Biomarker Responses in Whitefish (Coregonus lavaretus L. s.l.) Experimentally Exposed in a Large Lake Receiving Effluents from Pulp and Paper Industry

Physiological and biochemical biomarker responses were studied in juvenile whitefish (Coregonus lavaretus L. s.l.) exposed experimentally to effluent from the forest industry. The large study area (609 km²), Southern Lake Saimaa, in Southeast Finland, receives 330,000 m³ d⁻¹ of biologically and 55,000 m³ d⁻¹ of chemically treated effluents, discharged from two integrated elementary chlorine free (ECF) bleached kraft pulp and paper mills, from one ECF pulp mill, and from one mill producing unbleached pulp and cardboard. The assessment of exposure to effluent discharged from the mills was based on lake water chlorophenolics (CPs) and resin acids (RAs) measured in samples collected from the 22 experimental sites along the area. Despite the low levels of effluent constituents in the lake, they were still accumulated in detectable levels in fish bile, indicating an exposure to the bioactive compounds of effluents. In comparison to the reference area, a two- to four-fold increase in ethoxyresorufin O-deethylase (EROD) activity was observed in whitefish exposed in the vicinity (1–6 km) of all the mills. However, cytochrome P450 1A1 (CYP1A1) gene expression was increased in only one of the receiving areas, indicating higher sensitivity of the EROD activity in the present study. There were no statistically significant correlations between EROD activity and the ambient water concentrations of the CPs, the RAs, or effluent dilution expressed by water sodium concentration. Neither bile chlorophenolics nor bile resin acids showed a significant correlation with EROD. No significant changes in circulating reproductive steroids, 17β-estradiol and testosterone, in juvenile whitefish were observed. The vitellogenin gene was expressed in the vicinity of the pulp mill discharging the most wood-derived compounds, i.e. resin acids and wood-sterols, including β-sitosterol. No differences were observed in plasma immunoglobulin M, glucose, or lactate concentrations between the effluent sources. Received: 25 March 1997/Accepted: 28 July 1997     

Effects of metformin treatment on glucose transporter proteins in subcellular fractions of skeletal muscle in (fa/fa) Zucker rats.

1. The present study was designed to clarify the cellular mechanism through which the antihyperglycaemic drug, metformin, exerts its effects. For this purpose the contents of glucose transporter protein isoforms GLUT1 and GLUT4 were measured in plasma membrane and intracellular membrane fractions of skeletal muscle obtained from genetically obese, insulin-resistant Zucker rats. 2. Hindlimb muscles were dissected from metformin-treated (300 mg kg-1 day-1, p.o., for 12 days) and control rats in basal treatment state, and after acute stimulation with insulin (22 u kg-1, i.p.). Since metformin treatment reduces food intake, we also used a pair-fed control group to investigate the effects of altered insulinaemia per se. Glucose transporter levels were analysed by Western blot and slot blot-techniques. In addition, 2-deoxy-[14C]-glucose uptake in isolated muscle strips was evaluated. 3. No changes were noted in the contents of GLUT1 proteins in any of the subcellular fractions after metformin treatment. The contents of GLUT4 in subcellular fractions were not altered in the basal treatment state. After acute insulin exposure the content of GLUT4 in the intracellular membrane fraction declined significantly in the metformin-treated group, while no significant effect was seen in the plasma membrane fraction. In agreement with these results, metformin treatment did not alter 2-deoxyglucose uptake into isolated muscle strips. 4. In conclusion, the present study does not support the concept that metformin would enhance translocation of glucose transporter proteins from the intracellular compartment to the plasma membrane in skeletal muscle in vivo.     

Decision aids for localized prostate cancer treatment choice: Systematic review and meta‐analysis

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251. © 2015 American Cancer Society.     

Development of human fetal prostate in culture

Summary The direct influence of androgens on prostatic development was studied by culturing explants of urogenital sinuses of human embryos and fetuses aged 6 to 13 weeks in the presence of either 10^-7 mol/l testosterone or dihydrotestosterone for 6 days. The differentiation of prostatic epithelial cells started both in control and androgen-treated explants in the ninth week, and androgens accelerated the differentiation of the secretory pathway organelles in the epithelial cells. The amount of granular endoplasmic reticulum and the number of Golgi complexes increased in the presence of androgens, especially in the older fetuses. Incipient secretory activity appeared in some cells during the culture and the differentiation occurred sooner in the androgen-treated explants than in the controls or in vivo. The differentiation and maintenance of the urogenital mesenchyme was also better in the presence of the hormone. The direct epitheliomesenchymal cell contacts seen earlier in vivo were also seen during the differentiation in vitro. These contacts may indicate an inductive role of the mesenchyme in the glandular morphogenesis. Androgens were not able to induce the epithelial differentiation in vitro before the first signs of mesenchymal differentiation were evident in vivo. The results suggest either that the mesenchymal changes are not solely determined by androgens or that the early explants may require additional factors for proper differentiation.     

