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Urinary endogenous sex hormone levels and the risk of postmenopausal breast cancer.

To assess the relation between urinary endogenous sex steroid levels and the risk of postmenopausal breast cancer, a nested case-cohort study was conducted within a large cohort (the DOM cohort) in the Netherlands (n=9,349). Until the end of follow-up (1 January 1996), 397 postmenopausal breast cancer cases were identified and a subcohort of 424 women was then taken from all eligible women. Women using hormones were excluded, leaving 364 breast cancer cases and 382 women in the subcohort for the analyses. Concentrations of oestrone, oestradiol, testosterone, 5alpha-androstane-3alpha, 17beta-diol and creatinine were measured in first morning urine samples, which had been stored since enrolment at -20 degrees C. A Cox proportional Hazards model was used, with Barlow's adjustment for case-cohort sampling, to estimate breast cancer risk in quartiles of each of the, creatinine corrected, hormone levels, the lowest quartile being the reference group. Women with higher levels of all four of the hormones were at increased risk for postmenopausal breast cancer (highest vs lowest quartile: incidence rate ratio for oestrone (IRR(oestrone)=2.5, 95% CI: 1.6-3.8; IRR(oestradiol)=1.5, 95% CI: 1.0-2.3; IRR(testosterone)=1.6, 95% CI: 1.0-2.4; IRR(5alpha-androstane-3alpha, 17beta-diol)=1.7, 95% CI: 1.1-2.7). In conclusion, women with higher excretion levels of both oestrogens and androgens have an increased risk of breast cancer.

Adult↗

Study of the effect of pH, salinity and DOC on fluorescence of synthetic mixtures of freshwater and marine salts.

In order to provide support for the discussion of the fate of organic matter in estuaries, a laboratory simulation was performed by changing freshwater ionic strength, pH and organic matter content. The change in spectroscopic characteristics caused by variations in salinity, pH and organic matter concentration in the filtered samples was observed by UV-Vis and fluorescence spectroscopy. The increase in emission fluorescence intensity of dissolved organic matter (DOM) due to increasing salinity (in the range 0 to 5 g l-1) is affected by the pH of the samples. The emission fluorescence intensity at the three maxima observed in the fluorescence spectra, is linearly correlated with dissolved organic carbon (DOC) concentration at several salinity values in the same sample. The increase in organic matter concentration caused a shift in the emission peak wavelength at 410 nm for several salinity values. We concluded that it is necessary to take into account the influence of salinity and pH on emission fluorescence of dissolved organic matter if it is to be used as a tracer in estuarine or near shore areas.

Ecosystem↗

Adrenal androgen secretion and dopaminergic activity in anorexia nervosa.

The aim of the present study was to investigate if the postulated deficient adrenal androgen secretion in Anorexia Nervosa (AN), could be associated with a status of sustained dopaminergic hyperactivity. The adrenal responses to ACTH and PRL response to dopaminergic receptor blockade were studied in seven patients with Anorexia Nervosa and seven regularly menstruating women. AN patients showed lower baseline DHEA-sulphate (DHEA-S), androstenedione (Adione) and prolactin (PRL) levels than controls. The response to ACTH revealed evidences of significantly decreased 17-20 desmolase activity in AN, with apparent predominance of glucocorticoid over androgenic pathways relative to controls. Because dopaminergic receptor blockade with Domperidone (DOM) showed intense dopaminergic hyperactivity in AN, we postulate that the adrenal regression seen in the disease is the consequence of a reduced zona reticularis as a consequence of the lack of trophic support by PRL and/or intermediate lobe proopiomelanocortin (IL-POMC). This is consistent with our previous results in pre-adrenarchal dogs and rabbits.

Adolescent↗

Exercise-induced muscle damage.

Muscular overuse is associated with structural damage of the contractile elements and reflected in delayed onset muscle soreness (DOMS). Mechanical stress is supposed to be the major contributing factor for inducing muscle damage. The initial damage is followed by an inflammatory response and eventually by regeneration. Calcium is assumed to play an important role in triggering the inflammatory changes. Biopsy data in man indicate that the inflammatory changes in humans do not parallel the soreness ratings, leaving the delayed onset of muscle soreness unexplained. It is a well known phenomenon that one bout of eccentric exercise has a long lasting protective effect against damage induced by a second bout of exercise. Experimental evidence suggests that this adaptation can partly be attributed to an increase in connective tissue. Plasma CK activity has widely been used as a marker for the amount of muscle damage. It has been shown that gender differences in exercise-induced CK release are caused by sex hormones dependent differences in sarcolemmal permeability. Plasma CK activity does not necessarily reflect the amount of structural damage.

