administration on neural tube development in 48-h chick embryos.

Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. The aim of this study is to investigate the teratogenic effects of sugammadex on neural tube and embryonic development in early chick embryos. In this study, 50 0-day fertile specific non-pathogenic (SPF) eggs were used. Fifty eggs were divided into 5 different groups, each consisting of 10 pieces. While no substance was given to the control group at the 28th hour of the study, 4 different doses of sugammadex were administered to the experimental groups, respectively 2, 4, 8, 16 mg/kg. Cranio-caudal lengths of embryos, somite numbers, average number of argyrophilic nucleolar regulatory regions (AgNOR) per nucleus, total AgNOR area/total nuclear area (TAA/NA) ratios, Caspase-3 H-Score results, and presence of neural tube defect were compared among the groups. While the mean cranio-caudal lengths, somite counts, TAA/NA ratios and AgNOR counts of the embryos were found to be statistically significantly lower than the control group, Caspase-3 H-Score mean results were found to be significantly higher (p < .05). In addition, it was observed that there was an increase in neural tube patency and developmental delay. As a result, sugammadex crossing the placenta was revealed to increase the release of proapopitotic molecules and disrupt the developmental stages of embryos. Thus, it was determined that sugammadex in increased developmental delay and incidence of neural tube defects in early chick embryos with increased dose dependent. Despite these results, the effects of sugammadex on fetal development in in vivo and in vitro environments should be studied with further studies. RESEARCH HIGHLIGHTS: Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. It has been observed that different doses of sugammadex increase the risk of neural tube defect development on chick embryos and slow the embryo development in a dose-dependent manner.

Observation of the neuroprotective efficacy of vitamin K in a streptozocin-induced diabetes model in chick embryos.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia due to insulin deficiency and/or resistance. Vitamin K (VK) is a group of fat-soluble molecules, including naturally occurring vitamin K1 (phylloquinone). vitamin K2 (menaquinone), and synthetic vitamin K3 (menadione). Beyond coagulation, the health benefits of VK have been described to play different roles in both physiological and pathological processes such as inflammation, energy metabolism, neuroprotection, cellular growth, and survival. It was aimed to observe the antioxidant and/or neuroprotective activity of vitamin K1 in our model of chick embryo diabetic neuropathy (DN) induced by streptozotocin (STZ). Ninety White Leghorn, fertile and 0-day-old SPF (specific pathogen-free) eggs (57 ± 4 gr) were used in the study. Chick embryo blood brain tissues were taken for biochemical evaluation. Plasma insulin and glucose levels were measured. In addition, brain tissue total antioxidant level (TAS), total oxidant level (TOS), malondialdehyde (MDA), and vascular endothelial growth factor (VEGF) levels were measured. Plasma glucose levels were higher in the STZ-treated groups and lower in the treatment groups. Plasma insulin levels were observed to be higher in STZ groups in groups treated with high VK. Low TAS, high MDA, TOS, and VEGF levels were recorded in brain tissue STZ groups. Low VEGF, TOS, and MDA levels were recorded in the group treated with the highest VK, while high TAS levels were observed. In our STZ-induced chick embryo diabetic neuropathy model, we observed that VK1 reduced oxidant damage by showing antioxidant properties or by modulating antioxidant enzymes.

Protective Effects of Different Doses of Ginsenoside-Rb1 Experimental Cataract Model That in Chick Embryos.

