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The aim of this study was to evaluate the pretreatment hepatoprotective effect of the extract of marine-derived fungus Trichurus spiralis Hasselbr (TS) isolated from Hippospongia communis sponge on hepatotoxicity. Twenty-eight male Sprague-Dawley rats were divided into four groups (n = 7). Group I served as -ve control, group II served as the induced group receiving subcutaneously for seven days 0.25 mg heavy metal mixtures, group III received (i.p.) TS extract of dose 40 mg for seven days, and group IV served as the protected group pretreated with TS extract for seven days as a protection dose, and then treated with the heavy metal-mixture. The main pathological changes within the liver after heavy-metal mixtures administrations marked hepatic damage evidenced by foci of lobular necrosis with neutrophilic infiltration, adjacent to dysplastic hepatocytes. ALT and AST measurements show a significant increase in group II by 46.20% and 45.12%, respectively. Total protein, elevated by about 38.9% in induction group compared to the -ve control group, in contrast to albumin, decreased as a consequence of metal administration with significant elevation on bilirubin level. The results prove that TS extract possesses a hepatoprotective property due to its proven antioxidant and free-radical scavenging properties.

The detrimental health effects of cadmium (Cd) were first described in the mid 19th century. As part of industrial developments, increasing usage of Cd has led to widespread contamination of the environment that threatens human health, particularly today. Rather than acute, lethal exposures, the real challenge in the 21st century in a global setting seems to be chronic low Cd exposure (CLCE), mainly from dietary sources. Ubiquity of Cd makes it a serious environmental health problem that needs to be thoroughly assessed because it already affects or will affect large proportions of the world's population. CLCE is a health problem that affects increasingly organ toxicity, especially nephrotoxicity, without a known threshold, implying that there is currently no safe limit for CLCE. In this chapter, we summarize current knowledge on the sources of Cd in the environment, describe the entry pathways for Cd into mammalian organisms, sum up the major organs targeted by acute or chronic Cd exposure and review the impact of Cd on organ function and human health. We also aim to put early pioneering studies on Cd poisoning into perspective in the context of recent ground-breaking prospective long-term population studies, which link CLCE to leading causes of diseases in modern societies - cancer, diabetes, and cardiovascular diseases, and of state-of-the-art studies detailing cellular and molecular mechanisms of acute and chronic Cd toxicity.

Introduction: Melanotan products are currently purchased over the Internet and are designed to induce melanogenesis to create sunless tanning as well are used as sexual stimulants. We report a novel case of systemic toxicity with sympathomimetic excess and rhabdomyolysis after use of Melanotan II., Case Report: A 39 year-old Caucasian male injected subcutaneously 6 mg of Melanotan II purchased over the Internet in an attempt to darken his skin during wintertime. This dose was six times the recommended starting dose per the patient. In the emergency department two hours post injection, he complained of diffuse body aches, sweating, and a sensation of anxiety. Vital signs included BP 151/85 mmHg, HR 130 bpm that peaked at 146 bpm, and temperature of 97.8°F. Physical exam demonstrated a restless and anxious appearing male with mydriasis, diaphoresis, tachycardia, and diffuse muscle tremors. Pertinent laboratory values were creatinine 2.25 mg/dL, CPK 1760 IU/L, troponin 0.23 ng/mL, WBC 19.1 k/μL. Urinalysis demonstrated 3 + blood with red cell casts but 0-2 RBC/hpf. Qualitative urine drug screen was negative for metabolites of cocaine and amphetamines but positive for opiates. The patient received benzodiazepines for agitation and anxiety and had improvement in his symptoms. He was admitted to the ICU and during hospitalization his CPK elevated to 17773 IU/L 12 hours later. He continued to receive intravenous fluids with sodium bicarbonate for rhabdomyolysis and his CPK decreased to 2622 IU/L with improvement of creatinine to 1.23 mg/dL upon discharge from the ICU after 3 days. The substance, which he injected, was analyzed via mass spectrometry and was confirmed to be Melanotan II when compared with an industry purchased standard sample., Discussion: Melanotan products are purchased via the Internet and have three main formulations (Melanotan I, Melanotan II, and bremelanotide). Melanotan I increases melanogenesis and eumelanin content to produce sunless tanning. Melanotan II also increases skin pigmentation but also produces spontaneous penile erections and sexual stimulation. Bremelanotide is a variation of Melanotan II that is specifically designed for sexual stimulation. This unique case highlights the potential of systemic toxicity with sympathomimetic excess, rhabdomyolysis, and renal dysfunction from Melanotan II use., Conclusion: Melanotan II use resulted in systemic toxicity including apparent sympathomimetic symptoms, rhabdomyolysis, and renal dysfunction.

The present study investigated the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium to evaluate terminal cardiac function in routine forensic casework with particular regard to fatal drug intoxication (n = 18; sedative-hypnotics, n = 10; methamphetamine, n = 8), hypothermia (cold exposure, n = 13), and hyperthermia (heatstroke, n = 10), compared with that in acute ischemic heart disease (AIHD, n = 35) and congestive heart disease (CHD, n = 11) as controls (total n = 87; within 48 h postmortem). Quantitative analyses of myocardial ANP and BNP messenger RNA demonstrated that their expressions in bilateral atrial and ventricular walls were high in methamphetamine intoxication and hypothermia, comparable to those in AIHD and CHD, but were low in sedative-hypnotic intoxication and hyperthermia. In pericardial fluid, both ANP and BNP levels were increased in hypothermia, while CHD cases had an elevated BNP level, and ANP level showed a tendency to increase in hyperthermia; however, immunohistochemistry showed no evident differences in myocardial ANP and BNP among the causes of death. These findings suggest terminal high cardiac strain in methamphetamine intoxication, decreased cardiac strain in sedative-hypnotic intoxication and hyperthermia (heatstroke), and persistent congestion in hypothermia (cold exposure).