Creatine Kinase↗

Effects of prolonged L-carnitine administration on delayed muscle pain and CK release after eccentric effort.

Eccentric muscle effort is known to induce delayed muscle soreness (DOMS) and muscle damage which are not responsive to medical treatment with the most common analgesic agents. The aim of the study was to investigate the effects of oral L-carnitine supplementation on pain (VAS scale), tenderness (pain thresholds) and CK release induced by a 20-min eccentric effort of the quadriceps muscle. A single-blind study was carried out on 6 untrained subjects (mean age: 26 +/- 3.8 yrs; mean height: 173 +/- 4.6 cm; mean body weight, 68.3 +/- 4.5 kg) over 7 weeks during which each subject: a) was given 3 g/day of placebo for 3 weeks and, after a week's interval, 3 g/day of L-carnitine for 3 weeks: b) performed 2 step tests on the first day of the 3rd and 7th week inverting the order of the exercising limb. In a separate set of experiments carried out 8 months later, the possible effects of training on pain parameters and CK levels were also investigated in the same subjects who performed 2 step tests at a 4-weeks' interval, without medication. L-carnitine significantly reduced pain, tenderness and CK release after the effort with respect to placebo. In contrast, no significant difference was found in the parameters measured between the two tests performed without medication. It is concluded that L-carnitine has a protective effect against pain and damage from eccentric effort. This effect is mainly attributed to the vasodilatation property of the compound, which both improves energetic metabolism of the hypoxic/damaged muscle and enhances wash-out of algogenic metabolites.

Adult↗

Injury rates and physiological changes associated with lateral motion training in females.

The purpose of this investigation was to evaluate physiological changes and injury rates associated with lateral motion (slideboard) training. Twenty-five females performed slideboard exercise 3 days per week, 1 hour each session, over a 10 week period. Eleven females served as controls. The subjects were pre and post tested via treadmill exercise to determine VO2peak. Body composition was analyzed by a seven-site skinfold equation. The slideboard subjects (SBS) were evaluated daily for injury incidence. A factorial repeated measures ANOVA (p < 0.05) revealed a significant 14% increase in VO2peak. No significant modifications were shown for body composition. The incidence of injury was 80% for Grade I injuries, 52% for Grade II injuries, 0% for Grade III injuries, and 4% for Grade IV injuries. Thus, the primary injury reports were of a Grade I and Grade II level of severity. The present injuries were largely associated with delayed onset muscle soreness (DOMS) in the medial leg musculature during the first two weeks of training. These results show that during a 10 wk training program lateral motion exercise is an effective mode for improving cardiorespiratory fitness. In addition, the risk of incurring an injury requiring medical attention appears to be quite low. However, untrained women who perform this activity at a frequency, duration, and intensity similar to the present study may experience muscle soreness during the initial period of training.

Adult↗

The role of a 21-kDa viral membrane protein in the assembly of vaccinia virus from the intermediate compartment.

We have recently provided morphological evidence that a key event in the assembly of vaccinia virus is the formation of a novel cisternal domain of the intermediate compartment (IC) between the endoplasmic reticulum and the Golgi complex (Sodeik, B., Doms, R. W., Ericsson, M., Hiller, G., Machamer, C. E., van't Hof, W., van Meer, G., Moss, B., and Griffiths, G. (1993) J. Cell Biol. 121, 521-541). This tightly apposed cisternal domain incompletely surrounds the spherical immature virus that matures into the first of the two distinct infectious forms of vaccinia, the intracellular mature virus (IMV). In this study we describe the characterization of an abundant membrane protein of the IMV, the gene product of A17L, a 21-kDa protein that has recently been shown to be essential for the formation of the viral membranes (Rodriguez, D., Esteban, M., and Rodriguez, J. R. (1995) J. Virol. 69, 4640-4648). Upon translation in vitro, p21 associated with rough microsomal membranes in a co-translational manner. Using NH2- and COOH-terminal specific antibodies, we show that both in vitro as well as in vivo, p21 adopts a topology where the NH2 and COOH termini are cytoplasmically orientated. Immunocytochemical experiments demonstrated that p21 is a component of the inner of the two cisternal membranes of the immature virus as well as of membranes of the IC, identified using antibodies against Rab1. Taken together, these data provide the first molecular evidence in support of our assembly model; they show that an essential membrane protein of the IMV inserts into the rough endoplasmic reticulum, but gets efficiently targeted to the IC and membranes of the viral factory.

