The effect of idebenone and corticosteroid treatment on methanol-induced toxic optic nerve and retinal damage in rats: biochemical and histopathological examination.

PURPOSE: To evaluate the therapeutic effects of methylprednisolone, the CoenzymeQ10 (CoQ10) structural analogue idebenone, and both together on the optic nerve (ON) and retinal layers following methanol intoxication in rats with histopathological and biochemical methods. MATERIALS AND METHODS: This experimental study was conducted with 30 male Wistar rats. The rats were divided into five equal groups depending on the treatment protocol:healthy controls (HC), methanol (M), methanol + methylprednisolone (MM), methanol + idebenone (MI), and methanol + methylprednisolone + idebenone (MMI).Distilled water was provided orally to the HC group, while 20% methanol was administered orally at a dose of 3 g/kg with a nasogastric tube to all rats in groups except the HC group. Four hours later, group MM received 1 mg/kg of intraperitoneal methylprednisolone for 10 days using an insulin syringe, and group MI received 20 mg/kg idebenone by nasogastric catheter for 28 days. MMI group was administered oral idebenone and intraperitoneal methylprednisolone at the same dose. Serum samples were obtained on the 28th day for biochemical analysis and afterwards the rats were euthanized for histopathological examination and eyes were enucleated. ON was evaluated for circumference thickness, vascularization and number of astrocytes, also retinal layers were examined for structural changes by histopathological examination. RESULTS: Comparison of the antioxidant and oxidative stress biomarkers between the groups revealed no statistically significant difference (p > 0.05). By histopathological evaluation the most marked results were obtained by MMI group with an improvement of all parameters mentioned. There was no statistically significant difference between MM group and M group for RD score (p = 0.123). In addition, ON vacuolization in MI group (p < 0.001) and ON astrocyte increase in both MI and MMI groups were statistically significantly lower than in M group (p = 0.001, p = 0.001, respectively). CONCLUSIONS: The early use (within hours) of idebenone and short-term methylprednisolone treatment together may protect against the retinal and ON damage developing after methanol ingestion in rats as guided by the histopathological data.

The impact of TI-RADS in detecting thyroid malignancies: a prospective study.

INTRODUCTION: Thyroid ultrasonography (US) is the first-step noninvasive and easily accessible diagnostic method widely used in the detection and characterization of nodular thyroid disease. We aimed to develop a TI-RADS, which is easy to apply and only relies on the counting of suspicious criteria. In order to measure the reliability of the system, we investigated its correlation with fine needle aspiration biopsy (FNAB) and post-surgery histological results. MATERIALS AND METHODS: In this prospective study, 242 patients who had undergone FNAB with simultaneous cytopathologist in the radiology department between April and August 2016 were analyzed. Before FNAB, the thyroid gland was re-evaluated with US, and TI-RADS classification was made. Demographic characteristics, family thyroid cancer history and radiotherapy history to the neck region were noted. RESULTS: Of the 242 patients, 17.3% were male (42 males/200 females). US-guided FNAB was applied to all patients. Mean age was 50 ± 13 years (min: 19, max: 82). Both FNAB and final post-surgery histology results showed that sex and age were not statistically significantly associated with malignancy (p = 0.193) TI-RADS criteria and FNAB results revealed a statistically significant association between irregular contours, the state of anteroposterior diameter being longer than transverse diameter, microcalcifications, marked hypoechogenicity, and malignancy (p < 0,05). Thirty patients were TI-RADS ≥ 4, 206 patients were TI-RADS ≤ 3 and there was a significant correlation between TI-RADS and Bethesda classification (p = 0.001). In addition, statistically significant associations were found between malignancy and family history of thyroid cancer (p = 0.035) and radiotherapy history to the neck region (p = 0.01). CONCLUSION: TI-RADS system after nodule identification is based only on the counting of suspicious criteria. It will be safe and effective to recommend follow-up with low score TI-RADS, benign characters and insufficient FNAB results, and thus, unnecessary thyroidectomy operations will be prevented. It will be easier for surgeons to recommend surgery and persuade the patients for it when patients have high TI-RADS scores. TI-RADS has high power in detecting malignancy by recommending biopsy of suspicious nodules.

Evaluation of beneficial effects of dexpanthenol on hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a cause of serious morbidity and mortality in newborns. Dexpanthenol, which is metabolized into D-pantothenic acid, has antioxidant and other potentially therapeutic properties. We examined some effects of dexpanthenol on the brains of week-old rat pups with HIE induced by obstruction of the right carotid artery followed by keeping in 8% O2 for 2 hours. Dexpanthenol (500 mg/kg) was administered intraperitoneally to 16 of 32 pups with HIE. Protein, DNA, and lipid oxidation degradation products were assayed and hippocampal and cortical cell apoptosis and neuronal cell numbers were evaluated in stained sections. Dexpanthenol application reduced oxidative stress and inflammation. TNF-α and IL-6 cytokine levels in HIE also decreased with dexpanthenol treatment. The numbers of caspase-3 positive cells in the dentate gyrus and CA1/CA2/CA3 regions of the hippocampus was lower, and apoptosis was decreased in the dexpanthenol-treated animals. These findings suggest possible clinical applications of dexpanthenol in human HIE.

