Neurotoxicity in chronic lithium poisoning.

BACKGROUND: Lithium-induced neurotoxicity typically occurs with chronic accumulation rather than following acute overdose. There is little emphasis in the literature on the protracted nature of lithium neurotoxicity long after the lithium concentration returns to the therapeutic range. AIMS: To characterise lithium neurotoxicity, with a view of increasing awareness of this important phenomenon. METHODS: This is a retrospective observational study of patients presenting with lithium-induced neurotoxicity over a 5-year period to a clinical toxicology unit. Patients were identified through the unit's database, and clinical notes were analysed. RESULTS: There were 22 patients, with a median age of 65 (range: 36-89) years. Six patients (27%) had previous lithium toxicity, and nine (41%) were regularly prescribed medications that impair lithium excretion. The median lithium concentration on presentation was 2.2 mmol/L, taking a median of 3 days to return to the therapeutic range. Reversible acute kidney injury was observed in 21 patients (95%) on presentation. The median length of stay was 13 (range: 3-95) days due mostly to delayed neurological recovery. Confusion was the predominant symptom, present in 21 (95%) patients, followed by tremors (18(82%)) and ataxia (16(73%)). Multiple investigations were performed to exclude delirium differentials, including 11 computed tomography (CT) and five magnetic resonance imaging (MRI) brain scans, all unremarkable. CONCLUSIONS: Lithium neurotoxicity has a prolonged course. Its severity correlates poorly with lithium concentrations, which normalise quickly. Most poisonings occur in elderly patients with acute kidney injury. Prolonged delirium often prompts multiple unnecessary investigations. Rationalisation of lithium therapy is important in elderly patients.

The Safety of Fluoride Compounds and Their Effect on the Human Body-A Narrative Review.

Fluoride is one of the elements commonly present in the human environment. Due to its characteristics, it is very widely used in medicine, dentistry, industry or agriculture. On the other hand, its universality possesses a real threat to the human body in the form of acute and chronic poisoning. The aim of this paper is to characterize the properties of fluoride and its effects on the human body, as well as the sources of its occurrence. Particular emphasis is placed on the safety of its use and optimal dosage intake, which prevents accumulation and reduces its potential side effects. The positive effect of proper fluoride supply is widely described. In order to avoid overdose, it is best to consult a specialist to properly select the dosage.

Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic.

The industrial activities of the last century have caused massive increases in human exposure to heavy metals. Mercury, lead, chromium, cadmium, and arsenic have been the most common heavy metals that induced human poisonings. Here, we reviewed the mechanistic action of these heavy metals according to the available animal and human studies. Acute or chronic poisonings may occur following exposure through water, air, and food. Bioaccumulation of these heavy metals leads to a diversity of toxic effects on a variety of body tissues and organs. Heavy metals disrupt cellular events including growth, proliferation, differentiation, damage-repairing processes, and apoptosis. Comparison of the mechanisms of action reveals similar pathways for these metals to induce toxicity including ROS generation, weakening of the antioxidant defense, enzyme inactivation, and oxidative stress. On the other hand, some of them have selective binding to specific macromolecules. The interaction of lead with aminolevulinic acid dehydratase and ferrochelatase is within this context. Reactions of other heavy metals with certain proteins were discussed as well. Some toxic metals including chromium, cadmium, and arsenic cause genomic instability. Defects in DNA repair following the induction of oxidative stress and DNA damage by the three metals have been considered as the cause of their carcinogenicity. Even with the current knowledge of hazards of heavy metals, the incidence of poisoning remains considerable and requires preventive and effective treatment. The application of chelation therapy for the management of metal poisoning could be another aspect of heavy metals to be reviewed in the future.

[Plasmatic and urinary pyroglutamic acid measurement by capillary zone electrophoresis in chronic poisoning with acetaminophen in children]. / Dosage plasmatique et urinaire de l'acide pyroglutamique par électrophorèse capillaire de zone dans le cadre d'intoxication chronique par le paracétamol chez l'enfant.

