Monomethylmercury (CH
3
Hg) is a neurotoxic pollutant that biomagnifies in aquatic food webs. In sediments, the production of CH
3
Hg depends on the bacterial activity of mercury (Hg) methylating ...bacteria and the amount of bioavailable inorganic divalent mercury (Hg
II
). Biotic and abiotic reduction of Hg
II
to elemental mercury (Hg
0
) may limit the pool of Hg
II
available for methylation in sediments, and thus the amount of CH
3
Hg produced. Knowledge about the transformation of Hg
II
is therefore primordial to the understanding of the production of toxic and bioaccumulative CH
3
Hg. Here, we examined the reduction of Hg
II
by sulfidic minerals (FeS
(s)
and CdS
(s)
) in the presence of dissolved iron and dissolved organic matter (DOM) using low, environmentally relevant concentrations of Hg and ratio of Hg
II
:FeS
(s)
. Our results show that the reduction of Hg
II
by Mackinawite (FeS
(s)
) was lower (<15% of the Hg
II
was reduced after 24 h) than when Hg
II
was reacted with DOM or dissolved iron. We did not observe any formation of Hg
0
when Hg
II
was reacted with CdS
(s)
(experiments done under both acidic and basic conditions for up to four days). While reactions in solution were favorable under the experimental conditions, Hg was rapidly removed from solution by co-precipitation. Thermodynamic calculations suggest that in the presence of FeS
(s)
, reduction of the precipitated Hg
II
is surface catalyzed and likely involves S
−II
as the electron donor. The lack of reaction with CdS may be due to its stronger M-S bond relative to FeS, and the lower concentrations of sulfide in solution. We conclude that the reaction of Hg with FeS
(s)
proceeds
via
a different mechanism from that of Hg with DOM or dissolved iron, and that it is not a major environmental pathway for the formation of Hg
0
in anoxic environments.
We determined the host range of the parasitoid Trichomalus perfectus (Walker), a candidate for classical biological control of cabbage seedpod weevil, Ceutorhynchus obstrictus (Marsham), an important ...pest of canola in Canada. Studies were conducted in Europe and in North America. In laboratory experiments, the levels of parasitism (acceptance) of Ceutorhynchus turbatus Schultze, C. cardariae Korotyaev, C. omissus Fall and C. querceti (Gyllenhal) by T. perfectus were not significantly different than of the target host C. obstrictus. Although C. typhae (Herbst), C. pallidactylus (Marsham), C. americanus Buchanan, C. neglectus Blatchely and Ceutorhynchus sp. nr. nodipennis were parasitised by T. perfectus, the levels of parasitism were significantly lower on these species than on C. obstrictus. Ceutorhynchus peyerimhoffi Hustache, C. erysimi (Fabricius), C. alliariae H. Brisout, C. roberti Gyllenhal, Mogulones borraginis (Fabricius), Mononychus vulpeculus (Fabricius) and the leaf-mining fly Scaptomyza flava (Fallén) were not attacked. Ecological host range surveys in Europe corroborated the prediction that T. perfectus would attack C. cardariae at similar rates to C. obstrictus. In North America, the recent discovery of T. perfectus in a C. omissus population suggests that laboratory findings predicting that C. omissus is a preferred host may be the case in the field. We found that T. perfectus attacks larvae of some Ceutorhynchus spp. feeding on Brassicaceae and does not attack species outside of that host range. Thus, the parasitoid can be defined as narrowly oligophagous. These results demonstrate the value of ecological host range studies in the area of origin to validate hypotheses generated through laboratory host range experiments.
GeneXpert® MTB/RIF (Xpert) is now widely distributed in high human immunodeficiency virus (HIV)/tuberculosis (TB)-burden countries. Yet, whether the test improves patient-important outcomes within ...HIV treatment programs in limited resource settings is unknown.
To investigate whether use of Xpert for TB screening prior to initiation of antiretroviral treatment (ART) improves patient-important outcomes, in a pragmatic randomized controlled trial we assigned 424 patients to Xpert or fluorescence sputum smear microscopy (FM) at ART initiation. The primary endpoint was a composite of 3-month mortality and ART-associated TB.
There was no difference in overall TB diagnosis at ART initiation (20% n = 43 Xpert vs 21% n = 45 FM; P = .80), with most patients in both groups treated empirically. There was no difference in time to TB treatment initiation {5 days (interquartile range IQR, 3-13) vs 8 days IQR, 3-23; P = .26} or loss to follow-up (32 15% vs 38 18%; P = 0.38). Although a nonsignificant reduction in mortality occurred in the Xpert group (11 6% vs 17 10%; 95% CI, -9% to 2%; P = .19), there was no difference in the composite outcome (9% n = 17 Xpert vs 12% n = 21 FM; difference -3%; 95% CI, -9% to 4%).
