Objective: Diabetic nephropathy is one of the most significant causes of end-stage renal failure and is a common microvascular complication of diabetes (D). Resveratrol (RSV), a natural compound found in grape skins and red wine, has potent antioxidant properties. This study aimed to evaluate the effects of RSV in a streptozotocin (STZ)-induced diabetic rat model. Methods: Animals were divided into four groups: control, RSV, D, and D + RSV. The diabetic group received a single intraperitoneal dose of STZ (65 mg/kg). After 2 weeks, rats with basal blood glucose levels >250 mg/dL were considered diabetic. RSV(10 mg/kg/day) was administered orally by gavage for 8 weeks. Metabolic analyses were conducted throughout the study. At the study’s end, transmission electron microscopy and immunohistochemical analyses were performed. Additionally, the left kidney was isolated and suspended in an organ bath to study the functional changes without damaging the renal artery. Results: In the study, increased transforming growth factor-beta, fibronectin and inducible nitric oxide synthase immunoreactivity, which are markers of D-induced renal degeneration, were partially reduced by RSV treatment. In group D, decreased endothelial nitric oxide synthase uptake (weak immune reactivity) was observed, whereas this uptake increased with RSV treatment (moderate immune reactivity). Furthermore, both angiotensin II and phenylephrine responses were reduced in group D treated with RSV. Vasodilator responses to acetylcholine were also reduced in this group. Conclusion: RSV may protect against diabetic nephropathy by modulating key pathways involved in renal degeneration and vascular function and may have potential as a therapeutic agent for slowing disease progression.

BackgroundHumans are constantly exposed to sulfites and their derivatives, both endogenously and exogenously. Recent studies have shown that sulfite and its derivatives can cause oxidative stress. . Ghrelin has been reported to possess antioxidant properties and stimulates neurogenesis in hippocampal progenitor cells. This study aimed to investigate the effects of ghrelin on sulfite-induced changes in hippocampal oxidative status, spatial learning and locomotor activity in rats.MethodsForty male albino Wistar rats were randomized into four groups as follows; Group 1: Control (C); Group 2: Sodium metabisulfite (Na2S2O5) treated (S); Group 3: Ghrelin treated (G); Group 4: Na2S2O5 + Ghrelin treated (SG). Sodium metabisulfite (100 mg/kg/day) was given by gastric gavage, and ghrelin (20 mu g/kg/day) was administered intraperitoneally for 5 weeks. Thiobarbituric acid reactive substances (TBARS) were measured through fluorometric method. The spatial memory and locomotor activity of the rats were evaluated by Y-maze test.ResultsY-maze results revealed an enhancement of short-term spatial learning and memory in S and SG groups compared to C group. TBARS levels were increased significantly in S group with respect to C group. The increase in TBARS levels induced by sulfite was completely prevented by ghrelin in SG group.ConclusionWe suggest that systemic ghrelin administration might ameliorate ingested sodium metabisulfite-induced hippocampal oxidative damage without providing any changes in spatial learning, memory and locomotion. Further investigation concerning the mechanism of ghrelin action in hippocampus might provide valuable information for developing new therapeutic approaches to attenuate oxidative stress in hippocampal tissue.

Vasovasostomy is used to correct vas deferens (VD) transections encountered during surgery or to reverse sterilization vasectomies. Achieving vasal patency is the primary goal and the success is assessed on various factors including VD patency, flow rates, and pregnancy rates. While preserving vas motility is not a major concern in surgical practice, it is worth noting that VD has peristaltic activity which plays crucial role during ejaculation. Any disruption in its motility could potentially lead to negative outcomes in the future. We conducted an experimental study to assess vas motility changes following vasovasostomy. The study was approved by Gazi University, Animals Ethic Committee. Twenty-four rats were allocated to four groups. Left-sided VD was harvested in control group (Gr1). The rest of the animals were subjected to transection of VD. Gr2 and 3 underwent microscopic and macroscopic anastomosis, respectively, while Gr4 underwent vasal approximation. After 12 weeks, all left-sided VD were resected, electrical field stimulation (EFS) and exogenous drugs were applied to induce contractions. Statistical analyses were performed and p value < 0.05 was regarded as statistically significant. The first and second phases of EFS-induced contractile responses(CR) increased for Gr3 and decreased for Gr4 at submaximal and maximal frequencies. An increase only at maximal frequency for second phase EFS-induced CR was encountered for Gr2. α-β-methylene-ATP-induced CR decreased for Gr3 and 4. Noradrenaline-induced CR increased for Gr2, and 3 and decreased for Gr4. The results suggest that vasovasostomy performed using a surgical technique that minimizes disruption or damage to VD may have a favorable impact on motility.

