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Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant–antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms. [ABSTRACT FROM AUTHOR]

The article presents a study to investigate the effects of endothelin type B (ETB) receptor antagonist BQ-788 on amitriptyline-induced cardiotoxicity and the role of ETB receptors cardiovascular depression induced by amitriptyline. The study uses male Wistar rats that were anaesthetized with urethane/chloralose. Results of the study show that : Amitriptyline caused a significant decrease in mean arterial pressure (MAP) and decreased heart rate (HR).

Objective: The aim of this study was to analyse the caustic and household detergent exposure cases were admitted to the Department of Emergency Medicine at Dokuz Eylul University Hospital (EMDEU) between 1993 and 2008. Methods: Age, sex, reason of exposure, clinical signs, rate of endoscopy in oral exposures, treatment attempts, length of hospital stay and outcome were evaluated. A chi-square test was used to analyse statistical differences. Results: Caustic exposures accounted for 8.5% (1160 cases) and 4.1% (1988 cases) of all poisonings in children and adults, respectively. Female/male ratio of caustic exposure poisonings was 0.8. Most of the exposures were unintentional (158, 86.8%). Intentional exposures were common in cases between 19 and 29 years old (χ2 = 25.685, p < 0.001). The most common caustic substance was alkaline (106, 58.3%) followed by acidic (47, 25.8%) and other household detergents (28, 15.4%). Vomiting (35.7%), nausea (14.8%) and sore throat (13.1%) were the most common clinical signs. The patients who had endoscopy, the most frequent finding was first-degree damage (58.7%). A 48-year-old man died from intentional hydrochloric acid ingestion. Conclusion: Because of the large number of unintentional caustic exposures, parent education is very important to decrease the caustic exposures in children. [ABSTRACT FROM AUTHOR]

Pancytopenia is a rare but serious adverse effect of low- dose methotrexate (MTX) sodium therapy, and this case report describes a very early-onset of pancytopenia and cutaneous lesions after three days of ingestion. A 64- year-old man was presented to Emergency Department with weakness, fever, poor appetite, nausea, and vomiting after he had had accidentally ingested MTX tablets (2.5 mg) twice a day for the last three days. On initial examination, several painful lesions in his oral mucosa and a cutaneous ulceration on his right foot were also observed. He had severe pancytopenia, poor kidney functions, and abnormal coagulation parameters. The blood level of MTX was found to be within therapeutic range. He was treated with leucovorine, intravenous antibiotics, and appropriate blood transfusions; he was discharged from hospital without any sequela. Pancytopenia associated with low-dose (cumulative dose of 15 mg in 3 days) MTX therapy had not been reported previously. The Naranjo probability scale showed pancytopenia and skin ulcer associated with low-dose MTX therapy as probable adverse reactions. Risk factors for pancytopenia such as renal insufficiency, hypoalbuminemia, low folate levels, concomitant infections, concomitant use of drugs, and folate supplementation were not identified in our patient. Although pancytopenia associated with low-dose MTX therapy is not expected as early as 3 days after initiation of the therapy, physicians should also be aware of this life threatening adverse effect during the very first days of MTX therapy for rheumatoid arthritis patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of glucagon on cardiovascular parameters in anesthetized rat model of tricyclic antidepressant overdose. Toxicity was induced by infusion of amitriptyline 0.94 mg/kg/mm until a 40-45% of reduction in mean arterial pressure was observed. Amitriptyline infusion rats were then randomized into three groups. Control group of rats (group 1) received a bolus of 5% dextrose followed by the continuous infusion of dextrose, whereas treatment groups received 1 mg/kg (group 2) or 2 mg/kg (group 3) bolus doses of glucagon followed by continuous infusion (0.1 mg/kg/mm) of glucagons for 60 mm. Mean arterial pressure, heart rate, and electrocardiogram were recorded. Amitriptyline caused a significant decrease in mean arterial pressure and a prolongation in QRS, yet it did not change the heart rate. High.bolus dose of glucagon (2 mg/kg) followed by glucagon inftision significantly increased mean arterial pressure at 40, 50, and 60 mm (P < 0.05) and shortened the prolonged QRS at 50 and 60 mm (P < 0.05) when compared with control group. There was also a significant increase in heart rate. In conclusion, bolus doses followed by a continuous infusion of glucagon were found to be effective in reversing the hypotension and QRS prolongation in the rat model of amitriptyline toxicity. Further studies are needed to reveal the exact mechanism of the proposed effect. [ABSTRACT FROM AUTHOR]