Amino Acid Sequence↗

Supplemental protein degradation, bacterial protein synthesis and nitrogen retention in sheep eating sodium hydroxide-treated straw.

1. Alkali (sodium hydroxide)-treated wheat straw was given to six rumen- and abomasal-cannulated sheep to study the rumen degradation of cotton-seed meal (CSM) and barley (B), and the effects of these supplements on nitrogen retention and efficiency of bacterial protein synthesis were measured. 2. N degradation, using porous synthetic (nylon) bags incubated within the rumen (P), and in vivo measurement determined from the abomasal flow of N (V), distinguished quantitatively between the two supplements. Estimates of P, corrected for fractional outflow rates/h (FOR), underestimated estimates of V when FOR of undegraded protein from the rumen (k) of 0.05 and 0.08 were used. Estimates of V for CSM and B were 70.9 and 80.8% respectively. 3. Intakes of alkali-treated straw were not affected by the supplements. Intakes of digestible organic matter (DOM) for the diets comprising alkali-treated straw alone (W), straw plus CSM (WC) and straw plus barley (WB) were 477, 575 and 590 g/d respectively (P less than 0.05) and organic matter (OM) apparently digested in the rumen (OMADR) was 339, 399 and 435 g/d respectively (P less than 0.05). 4. On W, WC and WB respectively, flows at the abomasum were 11.0, 14.0 and 13.3 g/d for bacterial N (P less than 0.05) and 0, 2.8 and 0.5 g/d for dietary supplemental N; g bacterial N/kg OMADR were 32.4, 35.6 and 30.9 (P greater than 0.05) and N balances were 2.37, 4.27 and 3.29 g/d (P less than 0.05) on the respective treatments. It was suggested that supplements increased total OM intake as a result of increased OM digested in the rumen rather than OM flow from the rumen.

Animal Feed↗

Ruminal degradability of 15N labelled ribonucleic acid in grass.

The ruminal degradation of RNA in rye grass (Lolium perenne) was studied using the bag method. A non-lactating cow (BW 550 kg) fitted with a rumen cannula was used and fed twice daily at maintenance level with a chopped grass hay-based ration containing 30% ground barley. Rye grass, labelled during growth by fertilization with 15N2-urea (9.5 atom% 15N, 20 g N/m2), was cut at seven stages of growth and maturity and freeze-dried. RNA-N represented 6 to 17% of total N. Labelled grass samples (milled to 5.0 mm screen, 5.0+/-0.1 g DM) were incubated in polyester bags (100 x 200 mm, pore size 50 microm) in the rumen for periods of 1, 3, 6, 9, 12, 24, and 48 h. Data of N and RNA disappearances from the bags were fitted to an exponential equation to estimate parameters of degradation. The effective degradability of RNA in the rumen averaged 90+/-4%, for N it was 11% units lower (P < 0.001). Degradability of RNA was correlated to that of N (R2 = 0.92). Degradability of RNA (R2 = 0.96) and N (R2 = 0.93) decreased with increasing fibre content of grass. Increasing the fibre content by 1% diminished the degradability of RNA and N by 1.1% units and 2.4% units, respectively (P < 0.001). Assuming a microbial protein synthesis in the rumen of 150 g/kg DOM, a N: RNA ratio of 1:1.35 in rumen microbes and a rumen outflow rate of 0.06 h(-1), a model calculation indicates that about 9 to 19% of duodenal RNA are of dietary origin in animals fed grass. This should be taken into account for the calculation of microbial N on the basis of RNA as marker.

