Practically all lipid-soluble xenobiotics enter the conceptus through placental transfer. Many xenobiotics, including a number of clinically used drugs, are known to cause unwanted effects in the ...embryo or fetus, including in utero death, initiation of birth defects, and production of functional abnormalities. It is well established that numerous xenobiotics are not necessarily toxic as such, but are enzymatically transformed in the body to reactive and toxic intermediates. The cytochrome P450 (CYP) enzymes are known to catalyze oxidative metabolism of a vast number of compounds, including many proteratogens, procarcinogens, and promutagens. About 20 xenobiotic-metabolizing CYP forms are known to exist in humans. Most of these forms are most abundant in the liver, but examples of exclusively extrahepatic CYP forms also exist. Unlike rodents, the liver of the human fetus and even embryo possesses relatively well-developed metabolism of xenobiotics. There is experimental evidence for the presence of CYP1A1, CYP1B1, CYP2C8, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7 in the fetal liver after the embryonic phase (after 8 to 9 weeks of gestation). Significant xenobiotic metabolism occurs also during organogenesis (before 8 weeks of gestation). Also, some fetal extrahepatic tissues, most notably the adrenal, contain substantial levels of CYP enzymes. The full-term human placenta is devoid of many CYP activities present in liver. Placental CYP1A1 is highly inducible by maternal cigarette smoking. Other forms present in full-term placenta include CYP4B1 and CYP 19 (steroid aromatase), which also contribute to the oxidation of some xenobiotics. At earlier stages of pregnancy, the placenta may express a wider array of CYP genes, including CYP2C, CYP2D6, and CYP3A7. Due to the small size of the fetus and low abundance of CYPs in placenta, the contribution of feto-placental metabolism to overall gestational pharmacokinetics of drugs is probably minor. In contrast, several toxic outcomes have been ascribed to altered metabolic patterns in the feto-placental unit, including a putative association between reduced placental oxidative capacity and birth defects. Examples of human teratogens that are substrates for CYP enzymes include thalidomide, phenytoin, ethanol, and several hormonal agents. Recent studies have improved our understanding of the expression and regulation of individual CYP genes in the fetus and placenta, and the stage is set for applying this knowledge with more precision to the role of xenobiotic metabolism in abnormal intrauterine development in humans.
We present ten years of
R
-band monitoring data of 31 northern blazars which were either detected at very high-energy (VHE) gamma rays or listed as potential VHE gamma-ray emitters. The data comprise ...11 820 photometric data points in the
R
-band obtained in 2002–2012. We analyzed the light curves by determining their power spectral density (PSD) slopes assuming a power-law dependence with a single slope
β
and a Gaussian probability density function (PDF). We used the multiple fragments variance function (MFVF) combined with a forward-casting approach and likelihood analysis to determine the slopes and perform extensive simulations to estimate the uncertainties of the derived slopes. We also looked for periodic variations via Fourier analysis and quantified the false alarm probability through a large number of simulations. Comparing the obtained PSD slopes to values in the literature, we find the slopes in the radio band to be steeper than those in the optical and gamma rays. Our periodicity search yielded one target, Mrk 421, with a significant (
p
< 5%) period. Finding one significant period among 31 targets is consistent with the expected false alarm rate, but the period found in Mrk 421 is very strong and deserves further consideration.
