Introduction: Cocaine body packing, the internal concealment of cocaine for transportation between countries, may expose to life-threatening intoxications. No data is currently available on the pharmacokinetics of cocaine and its metabolites when a packet rupture occurs in a body packer. Case report: We report the first pharmacokinetic data associated with a severe cocaine intoxication in a body packer, resulting in cardiac arrest. Massive concentrations of cocaine (observed maximal concentration: 1.66 mg/L, 1 hour after the cardiac arrest) were measured in plasma up to about 15 hours, suggesting a prolonged absorption due to a slow-release in the gastrointestinal tract despite surgical extraction of the packets. Apparent cocaine elimination half-life was 7.6 hours. Conclusion: A prolonged apparent cocaine elimination half-life has been observed. Further pharmacokinetic studies are needed to understand better the pathophysiology of acute cocaine intoxication in body packers.

Few data exist on potentially adverse metaxalone (Skelaxin®) ingestions in adults. All metaxalone ingestions involving patients aged ≥20 years during 2000-2006 were retrieved from Texas poison control centers. Exclusion criteria were lack of follow-up or multiple substance ingestion. Cases were analyzed for selected demographic and clinical factors. Of the 142 patients, 66.2% were female. Dose ingested was reported for 61 patients. Of those cases with a reported dose, distribution by management site was 29.5% on-site, 59.0% already at/en route to health care facility, and 11.5% referred to health care facility. Final medical outcome was ‘no effect’ for 50.8% cases, ‘minor effect’ for 31.1%, and ‘moderate effect’ for 18.0%. The more common adverse clinical effects reported were drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), nausea (4.9%), dizziness (4.9%), slurred speech (4.9%), and tremor (4.9%). A moderate medical outcome occurred in 13.6% of ingestions of ≤2400 mg and 20.5% of ingestions of >2400 mg. Management involved a health care facility in 18.2% of ingestions of ≤2400 mg and 100.0% of ingestions of >2400 mg. This study found that adult ingestions of higher doses of metaxalone, particularly >2400 mg, were associated with more serious medical outcomes and were managed at health care facilities. This study also proposes triage guidelines for when ingestions can be safely managed at home.

Pyrethroid insecticides are very widely used in agriculture and household due to high effectiveness and low toxicity to humans. We have described a case of a fatal oral intoxication with decis, the insecticide containing pyrethroid (deltamethrin) in a hydrocarbon base. Pyrethroids, including deltamethrin, undergo rapid biotransformation by liver enzymes, which limit their systemic toxicity. Thus, we assume that in the presented case, fatal outcome of poisoning with decis was rather connected with toxic effects of hydrocarbon base (solvent naphtha) than with deltamethrin action. In the described case, detection of aromatic hydrocarbons in blood and lung tissue and their metabolites in urine confirms that these substances were absorbed from gastrointestinal tract to the systemic circulation. Predominant among the clinical outcomes in our patient was profound depression of CNS with apnea, which could be connected with narcotic action of organic solvents. The cardiac arrest was in mechanism of asystolia with prior non-responsive to catecholamines bradycardia and vascular collapse. We connect it with hydrocarbon-induced cardiotoxicity. It is worth remembering that many pyrethroid-containing insecticides are formulated in a hydrocarbon base. Intoxication with such preparations should always be considered not only as poisoning with pyrethroid alone but also as intoxication with hydrocarbons.

The toxicological effect of the aqueous extract of fresh, dried and boiled berries of Solanum aculeastrum Dunal at 1, 10 and 25 mg/kg body weight was investigated in male Wistar rats for 28 days. The parameters used were the body weight of the animals and absolute weights of the organs, haematological parameters, renal and liver functional endpoints. The animals gained appreciable weight and showed no signs of clinical toxicity. The dried (DB), boiled dried (BDB), fresh (FB) and boiled fresh berry (BFB) extracts reduced (p < .05) the heart-, liver- and spleen-body weight ratio of the animals whereas that of the lung was not altered. The kidney and testes-body weight ratios were specifically altered by the different extract. All these were not accompanied by any histomorphological changes. The extracts did not alter (p > .05) the levels of RBC, Hb, PCV and albumin of the animals. The platelets were decreased by the DB and FB whereas BFB increased this parameter. The FB and BFB at all the doses also reduced the mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) of the animals. With the exception of the FB where the creatinine and chloride levels decreased, other extracts did not alter the level of these kidney parameters. Only FB increased the levels of uric acid and urea. All the extract decreased the serum alanine aminotransferase (ALT) of the animal. The levels of total protein, globulin, total and conjugated bilirubin were not altered by DB and BDB whereas these indices were increased by FB and BFB. The DB and BDB increased the serum alkaline phosphatase (ALP) activity whereas FB decreased the activity of the enzyme. In contrast, DB and BDB decreased the serum aspartate aminotransferase (AST) activity of the animals whereas FB and BFB increased the activity of the enzyme. The FB and BFB also increased the levels of potassium, magnesium and phosphorus of the animals. Overall, the alterations in the biochemical parameters by the various extracts of S. aculeastrum berries at these doses indicated that the normal functioning of these organs may be adversely affected. However, drying and boiling might reduce the toxic effect of the berries.

