Example of digital exhibition in anthropology and medical education.

Technology brings new opportunities in terms of education and research, and global pandemics such as the recent COVID-19 pandemic require online education-style approaches. Visualisation is of great importance in digitised education. In this study, materials that are of interest to the disciplines of anthropology, dentistry and medicine were selected from the skeletal materials and presented in a virtual exhibition. The mandible samples were digitised by photogrammetric method, and the exhibition was made navigable by using the Unity game engine program. In the exhibition, information on dental and bone physiology and palaeopathology, as well as the mandibles of the skeletons obtained from the excavation area, and information on individuals are presented on informative boards. The exhibition can be visited online with the link provided. In this study, the opinions of 30 students, who visited the exhibition from Faculty of Medicine 3rd-5th classes, were asked to complete an online questionnaire. Results of this questionnaire show that students would like to see more of such digital education methods. Digitising educational presentations enables these exhibitions to transcend physical boundaries and reach a global audience. In addition, the images can be easily examined by anyone who visits and can be evaluated for educational purposes.

Melatonin is effective in attenuating cisplatin-induced neurotoxicity.

Cisplatin (Cis) is a chemotherapeutic agent that has many side effects. Neurotoxicity is one of the most important of these side effects. Oxidative stress and neuroinflammation are the best-known mechanisms in the pathogenesis of neurotoxicity development. In this study, we aimed to determine whether melatonin (Mel), with antioxidant and anti-inflammatory effects, is effective in preventing Cis-induced neurotoxicity. Forty-eight male Sprague-Dawley rats were divided into six groups (n = 8) as follows: control (0.9% NaCl), vehicle (5% ethanol), Cis (6 mg/kg), Cis (6 mg/kg) + vehicle (5% ethanol), Mel (20 mg/kg), and Cis (6 mg/kg) + Mel (20 mg/kg) groups. Cis was administered as a single dose on the 3rd day of the experiment while Mel was given for 5 days. All administrations were performed via intraperitoneal injection. After injections, T-maze, rotarod, and hot plate tests were performed to evaluate cognitive, motor, and sensory functions, respectively. Following sacrification oxidative stress markers, cholinergic function, and proinflammatory cytokines were studied from brain homogenates. Cis impaired cognitive function and motor performance in the Cis and Cis+Vehicle groups. The drug also increased oxidative stress in the brain. Mel significantly improved brain oxidant/antioxidant status and also decreased the overproduction of proinflammatory cytokines (superoxide dismutase activities in Cis+Vehicle and Cis+Mel groups: 104.55 ± 9.50 µU/mg protein vs. 150.13 ± 4.70 µU/mg protein, respectively, p < 0.05; tumor necrosis factor-α levels in Cis and Cis+Mel groups: 40 pg/ml vs. 20 pg/ml, respectively, p < 0.05). It seems that Mel can improve Cis neurotoxicity. For a more firm conclusion, further studies using Mel at different doses with larger groups should be performed.

Effects of Leontice leontopetalum and Bongardia chrysogonum on oxidative stress and neuroprotection in PTZ kindling epilepsy in rats.

We investigated the effects of Leontice leontopetalum and Bongardia chrysogonum on apoptosis, gamma-aminobutyric acid (GABAA) receptor positive cell number, cyclin-B1 and bcl-2 levels and oxidative stress in pentylenetetrazol (PTZ) kindling in rats. Kindling was produced by subconvulsant doses of PTZ treatments in rats. Wistar albino rats were divided into 4 groups; Control, PTZ treated (PTZ), PTZ+L. leontopetalum extract treated (PTZ+LLE) and PTZ+B. chrysogonum extract treated (PTZ+BCE) groups. Extracts were given a dose (200 mg/kg) 2h before each PTZ injection. PTZ treatment significantly decreased the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and bcl-2 levels and increased the total oxidant status (TOS), malondialdehyde (MDA), cyclin B1, oxidative stress index (OSI) and number of neurons that expressed GABAA receptors when compared to the control. LLE and BCE possessed antioxidant activity in the brain and ameliorated PTZ induced oxidative stress, decreased cyclin-B1, increased bcl-2 levels, and kept the GABAA receptor number similar to that of the control despite the PTZ application.

Effects of Cichorium intybus on serum oxidative stress, liver and kidney volume, and cyclin B1 and Bcl-2 levels in the brains of rats with ethanol induced damage.

