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1.  Qualitative thallium urinary assays are almost as valuable as quantitative tests: implication for outpatient settings in low and middle income countries 
Electronic Physician  2017;9(4):4190-4194.
Thallium (Tl), lead and steroid exposures were reported as a result of street drug consumption such as heroin and cocaine.
This study aimed to compare the values of qualitative and quantitative assays for detecting Tl as an adulterant in opioid-like compound drug users.
This case-control study was conducted throughout a specified time bracket ranging from May 2015 to November 2015 in Imam Reza Hospital, Mashhad, Iran. In general, urine thallium samples for 100 opioid overdosed subjects with a history of chronic opioid use and 50 non-drug users were studied. Qualitative 24 hours-urinary-thallium-level (QL) and quantitative 24 hours-urinary-thallium-level (QT) were conducted in both groups. Independent-samples t-test and Spearman’s Coefficient were applied for analytical purposes. SPSS software 16 was used to conduct statistical analyses with P values less than 0.05 regarded as significant.
A total of 150 cases were studied. Raw opium users accounted for 66% of the cases followed by mixed (28%) and heroin users (6%). Mean (SD) QT level for QL was 26.8 (1) μg/L, while it was 2.3 μg/L (0.4 μg/L) for negative QL, which was far below QL positive cases (p=0.002). The qualitative test showed more accuracy at higher quantitative levels. In all cases, qualitative test was fully sensitive (100%), highly specific (89%) with a positive likelihood ratio (PLR) of 9.1 and a negative likelihood ratio (NLR) of 0.
These results suggest that qualitative assays could be used with confidence in assessing Tl exposure in drug users. Physicians may easily and confidently use Tl qualitative tests in rehabilitation centers, where toxicology laboratories may not be available.
PMCID: PMC5459291
Drug user; Thallium; Quantitative assay; Qualitative assay
3.  Opium Addiction and Risk of Laryngeal and Esophageal Carcinoma 
Cigarette smoking and alcohol consumption have a well-known effect on the development of upper aerodigestive tract carcinomas, but such a role for opium is questionable. This study was designed to assess the correlation between opium inhalation and cancer of the larynx and upper esophagus.
Materials and Methods:
Fifty eight patients with laryngeal cancer, ninety eight patients with upper esophageal cancer and twenty seven healthy individuals with no evidence of head and neck or esophageal malignancies were selected from Otolaryngology and Radiation Oncology Department of Mashhad University of Medical Sciences. Duration and amount of cigarette smoking and opium consumption were recorded through comprehensive interviews.
The crude odds ratio for laryngeal cancer was 5.58 (95% CI 2.05-15.15, P=0.000) in cigarette smokers relative to non-smokers and 9.09 (95% CI 3.21-25.64, P=0.000) in opium users relative to non-users. The crude odds ratio for esophageal cancer was 0.44 (95% CI 0.18-1.09, P=0.07) in cigarette smokers relative to non-smokers and 1.44 (95% CI 0.57-3.62, P=0.43) in opium users relative to non-users. After adjusting for smoking, the odds ratio for laryngeal cancer in opium users relative to non-users was 6.06 (95% CI 1.10-33.23, P=0.05). Laryngeal cancer was detected at a significantly lower age in opium users (54.54±10.93 vs 62.92±10.10 years, P=0.02) than in smokers. This effect was not observed in esophageal cancer. Although the duration (year 17.50±14.84 vs 21.91±14.03; P=0.34) and amount (pack/day 0.625 vs 0.978; P=0.06) of smoking were higher among those who were opium dependent, these differences were not statistically significant (P=0.34 and P=0.06, respectively).
Opium addiction by snuffing is an independent risk factor for the development laryngeal cancer but not esophageal cancer. Cigarette smoking increases this risk. Opium dependency increases the likelihood of developing laryngeal cancer at a younger age.