Between 1993 and 2004, patients with antidepressant poisoning admitted to an emergency department (ED) were analysed retrospectively with regard to demographics, clinical findings and treatment attempts. Age, gender, suicide attempts, classification of antidepressants, Glasgow Coma Scale (GCS) score, ECG findings, need for endotracheal intubation, follow-up period and Antidepressant Overdose Risk Assessment (ADORA) criteria were analysed by SPSS software. A total of 356 antidepressant poisoning cases were evaluated. Tricyclic antidepressants (TCA), especially opipramol and amitriptyline, were the most common agents (58.4%). The most frequent ECG finding was sinus tachycardia (40.7%, n = 145). Endotracheal intubation was required in 9.6% of cases. Patients with TCA ingestion had a longer observation time in the ED, abnormal ECG findings, abnormal physical examination findings and more ADORA criteria, than patients who ingested selective serotonin re-uptake inhiitors (SSRI) (P = 0.008, P = 0.008, P <0.001,P <0.001). It was found that the patients who ingested TCA (P = 0.001), poisoned with amitriptyline (P = 0.001), patients with GCS scores of 8 and less (P = 0.001), patients with two or more ADORA criteria (P = 0.001), with seizures (P = 0.001), with abnormal ECG (P = 0.012), and patients with a history of two or more suicide attempts were intubated more frequently. Suicide attempts, classification of the antidepressant, ECG findings, seizure, GCS score and number of detected ADORA criteria affect the need for intubation in patients with antidepressant poisoning. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of an adenosine A1 agonist, phenylisopropyl adenosine (PIA), on metamidophos poisoning compared to specific antidotes. Rats were poisoned with metamidophos (30 mg/kg, oral) and observed for 24 hours. One group received sodium chloride (1 mL/kg) and four experimental groups received atropine (5 mg/kg), pralidoxime (PAM, 20 mg/kg), atropine/PAM (5/20 mg/kg) or PIA (1 mg/kg) intraperitoneally. Atropine reduced salivation and prevented respiratory distress when compared to sodium chloride-treated rats. Treatment with PAM did not cause any suppression of cholinergic signs. Atropine and PAM combination prevented salivation, convulsion and respiratory distress. PIA delayed initial time of the salivation, convulsion and time to death. However, PIA was found ineffective against the metamidophos-induced cholinergic symptoms and mortality. All treatments, except PIA, lead to survival of these animals. Acetylcholinesterase (AChE) activity was not normalized by PIA or PAM. PIA prevented metamidophos-induced diaphragmatic muscle necrosis as much as PAM. In conclusion, a single dose of PIA was unable to protect the rats from metamidophos toxicity. Further studies are needed involving a combination of PAM and/or atropine with repeated doses of PIA to clarify the efficacy of adenosine agonists in OP poisoning. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the presence of dysbiosis in patients with naive bladder cancer., Methods: Twelve male patients with non-invasive bladder cancer and twelve age-matched healthy males had midstream urine and tissue samples taken. A history of endourological interventions was determined as an exclusion criterion, ensuring that the study was designed solely with naïve participants. The bacterial 16s ribosomal RNA V3-V4 regions were used to examine urine and tissue samples. We compared the microbiota composition of the bladder cancer and control groups., Results: Escherichia Shigella (p &lt; 0.001), Staphylococcus (p &lt; 0.001), Delftia (p &lt; 0.001), Acinetobacter (p &lt; 0.001), Corynebacterium (p &lt; 0.001), and Enhydrobacter (p &lt; 0.001) were abundant in bladder cancer tissue samples. Escherichia Shigella (p &lt; 0.001), Ureaplasma (p &lt; 0.001), Lactobacillus (p = 0.005), Stenotrophomonas (p &lt; 0.001), Streptococcus (p &lt; 0.001), Corynebacterium (p &lt; 0.001), and Prevotella (p = 0.039) were abundant in bladder cancer urine samples. Midstream urine has a sensitivity of 83% for detecting dysbiotic bacteria in cancer tissue., Conclusions: Our research is the first microbiota study of bladder cancer done with naive patients who have never had an endourological intervention. Escherichia Shigella, Staphylococcus, Acinetobacter, Enhydrobacter, Delftia, Corynebacterium, and Pseudomonas were detected as dysbiotic bacteria in bladder cancer. The sensitivity of the midstream urine sample in detecting dysbiosis in tissue is 83%., (© 2024 S. Karger AG, Basel.)

Purpose: The contribution of androgen receptors (AR) on bladder cancer has been demonstrated in pre-clinical studies, however in clinical studies, only the canonical AR (AR-FL) protein was measured by immunohistochemistry and conflicting results were obtained. To get better insight into the alterations of AR signalling, we used western blotting (WB) method and simultaneously measured both mRNA and protein levels of AR-FL and AR-V7., Methods: 23 naive non-muscle invasive bladder cancer patients and 12 healthy individuals were included. AR-FL protein, AR-FL mRNA, AR-V7 protein and AR-V7 mRNA levels were quantitatively measured by WB and qRT-PCR., Results: While AR-FL protein and AR-V7 mRNA were significantly higher in bladder cancer, AR-FL mRNA and AR-V7 protein were lower. AR-V7 mRNA level was higher in patients with tumour size over 3 cm and AR-FL protein was higher in single tumours (p < 0,005). The small sampling size and the inclusion of only male participants were the main limitations., Conclusions: The increase of AR-FL protein in bladder cancer supports the contribution of the AR pathway in bladder cancer. The presence of high AR-FL protein despite low mRNA levels may be due to a disruption in post-transcriptional regulatory mechanisms. AR-V7 was demonstrated for the first time in bladder tissue and found significantly different in bladder cancer tissues. Our study reached new and valuable findings and will shed light on the studies that aim to clarify the role of the AR pathway in bladder cancer., (© 2024. The Author(s).)

Objective: This randomized, controlled, open-label, phase 2 clinical trial aimed to assess the efficacy and safety of low-dose methotrexate as maintenance therapy for recurrent postoperative chronic rhinosinusitis with nasal polyps (CRSwNPs)., Methods: Forty-one patients with CRSwNPs who experienced postoperative polyp recurrence(s) were randomly divided into three groups to receive one of the following treatments for 8 weeks: daily intranasal mometasone furoate monohydrate 200 mcg (control [intranasal corticosteroids (INCS)] arm, n = 13]); daily per oral methylprednisolone 8 mg (oral corticosteroids [OCS] arm, n = 14); and once weekly per oral 10 mg methotrexate (MTX arm, n = 14). All patients were assessed at three clinical visits according to the Lund-Kennedy endoscopic grading system (LKES), visual analog scale (VAS), Turkish version of the Sinonasal Outcome Test-22 (SNOT-22), peak nasal inspiratory flow (PNIF), butanol olfactory threshold test (BuOT), serum total IgE level, presence of peripheral eosinophilia, serum biochemical assays, and adverse events., Results: All efficacy outcome measures significantly improved in all three groups, except for the nonrecovery of peripheral eosinophilia in the INCS group. There was no significant difference among the groups in terms of LKES scores. Scores for the Turkish version of the SNOT-22, PNIF, BuOT, and serum IgE levels were also similar among the groups. However, total VAS scores recovered significantly better in the INCS group than in the MTX group. Serum biochemical assays remained normal in all groups. Adverse events were minor and observed only in the OCS group., Conclusion: Low-dose MTX was a safe and effective maintenance therapy for patients with recurrent postoperative CRSwNPs., (© 2022 ARS-AAOA, LLC.)