Background: Sulfur mustard (SM) is a chemical warfare agent that can cause serious pulmonary complications. This study was designed to determine serum highly sensitive C-reactive protein (hs-CRP) and evaluate its correlation with lung function parameters in patients with chronic obstructive pulmonary disease (COPD) due to SM poisoning. Methods: Fifty consecutive SM patients with stable COPD and a mean age 46.3 ± 9.18 years were enrolled in this cross sectional study. Thirty healthy men were selected as controls. Lung function parameters were evaluated. Serum hs-CRP by immunoturbidometry assay was measured in both the patients and controls. Results: In the case group, the mean forced expiratory volume in one second (FEV1) was 2.14 ± 0.76 L (58.98% ± 17.51% predicted). The mean serum hs-CRP was 9.4 ± 6.78 SD and 3.9 ± 1.92 SD mg/L in the cases and controls, respectively, with significant statistical differences (p < .001). There was negative correlation between the serum hs-CRP and FEV1 levels (p = .01). The serum hs-CRP levels were also correlated with Global Initiative for Chronic Obstructive Lung disease (GOLD) stages (r = .45, p < .001). Conclusions: Our findings suggest that the serum hs-CRP level is increased in SM patients with COPD and may have a direct correlation with disease severity. It may then be used as a marker for the severity of COPD in patients with SM poisoning.

Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for infant and children diseases. It is concentrated in breast milk and is absorbed by the infant. The purpose of the present study was to investigate the effects of maternal nicotine exposure during lactation on breast-fed rats and at the pubertal age by measuring biomarkers of oxidative stress. Particularly, a new parameter, the thiol concentration was evaluated. Two groups of lactating Wistar rats were used. For the first group, female rats were given an intraperitoenal injection of nicotine or saline (2 mg/kg per day) during lactation. For the second group, we reproduced the same process described above and then the female and male pups were separately kept after weaning without any treatment until the puberty (at 45 days of age). In the liver and lung of the offspring, we examined the malondialdehyde (MDA) level, the thiol concentration, and the activities of two antioxidant enzymes: superoxyde dismutase (SOD) and catalase (CAT). In the plasma, alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were measured. For rats aged 21 days, the treatment significantly reduced the thiol concentration, SOD, and CAT activities but increased MDA level, AST, and ALT activities. For rats aged 45 days, the males and females did not react the same way. In fact, the males were more affected. These results indicate that maternal nicotine exposure during the lactation period induces oxidative stress in the liver and lung of lactating offspring, which is maintained until the puberty, especially for the male rats.

In this study, African Catfish (Clarias gariepinus) were cultured in water contaminated with phthalate, benzene and cyclohexane (10 µg/mL), respectively, over a period of 65 days. They were, thereafter, used as protein source to formulate feed for albino rats (Wistar strain) for 28 days. The weights of the body and selected tissues of the rats were monitored and standard enzyme assays were conducted for some enzymes in the serum. Results showed that rats in cyclohexane group gained 58% whereas the control group gained 46% of body weight. Liver weight (absolute and relative) of test rats were found to be significantly lower than that of control (p < .05). Enzyme activity of serum of test rats was found to be significantly higher than that of control (p < .05). Experimental evidence suggests leakage of enzymes from the liver to the serum, thus the elevated serum enzyme activity and that the contaminants may damage the liver.

The aim of our study was to determine the role and dynamics of oxidative and nitrosative stress, as well as superoxide dismutase (SOD) and catalase activity in the hepatocytes and erythrocytes in early phase of acute lindane intoxication. Male Wistar rats were divided into groups: control, dimethylsulfoxide and lindane-treated groups (L, 8 mg/kg, intraperitoneally). Animals were sacrificed 0.5 and 4 hours after treatment (L_0.5 and L₄ groups, respectively). Oxidative and nitrosative stress parameters and antioxidant enzymes were determined spectrophotometrically. Liver and plasma thiobarbituric acid reactive substances (TBARS) concentration were significantly increased 0.5 after lindane administration (p < .01), with subsequent additional rise within 4 hours (p < .01), while plasma nitrite + nitrate level was significantly higher only 4 hours after lindane treatment. Total liver SOD activity was significantly increased in L₄ group in comparison with control group (p < .01). In conclusion, oxidative and nitrosative stress play an important role in early phase of acute lindane hepatotoxicity. Antioxidant capacity of hepatocytes is partly increased, due to an adaptive increase in SOD activity.