As a result of survey in process of treatment of 100 patients with severe acute poisoning of ethanol on the background of the toxic damage of the liver set that the severity of poisoning depends on the duration abuse of alcohol (Binge drinking). Inclusion in the intensive care infusion hepatoprotector remaxol compared with ademetionine leads to a faster dynamics of improvement of the patients condition, evaluated by the scale assessing the severity APACHE II. Also found, Use of remaxol can reduce development of complications such is alcoholic delirium on the background of long-term abuse of alcohol in percentage from 31.9% to 16%, as well as reduces the time of stay of patients in the departments of the resuscitation and intensive care unit from 7,3±0,6 to 5,6±0,3 days and duration of treatment of patients in the hospital from 11,8±1,1 to 9,0±0,4 days.

The article deals with the materials, which have been received in the process of the examination and treatment of 44 patients with acute severe methadone poisonings. It has been revealed, that gravity of these patient's condition depends on intensity of hypoxia due to breath deficiency because of the methadone. The development of hypoxia, in its turn, cause violations of antiradical protection system and intensification of processes of peroxide lipid oxidation. It has been registered that the including of reamberin into the complex program of the intensive therapy of acute severe methadone poisonings lead to a more rapid restoration of antiradical protection system and to a decrease of activity of processes of peroxide lipid oxidation. The correction of hypoxia and free-radical violations led to improvement of the acute poisonings clinic, what had been characterized by a decrease of coma-period duration, duration of treatment with artificial lung ventilation, a decrease of secondary lung complications and a decrease of lethality.

The results of forensic medical investigations of 100 corpses of the persons who died from combined intoxication with two and more poisons are presented. They were compared with clinical observations and summarized uisng the methods of tanatogenetic analysis. The main variants of fatal combined poisoning and the underlying tanatogenetic mechanisms were categorized into cardiac (disturbances of rhythm and conductivity, progressive hypotension, flabby heart muscle, extensive fragmentation of cardiomyocytes), cerebral (coma and massive death of brainstem neurons), and pulmonary (of pneumonia- or pulmonary oedema-type with fibrin precipitation in the alveoli and formation of hyaline membranes). This classification was supplemented by a variety of combinations of the above variants with necrotic nephrosis and disseminated intravascular coagulation syndrome. It is concluded that the results of this study may be of use for forensic medical diagnostics of combined poisoning and the elucidation of the contribution of individual toxic substances to the fatal outcome bearing in mind the low informative value of the relevant forensic medical data.

This article deals with materials, which have been received in the process of an examination and treatment of 69 patients with acute severe azaleptin (leponeks) poisonings. On the base of clinic data the special features of clinic of acute severe azaleptin (leponeks) poisonings has been shown. It has been registered that the using of substrate antihypoxant reamberin in the intensive therapy of severe forms of acute azaleptin (leponeks) poisonings led to significant improvement of clinic manifestations, such as a coma period duration, a duration of artificial lung ventilation, a period of holinolitic psychiatric violations and a decrease of lethal poisonings.

Background and Aim: Copper sulphate poisoning, while unusual in the West, is not rare in the Indian subcontinent, and mostly suicidal in intent. Unfortunately, data available on copper sulphate poisoning is limited. This study was planned to identify common presentations and complications of copper sulphate poisoning, and biochemical parameters that predict outcomes in these patients., Materials and Methods: A retrospective analysis of 35 patients presenting with copper sulphate poisoning over a period of 10 years (2001-2010) was performed, based on review of their medical records. Paediatric cases and patients with concomitant poisoning with other substances were excluded. Clinical presentation, laboratory parameters, complications and treatment modalities were studied., Results: Of the 35 cases, 23 were females (65.71%). Mean age was 29.18 ± 10.77 years. Vomiting was the commonest symptom (85.71%) followed by diarrhoea (45.71%), epigastric pain (42.86%) and rectal passage of blood (31.43%). Fourteen (40%) patients had pre-existing psychiatric disease. Medical signs included pallor (37.14%) and icterus (37.14%). Major complications included hemolysis (68.57%), renal failure (51.43%), acute hepatitis (45.71%) and upper gastrointestinal bleed (40%). Mean serum copper at presentation was 104.53 ± 56.67 μg/dL; mean methemoglobin level was 9.59 ± 8.28%. Twenty-seven patients survived yielding a mortality rate of 22.9%. Peak serum aspartate and alanine aminotransferases were significantly lower (223.8 ± 247.3 U/L, 66.3 ± 92.2 U/L) in survivors compared to non-survivors (489.6 ± 374.0 U/L, 192.9 ± 168.7 U/L; p = 0.03, p < 0.01, respectively). Analysis by receiver operating characteristic (ROC) curve showed sensitivities of 100% and 85.7%, and specificities of 73.1% and 69.2%, respectively for peak serum alanine aminotransferase levels greater than 55 U/L, and peak serum aspartate aminotransferase levels greater than 234 U/L in predicting mortality., Conclusion: Copper sulphate is a potent poison that can involve multiple organ systems. Elevated levels of serum aspartate and alanine aminotransferases beyond the aforementioned values can identify patients at greater risk of mortality, allowing for institution of aggressive treatment.

