Toxicity

Background: This analysis was designed to assess the efficacy and safety of aripiprazole compared with placebo in subpopulations of patients with acute manic or mixed episodes of bipolar I disorder. Methods: Acutely manic patients experiencing DSM-IV manic/mixed episodes of bipolar I disorder were pooled from two randomized, three-week, flexible-dose, double-blind, placebo-controlled trials (N = 516) and stratified by disease severity (Young Mania Rating Scale, YMRS), episode type, presence or absence of psychotic features, episode frequency, age, gender, and baseline severity of depressive symptoms. Safety and treatment-emergent adverse-event analyses were also performed. Results: Aripiprazole significantly reduced mean YMRS total scores at end point compared with placebo in patients with more severe or less severe illness, with mixed or manic episodes, with or without psychotic features, or with a history of rapid or nonrapid cycling (p b 0.01 for each subpopulation); in men and women (p = 0.001 for both); in patients in the 18-40 and 41-55 year age groups (p ≤ 0.001 for both); and in three subgroups stratified by baseline severity of depressive symptoms using the Montgomery-Åsberg Depression Rating Scale (p b 0.05). The treatment-emergent adverse events reported in ≥ 5% of patients aged 18-40 years receiving aripiprazole were similar to those reported for the overall population. Limitations: This post hoc analysis utilized pooled data from two short-term studies. Conclusion: Efficacy of the second-generation antipsychotic aripiprazole was noted across a broad range of subpopulations often associated with treatment resistance in patients experiencing manic or mixed episodes of bipolar I disorder.

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.

To evaluate the literature on the allergic cross-reactivity between penicillin, carbapenem, and monobactam antibiotics. A MEDLINE search (1950-June 2008) of the English literature was performed using the search terms beta-lactam, penicillin, monobactam, carbapenem, allergy, and cross-reactivity. References of review articles were also screened for inclusion. All articles in English from the data source were identified. Studies whose primary goal was to evaluate drug hypersensitivity and the potential for cross-reactivity were evaluated. Many patients have reported penicillin allergies that have not been verified by skin testing; many healthcare providers avoid the use of other beta-lactam antibiotics, namely carbapenems, in these patients due to fear of the potential for immunoglobulin E-mediated allergic cross-reactivity. A wide range of cross-reactivity between penicillins and carbapenems has been reported in various studies; however, more recent prospective studies have shown the...

Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagyinduced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy-and cell death-inducing effects of these polyphenolic compounds in cancer.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs.

Clinical data are urgently needed to specify the risk and safety of drug use during pregnancy. For several reasons pregnant women are usually excluded from clinical studies. Therefore, observational data are the main source of knowledge, cohort studies as well as case-control studies. Disadvantages of cohort studies based on observational data have been repeatedly discussed. However, being involved in individual risk characterisation of pregnant women it is the experience of clinical teratologists that even reports on small cohorts should not be disregarded if no other data are available. The recently published "Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement" underlines the value of observational data and provides a checklist regarding the most important inherent methodological problems. Our article describes how Teratology Information Services (TIS) document and evaluate their observations on pregnant women exposed to various drugs and discusses methodological problems and -considering the STROBE statement -how these could be addressed.

The use of the 14-d earthworm toxicity test to aid in the evaluation of the ecological impact of contaminated soils is becoming increasingly widespread. However, the method is in need of further standardization. As part of this continuing process, the choice of reference toxicants was evaluated. Reference toxicants were rated in relation to the following criteria: (a) reproducibility, (b) low human health hazard, (c) feasibility of measurement, and (d) chemical stability. Potassium chloride (KCl) and ammonium chloride (NH,CI) were evaluated as possible alternatives to the one currently in common use, 2-chloroacetamide. Potassium chloride rated the best for the combination of the four criteria, followed by NH4C1 and 2-chloroacetamide. Coefficients of variation (C.V.s) from control charts of six definitive tests were used to measure reproducibility. The best reproducibility (lowest C.V.) was shown by KC1, followed by NH4C1 and 2-chloroacetamide. Toxicants ranked KCl < NH4C1 << 2-chloroacetamide in terms of health hazard; and KC1 = NH,Cl> 2-chloroacetamide in terms of measurement feasibility. Both 2-chloroacetamide and NH,Cl changed in concentration during testing. Evidence is also presented that 2-chloroacetamide degrades rapidly during testing, and that, as dead worms decay, ammonification may be adding another toxicant, ammonia, to tests.