An increase of pyroglutamic acid, or 5-oxoproline plasmatic concentration was reported in metabolic acidosis observed after chronic intake of some drugs, as acetaminophen. We developed a simple, fast and reproducible method by capillary zone electrophoresis using a commercial Anion Analysis Kit® to quantify pyroglutamic acid, in plasma after acetonitrile precipitation, and after simple dilution in urines. Fumaric acid was used as internal standard in both. In less than 7 min, the method separates pyroglutamic acid from other organic and inorganic anions. The method is linear between 0.25 and 10 mmol/L in plasma, and 0.15 and 10 mmol/L in urines. The quantification limits are 0.25 mmol/L and 0.15 mmol/L for plasma and urines, respectively. For repeatability and intermediate precision, the variation coefficients are less than 15% and the bias values are between ± 10%. For the 2 matrices, the recoveries are between 88% and 101%. The method does not interfere with physiological organic and inorganic anions. Pyroglutamic acid concentrations measured in 9 children were between 0.45 and 3.96 mmol/L in the plasma and between 0.15 and 3.2 mmol/L in the urine. No correlation between pyroglutamic acid and acetaminophen concentrations were found, regardless of the biological media. In conclusion, our method measures pathophysiological concentrations of pyroglutamic acid and highlights the increase in other organic acids that may explain metabolic acidosis due to chronic acetaminophen intake.

Mercury as a cause of membranous nephropathy and Guillain-Barre syndrome: case report and literature review.

Secondary renal involvement in chronic exposure to metallic mercury is well known. Mercury also causes central nervous system damage and demyelinating polyneuropathy. Here, we describe a case of a patient with daily exposure to mercury in skin lightening cream and hair dyes who was diagnosed with Guillain-Barre syndrome and then developed nephrotic syndrome because of membranous neuropathy. By reviewing the literature describing mercury-associated diseases, we found that mercury components have an immunomodulatory activity, which is also involved in both peripheral neuropathy and glomerulonephritis.

Proteome analysis of the potential serum biomarkers for chronic benzene poisoning.

The aim of our study is to seek novel specific biomarkers which could provide clues to the mechanism of chronic benzene poisoning (CBP) and might also be used as specific markers for early detection and diagnosis. In this study, a comparative serological proteome analysis between normal controls and CBP patients at three different levels of poisoning were performed via a 2D-DIGE and MALDI-TOF-MS. As the result a total of 10 proteins were found significantly altered between the normal and the mild, moderate and severe poisoning. The identified differentially expressed proteins were classified according to their molecular functions, biological processes, and protein classes, and three important serum proteins among them, apolipoproteinA-1, alpha-1-antitrypsin and complement C3, were further confirmed by immune turbidimetric analysis for their significant up-regulation in the CBP patients. Our findings suggest that these differential proteins may help elucidate the mechanism of CBP and provide potential biomarkers for diagnosis.

Research progress on intestinal probiotics alleviating chronic heavy metal toxicity / 环境与职业医学

Human activities, especially industrial production, have aggravated the pollution of heavy metals in the environment, and especially after disrupting the food chain, such pollution can cause varying degrees of heavy metal poisoning in human beings. Studies have shown that exposure to heavy metals tends to upset the balance of the flora and further aggravate organ toxicity. Intestinal probiotics represented by Lactobacillus can actively adsorb heavy metal ions, promote their excretion, and reduce their induced oxidative stress injury and inflammatory response. Focusing on the chronic toxicity induced by long-term low-dose exposure to heavy metals, this article reviewed current pollution status of several common heavy metals (lead, cadmium, and mercury), analyzed the interaction between heavy metals, intestinal flora, and probiotics, and summarized proposed mechanisms of probiotics in mitigating chronic heavy metal toxicity, aiming to provide new ideas for effective prevention and treatment of organ toxicity induced by heavy metals.

Biomarkers of arsenic exposure in arsenic-affected areas of the Hetao Basin, Inner Mongolia.

