A New Approach in the Treatment of Traumatic Brain Injury: The Effects of Levosimendan on Necrosis, Apoptosis, and Oxidative Stress.

OBJECTIVE: Traumatic brain injury (TBI) is an essential and common health problem worldwide. Levosimendan is an inotropic and vasodilator drug used to treat heart failure. Moreover, it exerts pleiotropic effects and, thus, protective effects on many organs. The present study aimed to investigate the effect of levosimendan on necrosis, apoptosis, and reactive oxygen species in rats with TBI. METHODS: The study included 28 female Wistar-Albino rats weighing 200-250 g. The rats were divided into 4 groups with 7 rats each as follows: Group 1: No trauma group (Control), Group 2: Traumatized, untreated group (T), Group 3: Levosimendan was administered at a dose of 12 µg/kg intraperitoneally 1 hour after the trauma (L1), Group 4: Levosimendan was administered at a dose of 12 µg/kg intraperitoneally 2 hours after the concussion (L2). After the experiment, the rats were decapitated, and the brain tissue was removed. Necrosis was assessed with Cresyl violet staining, apoptosis was assessed with immunohistochemical analysis, superoxide dismutase and catalase levels were measured with the spectrophotometric method, and malondialdehyde (MDA) levels were assessed by High-Performance Liquid Chromatography. RESULTS: The number of necrotic cells in the L1 and L2 groups was significantly lower than in the K and T groups (P = 0.015 and P = 0.03, respectively). Although the active caspase-3 level was signified considerably in the T, L1, and L2 groups compared to the K group, no significant difference was found among these 3 groups (P > 0.05). The results of superoxide dismutase levels were similar to those of active caspase-3. catalase level was significantly higher in the K group than in the T and L2 groups (P = 0.045). Malondialdehyde activity was considerably higher in the L1 and L2 groups compared to the K group (P = 0.023). CONCLUSIONS: Our results indicated that levosimendan may exert a neuroprotective effect by reducing necrosis in TBI and that levosimendan does not affect apoptosis and antioxidant levels in TBI. Comprehensive studies are needed to elucidate the effect of levosimendan on TBI fully.

Relationship between MTHFR Gene Polymorphisms and Gastrointestinal Tumors Development: Perspective from Eastern Part of Turkey.

BACKGROUND: Gastric and esophageal cancers are 2 of the most prevalent cancer types worldwide. Polymorphisms in the genes that code the methylenetetrahydrofolate reductase (MTHFR) enzyme increase the formation of both cancer types. In this study, it was aimed to research the relationship between the existence of MTHFR C677T and A1298C polymorphisms in patients with gastric and esophageal cancer and the lifespans of patients. METHODS AND MATERIALS: This prospective study was performed at Van Yuzuncu Yil University. Included in the study were 30 patients with esophageal tumors, 70 patients with gastric tumors, and 61 healthy volunteers. From each of the patients, 5 mL of blood was drawn. DNA was isolated via kits with spin-column technology. RESULTS: It was concluded that the risk of developing gastric cancer was 4.13 times higher in individuals who had the AC genotype of the A1298C polymorphism when compared to those who had the AA genotype, while the risk was 2.91 times higher in individuals who had the CC genotype when compared to those who had the AA genotype (P = 0.001, P = 0.027). Carriers of the AC genotype of the A1298C polymorphism had 2.89 times higher risk of developing esophageal cancer when compared to those who had the AA genotype (P = 0.033). It was determined that individuals who had the 1298 CC genotype were not at higher risk of developing esophageal cancer when compared to those with the AA genotype (P = 0.863). It was concluded that individuals who had the TT genotype of the C677T polymorphism were not at higher risk of developing gastric and esophageal cancers when compared to those who had the 677CC genotype (P > 0.05). There was no difference in terms of the life spans of the patients with regards to the genotypes (P > 0.05). CONCLUSION: The results showed that the A1298C polymorphism on the MTHFR gene can be a risk factor for gastric and esophageal cancer in eastern Turkey. These polymorphisms may have no effect on the life spans of the patients.

Role of Sedative-Hypnotic Agents in Neurodegeneration: Effects of Midazolam and Thiopental on Apoptosis and Oxidative Stress Expression in Neonatal and Adult Rat Brains.

