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Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. The potential role of chronic acetaminophen administration in the etiology of hepatoxicity is discussed and prevention strategies are presented.

Intrоductiоn. The phthаlic аnhydride, which widely used in chemicаl industry in conditions of chronic ingestion, chrоnicаlly leаds tо а disаdаptаtiоn оf immunity, which is а risk fаctоr in the fоrmаtiоn оf аssоciаted prоductiоn relаted pаthоlоgy. The аim оf the wоrk is tо study the subpopulation prоfile оf lymphоcytes аnd cytоkine stаtus in wоrkers engаged in the prоductiоn оf phthаlic аnhydride with their wоrk experience. Mаteriаls аnd methоds. The оbservаtiоn grоup, tоtаlly 68 men, cоnsisted оf emplоyees wоrking аt the mаin phthаlic аnhydride prоductiоn fаcility. The wоrkers оf the оbservаtiоn grоup were divided intо twо subgrоups with their wоrk experience аt the enterprise: 44 persоns with 0 tо 10 yeаrs оf wоrk experience аnd 24 persоns with mоre thаn 10 yeаrs оf wоrk experience. The cоmpаrisоn grоup — 40 men whо hаd nо prоfessiоnаl cоntаct with hаrmful prоductiоn fаctоrs. The chemicаl-аnаlyticаl, cytоfluоrimetric, immunоenzyme methоds use during the study. Results. The wоrkers being expоsed tо phthаlic аnhydride with up tо 10 аnd mоre thаn 10 yeаrs оf wоrk experience аt the enterprise hаve а phthаlic аcid cоntent in their blооd thаt is 2.3 аnd 3.3 times higher, respectively thаn relаted tо persоns whо аre nоt in cоntаct with the аnаlyzed hаrmful prоductiоn fаctоr (p=0.002–0.033). It wаs fоund thаt lоngtime wоrkers, engаged in the prоductiоn оf phthаlic аnhydride, mаnifested the immune respоnse cellulаr link dysfunctiоn. Wоrkers emplоyed in the mаin prоductiоn оf phthаlic аnhydride with mоre thаn 10 yeаrs оf wоrk experience reveаled а prevаlence оf аctivаtiоn prоcesses (аccоrding tо CD25 + criteriоn), inhibitiоn оf cytоtоxic cell-mediаted respоnse (аccоrding tо CD3 + CD16 + CD56 + criteriоn), gyperexpressiоn оf Th2-cytоkines (аccоrding tо criteriоn IL4) relаtive tо vаlues оbtаined frоm wоrkers оf the prоductiоn with less thаn 10 yeаrs оf wоrk experience in hаzаrdоus prоductiоn cоnditiоns (p=0.002–0.033). Cоnclusiоns. The durаtiоn оf emplоyment оf the wоrkers, cоntаcting with excessive cоncentrаtiоns оf phthаlic аnhydride in wоrkplаce аir, cоntributes tо negаtive dynаmics in the imbаlаnce between T-cells аnd cytоkine prоducts. The dynаmic mоnitоring оf immunоregulаtоry indicаtоrs in wоrkers оccupied in the prоductiоn оf phthаlic аnhydride will cоntribute tо just-in-time reveаling оf the immune system viоlаtiоns in оrder tо reduce the risks оf fоrmаtiоn оf аssоciаted prоductiоn-relаted pаthоlоgy induced by the chemicаl prоductiоn fаctоrs.

The objective of this study was to evaluate the effect of depleted uranium (DU) on the rat immune system. Three-wk-old, specific pathogen-free Sprague-Dawley rats that received dietary DU for 4 mo were divided into four groups (30 rats per group) according to exposure dose: 0 (control group), 1.3 (DU1.3 group), 13 (DU13 group), and 130 mg U kg-1 (DU130 group). After 4 mo of exposure, the splenic tissues of the rats presented elevated uranium content in accordance with increasing dosage. The rats in the DU130 group exhibited immunological damage characterized by pathomorphological changes of immune organs and significantly lower thymic and splenic relative weight, whereas the influences of DU on the immune system were slight in the other groups. In addition, higher uranium exposure also resulted in reduced numbers of peripheral lymphocytes, lower lymphocyte proliferation, and reduced paw swelling. The authors concluded that the influences of DU on the immune system were slight after ingestion of DU at lower doses but severe after exposure to DU at higher doses.

