Triclosan: environmental exposure, toxicity and mechanisms of action

Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad spectrum antibacterial agent used in personal care, veterinary, industrial and household products. TCS is commonly detected in aquatic ecosystems, as it is only partially removed during the wastewater treatment process. Sorption, biodegradation and photolytic degradation mitigate the availability of TCS to aquatic biota; however the by-products such as methyltriclosan and other chlorinated phenols may be more resistant to degradation and have higher toxicity than the parent compound. The continuous exposure of aquatic organisms to TCS, coupled with its bioaccumulation potential, have led to detectable levels of the antimicrobial in a number of aquatic species. TCS has been also detected in breast milk, urine and plasma, with levels of TCS in the blood correlating with consumer use patterns of the antimicrobial. Mammalian systemic toxicity studies indicate that TCS is neither acutely toxic, mutagenic, carcinogenic, nor a developmental toxicant. Recently, however, concern has been raised over TCS's potential for endocrine disruption, as the antimicrobial has been shown to disrupt thyroid hormone homeostasis and possibly the reproductive axis. Moreover, there is strong evidence that aquatic species such as algae, invertebrates and certain types of fish are much more sensitive to TCS than mammals. TCS is highly toxic to algae and exerts reproductive and developmental effects in some fish. The potential for endocrine disruption and antibiotic cross-resistance highlights the importance of the judicious use of TCS, whereby the use of TCS should be limited to applications where it has been shown to be effective.     

Transfusion medicine during the summer of 2006: lessons learned in northern Israel

In July 2006 a Hizballah attack erupted at the Lebanon-Israel border. Reported here is the experience of the Rambam Health Care Campus--a level I trauma center--during 33 days of warfare. Two hundred ninety-five soldiers and 209 civilians were admitted to the emergency department (ED). Forty-eight wounded soldiers (16%) and 12 civilians (6%) had transfusion. Twenty soldiers and 1 civilian had massive transfusions. The ratio between packed red blood cells and fresh frozen plasma (FFP) used for patients who had massive transfusion was 3:2. In these patients, the median prothrombin time international normalized ratio and partial thromboplastin time increased during the first 2 hours after admission from 1.29 to 1.51 and from 33.6 to 39 seconds, respectively. Twenty patients who had massive transfusion survived. Patients with an injury severity score of at least 16 had a higher need for blood products than others, with a lower severity score, with a mean packed red blood cells unit transfusion of 7 vs 4 (P = .03) and FFP transfusion of 13 vs 1.5 (P = .002), respectively. In conclusion, we observed that early transfusion of FFP to casualties with penetrating wounds requiring massive transfusion is needed to overcome the coagulopathy present. The presence of a transfusion service representative on-site in the ED is recommended to ensure proper identification and labeling of blood samples. Real-time consultations provided by a transfusion medicine physician in the operation theater was also found to be essential.     

Assessing sources of PM2.5 in cities influenced by regional transport

The human health effects of fine particulate matter (PM2.5) have provided impetus for the establishment of new air quality standards or guidelines in many countries. This has led to the need for information on the main sources responsible for PM2.5. In urban locations being impacted by regional-scale transport, source-receptor relationships for PM2.5 are complex and require the application of multiple receptor-based analysis methods to gain a better understanding. This approach is being followed to study the sources of PM2.5 impacting southern Ontario, Canada, and its major city of Toronto. Existing monitoring data in the region around Toronto and within Toronto itself are utilized to estimate that 30-45% of the PM2.5 is from local sources, which implies that 55-70% is transported into the area. In addition, there are locations in the city that can be shown to experience a greater impact from local sources such as motor vehicle traffic. Detailed PM2.5 chemical characterization data were collected in Toronto in order to apply two different multivariate receptor models to determine the main sources of the PM2.5. Both approaches produced similar results, indicating that motor-vehicle-related emissions, most likely of local origin, are directly responsible for about 20% of the PM2.5. Gasoline engine vehicles were found to be a greater overall contributor (13%) compared to diesel vehicles (8%). Secondary PM2.5 from coal-fired power plants continues to be a significant contributor (20-25%) and also played a role in enhancing production of secondary organic carbon mass (15%) on fine particles. Secondary fine particle nitrate was the single most important source (35%), with a large fraction of this likely related to motor vehicle emissions. Independent use of different receptor models helps provide more confidence in the source apportionment, as does comparison of results among complementary receptor-based data analysis approaches.     

Kinetics of hydrolysis of dextran-methylprednisolone succinate, a macromolecular prodrug of methylprednisolone, in rat blood and liver lysosomes.