PMCID: PMC5307300
Esophageal carcinoma; Laryngeal carcinoma; Opium; Risk factors
4.  Mushroom Poisoning in the Northeast of Iran; a Retrospective 6-Year Epidemiologic Study 
Emergency  2017;5(1):e23.
Toxic mushrooms are distributed across the globe with over 5000 species. Among them, 100 species are responsible for most of the cases of mushroom poisoning. This study aimed to evaluate the epidemiologic pattern of mushroom poisoning among patients referred to the main toxicology center of Mashhad province located in North-east of Iran.
This cross-sectional study was conducted on patients with final diagnosis of mushroom poisoning referred to the toxicology center of Mashhad, Iran, from February 2005 to 2011. Patients’ demographic characteristics, clinical presentations, laboratory findings, outcomes, and therapeutic measures were collected using a predesigned checklist and searching patient’s profile.
32 cases with the mean age of 24.6 ± 16.7 years were presented to the toxicology center following mushroom poisoning (59% female). Mushroom poisoning accounted for 0.1% of all admitted cases. The mean time elapsed from consumption to referral to poisoning department was 61.9 ± 49.4 hours. 19 (59%) cases were discharged with complete recovery, 7 (22%) expired, and 6 (19%) cases left hospital against medical advice. Mushroom poisoning mortality accounted for 1.5% of deceased cases in the studied center. There was significant relationship between mortality rate and higher values of INR (p = 0.035), PT (p = 0.011) and PTT (p = 0.003). Likewise, there was significant relationship between the need for mechanical ventilation and higher values of INR (p = 0.035), PT (p = 0.006) and PTT (p = 0.014). The relationships between the need for ICU admission, mechanical ventilation, and mortality rate with the rise of hepatic transaminases and serum bilirubin were not significant.
Based on the findings, the prevalence of mushroom poisoning among patients referred to Mashhad toxicology center was very low (0.1%), but with a high mortality rate of 22%. Nausea and vomiting were the most common early symptoms of intoxication and higher values of coagulation profile were correlated with poor outcome.
PMCID: PMC5325892
Mushroom poisoning; epidemiology; mortality; toxicology; Iran
5.  Suicidal Attempt With Intentional Poisoning Seems a Comorbid Illness With an Increased Burden 
In measuring health utilities, the primary reason for selecting patients as a source for valuations is that they directly experience the impact of the disease.
Accordingly, the aim of this study was to examine the variation in generic utility measures with respect to acute poisonings by including a comparison between those subjects who had high intention and low intention to commit suicide.
Patients and Methods:
We evaluated the responses of patients who had attempted suicide and were admitted to a toxicology ward. We used multiple methods, including TTO, VAS, and EQ-5D.
We reviewed the collected questionnaires of one hundred patients admitted to the medical toxicology ward of Emam Reza teaching hospital in Mashhad, Iran. Our results show that the mental state after an incomplete suicide attempt can present either a real desire for suicide or a desire for attention from relatives and rejection of life problems.
This study demonstrates that the mental states associated with specific diseases should not be ignored in evaluating health states. Although there are benefits to relying on expert panels and the general population in evaluating various health states, attention to the particular health states of the patients (taking into account their associated mental well-being) should also be utilized.
PMCID: PMC4859999  PMID: 27162760
Acute Disease; Attempted; Illness Burdens; Global Health; Life Tables; Life Expectancy; Models; Statistical; Mortality; Poisoning; Suicide
6.  World Health Organization estimates of the global and regional disease burden of four foodborne chemical toxins, 2010: a data synthesis 
F1000Research  2015;4:1393.
Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population’s exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure. 
Methods and Findings
Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease.  The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin.  Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals.  From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated.  For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively.  Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios.  Virtually all human exposure to these four chemicals is through the food supply. 
Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer).  The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).