We investigated the effects of an aqueous root extract of Cichorium intybus on Bcl-2 and cyclin B1 levels in the brain, kidney and liver volumes and changes of serum total antioxidant status (TAS) and total oxidant status (TOS) levels in ethanol induced damage in rats. The rats were divided into five groups: non-treated controls (C), maltodextrin in tap water treated (MD), 6.4% ethanol in tap water treated (ET), Cichorium intybus + maltodextrin in tap water treated (CI+MD), and Cichorium intybus + 6.4% ethanol in tap water treated (CI+ET). Rats in the CI+MD and CI+ET groups were treated with 200 mg/kg water extract of Cichorium intybus. Chronic ethanol aMDinistration significantly increased cyclin B1 and decreased Bcl-2 levels in the brain and significantly decreased TAS values, increased TOS values of serum and significantly decreased kidney volume in the ET group. There was no significant difference in the liver volume or liver cell count. Our data revealed that ethanol aMDinistration induces an overexpression of cyclin B1 and decreases levels of Bcl-2 in rat brains and induced oxidative stress in the blood. C. intybus treatment possessed a partial amelioration effect on cyclin B1 levels and TAS values.

Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model.

Diabetes mellitus is causing serious health problems in the chronic period. Silibinin is a flavonoid obtained from the milk thistle (Silybum marianum), which is among the herbal ethnopharmacological administrations. In studies with silibinin, it has been reported that it increases the activity of pancreatic beta cells and insulin sensitivity and has a hyperglycemia-reducing effect. However, behavioral parameters have not been evaluated together with insulin levels and liver function tests. Our aim in this study was to examine the effects of silibinin on insulin secretion, anxiety-like behaviors, and learning in a streptozotocin (STZ)-induced rat diabetes model. Wistar albino rats weighing 200-250 g were divided into 4 groups. Control: Saline solution, Diabetes: STZ 45 mg/kg, S 100: STZ 45 mg/kg + Silibinin 100 mg/kg, S 200: STZ 45 mg/kg + Silibinin 200 mg/kg. Administrations were continued for 21 days. On the 21st day, open field and elevated plus maze as unconditional anxiety tests; Barnes maze for learning and memory; and rotarod test for locomotor activity were conducted. Following behavioral tests, blood samples were taken under anesthesia. Blood glucose levels and ALT values were measured. Insulin levels were measured with an ELISA plate reader. Silibinin shortened the time to find the correct hole. Silibinin prevented the decrease in insulin due to STZ, exhibited a hyperglycemia-reducing effect and decreased the elevation of ALT.

Investigation of hemorheological parameters in patients with major depressive disorder.

BACKGROUND: Hemorheological parameters have been reported to be altered in cardiovascular disease. Major depression has been associated with increased risk of cardiovascular disease. OBJECTIVE: Our hypothesis is that hemorheological parameters are disturbed in major depressive disorder. METHODS: Major depressive disorder and control groups consisted of 50 subjects. Plasma viscosity, erythrocyte aggregation, erythrocyte deformability, hematological parameters and hematological parameters were examined. RESULTS: Plasma viscosity was statistically significantly higher, erythrocyte elongation index at 0.53 Pa and 0.95 Pa was lower, and MCV, MCH, and MCHC values were also lower in the major depression group (P < 0.05). Elongation index and plasma viscosity were correlated with depressive symptomatology. CONCLUSIONS: The increased plasma viscosity and decreased elongation index of erythrocytes indicate an unfavorable hemorheological situation in patients with major depressive disorder compared with healthy controls. The results of this study confirm the findings of studies finding a potential threat to cardiovascular health from major depressive disorder. Increased plasma viscosity and decreased erythrocyte elongation index in depressed patients may be risk factors for cardiovascular events and provide data on the causality of the association between depression and cardiovascular disease.

Behavior, antioxidant, and metabolomics effects of Allium tuncelianum.