BACKGROUND: Chest X-ray imaging has been proved as a powerful diagnostic method to detect and diagnose COVID-19 cases due to its easy accessibility, lower cost and rapid imaging time. OBJECTIVE: This study aims to improve efficacy of screening COVID-19 infected patients using chest X-ray images with the help of a developed deep convolutional neural network model (CNN) entitled nCoV-NET. METHODS: To train and to evaluate the performance of the developed model, three datasets were collected from resources of “ChestX-ray14”, “COVID-19 image data collection”, and “Chest X-ray collection from Indiana University,” respectively. Overall, 299 COVID-19 pneumonia cases and 1,522 non-COVID 19 cases are involved in this study. To overcome the probable bias due to the unbalanced cases in two classes of the datasets, ResNet, DenseNet, and VGG architectures were re-trained in the fine-tuning stage of the process to distinguish COVID-19 classes using a transfer learning method. Lastly, the optimized final nCoV-NET model was applied to the testing dataset to verify the performance of the proposed model. RESULTS: Although the performance parameters of all re-trained architectures were determined close to each other, the final nCOV-NET model optimized by using DenseNet-161 architecture in the transfer learning stage exhibits the highest performance for classification of COVID-19 cases with the accuracy of 97.1 %. The Activation Mapping method was used to create activation maps that highlights the crucial areas of the radiograph to improve causality and intelligibility. CONCLUSION: This study demonstrated that the proposed CNN model called nCoV-NET can be utilized for reliably detecting COVID-19 cases using chest X-ray images to accelerate the triaging and save critical time for disease control as well as assisting the radiologist to validate their initial diagnosis.

We aimed to investigate the effects of epoxygenases on electrical field stimulation (EFS)-mediated nitric oxide (NO)-dependent and NO-independent nonadrenergic noncholinergic (NANC) relaxations in isolated rabbit corpus cavernosum. The tissues of 20 male adult albino rabbits (2.5-3 kg) were suspended in organ baths containing aerated Krebs solution, and isometric contractions were recorded. EFS-mediated NANC relaxations were obtained on phenylephrin (3 × 10-5  M)-contracted tissues in the presence of guanethidine (10-6  M) and atropine (10-6  M). Miconazole (10-9 -10-4  M), 17-octadecynoic acid (ODYA) (10-10 -10-5  M), 14,15-epoxyeicosatrienoic acid (EET) (10-11 -10-8  M), 11,12-EET (10-12 -3 × 10-8  M) and 20-hydroxyeicosatetraenoic acid (HETE) (10-11 -3 × 10-8  M) were added cumulatively (n = 5-7 for each set of experiments). For NO-independent relaxations, Nω -nitro-l-arginine methyl ester (l-NAME) (10-4  M) was added before a group of experiments. Depending on the concentration, miconazole, 17-ODYA, 14,15-EET, 11,12-EET, and 20-HETE significantly enhanced both NO-dependent and NO-independent EFS-mediated relaxations (p < 0.05). Epoxygenases showed similar effect on NO-dependent and NO-independent relaxant responses except 20-HETE which caused significantly more enhanced relaxation on NO-dependent responses (p < 0.05). No drug caused a significant relaxation response on tissues contracted with phenylephrine. Epoxygenases contribute to EFS-mediated NO-dependent and NO-independent NANC relaxations by presynaptic mechanisms, offering a new treatment alternative for erectile dysfunction which needs to be explored in further in vivo, molecular and clinical studies.