PURPOSE: There has been increased interest in phytochemical antioxidants to prevent protein damage and aggregate formation in cataract treatment. In this study, the protective effect of different doses of Rb1 (GRb1), one of the ginsenosides of Panax Ginseng, in the experimental cataract model formed in chick embryos was investigated. METHODS: Five different experimental groups were formed with 100 SPF fertilized eggs: Control (0.9% NaCl to physiological saline), hydrocortisone hemisuccinate sodium (HC), low dose (HC + L-GRb1 (1 mg/kg)), medium dose (HC+). M-GRb1 (2.5 mg/kg)), and high dose (HC + H-GRb1 (5 mg/kg)). All solutions were given to air sack at 15 days of incubation. On the 17th day, the bulbous oculi of the chick embryos were dissected. Cataract formations of the lenses, glutathione (GSH), malondialdehyde (MDA), total antioxidant (TAS), total oxidant (TOS) levels, Caspase-3 H-score, and TUNEL index were determined. In addition, crystalline alpha A (CRYAA) gene expression was evaluated. RESULTS: Cataracts were observed in the control, HC, HC + L-GRb1, HC + M-GRb1, and HC + H-GRb1 groups with a frequency of 0%, 100%, 75%, 56.25%, and 100%, respectively. There were statistically significant differences between the control and HC groups in terms of TAS, TOS, MDA, GSH, Caspase-3 H-score, and TUNEL index (p < .05). When the therapeutic effect of the GRb1 groups was evaluated, the HC group showed significant differences with the HC + L-GRb1 and HC + M-GRb1 groups in almost all parameters (p < .05), while there was no statistical difference with the HC + H-GRb1 group (p > .05). In addition, gene expression levels differed between the groups, although not statistically significant (p > .05). CONCLUSION: 1 mg/kg and 2.5 mg/kg GRb1 applications show therapeutic properties on the HC-induced cataract model. This effect is more pronounced at 2.5 mg/kg.

Automatic segmentation of the cerebellum using volBrain software in normal paediatric population.

BACKGROUND: Morphological differences that can lead to cerebellar volume changes are associated with the pathogenesis of paediatric diseases. The aim of this study was to examine cerebellum volume in a healthy paediatric population. MATERIALS AND METHODS: To provide MRI-based volumetric measurements of the cerebellum, images from the years 2019 to 2021 were scanned retrospectively. A total of 100 images, including the paediatric population aged 0-15 years, were imported into the volBrain software. Volumetric segmentations were obtained automatically, and each lobular cerebellar volume was obtained. The samples were divided into groups of 0-2 years (n = 18), 3-5 years (n = 24), 6-11 years (n = 34) and 12-15 years (n = 24). Obtained cerebellar volumes, age groups, gender and bilateral side comparisons were made. RESULTS: In the comparative analyses performed for the total cerebellum and each of the 12 lobular segments, statistically significant differences were found between the age groups in all measurements except Crus II, lobules VIIB, VIIIA and VIIIB (p < 0.05). In multiple comparison tests, statistically significant differences were found between defined age groups, especially infants and toddlers and early adolescence groups (p < 0.05). There was a significant positive correlation between the ages of the subjects and their cerebellum volumes (p < 0.05). Statistically significant differences were found in lobules I-II, VI, VIIIB, IX and X in right and left side volumes (p < 0.05). CONCLUSION: There is a tendency to increase in cerebellar volume during the transition from childhood to adolescence. The cerebellum has volumetric differences in the first years of life and during adolescence. When the development of a healthy cerebellum is analysed based on volumetric segmentation, differences are observed. The findings of this study may be useful in confirming various theories attributed to the cerebellum in the clinic.

Use of AgNOR staining to determine the effect of metoclopramide on neural tube development in early chick embryos.