Among HIV-infected initiating ART, centralized TB screening with Xpert did not reduce the rate of ART-associated TB and mortality, compared with fluorescence microscopy.
The oxidant source in alcohol-induced liver disease remains unclear. NADPH oxidase (mainly in liver Kupffer cells and infiltrating neutrophils) could be a potential free radical source. We aimed to ...determine if NADPH oxidase inhibitor diphenyleneiodonium sulfate (DPI) affects nuclear factor-kappaB (NF-kappaB) activation, liver tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g. kg(-1). day(-1)) continuously for up to 4 wk, using the Tsukamoto-French intragastric enteral feeding protocol. DPI or saline vehicle was administered by subcutaneous injection for 4 wk. Mean urine ethanol concentrations were similar between the ethanol- and ethanol plus DPI-treated groups. Enteral ethanol feeding caused severe fat accumulation, mild inflammation, and necrosis in the liver (pathology score, 4.3 +/- 0.3). In contrast, DPI significantly blunted these changes (pathology score, 0.8 +/- 0.4). Enteral ethanol administration for 4 wk also significantly increased free radical adduct formation, NF-kappaB activity, and TNF-alpha expression in the liver. DPI almost completely blunted these parameters. These results indicate that DPI prevents early alcohol-induced liver injury, most likely by inhibiting free radical formation via NADPH oxidase, thereby preventing NF-kappaB activation and TNF-alpha mRNA expression in the liver.
The bioaccumulation of inorganic mercury (HgI) and monomethylmercury (MMHg) by benthic organisms and subsequent trophic transfer couples the benthic and pelagic realms of aquatic systems and provides ...a mechanism for transfer of sedimentary contaminants to aquatic food chains. Experiments were performed to investigate the bioavailability and bioaccumulation of particle-associated HgI and MMHg by the estuarine amphipod Leptocheirus plumulosus to further understand the controls on bioaccumulation by benthic organisms. HgI and MMHg are particle reactive and have a strong affinity for organic matter, a potential food source for amphipods. Microcosm laboratory experiments were performed to determine the effects of organic matter on Hg bioaccumulation and to determine the major route of Hg uptake (i.e. sediment ingestion, uptake from water/porewater, or uptake from 'food'). Amphipods living in organic-rich sediment spiked with Hg accumulated less Hg than those living in sediments with a lower organic matter content. Feeding had a significant impact on the amount of HgI and MMHg accumulated. Similarly, amphipods living in water with little organic matter accumulated more Hg than those living in water with a greater percentage of organic matter. MMHg was more readily available for uptake than HgI. Experimental results, coupled with results from a bioaccumulation model, suggest that accumulation of HgI and MMHg from sediment cannot be accurately predicted based solely on the total Hg, or even the MMHg, concentration of the sediment, and sediment-based bioaccumulation factors. All routes of exposure need to be considered in determining the accumulation of HgI and MMHg from sediment to benthic invertebrates.
To develop a combination treatment consisting of combretastatin A-4-phosphate (CA4P) with radiation based on tumor oxygenation status.
In vivo near-infrared spectroscopy (NIRS) and diffusion-weighted ...(DW) magnetic resonance imaging (MRI) were applied to noninvasively monitor changes in tumor blood oxygenation and necrosis induced by CA4P (30 mg/kg) in rat mammary 13762NF adenocarcinoma, and the evidence was used to optimize combinations of CA4P and radiation treatment (a single dose of 5 Gy).
NIRS showed decreasing concentrations of tumor vascular oxyhemoglobin and total hemoglobin during the first 2 h after CA4P treatment, indicating significant reductions in tumor blood oxygenation and perfusion levels (p < 0.001). Twenty-four hours later, in response to oxygen inhalation, significant recovery was observed in tumor vascular and tissue oxygenation according to NIRS and pimonidazole staining results, respectively (p < 0.05). DW MRI revealed significantly increased water diffusion in tumors measured by apparent diffusion coefficient at 24 h (p < 0.05), suggesting that CA4P-induced central necrosis. In concordance with the observed tumor oxygen dynamics, we found that treatment efficacy depended on the timing of the combined therapy. The most significant delay in tumor growth was seen in the group of tumors treated with radiation while the rats breathed oxygen 24 h after CA4P administration.
Noninvasive evaluation of tumor oxygen dynamics allowed us to rationally enhance the response of syngeneic rat breast tumors to combined treatment of CA4P with radiation.
T2N0M0 esophageal cancer Rice, Thomas W., MD; Mason, David P., MD; Murthy, Sudish C., MD, PhD ...