The plant Artemisia annua L. is cropped in many countries for production of the antimalarial drug artemisinin. Artemisinin is phytotoxic and has insecticidal activity. Large-scale cultivation of A. annua may cause transfer of artemisinin to soil and, hence, may affect both soil organisms and the aquatic environment if the compound is leachable. In the present study, a new method for extraction of artemisinin from soil was developed, and field concentrations and degradation kinetics of artemisinin in sandy and loamy soils were measured. The soil concentrations in a Danish A. annua field were up to 11.7 mg/kg. The degradation kinetics could be modeled as the sum of two first-order reactions, a fast initial degradation followed by a reaction that was 11-to 25-fold slower. It took at least 35 d before artemisinin could not be detected (Ͻ0.36 mg/kg) at 20ЊC, classifying artemisinin as being relatively persistent in the environment. Combined with its water solubility of 49.7 Ϯ 3.7 mg/L, this makes it potentially leachable. In soil, artemisinin repelled the earthworm (Eisenia fetida; the 10 and 50% effect concentrations [EC10s and EC50s, respectively] were 5.24 Ϯ 2.64 and 21.57 Ϯ 4.73 mg/kg, respectively) and inhibited growth of lettuce (Lactuca sativa L.; EC50, 2.48 mg/kg). Springtails (Folsomia candida) were not affected in the tested concentration range of 1 to 100 mg/kg. Artemisinin had toxicity to the freshwater algae (Pseudokirchneriella subcapitata; EC50, 0.24 Ϯ 0.01 mg/L) and duckweed (Lemna minor; EC50, 0.19 Ϯ 0.03 mg/L) similar to that of the commercial herbicide atrazine. Based on the presented data, the risks of adverse environmental effects because of cultivation of A. annua are high and comparable to those when using commercial pesticides.

There is a need to develop efficient tools to prevent damage to marine ecosystems due to pollution. Since microalgae play a key role in marine ecosystems, they are considered potentially useful for quick and sensitive toxicity bioassays. In this study an integrative analysis has been carried out of the anti-oxidant enzyme activities of marine microalgae species. Three marine microalgae species (Cylindrotheca closterium, a benthic diatom; Phaeodactylum tricornutum, a diatom which has been used as model organism in toxicity bioassays; and Rhodomonas salina, a cryptophyceae which is considered to present a certain level of heterotrophy) were exposed to selected concentrations of three model pollutants: copper (5 and 10 mg L À 1 ), atrazine (25 and 50 mg L À 1 ) and Irgarol (0.5 and 1.0 mg L À 1 ). These pollutant concentrations are environmentally relevant for coastal ecosystems, and have been selected for checking the efficiency of the reactive oxygen intermediate (ROI) scavenging enzyme system of these organisms. Superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APx) and glutathione peroxidase (GPx) activities were measured at the end of 24 h exposure. The integrated biomarker response (IBR) indexin our case for oxidative stresshas been employed to evaluate the ROI-scavenging enzyme system for each species and each treatment. In general, the SOD and CAT enzyme activities measured were higher in exposed populations than in controls, whereas APx and GPx activities showed the opposite trend. These microalgae showed significant responses of oxidative stress biomarkers at environmentally relevant concentrations for the assayed pollutants and short exposure periods, conditions that most other model organisms cannot match. Therefore microalgae present clear advantages over other species for their prospective employment in an "early warning system".

We herein describe the synthesis and characterization of nine new 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine. We evaluate their toxic effects against the different evolutive forms of Trypanosoma cruzi, and the host cell (murine macrophages). The results obtained show that mesoionic hydrochloride MI possesses the best activity profile. Compound MI may be a prototype for use in the development of a new chemotherapeutic agent with high efficiency, which may be employed in the treatment of Chagas' disease.