AIM: To investigate the effects of midazolam (MDZ) and thiopental on neonatal and adult rat brains. MATERIAL AND METHODS: The study included adult and 7-day-old rats that were administered 9 mg/kg of MDZ, 60 mg/kg of thiopental, or both. The Bax, procaspase-3, and caspase-3 levels were assessed using Western Blot analysis and the total oxidative stress index (OSI) values were measured spectrophotometrically. RESULTS: The procaspase-3 and caspase-3 levels were 12% and 6% lower in the neonatal MDZ group when compared to the control group. The Bax, procaspase-3, and caspase-3 levels were higher in the neonatal thiopental group by 25%, 4%, and 34%, and in the MDZ group by 16%, 19%, and 43% when compared to the neonatal control group. In the adult rats, the caspase-3 levels were 10 times higher in the MDZ group when compared to the control and thiopental groups. Moreover, the caspase-3 levels were 7 times higher in the adult thiopental group when compared to the control group. The OSI values in the neonatal rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05). Similarly, the OSI values in the adult rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05). CONCLUSION: MDZ and thiopental may promote apoptosis and oxidative stress, and thereby result in neurotoxicity, with MDZ showing a greater effect in adults and thiopental showing a greater effect in neonates.

Effect of Paracetamol in the Proliferation of Glioblastoma Cell Line: The Role of Apoptosis, COX-2 and Cyclin B Expressions.

AIM: To investigate the relationship between paracetamol and expression levels of cyclooxygenase-2, cyclin B, cell viability and apoptosis in glioblastoma cell line. MATERIAL AND METHODS: The A172 glioblastoma cells were treated with different concentrations of paracetamol and phosphate buffer saline as a vehicle for 24, 48, and 72 hours. Cell viability was detected by MTT. Bax, procaspase 3, COX-2 and Cyclin B expressions were detected using Western blotting. RESULTS: A paracetamol treatment of 0.5 mg/mL for 24, 48, and 72 hours led to a 14%, 31%, and 37% decrease in cell viability. The expression of COX-2 and cyclin B levels decreased by 36% and 52% respectively, after treatment with 0.5 mg/mL paracetamol. Treatment with 0.5 mg/mL and 1 mg/mL paracetamol significantly induced the expression of cleaved caspase 3, procaspase 3 and Bax proteins compared to the control group (60%, 40%, 21%, %100, 18%, 17%, respectively). CONCLUSION: The results of our study showed that paracetamol has antitumoral effects on glioblastoma cells and this activity was induced by different signaling pathways.

Comparison of effects of high and low dose paracetamol treatment and toxicity on brain and liver in rats.

OBJECTIVE: Paracetamol is thought that it acts by inhibiting the central cyclooxygenase (COX) enzyme; its mechanism of action is still not fully explained. Although its most important side effect is hepatoxicity, it is thought to cause toxicity on the brain in recent years. The present study aims to investigate the treatment and toxic effects of low and high doses of paracetamol on the liver and brain. METHODS: Wistar-albino rats were used in this study. At doses of 20-500 mg/kg, paracetamol was administered intraperitoneally once a day for one and three days. The brain and liver were used for immunohistochemical evaluation using COX-3, prostaglandin E2 (PGE2) and caspase 3 antibodies and for total antioxidant (TAS), total oxidant (TOS) and oxidative stress index (OSI) measurements. Results were evaluated using the Kruskal Wallis test (SPSS ver.24). RESULTS: The liver COX-3 levels were significantly lower in both groups with higher doses (p<0.05). In the brain, there was no statistically significant difference in COX-3 levels between the groups. There was no statistically significant difference in PGE2 levels in the liver and brain between the groups (p>0.05). The caspase 3 level in the liver was statistically significantly higher in the low dose group compared to the other groups (p<0.05). In both liver and brain, OSI values were significantly higher in the 3-day high-dose group compared to others (p<0.05). There was no statistically significant difference between the groups in ALT and AST values (p>0.05). CONCLUSION: The results of our study show that paracetamol inhibits the COX-3 enzyme in the liver but has no effect in the brain, and COX-3 does not have an effect on PGE2. Paracetamol causes apoptosis in the liver only in low doses; higher doses may cause toxicity by increasing oxidative stress, especially in the brain.

A new approach at diabetic foot treatment: Phosphodiesterase 5 inhibitors.

