Comparative effects of phthalate monoesters on gap junctional intercellular communication and peroxisome proliferation in rodent and primate hepatocytes

Several phthalate esters, compounds used as plasticizers in a variety of commercial products, have been shown to induce hepatic tumors in rodents. In this study, the comparative effects of phthalate monoesters on inhibition of gap junctional intercellular communication and induction of peroxisomal beta-oxidation were assessed in primary cultured hepatocytes from rats, mice, hamsters, cynomolgus monkeys, and humans. A human liver cell line was also utilized. Eight monoesters examined included mono-2-ethylhexyl phthalate (MEHP), mono-n-octyl phthalate (MNOP), mono-isononyl phthalate (MINP, 3 types, -1, -2, and -3), mono-isoheptyl phthalate (MIHP), mono-isodecyl phthalate (MIDP), and mono-(heptyl, nonyl, undecyl) phthalate (M711P). Gap junctional intercellular communication was measured 4 and 24 h after treatment by lucifer yellow dye coupling. Gap junctional intercellular communication was inhibited in rat and mouse hepatocytes by all eight monoesters in a concentration-dependent manner. In most cases, gap junctional intercellular communication was significantly reduced at the lowest concentrations tested (50 pM). Inhibition of gap junctional intercellular communication in rodent cells was substantially reversed within 24 h of monoester removal. In contrast, cell-to-cell communication was not inhibited in hamster, cynomolgus, or human hepatocytes or in a human liver cell line at any concentration examined. In rat hepatocytes, peroxisomal beta-oxidation was elevated after treatment with MEHP, MINP, MIHP, and MIDP but not MNOP or M711P, and with all but MIHP in mouse hepatocytes. The eight phthalates produced no marked change on peroxisomal beta-oxidation in hepatocytes from other species. These data provide additional evidence that the toxicological effects of phthalate esters are species specific.     

Evaluation and development of spinosyns to control ectoparasites on cattle and sheep

The spinosyns are a novel family of fermentation-derived natural products that exhibit potent insecticidal activities. Spinosad, a naturally-occurring mixture of spinosyn A and spinosyn D, has successfully established its utility for crop protective applications in the agrochemical field. Potential applications of this unique chemical family of macrolides also have been investigated in the field of animal health. Applications for the control of blowfly strike and lice on sheep have now been commercially developed and registered in Australia and potential applications for the control of ectoparasites on cattle are being studied.     

Adolescent participation in the U.K. national lottery games

This study investigated illegal participation in the two U.K. National Lottery games (on-line game and scratchcards) by children under the age of 16 years. The sample consisted of 256 children aged between 13 and 15 years from four mixed-sex comprehensive schools/colleges, which serve city, town, rural and coastal catchment areas in the county of Devon, U.K. Pupils completed a questionnaire in a controlled environment at their respective schools/colleges. The findings indicated that 56% of the sample had participated in the National Lottery on-line game and 54% in the National Lottery Instants scratchcards. Regression analysis revealed that the best predictors of participation in the on-line game were income, household participation, whether the TV show was watched and whether a retailer had ever refused to sell a child a lottery ticket. The same variables (minus watching of the TV show) were also the best predictors of buying scratchcards.     

An evaluation of alcohol attendances to an inner city emergency department before and after the introduction of the UK Licensing Act 2003

Background  

The Licensing Act 2003 (The Act) was implemented on the 24th November 2005 across England and Wales. The Act allowed more flexible and longer opening hours for licensed premises. We investigated the effect of The Act on alcohol related attendances to an inner city emergency department in Birmingham, UK.     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Screening for a raised rectal temperature in Africa

The main purpose of this study was to compare rectal and axillary temperature measurements in African children. Altogether 573 sick children were seen in an outpatient setting in rural West Africa. Rectal and axillary temperatures were measured and the parent or guardian was asked if they thought that the child had a raised body temperature. Normal ranges were defined from an age matched population of 203 healthy children. A raised axillary temperature predicted a raised rectal temperature with a sensitivity of 98% and a specificity of 88%. The parents' impression that their child had a fever was a less sensitive (89%) and less specific (59%) indicator of raised rectal temperature. A raised axillary temperature is a good screening test for a raised rectal temperature in African children.