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OBJECTIVE: To investigate how well the Sysmex automated urine-analyzer's atypical-cell parameter can predict oncological outcomes when compared to cytology and pathology data in the follow-up of NMIBC patients. MATERIAL AND METHODS: We prospectively collected clinical data from 273 patients who underwent cystoscopic examination due to benign and malign reasons in our center between June 2020 and March 2021. Patients were divided into 2 groups. (Group-1: Patients with no previous diagnosis of bladder cancer(BC), Group-2: Patients with previously diagnosed NMIBC). The a typical-cell parameter was determined by studying the urine sample given by the patient for urinalysis. The atypical-cell parameter's sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were assessed. RESULTS: A total of 76(41.1%) patients underwent diagnostic procedures (Group-1) and remaining 109(58.9%) patients were NMIBC patients (Group-2) who subjected to control cystoscopy on follow-up. BC was detected in 70 patients, 28 of whom were newly diagnosed (Group-1). Remaining 42 patients had recurrence during their follow-up (Group-2). Atypical cell values of 70 patients with BC were determined to be statistically significantly higher than those without malignancy. In Group-2, median atypical-cell values for those with no malignancy, those with low-grade BC reccurrence, and those with high-grade BC recurrence were 0.00(IQR:0.00-0.80), 0.25(IQR:0.10â1.10) and 1.20(IQR:0.70-2.15), respectively (p<0.001). For a cut-off of 0.1 atypical cells/µL, sensitivity and specificity were measured as 83.33% and 53.73%, respectivel (AUC:0.727;p-value<0.001). CONCLUSION: Atypical-cell parameter of the Sysmex-UF-5000 automated urine-analyzer is a newly introduced research parameter. The results of this study are promising. Based on our results, we presume that the atypical-cell parameter may be used in surveillance of the NMIBC patients. Multi-center studies with larger patient populations are required to prove its efficacy.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Sensibilidad y Especificidad , Valor Predictivo de las PruebasRESUMEN
The aim of the present study was to compare follicular fluid (FF) levels of norepinephrine (NE) and dopamine (DA) in polycystic ovary syndrome (PCOS) and non-PCOS patients who underwent in vitro fertilization (IVF). Forty-seven PCOS patients (study group) and 61 patients with male factor infertility (control group) who underwent IVF using GnRH agonist protocol were recruited. Concentrations of NE and DA were measured in FF specimens of all patients. Demographic characteristics were comparable between the groups. Significantly higher levels of NE were measured in FF of PCOS patients (median: 61.05 nmol/l) compared to those with male infertility (median: 49.82 nmol/l). Similarly, significantly higher levels of DA were measured in FF of PCOS patients (median: 23.70 nmol/l) compared to those with male infertility (median: 18.28 nmol/l). In conclusion, the FF concentrations of both catecholamine are increased in PCOS patients when compared to non-PCOS patients.
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Dopamina/metabolismo , Líquido Folicular/metabolismo , Infertilidad Femenina/metabolismo , Norepinefrina/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Fertilización In Vitro , Humanos , Adulto JovenRESUMEN
BACKGROUND: Darbepoetin alpha is a hypersialylated analogue of erythropoietin effective for activating erythropoietin-receptors. This study investigated the vasodilator and neuroprotective effects of darbepoetin alpha on an experimental subarachnoid hemorrhage model and compared it with erythropoietin. METHODS: Forty adult male New Zealand white rabbits were randomly divided into four groups of ten rabbits each: group 1 (control), group 2 (subarachnoid hemorrhage), group 3 (erythropoietin), and group 4 (darbepoetin alpha). Recombinant human erythropoietin was administered at a dose of 1,000 U/kg intraperitoneally after the induction of subarachnoid hemorrhage and continued every 8 h up to 72 h. Darbepoetin alpha was administered at a single intraperitoneal dose of 30 µg/kg. Animals were killed 72 h after subarachnoid hemorrhage. Basilar artery cross-sectional areas, arterial wall thicknesses, hippocampal degeneration scores and biochemical analyses were measured in all groups. RESULTS: Both erythropoietin and darbepoetin alpha treatments were found to attenuate cerebral vasospasm and provide neuroprotection after subarachnoid hemorrhage in rabbits. Darbepoetin alpha revealed better morphometric and histopathological results than erythropoietin among experimental subarachnoid hemorrhage-induced vasospasm. CONCLUSIONS: Our findings, for the first time, showed that darbepoetin alpha can prevent vasospasm and provides neuroprotection following experimental subarachnoid hemorrhage. Moreover, darbepoetin alpha showed better results when compared with erythropoietin.