Diabetic foot (DF), is one of the most serious and prevalent complications of diabetes mellitus (DM). Disruption in tissue oxygenation due to atherosclerosis in peripheral veins has an important place in DF development. In recent years, phosphodiesterase type 5 (PDE5) inhibitor drugs like sildenafil, which cause peripheral vasodilation, are used commonly in cases of erectile dysfunction, pulmonary hypertension and cardiac insufficiency. In that sense, PDE5 inhibitors, which cause vasodilation in peripheral veins, can increase blood build up in tissues of patients with DF and its stand-alone usage or its usage with already used treatments can increase tissue healing speed and quality.

Can intravesical application of paracetamol benefit the chemotherapy treatment of bladder cancer?

Bladder cancer is one of the most common urogenital tumors. Its prevalence is increasing worldwide, especially men. The cyclooxygenase-2 (COX-2) enzyme has been shown to increase in bladder cancer and has a direct relationship with tumor progression. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the growth of the tumor by inhibiting the COX-2 enzyme. NSAIDs have other effects unrelated to COX that provide anticancer properties. Also, similar to NSAIDs, anticancer effects of paracetamol have been shown in many studies. Therefore we hypothesize intravesical paracetamol application will have beneficial effects in the treatment of non-muscle invasive bladder cancer (NMBIC).

Therapeutic potential of cyclooxygenase-3 inhibitors in the management of glioblastoma.

In this study we investigated the expression of COX-1, COX-2 and COX-3 mRNA in C6 glioblastoma and normal brain tissues and the effects of acetaminophen, indomethacin or metamizole treatments on the development of C6 glioblastoma in relation with COX inhibition. Glioblastoma cells were inoculated intracerebrally into frontal lobe of adult male Wistar albino rats. 10 days after inoculation, rats were treated with 150 mg/kg acetaminophen, 10 mg/kg indomethacin or 150 mg/kg metamizole. The tumor size was measured histologically and total RNA was isolated from tumor or normal brain tissue and mRNA levels of COX isoforms were determined by qRT-PCR. Our results showed the presence of COX-1, COX-2 and COX-3 expressions in both C6 glioblastoma and normal brain tissues. In tumor tissues COX-3 expression was significantly higher than normal brain tissue (p < 0.05) while there was no significant difference in COX-1 and COX-2 expressions. Acetaminophen and indomethacin decreased the tumor size by 71 and 43 % by inhibiting COX-3 mRNA expression around 87 and 91 % respectively. For the first time our study proposes a possible relationship between COX-3 mRNA expression and C6 glioblastoma development. We also suggested that the inhibition of COX-3 enzyme may be responsible for decrease in tumor size in part, the mechanism by which acetaminophen and indomethacin decreased rat C6 glioblastoma growth. However, the molecular events responsible for COX-3 effects on tumor development are still unresolved as these drugs exert their anti-cancer effect via both COX-3 dependent and independent mechanisms.

Evaluation of demographic characteristics, and general disease state of patients affliated with home health care unit of Malatya State Hospital.

OBJECTIVE: Home Health Care Unit a unit provides health services for elderly, bedridden and individuals with chronic diseases at home along within the frame of the diagnosis, and treatments of the relevant experts. Therefore, it is intended to reduce the probable physical and emotional burden related to the patient that arise by commuting to the hospital, to increase the number of empty beds for other patients and to improve the living standard by reducing the risk of hospital infection. In this study, the demographic characteristics of housebound patients, their general disease and its relationship with age and gender was investigated. METHODS: The following study was performed on 626 active patients of Malatya State Hospital Home Health Care Unit from January to November 2014. Data were analyzed using Microsoft Excel Program. RESULTS: The study included 60.5% (n=379) female and 39.5% (n=247) male patients. The highest group consisted of patients with 80 years or above 37.7% (n=236). Cerebrovascular disease (CVD) (n=95; 25.0%), senility (n=56; 14.8%) and Alzheimer's disease (n=50; 13.2%) were commonly observed in women. Male patients had CVD (n=54; 21.8%), femur fracture or gonarthrosis which required surgery (n=28; 11.3%), and fracture due to trauma or traffc accidents (n=28; 11.3%), senility and Alzheimer's disease (n=218.5%). CONCLUSION: In recent years home health care units became even more important after the gradual increase in the elderly population and injuries due to accidents. This study can help to provide home health care units in a more effcient manner by educating the staff and relatives who take care of the patients.