The authors present a case of a college student who suffered acute gallium poisoning as a result of accidental exposure to gallium halide complexes. This is extremely rare and has never been reported in the literature. Acute symptoms after the incident, which initially presented as dermatitis and appeared relatively not life-threatening, rapidly progressed to dangerous episodes of tachycardia, tremors, dyspnea, vertigo, and unexpected black-outs. Had there been effective emergency medical care protocols, diagnostic testing, treatment and antidotes, the latent manifestations of irreversible cardiomyopathy may have been prevented. Given how quickly exposure led to morbidity, this article aims to raise an awareness of the toxic potential of gallium. This has particular relevance for workers involved in the production of semiconductors where there is a potential for accidental exposure to gallium by-products during device processing. It may also have implications for dentists who use gallium alloys to replace mercury containing amalgam. In the absence of threshold limit values and exposure limits for humans, as well as emergency medical guidelines for treatment of poisoning, the case calls on the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration to establish guidelines and medical management protocols specific for gallium., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The objective of the present work was to develop the forensic medical criteria for chronic narcotic intoxication based on the results of morphological studies. The internal organs from 179 cadavers were available for the examination following death from acute poisoning with narcotic substances or as a result of chronic narcotic intoxication. The studies were carried out with the use of routine histological staining techniques and an immunohistological method. The data obtained provided a basis for the development of criteria to be employed in forensic medical diagnostics of acute poisoning with narcotic drugs and chronic narcotic intoxication. These criteria include ischemia of cerebral neurons, pulmonary emphysema with the formation of foreign body-type granulomas and fibrin/erythrocyte thrombi, morphological signs of ventricular fibrillation, the picture of bacterial endocarditis, follicular hyperplasia of the lymphoid organs, chronic portal hepatitis, and nodular degeneration of the adrenal cortex associated with its atrophy.

The objective of this study was to assess the patterns, severity and clinical outcome of poisoning incidents. A prospective assessment was conducted over a period of 1 year in tertiary-care teaching hospitals. Glasgow coma scale (GCS), poisoning severity score (PSS), and snake bite severity score (SSS) were used to predict the severity of poisoning, and then compared to the clinical outcome. The study involved 212 patients with a mean age of 26.7±12.7 years. Pesticides were found to be the most common poisoning agents. The incidents of intentional poisoning (n=178) were higher than accidental (n=34) poisoning. Poisoning incidents were higher in male population (n=132) compared to female population (n=80). The poisoning incidents were predominantly higher among literates (n=155). The poisoning incidents were higher in rural areas (n=129), followed by urban (n=53) and semi-urban (n=30) areas. The poisoning incidents were highest in the middle class population (n=108), followed by poor class (n=101) and rich class (n=3) population. A majority of patients whose severity of illness was predicted to be mild to moderate recovered from the poisoning. In contrast, patients whose illness was predicted to be severe were either discharged with severe morbidity or deceased. There was a moderate correlation between GCS and PSS scoring systems (r=0.51, p<0.001).

The effect of lyophilised aqueous extract of Telfairia occidentalis (TO) on induced cyanide toxicity in rats was investigated. Twenty 3-week old male wistar albino rats were randomly distributed into one control and three treatment groups of five rats each: control group (group1), group treated with 3mg/kg body wt of cyanide only (group2), group treated with 3mg/kg body wt. each of cyanide and extract (group3), and a group treated with 3mg/kg Body wt of extract only (group4) were used for the investigation. Cyanide toxicity reduced both food and water intake (p<0.05), while the food intake was improved in group3, this effect of the extract on food was not observed on water intake. Cyanide reduced average body weight of rats significantly (p<0.05). The reduction effect of cyanide on body weight was countered by Telfairia occidentalis extract. The extract did not have an observable effect on rats' body weight. Ocular lesion was observed in 67% of rats in group2 . This ocular effect of cyanide was mitigated significantly by Telfairia occidentalis as only 17% of the rats in group3 had ocular lesion. Cyanide toxicity produced nasal discharge in 39% of the rat population in group2 while there was a partial but considerable reduction (21%) in the severity of nasal discharge in group 3. There was no significant difference (p>0.05) in the organ/body wt.ratio between the treatments and the control groups for all the organs examined in the study. Biochemical analysis of liver enzymes showed that cyanide (group2) damaged the liver as there was significantly elevated presence (p<0.05) of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALP) above those of the control group. The damaging effect of cyanide on the liver was ameliorated by Telfairia occidentalis considerably.Histopathological effect of cyanide toxicity on the organs examined included multifocal degeneration and necrosis of the liver, mild kidney congestion and congestion of the brain. These effects were moderated mildly by Telfairia occidentalis. Group 4, treated with the vegetable alone had none of the observed histopathology in the organs examined. We concluded that lyophilised aqueous extracts of Telfairia occidentalis showed good potential as a safe antidote for cyanide poisoning when administered concomitantly or very shortly after ingestion of sub-lethal dose of cyanide. However, further bioassay guided fractionation and analytical studies are needed to identify the actual chemical compound or molecule in the vegetable responsible for or associated with the observed effects.

