Lack of modulation effects of praziquantel on DMN-induced lesion development in the Syrian hamster liver.

The effects of repeated praziquantel administration subsequent to dimethylnitrosamine (DMN) treatment of Syrian hamsters were investigated. The antihelminthic drug was given (200 mg/kg body wt. as a suspension in corn oil, by i.g. intubation) 11 times at 2 week intervals starting at week 4 after initial 20 mg/kg DMN i.p. injections at weeks 0 and 2. Sacrifice at week 28 revealed no differences in either hepatocellular or cholangiocellular lesion development between carcinogen-initiated groups with or without antihelminthic treatment. No lesions were observed in the praziquantel alone or untreated groups. The results thus indicate no promotion potential for praziquantel on nitrosamine-induced lesions in the hamster liver.     

Implementation of the World Health Organization Trauma Care Checklist Program in 11 Centers Across Multiple Economic Strata: Effect on Care Process Measures

Background

Trauma contributes more than ten percent of the global burden of disease. Initial assessment and resuscitation of trauma patients often requires rapid diagnosis and management of multiple concurrent complex conditions, and errors are common. We investigated whether implementing a trauma care checklist would improve care for injured patients in low-, middle-, and high-income countries.

Methods

From 2010 to 2012, the impact of the World Health Organization (WHO) Trauma Care Checklist program was assessed in 11 hospitals using a stepped wedge pre- and post-intervention comparison with randomly assigned intervention start dates. Study sites represented nine countries with diverse economic and geographic contexts. Primary end points were adherence to process of care measures; secondary data on morbidity and mortality were also collected. Multilevel logistic regression models examined differences in measures pre- versus post-intervention, accounting for patient age, gender, injury severity, and center-specific variability.

Results

Data were collected on 1641 patients before and 1781 after program implementation. Patient age (mean 34 ± 18 vs. 34 ± 18), sex (21 vs. 22 % female), and the proportion of patients with injury severity scores (ISS) ≥ 25 (10 vs. 10 %) were similar before and after checklist implementation (p > 0.05). Improvement was found for 18 of 19 process measures, including greater odds of having abdominal examination (OR 3.26), chest auscultation (OR 2.68), and distal pulse examination (OR 2.33) (all p < 0.05). These changes were robust to several sensitivity analyses.

Conclusions

Implementation of the WHO Trauma Care Checklist was associated with substantial improvements in patient care process measures among a cohort of patients in diverse settings.

     

Liver procollagen prolyl hydroxylase in Opisthorchis viverrini infected hamsters after praziquantel administration

Infection of hamsters by the human liver fluke Opisthorchis viverrini elevated liver procollagen prolyl hydroxylase activity, reflecting increased collagen biosynthesis. The increase was proportional to the intensity of infection. However, the infected liver procollagen prolyl hydroxylase activity decreased after administration of praziquantel 300 mg kg^?1 body weight, and approached normal levels two weeks after treatment. In the infected hamsters, praziquantel, at a curative dose, caused a transient increase in serum aminotransferase levels and a small but persistent rise in serum alkaline phosphatase. The drug, however, did not cause changes in these enzyme activities in the uninfected hamsters.     

Study of biodistribution and systemic toxicity of glucose functionalized SPIO/DOX micelles

The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r₂*) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system.     

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: a population study

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population.     

Histomorphological Characteristics of Cholangiocellular Carcinomas in Northeast Thailand, Where a Region Infection with the Liver Fluke, Opisthorchis viverrini is Endemic

Northeast Thailand has a very high incidence rate of intrahepatic biliary tumors which is believed to closely related to infestation with the liver fluke, Opisthorchis viverrini. This study was conducted to ascertain whether there are any phenotypic differences in such tumors between northeast Thailand and Japan, a country free of liver flukes. Forty one intrahepatic cholangiocarcinomas from patients in northeast Thailand were histopathologically compared with 39 lesions collected in Japan. The proportions of each type of adenocarcinoma in the Thailand cases were similar to those of the Japanese cases except that medullary type poorly differentiated tubular adenocarcinoma was only found in the series from Thailand. Whether the presence of medullary lesions only in the cases from the area of endemic fluke infection implies differences in etiology remains in question. The similarity in the majority of histological types, the inflammatory reactions observed in the bile ducts and the earlier development of tumors in association with parasites suggests that tumor promotion resulting from liver fluke infection rather than quantitative or qualitative differences in genetic alterations is responsible for the high frequency of cholangiocellular carcinomas in northeast Thailand. Acta Pathol Jpn 42: 734–739, 1992.     

Modulation of Dihydroxy-di-n-propylnitrosamine-induced Liver Lesion Development in Opisthorchis-infected Syrian Hamsters by Praziquantel Treatment in Association with Butylated Hydroxyanisole or Dehydroepiandrosterone Administration

The effects of praziquantel coupled with dehydroepiandrosterone (DHEA) or butylated hydroxyanisole (BHA) administration 16 weeks subsequent to dihydroxy-di- n -propylnitrosamine (DHPN) treatment and infection with Opisthorchis viverrini (OV) on lesion development in the liver of Syrian hamsters were investigated. Animals were given 80 OV metacercariae and then two i.p. injections of DHPN (500 mg/kg body weight) 4 and 5 weeks thereafter. At week 16, groups received praziquantel (250 mg/kg, i.g.) and were placed on normal diet or diet supplemented with BHA (1%) or DHEA (0.6%) until they were killed at week 24. Histopathological assessment revealed that, whereas antihelminthic treatment alone resulted in a clear reduction in hepatocellular lesion development, effects on cholangiocellular lesions were equivocal. BHA and DHEA, in contrast, were both associated with a significant reduction in frequency of cholangiofibrosis and cholangiocellular carcinoma. The former chemical, however, increased the numbers of liver nodules while the hormone brought about a decrease as well as a shift in the phenotype of the lesions. The results thus indicate that although cholangiocellular lesion development may, unlike generation of hepatocellular nodules, be to a certain extent independent of the continued presence of parasite, it can be influenced by exogenous treatments.