The neural mechanisms underlying benzodiazepine dependence remain equivocal. The present studies tested the hypothesis that similar neural systems are recruited during diazepam tolerance and withdrawal, and that these are associated with changes in GABA A receptor properties. 2-Deoxyglucose quantitative autoradiography was employed to map the brain structures affected during chronic treatment and withdrawal from diazepam (5 mg/kg IP daily) in rats. Acute administration of diazepam evoked widespread reductions in local rates of cerebral glucose (LCGU) utilization throughout the brain. Brain structures associated with sensory processing developed tolerance to these depressant effects of diazepam after 3 days of treatment, whereas tolerance occurred in the Papez circuit of emotion after 28 days of treatment. These data suggest that adaptive changes in different neuroanatomical circuits may underlie tolerance to the various effects of diazepam. During flumazenil-precipitated withdrawal from diazepam there were marked increases in glucose use in structures of the Papez circuit, the nucleus accumbens, and the basolateral amygdala. These data suggest that the Papez circuit features strongly in diazepam tolerance and withdrawal and supports a common adaptive process being involved in these phenomena. While GABA enhancement of benzodiazepine binding was reduced in the nucleus accumbens after repeated diazepam treatment, there was little evidence to support adapative changes in GABA A receptors or GABA A subunit gene expression (␥ 2 , ␣ 1 , or ␣ 4) as underlying the functional changes in the identified circuits. Alternative neurochemical mechanisms, such as changes in glutamatergic function should be considered.

In order to assess the potential of hydropsychid capture net anomalies as a bioindicator of chronic toxicity in streams and rivers, the e4ects of 2,4-dichlorophenol (2,4-DCP) exposure on the net-spinning behavior of Hydropsyche slossonae were examined for anomalies after 0, 5, 10, 15, and 20 exposure days to gradient concentration of 2,4-dichlorophenol. The net-spinning behavior was signi5cantly a4ected when larvae were exposed to 1.0, 10, 25, and 50 g ' L ؊1 , as expressed by the occurrence of two distinct abnormalities. The 5rst one was a distortion of the midline meshes, where the normal diamond-shape structure is disrupted and the meshes are separated by extra strands (called 99midline:: anomaly). The second aberration observed was called 99chaotic:: net, where the nets are highly irregular without any real structure or well-de5ned areas. A good correlation was found between the chaotic net frequencies and the reduction of ATP concentrations in the larvae, indicating possible uncoupling effects of 2,4-DCP on the oxidative phosphorylation process. Toxicity curves demonstrate that the sensitivity threshold of chaotic net frequencies ranged from 3.5 to 7 g ' L ؊1 , which is highly sensitive compared with other sublethal e4ects of 2,4-DCP on other aquatic species.

Previous studies have shown that high concentrations of ethanol (≥40%) cause functional damage of the gastrointestinal epithelial barrier by direct cytotoxic effect on the epithelial cells. The effects of lower noncytotoxic doses of ethanol on epithelial barrier function are unknown. A major ...

We investigated colour vision impairment in 45 male workers occupationally exposed to toluene (mean value of toluene concentration in ambient air = 119.96 ppm) and in 53 controls. Colour vision was evaluated by Lanthony-D-15 desaturated test and expressed as Age and Alcohol Intake Adjusted Colour Confusion Score (AACDS) or types of dyschromatopsia. Exposure was evaluated by measurement of toluene concentration in ambient air and blood, and hippuric acid and orthocresol determined in urine after the workshift. A statistically significant higher AACDS value was established in the exposed subjects compared to the controls (p < 0.0001). There was no significant difference between AACDS values on Wednesday morning compared to Monday morning. In the exposed group AACDS significantly correlated with the concentration of toluene in ambient air, concentration of toluene in blood and the concentration of hippuric acid in urine after the workshift (all p < 0.0001). Dyschromatopsias were detected in both groups, although no significant difference between groups was established. In the-exposed group, concentration of toluene in ambient air, alcohol intake and age explained 35.1%, concentration of toluene in blood, age and alcohol intake explained 19.9%, and concentration of hippuric acid in urine and age explained 19.2% of the variation in type III dyschromatopsia. Concentration of toluene in ambient air and age explained 28.3% of the variation in total dyschromatopsia, and concentration of hippuric acid and age explained 13.8%. In the control group, age and alcohol intake explained 19.6% of the variation in type III dyschromatopsia. In exposed workers a significant difference was found in the AACDS value compared to controls. However, no significant difference was found in the prevalence of colour vision loss in the yellow-blue and/or red-green axis. Based on the results of this study the authors conclude that the effect of toluene on colour vision can be chronic and that the possible reparation period in colour vision impairment is longer than 64 hours.