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Arteria Basilar/efectos de los fármacos , Eritropoyetina/análogos & derivados , Hematínicos/farmacología , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Hemorragia Subaracnoidea/complicaciones , Vasoconstricción/efectos de los fármacos , Vasoespasmo Intracraneal/etiología , Animales , Arteria Basilar/patología , Darbepoetina alfa , Epoetina alfa , Eritropoyetina/farmacología , Hipocampo/patología , Humanos , Masculino , Conejos , Proteínas Recombinantes/farmacología , Hemorragia Subaracnoidea/patología , Vasoespasmo Intracraneal/patología , Vasoespasmo Intracraneal/prevención & controlRESUMEN
OBJECTIVE: This study investigates the neuroprotective effects and functional recovery potential of Coenzyme Q10 (CoQ10) and ozone therapy in spinal cord injury (SCI). MATERIAL AND METHODS: In this study, 40 female Sprague-Dawley rats were divided into 5 groups of 8. Surgical procedures induced spinal cord trauma in all groups, except the control group. The ozone group received 0.7 mg/kg rectal ozone daily for 7 days, starting 1 hour postspinal cord trauma. The CoQ10 group was administered 120 mg/kg CoQ10 orally once daily for 7 days, beginning 24 hours prior to trauma. The CoQ10 + ozone group received both treatments. Examinations included a modified Tarlov scale and inclined plane test on days 1, 3, 5, and 7. Malondialdehyde (MDA) analysis was conducted on serum samples, and assessments of caspase-3, Bcl-2, and Bax levels were performed on tissue samples. Additionally, a comprehensive examination analyzed histopathological and ultrastructural changes. RESULTS: After SCI, there was a statistically significant increase in serum MDA, tissue caspase-3, and Bax levels (MDA P < 0.001, caspase-3 P < 0.001, Bax P = 0.003). In the CoQ10 + ozone group, serum MDA (P = 0.002), tissue caspase-3 (P = 0.001), and Bax (P = 0.030) levels were significantly lower compared to the trauma group. Tissue Bcl-2 levels were also significantly higher (P = 0.019). The combined treatment group demonstrated improved histopathological, ultrastructural, and neurological outcomes. CONCLUSIONS: This study shows that CoQ10 + ozone therapy in traumatic SCI demonstrates neuroprotective effects via antioxidant and antiapoptotic mechanisms. The positive effects on functional recovery are supported by data from biochemical, histopathological, ultrastructural, and neurological examinations.
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Fármacos Neuroprotectores , Ozono , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Ubiquinona , Animales , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquinona/uso terapéutico , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Femenino , Ozono/uso terapéutico , Ratas , Recuperación de la Función/efectos de los fármacos , Malondialdehído/sangre , Malondialdehído/metabolismo , Modelos Animales de Enfermedad , Caspasa 3/metabolismoRESUMEN
BACKGROUND: The agent, 2-mercaptoethane sulfonate (MESNA), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide. Because MESNA has potential antioxidant and cytoprotective effects, so we hypothesized that MESNA may protect the brain against traumatic injury. METHOD: Thirty-two rats were randomized into four groups of eight animals each; Group 1 (sham), Group 2 (trauma), Group 3 (150 mg/kg MESNA), Group 4 (30 mg/kg methylprednisolone). Only skin incision was performed in the sham group. In all the other groups, the traumatic brain injury model was created by an object weighing 450 g falling freely from a height of 70 cm through a copper tube on to the metal disc over the skull. The drugs were administered immediately after the injury. The animals were killed 24 h later. Brain tissues were extracted for analysis, where levels of tissue malondialdehyde, caspase-3, glutathione peroxidase, superoxide dismutase, nitric oxide, nitric oxide synthetase and xanthine oxidase were analyzed. Also, histopathological evaluation of the tissues was performed. RESULTS: After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity. Following trauma, both glutathione peroxidase and superoxide dismutase levels were decreased; MESNA increased the activity of both these antioxidant enzymes. Also, after trauma, nitric oxide, nitric oxide synthetase and xanthine oxidase levels were increased; administration of MESNA significantly decreased the levels of nitric oxide, nitric oxide synthetase and xanthine oxidase, promising an antioxidant activity. Histopathological analysis showed that MESNA protected the brain tissues well from injury. CONCLUSIONS: Although further studies considering different dose regimens and time intervals are required, MESNA was shown to be at least as effective as methylprednisolone in the traumatic brain injury model.