PMCID: PMC4755404  PMID: 26918123
public health; epidemiology; foodborne diseases; DALYs; aflatoxin; cassava; cyanide; dioxin; peanut allergen
7.  Comparing Motivational Interviewing-Based Treatment and its combination with Nicotine Replacement Therapy on smoking cessation in prisoners: a randomized controlled clinical trial 
Electronic Physician  2015;7(6):1318-1324.
The prevalence of smoking is much higher in prisoners than it is in the general population. Prisoners who smoke cause many health problems for themselves and other prisoners. Therefore, we should help them stop smoking.
To compare the effects of motivational interviewing-based (MI-based) treatment and its combination with nicotine replacement therapy (NRT) on smoking cessation in prisoners at Mashhad Central Prison.
The study was designed as a double-blind, randomized, controlled clinical trial, and it began in February 2013 and ended in February 2014. Two hundred and thirteen prisoners met the inclusion criteria and were enrolled in the study. They were divided randomly into three groups, i.e., MI-based treatment, MI with NRT, and the control group, which didn’t receive any therapy. The outcome measures were reported after intervention and at a 90-day follow-up, and changes in the CO levels in expired air and nicotine dependency were measured.
The average age of the subjects was 37.59 ± 8.76, and their mean duration of imprisonment was 3.3 ± 1.90 years. They smoked an average of 21.84 ± 8.72 cigarettes per day. Analysis of the concentration of CO in expired air in the pre-test, post-test, and at the follow-up for the three groups showed that the variations in the mean CO concentrations in the MI group and the MI with NRT group at the pre-test and at the post-test were statistically significant (p < 0.001), but no significant changes occurred between the post-test and the follow-up (p > 0.050). In addition, the results indicated that CO concentration in expired air in the MI with NRT group was statistically significant, with better efficacy of smoking cessation, compared with control group and the MI group after the follow-up (p = 0.02).
Motivational interviewing combined with NRT for smoking cessation is more effective than MI alone, and it resulted in a significant decrease in the CO concentration in expired air at the 90-day follow-up.
PMCID: PMC4623789  PMID: 26516436
motivational interviewing; nicotine replacement therapy; smoking cessation; prisoners
8.  Thallium exists in opioid poisoned patients 
Thallium (Tl) is a toxic heavy metal that exists in nature. Tl poisoning (thallotoxicosis) may occur in opioid addicts. This study was designed to evaluate the frequency and level of urinary Tl in opioid abusers. In addition, clinical findings were evaluated.
A total of 150 subjects were examined. Cases with a history of at least 3 years of abuse were admitted in the Imam Reza Hospital as the case group; 50 non-opioid abusers from the target population were included as the control group. Twenty-four hour urinary qualitative and quantitative Tl analyses were performed on both groups.
Out of the 150 subjects, 128 (85 %) were negative for qualitative urinary Tl, followed by 5 % (trace), 7 % (1+), 2 % (2+), and 1 % (3+). Mean (standard error (SE), Min–Max) quantitative urinary Tl level was 14 μg/L (3.5 μg/L, 0–346 μg/L). Mean urinary Tl level in the case group was 21 μg/L (5 μg/L, 0–346 μg/L) and that in the controls was 1 μg/L (0.14 μg/L, 0–26 μg/L), which were significantly different (P = 0.001). The most frequent clinical findings were ataxia (86 %), sweating (81 %), and constipation (54 %). In all cases (n = 150), the mean (SE) value for cases with positive qualitative urinary Tl was 26.8 μg/L (0.9 μg/L) and that in the negative cases was 2.3 μg/L (0.2 μg/L), which were significantly different (P = 0.002).
This study showed that long-term opioid abuse may lead to Tl exposure. In opioid abusers with the clinical manifestation of thallotoxicosis, urinary Tl should be determined.
PMCID: PMC4521340  PMID: 26231176
Thallium; Opioid; Poisoning
10.  Rhabdomyolysis in 114 patients with acute poisonings 
Rhabdomyolysis is a clinical and biochemical syndrome, which is observed in some patients with acute chemical and/or pharmaceutical poisonings. We aimed to investigate rhabdomyolysis in patients with acute poisonings due to different chemicals, natural toxins or drug overdose.
