ENVIRONMENTAL AND BIOLOGICAL MONITORING OF EXPOSURE TO MANCOZEB,ETHYLENETHIOUREA, AND DIMETHOATE DURING INDUSTRIAL FORMULATION

The results of environmental (11 subjects) and biological (57 subjects) monitoring of exposure to mancozeb, ethylenethiourea (ETU), and dim ethoate are reported for employees of a firm producing commercial formulations containing these active ingredients. Urinary excretion \[GM(GSD) ] of ETU (mug/g creatinine) and alkylphosphates \[dimethylphosphate (DMP) + dimethylthiophosphate (DMTP) + dimethyldithiophosphate (DMDTP)] (nmol/g creatinine) was 65.3(4.8) and 419.2(2.1), respectively, for employees engaged in the formulation of a product containing 80% mancozeb (n= 9), 36.6(1.9) and 296.4(2.4) for those formulating a product containing 35% mancozeb (n = 9), 9.5(6.1) and 1022.4(3.0) for those engaged in plant maintenance and internal transport of materials (n = 6), 10.3(4.2) and 322.8(3.3) for those engaged in packaging the mancozeb formulations (n = 16), 4.4(3.3) and 2545.4(3.9) for those formulating a product containing 40% dimethoate (n = 11), and 3.0(2.7) and 871.7(3.3) for those bottling the same dimethoate formulation (n = 10). Air concentrations (mug/m3) ranged from 25.3 to 194.4 for dimethoate, from 0.2 to 1.3 for ETU, and from 139.9 to 949.0 for mancozeb. Urinary excretion of ETU and alkylphosphates showed a significant correlation with mancozeb (r2= .971), and ETU (r2= .858), and dimethoate (r2= .955) contamination of the hands. Potential dose estimates showed that the potential respiratory doses of mancozeb and dimethoate accounted, on the average, for 38% of the total potential dose. The potential respiratory dose of ETU was 7% of the total potential dose. Total estimated absorption did not exceed the accepted daily dose (ADI) for ETU and mancozeb, but the ADI for dimethoate was exceeded. Serum and erythrocyte cholinesterase activities in workers formulating dimethoate products were not significantly different before and after exposure.     

Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum

Ethnopharmacological importance

Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms.

Aim of the study

To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001–10 μg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract.

Materials and methods

The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum.

Results

CPE exerted a tetrodotoxin- and ω-conotoxin-resistant inhibitory effect on rat ileum motility (IC₅₀: 0.24 ± 0.02 μg/mL; E_max: 99.0 ± 0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC₅₀: 0.26 ± 0.02 μg/mL; E_max: 99.1 ± 0.46%).

Conclusion

It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca²⁺-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms.     

Biologic monitoring of exposure to organophosphorus pesticides in 195 Italian children

One hundred ninety-five 6- to 7-year-old children who lived in the municipality of Siena (Tuscany, Italy), underwent biologic monitoring to evaluate urinary excretion of several alkylphosphates that are metabolites of organophosphorus pesticides. We evaluated dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP). We obtained urine samples taken in the children's schools, and each sample was accompanied by a questionnaire about lifestyle and dietary habits. We found DMP and DMTP in detectable concentrations in the greatest number of samples (96 and 94%, respectively). The DMP values were geometric mean (GM) 116.7, [geometric standard deviation (GSD) 2.5], and a range of 7.4-1,471.5 nmol/g creatinine. The corresponding DMTP values were GM 104.3 (GSD 2.8) and a range of 4.0-1,526.0 nmol/g creatinine. DMDTP, DEP, DETP, and DEDTP concentrations were GM 14.1, (GSD 3.0), and a range of 3.3-754.6 nmol/g creatinine in 34% of the children; GM 33.2, (GSD 2.4), and a range of 5.1-360.1 nmol/g creatinine in 75% of the children; GM 16.0, (GSD 2.9), and a range of 3.1-284.7 in 48% of the children; and GM 7.7, (GSD 2.1), and a range of 2.3-140.1 in 12% of the children, respectively. The significant variable for urinary excretion of these metabolites in children was pest control operations performed inside or outside the house in the preceding month; however, the presence of a vegetable garden near the house rarely emerged. The urinary excretion of alkylphosphates in children was significantly higher than in a group of the adult population resident in the same province.     

Exposure to Omethoate During Stapling of Ornamental Plants in Intensive Cultivation Tunnels: Influence of Environmental Conditions on Absorption ofthe Pesticide

This report describes a study of exposure to omethoate during manual operations with ornamental plants in two intensive cultivation tunnels (tunnel 8 and tunnel 5). Airborne concentrations of omethoate were in the range 1.48–5.36 nmol/m³. Total skin contamination in the range 329.94–12,934.46 nmol/day averaged 98.1 ± 1.1% and 99.3 ± 0.6% of the total potential dose in tunnel 8 and tunnel 5, respectively. Estimated absorbed doses during work in tunnel 5 were much higher than the acceptable daily intake of omethoate, which is 1.41 nmol/kg b.w. This finding shows that organization of the work or the protective clothing worn in tunnel 5 did not protect the workers from exposure. Urinary excretion of alkylphosphates was significantly higher than in the general population, increasing with exposure and usually showing a peak in the urine sample collected after the work shift. Urinary alkylphosphates showed a good correlation with estimated potential doses during work in tunnel 8 and are confirmed as sensitive biological indicators of exposure to phosphoric esters. The linear regression analysis between the urinary excretion of alkylphosphate, expressed as total nmol excreted in 24 h, and total cutaneous dose allows for estimating that the fraction of omethoate absorbed through the skin during work in tunnel 8 is about 16.5%.     

