Enhancement of enzyme activity by laser-induced energy propulsion of upconverting nanoparticles under near-infrared light: A comprehensive methodology for in vitro and in vivo applications.

If the appropriate immobilization method and carrier support are not selected, partial decreases in the activity of enzymes may occur after immobilization. Herein, to overcome this challenge, an excitation mechanism that enables energy transfer was proposed. Modified upconverting nanoparticles (UCNPs) were constructed and the important role of near-infrared (NIR) excitation in enhancing the catalytic activity of the enzyme was demonstrated. For this purpose, UCNPs were first synthesized via the hydrothermal method, functionalized with isocyanate groups, and then, PEG-L-ASNase was immobilized via covalent binding. UCNPs with and without PEG-L-ASNase were extensively characterized by different methods. These supports had immobilization yield and activity efficiency of >96 % and 78 %, respectively. Moreover, immobilized enzymes exhibited improved pH, thermal, and storage stability. In addition, they retained >65 % of their initial activity even after 20 catalytic cycles. Biochemical and histological findings did not indicate a trend of toxicity in rats due to UCNPs. Most importantly, PEG-L-ASNase activity was triggered approximately 5- and 2-fold under in vitro and in vivo conditions, respectively. Overall, it is anticipated that this pioneering work will shed new light on the realistic and promising usage of NIR-excited UCNPs for the immobilization of enzymes in expensive and extensive applications.

Effect of Melatonin on Increasing the Effectiveness of Liver Preservation Solution.

BACKGROUND/AIMS: Various tissue preservation solutions are used during the removal of the organ and during transplantation to protect the normal histological and biochemical characteristics of tissue while performing a successful liver transplant. In our study, it was aimed to investigate the effects of intraperitoneal melatonin administration on liver preservation damage before transplantation. MATERIALS AND METHODS: In our study, the histological and biochemical characteristics of University of Wisconsin+melatonin group rats treated with melatonin 45 minutes before hepatectomy were compared between serum physiologic group and University of Wisconsin group. RESULTS: When hematoxylin and eosin staining was evaluated in terms of hydropic degeneration, sinusoidal dilatation, and hepatocyte necrosis, there was no statistically significant difference. Caspase 3 immunohistochemical staining showed a significant increase in Caspase 3 immunoreactivity positivity at the 12th-hour University of Wisconsin group compared to University of Wisconsin+melatonin group. As a result of biochemical analysis, the malondialdehyde and total oxidant status levels in the University of Wisconsin+melatonin group decreased significantly compared to the University of Wisconsin group. When the reduced glutathione activity and total antioxidant capacity level were compared, a significant increase was observed in the University of Wisconsin+melatonin group compared to the University of Wisconsin group at the 12th hour. It was also found that aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels decreased significantly in the University of Wisconsin+melatonin 12th-hour group compared to the University of Wisconsin 12th hour and control group. CONCLUSION: When the findings were evaluated, intraperitoneal administration of melatonin, a cytoprotective antioxidant, was found to play an effective role in preserving immunohistochemical and biochemical properties of liver tissue integrity and hepatocytes in University of Wisconsin solution.

Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Modeling Based on Ensemble Learning Methods for Detection of Diagnostic Biomarkers from LncRNA Data in Rats Treated with Cis-Platinum-Induced Hepatotoxicity.

BACKGROUND: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods. METHODS: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values. RESULTS: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group (p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR_005492522.1, rna-XR_005492536.1, and rna-XR_005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity. CONCLUSIONS: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

Effects of the apricot diets containing sulfur dioxide at different concentrations on rat testicles.

Due to its antioxidant and antimicrobial properties, sulfur dioxide (SO2) is widely used in foods and beverages to prevent the growth of microorganisms and to preserve the color and flavor of fruits. However, the amount of SO2 used in fruit preservation should be limited due to its possible adverse effects on human health. The present study was designed to investigate the effects of different SO2 concentrations in apricot diets on rat testes. Animals were randomly divided into six groups. The control group was fed a standard diet, and the other groups were fed apricot diet pellets prepared with (w/w) 10% dried apricots containing SO2 at different concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm/kg) for 24 weeks. After sacrification, testicles were evaluated biochemically, histopathologically, and immunohistopathologically. Our results showed that an apricot diet containing 1500 ppm and 2000 ppm SO2 did not cause significant changes in testis. However, it was determined that tissue testosterone levels decreased as the amount of SO2 (2500 ppm and above) increased. Apricot diet containing 3500 ppm SO2 caused a significant increase in spermatogenic cell apoptosis, oxidative damage, and histopathological changes. In addition, a decrease in the expression of connexin-43, vimentin, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) was observed in the same group. In summary, the results show that sulfurization of apricot at high concentrations such as 3500 ppm may lead to male fertility problems in the long term through mechanisms such as oxidative stress, spermatogenic cell apoptosis, and inhibition of steroidogenesis.