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) develop neurological symptoms and die 6--7-day post-inoculation in the absence of high parasitemia. The effects of chronic intake of a high-fat diet on this process are largely unknown. In this study, we assessed the effect of a high-fat diet on the host-parasite response to malarial infection. Mice were fed ad libitum with either standard or a high-fat diet for 8 weeks and afterwards were infected with PbA. PbA-infected mice feeding a standard diet presented blood parasitemia, hepatic and cerebral histopathological alterations, and hepatic injury with increased hemozoin deposition in the liver. By contrast, these changes were not observed in the malaria high-fat diet group. In addition, mice fed a high-fat diet did not develop the expected neurological symptoms of cerebral malaria and were resistant to death. Taken together, our results indicate that chronic ingestion of high-fat diet prevents the development of experimental malaria induced by PbA injection, suggesting a relationship between a high-fat diet and malaria, which is an interesting subject for further study in humans.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is an important ingredient in spicy foods consumed throughout the world. Vinblastine (VBL) is a naturally occurring alkaloid prescribed to cancer patients. Many cancer patients treated with VBL were taking CAP at the same time. This study attempted to investigate the effect of CAP on the pharmacokinetics of VBL, which is the substrate of CYP3A, P-gp, and Mrp2. CAP, cyclosporine (CsA) or olive oil was given to rats for seven consecutive days, and on the seventh day, VBL (1.3 mg/kg) was administered intravenously. CsA was used as a CYP3A1/2 and transporter inhibitor, and olive oil was used as a vehicle. The results showed that pretreatment of rats with CAP (3.0 mg/kg) for seven consecutive days resulted in an increase in the AUC0-t of VBL of about 29.8% (P < 0.05) compared with the control group. Moreover, CAP decreased the CL of VBL to 75.5% (P < 0.05). At this time, CYP3A1/2 and Mrp2/Abcc2 in the liver was decreased at the mRNA and protein levels. These results demonstrate that chronic ingestion of CAP will increase systemic exposure and reduce clearance of VBL in rats. The food-drug interaction between CAP and VBL appears to be due to modulation of CYP3A1/2 and Mpr2 expression by CAP.

The widespread occurrence of microplastics (MPLs) and nanoplastics (NPLs), collectively abbreviated as M/NPLs, has markedly affected the ecosystem and has become a global threat to human health. Multiple investigations have shown that the chronic ingestion of M/NPLs negatively affects gut barrier function but the mechanism remains unclear. Herein, this research has investigated the toxic effects of pristine polystyrene (PS) M/NPLs, negatively charged carboxylated polystyrene M/NPLs (PS-COOH) and positively charged aminated polystyrene M/NPLs (PS-NH2) of two sizes (70 nm and 5 μm in diameter) in mice. Gavage of these PS M/NPLs for 28 days caused obvious injuries to the gut tract, leading to the decreased expression of tight junction proteins. The toxicity of the M/NPLs was ranked as PS-NH2 > PS-COOH > pristine PS. Oral administration of these M/NPLs resulted in marked gut microbiota dysbiosis. The M/NPLs-enriched genera generally contained opportunistic pathogens which are accompanied by a deteriorated intestinal barrier function, while most M/NPLs-decreased bacteria were beneficial microbes with known tight junction-promoting functions, implicating an important indirect toxic effect of gut microbiota dysbiosis in M/NPLs-induced gut barrier dysfunction. In conclusion, this research highlights the importance of gut microbiota in the toxicity of M/NPLs exposure on gut barrier function, providing novel insights into the adverse effects of M/NPLs exposure on human health.

Since the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, morphological abnormalities in lepidopteran insects, such as shrinkage and/or aberration of wings, have been reported. Butterflies experimentally exposed to radiocesium also show such abnormalities. However, because of a lack of data on absorbed dose and dose–effect relationship, it is unclear whether these abnormalities are caused directly by radiation. We conducted a low dose-rate exposure experiment in silkworms reared from egg to fully developed larvae on a 137CsCl-supplemented artificial diet and estimated the absorbed dose to evaluate morphological abnormalities in pupal wings. We used 137CsCl at 1.3 × 103 Bq/g fresh weight to simulate 137Cs contamination around the FDNPP. Absorbed doses were estimated using a glass rod dosimeter and Monte Carlo particle transport simulation code PHITS. Average external absorbed doses were approximately 0.24 (on diet) and 0.016 mGy/day (near diet); the average internal absorbed dose was approximately 0.82 mGy/day. Pupal wing structure is sensitive to radiation exposure. However, no significant differences were observed in the wing-to-whole body ratio of pupae between the 137CsCl-exposure and control groups. These results suggest that silkworms are insensitive to low dose-rate exposure due to chronic ingestion of high 137Cs at a high concentration.