Background: Despite therapeutic drug monitoring and pharmacogenetic-guided dose selection are recommended for pediatric patients, safety of voriconazole is mostly monitored by clinical assessment. Having comprehensive knowledge of safety profile and distinguishing incidental events from the reactions that are truly related to voriconazole use are crucial for safer and uninterrupted treatment., Objectives: This study aimed to address adverse reactions during the first month of voriconazole use by systematically evaluating retrospective records of all adverse events. Patients/Methods: It is a single-center, retrospective analysis of patients who received voriconazole from 1 September 2010 to 1 September 2020. Severity of abnormal findings in medical records were systematically graded. Causality between voriconazole and the events was evaluated by Liverpool Causality Assessment Tool (LCAT), Naranjo Algorithm and World Health Organization Causality Assessment System. The events with possible or probable causal relation to voriconazole are classified as adverse reaction., Results: Records of 45 patients included in the study. The overall frequency of adverse reactions was 51.1%. Hepatobiliary laboratory adverse reactions identified in 48.9% of the patients and led to treatment discontinuation in 20.0%. Amylase and lipase elevation (2.2%), ventricular extra systoles (2.2%), hallucination and nightmares (2.2%) were other adverse reactions., Conclusions: Hepatobiliary abnormalities were the most common adverse reactions and the most common cause of treatment discontinuation. For safer treatment in critically ill patients, the dose should be personalized. To clearly identify the accurate frequency and the causality of all adverse reactions, prospective studies with much larger sample size are needed.

Objectives: The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial KATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline., Methods: The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial KATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial KATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p < 0.05 was accepted as statistically significant., Key Findings: Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p < 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p < 0.05), myocardial damage and apoptosis (p < 0.01 and p < 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p < 0.05), myocardial damage and apoptosis (p < 0.05), it did not affect the changes in oxidative parameters (p > 0.05)., Conclusions: Our results suggest that nicorandil, a selective mitochondrial KATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial KATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to investigate the therapeutic effects of melatonin in an experimental AR model., Methods: Thirty-two Wistar rats were randomised into four groups (n = 8 each). The experimental AR model was established in the saline (SF), ethanol, and melatonin groups via intraperitoneal (i.p.) injections and intranasal application of ovalbumin. The SF, ethanol, and melatonin groups received daily i.p. saline, 2% ethanol dissolved in saline, and 10 mg/kg melatonin dissolved in 2% ethanol and saline. The control group received the same amount of i.p. and intranasal saline. Total nasal symptom scores were recorded in all rats on days 1 (baseline), 15, 20, 25, and 30. Serum ovalbumin-specific IgE, IL-13, and melatonin levels were measured on days 1 (baseline), 15, and 30. The nasal mucosa of all rats was scored histopathologically., Results: The total nasal symptom scores and serum ovalbumin-specific IgE values of the SF, ethanol, and melatonin groups were significantly higher on day 15 than those of the control group. On day 30, the scores and serum ovalbumin-specific IgE values of the melatonin group were similar to those of the control, whereas the SF and ethanol groups had statistically higher scores. The histological scores of the SF and ethanol groups were significantly higher than those of the control and melatonin groups, but no significant difference was found between the melatonin and control groups., Conclusion: Melatonin reduced total nasal symptom scores and serum ovalbumin-specific IgE levels and improved histological inflammation parameters in the ovalbumin-induced rat experimental AR model., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Objective: The aim of this study is to establish the optimal non-invasive urine sample collection method for the microbiota studies., Methodology: Twelve men with bladder carcinoma underwent first voided and midstream urine collection. Urine samples were analysed using V3-V4 regions of bacterial 16s ribosomal RNAs. Bacterial groups with relative abundance above 1% were analysed in first voided urine and midstream urine samples at phylum, class, order and family level. At the genus level, all of the identified bacterial groups' relative abundances were analysed. The statistical significance (P < .05) of differences between first voided and midstream urine sample microbiota was evaluated using the Wilcoxon test., Results: According to the analysis, 8 phyla, 14 class, 23 orders, 39 families and 29 different genera were identified in the first voided and the midstream urine samples. Statistical differences were not identified between first voided and midstream urine samples of all bacteria groups except the Clostridiales at order level (p:0.04) and Clostridia at class level (P: .04)., Conclusions: Either first voided or midstream urine samples can be used in urinary microbiota studies as we determined that there is no statistically significant difference between them regarding the results of 16s ribosomal RNA analysis., (© 2021 John Wiley & Sons Ltd.)

Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings., (© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: The aim of this study was to evaluate the short and long-term impact of pharmacovigilance (PV) training on the 5th year medical students' knowledge about definitions and on the awareness of the regulatory aspects in PV., Materials and Methods: In academic year 2010/11, the students completed structured, questionnaire before and just after training. They also completed the same questionnaire 1-year after the training., Results: The students' knowledge about PV significantly increased after training in the short term (P < 0.001). However, the improvement decreased significantly in the long-term (P < 0.001). Although long-term scores were higher than the baseline score, the difference was not statistically significant. Total scores were 17.5 ± 2.0, 20.8 ± 2.0 and 18.0 ± 2.5; before, at short and long-term after the training., Conclusion: PV training increased the students' knowledge significantly. However, in the long-term, the impact of the training is limited. Repeated training of PV should be planned.

Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity., Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour prior to citalopram. Other rats were pretreated with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; inhibitor of adenosine deaminase) and S-(4-Nitrobenzyl)-6-thioinosine (NBTI; inhibitor of facilitated adenosine transport). After pretreatment, group 2 received 5% dextrose and group 3 received citalopram. Adenosine concentrations, mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval were evaluated., Results: In the dextrose group, citalopram infusion caused a significant decrease in MAP and HR and caused a significant prolongation in QRS and QT. DPCPX infusion significantly prevented the prolongation of the QT interval when compared to control. In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. In EHNA/NBTI groups, citalopram-induced MAP and HR reductions, QRS and QT prolongations were more significant than the dextrose group., Conclusions: Citalopram may lead to QT prolongation by stimulating adenosine A1 receptors without affecting the release of adenosine.

We investigated the contribution of endogenous adenosine to amitriptyline-induced cardiovascular toxicity in rats. A control group of rats was pretreated with intraperitoneal (i.p.) 5% dextrose and received intravenous 0.94 mg/kg/min of amitriptyline for 60 minutes. The second and third groups of rats pretreated with i.p. 10 mg/kg of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, and i.p. 1 mg/kg of S-(4-nitrobenzyl)-6-thioinosine (NBTI), a facilitated adenosine transport inhibitor, received 5% dextrose and amitriptyline infusion, respectively. Outcome parameters were mean arterial pressure (MAP), heart rate (HR), QT and QRS durations, and plasma adenosine concentrations. Plasma adenosine concentrations were increased in all groups. In the control group, amitriptyline decreased MAP and HR and prolonged QT and QRS durations after 10 minutes of infusion. In EHNA/NBTI-pretreated rats, amitriptyline prolonged QRS duration at 10 and 20 minutes. In EHNA/NBTI pretreated rats, amitriptyline-induced MAP, HR reductions, and QRS prolongations were more significant than that of dextrose-infusion-induced changes. Our results indicate that amitriptyline augmented the cardiovascular effects of endogen adenosine by increasing plasma levels of adenosine in rats.

The aim of this study was to assess the role of serum S100B protein as a biomarker for cardiovascular effects in an anesthetized rat model of amitriptyline toxicity. Adult male Wistar rats (n = 28) were randomized into four groups. While the control group received normal saline, the experimental groups received different doses of amitriptyline (0.625 or 0.94 or 1.25 mg/kg/min) infusion. Mean arterial pressure (MAP), heart rate (HR), electrocardiogram parameters, and serum S100B protein levels were recorded during the experiment. Linear Pearson's correlation coefficient was used to examine the association between cardiovascular parameters and serum levels of S100B protein. In the experimental groups, amitriptyline caused a significant decrease in MAP and HR (P < 0.001), a prolongation in QRS duration and QT intervals (P < 0.01), but it did not change PR intervals significantly. At the end of the experiment of the second group, a significant correlation was found between HR and serum S100B protein levels (r = -0.963, P = 0.037). At the end of the experiment of the third and fourth groups, a significant correlation between MAP, HR, all ECG parameters, and serum S100B protein levels was found. Serum S100B protein levels correlate well with amitriptyline-induced cardiovascular toxicity and can be used as a biomarker for predicting cardiovascular toxic effects of amitriptyline.

A 69-year-old woman was awakened with redness and swelling of the left upper eyelid a few days before her presentation. She also noticed a dead spider on her bed. Ophthalmic examination revealed severe left periorbital hyperemia, edema and a wide necrotic area on the upper eyelid. Systemic condition of the patient was well. She was hospitalized with the diagnosis of necrotic arachnidism of the left upper eyelid. Systemic corticosteroid and antibiotic treatment was commenced. No surgical intervention was carried out. A week later, whole upper eyelid was covered with a black eschar. This black eschar shrank with time, and it detached completely within 8 weeks and the lesion healed without a disfiguring scar. Meanwhile, the offending spider was identified as Loxosceles rufescens. Although rare, eyelid may be a biting site for Loxosceles spiders and a favorable result may be obtained with conservative management.

Cardiovascular medications (CVMs) are frequently prescribed for cardiovascular diseases. The unconscious use of cardiovascular drugs may lead to severe clinical manifestations, even to death, especially when in overdose. The objective of this study is to clarify the profile of CVM exposures admitted to Department of Emergency Medicine in Dokuz Eylul University Hospital (EMDEU) between 1993 and 2006. Case demographics, type of the medication, route and reason for exposure, clinical effects and outcome were recorded. Related to the CVM exposures, 105 poisoning cases were admitted. Mean age of children and adults were 12.8 ± 1.0 and 30.1 ± 1.8, respectively. Females were dominating (77.1%). Poisoning by accident occurred mainly among children in the 0-6 age group (64.3%) and suicide attempt was predominant in the 19-29 age group (47.8%). The most common ingested CVMs admitted to EMDEU were calcium channel blockers (19.7%), beta-blockers (17.3%), angiotensin converting enzyme inhibitors and diuretics (11.8%). Most of the patients were asymptomatic (59.1%). Frequently observed symptom was altered consciousness (18.6%). Antihypertensive drugs are responsible for the most of the CVM exposures. Prospectively designed multi-centered studies are needed to reflect the epidemiological properties of cardiovascular drug exposures throughout our country and would be very valuable for the determination of preventive measures.

We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P < 0.05, respectively). There was no statistically significant difference in the results of arterial blood-gas analyses among the groups (P > 0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.

Objective: We investigated the effects of adenosine receptor antagonists on survival rates in a mouse model of amitriptyline poisoning., Materials and Methods: In the preliminary study, amitriptyline was given at doses of 75, 100, and 125 mg/ kg to mice intraperitoneally (i.p.; n = 20 for each dose) to determine the lethal dose at 50% (LD(50)). Different doses (1, 3, and 5 mg/kg) of DPCPX (selective adenosine A(1) antagonists, n = 10 for each dose, total n = 30) or CSC (selective adenosine A(2a) antagonists, n = 10 for each dose, total n = 30) were given i.p. to find the nonlethal dose. After the administration of the LD(50) dose of amitriptyline (125 mg/kg), mice were treated with DPCPX (3 mg/kg), CSC (3 mg/kg), saline, or DMSO (dimethyl sulfoxide) (n = 25 for each group). Mice were observed during a 24-hour period., Results: Kaplan-Meier estimates of the 24-hour survival rate was 52% (13/25) for saline and 68% (17/25), 52% (13/25), and 40% (10/25) for the DPCPX, CSC, and DMSO groups, respectively. There was no statistically significant difference in survival rates among the groups (P > 0.05)., Conclusions: Adenosine antagonists failed to increase the survival rates of amitriptyline-poisoned mice. Further studies are needed with repeated doses of adenosine antagonists.