Nausea and vomiting during pregnancy are common problems and prolonged pharmacological treatment often is needed; however, the teratogenic effects of anti-emetic drugs on neural tube (NT) development are not clear. We investigated the effects of different doses of metoclopramide on NT development in 48 and 72 h chick embryos using an argyrophilic nucleolar organizing region (AgNOR) staining method. We used 150 fertile, specific pathogen-free eggs incubated for 28 h, then randomly divided into five equal groups: group A, sham control was administered 0.9% saline; groups B - E were administered 0.15 mg/egg, 0.3 mg/egg, 0.6 mg/egg and 1.2 mg/egg, respectively. Half of the eggs in each group were taken from the incubator at 48 h incubation and the other half at 72 h incubation. After incubation, eggs were opened, embryos were dissected from their membranes, fixed with 10% formalin and examined by light microscopy. The NT status, i.e., open or closed, and somite number, crown-rump length, morphological features and gross developmental abnormalities were recorded. Excised embryos were sectioned and stained using hematoxylin and eosin or the AgNOR procedure and examined for morphology and histopathology. Delayed NT closure was observed in all 48 h drug exposed embryos, but in the 72 h groups, this occurred only in high-dose groups. Somite number was reduced significantly in groups C - E compared to the control group. Crown-rump length was decreased in both 48 and 72 h embryos. We found a decreased total AgNOR area:nuclear area ratio in 48 and 72 h embryos of all experimental groups. We found that metoclopramide delayed NT closure in chick embryos in a dose-dependent manner.

Effect of tramadol hydrochloride on neural tube development in 48-hr chick embryos: Argyrophilic nucleolar organizing region and genetic analysis study.

BACKGROUND: Tramadol hydrochloride or tramadol is an opioid analgesic that acts on the central nervous system. The pregnancy category of tramadol is determined as "C" according to the Food and Drug Administration. There are no adequate and well-controlled studies in pregnant women. In this study, we aimed to reveal the effects of tramadol on neural tube (midline) closure by analyzing morphologically, histologically and genetically in chick embryos. METHODS: Ninety White Leghorn species, fertile and 0-day-old specific pathogen-free eggs (60 ± 5 g) were used in the study. Eggs were divided into a total of six groups (control, sham, and drug groups). Four different doses of tramadol (1, 2.5, 5, and 7.5 mg/egg) were administered subblastodermically at the 28th hour of the incubation. All eggs were opened at the 48th hour of incubation and evaluated. RESULTS: Embryos in the control group according to Hamburger-Hamilton classification were compatible with stages 13 and 14. In the groups treated with tramadol, it was determined that the embryos had neural tube closure defects (such as neck, tail regions) and some embryos showed developmental retardation due to the increase in the drug dose. In the statistical analysis performed, a significant difference was found between the control group and the group receiving the highest dose of tramadol in terms of crown-rump length and number of somites (p < .05). The brain and reproductive expression gene expression was upregulated in embryos at each of tramadol doses compared to control group. CONCLUSIONS: It was determined that tramadol causes neural tube closure defects in embryos depending on the dose.

Investigation of the antioxidant effect of Chrysin in an experimental cataract model created in chick embryos.

PURPOSE: Cataract, which occurs as a result of lens opacification, is one of the most common causes of vision loss. In the literature, deterioration of the antioxidant system due to the increase in reactive oxygen species and oxidant levels is shown among the causes of cataract formation. The aim of this study was to investigate the antioxidant effect of chrysin on steroid-induced cataract development in an experimental chick embryo model using morphological, histological and biochemical parameters. METHODS: Within the scope of the study, 150 specific pathogen free (SPF) fertilized eggs were used. Eggs were divided into 6 groups as control (group 1), corn oil (group 2), hydrocortisone hemisuccinate sodium (HC) (group 3), low dose chrysin (group 4), medium dose chrysin (group 5) and high dose chrysin (group 6). On the 15th day of incubation, Chrysin and HC were applicated to the air sac of the eggs with Hamilton and/or insulin injector. On day 17, the chick embryos were removed from the eggs and the bulbus oculi of the embryos were dissected. Lenses of 9 embryos were used for morpholigical cataract grading in each group, lens of 8 embryos for biochemical analysis and intact eyes of 7 embryos for histological evaluation (TUNEL method). RESULTS: No opacity was observed in any of the lenses in Group 1 and 2. Cataract was observed in all lenses in Group 3. The mean opacity grades in group 3 were statistically significantly higher when compared to group 1 and 2 (p<0.05). The difference between group 6 and group 3 was statistically significant (p<0.05). GSH and TAS levels in the lenses were statistically significantly decreased compared to the control group due to HC application (p<0.05). It was determined that the decreased GSH and TAS levels in the lenses increased in relation to the Chrysin application doses. The increased levels of MDA, TOS, caspase 3 and caspase 9 in the HC group decreased significantly depending to the chrysin doses (p<0.05). In addition, while the rate of apoptotic cells determined by the TUNEL method was statistically significantly higher in the HC administered group than in the control group (p<0.05), it was statistically significantly decreased in the chrysin-administered groups, in relation to the dose of chrysin (p<0.05). CONCLUSIONS: We think that anti-cataract effect of crhysin may be due to the antioxidant and antiapoptotic properties of chrysin. However, more research is needed to clarify the anti-cataract effects of chrysin.