The B subunit (RTB) of ricin toxin is a galactose-/N-acetyl galactosamine-specific lectin that promotes attachment and entry of ricin into host cells. RTB is also the archetype of the so-called R-type lectin family, whose members include haemagglutinins of botulinum neurotoxin (BoNT) progenitor toxins, as well as the binding subunits of cytolethal distending toxins. Although RTB is an appealing subunit vaccine candidate, as well as a potential target for immunotherapeutics, the degree to which RTB immunization elicits protective antibodies against ricin toxin remains unresolved. To address this issue, groups of mice were immunized with RTB and then challenged with 5×LD(50)s of ricin administered intraperitoneally. Despite high RTB-specific serum antibody titers, groups of RTB immunized mice were only partially immune to ricin challenge. Analysis of a collection of RTB-specific B cell hybridomas suggested that only a small fraction of antibodies against RTB have demonstrable neutralizing activity. Two RTB-specific neutralizing monoclonal IgG(1) antibodies, 24B11 and SylH3, when passively administered to mice, were sufficient to protect the animals against a 5×LD(50) dose of ricin. Both 24B11 and SylH3 blocked ricin attachment to terminal galactose residues and prevented toxin binding to the surfaces of bone marrow-derived macrophages (BMM), suggesting that they function by steric hindrance and recognize epitopes located on RTB's carbohydrate recognition sub-domains (1α or 2γ). These data raise the possibility of using specific RTB sub-domains, rather than RTB itself, as antigens to more efficiently elicit neutralizing antibodies and protective immunity against ricin., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of work was to test the using of reamberin on patients with cerebral deficiency due to severe forms of acute poisonings. The investigation was made on 60 patients (38 men and 22 women), whose average age was 34.7 +/- 2.6 (for men) and 28.4 +/- 3.2 (for women). The main group was divided into two parts, which had compared age, sex and gravity of condition. The first one was given reamberin with standart therapy (I - 32 patients), the second - only standart therapy (II - 28 patients). It was revealed that using of reamberin in complex therapy of acute cerebral deficiency lead to decrease of intensity of cerebral deficiency and to increase of speed of cerebral activity rehabilitation. These changes lead to improvement of clinic tendency of cerebral deficiency, what was illustrated by decrease of comatose period from 55.0+/- 2.2 to 33.0 +/- 2.6 hours, decrease of the time of being in reanimatology department from 69.1+/- 3.6 to 53.4+/- 4.3 hours.

Objective: To evaluate records of dogs exposed to zinc phosphide rodenticides and characterize the patient population, including breed, sex, age, body weight, time since exposure, development of clinical signs, clinical signs observed, treatments performed, veterinary care received, outcome, and overall prognosis., Design: Retrospective case series., Animals: 362 dogs with presumed zinc phosphide exposure., Procedures: An electronic computer database from an animal poison control center was searched to identify dogs that ingested zinc phosphide between November 2004 and July 2009., Results: Accurate information regarding development of clinical signs was available in 94.5% (342/362) of cases. Over half the dogs (58.8% [201/342]) did not develop clinical signs, and specific clinical signs were reported for the remaining 41.2% (141/342) of dogs. There were 180 total clinical signs recorded for these 141 dogs, with some dogs having developed > 1 category of clinical signs. Clinical signs involving the gastrointestinal tract were the most commonly reported type of clinical sign (66.7% [n = 120/180 reported signs]), followed by generalized malaise (17.8% [32/180]), CNS signs (8.9% [16/180]), respiratory signs (3.3% [6/180]), and cardiovascular signs (1.7% [3/180]). Approximately 65% (234/362) of patients received veterinary care (including decontamination via induction of emesis, gastric lavage, or activated charcoal administration), and of these dogs, 51.3% (120/234) were hospitalized. For the 296 dogs for which survival data were available, the survival rate was 98.3% (291/296)., Conclusions and Clinical Relevance: Overall, the prognosis for zinc phosphide toxicosis was good. Zinc phosphide rodenticide toxicosis is a potential public health concern, and veterinary staff should be aware of this commonly used rodenticide.

Aluminum phosphide (ALP), a widely used insecticide and rodenticide, is also infamous for the mortality and morbidity it causes in ALP-poisoned individuals. The toxicity of metal phosphides is due to phosphine liberated when ingested phosphides come into contact with gut fluids. ALP poisoning is lethal, having a mortality rate in excess of 70%. Circulatory failure and severe hypotension are common features of ALP poisoning and frequent cause of death. Severe poisoning also has the potential to induce multi-organ failure. The exact site or mechanism of its action has not been proved in humans. Rather than targeting a single organ to cause gross damage, ALP seems to work at the cellular level, resulting in widespread damage leading to multiorgan dysfunction (MOD) and death. There has been proof in vitro that phosphine inhibits cytochrome c oxidase. However, it is unlikely that this interaction is the primary cause of its toxicity. Mitochondria could be the possible site of maximum damage in ALP poisoning, resulting in low ATP production followed by metabolic shutdown and MOD; also, owing to impairment in electron flow, there could be free radical generation and damage, again producing MOD. Evidence of reactive oxygen species-induced toxicity owing to ALP has been observed in insects and rats. A similar mechanism could also play a role in humans and contribute to the missing link in the pathogenesis of ALP toxicity. There is no specific antidote for ALP poisoning and supportive measures are all that are currently available., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: Fomepizole is the antidote of choice in toxic alcohol poisonings. Potential side effects from frequent use of fomepizole were studied in a patient admitted 154 times with ethylene glycol (EG) poisoning. The intra-individual correlation between the serum-ethylene glycol (serum-EG) and the osmolal gap (OG) EG-kinetics, and other laboratory parameters were also studied., Methods: Combined pro- and retrospective collection of material from three different hospitals, and results from autopsy., Results: A 26-year-old female with a dissociative disorder was admitted with EG poisoning a total of 154 times. Her admission data revealed a median pH of 7.31 (range 6.87-7.49), pCO(2): 4.2 kPa (1.2-6.7) (32 mmHg [9-50]), HCO-3: 15 mmol/L (4-26) (15 mEq/L [4-26]), base deficit (BD): 10 mmol/L (- 4 to 27) (10 mEq/L [-4 to 27]), serum-creatinine 65 μmol/L (40-133) (0.74 mg/dL [0.45-1.51]), OG 81 mOsm/kgH(2)O (25-132), and serum-EG 44 mmol/L (4-112) (250 mg/dL [25-700]). She was treated with fomepizole 99 times, ethanol 60 times (with a combination of both six times), and dialysis 73 times. The correlation between serum-EG and OG was good (r(2) = 0.76). She was finally found dead outside hospital with an EG blood concentration of 81 mmol/L (506 mg/dL). An autopsy revealed calcium oxalate crystals in the kidneys, slight liver steatosis, and slight edema of the lungs., Discussion: The frequent use of fomepizole in this young patient was not associated with any detectable side effects; neither on clinical examination and lab screening, nor on the later autopsy. Regarding the sequelae from the repetitive EG-poisoning episodes, her kidney function seemed to normalize after each overdose. She was treated with buffer and antidote without hemodialysis 81 times without complications, supporting the safety of this approach in selected cases.

