PURPOSE: Glyphosate herbicides (GHs) are widely used and increasingly associated with poisoning cases. Acute pancreatitis (AP) is among the many complications associated with the toxicity of GHs. We investigated the relationship between incidence of AP and its prognosis in patients with GH poisoning. METHODS: This was a retrospective cohort study conducted at a single tertiary hospital between January 2004 and December 2014. We enrolled all patients presented to the emergency department with GH poisoning. The Clinical and laboratory variables were analyzed to investigate the relationship between GH intoxication and AP. RESULTS: We studied 245 patients. Incidence of AP after GH poisoning was 6.5%. Patients with AP (mean 66 years) were older than the non-AP group (56 years). Systolic blood pressure, Glasgow Coma Scale, and amount of ingested poison differed significantly between the two groups. In the blood tests, white blood cell count, alanine aminotransferase, glucose, potassium, amylase, and lipase showed significant differences. The pH, bicarbonate, and lactate levels also differed significantly. Patients with AP demonstrated higher incidence of respiratory failure, pneumonia, acute kidney injury, rhabdomyolysis, and intensive care unit stay time. Additionally, 30-day mortality (n=11, 68.8%) was significantly higher in the AP group. On multivariate analysis, adjusted age, amount of ingestion, and lactate correlated with occurrence of AP. CONCLUSION: The incidence of GH-induced AP was 6.5% with a 30-day mortality of 68.8%. The patient's age, ingested dosage, and lactate levels were associated with GH-induced AP.
Acute Kidney Injury ; Alanine Transaminase ; Amylases ; Blood Pressure ; Cohort Studies ; Eating ; Emergency Service, Hospital ; Glasgow Coma Scale ; Glucose ; Hematologic Tests ; Herbicides ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Intensive Care Units ; Lactic Acid ; Leukocyte Count ; Lipase ; Mortality ; Multivariate Analysis ; Pancreatitis* ; Pneumonia ; Poisoning ; Potassium ; Prognosis* ; Respiratory Insufficiency ; Retrospective Studies ; Rhabdomyolysis ; Tertiary Care Centers

OBJECTIVES: The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis. METHODS: This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test. RESULTS: A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20–29 and 30–39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%). CONCLUSIONS: Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment.
Analgesics, Opioid ; Checklist ; Critical Care* ; Cross-Sectional Studies ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Intensive Care Units* ; Iran* ; Male ; Methadone ; Mortality ; Opium ; Poisoning* ; Potassium ; Renal Insufficiency ; Rhabdomyolysis* ; Sodium ; Street Drugs ; Urea

OBJECTIVES: The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis.METHODS: This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test.RESULTS: A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20–29 and 30–39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%).CONCLUSIONS: Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment.
Analgesics, Opioid ; Checklist ; Critical Care ; Cross-Sectional Studies ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Intensive Care Units ; Iran ; Male ; Methadone ; Mortality ; Opium ; Poisoning ; Potassium ; Renal Insufficiency ; Rhabdomyolysis ; Sodium ; Street Drugs ; Urea

This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.
Acrylamides ; chemistry ; isolation & purification ; toxicity ; Animals ; Anthozoa ; pathogenicity ; physiology ; Dinoflagellida ; pathogenicity ; physiology ; Dogs ; Guinea Pigs ; Haplorhini ; Humans ; Lethal Dose 50 ; Marine Toxins ; chemistry ; isolation & purification ; toxicity ; Mice ; Rabbits ; Rats ; Seaweed ; pathogenicity ; physiology ; Shellfish Poisoning ; physiopathology ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo investigate the protective effects of quercetin on cadmium-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells.

METHODSPrimary cultures of rPT cells undergoing exponential growth were incubated with 1.0 μg/mL quercetin and/or cadmium (2.5, 5.0 μmol/L), in a serum-free medium at 37 °C at different time intervals. Commercial kits were used and flow cytometric analyses were performed on rPT cell cultures to assay apoptosis and oxidative stress.

RESULTSExposure of rPT cells to cadmium acetate (2.5, 5.0 µmol/L) induced a decrease in cell viability, caused an increase in apoptotic rate and apoptotic morphological changes. Simultaneously, elevation of intracellular reactive oxygen species, malondialdehyde and calcium levels, depletion of mitochondrial membrane potential and intracellular glutathione, and inhibition of Na+, K+-ATPase, Ca2+-ATPase, glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were revealed during the cadmium exposure of rPT cells. However, simultaneous supplementation with 1 µg/mL quercetin protected rPT cells against cadmium-induced cytotoxicity through inhibiting apoptosis, attenuating lipid peroxidation, renewing mitochondrial function and elevating the intracellular antioxidants (non-enzymatic and enzymic) levels.

CONCLUSIONThe present study has suggested that quercetin, as a widely distributed dietary antioxidant, contributes potentially to prevent cadmium-induced cytotoxicity in rPT cells.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cadmium ; toxicity ; Cadmium Poisoning ; prevention & control ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Cells, Cultured ; Kidney Tubules, Proximal ; drug effects ; metabolism ; Malondialdehyde ; metabolism ; Membrane Potential, Mitochondrial ; drug effects ; Quercetin ; pharmacology ; therapeutic use ; Rats ; Reactive Oxygen Species ; metabolism ; Sodium-Potassium-Exchanging ATPase ; metabolism

Administration, Oral ; Adult ; Drug-Related Side Effects and Adverse Reactions ; nursing ; Female ; Humans ; Potassium Permanganate ; administration & dosage ; poisoning ; Powders

OBJECTIVETo investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin.