Allium species are consumed extensively as folkloric medicine and dietary elements, but limited studies have been conducted on them. In this study, the effects of an ethanol-water extract obtained from the underground bulb of Allium tuncelianum (Kollmann) Özhatay, B. Mathew & Siraneci (AT) on the behavioral, antioxidant, and metabolite parameters in rats were evaluated. AT was administered orally once a day at doses of 100 and 400 mg/kg to male Wistar albino rats for 10 consecutive days. The elevated plus maze, rotarod, and hotplate tests were used to examine anxiety-like behaviors, locomotor activities, and pain perception in the rats, respectively. Additionally, untargeted metabolomic analyses were performed on plasma samples and AT extracts using two orthogonal analytical platforms. The phenolic components, mainly fumaric acid, malic acid, vanillic acid, quercetin-3-arabinoside, hydrocinnamic acid, and gallocatechin, were determined in the extract. In addition, arbutin, salicylic acid, trehalose, and nicotinic acid were analyzed in the extract for the first time. The AT extract did not decrease the catalase, glutathione peroxidase, or superoxide dismutase levels; however, diazepam decreased some of those parameters significantly in the brain, liver, and kidney. Although both the AT and diazepam treatments resulted in an increase in anxiolytic-like effects compared to the control group, no significant differences were observed (p > .05). In the metabolomic analysis, significant changes were observed in the rats treated with AT and diazepam, and they caused significant changes in some metabolic pathways, including amino acid and fatty acid metabolism, compared to the control.

Aqueous extract of chives (Allium schoenoprasum L.) plant impairs erythrocyte deformability in sickle cell patients.

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis and the presence of erythrocytes with low deformability, which may trigger vaso-occlusive crises. We tested the in-vitro effects of aqueous extract of chives (Allium schoenoprasum L.) on erythrocyte deformability of SCA patients. Blood samples from 6 apparently healthy volunteers and 5 SCA patients were collected into heparin coated tubes. Both apparently healthy and SCA patient blood samples were incubated with 80µg/mL chives plant aqueous extract at 37°C for 60 min and erythrocyte deformability was measured by ektacytometry (3 Pa and 30 Pa; 37°C). Results of incubation of apparently healthy blood samples with plant extract showed that incubation did not alter erythrocyte deformability significantly. However, for SCA blood samples, erythrocyte deformability decreased significantly with plant extract exposure at 3 Pa (p < 0.043) and 30 Pa (p < 0.043). In conclusion, although ex-vivo incubation with plant extract does not fully model gastrointestinal processing of onions, the decrease in SCA erythrocyte deformability following incubation with aqueous chives should stimulate further studies to test the in-vivo effects of this diet in sickle cell mice.

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.

Effects of two selected SSRIs on hemorheological parameters in rats.

BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants commonly used in cardiovascular diseases (CVDs), inhibit the re-uptake of serotonin not only into neurons but also into platelets. Hence they increase the level of serotonin in plasma. OBJECTIVE: This study was aimed to clarify the effects of two selected SSRIs on plasma serotonin level, hemorheological parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity) and selected oxidative stress markers (MDA, GSH, GSSG levels in plasma and erythrocytes). METHODS: Two different SSRIs (Fluvoxamine and Sertraline) were administered to male Sprague-Dawley rats in acute (5 days) or chronic fashion (21 days) at 20 mg/kg/day dose. RESULTS: Aggregation amplitude (AMP) decreased significantly in the chronic sertraline and acute fluvoxamine groups; aggregation half time (t1/2) decreased significantly in the chronic fluvoxamine group. Biochemical parameters indicating oxidative stress significantly increased in the chronic sertraline group. CONCLUSIONS: Since SSRI's are commonly used in patients with CVDs, complementary studies are needed to assess the impact of such changes in hemorheological parameters on the risk for CVD, and to reveal the effects of other SSRIs on hemorheological parameters.

Blood Urea Nitrogen (BUN) is independently associated with mortality in critically ill patients admitted to ICU.