Materials and Methods:
Following approval of the University medical research committee and obtaining informed consents from the patients or their relatives, all patients with acute poisonings who were treated between March 2009 and February 2010 in the Toxicologic Ward of Imam Reza Hospital and had serum creatine phosphokinase (CPK) above 975 IU/L (as a definition for rhabdomyolysis) were studied.
Of 3555 hospitalized poisoned patients, 114 patients had rhabdomyolysis with CPK of 5996 ± 892 IU/L (mean ± standard error). The most common intoxication to induce the rhabdomyolysis was opioid overdose (28%). Acute renal failure (ARF) was diagnosed in 11 (8.7%) patients. There was a linear correlation between CPK and creatinine (P < 0.001), which in turn had a significant correlation with death (P < 0.05).
Patients with acute poisoning were at risk of rhabdomyolysis. Acute opioid poisoning was the most common cause of toxic rhabdomyolysis in the intoxicated patients, and ARF was the main complication.
PMCID: PMC4468227  PMID: 26109969
Acute poisoning; acute renal failure; creatine kinase; creatinine; intoxication; rhabdomyolysis
11.  Tramadol half life is dose dependent in overdose 
Tramalol overdose is disproportionately more common in Iran. In recent years, Tramadol overdose has become one of the most common causes of poisoning admissions to emergency departments in this country. To the best of our knowledge, there is little or no information regarding the toxicokinetic properties of Tramadol such as its half life. Given the fact that poisoning management should be based on the toxicokinetic of substances, we aimed at investigating the half life of Tramadol in man as a critical toxicokinetic variable in overdose.
Blood samples of each patient were collected on admission and repeated later. Plasma was harvested after separation from blood cells by centrifugation and quantified using HPLC method. Calculations were performed on Tramadol blood concentration quantities.
Demographic: Most of cases were men (81.81%). Mean (Standard Deviation (SD), min-max) age was 23 (8.142, 17-40). Serum Tramadol levels: Mean (SD, min-max) first Tramadol concentration was 786.91 (394.53, 391-1495). Mean (SD, min-max) second Tramadol concentration was 433.09 (269.63, 148-950). Mean (SD, min-max) of Tramadol half life was calculated as 9.24 hour (2.310, 4.99-13.45) Associations: Half life was associated with higher concentrations (r=0.708 Sig=0.015).
We report the mean half life of tramadol in overdose to be 9.24 hours which is remarkably higher than that measured in previous pharmacokinetic studies. We also concluded that Tramadol half life is dose dependent in overdose which may explain the further consequences of severe overdoses.
PMCID: PMC4348403  PMID: 25888861
Tramadol; Toxicokinetic; Half-Life; Overdose
13.  Analysis and Determination of Trace Metals (Nickel, Cadmium, Chromium, and Lead) in Tissues of Pampus argenteus and Platycephalus indicus in the Hara Reserve, Iran 
Journal of Toxicology  2014;2014:576496.
The accumulations of Cd, Ni, Pb, and Cr were measured in muscle, gill, kidney, and liver of Platycephalus indicus and Pampus argenteus. Our results indicated that all metals were found to be the highest in tissues in P. indicus (benthic species). Except Ni in P. indicus, concentrations of metals and bioaccumulation factor were in the following sequence: liver > kidney > gill > muscle. The data revealed that there is a significant negative correlation between concentrations of metals and size and age factors. The Ni and Cr levels in the muscles were higher than the maximum acceptable limit recommended by WHO and FEPA. Similarly, the concentration of Pb measured in P. indicus muscle exceeded the FAO standard limit.