Angiotensin II type 2 receptor agonist treatment of doxorubicin induced heart failure.

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.

An experimental rat model of electric shock injury with isolated electric shock and water conduction: the histopathological changes on the skin and internal organs and the effect on biochemical parameters.

It is difficult to determine the cause of death in electric shock injuries when no trace can be determined on the skin, and this is accepted as a reason for negative autopsy. We aimed to determine useful parameters in the definition of the cause of deaths associated with electric shock and particularly those formed with water conduction. This study used a total of 42 rats, applied with fatal electric shock formed of isolated electric shock at 220 V and with water conduction. The serum NT-ProBNP and H-FABP levels were examined together with histopathological changes in the brain, cerebellum, brainstem, heart, liver and skin and the Bax, caspase-3 and HSP-60 antibody status in these tissues. A statistically significant difference was determined between the groups in respect of the serum H-FABP values and the immunohistochemical staining of the samples taken from the organs. In conclusion, this study is the first in literature with an experimental model of electric shock with water conduction. Using immunohistochemical and biochemical markers in deaths associated with isolated electric shock and electric shock with water conduction, the results of this study can contribute to the clarification of one of the reasons for negative autopsy in forensic medicine.

Effects of apocynin on sciatic nerve injury in rabbits.

We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II-induced hypertension.

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin-angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II-induced hypertension in rats. Sprague Dawley rats were subject to 4-week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 µg/kg), AVE0991 (576 µg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail-cuff plethysmography at 1, 15, and 29 days post-treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin-A (CYP-A), monocyte chemoattractant protein-1 (MCP-1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase-2 and -9, NADPH oxidase-4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP-1 and CYP-A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin-converting enzyme-2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II-induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.

Fast Curing Multifunctional Tissue Adhesives of Sericin-Based Polyurethane-Acrylates for Sternal Closure.

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operator-induced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L-929 cells), biodegradable, and antibacterial (on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing.

Effects of taurine and apocynin on the zone of stasis.

BACKGROUND: Among the zones of coagulation, hyperemia and stasis that occur in the burned area, the most intense metabolic process and the highest sensitivity to recovery with treatment is the zone of stasis.This metabolic process is related to how well the tissues in the zone of stasis can cope with oxidative stress. If the tissues in the zone of stasis are saved, the burn area will potentially heal faster and with less scar. In this study, we examined the effects of taurine amino acids and apocynin molecules on saving the tissues in the burn zone of stasis. METHODS: The study was conducted with 48 rats. The burn zone of stasis was created according to the pattern previously described in the literature as comb burn model. In the 21-day study, biopsies were taken for histological examination on the 3rd, 7th and 21st days of the study. In addition, macroscopic photographic analysis was performed. Biopsies were taken for biochemical analysis on the 21st day. Histologically, inflammation, reepithelialization, and collagenization were evaluated, and the CD34 immunoreactivity was analysed. Biochemically, CAT, SOD, tGSH, TAS, TOS, MDA and PPC values were determined. RESULTS: In the histological examination, on the 3rd, 7th and 21st days, inflammation was found to be reduced in the groups given taurine and apocynin on the 3rd day. On the 7th day, better reepithelialization and collagenization were observed in the group given taurine. Significant reepithelialization, collagenization and hair follicle development were observed in the groups given taurine and apocynin on the 21st day. In the biochemical analysis, the effects of apocynin on antioxidant enzymes were determined to be prominent. While we found no significant difference on the 3rd and 7th days in the photographic analysis, taurine and apocynin were observed to act synergistically on the 21st day and significantly reduced the burned areas. CONCLUSION: On the 3rd day, taurine and apocynin prevented inflammation, the effects of taurine in the zone of stasis in the early period (7th day) are more pronounced, the effect of apocynin on antioxidant enzymes is more pronounced. In the late period (21st day), taurine and apocynin were found to be more effective in saving the zone of stasis by creating a synergistic effect.