Tramadol and codeine are both opioids used for pain control and management but are prone to misuse and abuse despite the various side effects. This study, therefore, examined the effects of chronic exposure to Codeine and Tramadol on feeding behaviour. Twenty-Four (24) Female Albino Rats weighing between 150-200g and 4-6 weeks old, were used. They were divided into 4 experimental groups of Codeine, Tramadol, combined Codeine and Tramadol and Control groups with 6 rats in each group and exposed to 8mg/kg of codeine, 20mg/kg of tramadol, combined 8mg/kg of codeine and 20mg/kg of tramadol, and normal saline for 28 days. Records of the amount of food ingested and the bodyweight of the rats were taken daily for the duration of the experiment. Randomized block ANOVA showed a significant effect of Codeine and Tramadol on feeding behavior (F (3,641) = 25.53, p < 0.001, η2= .11), and body weight (F (3,641) = 76.67, p < 0.001, η2= .26), among the female rats. Female rats in the combined codeine and tramadol group ingested less food (x ̅=33.45), compared to codeine group alone (x ̅=40.71), tramadol group alone (x ̅=39.96) and control group (x ̅=49.38). Female rats in the combined codeine and tramadol group gained less weight (x ̅=132.67), compared to codeine group alone (x ̅=137.67), tramadol group alone (x ̅=133.33), and control group (x ̅=164.25). The mean differences were significant (p

Objective: The aim of this study was to determine sucralose and acesulfame-potassium (ace-K) pharmacokinetics in breast milk following maternal ingestion of a diet soda. Methods: Thirty-four exclusively breast-feeding women (14 normal-weight, 20 obese) consumed 12 ounces of Diet Rite Cola, sweetened with 68-mg sucralose and 41-mg ace-K, before a standardized breakfast meal. Habitual non-nutritional sweeteners intake was assessed via a diet questionnaire. Breast milk was collected from the same breast before beverage ingestion and hourly for 6 hours. Results: Owing to one mother having extremely high concentrations, peak sucralose and acesulfame-potassium concentrations following ingestion of diet soda ranged from 4.0 to 7387.9 ng/mL (median peak 8.1 ng/mL) and 299.0 to 4764.2 ng/mL (median peak 945.3 ng/mL), respectively. Conclusions: Ace-K and sucralose transfer into breast milk following ingestion of a diet soda. Future research should measure concentrations after repeated exposure and determine whether chronic ingestion of sucralose and acesulfame-potassium via the breast milk has clinically relevant health consequences.

The ingestion of microplastics (plastic particles Echinogammarus marinus, using food consumption, growth, and moulting as endpoints. Amphipods were fed a gelatinous algal feed spiked with microbeads (8 μm) in concentrations of ~0.9, 9 and 99 microplastics/g for 35 days. E. marinus was also analysed for retention of microplastics, and egestion rate was calculated in a separate high-dose feeding experiment. No significant effects were found in the food consumption or growth assays. There was no accumulation of microplastics in the gut, with only one microbead recorded internally in three (8%) of the exposed amphipods. The low number is likely linked to gastrointestinal functions, allowing for easy egestion of indigestible items. This assumption was supported by the observation that after high-dose exposure, 60 % of E. marinus egested all microbeads within 24 hours. This study suggests that ingesting low concentrations of 8μm microplastics do not impair the feeding or growth of amphipods along the exposure period. We hope that negative results such as these may further assist in assessing the impact posed by microplastics to marine organisms.

Chronic ingestion of licorice is known to cause numerous metabolic and electrolyte disturbances. Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an apparent mineralocorticoid excess (AME). Treatment predominantly consists of cessation of licorice ingestion, potassium replenishment and aldosterone antagonists. Given the potentially lethal effects of chronic licorice ingestion, clinicians should be made aware of the presentation of AME and the proper management. We present the rare case of a 62-year-old male with licorice-induced apparent mineralocorticoid excess secondary to excessive licorice tea intake. Initial presentation included severe hypokalemia of 2.2mmol/L and hypertension of 180/110mmHg, while eunatremic (Na, 144meq/L).

In combat sports, anaerobic power and anaerobic capacity determine sport performance and the dominant metabolic pathways. The decline in performance during exercise that is attributed to the cumulative effects of fatigue, including excessive accumulation of metabolites, depletion of energy substrates, and water and electrolyte disturbances, seems to be of greatest significance. In our experiment, we evaluated the effectiveness of three weeks of bicarbonate-rich water ingestion on anaerobic performance in a state of hydration and dehydration in elite judo athletes. Eight male, elite judo athletes participated in two single-blind, repeated-measures trials. They were assigned to two hydration protocols, ingesting low mineralized table water and bicarbonate-rich water. Anaerobic performance was evaluated by two 30 s Wingate tests for lower and upper limbs, respectively, under conditions of hydration as well as exercise-induced dehydration. Resting, post-ingestion, and post-exercise concentrations of bicarbonate (HCO3), urine osmolality (UOSM), urine specific gravity (UGRAV), and lactate (La) were measured. The current investigation assessed two related factors that impair anaerobic performance—hypohydration and buffering capacity. High-bicarbonate water ingestion improved buffering capacity, and we demonstrated the potential role of this mechanism and its phenomenon in masking the adverse effects of dehydration in the context of repeated high-intensity anaerobic exercise (HIAE).

The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation.