The relationship between ultrasonographic plaque morphology and histopathology of embolic material captured in the protective filter during carotid artery stenting.

PURPOSE: We aimed to correlate the presence or absence of embolic debris in filter-type embolic protection devices (EPD), which are frequently used during carotid artery stenting (CAS), with possible risk factors and ultrasonographic plaque features. MATERIALS AND METHODS: Eighty patients, who underwent CAS using a filter-type EPD in the period between July 2016 and March 2019, were included in our study. The modified Gray-Weale classification (mGWC) subtypes obtained in the pre-procedural ultrasonographic examinations were recorded. In addition, other patient-related risk factors considered to be related to a distal embolism were recorded. After the procedure the filters were evaluated to detect and examine embolic debris in the pathology clinic. The presence and features of embolic debris in the filters were recorded. RESULTS: In the examinations performed after CAS, embolic debris was macroscopically and microscopically detected in 22 (27%) and 34 (42.5%) of the filter-type EPDs, respectively. A significant correlation was found between the change in the mGWC category of stenotic plaques from type 5 to type 1 and the presence of embolic debris in the filter (p < 0.05). Furthermore, a significant relationship was found between stenotic segment length and the presence of embolic debris in the filter (p < 0.05). The presence of embolic debris was not statistically significantly related to predisposing risk factors for atherosclerosis (p > 0.05). CONCLUSIONS: During CAS, the likelihood of the presence of embolic debris in the EPDs increases as mGWC categories change from type 5 to type 1 and as the length of the stenotic segment increases.

The value of routine measurement of serum calcitonin on insufficient, indeterminate, and suspicious thyroid nodule cytology.

Routine calcitonin measurement in patients with nodular thyroid disease is rather controversial. The aim of this study was to evaluate the contribution of serum calcitonin measurement in the diagnostic evaluation of thyroid nodules with insufficient, indeterminate, or suspicious cytology. Out of 1668 patients who underwent thyroidectomy with the diagnosis of nodular thyroid disease and were screened, 873 patients with insufficient, indeterminate, or suspicious fine needle aspiration biopsy results were included in the study. From the total number of patients in this study, 10 (1.1%) were diagnosed as medullary thyroid cancer (MTC) using histopathology. The calcitonin level was detected to be above the assay-specific cut-off in 23 (2.6%) patients ranging between 6.5 - 4450 pg/mL. While hypercalcitoninemia was detected in all 10 MTC patients, a false positive elevation of serum calcitonin was detected in 13 patients (1.5%). Of the MTC group, 7 patients had cytology results that were suspicious for malignancy (Bethesda V), one patient's cytology showed atypia of undetermined significance (Bethesda III) and two patient's cytology results were suspicious for follicular neoplasm (Bethesda IV). Among the cases with non-diagnostic cytology (Bethesda I), none of the patients were diagnosed with MTC. In conclusion, routine serum calcitonin measurement can be performed in selected cases rather than in all nodular thyroid patients. While it is reasonable to perform routine calcitonin measurement in patients with Bethesda IV and Bethesda V, this measurement was not useful in Bethesda I patients. In Bethesda III patients, patient-based decisions can be made according to their calcitonin measurement.

Role of magnetic resonance spectroscopy in differential diagnosis of solitary pulmonary lesions.

PURPOSE: The aim of our study was to evaluate the availability of magnetic resonance spectroscopy (MRS) for the differentiation of benign or malignant pulmonary nodules and masses. METHODS: A total of 59 patients (45 male, 14 female) with pulmonary nodules and masses were included in this prospective study. MRS was applied to the pulmonary lesions of the patients and choline levels were determined. Afterwards CT-guided percutaneous needle biopsy was performed. According to the biopsy results, pulmonary lesions were benign in 25 patients and malignant in 34 patients. RESULTS: Choline levels were significantly higher in malignant lesions compared with benign lesions (p < 0.001). When the other conditions were kept constant, the probability of malignancy significantly increased by 17.38-fold (95% CI, 3.78-79.93) in those with choline levels >1.65 µmol/g compared to those with choline levels ≤1.65 µmol/g (p < 0.001). CONCLUSION: MRS is a noninvasive method that can be used in the differential diagnosis of pulmonary nodules and masses.

Inhibition of Interleukin-6 signaling: A novel therapeutic approach to necrotizing enterocolitis.

