Establishment of an isotope dilution LC-MS/MS method revealing kinetics and distribution of co-occurring mycotoxins in rats

An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a fast sample preparation using homemade clean-up cartridges was developed for simultaneous determination of co-occurring mycotoxins exemplified with aflatoxin B1 (AFB1) and T-2 toxin (T-2) in representative biomatrices of rat plasma, heart, liver, kidney, spleen, lung and brain in a total run time of 7 min. The established approach using stable internal standards of [C-13(17)]-AFB1 and [C-13(24)]-T-2 was extensively validated by determining the specificity, linearity (R-2 >= 0.9990), sensitivity (lower limit of quantitation at 0.05 ng mL(-1)), accuracy (70.9-107.7%), precision (RSD = 70.8%). Based on this methodological advance, the subsequent kinetics and tissue distribution after oral administration of 0.5 mg kg(-1) b.w. of both AFB1 and T-2 in rats were thoroughly studied. As revealed, both AFB1 and T-2 were rapidly eliminated with the half-life time (t(1/2)) in plasma of 8.44 +/- 4.02 h and 8.12 +/- 4.05 h, respectively. Moreover, AFB1 accumulated in all organs where the highest concentration was observed in liver (1.34 mu g kg(-1)), followed by kidney (0.76 mu g kg(-1)). Notably, only low levels of T-2 were observed in spleen (0.70 mu g kg(-1)) and in liver (0.15 mu g kg(-1)). The achieved data as supporting evidence would substantially promote the practical application of the proposed LC-MS/MS method for in vivo toxicokinetics and toxicity studies of co-occurring mycotoxins imitating natural incidence in rat system

Human Ecology, Process Philosophy and the Global Ecological Crisis

This paper argues that human ecology, based on process philosophy and challenging scientific materialism, is required to effectively confront the global ecological crisis now facing us

Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics and ribosome

Abstract DNA topoisomerase I (Top1) is the target of camptothecin and novel Top1 inhibitors are in development as anticancer agents. Top1 inhibitors damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3'-end of the broken DNA. Tyrosyl-DNA phosphodiesterase (Tdp1) can repair Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. Inhibiting Tdp1 has the potential to enhance the anticancer activity of Top1 inhibitors (http://discover.nci.nih.gov/pommier/pommier.htm) and to act as antiproliferative agents. In the present study, we report that neomycin inhibits Tdp1 more effectively than the related aminoglycosides paromomycin and lividomycin A. Inhibition of Tdp1 by neomycin is observed both with single-and doublestranded substrates but is slightly stronger with duplex DNA, which is different from aclarubcin, which only inhibits Tdp1 with the single-stranded substrate. Inhibition by neomycin can be overcome with excess Tdp1 and is greatest at low pH. To our knowledge, aminoglycoside antibiotics and the ribosome inhibitors thiostrepton, clindamycin-2-phosphate and puromycin are the first reported pharmacological Tdp1 inhibitors

Addressing Parental Smoking in Pediatric Settings of Chinese Hospitals: A Qualitative Study of Parents

This study explored factors associated with SHS exposure from parental smoking in Chinese families and assessed nature of antismoking discussions parents had with their children's pediatricians and how pediatricians might best engage with parents in an effort to reduce children's exposure to SHS. Six focus group discussions (FGDs) were conducted among 33 Chinese parents attending six major hospitals in Guangxi province, China. Most participants (32/33) had family members who smoke, and only 21% had strict restriction on smoking at home. Some parents did not know about health consequences of smoking and effects of SHS exposure on children. Situations that made it especially hard to avoid the child's SHS exposure were having an elderly smoker at home and having a visitor who smoked. Only few parents were asked by pediatricians about child's exposure to SHS at home, but only when child's illness was related to smoking. Parents believed that suggestions coming from pediatricians about smoke-free home and parental quitting would be acceptable to parents and other household members. The findings provide insight into SHS exposure reduction effort among Chinese parents and underscore the demand for pediatrician's engagement in addressing parental tobacco use

Secondhand smoke exposure assessment and counseling in the Chinese pediatric setting: a qualitative study