A macromolecular prodrug of methylprednisolone (MP) was synthesized by conjugating MP with dextran with a M(W) of 70000 through a succinic acid linker. It has been shown previously that the dextran-MP conjugate (DMP) releases MP directly or indirectly through formation of methylprednisolone succinate (MPS) which is further hydrolyzed to MP. To investigate the suitability of DMP conjugate as a prodrug of MP for systemic administration, the kinetics of hydrolysis of the conjugate was studied in vitro in rat blood and liver lysosomes. In blood, the hydrolysis of MPS to MP was approximately ten-fold faster than that in buffer. However, the hydrolysis rate constants of DMP conjugate to MP or MPS in blood were not different from those in buffer. Overall, the hydrolysis of DMP in the rat blood occurred with a half life of approximately 25 h. Hydrolysis of MPS to MP also occurred in the liver lysosomal fraction, but not in the control samples lacking lysosomes. However, the rate constants for the hydrolysis of DMP conjugate to MP and MPS in the lysosomal fraction were not significantly different from those in the control samples. These data suggest that the slow hydrolysis of DMP conjugate to MP or MPS in both rat blood and liver lysosomes occurs mostly, if not completely, via chemical hydrolysis. However, the conversion of MPS to MP is apparently enzymatic. The data may have significant implications for systemic administration of the prodrug.     

Treatment of water for dialysis ‐ A European survey

The EDTNA/ERCA survey of the treatment of water for dialysis was the third project organised through the Collaborative Research Programme (CRP). Data was collected from 69 haemodialysis facilities in 14 countries. Water quality in European dialysis units was mainly self‐regulated. The majority of centres aimed to meet the requirements of the European Pharmacopoeia, but only 50% carried out tests to check compliance. All facilities used reverse osmosis to treat water for dialysis, most also used softening and carbon adsorption. There was a wide variation in policies for the maintenance of carbon filters, and for the control and monitoring of contamination in the distribution system. Endotoxin tests carried out in 27 facilities showed that higher levels of contamination are associated with systems that are infrequently disinfected, and also with older system designs. The survey indicated that guidelines for water treatment are urgently needed. EDTNA/ERCA guidelines for microbiological monitoring are now being drafted, additional guidelines are under consideration.     

Sensitivity and significance of nuclear magnetic tomography findings of finger joints in rheumatoid arthritis

Evaluation of the sensitivity and value of magnetic resonance imaging (MRI) findings and miniarthroscopic investigations (mini-/needle-arthroscopy = MA) of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA). 30 patients with RA (21 female, 9 male), disease duration 2 months to 22 years and mean disease activity score (DAS) of 3.90 (range: 2.00-7.67) were examined by MRI of the hand (MCP region) and following MA of the MCP-II joints. MRI parameters for arthritis (synovial enhancement, synovial extension, cortical alterations, joint gap width) and corresponding macroscopic items (synovial extension, synovial hyperemia and vascularity, cortical alterations) by MA, scored semiquantitatively for synovitis (graduated from 0-III degree), were correlated. Additionally, normal radiographs of the hands were performed and compared with MRI findings concerning the detection of bony lesions. Evaluation of the 30 MRI and MA examination revealed highly significant correlations (p < 0.0001) for the parameters of synovial extension (MRI/MA), cortical alterations (MRI/MA) and synovial enhancement (MRI) compared to synovial hyperemia and vascularity (MA). We found significant correlations for parameters of activity and chronicity of RA pathology as assessed by MRI and MA. The detection rate of cortical lesions by MRI was two and a half times higher than by X-ray. MRI findings of MCP-II joints compared to those of MCP III-V showed that the MCP-II joint was more strongly involved.     

A meta-analysis on depression and subsequent cancer risk

Background

The authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks.

Methods

Studies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjects

Results

Thirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26).No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91).No significant associations were found for lung, colon or prostate cancer.

Conclusion

This review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression.

     

幽门螺杆菌感染处理的当前观念——MaastrichtⅢ共识报告

名词缩写 欧洲幽门螺杆菌研究小组：European Helicobacter Study Group，EHSG 胃食管反流病：gastro-esophageal reflux disease，GERD     

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow‐up for patients with no residual mass

There is no consensus regarding optimal follow‐up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo‐ and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow‐up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed‐up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically‐based surveillance with dedicated imaging upon relapse suspicion (Group II). Five‐year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow‐up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression‐free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow‐up. The cost was 10 times higher for routine imaging.