Seventy saliva samples, seventy urine samples, seventy nail samples, seventy hair samples, eight drinking water samples and ninety-three crop samples were collected from four villages of the Hetao Basin in Inner Mongolia to determine arsenic (As) exposure biomarkers and evaluate relationship between As uptake and human health risk. Trivalent As (As(III)), pentavalent As (As(V)), dimethylarsinic acid (DMA), arsenobetaine (AsB) and monomethylarsonic acid (MMA) were found in all urine samples. Only As(III) and As(V) were detected in saliva samples. In nail and hair samples, DMA, MMA, As(III) and As(V) were observed. Based on total As contents in crops and drinking water, the local residents' daily intake of total arsenic (TDIAs), the hazard quotient (HQ), and the cancer risk (R) were assessed. Male, older and cases of skin lesion participants generally had higher As contents in saliva, urine, nail and hair samples in relative to others. Salivary, urinary, nail and hair As were not significantly affected by body mass index (BMI) and smoking. Good correlations were observed between TDIAs and salivary, urinary, nail and hair As, showing that saliva, urine, nail and hair samples can be used as biomarkers of As exposure. Individually, levels of arsenicosis were positively correlated with TDIAs. The relationship between TDIAs and prevalence of arsenicosis concluded that, although As levels in crops and drinking water did not exceed national standards, they still pose a potential threat to human health. It was suggested that the maximum permissible levels of crop As and drinking water As should be re-evaluated for protecting human health.

Cadmium-induced injury of duodenal epithelial cells in mice and its mechanism / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of cadmium (Cd) exposure in vivo and in vitro on duodenal epithelial cells in mice and the mechanism. METHODS In vivo, C57BL/6 mice were ig administered with CdCI210 mg-kg" once per day for 30 d to establish a chronic cadmium poisoning model, or were ig administered with a single dose of CdCh 80 mg • kg-1 to establish an acute cadmium poisoning model before the survival status and survival rate of mice were observed. Duodenal epithelial cells of acute and chronic cadmium poisoning mice were isolated and cultured. The cells were identified as epithelial cells by E-cadherin immunofluorescence. Then, the content of cadmium ion in duodenal epithelial cells was detected by confocal laser microscopy. In vitro, duodenal epithelial cells of normal C57BL/6 mice were isolated and cultured, and incubated with CdCI2 2.5-100 pmol-L-1 for 24 h. CellTiter-Blue was used to detect cell viability. Subsequently, the duodenal epithelial cells of normal mice were incubated with CdCI215 Mmol • L-1 for 24 h, and cell cycle was detected by flow cytometry. Then, the duodenal epithelial cells of normal C57BL76 mice were incubated with CdCI230 Mmol-L'1 for 3-12 h and the expression of cleaved-caspase 3 was detected by Western blotting. RESULTS Compared with the control group, the activities of mice with chronic cadmium poisoning were all normal. The mice with acute cadmium poisoning showed depression, less food intake and death. At the 5th day of acute cadmium exposure, the survival rate of mice decreased to 40%. The content of cadmium ion in duodenal epithelial cells of acute and chronic cadmium poisoning mice increased significantly (F<0.01). Furthermore, CdCI2 inhibited the viability of duodenal epithelial cells cultured in vitro and the half inhibitory concentration (IC50) was (24.55±0.84) pmol-L-1. Compared with the control group, CdCI2 blocked the cell cycle of duodenal epithelial cells at Go/G, phase (P<0.05), and the expression of cleaved-caspase 3 in duodenal epithelial cells was significantly increased after CdCI2 treatment for 6, 9 and 12 h (P<0.05, P<0.01). CONCLUSION Cadmium that enters the body through the digestive tract can be absorbed by duodenal epithelial cells and cause damage to the cells. The mechanism of cadmium-induced damage may be related to cell cycle arrest and caspase 3-mediated apoptosis.

Arsenic toxicosis in sheep: The first report from Iran.