The Journal of thoracic and cardiovascular surgery,
02/2007, Letnik:
133, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective The study objective was to develop a treatment algorithm for cT2N0M0 esophageal cancer by determining (1) errors in clinical staging and (2) consequences of overtreatment and undertreatment ...of incorrectly clinically staged patients. Methods Of 742 clinically staged patients, 61 (8.2%) had cT2N0M0 cancer; 45 underwent surgery alone; 8 underwent surgery and postoperative adjuvant therapy; and 8 underwent induction therapy, then surgery. As reference, 31 of 666 patients (4.7%) who underwent surgery first had pT2N0M0 cancer and a 5-year survival of 61% ± 9.3%. Referent values were calculated from 445 clinically staged patients who underwent surgery first. Unmatched and matched survival comparisons were made using the log-rank test. Results Only 7 of 53 cT2N0M0 cancers treated with surgery first were pT2N0M0 (13% positive predictive value). Of incorrectly staged cT2N0M0 cancers (46/53), 29 (63%) were overstaged and 17 (37%) were understaged. Most overstaged cancers were pT1 (11 38% T1a and 15 52% T1b), and most understaged cancers were pN1 (13 76%). Matched overstaged patients treated by surgery alone (25/28) had a 5-year survival similar to that of patients with pTNM (69% ± 9.8% vs 63% ± 13%, P = .8). Understaged patients did better at 5 years than patients with pTNM if they had postoperative adjuvant therapy, not surgery alone (43% ± 22% vs 10% ± 9.5%, P = . 17). Induction therapy decreased 5-year survival compared with all other treatment strategies (13% ± 12% vs 52% ± 7.4%, P = .05). Conclusions Patients with cT2N0M0 cancers should undergo surgery first with lymphadenectomy. Clinically understaged patients should receive postoperative adjuvant therapy. In the unlikely event that patients with cT2N0M0 cancers are found to have an uncommon pT2N0M0 cancer, they will have acceptable survival with surgery alone.
The understanding of the mechanism, oxidant(s) involved and how and what protein radicals are produced during the reaction of wild-type SOD1 (Cu,Zn-superoxide dismutase) with H2O2 and their fate is ...incomplete, but a better understanding of the role of this reaction is needed. We have used immuno-spin trapping and MS analysis to study the protein oxidations driven by human (h) and bovine (b) SOD1 when reacting with H2O2 using HSA (human serum albumin) and mBH (mouse brain homogenate) as target models. In order to gain mechanistic information about this reaction, we considered both copper- and CO3(*-) (carbonate radical anion)-initiated protein oxidation. We chose experimental conditions that clearly separated SOD1-driven oxidation via CO(*-) from that initiated by copper released from the SOD1 active site. In the absence of (bi)carbonate, site-specific radical-mediated fragmentation is produced by SOD1 active-site copper. In the presence of (bi)carbonate and DTPA (diethylenetriaminepenta-acetic acid) (to suppress copper chemistry), CO(*-) produced distinct radical sites in both SOD1 and HSA, which caused protein aggregation without causing protein fragmentation. The CO(*-) produced by the reaction of hSOD1 with H2O2 also produced distinctive DMPO (5,5-dimethylpyrroline-N-oxide) nitrone adduct-positive protein bands in the mBH. Finally, we propose a biochemical mechanism to explain CO(*-) production from CO2, enhanced protein radical formation and protection by (bi)carbonate against H2O2-induced fragmentation of the SOD1 active site. Our present study is important for establishing experimental conditions for studying the molecular mechanism and targets of oxidation during the reverse reaction of SOD1 with H2O2; these results are the first step in analysing the critical targets of SOD1-driven oxidation during pathological processes such as neuroinflammation.
Surveys were conducted to determine the parasitoid communities associated with the cabbage seedpod weevil, Ceutorhynchus obstrictus (Marsham), an important invasive pest of canola in Ontario and ...Quebec, Canada. More than 18 species of Chalcidoidea (Hymenoptera) were associated with this pest through mass rearings from canola siliques. In southwestern Ontario, the most abundant species were a species of Chlorocytus Graham (23.6%–48.6%), Lyrcus perdubius (Girault) (0%–53%), L. maculatus (Gahan) (2.8%–14.7%), and species of Pteromalus Swederus (0.6%–23.1%) (Pteromalidae). In contrast, the most abundant species in Quebec were Trichomalus lucidus (Walker) (Pteromalidae) (33.3%–56.4%), unidentified Eulophidae (2.1%–39.1%), Mesopolobus gemellus Baur and Muller (Pteromalidae) (1.3%21.4%), and Necremnus tidius (Walker) (Eulophidae) (11.5%–19.3%). In the Ottawa, Ontario, area, parasitoids were first recovered in 2008, and Trichomalus perfectus (Walker) (Pteromalidae), M. gemellus, and species of Pteromalus were most prevalent. Mesopolobus gemellus and T. perfectus are reported in North America for the first time. Although existing communities appear to provide substantial parasitism (e.g., 6.3%–26.3% in 2006), species composition varies among years and differs from that in other regions in North America. Thus, parasitism levels and parasitoid communities of the cabbage seedpod weevil should be monitored to assess whether these will increase or there is a need to introduce more host-specific species from Europe that could provide greater mortality.
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