Consequences of xenoestrogen exposure on male reproductive function in spottail shiners (Notropis hudsonius).

There is limited information on the physiological consequences associated with exposure to xenoestrogens under field conditions. The objectives of this study were to determine the presence of estrogenic chemicals in the St. Lawrence River and their effects on male reproduction in the spottail shiner (Notropis hudsonius). Hepatic vitellogenin (VTG) mRNA levels in immature shiners indicate extensive estrogenic contamination spanning almost 50 km both upstream and downstream from the island of Montreal. Stages of spermatogenesis were assessed in fish captured at sites having varying levels of estrogenic contamination. In control fish, 95% had testis of either stage IV (50%) or stage V (45%) of spermatogenesis. At Ile Dorval, where VTG mRNA levels are moderate, fish had testes of stage III (38%) and IV (45%) and only 15% of fish were at spermatogenic stage V. In contrast, at Ilet Vert and Ile Beauregard, located in the sewage effluent plume from the City of Montreal and where hepatic VTG mRNA levels are high in fish, none of the fish were at stage V and 8% of fish at Ilet Vert were at stage II of development. Sperm concentration and various motility parameters were significantly lower in shiners from Ilet Vert as compared with those from Iles de la Paix (reference). Histological analyses of testes revealed that more than one-third of the fish captured at sites with the highest estrogenic contamination displayed intersex, a condition in which ovarian follicles were developing within the testis. These data indicate that there is significant estrogenic contamination in the St. Lawrence River that is associated with impaired reproductive function in male fish.     

Respiratory response in simultaneous exposure to flax and hemp dust

Žuškin, E., and Valíc, F. (1973).British Journal of Industrial Medicine,30, 375-380. Respiratory response in simultaneous exposure to flax and hemp dust. The effect of exposure to high concentrations of mixtures of hemp and flax dust was studied in 124 workers in two textile mills (mill A: 65-70% hemp and the rest flax, mean dust concentration 13·9 mg/m³; and mill B: about 35% hemp and the rest flax, mean dust concentration 15·8 mg/m³). A high prevalence of byssinosis was found in both mills (80% in mill B; 46·8% in mill A) after a mean exposure of no more than 13 years. In both mills, byssinotics had a higher prevalence of all chronic respiratory symptoms than non-byssinotics. This difference was more pronounced in mill A. Forty-eight percent of byssinotic women and 43% of byssinotic men had byssinosis of grade 2 or 3. Significant mean acute reductions in FEV_1·0 and ˙V_max 50% VC on Monday were recorded in subjects with and without byssinosis with a significantly larger mean reduction in byssinotics (FEV_1·0, P < 0·01; ˙V_max 50% VC, P < 0·05). ˙V_max 50% VC proved to be a more sensitive test for detecting acute effects of vegetable dust than FEV_1·0. The acute respiratory response of the subjects exposed to similar concentrations of flax and mixtures of two different proportions of flax and hemp dust was found to be equal.     

The effect of DB-67, a lipophilic camptothecin derivative,on topoisomerase I levels in non-small-cell lung cancer cells

Purpose To determine the in vitro drug sensitivity of two non-small-cell lung cancer cell lines after treatment with the novel lipophilic camptothecin derivative, 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), to determine if topoisomerase I protein levels decrease after treatment with DB-67, and to assess the duration and extent of topoisomerase I modulation after DB-67 exposure, in order to provide information about drug resistance that may be useful in determining an appropriate dosing schedule for DB-67.Methods The growth inhibition of the non-small-cell lung cancer cell lines A549 and H460 after exposure to DB-67 was evaluated with the MTS assay. A549 and H460 cells were treated for various times with DB-67 and topoisomerase I levels were determined by western blot analysis. In addition, A549 and H460 cells were treated with DB-67 for 24 h and topoisomerase I levels were determined by western blot analysis daily for 1 week after drug removal.Results DB-67 inhibited the growth of both A549 and H460 cells grown in culture; the A549 cells were more resistant to the cytotoxic effects of DB-67 than H460 cells. Notably, A549 cells had approximately one-half the baseline topoisomerase I than H460 cells. Topoisomerase I protein levels significantly decreased after 8–18 h of exposure to DB-67. Both A549 and H460 cells treated with DB-67 for 24 h had only negligible amounts of topoisomerase I at the end of treatment. However, within 24 h of drug removal topoisomerase I levels returned to near baseline levels in both cell lines.Conclusions The decrease in topoisomerase I levels caused by DB-67 may represent a mechanism of resistance to this novel camptothecin derivative. Dosing DB-67 once every 48–72 h may maximize the interaction of the drug with topoisomerase I and should be considered as a potential dosing schedule in the preclinical and clinical development of this compound.     

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

Purpose

Identifying gastroduodenal uptake of ^99mTc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls.

Methods

Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements.

Results

Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver.

Conclusion

SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind.

     

Hydroelectrolytic balance of Brazilian jiu-jitsu athletes during a simulated competition

Purpose

To analyze the hydroelectrolytic balance of Brazilian jiu-jitsu athletes during a simulated competition.