Aims: To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation., Methods: Isolated rat hearts were randomized into three groups (n=8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5)M)., Results: Amitriptyline (5.5 x 10(-5)M) infusion following pretreatment with 5% dextrose or 10(-4)M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2)M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4)M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol+DPCPX group (168.8+/-4.9%, p<0.05; 170.8+/-6.9%, p<0.01; 174.0+/-6.9%, p<0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5+/-6.1%, p<0.05) compared to DPCPX pretreatment group., Conclusion: DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.

The aim of this study was to evaluate the effects of different doses of an adenosine A(1) selective agonist, phenylisopropyl adenosine (PIA), on metamidophos-induced cholinergic symptoms, mortality, diaphragm muscle necrosis, and brain oxidative stress. A LD(50) dose of metamidophos (20 mg/kg body weight, p.o.) was followed by 1 mL/kg body weight of 0.9% NaCl or 1 mg/kg, 2 mg/kg, 3 mg/kg, or 5 mg/kg body weight PIA ip. Incidence of clinical signs including chewing, salivation, convulsion, and respiratory distress did not show any significant difference among all treatment groups (p > 0.05). PIA was found to be effective to reverse the necrotic changes in diaphragm muscle induced by metamidophos significantly in all groups. Brain Thiobarbituric Acid Reactive Substance (TBARS) levels were significantly increased after the metamidophos poisoning. Administration of 2 to 5 mg/kg body weight PIA decreased brain TBARS levels compared to 0.9% NaCl treated rats. The results indicate that, although different doses of PIA reduced the OP-induced oxidative stress and diaphragm necrosis, a single dose of PIA was not able to recover cholinergic signs and symptoms of metamidophos poisoning.

The aim of this study was to analyse intoxications concerning sedative-hypnotic medication patients admitted to the Department of Emergency Medicine in Dokuz Eylul University Hospital (EMDEU) between 1993 and 2005. Demographics of the patients, characteristics of sedative-hypnotic exposures, performed treatment attempts and outcome of the poisoned patients were recorded on standard data forms that were later entered into a computerized database programme. Related to the sedative-hypnotic exposures, 686 poisoning cases were admitted to the EMDEU. Mean age was 10.8 +/- 6.5 years among the paediatric age group (<17 years old, 169, 24.6%) and 30.3 +/- 12.8 years among the adult group (>17 years old,509, 74.2%). The most common sedative-hypnotic agents were benzodiazepines (286, 35.8%), alprazolam accounted for41.6% of them (119). Most of the patients admitted to EMDEU were asymptomatic (61.7%). Observation alone was recommended in 53.9% of EMDEU cases. Although prescription of benzodiazepines is restricted, benzodiazepine was the most common cause of sedative-hypnotic medication exposures. As only a minority of patients (3%) had clinically serious signs and symptoms, most of the overdoses might be under toxic levels or the decontamination methods might be efficient. In this study, the clinical outcome of the patients is relatively better than previous results described in literature.

Objective: We investigated the effects of adenosine receptor antagonists on amitriptyline-induced cardiotoxicity in isolated rat hearts., Methods: The amitriptyline concentrations that prolonged the QRS duration more than 150% (10(-4) M) and 50-75% (5.5 x 10(-5) M) were accepted as the control groups for two experimental protocols, respectively. In the first protocol, amitriptyline (10(-4) M) was infused following pretreatment with a selective adenosine A(1) receptor antagonist, DPCPX (8-cyclopentyl-1,3-Dipropylxanthine,10(-4) to 10(-6) M) or a selective adenosine A(2a) receptor antagonist, CSC (8-3-chlorostyryl-caffeine,10(-4) to 10(-6) M). In the second protocol, amitriptyline (5.5 x 10(-5) M) was infused following pretreatment with DPCPX (10(-4) M) or CSC (10(-5) M). Left ventricular developed pressure (LVDP), dp/dt(max), QRS duration and heart rate (HR) were measured., Results: In the first protocol, 10(-4) M DPCPX pretreatment shortened QRS duration at 50 minutes when compared to the control group (p < 0.05). In the second protocol, pretreatment with 10(-4) M DPCPX shortened the QRS duration at 40, 50, and 60 minutes after amitriptyline infusion when compared to the control group (p < 0.05, p < 0.01 and p < 0.05, respectively). Pretreatment with 10(-5) M CSC prolonged QRS duration at 20, 30, and 60 minutes (p < 0.05). Amitriptyline infusion following pretreatment with DPCPX or CSC did not change LVDP, dp/dt(max), or HR when compared to control in both protocols (p > 0.05)., Conclusion: While 10(-4) M DPCPX shortened QRS prolongation, 10(-5) M CSC prolonged QRS duration in the isolated rat hearts with prolonged QRS duration induced by 5.5 x 10(-5)M amitriptyline. An adenosine A(1) receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.

Amatoxins are one of the most potent toxins that cause hepatic and renal failure. However, this is the first report demonstrating an elevation of cardiac enzymes in a patient with Amanita phalloides poisoning. A 56-year-old male was admitted to the emergency department (ED) 42 h after an unknown type of mushroom ingestion. Hepatic, renal function tests, amylase and cardiac enzymes (troponin I, creatine kinase (CK), CK-MB isoenzyme and myoglobin) were found elevated in his blood chemistry. The electrocardiogram disclosed sinus tachycardia. Aggressive treatment with fluids, activated charcoal, penicillin G and silibinin were started. The patient was sent to hemodialysis because of anuria. During follow-up, biochemical parameters and clinical findings improved. The patient was discharged from the hospital following the arrangement of hemodialysis schedule because of the chronic renal failure. False elevations of cardiac markers may confuse the clinicians in differential diagnosis of myocardial infarction in ED. In our patient, amatoxins that have bound the actin filaments within myocardiocytes or renal cells and/or its effects as circulating anti-troponin antibodies might result in elevation of cardiac markers. Elevated cardiac enzyme levels without any acute coronary syndrome are probable in mushroom poisoning cases involving amatoxin ingestion.