Animals↗

Structural characterization of metabolites after the microbial degradation of type A trichothecenes by the bacterial strain BBSH 797.

Contamination of feed with trichothecenes, a group of Fusarium mycotoxins, leads to losses in performance due to their immunosupressive effects and the negative effect on the gastrointestinal system in animal production. A possible way of detoxification is microbial degradation, which was the focus of this study. A bacterial strain--BBSH 797--which can degrade some mycotoxins of the trichothecene group, has already been isolated. It transforms deoxynivalenol (DON) into its metabolite DOM-1, the non-toxic deepoxide of DON. Analogous to the microbial degradation of DON, the transformation of six different type A trichothecenes was observed. The metabolites appearing were characterized by GC-MS after derivatization with TRI-SIL TBT. Two metabolites were additionally, identified by liquid chromatography-mass spectrometry with particle beam interface (LC-PB-MS) with electron impact (EI)-ionization mode. The major finding was that scirpentriol was completely transformed into its non-toxic metabolite deepoxy scirpentriol, while the mycotoxin T-2 triol underwent a more complicated metabolism. According to the study, T-2-triol was degraded into its non-toxic deepoxy form and into T-2 tetraol, which was then further metabolized to deepoxy T-2 tetraol. GC-MS after derivatization with TRI-SIL TBT was suitable for the structural characterization of trichothecenes and their degradation products. Besides the mass spectra of already known degradation products, spectra of new metabolites could be recorded by LC-PB-MS.

Animals↗

Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep.

The pharmacokinetics of deoxynivalenol (DON) were studied in sheep after administrating intravenous and oral doses (0.5 and 5.0 mg/kg, respectively). The plasma concentrations were measured using an electron-capture gas chromatographic method. After iv administration DON plasma levels were found to decrease biexponentially, showing a rapid distribution phase (t 1/2 alpha = 12-23 min), followed by a slower elimination phase (t 1/2 beta = 57-78 min). Only trace levels of DON could be detected in plasma 7 hr post-dosing. Further pharmacokinetic data suggest that DON was confined mainly to extracellular fluid, and did not appear to undergo any significant binding or uptake by tissue. After oral dosing, DON was quickly absorbed (t-max 4.0-5.3 hr), but had a systemic bioavailability of only 7.5%; due in part to its rapid and efficient metabolism by rumen microorganisms. Half-life of elimination (t 1/2 beta) was 100-125 min following oral administration, and depending on the animal, required 20-30 hr to be cleared from the system. The metabolic formation of the glucuronide conjugate after iv and oral administration of DON appeared to occur quite efficiently (iv, 21%; oral, 75%), and its elimination half-lives (iv, 150-200 min; oral 6.1-7.1 hr) were considerably longer than that of the parent toxin. Detection in plasma of the de-epoxide metabolite, DOM-1, accounted for only a minor portion of the dose after either dosing regimen (iv, less than 2.0%; oral, less than 0.3%), occurring predominantly as the glucuronide conjugate.

Administration, Oral↗

Influence of hay particle size at different concentrate and feeding levels on digestive processes and feed intake in ruminants. 2. Passage, digestibility and feed intake.

In order to study the main effects of particle size, three ruminally fistulated cows (550 to 580 kg BW) were fed a constant low concentrate level (3.56 kg DM/d, 20% of total DMI) and a fibre-rich hay (approximately 60% NDF in DM) in long (28.7 mm), chopped (9.2 mm) and fine ground (2.9 mm) form in a 3 x 3 Latin square design. In another three factorial experiment with 8 wethers (4 animals were ruminally fistulated, mean BW = 68 kg) the main effects and interactions of the above mentioned hay particle sizes at two concentrate levels (10.4 to 13.3% and 29.5 to 40.1% of DMI, resp.) and two intake levels (restricted and ad libitum) were investigated. In comparison to long hay (28.7 mm), feeding of chopped hay (9.2 mm) at low concentrate levels, increased not only the hay intake (7% in dairy cows and 13% in sheep) but also the intake of digestible organic matter (12% in dairy cows and 32% in sheep), due to an increase in the apparent digestibility of OM by 3.8% in dairy cows and 8.2% in sheep. Ad libitum feeding of fine ground hay in combination with low concentrate amount in the ration increased the passage rate in the hindgut and consequently the hay intake, but not the intake of DOM, due to a significant depression of digestibility, especially of fibre fractions (4 to 7% in dairy cows and 4.5 to 14% in sheep), in comparison to 28.7 and 9.2 mm hay particle sizes. The digestibility decreased significantly with restricted feeding of fine ground hay in sheep only in comparison to 9.2 mm particle size. A threefold increase of concentrate amount leveled out all effects of the particle size reduction. The effect of particle size was more pronounced in sheep than in dairy cows.