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Lesiones Encefálicas/patología , Lesiones Encefálicas/prevención & control , Mesna/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Apoptosis/fisiología , Lesiones Encefálicas/metabolismo , Modelos Animales de Enfermedad , Peroxidación de Lípido/fisiología , Masculino , Metilprednisolona/uso terapéutico , Estrés Oxidativo/fisiología , Ratas , Ratas WistarRESUMEN
Gene therapy has emerged as a promising therapeutic strategy for various conditions, including blood disorders, ocular disease, cancer, and nervous system disorders. The advent of gene editing techniques has facilitated the ability of researchers to specifically target and modify the eukaryotic cell genome, making it a valuable tool for gene therapy. This can be performed through either in vivo or ex vivo approaches. Gene editing tools, such as zinc finger nucleases, transcription activator-like effector nucleases, and CRISPR-Cas-associated nucleases, can be employed for gene therapy purposes. Among these tools, CRISPR-Cas-based gene editing stands out because of its ability to introduce heritable genome changes by designing short guide RNAs. This review aims to provide an overview of CRISPR-Cas technology and summarizes the latest research on the application of CRISPR/Cas9 genome editing technology for the treatment of the most prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Spinocerebellar ataxia.
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OBJECTIVE: Previous studies have shown niacin has neuroprotective effects on the central nervous system. However, its specific effect on spinal cord ischemia/reperfusion injury has not yet been explored. This study aims to evaluate whether niacin can contribute neuroprotective effects on spinal cord ischemia/reperfusion injury. METHODS: Rabbits were randomized into 4 groups of 8 animals: group I (control), group II (ischemia), group III (30 mg/kg methylprednisolone, intraperitoneal), and group IV (500 mg/kg niacin, intraperitoneal). The rabbits in group IV were premedicated with niacin for 7 days prior to inducing ischemia/reperfusion injury. The control group was subjected only to a laparotomy, while the remaining groups underwent spinal cord ischemia through a 20-minute occlusion of the aorta caudal to the left renal artery. Following the procedure, levels of catalase, malondialdehyde, xanthine oxidase, myeloperoxidase, and caspase-3 were analyzed. Ultrastructural, histopathological, and neurological evaluations were also performed. RESULTS: Spinal cord ischemia/reperfusion injury resulted in increased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3, with a concomitant decrease in catalase levels. Treatment with methylprednisolone and niacin led to decreased levels of xanthine oxidase, malondialdehyde, myeloperoxidase, and caspase-3 and an increase in catalase. Both methylprednisolone and niacin treatments demonstrated improvements in histopathological, ultrastructural, and neurological assessments. CONCLUSIONS: Our findings suggest that niacin has antiapoptotic, anti-inflammatory, antioxidant, and neuroprotective effects at least equal to methylprednisolone in ischemia/reperfusion injury of the spinal cord. This study is the first to report the neuroprotective impact of niacin on spinal cord ischemia/reperfusion injury. Further research is warranted to elucidate the role of niacin in this context.
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BACKGROUND: Mildronate is a useful anti-ischemic agent and has antiinflammatory, antioxidant, and neuroprotective activities. The aim of this study is to investigate the potential neuroprotective effects of mildronate in the experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals as groups 1 (control), 2 (ischemia), 3 (vehicle), 4 (30 mg/kg methylprednisolone [MP]), and 5 (100 mg/kg mildronate). The control group underwent only laparotomy. The other groups have the spinal cord ischemia model by a 20-minute aortic occlusion just caudal to the renal artery. The malondialdehyde and catalase levels and caspase-3, myeloperoxidase, and xanthine oxidase activities were investigated. Neurologic, histopathologic, and ultrastructural evaluations were also performed. RESULTS: The serum and tissue myeloperoxidase, malondialdehyde, and caspase-3 values of the ischemia and vehicle groups were statistically significantly higher than those of the MP and mildronate groups (P < 0.001). Serum and tissue catalase values of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). The histopathologic evaluation showed a statistically significantly lower score in the mildronate and MP groups than in the ischemia and vehicle groups (P < 0.001). The modified Tarlov scores of the ischemia and vehicle groups were statistically significantly lower than those of the control, MP, and mildronate groups (P < 0.001). CONCLUSIONS: This study presented the antiinflammatory, antioxidant, antiapoptotic, and neuroprotective effects of mildronate on SCIRI. Future studies will elucidate its possible use in clinical settings in SCIRI.