The effect of genistein on cisplatin induced ototoxicity and oxidative stress / Efeito da genisteína na ototoxicidade induzida pela cisplatina e estresse oxidativo

Abstract Highlights Cisplatin is an antineoplastic agent used malignant diseases. Cisplatin ototoxicity is generally bilateral, irreversible, and progressive. Genistein is a phytoestrogen. Genistein functions as antioxidant and cell cycle inhibitor by inhibiting DNA topoisomerase. Genistein showed positive effects on ototoxicity with its antioxidant. Objective Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. Methods 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. Results The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p < 0.05). Conclusion Genistein showed positive effects against ototoxicity with its antioxidant effect. Level of evidence Level 3.

Resumo DESTAQUES A cisplatina é um agente antineoplásico usado em lesões malignas. A ototoxicidade da cisplatina é geralmente bilateral, irreversível e progressiva. A genisteína é um fitoestrógeno. A genisteína funciona como antioxidante e inibidor do ciclo celular ao inibir a topoisomerase do DNA. A genisteína apresentou efeitos positivos sobre a ototoxicidade com seu efeito antioxidante. Objetivo A cisplatina é um agente antineoplásico usado em adultos e crianças para o tratamento de diversas lesões malignas. Pode causar ototoxicidade irreversível. A genisteína é um fitoestrógeno que funciona como antioxidante e inibidor do ciclo celular ao inibir as enzimas DNA topoisomerase e tirosina-quinase. O efeito protetor da genisteína na prevenção da ototoxicidade induzida pela cisplatina e os níveis de estresse oxidativo foram investigados. Método Trinta e dois ratos Sprague Dawley foram usados em 4 grupos (controle, cisplatina, cisplatina + genisteína, genisteína). As medidas das emissões otoacústicas por produto de distorção foram tomadas nos dias 1, 2 e 5 do protocolo do teste. Foram medidos os níveis séricos de malondialdeído, superóxido dismutase, catalase, glutationa peroxidase, estado antioxidante total, estado oxidante total e índice de estresse oxidativo. Resultados A audição do grupo cisplatina + genisteína foi melhor do que a do grupo cisplatina. Enquanto os parâmetros malondialdeído, estado oxidante total e índice de estresse oxidativo diminuíram significantemente no grupo cisplatina + genisteína em comparação com o grupo cisplatina, o superóxido dismutase mostrou aumento significantemente (p < 0,05). Conclusão A genisteína apresentou efeitos positivos contra a ototoxicidade com seu efeito antioxidante. Nível de evidência Nível 3.

Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

The effect of genistein on cisplatin induced ototoxicity and oxidative stress.

OBJECTIVE: Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. METHODS: 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. RESULTS: The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p < 0.05). CONCLUSION: Genistein showed positive effects against ototoxicity with its antioxidant effect. LEVEL OF EVIDENCE: Level 3.

Effects of antiepileptic drugs on ovaries of female Wistar rats.

Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.

Preoperative and Postoperative Endogenous Melatonin and Anxiety Levels and Their Correlation in Living Liver Donors.

OBJECTIVES: High anxiety levels may lead to mental and physical changes that may affect quality of life. Melatonin has anxiolytic properties. It has been reported that administration of melatonin reduces anxiety. In this study, we examined the preoperative and postoperative anxiety levels of living liver donors and the correlation between anxiety levels and endogenous melatonin levels. MATERIALS AND METHODS: This prospective clinical study included 56 living liver donors who underwent right hepatectomy (39 women, 17 men; average age of 29 ± 7 years). The anxiety levels were evaluated by using the Spielberger State-Trait Anxiety Inventory Test with a form for this test used to measure the current state of anxiety score and another form used to measure the underlying anxiety score of the patient. These forms were applied preoperatively and postoperatively. Blood samples were taken simultaneously for melatonin levels. Melatonin levels were measured using high-pressure liquid chromatography. Our primary outcomes were to determine the preoperative and postoperative endogenous melatonin and anxiety levels of living liver donors and to investigate their correlations. RESULTS: A statistically significant difference was observed between preoperative and postoperative state of anxiety scores. The preoperative and postoperative underlying anxiety scores were similar. A statistically significant difference was found between the preoperative endogenous melatonin level and postoperative endogenous melatonin level. A significant correlation was not observed between the preoperative and postoperative current and underlying anxiety levels or endogenous melatonin levels. CONCLUSIONS: Living liver donors had high anxiety levels during the preoperative and postoperative periods. A significant decrease was identified in the postoperative hour 24 endogenous melatonin level. These results may lay the foundation for interventions that can identify emotional changes as well as control and improve the mental health of living liver donors.

The Protective Effects of Compound 21 and Valsartan in Isoproterenol-Induced Myocardial Injury in Rats.