Exercise is recommended to enhance bone health but data on the maintenance of the exercise-induced bone benefit is sparse. The purpose of the study was to assess the maintenance of the ...musculoskeletal benefits obtained in an 18-month intervention of high-impact exercise in premenopausal women (34 former trainees and 31 controls). Physical performance and areal bone mineral density (aBMD, g/cm2) were measured at baseline, after 18 months, and after 5 years. All significant 18-month improvements relative to controls in the trainees' neuromuscular performance (isometric leg press, and vertical jump with and without additional 10% weight of the body mass) had been lost at the 5-year follow-up. However, since the changes in aBMD in both former trainees and controls by time were similar, the exercise-induced aBMD gain (i.e. the mean statistically significant intergroup differences of 1-3% in favor of the trainees) was maintained at the femoral neck, distal femur, patella, proximal tibia, and calcaneus at the 5-year follow-up. At lumbar spine, the difference was 1.7% at both 18-month and at the 5-year follow-ups but the difference was not statistically significant (NS) in the latter follow-up. At the trochanter and unloaded distal radius, the intergroup aBMD differences were NS at both the 18-month and 5-year follow-ups. In conclusion, the bone sites aBMD increased in response to the 18-month intervention, also demonstrated maintenance of this gain 3.5 years after the intervention. In contrast, the exercise-induced improvements in the neuromuscular performance vanished during the post intervention follow-up. These findings suggest the possibility of long-term bone benefits of high-impact training in women.
Background: Operations are typically associated with sleep and other circadian rhythm disturbances. The present study was set up to evaluate the influence of spinal and general anaesthesia associated ...with knee surgery on the circadian rhythm of melatonin, which has sleep inducing properties. Previously this context has been studied only in some invasive operations and it might be that general anaesthesia induces more disturbances on circadian rhythm of melatonin than operations done with patients awake.
Methods: The circadian secretion pattern of melatonin was monitored during the pre‐ and postoperative evenings, nights and mornings to clarify possible anaesthesia/surgery‐induced changes in the nocturnal secretion of melatonin and in the phase of the melatonin rhythm. The study included 20 patients scheduled for minor orthopaedic operations. The patients were randomised to receive either spinal or general anaesthesia. Melatonin was measured from evening and morning saliva samples radioimmunologically. The nocturnal urine before and after surgery was radioimmunologically examined for 6‐hydroxymelatonin sulphate.
Results: Melatonin secretion evaluated from the saliva samples was significantly diminished during the first postoperative evening as compared with that during the preoperative evening (P<0.001). There was also a significant decline of 26% (P<0.05) in postoperative 6‐hydroxymelatonin sulphate excretion. There was no significant difference in melatonin secretion between the spinal and general anaesthesia groups.
Conclusion: Our findings suggest that anaesthesia in conjunction with surgery acutely disturbed the normal circadian rhythm of melatonin by delaying the onset of nocturnal melatonin secretion.
Transportation of selenium from mother to fetus and its possible effects on mother's zinc, copper, cadmium, and mercury levels were studied together during the first trimester and at term in 216 ...mothers. Mothers came from three geographical places with different selenium intakes. The role of selenium as a biomarker for the vital function was estimated by studying the associations between tissue or blood selenium content and placental cytochrome P450 enzyme activities and the newborn's birth weight. Regardless of the selenium intake of the mothers, higher concentrations were found in the cord blood than in mother's blood reflecting active transportation of selenium to the fetus. Active smoking was associated with higher placental selenium concentrations like it is associated with higher placental zinc concentrations. When the cadmium concentrations were high in placenta, as in smokers, the transfer of selenium from blood to placenta was increased, decreasing the selenium levels in blood. On the other hand, the high selenium concentrations in blood were connected to lower cadmium concentrations in placenta also in nonsmokers. Selenium had correlations with copper and zinc. ECOD activity in placental tissue, mercury in mothers’ hair, mothers’ age, and selenium concentrations in cord blood and placental selenium all seem to have connections with xenobiotic-metabolizing enzymes linked effects among mothers. These data suggest that selenium has an active role in the mother's defense systems against the toxicity of environmental pollutants and the constituents of cigarette smoke.