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Fármacos Neuroprotectores , Daño por Reperfusión , Isquemia de la Médula Espinal , Animales , Conejos , Catalasa/farmacología , Peroxidasa , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Caspasa 3 , Médula Espinal/patología , Isquemia de la Médula Espinal/patología , Metilprednisolona , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Isquemia , Malondialdehído/farmacología , Modelos Animales de EnfermedadRESUMEN
AIM: To investigate the effects of cerebrolysin on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of an experimental rabbit model of spinal cord ischemia/reperfusion injury (SCIRI). MATERIAL AND METHODS: Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent only laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 minutes. Neurologic examination after 24 hours was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. RESULTS: After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p < 0.01?0.001). Catalase levels were significantly diminished (p < 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p < 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. CONCLUSION: For the first time in the literature, the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.
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Fármacos Neuroprotectores , Daño por Reperfusión , Isquemia de la Médula Espinal , Animales , Conejos , Catalasa , Peroxidasa/farmacología , Caspasa 3 , Xantina Oxidasa/farmacología , Médula Espinal , Isquemia de la Médula Espinal/patología , Antioxidantes/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , MalondialdehídoRESUMEN
BACKGROUND: Darbepoetin-alpha (DA) is a novel erythropoiesis-stimulating agent developed for treating anemia. In animal models, recombinant human erythropoietin has been reported to be beneficial for neuroprotection. In this study, we determined whether DA would protect the spinal cord against ischemia-reperfusion injury in a rabbit model. METHODS: Forty rabbits were randomized into five groups of eight animals each: group 1 (sham), group 2 (ischemia), group 3 (vehicle), group 4 (30 mg/kg methylprednisolone), group 5 (30 µg/kg DA). Only laparotomy was performed in the sham group. In all the other groups, the spinal cord ischemia model was created by a 20-min occlusion of the aorta just caudal to renal artery with an aneurysm clip. The drugs were administered immediately after the clamp was removed. The animals were killed 24 h later. Spinal cord segments between L2 and L5 were harvested for analysis. Neurological evaluation was performed with the Tarlov scoring system just before the animals were killed. Level of tissue malondialdehyde was analyzed as a marker of lipid peroxidation and tissue caspase-3 activity as a marker of apoptosis. Also, histopathological evaluation of the tissues was performed. RESULTS: Both malondialdehyde and caspase-3 levels were significantly decreased by DA administration. Histopathological evaluation of the tissues also demonstrated decrease in neuronal degeneration and infiltration parameters after DA administration. In the DA group, neurological outcome scores were statistically significantly better compared with the ischemia and the vehicle groups. CONCLUSIONS: Although further studies considering different dose regimens and time intervals are required, DA was shown to be at least as effective as methylprednisolone in spinal cord ischemia/reperfusion model.
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Eritropoyetina/análogos & derivados , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Isquemia de la Médula Espinal/tratamiento farmacológico , Anemia/tratamiento farmacológico , Anemia/patología , Animales , Darbepoetina alfa , Modelos Animales de Enfermedad , Eritropoyetina/farmacología , Eritropoyetina/uso terapéutico , Hematínicos/farmacología , Hematínicos/uso terapéutico , Masculino , Fármacos Neuroprotectores/uso terapéutico , Conejos , Daño por Reperfusión/fisiopatología , Isquemia de la Médula Espinal/fisiopatologíaRESUMEN
Objectives: To analyze the change in circulating angiogenic factor levels after transarterial radioembolization (TARE) for colorectal cancer liver metastases (CRCLMs) and its prognostic significance. Methods: Blood samples immediately before TARE and on 1 day, 1 week and 6 weeks after were collected for angiogenic factor analysis in 23 patients. Results: Patients with elevated serum basic fibroblast growth factor and platelet-derived growth factor levels in the 1st week and vascular endothelial growth factor (VEGF) levels in the 6th week after TARE had significantly shorter median overall survival (OS) times. Conclusion: Some early increases in serum angiogenic factor levels and in serum VEGF in the 6th week after TARE for CRCLMs are related to short OS and progression-free survival.