Purpose: To investigate the effect of Bosentan (non-selective endothelin receptor antagonist) and BQ123 (ETA receptor antagonist) on intraocular inflammation in an endotoxin-induced uveitis (EIU) rabbit model.Methods: Uveitis was induced by intravitreal injection of lipopolysaccharide (LPS). The animals were divided into 7 groups and there were six rabbits in each group (saline, saline and ethanol, bosentan, BQ123, lipopolysaccharide (LPS), bosentan and LPS, BQ123 and LPS-injected groups). Bosentan and BQ123 were applied before LPS injection. Aqueous humour was collected at 24th hour post-injections and enucleation was performed for the evaluation of histopathological changes.Results: BQ123 decreased clinical score, cell counts and protein amount more than bosentan and it was significant for cell counts (p = 0.018). Bosentan significantly diminished inflammatory reactions more than BQ123 as shown in histopathological specimens (p = 0.002).Conclusions: ETA receptor blockage is effective on uveitis treatment by its protective effect on blood aqueous barrier.

BACKGROUND/AIMS Mammalian target of rapamycin (mTOR) signaling serves as a central regulator of cell growth, proliferation, and survival. In this study, we planned to evaluate the expressions of mTOR signaling constituents (p-p70S6K, p-mTOR, and p-Tuberin) in rat gastric mucosa and to compare the results in sulfite- and sulfite+ghrelin-exposed groups. MATERIALS AND METHODS Rats were divided into three groups: the control group (C), the sodium metabisulfite (Na2S2O5) (S) group, and sulfite+ghrelin (SG) group. Sodium metabisulfite at 100 mg/kg/day was administered via gavage, and ghrelin at 20 μg/kg/day was administered intraperitoneally for 35 days. We have used immunohistochemistry for mTOR signaling pathway components. RESULTS There were no significant differences for p-p70S6K and p-mTOR expression among the C, S, and SG groups. Tuberin expression was significantly increased in the S group compared to the C group. Furthermore, tuberin expression was found to be significantly decreased in the SG group. CONCLUSION This study is the first one in the literature that shows the expression of mTOR signaling proteins in gastric mucosa of rats exposed to sulfite and ghrelin. Furthermore, it demonstrates that ghrelin treatment reduces p-Tuberin expression induced by ingested sulfite.

BackgroundDopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of l-DOPA induces yawning and penile erection in some species. The possible effects of l-DOPA on nitric oxide (NO)-dependent and -independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study.MethodsThirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n=4), 3mg/kg/day (low dose) l-DOPA-injected groups (n=6) and 12mg/kg/day (high dose) l-DOPA-injected groups (n=6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed.ResultsThe two-week treatment with high-dose l-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO-independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week l-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls.ConclusionsThe observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following l-DOPA administration.

BACKGROUND:Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits.METHODS:An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer. The nerve-evoked contractile responses were obtained by EFS. The contractile responses were obtained as biphasic "on" and "off" phases seen at the beginning and end of EFS, respectively.RESULTS:Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated "off" phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) "off" phase. NaHS reduced the EFS-mediated "on" phase as well. l-Cysteine ​​reduced the EFS-mediated "off" phase and the EFS-mediated NANC "off" phase. l-Propargylglycine (PAG) did not affect the EFS-mediated "off" phase or the EFS-mediated NANC "off" phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO-independent "off" phase. The effect of NaHS in all of the experiments returned in time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution induced-contractions, while l-cysteine ​​and PAG did not cause a significant relaxation.CONCLUSION:These findings suggest that H2S has an inhibitory effect on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution-induced contractions. This shows that H2S may have an effect on neurotransmission at the nerve terminal.