The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers. Copyright © 2005 John Wiley & Sons, Ltd.

Purpose: To develop an optimal nonviral aerosol formulation for locoregional treatment of early lung cancer. Experimental Design: The formulation was made of polylysine/protamine combination (AND) as the carrier and p53 gene (p53sm) as therapeutic agent. To estimate the aerosol deposition, the aerodynamic size of the AND-p53sm was measured with extrusion-precipitation method. To accurately determine the dose, the aerosol efficiency in mice was measured with a fluorescent dye. The transfection efficiency and DNA protection function of the aerosolized formulation in cultured cells and mouse lungs were detected with reporter gene assays and/or reverse transcription-PCR.The preclinical safety and efficacy of AND-p53sm were studied in healthy mice and mice bearing orthotopic human non^small-cell lung cancer (NSCLC) xenograft. Results: After aerosolization, AND is 3-to 17-fold more effective than commonly used PEI or cationic lipid formulations in transfecting the NSCLC cells (relative light units, 1,494 versus 534 and 86; P < 0.003). Aerodynamic size of AND-p53sm ranged 0.2 to 3 Am is the optimal aerosol droplets for deposition in the entire human respiratory tract. Significant gene expression was detected in the lungs of mice given aerosolized AND-p53sm and AND-luciferase. Aerosolized AND-p53sm significantly prolonged the life of mice bearing orthotopic human NSCLC xenografts, and it was more effective than an optimal i.v. cisplatin chemotherapy (increased life span, 93% versus 25%; P = 0.014). Inhalation of AND produced low and reversible pulmonary toxicity and no systemic toxicity. Conclusions: This optimal formulation is suitable for delivering biological materials to human lung with aerosol administration. This therapeutic strategy is an option for patients with early lung cancer and bronchoalveolar carcinoma.

Cuprizone is used to obtain demyelination in mice. Cuprizone-treated mice show symptoms similar to several neurodegenerative disorders such as severe status spongiosus. Although it has a simple chemical formula, its neurotoxic mechanism is still unknown. In this work, we examined both physico-chemical properties and biological effects of cuprizone. Our results indicate that cuprizone has very complicated and misunderstood solution chemistry. Moreover, we show here the inability of cuprizone to cross neither the intestinal epithelial barrier nor the neuronal cell membrane, as well its high tolerability by cultured neurons. If added to mice diet, cuprizone does not accumulate in liver or in brain. Therefore, its neurotoxic effect is explainable only in terms of its capability to chelate copper, leading to chronic copper deficiency.

A molecular PCR-based assay was developed and applied to macrophyte and seawater samples containing mixed microphytobenthic and phytoplanktonic assemblages, respectively, in order to detect toxic Ostreopsis species in Mediterranean Sea. The specificity and sensitivity of the molecular PCR assay were assessed with both plasmidic and genomic DNA of the target genus or species using taxon-specific primers in the presence of background macrophyte DNA. The PCR molecular technique allowed rapid detection of the Ostreopsis cells, even at abundances undetectable within the resolution limit of the microscopy technique. Species-specific identification of Ostreopsis was determined only by PCR-based assay, due to the inherent difficulty of morphological identification in field samples. In the monitoring of the toxic Ostreopsis blooms PCR-based methods proved to be effective tools complementary to microscopy for rapid and specific detection of Ostreopsis and other toxic dinoflagellates in marine coastal environments.

Purpose: Tookad® is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy. Materials and Methods: Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes. Results: Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained. Conclusions: Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.