Arsenic contamination of groundwater has been previously reported in Ghopuz, a village located in the Northwest of Iran. Samples were taken from consuming and irrigation water and plants of the region for chemical analysis. A seven-year old ewe, which had lived in and fed a lifelong at the same place, with clinical signs such as weakness, wasting and inappropriate integument was necropsied. Grossly, buccal erosion, stomatitis, cutaneous ulcers and serous atrophy of fat deposits were observed. Rumen contents, wool and several tissue samples were obtained for toxicological and histopathological examinations. Mean arsenic concentration in the spring water, irrigation water and grass/algae were 70.11, 48.74 and 141.85 ppb (µg/kg), respectively. Arsenic levels were 486.73, 247.94, 127.92, 125.97 and 231.24 ppb in wool, skin, rumen contents, liver and kidney, respectively. Microscopic study revealed hyperemia and heavy parasitic infestation of the abomasal wall. Hyperemia and regeneration of renal tubule epithelia were observed in kidneys and hyperkeratosis, suppurative deep dermatitis and paniculitis were found in skin. Periacinar fibrosis and a poorly differentiated cholangiocarcinoma were seen in liver. In pancreas, reduced cell density of islands of Langerhans was noticeable. In the central nervous system, perineuronal and perivascular edema, ischemic changes in gray matter neurons, and microcavitation of white matter were present. Our findings confirmed chronic arsenic toxicosis in small ruminants in this region. It can be concluded that long-term consumption of arsenic contamined water and forage may be associated with chronic arsenic poisoning in domestic animals and human beings, with consequent neoplastic disease and induction of diabetes in this region.

Report of 2 cases of atypical occupational chronic mercury poisoning / 中国职业医学

OBJECTIVE: To analyze the clinical characteristics of atypical occupational chronic mercury poisoning cases and explore ways to avoid misdiagnosis. METHODS: The clinical data of 2 atypical occupational chronic mercury poisoning cases were retrospectively analyzed. RESULTS: The two cases were in the same instrument factory. They were engaged in the inspection and filling of thermometers, with a long history of occupational mercury exposure. The main clinical manifestations were the nervous system damage. In the two cases,one case showed severe pain in limbs and joints accompanied with neurasthenia syndrome, oral-gingivitis and increased urine mercury; while the other one showed Parkinson's syndrome-like involuntary tremor whenever at rest or activity accompanied with neurasthenic syndrome and increased urine mercury,without oral-gingivitis. The physical examination showed notable finger tremor,tongue tremor,and eyelid tremor,and one case had coarse tremor of upper limb. Both cases were diagnosed as occupational chronic mercury poisoning. CONCLUSION: The nervous system is the most common site of involvement of patients with occupational chronic mercury poisoning,whose clinical manifestations are diverse. Clinicians should raise awareness of mercury poisoning,consult medical history in detail and reduce misdiagnosis.

Study on the epidemic characteristics and trends of occupational chemical poisoning in Guangdong Province / 中国职业医学

OBJECTIVE: To analyze the epidemiological characteristics and predict epidemiological trends of occupational chemical poisoning,based on directly reported data during 2006-2015 in Guangdong Province. METHODS: The data of patients with occupational chemical poisoning reported from National Information Surveillance System for Occupational Disease and Occupational Health from 2006 to 2015 in Guangdong Province were collected. The epidemiological characteristics were retrospectively analyzed. The autoregressive integral moving average model( ARIMA model) was established and validated based on the number of the new onset cases and was used to predict the trends of occupational chemical poisoning from 2017 to 2020 in Guangdong Province. RESULTS: From 2006 to 2015,1 288 new cases of occupational chemical poisoning were reported in Guangdong Province,which accounted for 24. 4% of the total number of new cases of occupational diseases in the province( 5 283 cases). Among the new cases,the percentage of acute and chronic poisoning was 21. 7%( 279/1 288) and 78. 3%( 1 009/1 288). There was 74. 7%( 962/1 288) of organic solvent poisoning. Five kinds of new occupational chemical poisoning were found. Most of the new cases were male,accounting for 56. 7%( 729/1 288). They were mainly distributed and concentrated in Pearl River Delta Region,accounting for 95. 9%(1 235/1 288). Shenzhen,Dongguan and Guangzhou were the most three cities which had 425,325 and 209 cases respectively,all of them accounted for 74. 4%( 959/1 288). The new cases of poisoning mainly distributed in medium and small enterprises( 72. 0%),private economic enterprises( 50. 9%) and manufacturing industries(70. 5%). The number of occupational chemical poisoning diseases decreased first,and increased,and the proportion to the total number of occupational diseases in Guangdong Province showed a straight downward trend(P < 0. 01). The median age at diagnosis was 35 years old and the median work year at diagnosis was 2. 0 years,and both of them showed an increasing trend( P < 0. 01). CONCLUSION: Occupational chemical poisoning in Guangdong Province has certain characteristic of crowd aggregation and epidemic trends.