METHODSThe experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR.

RESULTSElectron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F.

CONCLUSIONThe potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

Animals ; Disease Models, Animal ; Fibronectins ; genetics ; metabolism ; Kidney ; drug effects ; metabolism ; ultrastructure ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Lead Poisoning ; complications ; metabolism ; pathology ; Male ; NF-kappa B ; genetics ; metabolism ; Potassium Iodide ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate suitable biomarkers for workers exposure to trimethyltin chloride (TMT-cl).

METHODSUrinary samples of 44 male workers from five TMT-cl occupational poisoning incidents were collected. Methyltin mercaptide stabilizers and waste plastics used in the incidents were also collected. The levels of TMT-cl in all the samples were determined by gas chromatography. The concentration of blood potassium for each poisonings was determined compared to control group (50 male workers of a food company), and the correlation between blood potassium and urinary TMT-cl were also determined.

RESULTSTMT-cl was detected in urine of all the poisonings. The results were (0.869 +/- 0.392) microg/L (severe poisoning), (0.963 +/- 0.482) microg/L (moderate poisoning), (0.716 +/- 0.384) microg/L (mild poisoning) respectively and the difference was statistically significant (P < 0.01). But the severity of the clinical status did not seem to be closely correlated to the level of urinary TMT-cl (F = 1.88, P > 0.05). In the severe poisonings, there were no differences in urinary TMT-cl on day 4 after poisoning from day 1 (P > 0.05). In contrast, urinary TMT-cl was decreased significantly on day 4 than on day 1 in mild and moderate poisonings (P < 0.01). On day 21, levels of urinary TMT-cl of all the poisonings were higher than those of the workers exposed to TMT-cl who had no clinical status (P < 0.01). Blood potassium levels of exposed group was 77.3% which was significantly lower than normal value (P < 0.01). The concentration of blood potassium was lower than normal value (3.5 mmol/L) and was correlated with the severity of the clinical status (F = 4.45, P < 0.05). Level of urinary TMT-cl of exposed group was negatively correlated with blood potassium (r = -0.4456, P < 0.01).

CONCLUSIONLevel of urinary TMT-cl can be used as exposure biomarker of TMT-cl poisoning. Blood potassium is an early biomarker of effect for TMT-cl poisoning so as to find poisoning population early.

Adult ; Biomarkers ; blood ; urine ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Potassium ; blood ; Trimethyltin Compounds ; poisoning ; urine ; Young Adult

OBJECTIVETo investigate the effects of pre-treatment of alpha-ketoglutarate (alpha-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents.

METHODSThe LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence alpha-KG given po, ip or iv. alpha-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of alpha-KG (protected animals) and LD50 of KCN in the absence of alpha-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) alpha-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po).

RESULTSPI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with a-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg alpha-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg alpha-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg alpha-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of alpha-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of alpha-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of alpha-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of alpha-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of alpha-KG.

CONCLUSIONSCyanide antagonism by alpha-KG is best exhibited when both alpha-KG and KCN are given by po route. The protective effect of a-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of alpha-KG as an alternative cyanide antidote.

Administration, Oral ; Animals ; Antidotes ; administration & dosage ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Injections, Intravenous ; Injections, Subcutaneous ; Ketoglutaric Acids ; administration & dosage ; Lethal Dose 50 ; Male ; Mice ; Potassium Cyanide ; poisoning ; Rats ; Rats, Wistar

OBJECTIVE: Morphologic features of the corpse of rabbits died of potassium intoxication were studied in order to elucidate an objective evidence for forensic determination of death caused by potassium intoxication. METHODS: Macroscopic, microscopic, and ultrastructural (by transmission electron microscopy) changes were observed in the heart, brain, and kidney of rabbits killed by intravenous push or continuous infusion at 100 drips per minute with 0.3% and 1% KCl, respectively. Normal rabbits without any treatment killed by bleeding were used as controls. RESULTS: Macroscopically, cardiac dilatation and congestion/stasis as well as ischemic and hypoxic changes in various organs were observed in rabbits died of potassium injection. Microscopically and ultrastructurally, there were destruction of the cardiac fibers with thickening, concentrating, or disappearing of the Z-line, constriction of the glomerular capillaries, enlargement of the Bowman capsule, thinning and fusion of foot processes, as well as apoptosis with phagocytosis in brain observed, particularly in the group infused with 1% KCl. CONCLUSION The morphologic changes observed in the heart and kidney appear to be characteristic, supporting death caused by potassium intoxication.
Animals ; Apoptosis ; Brain/pathology* ; Cadaver ; Capillaries/pathology* ; Forensic Pathology ; Injections, Intravenous/methods* ; Kidney Glomerulus/pathology* ; Male ; Myocardium/pathology* ; Phagocytosis ; Postmortem Changes ; Potassium/poisoning* ; Potassium Chloride/administration & dosage* ; Rabbits