Background: Assisting smoking parents to quit smoking and eliminating the secondhand smoke (SHS) exposure of their children is a global health priority. Engaging healthcare workers in developing countries to address this priority has been a challenge. This study intends to explore issues around current practice related to SHS exposure assessment and counseling and identify barriers to SHS exposure reduction counseling in the Chinese pediatric setting. Methods: We conducted qualitative interviews (11 focus groups discussions (FGDs) with pediatricians, 6 FGDs with pediatric nurses and 11 in-depth interviews (IDIs) with hospital administrators) among 101 health-care professionals (HCP) from 5 hospitals in four major cities of Guangxi Province, China. All FGDs/ IDIs were audio recorded and analysed thematically. Results: The findings suggest that few Chinese pediatricians routinely address the SHS exposure of children in their usual practice. All HCPs felt the need for clinical interventions to promote SHS exposure reduction for children. Primary barriers to SHS exposure reduction counseling in the Chinese pediatric setting included: lack of skills and training in tobacco use reduction and cessation counseling; time constraints and heavy workloads, uncertainty about the usefulness of smoking cessation interventions and lack of hospital-wide systems requiring pediatricians to record tobacco use or SHS exposure information. Ideas for overcoming these barriers were building capacity of pediatricians, collaboration with international organization to initiate training, engaging top level leaders in the effort and ensuring financial resources to support the program. Conclusions: This study among hospital administrators and service providers in China demonstrated a high level of interest in delivering SHS exposure reduction interventions in the pediatric setting. The findings can inform the creation and delivery of clinical interventions in China to promote SHS exposure reduction to children in the pediatric setting. Electronic supplementary material The online version of this article (doi:10.1186/1471-2431-14-266) contains supplementary material, which is available to authorized users

Organophosphate ester pollution in the oceans

The large-scale use of organophosphate esters (OPEs) as flame retardants and plasticizers has led to their prevalence in the environment, with still unknown broader impacts. This Review describes the transport and occurrence of OPEs in marine systems and summarizes emerging evidence of their biogeochemical and ecosystem impacts. Long-range environmental transport via the atmosphere and ocean currents distributes OPEs from industrialized regions to the open ocean. OPEs are most prevalent in coastal regions, but notable concentrations are also found in the Arctic and regions far from shore. Air–water interactions are important for the transport of OPEs to remote oceans and polar regions. Processes such as degradation and sinking of particle-bound compounds modulate the properties and fate of OPEs in the water column, where they are potentially a non-accounted source of anthropogenic organic phosphorus for microbial communities. Some OPEs have toxic effects in marine species and are found in measurable quantities in fish and other aquatic organisms. However, there is conflicting evidence on the potential for bioaccumulation and biomagnification of OPEs. Future work must constrain the large-scale impact of OPEs on marine biota and biogeochemistry to support more effective regulation and mitigation

Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation.

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell migration, microtubule reorganization, and heterotypic adhesion of prostate cancer cells to endothelial cells. IL-6-driven metastasis was predominantly mediated by Stat3 and to lesser extent by ERK1/2. Most importantly, pharmacologic inhibition of Jak1/2 by AZD1480 suppressed IL-6-induced signaling, migratory prostate cancer cell phenotypes, and metastatic dissemination of prostate cancer in vivo in nude mice. In conclusion, we demonstrate that the cytokine IL-6 directly promotes prostate cancer metastasis in vitro and in vivo via Jak-Stat3 signaling pathway, and that IL-6-driven metastasis can be effectively suppressed by pharmacologic targeting of Jak1/2 using Jak1/2 inhibitor AZD1480. Our results therefore provide a strong rationale for further development of Jak1/2 inhibitors as therapy for metastatic prostate cancer

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with 500 CD4+ cells/mm 3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation

Are Chinese pediatricians missing the opportunity to help parents quit smoking?

Background: Secondhand smoke (SHS) exposure of children due to parental tobacco use is a particularly prevalent health issue and is associated with adverse health outcomes. Following the US Clinical Practice guidelines, pediatricians in the United States deliver 5A’s (ask, advise, assess, assist, and arrange) counseling to smoking parents which has proven to be effective. We examined Chinese pediatricians’ adherence to the clinical practice guidelines for smoking cessation (i.e. 5A’s counseling practices) with smoking parents, and identified factors associated with these practices. Methods: A cross-sectional paper-and-pencil survey of pediatricians was conducted in twelve conveniently selected southern Chinese hospitals. Factors associated with any of the 5A’s smoking cessation counseling practices were identified by logistic regression. Results: Of respondents (504/550), only 26 % routinely provided 5A’s smoking cessation counseling to smoking parents. More than 80 % of pediatricians didn’t receive formal training in smoking cessation and had not read China smoking cessation guidelines; 24 % reported being “very confident” in discussing smoking or SHS reduction with parents. Pediatricians who had never smoked (OR: 2.29, CI:1.02-5.12), received training in smoking cessation (OR: 2.50, CI:1.40-4.48), had read China smoking cessation guidelines (OR: 2.17, CI:1.10-4.26), and felt very (OR: 7.12, CI:2.45-20.70) or somewhat (OR: 3.05, CI:1.11-8.37) confident in delivering cessation counseling were more likely to practice 5A’s. Pediatricians who reported “it is hard to find a time to talk with parents” (OR: 0.32, CI: 0.11-0.92) or “lack of a standard of care requiring pediatricians to provide smoking cessation or SHS exposure reduction intervention” (OR: 0.45, CI: 0.21-0.98) as a barrier were less likely to follow the 5A’s guidelines. Conclusions: Smoking cessation counseling to address parental smoking is infrequent among Chinese pediatricians. There is a need to develop and test intervention strategies to improve the delivery of 5A’s smoking cessation counseling to parental smokers