Drugs containing 5-acetylsalicylic acid (5-ASA) have been commonly used for inflammatory bowel diseases for more than half a century, but no case about overdose of suppository form of mesalazine which was taken both orally and rectally has been reported in the related literature up to now. In the present case, a 20-year-old male patient who took 14.5 g of mesalazine rectally and orally for suicide purpose is discussed. He was an ulcerative colitis patient and depressed about his illness and routine life traffic. Although it was hard for him to take the suppository form orally because of its bad taste and structure, he took it with the help of water. In the patient's colonoscopy, diffuse hyperemia and edema extending from the anal channel to the proximal rectal mucosa and a 1.5 cm diameter ulcer expanding from anal channel through the rectum were identified. No pathology was found in the upper gastrointestinal endoscopy. Routine laboratory examination was performed and no abnormality was identified in the patient's total blood account, biochemical parameters and full-urine examination. In the control rectoscopy applied to the patient 15 days later, recovery of the ulcer was observed and he was discharged to be followed in the psychiatry clinic.

Detailed postmortem examinations were performed on 167 free-ranging Eurasian Cranes (Grus grus) from Germany, collected between September 1998 and December 2008 to evaluate causes of death and diseases. The most common causes of mortality were traumatic injuries (n=105, 62.9%) from collisions with power lines (n=39, 23.4%) and wire fences (n=12, 7.2%). A group of 28 Eurasian Cranes (16.8%) died from organophosphate intoxication. Predation by White-tailed Sea Eagles (Haliaeetus albicilla) and red foxes (Vulpes vulpes) occurred in four cases (2.4%). Pathologic changes due to infectious diseases were associated with Aspergillus spp. (n=7, 4.2%), endoparasites (n=7, 4.2%), avian poxvirus (n=6, 3.6%), Mycobacterium spp. (n=2, 1.2%), and adenovirus infection (n=1, 0.6%). A severe Strigea spp. infection (n=1, 0.6%) and a leiomyosarcoma (n=1, 0.6%) were newly recognized diseases in Eurasian Cranes in this study.

Topoisomerase IIα (Topo IIα) has been implicated in the benzene-induced hemotoxicity in vitro. This study was to examine the effect of in vivo chronic benzene exposure on Topo IIα in human bone marrow mononuclear cells, and to further explore the mechanism underlying decreased Topo IIα expression in patients with chronic benzene exposure. Topo IIα activity, expression, and mRNA level assessed by DNA cleavage/relaxation assay, Western blot, and reverse transcriptase-PCR, decreased in patients with benzene exposure. These changes were accompanied by reduced histone H4 and H3 acetylation and H3K4 methylation, and increased H3K9 methylation in the Topo IIα promoter, which were evaluated by chromatin immunoprecipitation (ChIP) assay. In addition, there were alterations in mRNA levels of Topo IIα promoter regulatory factors such as SP1, ATF-2, SP3, NF-YA, NF-M, P53, C-MYB, C-JUN, and ICBP90. Our results demonstrate that Topo IIα expression was reduced in patients with chronic benzene exposure, which was accompanied by alterations in histone acetylation and methylation and regulatory factor mRNA levels of Topo IIα promoter., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Acquired methemoglobinemia is a common, potentially fatal syndrome that can occur as a result of exposure to numerous xenobiotics. A case report of a 14-month-old female who developed methemoglobinemia following a dapsone ingestion. The child was treated with numerous boluses of methylene blue and ultimately required a continuous infusion of methylene blue. The common causes of methemoglobinemia, as well as the underlying pathophysiology, diagnosis, and treatment strategies are discussed.

The basal ganglia and thalamus are paired deep gray matter structures that may be involved by a wide variety of disease entities. The basal ganglia are highly metabolically active and are symmetrically affected in toxic poisoning, metabolic abnormalities, and neurodegeneration with brain iron accumulation. Both the basal ganglia and thalamus may be affected by other systemic or metabolic disease, degenerative disease, and vascular conditions. Focal flavivirus infections, toxoplasmosis, and primary central nervous system lymphoma may also involve both deep gray matter structures. The thalamus is more typically affected alone by focal conditions than by systemic disease. Radiologists may detect bilateral abnormalities of the basal ganglia and thalamus in different acute and chronic clinical situations, and although magnetic resonance (MR) imaging is the modality of choice for evaluation, the correct diagnosis can be made only by taking all relevant clinical and laboratory information into account. The neuroimaging diagnosis is influenced not only by detection of specific MR imaging features such as restricted diffusion and the presence of hemorrhage, but also by detection of abnormalities involving other parts of the brain, especially the cerebral cortex, brainstem, and white matter. Judicious use of confirmatory neuroimaging investigations, especially diffusion-weighted imaging, MR angiography, MR venography, and MR spectroscopy during the same examination, may help improve characterization of these abnormalities and help narrow the differential diagnosis., (RSNA, 2011)

Background: High mortality in the 2001 US and recent European anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment., Methods and Results: Here, 24-h edema (ETx) and lethal (LeTx) toxin infusions were investigated for 96 hin sedated canines receiving mechanical ventilation. The initial study compared similarly lethal doses of ETx (n=8) or LeTx (n=15) alone. ETx was 24 times less lethal than LeTx, and the median time to death in nonsurvivors (n=6 and n=9, respectively) was shorter with ETx (42 vs 67 h; P=.04). Compared with controls(n=9), both toxins decreased arterial and central venous pressures and systemic vascular resistance and increased heart rate, cardiac index, blood urea nitrogen (BUN) level, creatinine (Cr) concentration, BUN:Cr ratio, and hepatic transaminase levels (P ≤ .05 for toxin effect or time interaction). However, ETx stimulated early diuresis,reduced serum sodium levels, and had more pronounced vasodilatory effects, compared with LeTx, as reflected by greater or earlier central venous pressures, systemic vascular resistance, and changes in the BUN:Cr ratio(P ≤ .01). LeTx progressively decreased the left ventricular ejection fraction (P ≤ .002). In a subsequent study, a lethal dose of LeTx with an equimolar nonlethal ETx dose (n=8) increased mortality, compared with LeTx alone (n=8; P= .05)., Conclusion: Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins.