Methods

Eight athletes were analyzed in simulated competition (four matches of 10 min). Blood lactate and rating of perceived exertion (6–20 scale) were used to infer the intensity of the matches. Blood samples were taken to determine the serum levels of osmolality, total protein and some electrolytes (chlorides, sodium, potassium, calcium, magnesium, phosphorus and iron).

Results

The lactate concentration changed during the simulated competition (F _7.49 = 35.5; P < 0.001; η ² = 0.85), with an increase post-match compared to the pre-match in matches 1, 2 and 4, but not for match 3. For rating of perceived exertion, no changes were found during the competition (F _3.21 = 9.4; P = 0.440; η ² = 0.12). The matches did not change the osmolality, chlorides, sodium, potassium, magnesium and iron values. For total protein, a difference was observed between the time-points (F _{2.8; 19.6} = 4.6; P = 0.015; η ² = 0.40), with lower concentrations in pre-match 2 than pre-match 1, post-matches 2 and 3. The calcium concentration was also affected by the simulated competition (F _7.49 = 4.0; P = 0.002; η ² = 0.37), with values lower in pre-match 2 than post-matches 1 and 2. The phosphorus serum was changed by matches (F _{3.1; 21.7} = 18.6; P < 0.001; η ² = 0.73), with post-match 1 values higher than the pre-matches 1, 2, 3 and 4 and post-match 3. The pre-match 4 values were lower than post-matches 2 and 4.

Conclusion

Although there were some changes during simulated competition, important alterations in the hydroelectrolytic balance did not occur.

     

Primary infection of C57BL/6 mice with Plasmodium yoelii induces a heterogeneous response of NKT cells

NKT cells are a population of innate-like lymphocytes that display effector functions and immunoregulatory properties. We characterized the NKT cell response induced in C57BL/6 mice during a primary infection with Plasmodium yoelii sporozoites. We observed a heterogeneous NKT cell response that differed between liver and spleen. Hepatic NKT cells found in infected livers consisted mainly of CD1d-dependent CD4+ and double-negative (DN) NKT cells, whereas CD1d-independent NKT cells exhibiting a TCR(high) CD4(high) phenotype were prominent among splenic NKT cells during the infection. Hepatic and splenic NKT cells isolated from infected mice were activated and secreted mainly gamma interferon and tumor necrosis factor alpha in response to stimulation. Finally, P. yoelii-activated hepatic DN NKT cells inhibited the parasite's liver stage in a CD1d-dependent manner in vitro. However, experiments using B6.CD1d-deficient mice showed that CD1d and CD1d-restricted NKT cells are not necessary to control the parasite's development in vivo during neither the preerythrocytic stage nor the erythrocytic stage. Thus, our results show that a primary P. yoelii infection induces a heterogeneous and organ-specific response of NKT cells and that CD1d-dependent NKT cells play a minor role in the control of the development of Plasmodium in vivo in our model.     

The effects of maternal depression on fetal heart rate response to vibroacoustic stimulation

To better understand the effects of untreated maternal depression on the fetus, this study examined fetal heart rate (FHR) and FHR reactivity to vibroacoustic stimulation in pregnant women with untreated depression. The 20 participants were 32- to 36-week pregnant women divided into groups with depression (N = 10) and without depression (N = 10) based on the Beck Depression Inventory (BDI; Beck, 1977; Beck & Steer, 1987). Participants were attached to a fetal heart monitor, and 10 min of baseline FHR were recorded. A vibroacoustic stimulus (VAS) was presented, and an additional 10 min of FHR were recorded. Fetuses of mothers with depression had an elevated baseline FHR and a 3.5-fold delay in return to baseline FHR after VAS presentation. Additionally, mothers with depression had significantly higher anxiety levels and took fewer prenatal vitamins during pregnancy. Delayed habituation of FHR in the fetuses of mothers with depression may be due to alterations in the internal hormonal environment and could have implications for postnatal information processing.     

Resistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16

Toll-like receptors (TLRs) are innate sentinels required for clearance of bacterial and fungal infections of the cornea, but their role in viral immunity is currently unknown. We report that TLR signaling is expendable in herpes simplex virus (HSV)-1 containment as depicted by plaque assays of knockout mice (MyD88(-/-), Trif(-/-) and MyD88(-/-) Trif(-/-) double knockout) resembling wild-type controls. To identify the key sentinel in viral recognition of the cornea, in vivo knockdown of the DNA sensor IFI-16/p204 in the corneal epithelium was performed and resulted in a loss of IFN-regulatory factor-3 (IRF-3) nuclear translocation, interferon-α production, and viral containment. The sensor seems to have a similar function in other HSV clinically relevant sites such as the vaginal mucosa in which a loss of p204/IFI-16 results in significantly more HSV-2 shedding. Thus, we have identified an IRF-3-dependent, IRF-7- and TLR-independent innate sensor responsible for HSV containment at the site of acute infection.