The skeletal response to exercise and training on bone is exceptionally good during the growing years. However, it is not known whether the benefit of training on bone is maintained after the ...training. This 20-month follow-up study assessed the effect of a 9-month jumping intervention on bone gain and physical performance in 99 girls (mean age 12.5 +/- 1.5 years at the beginning of the study) one year after the end of the intervention. Both bone mineral content (BMC), by dual energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur, and physical performance parameters (standing long jump, leg extension strength, and shuttle run tests) were measured at baseline and at 20 months. A multivariate regression analysis was first used to determine the best predictors of the BMC accrual by time. Analysis showed that age at baseline and square of age, changes in height and weight, and pubertal development into Tanner stages 4 and 5 during the follow-up explained the majority of the BMC gain. Then, the effect of participation in the 9-month exercise intervention on BMC accrual and physical performance was analysed adding this variable (participation: yes/no) into the model. The regression analysis showed that the trainees (N = 50) had 4.9 % (95 % CI, 0.9 % to 8.8 %, p = 0.017) greater BMC increase in the lumbar spine than the controls (N = 49). The mean 20-month BMC increase in the lumbar spine was 28 % (SD 19) in the trainees compared to 22 % (12) increase in the controls. In the proximal femur, the trend was similar but the obtained 2 to 3 % higher BMC accrual in the trainees (compared to that in controls) were statistically insignificant. Among the performance variables, using the same model that best predicted the BMC accrual, the only statistically significant between-groups difference, in favour of the trainees, was the improvement in the standing long jump test (6.4 %, 95 % CI, 2.3 % to 10.4 %, p = 0.002). Improvements in the leg extension strength and shuttle run tests showed no between-groups difference. In conclusion, although the greatest proportion of bone mineral accrual in growing girls is attributable to growth, an additional bone gain achieved by jumping training is maintained at the lumbar spine at least a year after the end of the training.
The purpose of this study was to evaluate the test-retest and inter-rater reliability of nine selected tests for the following basic motor skills: balance, orientation, sense of rhythm, kinaesthetic ...precision and flexibility. Twenty-five healthy, non-sporting volunteers (14 men, 11 women, aged 36-72 years) were tested in three sessions at one-week intervals by two raters. For the tests of balance on a bar, tandem walking backwards and forwards and ball bouncing, the within-participant and between-session repeatability, as assessed by the intraclass correlation coefficient (ICC), was high (ICC 0.83-0.96), and for the rhythm test it was fair (ICC 0.70). The inter-rater reliability was also high for all the tests (ICC 0.88-0.96) except that for rhythm (ICC 0.76). In a test-retest design, these tests were sensitive enough to produce sufficient variation between participants in terms of differentiating between individuals. The learning effect was the most remarkable between the pretest and test sessions, and the reliability was better for the test-retest session although a statistically significant difference existed only for tandem walking forwards (p<0.02) and balance on a bar (p<0.004). The tests with quantitative scores had a smaller margin of error than those with qualitative scores. These tests provide reliable alternatives for assessing basic motor skills of non-sporting adults in the context of physical activity promotion.
We compared the effects of one vs two daily bouts of walking on aerobic fitness and body composition in postmenopausal women. One hundred and thirty‐four subjects were randomized into exercise groups ...or a control group and 130 completed the study. The subjects walked 5 d/week for 15 weeks at 65% of their maximal aerobic power expending 300 kcal (1255 kJ) in exercise in one (Group S1) or two daily sessions (Group S2). VO2max was measured in a direct maximal treadmill test. Body mass index (BMI) was calculated and the percentage of body fat (fat%) estimated using skinfold measurements. The net change in the VO2max was 2.5 mL min/kg (95% CI 1.5, 3.5) (8.7%) in Group S1 and 2.5 mL min/kg (95% CI 1.5, 3.5) (8.8%) in Group S2. The net change in body mass was −1.2 kg (95% CI−1.9, −0.5) in Group S1 and −1.1 kg (95% CI −1.8, −0.4) in Group S2. The net fat% change was −2.1% (95% CI−2.7, −1.4) in Group S1 and −1.7% (95% CI−2.3, −1.0) in Group S2. Exercise improved the maximal aerobic power and body composition equally when walking was performed in one or two daily bouts.
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