PMCID: PMC4123597  PMID: 25132850
14.  Effect of long-term treatment of morphine on enzymes, oxidative stress indices and antioxidant status in male rat liver 
In this study, biochemical changes due to long term usage of morphine in rat’s liver were assessed. Twenty male Wistar rats (180-220 g) were included and divided into two groups. Normal saline was given intraperitoneally in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, and 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and liver malondialdehyde (MDA) level as well as activities of superoxide dismutase (SOD), glutathione-s-transfrase (GST) and catalase (CAT) were measured. Serum levels of AST, ALT and LDH were significantly higher in the morphine group compared with the control group. The mean MDA level of liver was significantly higher in the morphine group compared with the control group (P < 0.05). The activities of SOD, GST and CAT were significantly lower in the morphine group compared with the control group (P < 0.01). Our findings pointed out the risk of hepatic damage due to long term usage of morphine via disturbance oxidant-antioxidant balance. Although morphine is showed to be effective in pain treatment, their toxic effects should be kept in mind during the chronic usage.
PMCID: PMC4073771  PMID: 24995110
Morphine; oxidative stress; liver; antioxidant; rat
15.  Delayed Polyneuropathy in Farm Sprayers Due to Chronic Low Dose Pesticide Exposure 
The use of organophosphates (OPs) in developing countries is rising in large quantities and non-secure methods. This problem not only causes acute poisoning but also may lead to chronic diseases such as polyneuropathy. In Iran, 60% of pesticides are organophosphate compounds that may lead to delayed polyneuropathy.
The purpose of the current study was to evaluate delayed polyneuropathy in farm sprayers due to chronic low dose pesticide exposure.
Patients and Methods:
In our cross-sectional study, non-randomized sampling method was performed and 100 farm sprayers (cases) and 100 hospital personnel (controls) after precise systemic and neurological examination were recruited to this study from June 2011 to august 2011. The nerve conduction studies were performed and these indices were recorded: Compound Muscle Action Potential (CMAP), amplitude and Distal Latency (DL) and Nerve Conduction Velocity (NCV) of common peroneal nerve, Peak Latency (PL) and amplitude of Sensory Nerve Action Potential (SNAP) and Nerve Conduction Velocity (NCV) of sural and radial sensory nerves.
Among 100 cases, 55 farm sprayers complained of non-neurological problems including: ophthalmologic, dermatologic and pulmonary complications. The ophthalmologic complaints (44%) were the most. The mean peroneal CMAP amplitude and NCV, sural PL, radial SNAP amplitude, PL and NCV in the case group were significantly different compared to control group. Mean exposure time to OPs in farm sprayers without neurological problem (40%) was 11.81 ± 5.84 years but in farm sprayers with neurological problems (60%) was 15.70 ± 9.08 years, which represents the effect of OPs exposure duration on neurologic problems.
Chronic low dose pesticide exposure could lead to delayed peripheral neuropathy as well as systemic (skin, eyes and lungs) complications. In farm sprayers electrodiagnostic indices were significantly abnormal as compared to control group. The normal indices did not rule out neurologic involvement and it seems that measurement of these indices at the beginning of the farm sprayers employment and intermittently during their work is helpful for detecting delayed polyneuropathy.
PMCID: PMC4082521  PMID: 25031861
Pesticides; Neurotoxicity Syndromes; Polyneuropathies; Electrodiagnosis; Organophosphates
16.  Evaluation of Lung and Bronchoalveolar Lavage Fluid Oxidative Stress Indices for Assessing the Preventing Effects of Safranal on Respiratory Distress in Diabetic Rats 
The Scientific World Journal  2014;2014:251378.