OBJECTIVES: This study investigated the effects of tocilizumab on the prevention and treatment of experimental necrotizing enterocolitis (NEC) in newborn rats. METHODS: Forty-two newborn Sprague-Dawley rats were randomly separated into three groups: NEC + placebo, NEC + tocilizumab, and the control group. NEC + placebo and NEC + tocilizumab groups were given 1 mg/kg lipopolysaccharide intraperitoneally once only on the first day, were fed with a special rodent formula every 3 h, inhaled 100% CO2 for 10 min, were exposed to cold stress at + 4 °C for 5 min, and 97% O2 for 5 min twice a day for 3 days. NEC + tocilizumab group was treated with 8 mg/kg/day tocilizumab (Actemra®) intraperitoneally, while NEC + placebo group was given intraperitoneal 0.9% saline at a dose of 2 mL/kg/day from the first day to the end of the study. All newborn rats were sacrificed on day 4. Specimens were taken for histopathologic, immunohistochemical and biochemical evaluation from the ileum and proximal colon. RESULTS: NEC + tocilizumab group had higher weight gain and survival rate compared to NEC + placebo group and clinical sickness score was reduced in NEC + tocilizumab group (p < 0.05). Lower tissue damage and apoptosis were found in the NEC + tocilizumab group compared to the NEC + placebo group (p < 0.01). Tissue Interleukin-6, Interleukin-1ß, TNF-α, myeloperoxidase and caspase-3 levels were significantly decreased in the NEC + tocilizumab group (p < 0.01). CONCLUSIONS: Tocilizumab could be a potential option in the prevention and treatment of NEC.

The effectiveness of Teucrium chamaedrys L. extracts on endometriotic implant regression in rat endometriosis model.

The aim of the present study was to investigate the therapeutic effects of Teucrium chamaedrys L. (Lamiaceae) in the experimentally induced endometriosis in rats. Endometrial tissue was implanted into the abdominal wall of thirty Sprague Dawley rats; the rats with endometriosis were randomized into five groups and treatment procedure was performed for three weeks. The treatment groups were orally treated with three different extracts of Teucrium chamaedrys. Buserelin acetate (20.00 mg) was given as a reference drug. Vehicle was administered alone to the control group. All rats were sacrified at the end of the experiment. The endometriotic implants were measured, intra-abdominal adhesions were scored and the tissue samples were histopathologically investigated. After the treatment procedure, the volumes of endometrial implant and adhesions were detected to be significantly decreased in the T. chamaedrys extracts treated groups compared to the control group. Therapeutic effect of the T. chamaedrys extracts could be attributed to the both nonpolar and polar secondary metabolites. The study conceived that the different polarity extracts of T. chamaedrys could be beneficial in the treatment of endometriosis.

Invasive squamous cell carcinoma arising in an inverted papilloma involving oral cavity.

Inverted papilloma (IP) is a benign tumour characterized by the growth of epithelial cells downward into the underlying supportive tissue. The tumour derives from the lining mucosa of the nasal cavity and paranasal sinuses. IP typically arises as a unilateral lesion from the lateral wall of the nasal cavity and extends secondarily to the paranasal sinuses. The aggressive behaviour of IP causing local invasion, its tendency for local recurrence, and its propensity to be associated with carcinoma constitute serious complications. This paper describes a very rare case of IP associated with squamous cell carcinoma, extending into paranasal sinuses, causing destruction of the bony wall of maxillary sinus and involvement of the oral cavity.

Preventative and therapeutic effects of fennel (Foeniculum vulgare) seed extracts against necrotizing enterocolitis.

We aimed to understand the efficacy of fennel (Foeniculum vulgare: FV) extract in an experimental necrotizing enterocolitis (NEC) model. Forty-two rat pups were divided into three groups as NEC, NEC treated with fennel extract, and control. At the end of the experiment, tissue samples were taken from the proximal colon and ileum for biochemical and immuno-histological studies including hematoxylin-eosin and Caspase-3-8-9 immunohistochemical staining. Bowel damage and apoptosis were found to be less in the NEC + FV group. Oxidant stress, caspase 3, TNF-α, and IL-6 levels were considerably decreased in the NEC + FV group. Antioxidants were significantly higher in the NEC + FV group more than in the NEC group. Moreover, protein, DNA damage, and lipid peroxidation were found to be decreased in the NEC + FV group compared to the NEC group. PRACTICAL APPLICATIONS: Intense inflammation, oxidant stress, apoptosis, and infection are important in the development of NEC. Fennel has anti-oxidant, anti-inflammatory, antibacterial, antifungal, antiviral, immunomodulatory effects. Fennel extract might be a novel option in the treatment of NEC through its anti-oxidant, anti-inflammatory, anti-apoptotic, and cytoprotective features.