The objective of this study is to analyze exposures concerning analgesics that were reported to Dokuz Eylul University Drug and Poison Information Center (DPIC) and admitted to the Department of Emergency Medicine in Dokuz Eylul University Hospital (EMDEU) between 1993 and 2004. Demographics of the patients, characteristics of analgesic exposures, performed treatment attempts and outcome of the poisoned patients were recorded on standard data forms and were then entered into a computerized database program. Statistical analysis was performed by using the chi-square test. The DPIC recorded 55 962 poisoning calls, 48 654 (86.9%) of them related to medicines. Analgesics accounted for 16.3% (7 939 cases) of all medicine-related exposures; among them 446 exposures were admitted to EMDEU. More than half of the analgesic exposure calls and admitted cases involved adults (55.9%, 4 440). Females dominated in all age groups (70.3%, 5 578). Mean age was 20.2 +/- 11.8. The most involved analgesics were paracetamol (47.9%), propionic acid derivatives (16.1%) and salicylates (13.7%). Most of the poisonings were intentional (75.1%), especially in 19-29 years age group of adults and 13-18 years age group of children. Most of the patients reported to DPIC and admitted to EMDEU were asymptomatic (84.4% and 54.7%, respectively). Gastrointestinal decontamination methods were performed more frequently for admitted poisoning cases before hospital admission than reported poisoning cases (61% vs. 23%). Paracetamol ingestion was the most common cause of analgesic exposures reported to our DPIC. Most of the analgesic exposures reported to DPIC were asymptomatic or mild. DPICs have an important role for the referral of analgesic exposures without unnecessary gastrointestinal decontamination procedures.

Background: Although we have previously demonstrated the beneficial effects of adenosine receptor antagonists in preventing cardiovascular toxicity of amitriptyline in rats, it is not clear whether adenosine receptors in heart or in vasculature are dominant. The aim of the current study was to investigate the role of adenosine A(2a) receptors on amitriptyline-induced vasodilation in rat isolated aorta., Methods: After determining EC(80) of noradrenalin (NA) (the concentration of noradrenalin that produces 80% of maximal contractile response) as 10(-5)M, the IC(50) value of amitriptyline was measured in rat isolated aorta (the drug concentration causing a half- maximal inhibition of contractile responses to NA); IC(50) of amitriptyline was then compared in the presence of the DPCPX (a selective adenosine A(1) antagonist), CSC (a selective A(2a) antagonist) or DMSO (a solvent for adenosine antagonists). Statistical analysis was done using the Student t test., Results: Amitriptyline-inhibited 49.9 +/- 3.7 % contractile response to NA on aorta segments at 1.8 x 10(-5)M (IC(50)). While DPCPX increased amitriptyline-induced inhibition on contractile response to NA dose dependently, CSC decreased the contractile response to NA only at 10(-5)M. DMSO did not change amitriptyline-induced IC(50)., Conclusion: Adenosine A(2a) receptor stimulation seems to be responsible partly for amitriptyline-induced vasodilation and hypotension since the adenosine A(1) antagonist, DPCPX, increased amitriptyline-induced vasodilation in rat isolated aorta.

Objective: To investigate the role of adenosine triphosphate-regulated potassium (KATP) channels in the propofol-induced changes in the contractile function of hypercholesterolemic rabbit hearts., Methods: This study was carried out in the Department of Pharmacology Laboratory, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey during the period January to December 2003. Twenty-two isolated rabbit hearts were grouped into 4. Group I (n=6) were infused with 50 microM propofol during a 60 minutes perfusion. Group II (n=6) were also infused with 100 microM propofol over the same period. Group III (n=5) was perfused with solutions containing 10 microM glybenclamide and group IV (n=5) 100 microM diazoxide for 5 minutes before and during a 60 minutes infusion with 100 microM propofol., Results: The 50 microM propofol infusion decreased left ventricular pressure (LVP) significantly (p<0.05) but it did not change dP/dt max and dP/dt min. The 100 microM propofol infusion caused a significant increase in LVP at 20 minutes. Furthermore, a 100 microM propofol infusion resulted in a significant increase in maximal positive left ventricular pressure (dP/dt max) and maximal negative left ventricular pressure (dP/dt min) compared to baseline (p<0.05). The increase in dP/dtmax and dP/dt min induced by 100 microM propofol was inhibited by glybenclamide (p<0.05), a KATP channel blocker, but was not affected by diazoxide (p>0.05), a KATP channel opener., Conclusion: The activation of KATP channels seems to be one of the mechanisms by which propofol induced beneficial effect on contractility of myocardium in hypercholesterolemic rabbit hearts.

The objective of this study was to evaluate the effects of an adenosine A1 agonist, phenylisopropyl adenosine (PIA), on metamidophos poisoning compared to specific antidotes. Rats were poisoned with metamidophos (30 mg/kg, oral) and observed for 24 hours. One group received sodium chloride (1 mL/kg) and four experimental groups received atropine (5 mg/kg), pralidoxime (PAM, 20 mg/kg), atropine/PAM (5/20 mg/kg) or PIA (1 mg/kg) intraperitoneally. Atropine reduced salivation and prevented respiratory distress when compared to sodium chloride-treated rats. Treatment with PAM did not cause any suppression of cholinergic signs. Atropine and PAM combination prevented salivation, convulsion and respiratory distress. PIA delayed initial time of the salivation, convulsion and time to death. However, PIA was found ineffective against the metamidophos-induced cholinergic symptoms and mortality. All treatments, except PIA, lead to survival of these animals. Acetylcholinesterase (AChE) activity was not normalized by PIA or PAM. PIA prevented metamidophos-induced diaphragmatic muscle necrosis as much as PAM. In conclusion, a single dose of PIA was unable to protect the rats from metamidophos toxicity. Further studies are needed involving a combination of PAM and/or atropine with repeated doses of PIA to clarify the efficacy of adenosine agonists in OP poisoning.