Investigation of developmental toxicity of favipiravir on fetal bone and embryonic development.

BACKGROUND: Favipiravir is one of the essential antiviral drugs used for the treatment of coronavirus disease (COVID-19) in some countries. However, there is not enough information about used, especially in pregnancy. Therefore, in this study, it was aimed to determine the developmental toxicity of favipiravir on fetal bone development and embryonic development. METHODS: In this study, 16 pregnant wistar albino rats were used. The rats were divided into four groups: Control (saline) and Group A (50 mg/kg × 5 days), Group B (50 mg/kg × 1 days + 20 mg/kg × 4 days), Group C (20 mg/kg × 5 days). Solutions were administered to the rats by oral gavage from the 10th to 14th days of pregnancy, twice a day. The skeletal system development of fetuses was examined with double skeletal staining and immunohistochemical staining methods. RESULTS: A total of 72 fetuses from pregnant rats, 18 in each group, were included in the study. As a result, depending on favipiravir dose increase, in experimental groups, it was determined that the statistically significant decrease on the ossification rates of anterior and posterior extremity bones, and length and weight of fetuses. CONCLUSION: Exposure to favipiravir during pregnancy impairs bone metabolism and bone formation-resorption stages and may cause developmental delay.

Investigation of teratogenic effects of letrozole on fetal bone development / Investigación de los efectos teratogénicos de letrozol en el desarrollo óseo fetal

SUMMARY: Letrozole is mainly used for the treatment of unexplained infertility, breast cancer and polycystic ovarian syndrome, with secondary use in ovarian stimulation. In cases of unexpected or unknown pregnancy during the use of letrozole, letrozole may cause a teratogenic effect on the fetus. In this reason, in this study, we aimed to determine the effect of letrozole on fetal bone development. In this study, 32 pregnant Wistar albino rats were used. The rats were divided into four groups: Control (saline) and high; 0.3 mg/kg, medium; 0.03 mg/kg, low; 0.003 mg/ kg letrozole. Saline and letrozole were administered in 100 mL solutions by intraperitonaly from day 11 to day 15 of pregnancy. The skeletal system development of fetuses was examined with double skeletal staining, immunohistochemical staining methods and mineral density scanning electron microscopy. A total of 100 fetuses from female rats, 25 in each group, were included in the study. As a result of that, ossification rates were observed to decrease depending on the dose of letrozole in the forelimb limb (scapula, humerus, radius, ulna) and hindlimb (femur, tibia, fibula) limb bones. As a result of the statistical analysis, a statistically significant decrease was found in the ossification rates of all bones between the control group and low, medium, high letrozole groups (p<0.001). Exposure to letrozole during pregnancy adversely affected ossification and bone growth. However, the teratogenic effects of letrozole are unclear. Therefore, it needs to be investigated more extensively.