Animal Feed↗

[Influence of the ration content on the fecal phosphorus excretion of growing bulls varying in body weight].

Five smaller (body weight: 227.9 +/- 23.7 kg) and large growing bulls (435.2 +/- 14.3 kg per animal) each were fed with rations rich (chopped wheat straw:concentrate = 1:1) or poor in roughage (straw: concentrate = 1:4). Animals were kept in balance cages; 20 days adaptation period were followed by 10 days collection period. Body weight of bulls did not significantly influence apparent digestibility of rations. digestibility of organic matter of fibre rich ration was significantly lower (66.8%) than those of concentrate rich ration (74.4%). Feeding and body weight did not significantly influence metabolic parameters of mineral status. The fecal P-excretion amounted to 0.94 and 1.08 g per kg DMI in bulls fed with rations rich and poor in roughage. No influence of body weight was measured. Feeding and body weight did not significantly influence fecal P-excretion per kg DOMI (between 1.44 and 1.58 g P/kg DOM). For calculation of P-requirements for growing cattle fecal P-excretion amounted to 1.0 or 1.5 g P/kg DM and DOMI, respectively.

Animal Feed↗

The use of an in vitro cellulase enzyme technique for predicting the digestibility of tropical feeds and fodders.

An attempt has been made to find out if the organic matter digestibility of tropical feeds and fodders can be predicted from the results of an in vitro cellulase enzyme technique. The in vivo digestibility coefficient of 27 tropical feeds and fodders was determined in wethers. The enzyme insoluble organic matter content of these feeds was determined using a cellulase enzyme technique. The indigestible OM (g/kg feed DM) in vivo (y) was plotted against enzyme insoluble organic matter (g/kg DM) (x). The equation is y = 60 + 0.817x, R2 = 0.95; RSD = 32 g/kg DM. Equations for predicting DOM (g/kg DM) and digestibility of OM (%) are calculated. The testing of the equation on an independent data base of 40 individual feeds and fodders showed that the validity of the equation is fairly general.

Animal Feed↗

Feasibility study of UV disinfection for agricultural reuse of secondary level effluent in Korea.

A pilot study was performed to examine the feasibility of UV disinfection for agricultural reuse of reclaimed water. The effluent from the bio-filter of a 16-unit apartment was used as input to the flow-through type UV disinfection system, with average suspended solid (SS) and biological oxygen demand (BOD) concentrations of 3.4 and 5.9 mg/L, respectively, and a mean level of total coliforms in the range of 1.5 x 10(4) MPN/100 mL. UV disinfection was found to be effective, in that it reduced mean concentration of indicator microorganisms (total coliform [TC], fecal coliform [FC], and E. coli) to less than 100 MPN/ 100 mL within 60s exposure using 17, 25, and 40 W lamps. The microorganisms often exceeded 200 MPN/100 mL with 17 and 25W lamps, but were completely removed with 40W lamp in one cylindrical chamber. Disinfection with two chambers in series demonstrated complete removal for all the experiments. About 30 mW x s/cm2 was thought to be adequate for the disinfection of secondary effluent to keep the suggested bacterial standards of 100 MPN FC/100 mL for agricultural reuse. Water quality effect on the UV efficiency was not apparent within the experimental conditions. Statistical analysis showed that the removal rates of TC, FC, and E. coli did not significantly vary with turbidity, dissolved organic matter (DOM), or SS concentrations (p = 0.05). Photo-reactivation problems after UV disinfection might be a lesser concern in agricultural reuse than for other uses, due to exposure of water to solar radiation and resulting inactivation. Overall, UV disinfection of effluent from secondary level wastewater treatment plants in Korea was thought to be an effective and feasible alternative for agricultural reuse, and thus it is strongly recommended.