Sodium fluoroacetate (SFAC) is a potent rodenticide, largely used for rodent and domestic pest control. The toxic effects of SFAC are caused by fluoroacetate, a toxic metabolite, whose toxic action blocks the Krebs cycle and also induces the accumulation of citrate in the body, which is a serum calcium chelator. The most common clinical signs of this intoxication are the cardiac and neurological effects. However, the hematological, biochemical and histopathological findings occurring in intoxication are still unknown in different species. In the present study, 16 domestic cats were experimentally intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The hematological and biochemical profiles and histopathological findings were made to look for auxiliary diagnosis methods in SFAC intoxications. The hematological profile showed transitory leucopenia and thrombocytopenia; in the biochemical profiles were detected hyperglycemia, increase of creatinequinase enzyme (CK) and creatinequinase cardiac isoenzyme (CK-MB), hypokalemia and hypophosfatemia. In the macroscopic and histopathological findings were observed lesions characteristic of degenerative and ischemic processes in heart, kidneys, liver, brain and lungs. These changes may be auxiliary to the diagnosis of intoxication by SFAC in cats, when associated with clinical signs described for the species. Thus, the complete blood count with platelet count, serum glucose, enzymes CK and CK-MB isoenzyme, as well as the electrolytes potassium and phosphorus, can facilitate the laboratory diagnosis during intoxication by SFAC, associated with the pathological findings in the case of death of the intoxicated animal.

The present paper reports results of a quantitative morphometric study of neuron and macroglyocyte populations in layers III and V of the brain somatosensory cortex in subjects with ethanol poisoning (EP), alcohol withdrawal (AW), and chronic alcoholic intoxication (CAI). The study was carried out during a more than 7-day period of abstinence in patients presenting with early manifestations of alcoholic illness. In subjects with ethanol poisoning, acute swelling of neurons in layer III was more pronounced than in layer V. Dynamic changes in the number of satellites near bodies of slightly affected neurons were recorded in layer III in patients with EP and AW as well as during the long-term break in intoxication. Layer V in EP, AW, and CAI exhibited phagocytosis of neurons, an elevated number of macroglyocytes and their enhanced proliferation along the course of blood vessels. The morphological changes of neurons and macroglyocytes under the above conditions can be categorized in terms of their degeneration rate from the beginning of the abstinence period into transient (disappearing within 7 days), persistent, and combined.

Alcoholism remains one of the main causes of premature death in the population of Russia. Hence, the importance of the problem of uncontrolled distribution and consumption of surrogate alcoholic products, such as alcohol-containing liquids of uncertain origin. The objective of the present study was to detect ethyl alcohol, polyhexamethylene guanidine hydrochloride, and diethylphthalate in disinfectant liquids, biological fluids and human tissues and to analyse qualitative and quantitative composition of these materials.

Antimicrobial pesticides (e.g., sterilizers, disinfectants, and sanitizers) are chemicals used to destroy or suppress the growth of harmful microorganisms on inanimate objects and surfaces. Health-care facilities use antimicrobial pesticides to prevent pathogen transmission from contaminated environmental surfaces. Occupational exposures to antimicrobial pesticides are known to cause adverse health effects. To assess the nature and frequency of such exposures in health-care settings, CDC analyzed data from pesticide poisoning surveillance programs in California, Louisiana, Michigan, and Texas (the only four states that regularly collect data on antimicrobial pesticide-related illness) for the period 2002-2007. This report summarizes the results of that analysis, which identified 401 cases of work-related illness associated with antimicrobial pesticide exposures in health-care facilities. Most cases were identified through workers compensation systems (61%) and occurred among females (82%) and persons aged 25-54 years (73%). The most frequent occupations reported were janitors/housekeepers (24%) and nursing/medical assistants (16%). The reported mechanism of injury usually was splashes/spills (51%). The eyes were the most common organ/system affected (55%); only 15% of the 265 persons who had exposures while handling antimicrobial pesticides reported using eye protection. Reported symptoms were mostly mild and temporary. One fatality due to acute asthma and subsequent cardiopulmonary collapse was identified. Health-care facilities should educate workers about antimicrobial pesticide hazards, promote the use of personal protective equipment (PPE) as appropriate, and implement effective risk communication strategies for antimicrobial pesticide use to prevent bystander exposure. Improved design of handling equipment might prevent handler and bystander exposure.

The paper presents a retrospective analysis of 16,541 external post-mortem examinations carried out before cremation by the Institute of Forensic Medicine of the University of Bonn between 1998 and 2008 with regard to different variables (age, sex, place of death, cause of death etc.). In more than 50 % of cases, the individuals had died in a hospital followed by their apartment or a nursing home. The first post-mortem examination was mainly performed by hospital doctors followed by emergency doctors and office practitioners. As to the age distribution, the 6th to 8th decade of life was prevalent. In 99.8 %, a natural death was certified in the first external post-mortem and only in 0.2 % the manner of death was determined to be non-natural or unclear. In more than half of the cases, the non-natural deaths were determined by emergency doctors. Deaths wrongly classified in the first external post-mortem were mostly accidents and deaths associated with medical procedures. Although the second external examination before cremation is very useful in detecting previously overlooked signs of homicide, it is only of limited value in homicides with few external traces or for detecting underlying diseases and causes of death. In this respect, the second external examination before cremation can only check the plausibility of the cause of death given by the attending physician. The gold standard for a reliable certification of the manner and cause of death remains the autopsy.