We investigated the effects of antioxidant activity of safranal, a constituent of Crocus sativus L., against lung oxidative damage in diabetic rats. The rats were divided into the following groups of 8 animals each: control, diabetic, and three diabetic + safranal-treated (0.25, 0.50, and 0.75 mg/kg/day) groups. Streptozotocin (STZ) was injected intraperitoneally (i.p.) at a single dose of 60 mg/kg for diabetes induction. Safranal was administered (i.p.) from 3 days after STZ administration to the end of the study. At the end of the 4-week period, malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) contents, activity of superoxide dismutase (SOD), and catalase (CAT) were measured in the bronchoalveolar lavage fluid (BALF) and lung tissue. Safranal in the diabetic groups inhibited the level of MDA and NO in BALF supernatant and lung homogenate. The median effective dose (ED50) values were 0.42, 0.58, and 0.48, 0.71 mg/kg, respectively. Safranal in the diabetic groups increased the level of GSH and the activity of CAT and SOD in BALF supernatant and lung homogenate. The ED50 values were 0.25, 0.33, 0.26 in BALF and 0.33, 0.35, 0.46 mg/kg in lung, respectively. Thus, safranal may be effective to prevent lung distress by amelioration oxidative damage in STZ diabetic rats.
PMCID: PMC3950999  PMID: 24701146
17.  Snakebite management in Iran: Devising a protocol 
Snakebite in Iran has been a health concern. However, management of snakebite is not standardized and varies from center to center. This study is aimed at devising an evidence-based comprehensive protocol for snakebite management in Iran, to reduce unnecessary variations in practice.
Materials and Methods:
A narrative search in electronic databases was performed. Fifty peer-reviewed articles, guidelines, and textbooks were reviewed and practical details were extracted. Our currently used protocol in the Mashhad Toxicology Center was supplemented with this information. Consequently an improved wide-range protocol was developed. The protocol was then discussed and amended within a focus group comprised of medical toxicologists and internal medicine specialists. The amended version was finally discussed with expert physicians specialized in different areas of medicine, to be optimized by supplementing other specific considerations.
During a one-year process, the protocol was finalized. The final version of the protocol, which was designed in six steps, comprised of three components: A schematic algorithm, a severity grading scale, and instructions for supportive and adjunctive treatments. The algorithm pertains to both Viperidae and Elapidae snakebite envenomations and consists of a planned course of action and dosing of antivenom, based on the severity of the envenomation.
Snakebite envenomation is a clinical toxicologic emergency, which needs to be treated in a timely and organized manner. Hence, a multi-aspect protocol was designed to improve the clinical outcomes, reduce unnecessary administration of antivenom, and help physicians make more proper clinical judgments.
PMCID: PMC3999602  PMID: 24778670
Clinical protocols; emergency treatment; Iran; snake bite; therapeutics
18.  Cholestasis and Seizure Due to Lead Toxicity: A Case Report 
Hepatitis Monthly  2013;13(11):e12427.
Lead poisoning is a major public health risk which may involve major organs. Recently, there have been reports of opioid adulteration with lead in Iran. The following case report is the first of its kind in that intrahepatic cholestasis due to lead toxicity has been described.
Case Presentation
A 65-year-old man presented to the emergency department with abdominal pain, abnormal liver function tests (cholestatic pattern), and normocytic anemia. He had been an opium user for 20 years. Clinical and preclinical findings including the bluish discoloration of periodontal tissues, or Burton’s sign, and generalized ileus on abdominal x-ray led us to the possibility of lead poisoning. Lead levels were higher than normal (150 μg/dL). Magnetic resonance cholangiopancreatography (MRCP) and abdominal ultrasound were performed to rule out extra hepatic causes of cholestasis. To evaluate the possibility of lead-induced hepatotoxicity, a liver biopsy was performed. Histological features of lead-induced hepatotoxity have rarely been described in humans. In this patient, focal canalicular cholestasis and mild portal inflammation were confirmed. Thus, treatment with ethylenediaminetetraacetic acid (EDTA) and British anti-lewisite (BAL) were initiated and continued for five days. The patient’s liver function tests returned to their normal values, clinical findings including nausea, vomiting, and abdominal pain subsided, and the patient was discharged from the hospital in good condition.