Dimethyl sulfoxide (DMSO) has been widely used in the treatment of arthritis and certain inflammatory diseases, and is also considered an alternative remedy for cancer even if not supported by concrete evidence. This report illustrates the first case of a fatal complication following the illicit use of this agent. A 55-y-old man who reportedly ingested 500 mg acetaminophen and approximately 1 ml DMSO solution was brought to the emergency department after experiencing 2 tonic-clonic seizures. He had been diagnosed with lung mesotelioma with brain metastases which caused no neurologic deficit. The ingested DMSO was the first dose within the last 3 mo. Examination revealed right-sided hemiplegia. Unenhanced computed tomography of the head showed 3 hemorrhagic areas with blood-cerebrospinal fluid at the left parietal, occipital and frontal regions accompanied by a midline shift. Despite initial resuscitation, 2 units of fresh frozen plasma and antiedema treatment, the patient experienced cardiac arrest that did not respond to resuscitative measures. DMSO can cause massive intrametastatic hemorrhage, and neurologic deterioration can be profound in patients with metastatic brain lesions.

This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 +/- 0.1 microg/ml to 0.1 +/- 0.0 microg/mL in rats pretreated with 90 mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (F(p.o.)) in the 60 or 90 mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90 mg/kg but not 60 mg/kg of diltiazem increased the AUC(0-infinity), elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CL(i.v.)) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.

We present a case with angioedema of the tongue, following 1 dose of an angiotensin-converting enzyme (ACE) inhibitor ingestion. A gradual progression of angioedema required tracheotomy despite aggressive medical treatment and illustrates the severity of this adverse reaction. Although ACE inhibitors are considered safe, emergency physicians should be alert for minor angioedema at presentation that may progress to life threatening airway compromise.

Objective: The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline-induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication., Methods: Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40-45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor-mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n=8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8-cyclopentyl-1,3-Dipropylxanthine, 20 microg/kg/min, n=8) or a selective A2a antagonist CSC (8-(3-chlorostyryl) caffeine, 24 microg/kg/min, n=8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n=8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 microg/kg/min, n=8) or CSC (24 microg/kg/min, n=8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate., Results: In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 +/- 2.8%, 75.6 +/- 4.7% and 50.1 +/- 14.7%, p<0.01, p<0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 +/- 2.6%, 102.4 +/- 2.6%, 81.8 +/- 5.4, p<0.01 at 30 min; 98.0 +/- 2.9%, 93.5 +/- 6.0%, 64.9 +/- 4.7, p<0.001, p<0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.0001)., Conclusion: Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline-induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline-induced cardiovascular toxicity.

The demographics, sources and outcomes of methanol poisoning have not been described in Turkey. Our study identified the profile of acute methanol exposures reported to Drug and Poison Information Center (DPIC) in Izmir, Turkey, from 1993 to 2002. Data analysis included patient demographics, sources of methanol, reason for the exposure, clinical effects and outcomes of methanol poisoning. The DPIC recorded 30,485 calls concerning poisoning; 996 (3.3%) alcohol poisonings were recorded and 113 (11.3%) of them were methanol poisonings. There were 91 (80.5%) males and 22 (19.5%) females with a mean age of 34.7+/-1.3 y (range 19-65) and 4.8+/-0.9 y (range 1-18) in adults and children, respectively. The sources of methanol were eu de cologne (72.6%), spirits (10.6%) and antifreeze (2.7%). Accidental poisoning occurred in all children between 0 and 12 y old, abuse (55.7%) and intentional poisoning (27.3%) were predominant in adults. Clinical signs in all cases were central nervous system symptoms (45.1%), metabolic acidosis (23.0%), visual symptoms (21.2%) and gastrointestinal symptoms (10.6%). Sixteen patients (14.1%) died, 63 (55.8%) had complete recovery and 1 (0.9%) had irreversible visual problems. Most patients with methanol poisoning may die or present serious morbidity without appropriate treatment in a health care facility. Methanol for producing cheap "eu de colognes" in Turkey is the principal reason for severe poisoning and deaths. Public education about colognes and legislative control of cologne production are important in preventing methanol poisoning.

This study analyzed poisonings caused by pesticides that were reported to Drug and Poison Information Center (DPIC), in Izmir from 1993 to 2001. Patient demographics, type of the pesticide, distribution according to month and year, route and reason for exposure, clinical effects and outcome were analyzed from 25,572 poisoning calls. Pesticide intoxications accounted for 8.8% of the poisonings, with 80.3% insecticides and 19.7% rodenticides. The majority of poisonings ranged from 0 to 6 y (28.2%) and 19-29 y (23.2%). Half the accidental exposures (57.7%) were in the 0-6-y group; the attempted suicide was predominant in the 19-29 y group (39.8%). Most were intoxicated with organophosphates (47.6%); 54.1% did not develop signs and symptoms of toxicity. Fatality due to pesticide poisoning was 0.4%. Preventive education against pesticide poisoning is needed.