PURPOSE: Blood urea nitrogen (BUN) was reported to be associated with mortality in heart failure patients. We aimed to evaluate admission BUN concentration in a heterogeneous critically ill patient collective admitted to an intensive care unit (ICU) for prognostic relevance. METHODS: A total of 4176 medical patients (67±13 years) admitted to a German ICU between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. Association of admission BUN and both intra-hospital and long-term mortality were investigated by Cox regression. An optimal cut-off was calculated by means of the Youden-Index. RESULTS: Patients with higher admission BUN concentration were older, clinically sicker and had more pronounced laboratory signs of multi-organ failure including kidney failure. Admission BUN was associated with adverse long-term mortality (HR 1.013; 95%CI 1.012-1.014; p<0.001). An optimal cut-off was calculated at 28 mg/dL which was associated with adverse outcome even after correction for APACHE2 (HR 1.89; 95%CI 1.59-2.26; p<0.001), SAPS2 (HR 1.85; 95%CI 1.55-2.21; p<0.001) and several parameters including creatinine in an integrative model (HR 3.34; 95%CI 2.89-3.86; p<0.001). We matched 614 patients with admission BUN >28 mg/dL to case-controls ≤ 28mg/dL corrected for APACHE2 scores: BUN above 28 mg/dL remained associated with adverse outcome in a paired analysis with the difference being 5.85% (95%CI 1.23-10.47%; p = 0.02). CONCLUSIONS: High BUN concentration at admission was robustly associated with adverse outcome in critically ill patients admitted to an ICU, even after correction for co-founders including renal failure. BUN might constitute an independent, easily available and important parameter for risk stratification in the critically ill.

Comparison of endothelin and nitric oxide synthase blockers on hemorheological parameters in endotoxemic rats.

BACKGROUND/AIM: Septic shock is an important health problem that vastly alters cardiovascular and hemodynamic status. Increased production of nitric oxide (NO) and endothelin is a counterpart of this endotoxemic state. This study was conducted to test the hypothesis that nonselective NO synthesis blocker (L-NAME), inducible NO synthesis blocker (L-canavanine), or endothelin receptor antagonist (bosentan) will reverse the effects of sepsis on hemorheological parameters. MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats were used in 8 groups: saline (control), endotoxin, bosentan, L-NAME, L-canavanine, endotoxin + bosentan, endotoxin + L-NAME, and endotoxin + L-canavanine. Blood was withdrawn at the 4th hour of endotoxemic state. Erythrocyte deformability and erythrocyte aggregation were determined by laser-assisted optical rotational cell analyzer at 37 °C. Plasma viscosity (mPa.s) was measured by a cone-plate viscometer with 0.5 mL of plasma. RESULTS: Endotoxin administration significantly increased aggregation half-time and lowered erythrocyte aggregation amplitude and aggregation index compared to the control, indicating a slower and weaker aggregation pattern. L-NAME and L-canavanine alleviated the effects of endotoxin on erythrocyte aggregation without altering the values in the control animals. However, bosentan did not perform such a restoration. CONCLUSION: This finding suggests that these restoration effects of the blockers occur via their modulation of nitric oxide synthesis rather than through the endothelin pathway.

Hemorheological parameters in patients with fibromyalgia syndrome.

AIM: To evaluate hemorheological parameters in patients with fibromyalgia syndrome (FMS) in order to elucidate the etiology of the disease. METHODS: Twenty-three adult FMS patients and 20 healthy controls were enrolled in the study. Diabetics, hypertensives and those with any rheumatological disorder or use drugs or smoking cigarette were excluded from the study. Following parameters were analyzed in each subject; erythrocyte deformability, erythrocyte aggregation, plasma viscosity, complete blood count, fasting blood glucose, fibrinogen, albumin, globulin and lipid profile. RESULTS: Erythrocyte elongation indices indicating deformability of erythrocytes were higher in FMS patients (0.564±0.002 at 16.87 mPa and 0.605±0.002 at 30 mPa shear rate) than controls (0.558±0.001 at 16.87 mPa and 0.600±0.003 at 30 mPa shear rate). Erythrocyte aggregation speed was higher in FMS patients (2.1±0.1 s) than controls (2.3±0.2 s). Erythrocyte aggregation index was also higher in FMS patients (65.5±1.3) than controls (62.9±1.5). Erythrocyte aggregation amplitude and plasma viscosity values were similar in both groups (both p > 0.05). Among the complete blood count and biochemical parameters, only albumin levels were lower in the FM patients than controls (p < 0.05). CONCLUSION: Our results indicate higher erythrocyte deformability and quicker erythrocyte aggregation in FM patients.