RESUMEN: Letrozol se usa principalmente para el tratamiento de la infertilidad inexplicable, el cáncer de mama y el síndrome de ovario poliquístico, con estimulación ovárica de uso secundario. En casos de embarazo inesperado o desconocido durante el uso de letrozol, puede causar un efecto teratogénico en el feto. Por esta razón, en este estudio, nuestro objetivo fue determinar el efecto de letrozol en el desarrollo óseo fetal. Se utilizaron 32 ratas albinas Wistar preñadas las cuales se distribuyeron en cuatro grupos: Control (solución salina) y alta; 0,3 mg/kg, medio; 0,03 mg/kg, bajo; 0,003 mg/kg de letrozol. Se administró solución salina y letrozol en soluciones de 100 mL por vía intraperitoneal desde el día 11 hasta el día 15 de la preñez. El desarrollo del sistema esquelético de los fetos se examinó con tinción esquelética doble, métodos de tinción inmunohistoquímica y microscopía electrónica de barrido de densidad mineral. Se incluyeron en el estudio un total de 100 fetos de ratas hembra, 25 en cada grupo. Como resultado, se observó que las tasas de osificación disminuían dependiendo de la dosis de letrozol en los huesos de los miembros torácicos (escápula, húmero, radio, ulna) y de las miembros pélvicos (fémur, tibia, fíbula). Se encontró una disminución estadísticamente significativa en las tasas de osificación de todos los huesos entre el grupo control y los grupos de letrozol bajo, medio y alto (p<0,001). La exposición a letrozol durante la preñez afectó negativamente la osificación y el crecimiento óseo. Sin embargo, los efectos teratogénicos del letrozol no están claros por lo que debe ser investigado más extensamente.

A novel model of early type 1 diabetes mellitus: The chick embryo air sack model.

Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia. Chronic hyperglycemia is associated with long-term dysfunction such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. These complications increase rates of death and disability worldwide. Due to the negative effects of DM on the quality of life, the mechanism and treatments of the disease should be investigated in more detail. Most of the research in diabetes is performed in experimental animals. Experimental animal models contributed to the advancement of clinical research, the development of new therapeutic approaches, the discovery of insulin and the purification of insulin. There are many animal models of DM in the literature. But there are a few DM model studies created with chick embryos. In these studies, it was seen that there were differences in STZ doses and STZ administration techniques. The objective of this study was to create a more acceptable and easier DM model. 180 specific pathogen free (SPF) fertilized chicken eggs (White Leghorn chicken) were used in this study. STZ was administered to 160 SPF eggs for an induced DM model. The remaining 20 SPF eggs were separated as a control group. We used two different DM models (Air sack model (ASM) and Chorioallantoic membrane model (CAMM)) and blood sampling technique in our study. 160 SPF eggs were divided into two groups with 80 eggs in each group, according to the model in which STZ was administered. When the relationship between blood glucose and blood insulin levels were examined, it was determined that there was a significantly strong negative correlation in the control group and ASM 1 group; and a significantly very strong negative correlation was found in the ASM 2 group and ASM 3 group. Our data indicate that the optimal STZ dose to create a DM model was 0.45 mg/egg and the best DM model was ASM. The second technique to be the best blood sampling technique for determining blood glucose levels. We believe that ASM can be used in DM studies and anti-DM drug studies in terms of its easebly, applicability, reproducibility and low cost.

Effect of buscopan, a compound that alleviates cramps, on the developing nervous system of the chick embryo.

BACKGROUND: Buscopan is used to treat stomach cramps including those resulting from irritable bowel syndrome, bladder cramps, and pain related to menstruation. Its pregnancy category is determined as C. It has been shown in experimental animal studies that the drug has a negative effect on the embryo, but sufficient and well-controlled studies have not been conducted in humans. The aim of this study is to investigate effects of buscopan on the development of the neural tube (NT) in chick embryos. METHODS: Sixty specific pathogen-free (SPF) fertilized eggs were used. SPF eggs were placed in an incubator and divided into six groups at 28 hr of incubation. Five different doses (low to high) of buscopan were injected sub-blastodermally. At the end of 48 hr, the embryos were evaluated morphologically and histopathologically. The argyrophilic nucleolar-organizing region (AgNOR) method was used in this study to determine the proliferation activity of cells in NT development in chick embryos. AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each embryo. RESULTS: Depending on the dose, the embryo's crown-rump length and somite number decreased (p < .05). Significant differences were detected among all groups for mean AgNOR number (p < .05) and TAA/NA ratio (p < .05). CONCLUSIONS: Considering the average count of AgNOR cells and TAA/NA ratio, it was found that there was a decrease in cell division depending on the dose. It was determined that buscopan treatment on chick embryos adversely affected early nervous system and NT development.