The present investigations influence of Penicillium species and
their culture filtrates on the seed germination and seedling growth
of sorghum was studied. Culture filtrate of P. nordicum, P.
verrucosum, P. chrysogenum, P. commune, P. citrinum,
P.camemberti and P. digitatum were comparatively more toxic and
significantly inhibited the seed germination and seedling growth
varied with the species. However, pathogenicity of different
inoculum of Penicillium species also exhibited varying seedling
growth inhibition with P. citrinum, P. chrysogenum, P. commune, P.
italicum, P. verrucosum and P. expansum assayed by water agar
method. A significant phytotoxicity of these species inhibited
coleoptile 32-70%, radicle 10-87% and leaf growth 20-86% with
correlation coefficient 0.65, 0.67 and 0.79%, and were observed
respectively. In-vitro mycotoxin production was assayed by culture
filtrates of major mycotoxigenic strains revealed production of
ochratoxin A (OTA), cyclopiazonic acid (CPA), rubratoxin B
(RTB), griseofulvin (GRI), citrinin (CIT), patulin (PAT), penitrem
A (PENA) and mycophenolic acid (MPA) screened by TLC/HPLC.
Toxicity of species of Penicillium on seed germination, coleoptile,
radicle, and leaf elongation inhibition may be attributed to the toxinchemotypes
produced by the species of Penicillium. However, even
non-toxigenic strains of Penicillium also caused mild inhibition
which may be attributed to the presence of other toxin-chemotypes.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has looked at the effects of contrast media (CM) on the kidney including prevention of contrast mediuminduced nephropathy (CIN) as well as at the possibility of identifying patients with increased risk of CIN nephropathy. This has resulted in five reports dealing with (i) serum creatinine; (ii) contrast medium-induced nephrotoxicity; (iii) haemodialysis and contrast media; (iv) use of gadolinium CM instead of iodinated CM; and (v) CM injection in diabetic patients receiving metformin. The review presents an overview of four of these five reports.

Dental laboratory technicians may be exposed to metal alloys that are used in the production of crowns, bridges and removable partial dentures. These alloys consist of 35-65% cobalt, 20-30% chromium, 0-30% nickel, and small amounts of molybdenum, silica, beryllium, boron and carbon. The aim of this study was to assess whether dental technicians are occupationally exposed to chromium, cobalt and nickel, by analyzing urinary excretion levels of these metals and to investigate the genotoxic effects of occupational exposure associated with dental prostheses production operations by analyzing cytokinesis-blocked micronucleus (CB-MN) frequencies in peripheral lymphocytes and micronucleus (MN) frequencies in exfoliated nasal cells from 27 dental laboratory technicians and 15 control subjects. The differences in the urinary excretion of metals between technicians and controls were statistically significant. The mean (±S.D.) CB-MN frequencies (‰) in peripheral lymphocytes were 4.00 (±2.98) among the dental technicians and 1.40 (±1.30) among the controls, a statistically significant difference (P < 0.005). The mean (±S.D.) MN frequencies (‰) in nasal cells were 3.50 (±1.80) among the dental technicians and 1.19 (±0.53) among the controls, which was also a statistically significant difference (P < 0.005). There was a significant correlation between duration of exposure and MN frequencies in lymphocytes (r = 0.642, P < 0.01), but not in nasal cells of technicians. Our data reveal that in vivo exposure to chromium, nickel and cobalt metals is evident and that this occupational exposure may contribute to the observed genotoxic damage in two types of cells, e.g. lymphocytes and exfoliated nasal cells. However, it cannot be determined which compound(s) are responsible for the genotoxic damage observed in this study.

Transdermal drug delivery systems (TDDS), also known as ''patches,'' are dosage forms designed to deliver a therapeutically effective amount of drug across a patient's skin. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. In the Drug Quality Reporting System (DQRS), the United States Food and Drug Administration (FDA) has received numerous reports of ''adhesion lacking'' for transdermal drug delivery systems. This article provides an overview of types of transdermals, their anatomy, the role of adhesion, the possible adhesion failure modes and how adhesion can be measured. Excerpts from FDA reports on the lack of adhesion of transdermal system products are presented. Pros and cons of in vitro techniques, such as peel adhesion, tack and shear strength, in vivo techniques used to evaluate adhesive properties are discussed. To see a decrease in ''adhesion lacking'' reports, adhesion needs to become an important design parameter and suitable methods need to be available to assess quality and in vivo performance. This article provides a framework for further discussion and scientific work to improve transdermal adhesive performance.

The aim of this study was to investigate the possible involvement of the glutamatergic system in the toxicity of organochalcogens, since this is an important neurotransmitter system for signal transduction and neural function. The results indicated that 100 μM diphenyl diselenide ( ...