Theophylline attenuates bleomycin-induced oxidative stress in rats: The role of IL-6, NF-κB, and antioxidant enzymes

Abstract The purpose of this study was to evaluate the antifibrotic and antioxidant roles of theophylline (Theo), a bioactive compound, in bleomycin (BLM)-induced pulmonary fibrosis in Wistar albino rats. Assigned into 4 groups were 32 Wistar albino rats, comprising the control group (administered 0.9% isotonic saline), BLM group (treated with BLM at a dose of 2.5 mg/kg), BLM+Theo group (treated with Theo at a dose of 75 mg/kg + BLM at a dose of 2.5 mg/kg), and Theo group (treated with Theo at a dose of 75 mg/kg). In the BLM group, a significant decrease was observed in the catalase and glutathione peroxidase enzyme activities, and reduced glutathione (GSH) (p < 0.05, p< 0.05, p< 0.001, respectively), while the malondialdehyde (MDA) levels (p< 0.001) were significantly elevated when compared to the control group. However, the MDA levels in the BLM+Theo group were also significantly higher than in the control group (p< 0.01). Similarly, the GSH levels were significantly higher in the BLM+Theo group than in the BLM group (p< 0.05). The results indicated that Theo reduced the BLM-induced activation of nuclear factor-kappaB (NF-κB) and decreased interleukin-6 (IL-6) levels, together with significant amelioration of the immunohistochemical and histopathological architecture in the lung tissues. It was concluded that the administration of Theo had a positive effect on the GSH level, and activation of NF-κB and IL-6 expression, which were significant proinflammatory markers in the BLM-treated rats.

Acute carbon monoxide poisoning alters hemorheological parameters in human.

Acute carbon monoxide (CO) poisoning seriously hinders oxygen delivery to tissues. This harmful effect of CO may be aggravated by accompanying changes in the viscosity of blood. We had previously reported increased plasma viscosity in people chronically exposed to CO. This study was planned to test our hypothesis that acute CO poisoning increases blood viscosity. For this purpose four main parameters contributing to blood viscosity - hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity - were determined in patients with acute CO poisoning and compared with healthy controls. Plasma viscosity and erythrocyte aggregation tendency were lower in the CO group (p <  0.05). Erythrocyte deformability was also lower in CO group (p <  0.05). Our results indicate that acute CO poisoning has diverse effects on hemorheological parameters such as attenuating hematocrit value, plasma viscosity, erythrocyte aggregation tendency and erythrocyte deformability.

Investigation of hemorheological parameters in periodontal diseases.

Periodontal diseases are frequently associated with cardiovascular diseases (CVD). On the other hand, occurrence of CVD has also been related with increased blood viscosity. This study was planned to investigate four main hemorheological parameters contributing to blood viscosity - hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity - and also some biochemical parameters (hs-CRP, fibrinogen, globulin etc.) in patients with periodontal disease. We hypothesized that poor periodontal health would be associated with deterioration of hemorheological properties. According to periodontal health status, subjects were divided into three groups as control (healthy), with plaque induced gingivitis and with chronic periodontitis. All groups included 15 males who had not received periodontal therapy in the last six months before the study, were non-smokers, had no systemic diseases and were not on any medication. Erythrocyte deformability and erythrocyte aggregation were measured with laser-assisted optical rotational cell analyzer (LORCA). Plasma viscosity was measured by a cone-plate viscometer. Data were analyzed with Kruskal-Wallis, Mann-Whitney U Test and Spearman Correlation Coefficient. Plasma viscosity (1.36 ± 0.01 mPa.s in the control group and 1.43 ± 0.02 mPa.s in the chronic periodontitis group, P <  0.01), erythrocyte aggregation tendency (aggregation index, amplitude and t½ were 58.82 ± 1.78% , 20.22 ± 0.40 au, 2.80 ± 0.25 s respectively in the control group, and 67.05 ± 1.47% , 22.19 ± 0.50 au, 1.84 ± 0.15 s in the chronic periodontitis group, P <  0.01), hs-CRP, fibrinogen and globulin levels were significantly higher, whereas HDL level was significantly lower in the chronic periodontitis group (P <  0.05) compared to the control group. All of these conditions may contribute to cardiovascular morbidity and mortality observed in people with periodontal disease, via increasing blood viscosity.

Effects of oral acrylamide intake on blood viscosity parameters in rats.