What proportion of dermatological patients receive evidence-based treatment?

OBJECTIVE: To determine the proportion of dermatological patients who are offered evidence-based therapy in the routine dermatological practice. METHODS: For every patient seen for the first time at one of our tertiary hospital setting clinics between April and May 1999, the primary diagnosis and the primary intervention were recorded. For each primary diagnosis-primary intervention combination, evidence was searched for in electronic databases from January 1966 to December 1999. The proportion of patients who were offered evidence-based interventions was calculated as the main outcome measure. RESULTS: With a study sample of 136 patients, 61 different diagnosis-treatment couples were generated and 94 queries on electronic databases were performed (to account for "primary interventions" including more than 1 drug or treatment modality). Eighty-seven (64%) of 136 patients received evidence-based interventions. Evidence from randomized controlled trials was found for 69 patients (50.7% of the sample). Controlled studies lacking randomization or double blinding or including fewer than 20 patients per treatment group dealt with treatments offered to 14 patients (10.3%). The treatments offered to 4 patients (2.9%) were judged to have self-evident validity (ie, trials unanimously judged unnecessary). Symptomatic and supportive measures accounted for most interventions lacking substantial evidence (36% of the patients), but we had to include in this class other important treatment regimens, mainly for rare conditions. CONCLUSIONS: Most of the study patients received evidence-based care. However, published trials should be carefully appraised, and relevance of clinical end points should be evaluated together with methodological issues. More accessible, clinically oriented, evidence-based information sources are needed.     

RETRACTED ARTICLE: Peripheral blood mono-nuclear cells implantation in patients with peripheral arterial disease: a pilot study for clinical and biochemical outcome of neoangiogenesis

Background

Substantial progresses in the management of peripheral arterial disease (PAD) have been made in the past two decades. Progress in the understanding of the endothelial-platelet interaction during health and disease state has resulted in better antiplatelet drugs that can prevent platelet aggregation, activation and thrombosis during angioplasty and stenting. A role in physiological and pathological angiogenesis in adults has been recently shown in bone marrow–derived circulating endothelial progenitors (BM-DCEPs) identified in the peripheral blood. These findings have paved the way for the development of therapeutic neovascularization techniques using endothelial progenitors.

Methods

This pilot study includes five patients, aged 60 to 75, with a history of claudication and recruited from September 2010 to February 2011 at the A.O.U. Federico II of Naples.PBMNCs have been implanted three times in the limb with the worst ABI value in all the patients included in the study.The clinical follow up was performed during the subsequent 12 months from the beginning of the treatment.

Results

In four patients there was a regression of ulcerative lesions.One patient’s condition improved after the first implantation but later did not respond to the further treatments.All patients achieved a pain relief as judged by the numeric pain scale. Pain relief remained satisfactory in three patients for one year. Pain gradually returned to the pre-treatment level in two patients.All patients referred an ameliorating in their quality of life expressed even by an improvement in claudication free walking distance.These improvements are reflected also by intra-arterial digital subtraction angiography (IADSA) that shows an improvement of arterial vascularization.

Conclusions

The data from this study suggest an efficacy of BM-DCEPs implantation in terms of improvement of the vascularization and quality of life in patients affected by Peripheral Arterial Disease. Nevertheless a double-blind placebo-controlled study is needed to confirm our findings.

     

Prolonged Treatment of Children with Chronic Hepatitis B with Recombinant α2a-Interferon: A Controlled, Randomized Study

A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.     

Surgical treatment and prognostic factors in colorectal cancer

AIM: The aim of this study was to make a contribution to improve the care of patients with colorectal cancer by optimizing times and methods of the follow-up; particular attention is given to factors which may be important for the prognosis and for the quality of life in the immediate postoperative period. METHODS: The study includes all the patients with colorectal cancer who underwent laparotomic surgical treatment from 1996 to 2003. The total number of patients was 226 with an average age of 65 years; male to female ratio was 1.57:1. According to the stage of tumor, an adjuvant radiotherapeutic and/or chemiotherapeutic treatment was associated to surgery. RESULTS: On the basis of the preoperative staging and tumor localization, our patients underwent: 3 total colectomies, 57 right hemicolectomies, 137 left hemicolectomies, 6 Hartmann resections, 19 Miles resections, 4 transverse resections. CONCLUSION: The results obtained show that the 5-year overall survival is particularly influenced by the stage and the factors which directly or indirectly affect the primary tumor; thus the prognostic factors which should be considered for the survival and in the follow-up of these patients are: stage, grading and nodal involvement of the tumor.