Agriculture↗

Copper phytoavailability and uptake by Elsholtzia splendens from contaminated soil as affected by soil amendments.

Pot and field experiments were conducted to evaluate bioavailability of Cu in contaminated paddy soil (PS) and phytoremediation potential by Elsholtzia splendens as affected by soil amendments. The results from pot experiment showed that organic manure (M) applied to the PS not only remarkably raised the H2O exchangeable Cu, which were mainly due to the increased exchangeable and organic fractions of Cu in the PS by M, but also stimulated plant growth and Cu accumulation in E. splendens. At M application rate of 5.0%, shoot Cu concentration in the plant increased by four times grown on the PS, so as to the elevated shoot Cu accumulation by three times as compared to the control. In the field trial, soil amendments by M and furnace slag (F), and soil preparations like soil capping (S) and soil discing (D) were performed in the PS. Soil capping and discing considerably declined total Cu in the PS. Application of M solely or together with F enhanced plant growth and increased H2O exchangeable Cu levels in the soil. The increased extractability of Cu in the rhizosphere of E. splendens was noted, which may have mainly attributed to the rhizospheric acidification and chelation by dissolved organic matter (DOM), thus resulting in elevating Cu uptake and accumulation by E. splendens. Amendments with organic manure plus furnace slag (MF) to the PS caused the highest exactable Cu with saturated H2O in the rhizospheric soil of E. splendens after they were grown for 170 days in the PS, thus achieving 1.74 kg Cu ha(-1) removal from the contaminated soil by the whole plant of E. splendens at one season, which is higher than those of the other soil treatments. The results indicated that application of organic manure at a proper rate could enhance Cu bioavailability and increase effectiveness of Cu phytoextraction from the contaminated soil by the metal-tolerant and accumulating plant species (E. splendens).

Biodegradation, Environmental↗

The energy-dependent electron loss model: backscattering and application to heterogeneous slab media.

Electron backscattering has been incorporated into the energy-dependent electron loss (EL) model and the resulting algorithm is applied to predict dose deposition in slab heterogeneous media. This algorithm utilizes a reflection coefficient from the interface that is computed on the basis of Goudsmit-Saunderson theory and an average energy for the backscattered electrons based on Everhart's theory. Predictions of dose deposition in slab heterogeneous media are compared to the Monte Carlo based dose planning method (DPM) and a numerical discrete ordinates method (DOM). The slab media studied comprised water/Pb, water/Al, water/bone, water/bone/water, and water/lung/water, and incident electron beam energies of 10 MeV and 18 MeV. The predicted dose enhancement due to backscattering is accurate to within 3% of dose maximum even for lead as the backscattering medium. Dose discrepancies at large depths beyond the interface were as high as 5% of dose maximum and we speculate that this error may be attributed to the EL model assuming a Gaussian energy distribution for the electrons at depth. The computational cost is low compared to Monte Carlo simulations making the EL model attractive as a fast dose engine for dose optimization algorithms. The predictive power of the algorithm demonstrates that the small angle scattering restriction on the EL model can be overcome while retaining dose calculation accuracy and requiring only one free variable, chi, in the algorithm to be determined in advance of calculation.

Algorithms↗

Out of step with the Lancet homeopathy meta-analysis: more objections than objectivity?

The meta-analysis of homeopathy trials that appeared in the Lancet in 1997 seemed to endorse the experience of practitioners and patients that homeopathic medicines have specific clinically relevant effects. However, results from later unsuccessful trials, and negative inferences from a review of trials for a condition excluded from the meta-analysis--delayed onset muscle soreness (DOMS)--have since been presented to suggest that the meta-analysis may well have overestimated the positive effects of homeopathy, and that the "placebo question is still not resolved." This article reviews the evidence underlying this challenge to the meta-analysis and homeopathy, and demonstrates that it would be valid if it were based on: a comprehensive literature search; appropriate classification of primary studies; clear discrimination between clinical effectiveness and placebo questions; sound and transparent review methods; and a reliable and unconfounded clinical treatment model for testing the ultramolecular hypothesis. It is suggested that different models are needed to answer different questions.

Bias↗