Background Sodium metabisulfite is commonly used as preservative in foods but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory effects in many organs. This study aimed to assess endogenous omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in rat peripheral organs following sodium metabisulfite treatment and determine the possible effect of ghrelin on changes in n-6 inflammatory pathway. Methods Male Wistar rats included in the study were allowed free access to standard rat chow. Sodium metabisulfite was given by gastric gavage and ghrelin was administered intraperitoneally for 5 weeks. Levels of arachidonic acid (AA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in liver, heart and kidney tissues were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Cyclooxygenase (COX) and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in n-6 inflammatory pathway. Results Omega-6 PUFA levels, AA/DHA and AA/EPA ratio were significantly increased in liver tissue following sodium metabisulfite treatment compared to controls. No significant change was observed in heart and kidney PUFA levels. Tissue activity of COX and PGE2 levels were also significantly increased in liver tissue of sodium metabisulfite treated rats compared to controls. Ghrelin treatment decreased n-6 PUFA levels and reduced COX and PGE2 levels in liver tissue of sodium metabisulfite treated rats. Conclusion Current results suggest that ghrelin exerts anti-inflammatory action through modulation of n-6 PUFA levels in hepatic tissue.

Sodium metabisulfite is used as a preservative in many food preparations but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory and anti-oxidant effects on gastrointestinal and cardiovascular systems. This study was performed to elucidate the effect of ghrelin on sulfite-induced endoplasmic reticulum (ER) stress and caspase activation in rat peripheral organs. Xanthine oxidase (XO), xanthine dehydrogenase (XDH) enzyme activities, ER stress markers [phosphorylated PKR-like ER kinase (pPERK); C/EBP-homologous protein (CHOP)], caspase-3, -8, -9 activities, nuclear factor kappa-B (NF-κB) levels were determined in liver, heart and kidney of rats treated with sodium metabisulfite and/or ghrelin for 5 weeks. Sodium metabisulfite treatment significantly elevated XO activity, induced expression of GRP78, CHOP and increased caspase-3, -8 and -9 activities in liver but had no significant effect in heart and kidney. Ghrelin treatment decreased XO activity to baseline levels and attenuated ER stress and caspase activation in liver tissue of sodium metabisulfite treated rats. In conclusion, metabolism of sodium metabisulfite in liver tissue increased XO activity, induced ER stress and caused caspase activation which was attenuated by ghrelin treatment. Ghrelin's hepatoprotective effect could be through modulation of XO activity.

PURPOSE:We investigated the effect of eritoran, a Toll-like receptor 4 antagonist, on retinochoroidal inflammatory damage in an endotoxin-induced inflammatory rat model.METHODS:Endotoxin-induced inflammatory model was obtained by intraperitoneal injection of 1.5 mg/kg lipopolysaccharide (LPS). Group 1 had control rats; in groups 2-3 LPS and 0.5 mg/kg sterile saline were injected; and in groups 4-5 LPS and 0.5 mg/kg eritoran were injected. Blood samples were taken and eyes were enucleated after 12 hours (h) (groups 2 and 4) or 24 hours (Groups 3 and 5). Tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels in the serum and retinochoroidal tissue and nuclear factor kappa-B (NFκB) levels in retinochoroidal tissue were determined. Histopathological examination was performed and retinochoroidal changes were scored.RESULTS:Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. Serum TNF-α and retinochoroidal tissue NFκB levels were similar to control animals at the 24th h of the study. Eritoran significantly reversed histopathological damage after 24 h.CONCLUSIONS:Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters.

This study aimed to investigate the effect of ghrelin administration on sulfite induced oxidative and apoptotic changes in rat gastric mucosa. Forty male albino Wistar rats were randomized into control (C), sodium metabisulfite (Na2S2O5) treated (S), ghrelin treated (G) and, Na2S2O5+ghrelin treated (SG) groups. Sodium metabisulfite (100mg/kg/day) was given by gastric gavage and, ghrelin (20μg/kg/day) was given intraperitoneally for 5weeks. Plasma-S-sulfonate level was increased in S and SG groups. Na2S2O5 administration significantly elevated total oxidant status (TOS) levels while depleting total antioxidant status (TAS) levels in gastric mucosa. Ghrelin significantly decreased gastric TOS levels in the SG group compared with the S group. Additionally, TAS levels were found to be higher in SG group in reference to S group. Na2S2O5 administration also markedly increased the number of apoptotic cells, cleaved caspase-3 and PAR expression (PARP activity indicator) and, decreased Ki67 expression (cell proliferation index) in gastric mucosal cells. Ghrelin treatment decreased the number apoptotic cells, cytochrome C release, PAR and, caspase-3 expressions while increasing Ki67 expression in gastric mucosa exposed to Na2S2O5. In conclusion, we suggest that ghrelin treatment might ameliorate ingested-Na2S2O5 induced gastric mucosal injury stemming from apoptosis and oxidative stress in rats.