The principal toxic ingredients of aconite roots include aconitine, mesaconitine and hypaconitine, which are known cardiotoxins and neurotoxins. A 58-year-old man took a decoction of 11 g each of processed ‘chuanwu’ (the main root of Aconitum carmichaeli) and processed ‘caowu’ (the root of A. kusnezoffii) as treatment for his neck pain. One hour later, he experienced numbness of tongue and the four limbs, generalized weakness, nausea, vomiting, diarrhoea and dizziness. Three hours after ingestion, he was admitted to hospital. His blood pressure was 106/53 mmHg and heart rate 65 beats/min. Six hours after ingestion, he became hypotensive (systolic blood pressure <100 mmHg) with bradycardia (heart rate <60 beats/min). As treatments for the hypotension, he was given intravenous infusions of 0.9% saline (125 mL/hour) for 15 hours (7-21 hours after ingestion) and dopamine (3 µg/kg/min) for 36 hours (10-45 hours after ingestion). He was given atropine 0.6 mg intravenously 7 and 24 hours after ingestion. He was hypotensive for 31 hours (6-36 hours after ingestion), with a systolic blood pressure of 84-106 mmHg (mean 93.5) and a diastolic blood pressure of 40-59 mmHg (mean 51.8). He had bradycardia for 36 hours (6-41 hours after ingestion), with a heart rate of 45-68 beats/min (mean 56.5). On discharge (48 hours after ingestion), his blood pressure was 117/82 mmHg and heart rate 70 beats/min. In patients with aconite poisoning, prolonged hypotension and sinus bradycardia may occur and supportive therapy with close monitoring of blood pressure and cardiac rhythm are essential.

In order to probe into the effects of garlic oil (GO) on the hepatic CYP2E1, CYP1A2 and CYP3A, male Kun-Ming mice were treated with GO (100 mg/kg body weight) or corn oil for 1 day or consecutive 60 days, respectively, and then the protein expressions and the activities of the enzymes were examined. GO did not alter the physical activities of mice and did not induce lesion to the liver. However, it dramatically inhibited the activities and protein levels of hepatic CYP2E1 and 1A2, but not CYP3A. In addition, we noticed that the inhibition of CYP2E1 and 1A2 by GO was more potent in group of 1 day treatment than those in group of 60 days treatment. Compared with the respective control value, the protein levels of CYP2E1 were decreased by 87.40% (p < .01) and 62.26% (p < .01) by 1 day and 60 days of GO treatment, respectively, while the CYP1A2 protein levels were decreased by 70.76% (p < .01) and 41.49% (p < .01), respectively. These data indicated that the mice could adapt to the prolonged treatment, which might be one reasonable explanation for the conflicting data in the literature. The CYP2E1 and 1A2 suppression might contribute to its hepatoprotection, and data about CYP3A indicated that GO was unlikely to alter the metabolism of the concomitantly used drugs.

It is well documented that enhanced garlic (Allium sativum) consumption leads to decrease in the cancer incidences. Diallyl sulfide (DAS), one of the components of garlic, induces cytotoxicity and apoptosis in many cancer cell lines. The present studies are focused on the in vivo effects of DAS on leukemia WEHI-3 cells in the BALB/c mice. We examined the effects of DAS on the cytotoxicity of WEHI-3 cells and results indicated that DAS decreased the percentage of viable WEHI-3 cells and these effects are dose-dependent. We examined the effects of DAS on WEHI-3 in vivo and the results indicated that DAS decreased the percentage of Mac-3 and CD11b, indicating that the differentiation of the precursor of macrophage cells was inhibited. DAS stimulated the percentage of CD3 and CD19, indicating that the differentiation of the precursor of T and B cells promoted. The weights of liver and spleen indicated that DAS decreased the weight of these organs after being compared to the control groups. One of the major characteristic of WEHI-3 leukemia is the enlarged spleen in murine after intraperitoneal (i.p.) injection of WEHI-3 cells. In conclusion, DAS affects WEHI-3 cells both in vitro and in vivo.

Acute renal failure is a recognized manifestation of paracetamol toxicity, but comparatively little data is available concerning its onset and duration. The present study sought to characterize the time course of rising serum creatinine concentrations in paracetamol nephrotoxicity. Renal failure was defined by serum creatinine concentration ≥150 µmol/L (1.69 mg/dL) or ≥50% increase from baseline. Serum creatinine concentrations and alanine aminotransferase activity were considered with respect to the interval after paracetamol ingestion. There were 2068 patients with paracetamol overdose between March 2005 and October 2007, and paracetamol nephrotoxicity occurred in 8 (0.4%). All had significant hepatotoxicity, and peak serum alanine aminotransferase activity occurred at 2.5 days (2.2 to 2.9 days) after ingestion. Peak serum creatinine concentrations did not occur until 5.5 days (4.4 to 5.9 days) after ingestion (p = .031 by Wilcoxon test). Serum creatinine concentrations slowly restored to normal, and renal replacement was not required. In this patient series, rising serum creatinine concentrations only became detectable after more than 48 hours after paracetamol ingestion. Therefore, renal failure might easily be missed if patients are discharged home before this. Further work is required to establish the prevalence of paracetamol-induced nephrotoxicity, and its clinical significance.