There are no verified statistics about deaths occurring in hotels, and only a few cases have been described in the literature. A recent case induced us to conduct a systematic search for deaths in hotels in the autopsy reports of the Institute of Legal Medicine in Giessen for the period from 1968 to 2009. This search yielded 22 evaluable cases in which persons had been found dead or had died in hotels. Data evaluated in the study were sex and age of the deceased, reason for the stay in the hotel and cause of death. Among the deaths, 18 were males and 4 females and the average age was 41 and 40 years respectively. 6 of the male guests had died from a natural and 10 from a non-natural cause. In the remaining two cases, the cause of death could not be determined, but as there was no evidence that another party had been involved, the cases were not further investigated. Of the 4 female guests, 3 had died of a natural cause; in one case, the cause of death remained unclear even after morphological and toxicological investigations. Surprisingly, a third of the men were found to be temporarily living in hotels due to social circumstances. This was not true for any of the women. Our retrospective analysis is based on a comparatively small number of deaths in what were mostly hotels in small to medium-sized towns. Interestingly, the gender ratio of 18:4 for deceased men and women was significantly higher than the usual gender ratio of 2:1 found for forensic autopsies. To be able to draw further conclusions, a greater number of cases would have to be analysed, for example by recruiting additional case files from other institutes of legal medicine. This would also open up the option of investigating possible regional variations.

The aim of this work was to study morphological changes in brain during acute hemorrhage. The following changes were revealed in drug intoxicated subjects compared with non-drug users: 2.2 and 2.6 times higher degree and severity of brain lesions respectively, a 1.3-fold increase of the brain perivascular oedema area, a 1.6-fold rise in the pericellular oedema area, a 3-fold decrease of the mean glial distance, and 3.3 times greater glial density.

Fungi in the genus Penicillium, particularly P. crustosum, produce tremorgenic mycotoxins, as well as suspected tremorgenic compounds. The accidental intoxication of six dogs with such toxins are reported. The clinical signs included vomiting, convulsions, tremors, ataxia, and tachycardia, all of which are indicators of intoxications affecting the nervous system. This symptomatology caused us to think that the dog poisoning was the result of tremorgenic mycotoxins. One dog was euthanized in the acute phase, while three others recovered completely within a few days. However, neurological symptoms were still observed four months after the poisoning of two of the dogs. One of these recovered completely within the next 2-3 months, while the other still suffers from ataxia three years later. Available samples of feed, stomach content and/or tissues from the intoxications were subjected to mycological and chemical analysis. Penitrem A was found in all reported poisonings and roquefortine C in all cases when this toxin was included in the analysis. The producer of these toxins, Penicillium crustosum, was detected in all cases where material suitable for mycological examinations (feed or vomit) was available. To our knowledge, this is the first report documenting the presence of penitrems and roquefortine C in organs from poisoned dogs. Furthermore, the report indicates that the recovery period after severe poisonings with P. crustosum may be protracted.

A term neonate was born to a mother who had consumed an organophosphorus compound with suicidal intent 50 hours before delivery. At birth, the infant showed signs and symptoms of organophosphorus poisoning and was treated with atropine and pralidoxime to which she responded well. Unfortunately, the mother died despite appropriate treatment. This is only the second report documenting transplacental organophosphate poisoning.

The purpose of this study was to detect the interrelationship between the increased serum concentration of the medium weight molecules (MWM) and echinocytosis, to establish the rate of echinocyte appearance in blood in endogenous and exogenous intoxications and the dependence of echinocytosis on phosphacol and carbophos doses or the degree of endogenous intoxication. Two series of studies were conducted. In the 1st series, the experiments were conducted on outbred albino rats. Rats of the 1st group received phosphacol in doses equal to 0.5, 5.0 and 50 LD50, while the rats of the 2nd group were given carbophos in doses equal to 0.1 and 1.0 LD50. In the 2nd series, the blood of cats with chronic renal failure at uremic stage was studied (as an example of endogenous intoxication). In all the animals, serum MWM concentrations were measured together with the relative echinocyte content and echinocytes were examined with electrone microscope. The ability of MWM to influence erythrocyte deformation was evaluated. Increased MWM concentrations and echinocyte content was found in association with the increase of intoxication severity, while echinocyte percentage in cats' blood was augmented under the action of MWM.

Many toxic substances have been distributed to the environment, some of which have properties that promote accumulation and biomagnification in living organisms. Approximately 1.2 million metric tons of polychlorinated biphenyls (PCBs) have been produced and about 30% have been discharged to the environment. Approximately 200 000 metric tons of brominated flame retardants (BFRs) are produced annually, of which considerable amounts have been spread globally, even to the Polar Regions. Behavioral testing of animals has shown that these compounds may affect learning, memory and fine motor functions. Animals are most sensitive during early development. Several epidemiological studies have shown that PCBs and BFRs may be responsible for similar effects in humans. Of especially concern are possible effects of PCBs and BFRs in mixtures containing the highly neurotoxic methyl mercury. The compounds affect several targets in the nervous system that seem to be interconnected, and may be responsible for the observed behavioral deficits. It was shown early that PCBs affect dopamine and serotonin levels in the brain. Later studies showed that transport mechanisms of these neurotransmitters appear to be particularly sensitive to PCBs. Furthermore, PCBs affect intracellular calcium levels and induce formation of reactive oxygen species both in vivo and in vitro, and reduce cell viability in vitro. Neuroendocrine functions, particularly the thyroid hormone system, are also sensitive to disruption by PCBs and BFRs. Their metabolites, such as hydroxy-metabolites, appear to be particularly potent. We conclude that PCBs are particularly toxic during early development and that the toxic effects are a combination of several factors, including disturbance of calcium homeostasis, oxidative stress, and influence on neurotransmitter transport. Monoaminergic cells appear to be particularly vulnerable.