Posterior Fossa Decompression and superficial durotomy rather than complete durotomy and duraplasty in the management of Chiari 1.

Objective: We aimed to evaluate the effectiveness and reliability of posterior fossa decompression (PFD) and superficial durotomy in patients who underwent surgery for Chiari malformation type 1 (CM1).Materials and Methods: Our study included 54 patients with the diagnosis of CM1 who had surgery between January 2012 and June 2019. The patients were divided into two groups according to the surgical technique applied. Group 1 included 10 patients who underwent classic PFD and duraplasty, and Group 2 included 44 patients who underwent PFD and superficial durotomy surgery. Pre- and postoperative clinical signs and symptoms of each patient were recorded. Simultaneously, morphometric measurements were compared from computed tomography (CT) and magnetic resonance (MRI) images taken pre- and postoperatively. The data of the two groups were compared.Results: Of the 54 patients, 18 were male, and the mean age was 37.51 ± 15.14. A statistically significant difference was found between the pre- and postoperative morphometric measurements of the subarachnoid distance, craniocervical angle, syringomyelia, and hydrocephalus at the cerebellum level in Group 2 patients who underwent PFD and superficial durotomy surgery (p < 0.05). When morphometric measurements and clinical signs and symptoms of both groups were compared, no significant difference was found (p > 0.05). There was a 92% improvement in clinical signs and symptoms postoperatively. The complications seen in Group 1 decreased to a minimum in Group 2.Conclusion: We believe that a minimally invasive surgical method is superior to avoid major complications. We also found PFD and superficial durotomy shorten the duration of the patient's hospital stayAbbreviations: C1: cervical vertebra 1C2: cervical vertebra 2CM: Chiari malformationCM1: Chiari malformation type 1CSF: cerebrospinal fluidCT: computed tomographyMRI: magnetic resonance imagingPFD: posterior fossa decompressionUSG: ultrasonography.

Impact of Bisphenol A on neural tube development in 48-hr chicken embryos.

OBJECTIVES: Bisphenol A (BPA) is one of the most heavily produced chemicals in the world. BPA is involved in the production of many substances such as cosmetics, various foodstuffs, toys, personal care products, detergents and plastic bottles all that are frequently used in daily life. Depending on BPA exposure, sexual maturation and reproductive function, and bone and brain development are adversely affected. The aim of this study is to investigate the possible effects of BPA on the development of the nervous system and neural tube in 48-hr chicken embryos. METHODS: Thirty specific pathogen-free (SPF) fertilized eggs were used in the study. SPF eggs were placed in the incubator and divided into three groups at 28 hr of incubation; control, BPA 1 and BPA 2 (10 eggs in each group). At this stage of incubation, two different doses of BPA were injected sub-blastodermically with the Hamilton microinjector. At the end of 48 hr of incubation, all eggs were opened and embryos were dissected and separated from the embryonic membrane. All embryos were evaluated morphologically and histopathologically. RESULTS: As the BPA dose increased, delays in the development of the nervous system and midline closure increased in the early period of chicken embryos. Depending on the dose, it was found that the embryo's crown-rump length and somite number decreased (p < .05). CONCLUSION: It was determined that BPA application on early chicken embryos adversely affected neural tube development. It was also found to delay midline closure.