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OBJECTIVE: Dexpanthenol (DXP) reportedly protects tissues against oxidative damage in various inflammation models. This study aimed to evaluate its effects on oxidative stress, inflammation, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia/reperfusion injury (SCIRI) model. METHODS: Rabbits were randomized into 5 groups of 8 animals each: group 1 (control), group 2 (ischemia), group 3 (vehicle), group 4 (methylprednisolone, 30 mg/kg), and group 5 (DXP, 500 mg/kg). The control group underwent laparotomy only, whereas other groups were subjected to spinal cord ischemia by aortic occlusion (just caudal to the 2 renal arteries) for 20 min. After 24 h, a modified Tarlov scale was employed to record neurological examination results. Malondialdehyde and caspase-3 levels and catalase and myeloperoxidase activities were analyzed in tissue and serum samples. Xanthine oxidase activity was measured in the serum. Histopathological and ultrastructural evaluations were also performed in the spinal cord. RESULTS: After SCIRI, serum and tissue malondialdehyde and caspase-3 levels and myeloperoxidase and serum xanthine oxidase activities were increased (P < 0.05-0.001). However, serum and tissue catalase activity decreased significantly (P < 0.001). DXP treatment was associated with lower malondialdehyde and caspase-3 levels and reduced myeloperoxidase and xanthine oxidase activities but increased catalase activity (P < 0.05-0.001). Furthermore, DXP was associated with better histopathological, ultrastructural, and neurological outcome scores. CONCLUSIONS: This study was the first to evaluate antioxidant, anti-inflammatory, antiapoptotic, and neuroprotective effects of DXP on SCIRI. Further experimental and clinical investigations are warranted to confirm that DXP can be administered to treat SCIRI.
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Fármacos Neuroprotectores , Daño por Reperfusión , Isquemia de la Médula Espinal , Animales , Conejos , Catalasa/farmacología , Catalasa/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Peroxidasa , Caspasa 3 , Xantina Oxidasa/farmacología , Xantina Oxidasa/uso terapéutico , Médula Espinal/patología , Isquemia de la Médula Espinal/patología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Inflamación/patología , Malondialdehído , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. METHODS: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. RESULTS: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. CONCLUSION: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.
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BACKGROUND: The aim of our study is to assess the neuroprotective effects of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept (ETA) on histopathological and biochemical changes following spinal cord injury (SCI). PATIENTS AND METHODS: Fifty-four male Wistar albino rats were randomly assigned into three main groups: The sham, trauma, and ETA group (n = 18 per group). Each of these groups was further divided into three subgroups (n = 6 per subgroup) based on the different tissue sampling times postinjury: 1 h, 6 h, and 24 h. Clip compression model was used for SCI. Rats in the ETA group were treated with 5 mg/kg of ETA immediately after the clip was removed. After 1, 6, and 24 h, the spinal cord was totally removed between the levels T8-T10. Sample tissue was immediately harvested and fixed for histopathological and electron microscopic examination and were analyzed for TNF-α, interleukin-1ß (IL-1ß), superoxide dismutase (SOD), adenosine deaminase, catalase (CAT), and malondialdehyde levels in both the tissue and serum. RESULTS: The serum and tissue levels of cytokines and enzymes were seen to change after SCI between hyperacute, acute, and subacute stages. Treatment with ETA selectively inhibited TNF-α, and IL-1ß expression together with increased levels of antioxidative enzymes (SOD, CAT). CONCLUSION: Early administration of ETA after SCI may remarkably attenuate neuronal injury by decreasing tissue and serum TNF-α and IL-1ß levels, while increasing antioxidative enzymes such as SOD and CAT in subacute and acute stages, respectively.
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INTRODUCTION: Tetracosactide is an engineered peptide that applies the same biological impacts as the endogenous adrenocorticotropic hormone. Previous studies indicated that tetracosactide has anti-inflammatory, antioxidant and neurotrophic activity. In this study, we hypothesized that tetracosactide may have protective effects in spinal cord ischemia-reperfusion injury. MATERIAL AND METHODS: Rabbits were randomized into the accompanying four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (tetracosactide). In the control group, just a laparotomy was performed. In the various groups, the spinal cord ischemia model was made by the impediment of the aorta only caudal to the renal vein. Neurological assessment was conducted with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, similar to the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural assessments were additionally performed. RESULTS: After ischemia-reperfusion injury, increments were found in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p < 0.001), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both serum and tissue catalase levels were diminished (p < 0.001 for both). After the administration of tetracosactide, declines were seen in the tissue myeloperoxidase levels (p < 0.001), malondialdehyde levels (p = 0.003), xanthine oxidase action (p < 0.001) and caspase-3 movement (p < 0.001). Conversely, both the serum and tissue catalase levels were expanded (p < 0.001). Besides, tetracosactide treatment indicated enhanced results related to the histopathological scores (p < 0.001), the ultra-structural score (p = 0.008) and the Tarlov scores (p < 0.001). CONCLUSIONS: The findings showed for the first time that tetracosactide shows significant neuroprotective activity against ischemia-reperfusion injury of the spinal cord.