Lead toxicity should always be taken into account in cases of intrahepatic cholestasis with an unknown etiology, especially in a setting where opium abuse is common.
PMCID: PMC3860072  PMID: 24348646
Lead; Cholestasis; Opium
19.  Crocus sativus L. (Saffron) Stigma Aqueous Extract Induces Apoptosis in Alveolar Human Lung Cancer Cells through Caspase-Dependent Pathways Activation 
BioMed Research International  2013;2013:417928.
Worldwide, lung cancer is the most common form of cancer. Saffron has been used in folk medicine for centuries. We investigated the potential of saffron to induce cytotoxic and apoptotic effects in lung cancer cells (A549). We also examined the caspase-dependent pathways activation of saffron-induced apoptosis against the A549 cells. A549 cells were incubated with different concentrations of saffron extract; then cell morphological changes, cell viability, and apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V and propidium iodide, and flow cytometric analysis, respectively. Activated caspases were detected by treatment of saffron in lung cancer cells using fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549 cells were decreased after treatment with saffron in a dose- and time-dependent manner. The percentage of apoptotic cells increased with saffron concentrations. Saffron induced morphological changes, decreased percentage of viable cells, and induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate caspase pathways. The levels of caspases involved in saffron-induced apoptosis in the A549 cells indicating caspase-dependent pathway were induced by saffron. The anticancer activity of the aqueous extract of saffron could be attributed partly to its inhibition of the cell proliferation and induction of apoptosis in cancer cells through caspase-dependent pathways activation.
PMCID: PMC3830877  PMID: 24288678
22.  Chlordiazepoxide Preventive Effect on Tramadol Overdose Induced Serotonin Syndrome Evaluated by Hunter and Radomski Criteria: A Clinical Trial 
Toxicology International  2013;20(2):126-131.
Tramadol is an analgesic medication that is frequently abused. It has two functions; mu-opioid receptors agonism, as well as, serotonergic activities. It has shown that tramadol overdose may induce serotonin syndrome (SS). This study evaluates whether early treatment with chlordiazepoxide could prevent SS in admitted tramadol overdoses.
Materials and Methods:
In this single blind randomized control trial, 50% of admitted tramadol overdoses in Imam Reza (p) Hospital from 21 September 2011 to 21 January 2012 were recruited. Cases received chlordiazepoxide and controls received placebo. Clinical findings were recorded in a pre-designed spread sheet every 6 hours in the first 24 hours of admission. SS was determined by two independent methods; Hunter Criteria (HC) and Radomski Criteria (RC).
In total, five patients developed SS when HC or RC was taken into account. Among them, four cases were shared. None of the SS cases diagnosed with HC received chlordiazepoxide. However, just one SS case diagnosed with RC was from the case group. Based on HC, chlordiazepoxide decreased the Risk Ratio (CI 95%) of SS to 0.80 (0.66-0.97) (P = 0.025). This effect did not reach statistically significant levels when SS was diagnosed with RC.
This study supports the fact that pre-treatment with chlordiazepoxide could prevent tramadol overdose induced SS.
PMCID: PMC3783678  PMID: 24082505
Hunter criteria; radomski criteria; serotonin syndrome; tramadol
23.  Respiratory Symptoms and Pulmonary Function Testes in Lead Exposed Workers 
The exposure to noxious agwents such as lead my cause lung disorders.
In the present study, pulmonary function tests and self-reported respiratory symptoms in lead exposure workers were compared with matched control subjects.
Materials and Methods
The frequency of respiratory symptoms were evaluated in a sample of 108 lead exposure workers and 100 control subjects with similar age using a questionnaire including questions on respiratory symptoms in the past year. Pulmonary function tests (PFT) were also measured in lead exposure workers and in controls.