Is there effect of intervertebral disc herniation on the lumbar spine in early period? A morphometric and stereological study / ¿Existe algún efecto de la hernia de disco intervertebral en la columna lumbar en el período temprano? Un estudio morfométrico y estereológico

The degeneration of the Lumbar Intervertebral Disc (LIVD) and the other elements of the spine are an inevitable result of aging. However, it is observed that the same degree of degenerative change does not occur in each individual. In the present study, the purpose was to compare the morphometric changes on the lumbar spine with or without intervertebral disc herniation in early period. Group 1 (the Patient Group) consisted of the patients who were diagnosed with lumbar intervertebral disc hernia and who were not operated at least one month clinical duration. Group 2 (the Control Group) consisted of individuals who were selected randomly, had only back pain, underwent magnetic resonance imaging (MRI), and were determined to have intact intervertebral disc. The sagittal and axial MRI sections of lumbar spine was used for measurements and statistical evaluation. There were no statistically significant differences between the intervertebral disc volumes, vertebral body volumes and intervertebral disc anterior and posterior heights of Group 1 and 2 (p>0.05). In terms of anterior-posterior length, the length of the L5 vertebral body was determined to be more in the Patient Group (p<0.05). A correlation was determined in terms of the increase in L2, L4 and L5 volumes with increasing age; however, there were no statistically significant correlations between age increase and a decrease in the intervertebral disc volumes. There were no correlations between the increase in age and the decrease in intervertebral disc heights (p>0.05). There were no apparent relations between the change on the lumbar vertebra corpus and intervertebral disc in early period. It was concluded that the intact intervertebral disc could protect the lower lumbar vertebra corpus from degenerative changes. Although the herniation of the intervertebral disc is newly formed, it is understood that the physiological process or morphometric changes started earlier.

La degeneración del disco intervertebral lumbar y de otros elementos de la columna vertebral son un resultado inevitable del envejecimiento. Sin embargo, no se observa el mismo grado de degeneración en cada individuo. En el presente estudio, el objetivo era comparar los cambios morfométricos en la columna lumbar con o sin hernia de disco intervertebral en el período temprano. El grupo 1 (grupo de pacientes) estaba formado por los pacientes diagnosticados con hernia de disco intervertebral lumbar y que no fueron operados durante al menos un mes. El Grupo 2 (Grupo de Control) consistió en sujetos que fueron seleccionados al azar, reportaban solamente dolor de espalda, fueron sometidos a una resonancia magnética (MRI) y se determinó un disco intervertebral intacto. Las secciones de resonancia magnética sagital y axial de la columna lumbar se utilizaron para las mediciones y la evaluación estadística. No hubo diferencias estadísticamente significativas entre los volúmenes del disco intervertebral, los volúmenes del cuerpo vertebral y las alturas anterior y posterior del disco intervertebral de los Grupos 1 y 2 (p> 0,05). En términos de longitud anterior-posterior, se determinó que la longitud del cuerpo vertebral L5 era mayor en el grupo de pacientes (p <0,05). Se determinó una correlación en términos del aumento en los volúmenes L2, L4 y L5 con el aumento de la edad; sin embargo, no hubo correlaciones estadísticamente significativas entre el aumento de la edad y una disminución en los volúmenes del disco intervertebral. No hubo correlaciones entre el aumento de la edad y la disminución de las alturas de los discos intervertebrales (p> 0,05). No hubo relaciones aparentes entre el cambio en el cuerpo de la vértebra lumbar y el disco intervertebral en el período temprano. Se concluyó que el disco intervertebral intacto podría proteger el cuerpo de la vértebra lumbar inferior de los cambios degenerativos. Aun cuando la formación de la hernia del disco fue reciente, se entiende que el proceso fisiológico o los cambios morfométricos habían comenzado antes.

Potential Anti-Tumor Activity of Kefir-Induced Juglone and Resveratrol Fractions Against Ehrlich Ascites Carcinoma-Bearing BALB/C Mice.