Sumac (Rhus coriaria) for the prevention and treatment of necrotizing enterocolitis.

Leukotrienes, free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of necrotizing enterocolitis (NEC). Rhus coriaria (RC: sumac) extracts may enhance cell viability by reinforcing defenses against free radical species in several progressive diseases as well as inflammatory diseases. The aim of the present study was to evaluate the effects of RC in a rat NEC model in terms of intestinal damage. Newborn pups were separated into three groups: control, NEC, and NEC treated with RC. Mortality and clinical sickness scores were evaluated. At the end of the study, ileum and proximal colon were obtained from all rats and histopathological and immunohistochemical studies were performed. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model, which suggests RC as a promising treatment option for preventing intestinal tissue damage. PRACTICAL APPLICATIONS: Free oxygen radicals, tumor necrosis factor-alpha, and inflammatory mediators play major roles in the development of NEC. Intestinal tissue damage is caused by necrosis and apoptosis as a result of intestinal inflammation and release of pro-inflammatory cytokines. Anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC are especially due to its phenolic compounds. In this study, the anti-inflammatory, antioxidant, immunomodulatory, and anti-apoptotic activities of RC were demonstrated in a rat NEC model. RC can suggest as a new treatment option for preventing intestinal injury.

Therapeutic and preventative effects of ankaferd blood stopper in an experimental necrotizing enterocolitis model.

Necrotizing enterocolitis (NEC) is a major neonatal health problem that especially affects preterm infants and causes severe morbidity and mortality. Although its pathogenesis is not fully understood, important risk factors include prematurity, oxidative stress, inflammation, and apoptosis. Ankaferd Blood Stopper® (ABS) has antioxidant, antiinflammatory, antimicrobial, antiapoptotic, and wound healing accelerant properties. In this study, we aimed to investigate whether treatment with ABS reduced the severity of NEC in rat pups in an experimental NEC model. Thirty-six newborn Wistar albino rat pups were randomly assigned to the control, NEC + saline, or NEC + ABS groups. NEC was induced by intraperitoneal injection of lipopolysaccharide, feeding with hyperosmolar enteral formula, and exposure to hypoxia/hyperoxia and cold stress. ABS was administered intraperitoneally to the pups in the NEC + ABS group daily starting on day 1 of the study at a dose of 2 ml/kg by diluting 2 ml with saline at a ratio of 1:3. All pups were sacrificed on day 4. The terminal ileum including the proximal colon was removed for histopathological and immunohistochemical examination and biochemical analysis. Macroscopic assessment and intestinal injury scores were lower in NEC + ABS group compared to the NEC + saline group (p < 0.05). Immunohistochemical evaluations of caspase-3, -8, and -9 revealed significantly reduced apoptosis in the NEC + ABS group compared to the NEC + saline group (p = 0.001). Total oxidant status, oxidative stress index, tumor necrosis factor α and interleukin-1ß levels, and lipid, protein, and deoxyribonucleic acid oxidation products were significantly lower in the NEC + ABS group compared to NEC + saline group (p < 0.001 for all), while total antioxidant status, glutathione, and superoxide dismutase levels were higher in the NEC + ABS group (p < 0.001, p < 0.001, p = 0.01, respectively). ABS treatment has the potential to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, antiinflammatory, and antiapoptotic properties. Therefore, NEC may be an alternative option for treatment.

The Malignancy Risk Assessment of Cytologically Indeterminate Thyroid Nodules Improves Markedly by Using a Predictive Model.

OBJECTIVES: The majority of thyroid nodules are discovered incidentally, and the management may be a challenge if the fine needle aspiration specimen yields indeterminate findings. Our aim was to develop an individualized risk prediction model to provide an accurate estimate of cancer risk in patients with cytologically indeterminate thyroid nodules. MATERIALS AND METHODS: Clinical records, ultrasound images, and cytopathology reports of patients who underwent thyroidectomy were retrospectively reviewed. Logistic regression analysis was used to identify the predictive ability of each variable for malignancy, and a nomogram was built by integrating patients' age, multiplicity of nodules, cytology results, and suspicious ultrasound features, such as microcalcifications and irregular margins. RESULTS: For the 233 indeterminate nodules according to the Bethesda System for Reporting Thyroid Cytopathology, the malignancy rates of the subgroups "atypia of undetermined significance," "suspicious follicular neoplasia," and "suspicious for malignancy" were 44.3, 47.7, and 88.0%, respectively. It was found that the Bethesda category "suspicious for malignancy," microcalcifications, and irregular margins were independent risk factors for malignancy. The area under the receiver operating characteristics curve was 0.784, which suggested that the presented nomogram had considerable discriminative performance. CONCLUSIONS: The nomogram developed in our study accurately predicts the malignancy risk of thyroid nodules with indeterminate cytology by using clinical, cytological, and ultrasonographic features.