Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control (C) and Treated (T). The females of the T group received DBP (100 mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial (C=32.86; T=42.04*) and stromal (C=21.61; T=27.88*) compartments were increased, while the luminal compartment was decreased (C=45.54; T=30.08*), *p < 0.05. In T, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

OBJECTIVE: To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor. METHOD: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in Vitro I-125-hGH receptor binding and cell proliferation. RESULTS: Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH. CONCLUSIONS: Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.

Genetic and non-genetic factors affecting birth-weight and adult body mass index

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (rg = 0.16, p = 0.005) and environmental (re = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.

Molecular weight changes and scission and crosslinking in poly(dimethyl siloxane) on gamma radiolysis

The molecular weight changes which occur on the gamma -radiolysis of poly(dimethyl siloxane) under vacuum between 77 and 373 K and in air at 303 K have been investigated using triple detection GPC to obtain the complete molecular weight distributions for the irradiated samples and to determine the number and weight average molecular weights. The results have been interpreted in terms of the relative yields of scission and crosslinking. The total yields for crosslinking predominate over those for scission at all the temperatures investigated for radiolysis under vacuum. Based on a solid-state Si-29 NMR analysis of PDMS irradiated under vacuum at 303 K, which yielded a value of G(Y) of 1.70, the values of G(S) = 1.15 +/-0.2 and G(H) = 1.45 +/-0.2 were obtained for radiolysis under vacuum at 303 K. For radiolysis in air at 303 K, crosslinking was also predominant, but the nett yield of crosslinking was much less than that observed for radiolysis under vacuum. Under the conditions of the radiolysis in air at 303 K, because of the low solubility of oxygen in PDMS, it is likely that the radiation chemistry is limited by oxygen diffusion. (C) 2001 Elsevier Science Ltd. All rights reserved.

Neonatal hepatic drug elimination

After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood how and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.

A test of the ash-free dry weight technique on the developmental stages of Patiriella spp. (Echinodermata : Asteroidea)

Determination of the ash-free dry weight (AFDW) of marine specimens requires samples to be rinsed, soaked, and centrifuged. Problems associated with this technique were examined with the developmental stages of seastar species (Patiriella) with different modes of development. The influence of three rinsing solutions (ammonium formate [AF], filtered seawater [FSW], and reverse osmosis water [RO]) was assessed. The hypothesis that the AFDW technique is a measure of organic material was addressed by drying inorganic salts. Developmental stages of Patiriella calcar rinsed in FSW were twice as heavy as those rinsed in RO or AE indicating that samples should be rinsed in RO or AF before weighing. Soaking treatments had a significant effect on the AFDW of samples of P. calcar (planktonic developer), indicating that the rinsing period should be brief. Zygotes of Patiriella re gularis (planktonic developer) were significantly heavier than ova or gastrulae, regardless of treatment. In contrast, there were no significant differences in the AFDW of any stages or treatments of Patiriella exigua (benthic developer). This may be due to the presence of a modified fertilization envelope, which protects these benthic embryos. Inorganic salts with water of crystallization and FSW lost 20-75% and 14% of their dry weight, respectively, after ashing. We propose that salt ions may retain water, which does not evaporate during drying but is lost during ashing, resulting in the overestimation of sample AFDW. If a similar process occurs in the developmental stages of marine invertebrates, changes in the intracellular ionic composition through development may result in inaccurate estimates of biomass.

The influence of age on weight-bearing joint reposition sense of the knee

Knee joint-position sensitivity has been shown to decline with increasing age, with much of the research reported in the literature investigating this age effect in non-weight-bearing (NWB) conditions. However, little data is available in the more functional position of weight-bearing conditions. The objective of this study was to identify the influence of age on the accuracy and nature of knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial weight-bearing (PWB) conditions and to determine the effect of lower-extremity dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35 years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests were conducted on both the right and left legs to examine the ability of subjects to correctly reproduce knee angles in an active criterion-active repositioning paradigm. Knee angles were measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the test limb. Errors in FWB knee joint repositioning did not increase with age, but significant age-related increases in knee joint-repositioning error were found in PWB. It was found that elderly subjects tended to overshoot the criterion angle more often than subjects from the young and middle-aged groups. Subjects in all three age groups performed better in FWB than in PWB. Differences between the stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance. Results demonstrated that for, normal pain-free individuals, there is no age-related decline in knee JPS in FWB, although an age effect does exist in PWB. This outcome challenges the current view that a generalised decline in knee joint proprioception occurs with age. In addition, lower-limb dominance is not a factor in acuity of knee JPS.

Childhood neglect and cognitive development in extremely low birth weight infants: A prospective study

Objective. To examine the relationship between child maltreatment and cognitive development in extremely low birth weight infants, adjusting for perinatal and parental risk factors. Methods. A total of 352 infants with birth weight of

Minimum acceptable standards for digital compression of a fetal ultrasound video-clip

If the Internet could be used as a method of transmitting ultrasound images taken in the field quickly and effectively, it would bring tertiary consultation to even extremely remote centres. The aim of the study was to evaluate the maximum degree of compression of fetal ultrasound video-recordings that would not compromise signal quality. A digital fetal ultrasound videorecording of 90 s was produced, resulting in a file size of 512 MByte. The file was compressed to 2, 5 and 10 MByte. The recordings were viewed by a panel of four experienced observers who were blinded to the compression ratio used. Using a simple seven-point scoring system, the observers rated the quality of the clip on 17 items. The maximum compression ratio that was considered clinically acceptable was found to be 1:50-1:100. This produced final file sizes of 5-10 MByte, corresponding to a screen size of 320 x 240 pixels, running at 15 frames/s. This study expands the possibilities for providing tertiary perinatal services to the wider community.

Realtime fetal ultrasound by telemedicine in Queensland. A successful venture?

We have established a realtime fetal tele-ultrasound consultation service in Queensland, which has been integrated into our routine clinical practice, The service, which uses ISDN transmission at 384 kbit/s, allows patients in Townsville to be examined by subspecialists in Brisbane, 1500 km away. For the 90 tele-ultrasound consultations performed for the first 71 patients, 90% of the babies have been delivered, and outcome data have been received on all the pregnancies. All significant anomalies and diagnoses have been confirmed. The referring clinicians would have physically referred 24 of the 71 patients to Brisbane in the absence of telemedicine. A crude cost-benefit calculation suggests that the tele-ultrasound service resulted in a net saving of A$6340, and at the same time enabled almost four times the number of consultations to be carried out.