Acrylamide which is formed via reaction of reducing sugars with amino acids during food processing at high temperatures is not only neurotoxic and carcinogenic, but it also damages erythrocyte membrane and generates micronucleated erythrocytes. In the present study, effects of chronic administration of acrylamide at a dose which does not induce neurotoxicity were evaluated on blood viscosity parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity). Twenty adult male Sprague-Dawley rats were divided into control and acrylamide groups. The acrylamide group received 10 mg/kg/day acrylamide, whereas the control group received saline (vehicle), both in 10 ml/kg/day volume via gastric gavage. Erythrocyte aggregation and deformability were measured with LORCA and plasma viscosity with cone-plate viscometer. Erythrocyte deformability was measured before, and at the end of the 3rd and the 5th weeks of acrylamide administration. Hematocrit, erythrocyte aggregation and plasma viscosity were measured only at the end of the 5th week. Acrylamide caused a significant decrease in the deformability index of erythrocytes (at the end of the 3rd week, control: 0.606 ± 0.003, acrylamide: 0.595 ± 0.003, p < 0.05) (at the end of the 5th week, control: 0.606 ± 0.002, acrylamide: 0.588 ± 0.002, p < 0.01). Aggregation tendency and plasma viscosity were slightly higher in the acrylamide group, however the difference was not statistically significant. These results imply that acrylamide which does not cause neurotoxicity in rats may alter blood viscosity if chronically taken.

Antinociceptive, free radical-scavenging, and cytotoxic activities of Acanthus hirsutus Boiss.

In vivo antinociceptive and in vitro radical scavenging and cytotoxic activities of Acanthus hirsutus Boiss. aqueous extract were investigated to give a new insight into plant usage in traditional medicine. The extract showed significant antinociceptive activity in acetic acid-induced writhing test in mice after oral application and did not change the hind-leg retraction period in the hot-plate test for any dose applied. In addition, the extract showed radical-scavenging activity against 2,2-diphenyl-1-picryl-hydrazyl, nitric oxide, and superoxide radicals similar to those of standard compounds 3-t-butyl-4-hydroxyanisole, ascorbic acid (vitamin C), and quercetin. The gallic acid equivalent total phenolic content of the plant was found to be 65.4 mg/g dry extract. Cytotoxic activity of the aqueous extract was tested against 3 different cancer cell lines-Hep-2 (human larynx epidermoid carcinoma), RD (human rhabdomyosarcoma), and L20B (transgenic murine L cells)-and 1 noncancerous cell line (VERO) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Through the phytochemical studies, the following compounds were isolated: 3 lignan glucosides [(-)-syringaresinol-di-O-ß-glucopyranoside, (-)-medioresinol-di-O-ß-D-glucopyranoside, (-)-pinoresinol-4'-O-ß-glucopyranoside], 2 benzoxazinoids [2-hydroxy-1,4-benzoxazin-3(4H)-one, (2R)-2-O-ß-glucopyranosyl-1,4-benzoxazin-3(4H)-one], 4 phenylethanoid glycosides (acteoside, leucosceptoside A, martynoside, hattushoside), and 2 phenylpropanoid glucosides (sinapyl aldehyde-4-O-ß-glucopyranoside, sinapyl alcohol-4-O-ß-glucopyranoside). Cytotoxic and radical-scavenging activities of the isolated compounds were also determined. 2-hydroxy-1,4-benzoxazin-3(4H)-one and acteoside were the most active compounds in both experiments.

Antinociceptive activity of coniine in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemlock was used as an analgesic in certain ethnopharmacological traditions and there has been no record about the antinociceptive effect of coniine which is the major alkaloid compound of Hemlock. AIM OF THIS STUDY: The present study was undertaken to evaluate the possible antinociceptive activity of coniine. MATERIAL AND METHODS: Antinociceptive activity of coniine was tested dose in Hotplate test (thermal pain model) and in Writhing test (chemical pain model) in different nociception models. RESULTS: Coniine caused a prolongation in reaction time in Hotplate test at 20mg/kg dose. In addition, it was observed that coniine decreased the number of writhes in Writhing test. Both data indicated an antinociceptive effect of coniine. A rotarod test was also conducted in order to clarify, whether this activity was related with a loss of locomotion or with an analgesic activity. None of the chemical agents at those doses used in experiments caused a loss of locomotor activity. It was also shown that antinociceptive effect of morphine was potentialized by coniine which was inhibited by nicotinic receptor blocker mecamylamine (1mg/kg). CONCLUSION: Coniine has antinociceptive effect via the nicotinic receptors. A pharmacological assessment about the painless death of Socrates due to Hemlock (coniine) toxicity has also been presented by using this data.