Brucine is the predominant alkaloid present in the bark of the tree Strychnos nux vomica and is a weaker alkaloid when compared to strychnine. However, its toxicological property is akin to strychnine. We report a rare case of brucine poisoning complicated by acute renal failure and rhabdomyolysis. A 24-year-old male presented with a history of consumption of a decoction made from the bark of the Strychnos nux vomica tree. Soon after, he developed widespread muscle spasms and convulsions, which were promptly treated. On the fifth day of admission, he developed features of rhabdomyolysis and acute renal failure. Investigations revealed elevated creatine phosphokinase levels and elevated blood urea and serum creatinine. The patient was managed with hemodialysis and recovered gradually. There are many reports of strychnine poisoning producing rhabdomyolysis and renal failure. In this case report, attention is drawn to the fact that brucine, although a weaker alkaloid, can also produce life threatening complications like rhabdomyolysis and acute renal failure.

The present study immunohistochemically investigated single-stranded DNA (ssDNA) as a marker of DNA injury during apoptosis and programmed cell death to evaluate neuronal damage in the hippocampus with regard to the cause of death in serial medicolegal autopsy cases (n=335, <48 h postmortem). Formalin-fixed paraffin-embedded brain tissue specimens were used. Neuronal ssDNA-immunopositivity in CA1 and CA4 regions was independent of the age, gender or postmortem interval, and generally low in acute deaths. Positivity in these regions was moderately correlated in all cases (r=0.64, P<0.001), and marked correlations were detected in drowning (r=0.98, P<0.001) and drug intoxication (r=0.86, P<0.001). In brain injury, survival time-dependency within 48 h was not detected in CA1, but mildly present in CA4 (r=0.38, P<0.01). However, a rapid increase was shown in cerebral contusion and brain stem injury. These findings suggested that the analyses of ssDNA-immunohistochemistry in the hippocampus may be useful for evaluating neuronal damage in various causes of death.

Effects in the liver of fatal intoxication with the binary toxin ricin are unclear. We report a robust neutrophil influx into the liver of C57BL/6 mice after lethal parenteral ricin challenge, occurring in peri-portal and centro-lobular hepatic areas within 2 h, followed by the abrupt disappearance of hepatic macrophages/Kupffer cells. Chemokine profiles determined by microarray, ribonuclease protection assays, northern blotting, and enzyme-linked immunosorbent assays showed rapid (2 h) upregulation and persistence of those for neutrophils (CXCL1/KC, CXCL2/MIP-2) and monocytes (CCL2/MCP-1). Red blood cell pooling (8-12 h), loss of hepatocyte glycogen (8-48 h) associated with progressive hypoglycemia, fibrin deposition (24-48 h), and death (72-96 h) followed. Monoclonal antibody to ricin A chain, administered intravenously, blunted hypoglycemia, and abrogated death. This outcome was observed when anti-ricin antibody was given before toxin exposure as well as when administered approximately 10 h after toxin exposure. Targeting antibody to specific amino-acid sequences on the ricin A chain (HAEL and QXXWXXA) was critical to the therapeutic effect. Re-emergence of liver macrophages/Kupffer cells and replenishment of glycogen in previously depleted hepatocytes preceded full recovery of the host. These data identify critical events for liver injury and healing in ricin intoxication, as well as a new means and specific targets for post-exposure therapeutic intervention.

Clinical and morphological signs of poisoning with surrogate alcoholic beverages and their effect on human internal organs are described. Acute respiratory failure is believed to be the key element in patho- and tanatogenesis of alcoholic intoxication, the immediate cause of death being hepatic and/or renal insufficiency. Histologic examination revealed marked dystrophic changes in all internal organs of the affected subjects.

We describe lesions in 29 adult domestic pigeons (Columba livia) poisoned with chlorophacinone, an indandione anticoagulant rodenticide. Birds were found dead in the field and in dovecotes after a wide-area treatment against common voles (Microtus arvalis) based on the dispersion in the open field of wheat grain treated with 0.005% chlorophacinone. At necropsy, most pigeons showed crops full of red-colored wheat grain, extensive subcutaneous hematoma in neck and breast zones, and hemorrhages in lungs and the coelomic cavity. Chlorophacinone was determined in liver samples by high-performance liquid chromatography with ultraviolet detection, and the mean (range) concentration was 11.2 (1.48-50.1) microg/g. Pigeons have a venous subcutaneous plexus in the neck zone (plexus venosus subcutaneus collaris), which has been described as an erectile tissue with a thermoregulation function. This case report describes a relationship between the subcutaneous hemorrhagic lesions and the plexus venosus collaris.

Medical cards of 1,116 inpatient victims of surrogate alcohol poisoning and 242 cases of its fatal outcome associated with jaundice were available for analysis form Irkutsk Region and other regions of the Russian Federation in the second half of 2006 and early 2007. The study revealed differences in hepatic lesions depending on the chemical nature of toxicants. Mixtures containing guanidine derivatives caused highly specific irreversible disturbance of bile transport in hepatocytes and biliary capillaries in the absence of cholestasis at the level of biliary ducts. Changes in hepatocytes of different type and genesis appear to be due to other toxic components and may be of use for the establishment of causal relation between hepatic lesions and concrete toxic mixtures.