For the first time, the levels of benzo(a)anthracene (BaA), chrysene (CHR), benzo(b)fluoranthene (BbF) and benzo(a)pyrene (BaP) and their sum (PAH4) were investigated in a total of 180 samples of fish, shellfish and meat products produced in Croatia. In addition, dietary polycyclic aromatic hydrocarbons (PAHs) intake of adult Croatian consumers was estimated for both acute and chronic ingestion circumstances. None of the food samples exceeded the currently legal PAHs levels according to the European legislation. The mean PAH4 level was 1.47 µg/kg for meat and 1.48 µg/kg for shellfish products. The acute daily ingestion of BaP and PAH4 through meat and shellfish products was 2? to 7? fold higher in comparison to chronic intake, with meat products being the major contributors. Consequently, the evaluation of consumption patterns that used the margin-of-exposure approach indicated a negligible risk to human health. © 2018 Elsevier Inc.

Introduction: Bisphenol A (BPA) is a chemical used in synthesis of plastic. BPA seeps into food from the plastic containers used to store food items. Exposure to BPA is implicated as a causative factor for detrimental effects on fetal development and various body systems like endocrine, reproductive and immune. Few studies report that BPA ingestion impair small intestinal contractility in-vitro. Government organisations of many countries have probed into the matter and imposed regulations on marketing of BPA. To meet the terms with regulations on BPA, manufacturers are increasingly replacing BPA with Bisphenol S (BPS). BPS has been advertised as a safer substitute to BPA. The various ill effects on BPS are being explored but the effect on gut motility is less clear. Aim: To examine the effect of chronic ingestion of BPA and BPS on rat gut contractions in-vitro. Materials and Methods: Healthy male adult albino rats (175- 225 g) were fed BPA (50 mg/kg/day) or BPS (50 mg/kg/day) or vehicle (Dimethyl sulphoxide) for four weeks by oral gavage. The animals were gently restrained so that the head is immobilised by retaining the animal in an upright position. Gavage needle was passed along the side of the mouth and moved into the esophagus and towards the stomach. After four weeks, they were sacrificed and isometric contractions of gut muscle strips were recorded in an organ bath (maintained at 37±0.5°C) using force transducer, computerised polygraph (power lab 4ST) and chart-5 for Windows, ADI, Sydney, Australia. Results: Acetylcholine (Ach) (0.1-100 µM) evoked gut contractions in-vitro and the basal tone and maximum contractile tension increased in a concentration-dependent manner. However, in both the treated groups, the Ach induced contractions were significantly (p

Inorganic arsenic (InAs) is ubiquitous in the environment and has greater toxicity than do organic arsenic species. It is a proven fact based on epidemiologic studies in groundwater-contaminated regions that chronic ingestion of InAs can lead to adverse health effects. This chapter deals with InAs intake, as well as its health risk from diet in Asia. Dietary intake of InAs in contaminated regions is at least an order of magnitude higher than that in non-contaminated regions. In the contaminated region, daily intake of InAs increased not only by drinking contaminated water but also by the consumption of crops grown with contaminated water and/or by consumption of foods cooked with contaminated water. Consumption of rice is a dominant source of InAs intake in the non-contaminated regions. The mean dietary InAs intake ranges 36–1200 and 3.8–53 μg/day in contaminated and non-contaminated regions, respectively. On the basis of these data and the benchmark dose reported by the EFSA for InAs, the margin of exposure was estimated to be less than 200. Therefore, Asian people are exposed to the levels of InAs that could not be free from cancer and non-cancer risk in the contaminated and non-contaminated regions.

The article describes the clinical case of a patient with multi-organ failure and ischemic colitis secondary to magnesium poisoning, due to the chronic intake of a parapharmacy product, used for the treatment of chronic constipation. The clinical case is described and a review of the literature is made.

An 84-year-old woman was referred to our clinic with grey discolouration of her face. She had a history of hypertension that was managed with amlodipine and olmesartan. She reported that she had ingested an ionic silver solution (1 mg/mL), which she purchased from a naturopathic practitioner, every

Resumo: A ingestão crônica de braquiária induz lesões hepáticas em bovinos caracterizadas por fibrose, atrofia do lobo esquerdo, hipertrofia compensatória do lobo direito e proliferação de ductos biliares. Tipicamente, essas lesões são associadas com agregados de macrófagos espumosos no parênquima hepático. Nesse trabalho foram estudados fígados com essas lesões num abatedouro frigorífico do Brasil Central e as perdas econômicas causadas pela condenação de tais fígados afetados foram estimadas. Durante o período estudado, 488.476 bovinos foram abatidos nesse matadouro frigorífico, dos quais 5.295 fígados foram condenados devido à fibrose, e 192 com lesão hepática foram estudados. Cálculos econômicos permitiram inferir que essas condenações representaram uma perda de R$ 108.817,60. Conclui-se que a condenação de fígados em razão de fibrose induzida pela ingestão de braquiária causa uma perda significativa para a indústria de carne e produtos bovinos devido à condenação de 23,6 toneladas de fígado em um ano em apenas um frigorífico, com perdas estimadas acima de R$ 100.000,00. Abstract: Chronic ingestion of Brachiaria spp. by cattle causes in the liver fibrosis, atrophy of left lobe, compensatory hypertrophy of the right lobe, and bile duct proliferation. Typically, these lesions are associated with accumulation in the hepatic parenchyma of cluster with foamy macrophages. This study surveyed bovine livers with those lesions in a slaughterhouse in Central Brazil and estimated the economic losses caused by condemnation of such affected livers. During the study period, 488,476 cattle were slaughter in this particular abattoir. From 5,295 livers condemned due to fibrosis, 192 with lesions were sampled and studied. Economic calculations permitted to infer that the condemnations represented a loss of R$ 108,817.60. It is concluded that the condemnation of livers due to brachiaria-induced fibrosis causes significant economic losses for the meat industry due to condemnation of 23.6 tons of beef liver with an estimate annual loss of more than R$ 100,000.00 in a single slaughterhouse.

A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr.

Energy drinks are emerging as a major component of the beverage market with sales projected to top $60 billion globally in the next five years. Energy drinks contain a variety of ingredients, but many of the top-selling brands include high doses of caffeine and the amino acid taurine. Energy drink consumption by children has raised concerns, due to potential caffeine toxicity. An additional risk has been noted among college-aged consumers of energy drinks who appear at higher risk of over-consumption of alcohol when the two drinks are consumed together. The differential and combinatorial effects of caffeine and taurine on the developing brain are reviewed here with an emphasis on the adolescent brain, which is still maturing. Key data from animal studies are summarized to highlight both reported benefits and adverse effects reported following acute and chronic exposures. The data suggest that age is an important factor in both caffeine and taurine toxicity. Although the aged or diseased brain might benefit from taurine or caffeine supplementation, it appears that adolescents are not likely to benefit from supplementation and may, in fact, suffer ill effects from chronic ingestion of high doses. Additional work is needed though to address gaps in our understanding of how taurine affects females, since the majority of animal studies focused exclusively on male subjects.

Rodent self-grooming comprises behaviors devoted to caring of the body surface; presentations that have apparent stereotyped and recurring characteristics which makes rodent grooming a appropriate translational tool for studying the effects of substance abuse in humans. Two opioids, codeine and tramadol, both used for the relief of mild to moderately severe pain but overtime has been abused by people to relieve emotional pain were considered in this study. 54 male and female albino rats (24 females and 30 males) with weight ranging from 120g-180g rats were assigned to three experimental groups (codeine, tramadol and combined group) and one control group. In the study, 6 rats were assigned per group. Rats in the codeine group were orally administered 8mg/kg of codeine while rats in the tramadol group were administered with 20mg/kg of tramadol. Rats in the combined group were administered both 8mg/kg of codeine and 10mg/kg of tramadol. Female rats exposed to chronic intake of Tramadol only (Mean =3.14) were found to significantly displayed more body licking grooming behavior compared to female rats administered Codeine only (Mean = 1.33), combination of Codeine and Tramadol (mean = .67) and the control (mean =1.79) (p < .001). Whereas, male rats in the control (mean = 4.23) significantly displayed more body licking grooming behavior compared to male rats administered Codeine only (mean = 3.01), Tramadol only (mean = 3.35), and the combination of Codeine and Tramadol (mean = 2.49) (p < .05). Also, female rats exposed to chronic intake of Codeine only (mean = 4.92), significantly displayed more daily face washing grooming behavior compared to female rats administered Tramadol only (mean = 3.33), combination of Codeine and Tramadol (mean = 3.29) and the control group (mean = 4.76) (p < .001). Whereas, male rats exposed to chronic intake of Codeine only (mean = 4.92), significantly displayed more daily face washing grooming behavior compared to male rats administered Tramadol only (mean = 3.33), combination of Codeine and Tramadol (mean = 3.29) and the control group (mean = 4.76) (p < .001). The findings demonstrated that chronic administration of opioids, codeine and tramadol affected grooming behaviors i.e. face washing and body licking behaviors which are related to possible deterioration of physical appearance and personal grooming habits in humans. Hence, the study suggests that further exploration to unravel the risks related to the consistent consumption of codeine and tramadol on other body systems be considered.

Tramadol and codeine are opioids known to have effective analgesic effects and potentials for the possible development of tolerance and addiction. The recent increase in the use and abuse of these substances coupled with research evidence implicating the ability of these opioids to readily access opioid receptors in the central nervous system (CNS) is a source of research concern. This study, therefore, examined the effects of chronic exposure to codeine and tramadol on exploratory learning behaviour. Twenty-four (24) male albino rats weighing between 150-200g and 4-6 weeks old, collected from the University of Ibadan Veterinary animal farm were used for this study. They were divided into 4 experimental groups of codeine, tramadol, combined codeine and tramadol and control groups with 6 rats in each group. They were exposed to 8mg/kg of codeine, 20mg/kg of tramadol, combined 8mg/kg of codeine and 20mg/kg of tramadol, and normal saline for the codeine, tramadol, combined codeine and tramadol and control groups respectively for 28 days. The rats were administered with the drugs every other day and observed after each treatment day for exploratory learning behaviour using the T-maze. randomized block ANOVA showed a significant effect of codeine and tramadol on exploratory learning behaviour among male albino rats, f (3,67) = 19.08, p < 0.001, η2=.08. Male albino rats in the codeine treatment group significantly took more time exploring the maze (Mean = 176.64) than combined group (Mean =168.13), tramadol group (Mean =131.10) and control group (Mean =92.48). The mean differences were significant (p

Dear Editor,Systemic fluorosis is described in regions with elevated water fluoride concentrations, after industrial exposures, from chronic ingestion of certain teas or fluoridated toothpaste, and...

To assess the dosimetry of Ra-226 in a two-year chronic ingestion study in laboratory maintained fathead minnow fed environmentally relevant levels of the isotope known to occur in gut contents of fish from a uranium mining area.Fish were established on reconstituted commercial fish food containing 10 mBq-10 Bq Ra-226.g(- 1) dry food. The fish were sampled at 1, 6, 18 and 24 months and the Ra-226 levels in the whole fish were directly determined using measurement performed using inorganic mass spectrometry. Pilot experiments using higher doses were also done during development of a liquid scintillation detection system which support some data.The data show that after 1 month the levels of accumulation in the fish were below detection. At 6 months there was an activity dependent accumulation which was relatively higher in the low activity groups. By 18 and 24 months the radium was very low in all groups - well below 6 month levels suggesting considerable loss of radium from the fish. These data were confirmed in a small and shorter study using higher dietary activities. The highest dose calculated for any measurement point was 16 μGy.h(- 1) in the 6-month-old fish fed the diet containing 10 Bq.g(- 1).We conclude that environmentally relevant levels of Ra-226 have a maximum impact at early time-points when the fish are still growing. After that they appear to depurate accumulated radium. In terms of environmental impact, the maximum accumulation peaks at the age where fish could be spawning but is extremely low leading to μGy.year(- 1) doses even after exposure to the high activity diets.

This chapter presents an up-to-date review on the effect of ingestion of Rhodiola rosea ( R. rosea ) on cardiovascular health, mood alleviation, and energy metabolism. R. rosea , also known as Golden Root, is an herb that grows in high-altitude, mountainous regions of the world. Historically, R. rosea has long been used to enhance mental and physical performance and fight fatigue. However, only recently have scientists and nutritional researchers robustly examined the efficacy of R. rosea . This chapter focuses on the extant data relating to exercise performance following both acute and chronic ingestion of R. rosea and the subsequent impact of R. rosea ingestion on cardiovascular parameters, mood, metabolism, and other related variables. It explores the active constituents of R. rosea and explores the studies that have also examined the effect of R. rosea ingestion combined with other substances. The purported mechanisms of action for the potential ergogenic effect of R. rosea are unpacked alongside direction on how to take R. rosea and the reported side effects arising from R. rosea ingestion. This chapter also presents a gap analysis and clear direction for future research related to the efficacy of R. rosea as a nutritional supplement.

Objective: To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance.\ud \ud Design: This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data.\ud \ud Data sources: 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms (‘β-alanine’ and ‘Beta-alanine’ combined with ‘supplementation’, ‘exercise’, ‘training’, ‘athlete’, ‘performance’ and ‘carnosine’).\ud \ud Eligibility criteria for selecting studies: Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses.\ud \ud Results: 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5–10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI −0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)).\ud \ud Summary/conclusions: β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-alanine supplementation based on their chosen exercise modality.

This study examined effects of 4 weeks of caffeine supplementation on endurance performance. Eighteen low-habitual caffeine consumers ( 0.05). Before supplementation, all participants completed one VO2peak test, one practice trial and 2 experimental trials (acute 3 mg · kg−1 caffeine [precaf] and placebo [testpla]). During the supplementation period a second VO2peak test was completed on day 21 before a final, acute 3 mg · kg−1 caffeine trial (postcaf) on day 29. Trials consisted of 60 min cycle exercise at 60% VO2peak followed by a 30 min performance task. All participants produced more external work during the precaf trial than testpla, with increases in the caffeine (383.3 ± 75 kJ vs. 344.9 ± 80.3 kJ; Cohen’s d effect size [ES] = 0.49; P = 0.001) and placebo (354.5 ± 55.2 kJ vs. 333.1 ± 56.4 kJ; ES = 0.38; P = 0.004...

Insect pests have caused economic losses valued at billions of dollars in agricultural production. Anagasta kuehniella (Zeller), the Mediterranean flour moth, is of major economic importance as a flour and grain feeder and is often a severe pest in flourmills. This study provides a suitable route for the direct preparation of thiosulfonates 2 and 3 from thiols, under mild conditions, with good yields; these thiosulfonates were tested for their regulatory effect on insect growth. The chronic ingestion of thiosulfonates resulted in a significant reduction in larval survival and weight. In addition, the tryptic activity of larvae was sensitive to these thiosulfonates. Results suggest that thiosulfonates 2 and 3 have a potential antimetabolic effect when ingested by A. kuehniella. The use of AgNO(3)/BF(3)·OEt(2) and Al(H(2)PO(4))(3)/HNO(3) provides a suitable route for the direct preparation of thiosulfonates from thiols under mild conditions with good yields. These thiosulfonates were toxic for A. kuehniella larvae, suggesting their potential as biotechnological tools.

Liquorice is well known to inhibit the renal tubular enzyme 11-β-hydroxysteroid dehydrogenase, causing a syndrome of apparent mineralocorticoid excess. This is a rare condition, usually resulting from chronic ingestion of liquorice-containing products. The case report relates to an 84-year-old woman with chronic hypertension who developed profound weakness following a liquorice ‘binge’ which, to our knowledge, is only the second reported case of profound metabolic disturbance as a result of acute liquorice ingestion. The differential diagnosis of hypokalaemia and the importance of the clinical history are discussed, with a review of medication and analysis of the acid-base status.

International audience; The knowledge of the absorbed radiation dose is essential in order to interpret the results of animal experiments with chronic ingestion of radionuclides by rodents. In order to evaluate this absorbed dose, we applied the dose conversion factors proposed by ICRP publication 108 to mouse chronic ingestion experiments with 20 kBq.L-1 137Cs- or 90Sr-contaminated water. The results indicated that whole-body absorbed doses were 9 mGy and 10 mGy by the end of 20 weeks of 137Cs or 90Sr ingestion, respectively. These results of dose calculations were compared with results obtained with a more refined method using published organ-specific absorbed fractions of energy. There was good agreement between the two methods, indicating that, despite the simple hypotheses used to apply the ICRP 108 dose conversion factors to our mouse model, this method allows one to calculate in a simple and reliable way the absorbed radiation dose received by the rodents during long-term experiments on chronic ingestion of radionuclides. © 2012 EDP Sciences.

Translational research is an emerging discipline that aims to fill the gap through the whole pipeline from bench to bedside. This review highlights the importance and urgency of incorporating translational research into the study of pharmacokinetic herb drug interactions (PHDI), based on an intensive discussion on the controversial and inconsistent reports from preclinical to clinical, in vitro to in vivo, and across different studies concerning PHDI. Current controversial and dispersed reports confer poor translational capacity of experimental research data to guiding the clinical practices. We propose that the herbal complexities in their chemical compositions, biphasic and tissue-specific effects of enzymes, and the present incomplete understanding of the disposition properties of herbal medicines themselves; and the enzymatic complexities in the species differences, individual genotype and phenotype, differential regulation during healthy and pathological conditions, substrate dependent modulations, and their interplay with transporters, collectively constitute the major translational blocks in PHDI from experimental research to daily clinical practice. In clinical considerations, this review indicates that PHDI are far from clear based on the isolated preclinical findings, and that the intestine is a much more susceptible site than liver when subjected to herbal regulations, and that enzymatic induction could be more predominant than inhibition upon chronic ingestion of herbal medicines. Hopefully, this review would be helpful for better understanding the nature of hurdles in PHDI research, and for igniting the future translational research initiatives.

The aim of our study was to define the biokinetics of 90Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested 90Sr by drinking water containing 20 kBq l -1 of 90Sr. For the juvenile model, parents received 90Sr before mating and their offspring were killed between birth and 20 weeks of ingestion. For the adult model, 90Sr ingestion started at 9 weeks of age and they were killed after different ingestion periods up to 20 weeks. The body weight, food and water consumption of the animals were monitored on a weekly basis. Before killing and sampling of organs, animals were put in metabolic cages. 90Sr in organs and excreta was determined by liquid scintillation \textgreekb counting. Highest 90Sr contents were found in bones and were generally higher in females than in males, and 90Sr retention varied according to the skeletal sites. An accumulation of 90Sr in the bones was observed over time for both models, with a plateau level at adult age for the juvenile model. The highest rate of 90Sr accumulation in bones was observed in early life of offspring, i.e. before the age of 6 weeks. With the exception of the digestive tract, 90Sr was below the detection limit in all other organs sampled. Overall, our results confirm that 90Sr mainly accumulates in bones. Furthermore, our results indicate that there are gender- and age-dependent differences in the distribution of 90Sr after low-dose chronic ingestion in the mouse model. These results provide the basis for future studies on possible non-cancerous effects during chronic, long-term exposure to 90Sr through ingestion in a mouse model, especially on the immune and hematopoietic systems. © 2011 Springer-Verlag.

Urinary bladder tumours in cattle are caused by chronic ingestion of bracken fern and BPV-1/2 infection. The objective of the present study was to assess if BPV-2 was present in urinary bladder lesions from cattle with chronic enzootic haematuria (CEH) from the Azores archipelago (Portugal), in order to gain further information regarding the epidemiologic distribution of this virus. Samples were analysed using PCR specific primers for BPV-2 DNA and an immunohistochemistry for BPV E5 oncoprotein detection. We found a 28% incidence rate of BPV-2 DNA in different types of tumours and cystitis cases (13 out of 46 samples). Tested positive samples for PCR were also positive for the viral E5 oncoprotein; protein immunolabeling was mainly detected within the cytoplasm of urothelial cells, displaying a juxtanuclear distribution. This is the first report of BPV-2 detection in urinary bladder tumours associated with CEH in cattle from the Azores archipelago.

International audience; Uranium is naturally found in the environment, and its extensive use results in an increased risk of human exposure. Kidney cells have mainly been used as in vitro models to study effects of uranium exposure, and very little about the effects on other cell types is known. The aim of this study was to assess the impact of depleted uranium exposure at the cellular level in human kidney (HEK-293), liver (HepG2), and neuronal (IMR-32) cell lines. Cytotoxicity studies showed that these cell lines reacted in a roughly similar manner to depleted uranium exposure, responding at a cytotoxicity threshold of 300-500 μM. Uranium was localized in cells with secondary ion mass spectrometry technology. Results showed that uranium precipitates at subtoxic concentrations (>100 μM). With this approach, we were able for the first time to observe the soluble form of uranium in the cell at low concentrations (10-100 μM). Moreover, this technique allows us to localize it mainly in the nucleus. These innovative results raise the question of how uranium penetrates into cells and open new perspectives for studying the mechanisms of uranium chemical toxicity.

Recently, arsenic-toxicity has become the major focus of strenuous assessment and dynamic research from the academy and regulatory agency. To elucidate the cause and the mechanism underlying the serious adverse health effects from chronic ingestion of arsenic-contaminated drinking water, numerous studies have been directed on the investigation of arsenic-toxicity using various in vitro as well as in vivo systems. Neverthless, some questions for arsenic effects remain unexplained, reflecting the contribution of unknown factors to the manifestation of arsenic-toxicity. Interestingly, very recent studies on arsenic metabolites have discovered that trivalent methylated arsenicals show stronger cytotoxic and genotoxic potentials than inorganic arsenic or pentavalent metabolites, arguing that these metabolites could play a key role in arsenic-associated disorders. In this review, recent progress and literatures are summarized on the metabolism of trivalent methylated metabolites and their toxicity on body systems including cardiovascular system in an effort to provide an insight into the future research on arsenic-associated disorders.

This work is aimed at determining (226)Ra concentration in cheese produced by dairy manufacturers from Pedra and Venturosa, which are two districts in the rural region of Pernambuco-Brazil. Analyses showed concentrations of (226)Ra in cheese samples varying from 54 to 2,080 mBq kg(-1) (wet matter). Using the cumulated risk method, the excess carcinoma and bone sarcoma were estimated for chronic ingestion of cheese containing this radioisotope. In this context, this report discusses the methodology of sample analyses as well as possible consequences of the (226)Ra intake for human health.

Human bone/Plutonium/Uranium/Semipalatinsk nuclear test site/Internal dose. To evaluate the present levels of 239,240 Pu and U in residents living near the Semipalatinsk nuclear test site, more than 70 bone samples were obtained at autopsy. The subjects ranged in age from 30 to 86 years (mean 59.3±12.9). Most of the samples consisted of victims who died of various diseases. Plutonium and U were radiochemically separated and determined by α-ray spectrometry. The mean concentrations of 239,240 Pu and 238 U observed were 0.050±0.041 mBq/g-ash (vertebrae 71, long-bones 18) and 0.28±0.13 mBq/g-ash (22.8±10.6 µg U/kg-ash) (vertebrae 58, long bones 16), respectively. The present 239,240 Pu levels were within the range found for human bone samples from other countries due solely to global fallout in the early 1980s. The average U concentration was close to the estimate (mean 22.5 µg U/kg-ash) for the UK, and about 10 times higher than those estimated for residents in New York City and Japan. By assuming that the average concentration of 239,240 Pu in bone samples is the value at 45 years after instantaneous inhalation in 1955, the initial total intake and the effective dose for 45 years were estimated as 10 Bq and 0.2 mSv, respectively. The annual intake of total U ( 234,235,238 U) and its effective dose for 60 years were estimated as 30 Bq for adult and 0.1 mSv, respectively, for chronic ingestion.