This minireview describes the health effects of antimony exposure in the workplace and the environment. To collate information on the consequences of occupational and environmental exposure to antimony on physiological function and well-being. The criteria used in the current minireview for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust. The proportion of utilised and non-utilised articles was tabulated. Antimony toxicity is dependent on the exposure dose, duration, route (breathing, eating, drinking, or skin contact), other chemical exposures, age, sex, nutritional status, family traits, life style, and state of health. Chronic exposure to antimony in the air at levels of 9 mg/m(3) may exacerbate irritation of the eyes, skin, and lungs. Long-term inhalation of antimony can potentiate pneumoconiosis, altered electrocardiog...

The present study determines lead content in onion root tip cells (Allium cepa L.), correlating it with its toxicity. The treatment was carried at 25±0.5°C using aqueous solutions of lead chloride at 0.1, 0.25, 0.50, 0.75, and 1 ppm for 12, 24, 48, and 72 h. For each treatment, a control where the lead solution was substituted by distilled water was included. After treatment, the meristems were fixed with a mixture of alcohol-acetic acid (3:1) and colored according to the technique of Feulgen. Lead content was quantified by graphite furnace absorption atomic spectrometry. The lead content in the roots ranged from 3.25 to 244.72 µg/g dry weight, with a direct relation with the concentration and time of exposure. A significant negative correlation was presented (r=−0.3629; p<0.01) among lead content and root growth increment, and a positive correlation (r=0.7750; p<0.01) with the induction of chromosomic aberrations. In conclusion, lead is able to induce a toxic effect in the exposed roots, correlated with its content.

The few controlled studies dealing with the action of alcohol on core body temperature in humans have focused on the effect of a single dose of ethanol and reported that it has a hypothermic effect. No studies report the effects of repeated ethanol intake over a 24-h period, a pattern of consumption much closer to the clinical condition of chronic alcoholism. We therefore designed a trial in which alcohol was repeatedly and regularly administered, with a total dose of 256 g. Nine healthy male volunteers (mean age 23.3 +/- 2.9 yr; range 21-30) each served as his own control. The circadian temperature rhythm was studied by a single-blind, randomized, crossover study that compared a 26-h alcohol session to a 26-h placebo session. The trial controlled for so-called masking effects known to affect temperature. The volunteers were in bed; the ambient temperature was maintained between 20 and 22 degrees C. Meals were standardized. And light was controlled during the night. All sessions too...

Aromatic amines represent one of the most important classes of industrial and environmental chemicals: many of them have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants. Their toxicity has been studied also with quantitative structure-activity relationship (QSAR) methods: these studies are potentially suitable for investigating mechanisms of action and for estimating the toxicity of compounds lacking experimental determinations. In this paper, we first summarized the QSAR models for the rodent carcinogenicity of the aromatic amines. The gradation of potency of the carcinogenic amines depended firstly on their hydrophobicity, and secondly on electronic (reactivity, propensity to be metabolically transformed) and steric properties. On the contrary, the difference between carcinogenic and non-carcinogenic aromatic amines depended mainly on electronic and steric properties. These QSARs can be used directly for estimating the carcinogenicity of aromatic amines. A two-step prediction is possible: (1) estimation of yes/no activity; (2) if the answer from step 1 is yes, then prediction of the degree of potency. The QSARs for rodent carcinogenicity were put in a wider context by comparing them with those for: (a) Salmonella mutagenicity; (b) general toxicity; (c) enzymatic reactions; (d) physical-chemical reactions. This comparative QSAR exercise generated a coherent global picture of the action mechanisms of the aromatic amines. The QSARs for carcinogenicity were similar to those for Salmonella mutagenicity, thus pointing to a similar mechanism of action. On the contrary, the general toxicity QSARs (both in vitro and in vivo systems) were mostly based on hydrophobicity, pointing to an aspecific mechanism of action much simpler than that for carcinogenicity and mutagenicity. The oxidation of the amines (first step in the main metabolic pathway leading to carcinogenic and mutagenic species) had identical QSARs in both enzymatic and physical-chemical systems, thus providing evidence for the link between simple chemical reactions and those in biological systems. The results show that it is possible to generate mechanistically and statistically sound QSAR models for rodent carcinogenicity, and indirectly that the rodent bioassay is a reliable source of good quality data.