We investigated the potential influence of kefir-induced juglone and resveratrol fractions (JRK) against Ehrlich Ascites Carcinoma (EAC) bearing BALB/c male mice. Kefir yeast was grown in the cell culture supplemented with juglone and resveratrol (1:2). After 48 h incubation, JRK solution was applied (0.1 mL/day i.p.) to the EAC-bearing mice throughout five days. Molecular regulatory mechanisms of apoptotic and anti-apoptotic pathway components were evaluated in the plasma of mice and isolated EAC cells with ELISA, qRT-PCR, and immunocytchemical experiments. EAC-induced upregulation in Bcl-2 and downregulation in Caspase-3 were normalized with JRK in the plasma of mice. Additionally, JRK upregulated the expression levels of apoptotic Bax, p53, Caspase-3,8,9, and APAF-1 proteins together with BAX, CASPASE-8, and CASPASE-9 genes in isolated EAC cells. These changes were also associated with decreased expression levels of anti-apoptotic Bcl-2 and Bcl-xl proteins. Immunocytochemical studies also confirmed the activation of apoptotic pathways and repression of anti-apoptotic proteins in EAC cells with JRK treatment. JRK activates apoptotic pathway and inhibits anti-apoptotic genes and proteins in Ehrlich ascites carcinoma- bearing BALB/c mice that could be beneficial in cancer treatment.

Impact of prenatal exposure to bisphenol A on pregnant rats: Fetal bone development and immunohistochemistry implications.

BACKGROUND:: Bisphenol A (BPA) is one of the most commonly produced chemicals in the world. BPA is used in products such as food packaging, personal care products, detergents, and plastic bottles. This study was conducted to determine the effect of BPA on fetal bone development. MATERIAL AND METHODS:: In this study, 16 pregnant female Sprague-Dawley rats were used. The rats were divided into four groups: the control group and 0.5 mg/kg/day, 5 mg/kg/day, and 50 mg/kg/day dose BPA groups. The skeletal system development of fetuses was examined with double skeletal and immunohistochemistry (IHC) staining (tartrate resistant acid phosphatase (TRAP) and the alkaline phosphatase (AP) expressions) methods. RESULTS:: The highest ossification rates in the humerus, radius, and ulna were detected as 41.05%, 39.25%, and 37.26% in the control group, respectively. The highest ossification rates in the femur, tibia, and fibula were detected as 23.04%, 30.73%, and 32.78% in the control group, respectively. Statistically significant differences were found between control and experimental groups in the TRAP and AP expression of the femur by IHC staining ( p < 0.001). CONCLUSION:: Exposure to BPA during pregnancy adversely affected ossification and bone growth. A dose-dependent decrease was observed in the rate of ossification.

Antioxidant role of melatonin against nicotine's teratogenic effects on embryonic bone development.

OBJECTIVES: This study investigated the possible effects of low (3 mg/kg) and high (6 mg/kg) doses of nicotine on the skeletal development of rat fetuses by the double staining method and the protective role of melatonin (10 mg/kg) against these effects. MATERIALS AND METHODS: Eighteen adult female Wistar-Albino rats were divided into six groups (n=3, each) as control, low-dose nicotine, high-dose nicotine, low-dose nicotine+melatonin, high-dose nicotine + melatonin and melatonin. While nicotine was given to the experimental groups on gestation days 1-20, nicotine and melatonin were administered together to the treatment groups. The fetuses were delivered by cesarean section on the 20th day of pregnancy. The skeletal systems of the fetuses were stained using the double staining method. The forelimbs and hindlimbs of the fetuses were firstly investigated under a stereomicroscope, and then their photos were taken. The total bone length, the length of the ossified part and the ossification rate were calculated using the ImageJ program. RESULTS: The degree of ossification in the bones of the feet and the hands was determined. When the total bone length and the length of the ossified part were evaluated, they were significantly decreased in the nicotine groups (P<0.05), but were close to each other in the treatment and the control groups (P<0.05). CONCLUSION: It has been found that the use of nicotine during pregnancy delays skeletal ossification and that melatonin, a powerful antioxidant, eliminates the teratogenic effects of nicotine.