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BACKGROUND: The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is well known. Decorin (DC) inactivates transforming growth factor ß1, complement system, and tumor necrosis factor α, which are related to oxidative stress and apoptosis. Consequently, the aim of the present study was to evaluate the role of DC on TBI. METHODS: A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, DC, and methylprednisolone (MP). The trauma, DC, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with intraperitoneal saline, DC, or MP, respectively. All the animals were killed at the 24th hour after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, and NO) and caspase 3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. RESULTS: Levels of malondialdehyde, NO, and activity of caspase 3 were significantly reduced, and in addition glutathione peroxidase and superoxide dismutase levels were increased in the DC and MP groups compared with the trauma group. The pathology scores and the percentage of degenerated neurons were statistically lower in the DC and MP groups than in the trauma group. CONCLUSIONS: The results of the present study showed that DC inactivates transforming growth factor ß1 and protects the brain tissue and neuronal cells after TBI.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/inmunología , Decorina/administración & dosificación , Decorina/farmacología , Neuronas/efectos de los fármacos , Neuronas/inmunología , Especies Reactivas de Oxígeno/inmunología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Lesiones Traumáticas del Encéfalo/patología , Supervivencia Celular/efectos de los fármacos , Citocinas/inmunología , Masculino , Neuronas/patología , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
INTRODUCTION: Recent studies have demonstrated the neuroprotective and immunomodulatory effects of 1,25-dihydroxyvitamin D3 (calcitriol), but no previous study has examined these effects on spinal cord ischemia/reperfusion (I/R) injury. Therefore, the present study aimed to evaluate whether calcitriol protects the spinal cord from I/R injury. METHODS: Rabbits were randomized into four groups of eight animals: group 1 (laparotomy control), group 2 (ischemia control), group 3 (30mg/kg intraperitoneal methylprednisolone at surgery), and group 4 (0.5µg/kg, intraperitoneal calcitriol for 7 days before I/R injury). The rabbits in the laparotomy control group underwent laparotomy only, whereas all rabbits in the other groups were subject to spinal cord ischemia by aortic occlusion for 20min, just caudal to the renal artery. Malondialdehyde and catalase levels, myeloperoxidase and xanthine oxidase activities, and caspase-3 concentrations were analyzed. Finally, histopathological, ultrastructural, and neurological evaluations were performed. RESULTS: After I/R injury, increases in malondialdehyde levels, myeloperoxidase and xanthine oxidase activities, and caspase-3 concentrations were found (p<0.001 for all); by contrast, catalase levels decreased (p<0.001). Calcitriol pretreatment was associated with lower malondialdehyde levels (p<0.001), reduced myeloperoxidase (serum, p=0.018; tissue, p<0.001) and xanthine oxidase (p<0.001) activities, and caspase-3 concentrations (p<0.001), but increased catalase levels (p<0.001). Furthermore, calcitriol pretreatment was associated with better histopathological, ultrastructural, and neurological scores. CONCLUSION: Calcitriol pretreatment provided significant neuroprotective benefits following spinal cord I/R injury.
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Metilprednisolona/farmacología , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Isquemia de la Médula Espinal/complicaciones , Vitamina D/farmacología , Animales , Caspasa 3/metabolismo , Catalasa/metabolismo , Modelos Animales de Enfermedad , Masculino , Malondialdehído/sangre , Metilprednisolona/uso terapéutico , Peroxidasa/metabolismo , Conejos , Daño por Reperfusión/sangre , Daño por Reperfusión/metabolismo , Vitamina D/uso terapéutico , Xantina Oxidasa/sangreRESUMEN
BACKGROUND: The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. METHODS: A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. RESULTS: Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. CONCLUSIONS: The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI.
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Contusión Encefálica/prevención & control , Modelos Animales de Enfermedad , Omeprazol/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Contusión Encefálica/patología , Contusión Encefálica/fisiopatología , Masculino , Metilprednisolona/farmacología , Estrés Oxidativo/fisiología , RatasRESUMEN
INTRODUCTION: In this study, we tried to determine whether darbepoetin-α would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model. MATERIAL AND METHODS: The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin α), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied. RESULTS: Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-α increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-α significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-α administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016). CONCLUSIONS: In this study, darbepoetin-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis.