In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads.

The aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977µm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 µg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.

Bile acid sequestrants for glycemic control in patients with type 2 diabetes: A systematic review with meta-analysis of randomized controlled trials.

AIM: To evaluate the effects of bile acid sequestrants (BASs) versus placebo, no intervention or active comparators on glycemic control in type 2 diabetes. METHODS: Data were retrieved and a systematic review with meta-analyses was performed. We evaluated bias control and subgroup and sensitivity analyses were performed to evaluate heterogeneity and bias. RESULTS: We included 17 trials with a total of 2950 patients randomized to BASs (colesevelam or colestimide) versus placebo, no intervention, statins or sitagliptin. Random-effects meta-analysis showed that patients randomized to BASs had a lower hemoglobin A1c at the end of treatment compared with the control group (mean difference-0.55%; 95% confidence interval-0.64 to -0.46). Analysis of trials with low risk of bias in all domains confirmed the findings. Data on adverse events were limited. There were no differences between trials stratified by the control group and no evidence of publication bias or small study effects. CONCLUSIONS: Our analyses found that BAS treatment improves glycemic control. The size of the effect was clinically relevant and despite limited safety data, our findings support the inclusion of BASs in current diabetes management algorithms for type 2 diabetes.

[On the problem of the study of the chemical air pollution with chlororganic hydrocarbons at productions of polyvinyl chloride and epichlorohydrin].

Hygienic assessment of working conditions at the chemical productions of polyvinyl chloride (PVC) and epichlorohydrin (EPCH) in East Siberia has shown that the employees are exposed to the chlororganic hydrocarbons of hazard category 1-2, out of them there were found to be more toxical pollutants such as vinyl chloride, 1.2-dicloroethane in the production of polyvinyl chloride; allyl chloride and epichlorohydrin in the production of epichlorohydrin. Multistageness of the technological processes, the absence of the isolation of main stages of the technological processes as well as the heating microclimate contribute to the chemical pollution of the air environment. In spite of the significant improvement of the hygienic situation at the productions mentioned in the recent 10 years according to the chemical factor due to the introduction of the complex of curative measures, the working conditions of the employees still belonged to the harmful category. According to the content of the harmful chemical substances in the air of the working zone and the parameters of microclimate, the working conditions of the employees working at the production of epichlorohydrin and in the shop of vinyl chloride production must be qualified as the harmful ones of the first category of the hazard and danger (Class 3.1), in the production shop for PVC- as the harmful ones which correspond to the second category of the hazard and danger (Class 3.2).

Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae.

Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum.

Comparison of efficacy of pitavastatin and colestimide in Japanese patients with diabetes mellitus complicated by hyperlipidemia and metabolic syndrome.

The present study was undertaken to compare the efficacy of pitavastatin and colestimide in patients with diabetes mellitus complicated by hyperlipidemia and metabolic syndrome. 48 diabetic patients with metabolic syndrome were randomly assigned to a pitavastatin group or colestimide group. The clinical parameters, serum lipids, fasting (FPG) and postprandial plasma glucose(PPG), HOMA-IR, hemoglobin A1c(HbA1c), hs-CRP and urinary albumin were measured before/after 24-week administration. Treatment with pitavastatin reduced LDL-C and TG, while that with colestimide significantly reduced waist circumference, BMI, LDL-C, HbA1c, FPG, PPG, HOMA-R , hs-CRP and urinary albumin. Percent improvement in LDL-C was greater in the pitavastatin group than in the colestimide group. Colestimide appeared to be useful in the management of Japanese patients with diabetes mellitus complicated by metabolic syndrome, since it alleviates obesity and insulin resistance in addition to exhibiting lipid profile-improving effects, and can thus improve markers of atherosclerosis.

[Peculiarities of immunologic reactivity in workers exposed to various neurotoxic chemicals].

The author presents results of immunologic examination in workers contacting mercury, chlorinated hydrocarbons at work. Research revealed peculiarities of immune response of the workers to neurotoxic chemicals varying in chemical nature. Discussion covered a topic of pathogenetic value of hyperactivated inflammatory cytokines and increased levels of antibodies to nervous tissue antigens in occupational neurointoxications.

[Patterns of biochemical disorders under exposure to neurotoxic chemicals varying in nature].

The article covers results of examination of workers engaged into chemical production and contacting neurotoxic factors varying in nature. Findings are disorders of cholesterol metabolism in individuals engaged into vinylchloride and metallic mercury production, modified protein metabolism, activated lipid peroxidation and depressed antioxidant

Eczema alérgico de contacto por resina epoxi / Allergic contact eczema from epoxy resin

Las resinas epoxi son plásticos muy empleados como aislantes eléctricos, en recubrimientos y como adhesivos y pinturas. Presentan un gran poder sensibilizante y son una de las principales causas de eczema alérgico de contacto, tanto en el medio laboral como fuera de éste. Presentamos el caso de un trabajador de una planta plastoquímica que manipulaba componentes de material aeronáutico en el proceso de fabricación de piezas de fuselaje. Consultó por lesiones eczematosas en los dedos, manos y antebrazos, de 2 años de evolución, en clara relación con su actividad laboral. Se realizaron pruebas epicutáneas con la batería estándar, la de plásticos y adhesivos y sus productos propios. Se objetivaron positividades a resinas epoxi (batería estándar) y a sus productos propios, entre los que se encontraban distintas láminas de fibras de vidrio y carbono impregnadas con resinas epoxi y adhesivos epoxi

Epoxy resins are plastics that are widely used as electrical insulation, in coatings, and as adhesives and paints. They have strong sensitizing power and are one of the main causes of allergic contact eczema, both in the workplace and elsewhere. We present the case of a worker at a plastics/ chemical plant, who handled aeronautical components in the process of manufacturing fuselage parts. He consulted his physician because of eczematous lesions on his fingers, hands and forearms which had developed over a two-year period and were clearly related to his work. The standard battery of skin tests was performed, along with the plastics and adhesives series and tests using the products from his workplace. Positivity was shown to epoxy resins (standard battery) and to the products from his workplace, which included different fiberglass and carbon fiber sheets impregnated with epoxy resins and epoxy adhesives

Pulmonary function abnormality and respiratory tract irritation symptoms in epichlorohydrin-exposed workers in Taiwan.

BACKGROUND: Epichlorohydrin (ECH) is a strong irritant of the eyes, respiratory tract, and skin. The aims of this study were to examine the dose-response relationship between observed abnormal pulmonary function tests and respiratory tract irritation symptoms among epichlorohydrin-exposed workers in Taiwan. METHODS: A total of 167 workers were randomly selected from a resin synthesis factory. Sixty-six air samples were taken to determine ECH concentration in the workplace. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. RESULTS: There were 13 of 41 (31.7%) abnormal mean mid-expiratory flow (MMEF) among the high-ECH-exposed workers, 11 of 38 (29%) among the low-ECH-exposed workers, and 4 of 59 (6.8%) among non-ECH-exposed workers. There was a significant linear trend between ECH exposure and the prevalence of small airway abnormalities (P = 0.007) after adjusting for other factors. There was also a significant dose-response relationship of respiratory tract irritation symptoms (cough, phlegm, chest tightness, and dyspnea) among the ECH-exposed workers. CONCLUSIONS: This study suggests that obstructive lung abnormalities and small airway lung damage are associated with ECH exposure. The study also suggests that exposure to very low concentrations (<0.2 ppm) causes significant higher prevalence of respiratory tract irritation symptoms. Causal inferences from the findings cannot be made from this cross-sectional study and further longitudinal studies are needed to better clarify the nature of the observed associations.

[Role of genetic blood markers (ABO-HLA systems) in the formation of increased sensitivity to occupational allergen epichlorohydrin]. / Rol' geneticheskikh markerov krovi ABO-HLA-sistem v formirovanii povyshennoi chuvstvitel'nosti organizma k proizvodstvennomu allergenu épikhlorgidrinu.

The authors demonstrated that genetic factors play the certain role in hypersensitivity to occupational allergen epichlorohydrin. The sensibilized workers demonstrated higher incidence of individuals with OB (III) blood group and having phenotypic B8 antigen of HLA-system.

32P-post-labelling of 7-(3-chloro-2-hydroxypropyl)guanine in white blood cells of workers occupationally exposed to epichlorohydrin.

Epichlorohydrin (ECH) is a simple 3-carbon epoxide of industrial importance. It has been shown to be genotoxic in several systems and carcinogenic in experimental animals. The aim of the present investigation was to study DNA adducts of ECH as a biomarker of occupational exposure to this chemical. 7-(3-Chloro-2-hydroxypropyl)guanine (7-CHP-guanine) was analysed in DNA from white blood cells using an anion exchange-based adduct enrichment protocol of the (32)P-post-labelling/HPLC-based assay. Blood samples were collected from seven workers handling ECH (exposed), nine workers not handling ECH but normally present in the premises where this chemical is used (potentially exposed) and 13 office and factory workers from locations in the plant where ECH is not handled (controls). 7-CHP-guanine was detected in five of the seven workers exposed to ECH (1.6-7.1 mol/10(9) mol nucleotides) and in two of the nine workers potentially exposed to ECH (0.8-1.5 mol/10(9) mol nucleotides). This adduct was not detected in any of the 13 controls. The difference in adduct levels between exposed workers and controls was statistically significant (Mann-Whitney test, P < 0.001), as was the difference between exposed workers and potentially exposed workers (P = 0.017). The recovery of 7-CHP-guanine in the (32)P-post-labelling assay was on average 48 +/- 7%, which is considerably higher than previously reported for other 7-alkylguanines. The method used had a limit of detection of approximately 0.4 mol adduct/10(9) mol nucleotides using 20 microg DNA. This study shows for the first time ECH-induced DNA adducts in humans and suggests that 7-CHP-guanine may be used as a biomarker of occupational exposure to ECH.

Genetic toxicology of epichlorohydrin: a review.

Epichlorohydrin (ECH) is one of the more commercially important aliphatic epoxides used extensively as an industrial intermediate, a laboratory reagent, and as an insecticide. It is a volatile, colourless liquid with an ethereal odour. It behaves as an alkylating agent. Reports have shown it to cause the respiratory and dermal toxicity in animals and humans. It has also been reported to be carcinogenic in experimental models. Thus, the wide-spread use of this aliphatic epoxide is of great concern in human health problem. The purpose of this paper is to critically review and update the mutagenic and clastogenic effects of ECH based on available literature.

Misdiagnosis of cancer due to multiple glove powder granulomas.

A biologically absorbable powder, the cornstarch lubricant used in the production of gloves, is treated with epichlorohydrin, a cross-linking agent forming one to three diether glycerine groups to create a glove lubricating powder. This agent, together with chemicals used in glove fabrication is able to interfere with important biological diagnostic procedures, such as polymerase chain reaction (PCR) and enzyme immunoassay as well as to induce a granulomatous reaction in traumatised surgical tissue.

Mortality study of employees with potential exposure to epichlorohydrin: a 10 year update.

OBJECTIVES: A 10 year extension of follow up (up to 1993) of 863 employees who had potential exposure to epichlorohydrin at two chemical plants between May 1948 and December 1965 was conducted to further evaluate the previously reported potential association between exposure to epichlorohydrin and heart disease. METHODS: The mortality observed was compared with that expected from the death rates from the local male population where these chemical plants are located. Workers were assigned to one of five exposure categories based on their job with the highest level of potential exposure. Vital status was ascertained to the end of 1993. RESULTS: Among diseases of particular interest, there were no excess deaths from heart disease (standardised mortality ratio (SMR) 63.3), lung cancer (SMR 63.8), or non-malignant respiratory disease (SMR 37.7) for employees with 20 or more years after first exposure. Based on the level of potential exposure to epichlorohydrin, mortality for heart disease was slightly higher (SMR 75.7, 95% confidence interval (95% CI) 51.8-106.7) in the moderate to heavy exposure group than in the none to light exposure group (SMR 59.5, 95% CI 37.7-89.3); this difference is well within the range of random variation. The SMR for heart disease was 90.4 among employees who had both probable exposure to allyl chloride and moderate to heavy exposure to epichlorohydrin, although it was 88.1 among employees who had moderate to heavy potential exposure to epichlorohydrin but no exposure to allyl chloride. CONCLUSIONS: This study does not support an association between exposure to epichlorohydrin and heart disease or lung cancer. There were no additional deaths from leukaemia in this update; the raised SMR for leukaemia noted in the previous study has substantially decreased from 500.0 to 161.3 (95% CI 33.2-471.0) and is not significant. The overall mortality and cancer mortality of employees potentially exposed to epichlorohydrin continued to be lower than that of the local population.

Evaluating the effect of glove coating on the shear bond strength of porcelain laminate veneers.

Gloves have become a standard tool in dentistry due to infection control concerns. But the starch powder with which many of these gloves are coated may contaminate surfaces on contact, creating potential problems during adhesive procedures such as the placement of porcelain veneers. The authors studied the powder's effect on the strength of the shear bond of etched porcelain to etched human tooth enamel and compared it to the effect of a powder-free polymer glove coating. While the starch coating led to a statistically significant decrease in shear bond strength, the powder-free coating produced no significant decrease in strength.

Retrospective cohort mortality study of workers with potential exposure to epichlorohydrin and allyl chloride.

Previous epidemiologic research has associated potential epichlorohydrin exposure with lung cancer and, in conjunction with allyl chloride exposure, to heart disease mortality. The study was designed to test both hypotheses by examining the mortality experience of 1,064 male employees (12,574 person-years) who had a minimum of 1 month work experience between 1957-1986 in the production or use of epichlorohydrin and allyl chloride and 1 year total employment duration at Dow Chemical's Texas Operations. Vital status follow-up occurred through 1989 of which there were 66 total deaths (standardized mortality ratio [SMR] = 80, 95% confidence interval [CI] 62-101). There were no significantly elevated SMRs for all malignant neoplasms, lung cancer, circulatory system disease, or arteriosclerotic heart disease when compared to external (U.S.) or internal (Texas Operations) populations. There were no apparent mortality trends with cumulative exposure analyses of potential epichlorohydrin exposure with and without accompanying allyl chloride exposure. A high prevalence of circulatory system death certificates were certified by nonphysicians in the local county and more than one third were described in nonspecific terms. The study results are not consistent with the prior hypothesized associations. However, the study results are limited by the cohort's size, duration of follow-up, relatively few number of observed and expected deaths, and the level of potential epichlorohydrin exposure experience.