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats.

Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent.

Comparison of therapeutic effects between comprehensive therapy and routine therapy in treatment of occupational chronic n-hexane poisoning / 中国职业医学

OBJECTIVE: To evaluate the therapeutic effects between comprehensive therapy and routine therapy in treatment of occupational chronic n-hexane poisoning. METHODS: By randomized controlled trial,116 cases with occupational chronic n-hexane poisoning were divided into two groups: the control group( n = 58) and the treatment group( n = 58). Subjects in the control group were given vitamin B_(12) and vitamin B_1 for neural nutrition; and Danshen and deproteinized calf blood extractive injection for activating blood circulation to dissipate blood stasis. Subjects in the treatment group were treated with comprehensive treatment including traditional Chinese and Western medicine,which including mouse nerve growth factor,acupuncture,physical therapy( infraredtherapy,microwave irradiation therapy),Chinese medicine steamingwashing and comprehensive rehabilitation therapy for a period of 12 weeks in addition to the conventional treatment. The curative effect and adverse reactions of both groups were observed after 12 weeks,and the treatment results and hospital stay were followed up. RESULTS: Before treatment,no significant differences( P > 0. 05) were noted in both groups in scores of neurological symptoms,signs,activities of daily living and neurogenic damage indexes of electroneuromyography[including motor digital latency( MDL),motor nerve conduction velocity( MCV),sense nerve conduction velocity( SCV) of median nerve,ulnar nerve,sural nerve or common peroneal nerve; and the detection of lengthen MDL,shorten MCV and SCV]. After treatment,patients in both groups got better in terms of the above indicators( P < 0. 05),with larger extend of improvement noted in the treatment group than in the control group( P < 0. 05). No obvious adverse reactions were noted in the 2 groups. Hospital stay of patients in the treatment group was about 2 months shorter than that in the control group( P < 0. 05). CONCLUSION: The therapeutic effects of comprehensive therapy on occupational chronic n-hexane poisoning are obviously better than routine therapy,which is an effective and safe therapeutic method.

Risk assessment of chronic poisoning among Indian metallic miners.

The estimated average daily employment in the Indian mining sector is 5,60,000, which comprises 87% in the public sector and 13% in the private sector, of which around 70,000 are working in metallic mines. The mine workers are exposed to dust of various potentially toxic substances. The common toxicants present in the mining environment are lead, mercury, cadmium, manganese, aluminium, fluoride, arsenic, etc. Inhalation and absorption through the skin are common routes of exposure. Low-dose chronic exposure of toxic substances results in the accumulation of toxicants in the body. Hence, there is a need to monitor the mining environment as well as the miners for these toxicants.

Chronic toxicity of tea polyphenols in dogs / 中国临床药理学与治疗学

Aim The chronic toxicity of tea polyphenols(TP) in dogs was observed. Methods 18 dogs were randomly divided into high, middle and low dose TP groups and one control group . When TP was given(po) by 650 mg?kg-1?d-1,65 mg?kg-1?d-1,6.5 mg?kg-1?d-1 respectively for 90 d and after TP was stopped for two weeks, the general conditions, ECG, blood routine, urine routine, serum lipids, blood sugar, coagulation time, and hepatic and kidney function were detected respectively. Results These mdices were not different from each other among the 4 groups before, during and after administration of TP . The level of serum total cholesterol was progressively decreased in TP groups. Conclusion TP has no toxic effect on dogs and can decrease the level of serum total cholesterol in normal dogs.