Due to the relatively high activity concentrations of 210 Po and 210 Pb that are found in tobacco and its products, cigarette smoking highly increases the internal intake of both radionuclides and their concentrations in the lung tissues. That might contribute significantly to an increase in the internal radiation dose and in the number of instances of lung cancer observed among smokers. Samples of most frequently smoked fine and popular brands of cigarettes were collected from those available on the Egyptian market. 210 Po activity concentrations were measured by alpha spectrometry, using surface barrier detectors, following the radiochemical separation of polonium. Samples of fresh tobacco, wrapping paper, fresh filters, ash and postsmoking filters were spiked with 208 Po for chemical recovery calculation. The samples were dissolved using mineral acids (HNO 3 , HCl and HF). Polonium was spontaneously plated-out on stainless steel disks from diluted HCl solution. The 210 Po activity concentration in smoke was estimated on the basis of its activity in fresh tobacco and wrapping paper, fresh filter, ash and post-smoking filters. The percentages of 210 Po activity concentrations that were recovered from the cigarette tobacco to ash, post-smoking filters, and smokes were assessed. The results of this work indicate that the average (range) activity concentration of 210 Po in cigarette tobacco was 16.6 (9.7-22.5) mBq/cigarette. The average percentages of 210 Po content in fresh tobacco plus wrapping paper that were recovered by post-smoking filters, ash and smoke were 4.6, 20.7 and 74.7, respectively. Cigarette smokers, who are smoking one pack (20 cigarettes) per day, are inhaling on average 123 mBq/d of 210 Po and 210 Pb each. The annual effective doses were calculated on the basis of 210 Po and 210 Pb intake with the cigarette smoke. The mean values of the annual effective dose for smokers (one pack per day) were estimated to be 193 and 251 µSv from 210 Po and 210 Pb, respectively.

Cyclosporine A (CsA) is the first choice immunosuppressant used for the prevention of allograft rejection in solid organ transplantation and immune-mediated diseases. Reactive oxygen species-induced oxidative stress and lipid peroxidation are implicated in the pathophysiology of CsA-induced renal injury. In this work, we have studied the effect of a garlic-derived compound, S-allylcysteine (SAC) on CsA-induced nephrotoxicity. CsA-induced nephrotoxicity was assessed in terms of increased activities of serum marker enzymes and levels of kidney markers. CsA administration induced significant elevation in lipid peroxidation along with abnormal levels of enzymic and non-enzymic antioxidants in the kidneys of the rats. SAC administration improved renal function by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. Elevated expressions of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) due to CsA administration were reduced by SAC treatment. An increase in the expression of matrix metalloproteinase-2 (MMP-2) was evident in CsA-induced groups of rats, which was moderately reduced in SAC treated rats. An increase in the levels of serum constituent's urea, uric acid and creatinine was observed in the CsA-induced rats, which was reduced upon treatment with SAC. These results indicate that SAC has a protective action against CsA-induced nephrotoxicity which is also supported by histopathological studies. A comparative study of the antioxidant vitamin C and SAC is more valuable to assess the efficacy of the drug that can be used for the treatment of nephrotoxicity. Copyright © 2009 John Wiley & Sons, Ltd.

A series of N-unsubstituted hydroxy-10H-acridin-9-ones were synthesized and evaluated for inhibitory action against HaCaT keratinocyte growth, in order to explore their potential as antipsoriatic agents. For structureeactivity relationship studies, the number and position of the hydroxyl groups were modified, the oxygen functions substituted or replaced, or additional functional groups were introduced into the acridone scaffold. 1,8-Dihydroxy-10H-acridin-9-one (4), which is an aza-analogue of the antipsoriatic anthralin, was only marginally active. However, 1,3-dihydroxy-substituted 5ee was the most potent acridone within this series and inhibited keratinocyte growth with an IC 50 value comparable to that of anthralin. In contrast to anthralin, nearly all members of the acridone series were devoid of radical generating properties, which were determined by their capability to interact with the free radical 2,2diphenyl-1-picrylhydrazyl. Structures with a phenolic hydroxyl or an aromatic amine arranged ortho or para to the acridone NH group were exceptions. Also in contrast to anthralin, membrane-damaging effects as documented by the release of lactate dehydrogenase into the culture medium were not observed for acridones.