BACKGROUND Anaplastic pleomorphic xanthoastrocytoma is an aggressively growing, malignant, and eventually fatal tumor of the central nervous system. Testing chemotherapeutic drug sensitivity under in vitro conditions would be a useful strategy to determine sensitive or resistant drugs for fatal brain cancers. OBJECTIVE To establish primary cell cultures of excised tumor tissue from pleomorphic xanthoastrocytoma–bearing patients and to test their sensitivity against various anticancer chemotherapy drugs. METHODS Prepared suspensions of the excised tumor tissue from a patient who had a recurrent grade 3 pleomorphic xanthoastrocytoma was cultured in culture dishes until cells began to grow. Immunofluorescent and immunohistochemical visualizations were performed using confocal and light microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in comparison with 3H-thymidine incorporation assay was used to test cellular toxicity of several anticancer drugs. RESULTS We established vigorously growing primary cells of the tumor. Drug sensitivity testing was conducted successfully. CONCLUSION Primary cell cultures of surgically removed tumor tissues may be useful in studies of cancer biology and chemotherapeutic drug sensitivity for recurrent malignant brain tumors, particularly for anaplastic pleomorphic xanthoastrocytoma.

BACKGROUND Anaplastic pleomorphic xanthoastrocytoma is an aggressively growing, malignant, and eventually fatal tumor of the central nervous system. Testing chemotherapeutic drug sensitivity under in vitro conditions would be a useful strategy to determine sensitive or resistant drugs for fatal brain cancers. OBJECTIVE To establish primary cell cultures of excised tumor tissue from pleomorphic xanthoastrocytoma–bearing patients and to test their sensitivity against various anticancer chemotherapy drugs. METHODS Prepared suspensions of the excised tumor tissue from a patient who had a recurrent grade 3 pleomorphic xanthoastrocytoma was cultured in culture dishes until cells began to grow. Immunofluorescent and immunohistochemical visualizations were performed using confocal and light microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in comparison with 3H-thymidine incorporation assay was used to test cellular toxicity of several anticancer drugs. RESULTS We established vigorously growing primary cells of the tumor. Drug sensitivity testing was conducted successfully. CONCLUSION Primary cell cultures of surgically removed tumor tissues may be useful in studies of cancer biology and chemotherapeutic drug sensitivity for recurrent malignant brain tumors, particularly for anaplastic pleomorphic xanthoastrocytoma.

EFS mediated NO‐dependent and ‐independent NANC relaxation responses in isolated rabbit corpus cavernosum and the contributions of chloride channels to these responses were examined.

Sodium metabisulfite (Na 2 S 2 O 5 ) is used as an antioxidant and antimicrobial agent in a variety of drugs and functions as a preservative in many food preparations. This study was performed to elucidate the dose-dependent effects of sodium metabisulfite ingestion on rat gastric tissue apoptotic changes and lipid peroxidation. Forty male wistar rats, aged 3 months were used. They were randomly divided into four groups: control (C), the group treated with Na 2 S 2 O 5 (10 mg/kg; S1), the group treated with Na 2 S 2 O 5 (100 mg/kg; S2), the group treated with Na 2 S 2 O 5 (260 mg/kg; S3). Na 2 S 2 O 5 was given by intragastric intubation for 35 days. In the S2 and S3 groups, malondialdehyde (MDA) levels increased markedly when compared with the control group. High doses of sulfite administration elevated number of apoptotic cells both in mucosa and submucosa layers of stomach in parallel with increased MDA levels. These results suggest that sodium metabisulfite increased lipid peroxidation and thus number of apoptotic cells on gastric tissue in dose-dependent manner.