This study investigated the protective effects of Compound 21 (C21), the first specific non-peptide AT2 receptor agonist, on cardiac injury in rats with isoproterenol-induced heart failure in vivo and compared it with valsartan, an AT1 receptor antagonist. In this study, 56 Wistar albino male rats (estimated body weights 250-400 g) were divided into eight groups (n = 7). Group 1 (Control) received no drug. Group 2 (ISO) was given 180 mg/kg of isoproterenol subcutaneously (s.c.); two doses were administered at 24-h intervals on days 29 and 30 of the experiment. Groups 3, 4, and 5 were given valsartan (30 mg/kg orally), C21 (0.03 mg/kg intraperitoneally), and a combination of Valsartan + C21, respectively, for 30 days. Groups 6, 7, and 8 were administered Valsartan, C21, and Valsartan + C21 in the same application, duration, and dose, respectively, and isoproterenol (180 mg/kg s.c.) was given on days 29 and 30 of the experiment. Transthoracic echocardiography was performed on the rats at the beginning and end of the experiment. Blood pressure, heart rate, and ECG alterations were monitored via a carotid artery cannula at the end of the experiment. Histopathological and biochemical measurements were performed on the cardiac tissue of the rats. For histopathological findings, C21 and Valsartan + C21 combination therapy significantly reduced the development of heart failure compared to valsartan alone. Also, the protective effect of C21 on myocardial injury was superior to that of valsartan. According to the results of echocardiographic and biochemical evaluations, C21, and Valsartan showed protective effects against heart failure. C21, valsartan, and combined therapy significantly prevented the decrease of ejection fraction. This report describes the cardioprotective effects of C21 and valsartan in ISO-induced myocardial damage.

Comparison of the effects of losartan, captopril, angiotensin II type 2 receptor agonist compound 21, and MAS receptor agonist AVE 0991 on myocardial ischemia-reperfusion necrosis in rats.

Myocardial ischemia may occur as a result of pathophysiological and therapeutical applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery bypass, and transplantation. In this study, we aimed to compare the effects of angiotensin (Ang) II type 2 (AT2 ) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT1 ) selective receptor blocker losartan, and Ang-converting enzyme inhibitor captopril on haemodynamic parameters and infarct size on myocardial ischemia/reperfusion (MI/R)-induced necrosis in rats. To induce necrosis in the heart of rats, reperfusion for 2 h following ischemia for 30 min to the descending branch of the left main coronary artery was achieved. C21 (0.03 mg/kg), AVE 0991 (576 µg/kg), losartan (2 mg/kg), and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. Then, the infarct size and risk area were calculated from the heart. The percentage of myocardial infarct size to area at risk ratio (%IS/AR) of groups was Control (MI/R) group: 48.9 ± 8.8%; C21 group: 31.1 ± 7.8%; AVE 0991 group: 29.9 ± 4.8%; C21 + AVE 0991 group: 28.2 ± 3.3%; Losartan + AVE 0991 group: 30.8 ± 5.8%; Captopril + AVE 0991 group: 31.7 ± 7.7%. %IS/AR of the drug-treated groups decreased significantly when compared to the MI/R group (P < 0.05). Our results indicate that the importance of AT1 , AT2 , and MAS receptors in the MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT1 receptor with losartan, and stimulation of AT2 receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing infarct size.

Therapeutic effects of dexpanthenol on the cardiovascular and respiratory systems following cecal ligation and puncture-induced sepsis in rats.

Cecal ligation and puncture (CLP) is a commonly used model of sepsis in vivo. We investigated the effects of dexpanthenol (DXP) on heart, lung and aorta in CLP-induced sepsis in rats. Rats were divided into four groups of eight: group 1, sham (SH); group 2 (DXP), 500 mg/kg DXP injected intraperitoneally (i.p.); group 3 (CLP), CLP performed; group 4 (CLP + DXP), 500 mg/kg DXP injected i.p. after CLP. Heart, lung and aorta specimens were harvested for histopathological and biochemical analysis. Heart rate increased in group 3 compared to group 1; DXP administration to group 4 did not alleviate this change. In heart tissue samples, MDA levels were decreased significantly in groups 2 and 4 compared to group 3. The levels of GSH in groups 2 and 3 were elevated compared to groups 1 and 2. SOD activity was increased significantly in group 4 compared to group 3. CAT activity for group 4 was increased significantly compared to groups 1 and 3. We found that caspase-9 and caspase-3 activity was increased after application of CLP. Also, DXP treatment decreased the number of caspase-positive cells significantly compared to group 3. DXP appears to be promising for reducing sepsis-related mortality.

Acute and Subacute Effects of Low Versus High Doses of Standardized Panax ginseng Extract on the Heart: An Experimental Study.

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.