Recently, a novel approach to a highly sensitive and quantitative detection of rare earth element (REE) ions including La3+, Eu3+ and Tb3+, by the polymerase chain reaction (PCR) technique, has been reported. The detection of REE ions is based on the catalytic nature of REE ions targeting the deoxyribonucleic acid (DNA), thus monitoring of the ions can be achieved by reading the level of intact DNA by PCR. Despite of its high sensitivity (at ppb to ppt levels), the conventional PCR-based REE detection protocol requires certain length of time (1-2 hours). In the present study, we modified the PCR-based REE detection protocols by employing the high-speed PCR, and performed the automated and rapid detection of La3+ in small-sized aqueous samples within 5min.

Background: There is accumulating evidence for a link between trauma exposure, posttraumatic stress disorder (PTSD) and diminished health status. To assess PTSD-related biological burden, we measured biological factors that comprise metabolic syndrome, an important established predictor of morbidity and mortality, as a correlate of long-term health risk in PTSD.

This paper reviews the literature on safety culture, placing particular focus on research undertaken from 1998 onwards. The term culture is clariWed as it is typically applied to organizations, to safety, and particularly to construction safety. Some clariWcation in terms of positive safety culture, safety culture models, levels of aggregation and safety performance is provided by presenting appropriate empirical evidence and its theoretical developments. In general, safety culture is thought to inXuence employees' attitudes and behavior in relation to an organization's ongoing health and safety performance. Implications for future research in the area are addressed, as in recent years safety culture has become the focus of much attention in all industries, including the construction industry.

A pilot study addressed potential effects of long-term exposure to chlorination products in swimming pools. The indicator compound chloroform was detectable in blood from competitive swimmers in an indoor pool (mean = 0.89 * 0.34 &l; n = lo), but not in outdoor pool swimmers. No hepatotoxic effect was indicated by serum glutamate oxaloacetate transaminase @GOT), serum glutamate pyruvate transaminase (SGPT) or y-glutamyl transpeptidase (y-GT) enzyme levels. &Zmicroglobulin, an indicator of renal damage, was significantly elevated in urine samples of the slightly, but significantly, younger indoor swimmers. The precise ratio between these 2 possible causes, age and chloroform exposure, as well as the mechanism of the former, remain to be elucidated.

Palabras clave: biorremediación, toxicidad, bacterias, rutas catabólicas, mecanismos moleculares RESUMEN Los plaguicidas N-metilcarbamatos, son muy utilizados a nivel mundial para controlar insectos, ácaros, nemátodos, hongos y malezas en diferentes cultivos. Son altamente tóxicos para humanos y animales, persisten en el ambiente y tienen movilidad significativa en suelos. Una posible alternativa para mitigar los efectos provocados por estos plaguicidas, es la biorremediación, que puede ser mediada por microorganismos capaces de degradar moléculas tóxicas y altamente complejas a moléculas menos complejas, no tóxicas y que pueden ser utilizadas por otros organismos. En esta revisión, se pretende hacer un análisis detallado acerca de los microorganismos biorremediadores de plaguicidas N-metilcarbamatos, puesto que se ha encontrado una gran diversidad de especies con rutas catabólicas de degradación diferentes; además, se analizarán las enzimas carbamato hidrolasas, que actúan sobre un amplio rango de sustratos, bajo distintas condiciones y los diversos mecanismos moleculares (plásmidos y genes) involucrados en los procesos de biodegradación de plaguicidas. La información recopilada es útil para entender los mecanismos que han desarrollado los microorganismos para degradar los plaguicidas N-metilcarbamatos.

The excretion of inorganic, and total lead was investigated in the urine of workers who were exposed to tetraetbyllead (TEL) at gasoline stations. Concentrations of total and inorganic lead after chelation-extraction were determined by flame atomic absorption spectrophotometry (FAAS) in combination with a slotted quartz tube. The limit of detection was 5.2 X lop3 pg Pb/ml; average total lead and inorganic lead concentrations in the urine of workers were 79.0 (range 22.6-158.9 pg Pb/g creatinine) and 37.3 pg Pb/g creatinine (range 5.1-121.01, respectively. In the control group, the mean of the urinary total lead and inorganic lead levels were 5.5 and 3.9 pg Pb/g creatinine, respectively. The difference between total and inorganic lead concentrations could be due to organic lead present in the urine.