Objective: Hypotension induced by tricyclic antidepressants is multifactorial. Previous animal experiments suggest a contribution from nitric oxide production. Our study aimed to evaluate the role of nitric oxide in amitriptyline-induced hypotension using N-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, and 3-morpholino sydnonimine, a nitric oxide donor, in anesthetized rats., Methods: Amitriptyline intoxication was induced by the continuous infusion of amitriptyline 0.625 mg/kg/min throughout the experiment in anesthetized rats. Fifteen and 25 minutes after amitriptyline infusion began, two bolus doses of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 8) or an equivalent volume of 5% dextrose solution (n = 8) was administered to each rat (Protocol 1). To investigate whether the effect of N-nitro-L-arginine methyl ester on blood pressure is counteracted by 3-morpholino sydnonimine, after the same protocol of amitriptyline infusion and 5 minutes after an N-nitro-L-arginine methyl ester bolus, a bolus of 3000 nmol/kg of 3-morpholino sydnonimine was administered (n = 8) to each rat (Protocol 2). To investigate the effect of N-nitro-L-arginine methyl ester on 3-morpholino sydnonimine induced hypotension, a group of rats received a continuous infusion of 0.54 mg/kg/h of 3-morpholino sydnonimine until 50% reduction was observed in mean arterial blood pressure followed by a bolus dose of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 6) or 5% dextrose solution (n = 6) (Protocol 3). Outcome measures included mean arterial blood pressure, heart rate, and QRS duration in electrocardiogram. Student's t test and survival analysis were used for selected comparisons., Results: For all parameters, the treatment groups were similar at baseline and at postamitriptyline periods before therapy was rendered. Amitriptyline infusion significantly reduced mean arterial blood pressure by 50.8 +/- 2.2% and prolonged QRS by 23.9 +/- 7.2% after 15 minutes. In Protocol 1, N-nitro-L-arginine methyl ester significantly increased mean arterial blood pressure compared to dextrose-treated control animals within 30 minutes (77.9 +/- 8.5% vs. 49.7 +/- 5.0% mmHg, p < 0.01, 95% CI 57.1-98.7%). QRS duration progressively increased during the amitriptyline infusion; however, there was no significant difference in QRS width between N-nitro-L-arginine methyl ester and control groups at any time point. N-nitro-L-arginine methyl ester increased survival time compared to controls (33.4 +/- 4.1 vs. 19.9 +/- 2.7 minutes, p < 0.01, 95% CI 25.4-41.3) but did not affect mortality. In Protocol 2 of continuous infusion of amitriptyline, 3-morpholino sydnonimine counteracted the N-nitro-L-arginine methyl ester-induced increase in mean arterial blood pressure. In both protocols, heart rate decreased significantly during amitriptyline infusion but there was no difference between treatment and control groups. In Protocol 3, N-nitro-L-arginine methyl ester bolus reversed 3-morpholino sydnonimine-induced hypotension compared to dextrose bolus. (83.8 +/- 5.7% vs. 54.6 +/- 4.8%, p < 0.01, 95% CI 69.2-98.4)., Conclusion: N-nitro-L-arginine methyl ester is found to be effective in temporarily improving hypotension and prolonging survival time but does not affect overall mortality. Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension.

The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/-3.4 ng x h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.

Latrodectism is considered dangerous for human beings. Acute renal failure after envenomation is not common and usually results from prerenal failure. We report a 59-y-o man with acute oliguric renal failure due to a combination of prerenal and renal causes after being bitten by a black Latrodectus spider. He had the characteristic anxiety, severe hypertension, tremor, facial edema, and generalized diaphoresis. The patient recovered within a week without sequelae. Clinicians should not overlook the possibility of acute renal failure in latrodectism.

The ability of a nicotine vaccine to protect against nicotine-induced seizures was studied in rats. Groups of 10 rats were vaccinated with 3 doses of either a nicotine conjugate vaccine over 6 weeks to elicit high titers of nicotine-specific antibodies or with a control vaccine. Rats were then pretreated with a 1-week subcutaneous infusion of either nicotine 1 mg/kg/day or saline and then received a single 2 mg/kg ip dose of nicotine to provoke seizures. Vaccination reduced the incidence of seizures. The combination of vaccination and pretreatment with nicotine infusion was more effective than either treatment alone. These data suggest that vaccination is protective against this toxic effect of nicotine and that combining vaccination and chronic nicotine administration may provide a novel strategy for blocking some effects of nicotine.

The aim of the present study was to compare the effects of propofol on cardiac contractile force in normal and hypercholesterolemic isolated rabbit hearts. While one group was fed with standard chow pellets (150 g/day), the other group received cholesterol (1% w/w) in addition to the same amount of rabbit chow pellets during 1 month. Hearts from standard-fed rabbits were given intralipid solvent or 25, 50 and 100 microM propofol by infusion. Hypercholesterolemic rabbit hearts were administered 25, 50 and 100 microM propofol by infusion. All concentrations of propofol did not result in any significant change of the heart rates (HR) in two groups. Propofol (25, 50 and 100 microM) infusion induced a concentration- and time-dependent inhibition in left ventricular pressure (LVP) in standard chow diet group (P<.05,.05 and.05, respectively). In hypercholesterolemic rabbit hearts, 25 and 50 microM propofol infusion developed a significant inhibition in LVP when compared with the standard chow diet group (P<.05 and.05, respectively). Propofol (100 microM) infusion developed a significant increase in LVP after 20 min in hypercholesterolemic rabbit hearts when compared with normal rabbit hearts (P<.05). Supratherapeutic concentration of propofol might have cardioprotective effect on hypercholesterolemic rabbit hearts.

A 54-y-o woman presented to the Emergency Department with shortness of breath and sore throat after intranasal administration of Ecbalium elaterium as a folk remedy for her sinusitis. The patient's history included nasal aspiration of the juice of the squirting cucumber (Ecbalium elaterium) for acute maxillary sinusitis. An airway obstruction due to severe uvular angioedema was detected and confirmed by airway X-ray. The patient was treated with 100% oxygen with mask, 0.3 mg epinephrine s.c., and 80 mg prednisolone i.v. Renal and hepatic function tests were normal. After a 24-h observation, the patient was discharged in her previous state of health.

Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors., (Copyright 1999 The Italian Pharmacological Society.)