Molecular epidemiology of tick-borne encephalitis virus in Ixodes ricinus ticks in Lithuania

In Lithuania, 171-645 serologically confirmed cases of tick-borne encephalitis occurred annually [Mickiene et al. (2001): Eur J Clin Microbiol Infect Dis 20:886-888] in 1993-1999, and the tick-borne encephalitis virus (TBEV) seroprevalence in the general population was found previously to be 3.0% [Juceviciene et al. (2002): J Clin Virol 25:23-27]. To assess the risk for TBEV virus infection in Lithuania and to characterize the agent a panel of 3,234 ticks combined into 436 pools [Juceviciene et al., 2005] were tested for presence of TBEV RNA by a nested RT-PCR targeting at the NS5 gene. Six pools were confirmed positive and the prevalence of the infected ticks was 0.2% (if one tick per pool [Juceviciene et al., 2005] was considered positive) and the proportion of positive tick pools was 1.4%. The prevalence of the infected ticks in the Panevezys, Siauliai, and Radviliskis regions (in central Lithuania) was 0.1%, 0.4%, and 1.7% corresponding with a higher TBE disease burden in these regions. The 252-nucleotide NS5-region amplicons, and a longer sequence (737 nucleotides) obtained from one sample from the PrM-E gene region, were sequenced. Phylogenetic analysis of the latter showed that all western type TBEV PrM-E sequences, including the Lithuanian strains, were monophyletic, showed no clustering and had very little variation. The NS5 sequences, although identical within one locality, did not show any mutations common to strains from the two Lithuanian regions, nor could any geographical clustering be found among western type TBEV strains from other areas.     

COX-1 and -2 expressions in sex-related organs of neonatally estrogen-treated rats and in activated and nonactivated macrophage RAW264.7 cells with phytoestrogen

Cyclooxygenase (COX)-2 is an inducible isoform, expressed in inflamed leukocytes and cancer cells. It is known that estrogen causes prostate dysplasia, but little is known about COX-2 expression and its influence on male reproductivity. In this study, we show that COX-2 was abolished in the distal end of the vas deferens in neonatally estrogenized (diethylstilbestrol, NeoDES) Sprague-Dawley (SD) rats at age of 15 mo, but the control normal rats were found to remain constitutive expression at the same age, while the levels of COX-1 in these rats remained intact. Furthermore, BAX, an indicator of sperm quality, was observed in the endothelium of vas deferens and sperm of the aged rats. However, COX-2 was not detected in the inflamed lesions of NeoDES rat's prostate by immunohistochemistry. In addition to estrogen, hydroxymatairesinol (HMR), a phytoestrogen, was analyzed in vitro for possible regulation on COX-2. Through Western blot analysis, HMR was shown to have no inhibitory affect on COX-2 expression. These results indicated that estrogen treatment strongly influences the expression of COX-2 that is associated with fertility, but no induction of COX-2 by estrogen may not exclude COX-2's role in prostatitis, and the anti-tumor mechanism of HMR largely remains elusive.     

Division of the male rat rhabdosphincter into structurally and functionally differentiated parts

In order to understand the structure-function relationship in the male rat rhabdosphincter, the 3D structure of the striated muscle and associated dense connective tissue was reconstructed from representative serial sections cut from the proximal urethra harboring the muscle. The 3D structure was correlated with electromyography (EMG) of the rhabdosphincter, urodynamic parameters (bladder pressure and flow rate), and longitudinal contraction force of the proximal urethra. The muscular component of the rhabdosphincter consisted of a homogeneous population of the fast-twitch-type fibers. In the cranial part, striated muscle formed a complete ring encircling the urethra, deferent ducts, and ducts from seminal vesicles and prostatic lobes. Toward the middle part, the amount of densely packed connective tissue lacking type III collagen increased anteriorly and posteriorly and penetrated the muscular ring that became divided first posteriorly and then anteriorly into two symmetrical halves. In the caudal part, a thin midsagittal dense connective tissue septum remained posteriorly. EMG recordings suggested that the rhabdosphincter muscle was functionally divided into two parts. Unlike the cranial and middle parts, the caudal part did not show the first depolarization peak. It appears that rapid oscillatory oblique-to-circular muscular contractions proceeding in craniocaudal direction in the cranial and middle part draw the anterior wall supported by arch-like dense connective tissue closer to the posterior wall supported by a more rigid rhomboidal raphe. Longitudinal contractions of the urethra are possibly evoked from the proximal and caudal parts of rhabdosphincter. These could lead to simultaneous increase in urethral pressure ensuring rapid urine flow rate. The caudal part could augment the opening of urethral lumen during oscillatory voiding.