Most lead exposure workers (63%) reported work-related respiratory symptoms. Chest tightness (26%), cough (17%) and sputum (16%) were the most common symptoms and only 6% of lead exposure workers reported wheezing (P < 0.001 for all case except wheezing). Most PFT values were also significantly reduced among lead exposure workers (P < 0.05 to P < 0.001 except MEF75, MEF50, MEF25, and MMEF. The lead concentration in urine and serum of lead exposure workers were significantly higher than control (P < 0.001 for both cases).
These results showed that c lead exposure workers have higher frequencies of respiratory symptoms higher serum and urine lead concentration but lower PFT values.
PMCID: PMC3560546  PMID: 23396762
Lead; Signs and Symptoms, Respiratory; Respiratory Function Tests
24.  Factors Related to Seizure in Tramadol Poisoning and Its Blood Concentration 
Journal of Medical Toxicology  2011;7(3):183-188.
This study examines the relation between seizure and plasma tramadol concentration in patients with tramadol poisoning, as a novel centrally acting analgesic used for the treatment of mild to severe pain. All patients admitted with a history of tramadol overdose accompanied by unconsciousness or seizures referred to Baharloo Hospital Poison Center, Tehran, Iran from March 2008 to March 2009 were included. Demographic information, clinical findings, and blood tramadol concentrations were studied. There were 401 patients with a history of tramadol overdose; 121 (30.2%) with a history of seizure and 14 (3.5%) with a history of unconsciousness were included. Most of overdoses involved men (83%). The mean age was 22.9 years (range, 14–50 years). Intentional overdose was the most common mode of poisoning (51.9%). The mean dose ingested was 1,511 mg (SD, 1,353; range, 200–7,000). Mean back-extrapolated tramadol blood concentrations were 3,843 ng/mL (3,715; 269–20,049). Back-extrapolated blood concentrations were correlated with dose (r = 0.313; P < 0.001) as well as blood concentration levels (r = 0.801; P < 0.001). Seizure was significantly correlated to higher reported dose (P < 0.001) and tramadol only to overdose (P < 0.001). However, it was neither related to higher tramadol blood concentrations, nor related to time elapsed, age, sex, history of addiction, and observed Glasgow Coma Scale of patients. Most patients experienced just one seizure (76%). The tramadol-induced seizure is dose dependent. Although higher doses of tramadol was related to higher blood concentration, blood tramadol concentrations was not associated with seizure.
PMCID: PMC3550210  PMID: 21735309
Tramadol; Seizure; Blood concentration; Poisoning
25.  Acute Datura Stramonium poisoning in East of Iran - a case series 
Objectives: Datura Stramonium (DS) is a common weed along roadsides, in cornfields and pastures and in waste areas. It belongs to the family Solanaceae and its toxic components are tropane belladonna alkaloids. It has been used voluntarily by teenagers for its hallucinogenic effect. The plant is named in Iran as Tatoore. Symptoms and signs of acute D. Stramonium poisoning usually are similar to anticholinergic syndrome. This study is done in order to clarify the status of this poisoning in our region.
Materials and Methods: This study is a case series on all patients admitted to Imam Reza Hospital, Mashhad, Iran, with acute D. Stramonium poisoning between 2008 and 2011. We observed their symptoms, signs, routine laboratory test results and treatment used to control their symptoms.
Results: There were 19 patients included in our study. Children were poisoned more commonly than teenagers and poisoning in adults was rare. All of the children ingested the plant accidentally. The most presenting symptom was irritability and the most common sign was sinus tachycardia. There was not any presentation of seizure or coma. Most of the symptoms were controlled by parenteral benzodiazepines and there were no need to use of cholinergic agents such as physostigmine.
Conclusion: Our study showed most of D. Stramonium poisoned population in our region are children. We suggest decreasing accessibility to the plant in order to decrease the incidence of its poisoning.
PMCID: PMC4075664  PMID: 25050235
Alkaloids; Atropine; Cholinergic Antagonists; Datura Stramonium; Poisoning

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