Estrogenicity of butylparaben in rainbow trout Oncorhynchus mykiss exposed via food and water

The estrogenic effect of butylparaben was investigated in a rainbow trout Oncorhynchus mykiss test system. Butylparaben was administered orally to sexually immature rainbow trout every second day for up to 10 days in doses between 4 and 74 mgkg(-1)2d(-1) and in the water at 35 and 201 microgl(-1) for 12 days. Plasma vitellogenin was measured before and during the exposures and the concentrations of butylparaben in liver and muscle were determined at the end of experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 9 mg butylparaben kg(-1)2d(-1). The ED50 values for increase in vitellogenin synthesis were 46, 29 and 10.5 mg butylparaben kg(-1)2d(-1), respectively, at day 3, 6 and 12. Exposure to 201 microg butylparaben l(-1) increased vitellogenin synthesis, but exposure to 35 microgl(-1) did not. Butylparaben showed little tendency to bioaccumulation in rainbow trout; less than 1 per thousand of the total amount of butylparaben administered orally at 51 mgkg(-1)2d(-1) over the 12 days experimental period was retained in liver at the end of the experiment. After 12 days exposure to 35 and 201 microg butylparaben l(-1), plasma concentrations were 9 and 183 microgl(-1), respectively, and for the fish exposed to 201 microgl(-1) there was a positive correlation between concentrations of vitellogenin and butylparaben in the plasma. On the assumption that butylparaben removed from the water phase during water exposure were taken up into the fish, butylparaben uptake rates in the fish exposed to 35 and 201 microg butylparaben l(-1) were 13 and 78 mgkg(-1)day(-1), respectively.     

Umbilical cord mercury concentration as biomarker of prenatal exposure to methylmercury

Biomarkers are often applied to assess prenatal exposure to methylmercury in research and surveillance. In a prospective study in the Faroe Islands, the main exposure biomarkers were the mercury concentrations in cord blood and maternal hair obtained at parturition. We have now supplemented these exposure biomarkers with mercury analyses of umbilical cord tissue from 447 births. In particular, when expressed in relation to the dry weight of the tissue, the cord mercury concentration correlated very well with that in cord blood. Structural equation model analysis showed that these two biomarkers have average total imprecision of about 30%, which is much higher than the laboratory error. The imprecision of the dry-weight-based concentration was lower than that of the wet-weight-based parameter, and it was intermediate between those of the cord blood and the hair biomarkers. In agreement with this finding, regression analyses showed that the dry-weight cord mercury concentration was almost as good a predictor of methylmercury-associated neuropsychologic deficits at 7 years of age as was the cord-blood mercury concentration. Cord mercury analysis can therefore be used as a valid measure of prenatal methylmercury exposure, but appropriate adjustment for the imprecision should be considered.     

Highly efficient and reliable chemically assisted enucleation method for handmade cloning in cattle

The purpose of the present study was to find an efficient and reliable chemically assisted procedure for enucleation related to the handmade cloning (HMC) technique. After in vitro maturation oocytes were incubated in 0.5 microg mL(-1) demecolcine for 2 h. Subsequently, zonae pellucidae were digested with pronase, and one-third of the cytoplasm connected to an extrusion cone was removed by hand using a microblade. The remaining two-thirds were used as recipients for HMC, and reconstructed and activated embryos were cultured for 7 days. The time-dependent manner of the development of extrusion cones, the efficiency (oriented bisection per oocyte; 94%), reliability (success per attempted enucleation; 98%), and the blastocyst per reconstructed embryo rates (48%) were measured. Ultrastructural analyses demonstrated that demecolcine treatment resulted in disoriented and haphazardly orientated microtubules. The general ultrastructure of the oocyte organelles, however, appeared to be unaltered by the treatments. Considering that no oocyte selection based on polar body presence was performed, this system seems to be more efficient and reliable than any other enucleation method. Moreover, expensive equipment (inverted fluorescence microscope) and a potentially harmful step (staining and ultraviolet illumination) can be eliminated from the HMC procedure without compromising the high in vitro efficiency.     

Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of inguinal hernia

BACKGROUND: According to a Cochrane review, laparoscopic inguinal hernia repair compares favourably with open mesh repair, but few data exist from surgical practice outside departments with a special interest in hernia surgery. This study compared nationwide reoperation rates after laparoscopic and Lichtenstein repair, adjusting for factors predisposing to recurrence. METHODS: Some 3606 consecutive laparoscopic repairs were compared with 39 537 Lichtenstein repairs that were prospectively recorded in a nationwide registry between 1998 and 2003. Patients were subgrouped according to type of hernia: primary or recurrent and unilateral or bilateral. Overall reoperation rates and 95 per cent confidence intervals were calculated. Long-term reoperation rates were estimated using the Kaplan-Meier method. RESULTS: The overall reoperation rates after laparoscopic and Lichtenstein repair of unilateral primary indirect hernia (0 versus 1.0 per cent), primary direct hernia (1.1 versus 3.1 per cent), unilateral recurrent hernia (4.6 versus 4.8 per cent) and bilateral recurrent hernia (2.6 versus 7.6 per cent) did not differ. However, laparoscopic repair of a bilateral primary hernia was associated with a higher reoperation rate than Lichtenstein repair (4.8 versus 3.0 per cent) (P = 0.017). CONCLUSION: Laparoscopic repair compared favourably with Lichtenstein repair for primary indirect and direct hernias, and unilateral and bilateral recurrent hernias, but was inferior for primary bilateral hernias.     

Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

Fertilization is a unique and exquisitely choreographed cellular interaction between the male and female gamete that results in the creation of a genetically unique individual. Despite the fundamental importance of fertilization, there remains a dearth of information about the basic biochemical mechanisms that underpin this process. One of the key issues that remain unresolved is the molecular basis of sperm–egg recognition. From the female perspective, it is well established that the sperm recognition sites reside in the zona pellucida (ZP), an acellular coat that surrounds the oocyte. In contrast, numerous studies into the cognate zona receptors residing on the sperm surface have failed to shed significant light on the biochemical identity of these molecules. Such difficulties may, in part, have arisen because investigations have traditionally been based on the precept that the zona receptor represents a single molecular entity that is constitutively expressed on the sperm surface. While such a view holds obvious appeal, it fails to account for growing evidence that gamete interaction is not mediated by a simple lock-and-key mechanism. In this review, we present a novel hypothesis in which the zona recognition site is portrayed as a multimeric molecular structure that is assembled into a functional complex during a maturation process known as ‘capacitation’. Furthermore, we consider the possibility that this previously cryptic complex is assembled and delivered to the outer surface of the sperm plasma membrane through the concerted action of several members of the molecular chaperone family of proteins.     

Intravenous immunoglobulin ameliorates experimental autoimmune encephalomyelitis and reduces neuropathological abnormalities when administered prophylactically

BACKGROUND AND METHODS: Immunomodulation with intravenous immunoglobulin (IVIG) represents a way of interfering with the disease process in multiple sclerosis (MS). In this study, the effects of IVIG on neurological symptoms and central nervous system (CNS) pathology were evaluated in experimental autoimmune encephalomyelitis (EAE), an MS animal model. EAE was induced in susceptible Dark Agouti rats by active immunization with a spinal cord homogenate, and infusions of 1 g/kg IVIG were given prophylactically or therapeutically.RESULTS: The administration of IVIG at the time of immunization significantly suppressed the development of neurological symptoms compared with infusions of placebo (mean EAE score 0.6+/-0.3 versus 2.3+/-0.4). Moreover, the prophylactic IVIG administration resulted in a significant inhibition of the inflammatory response in CNS tissue (inflammation score 1.1+/-0.2 versus 1.8+/-0.2 after placebo). No beneficial effects were obtained by therapeutic IVIG infusions as the EAE disease course and the degree of inflammation and demyelination in the CNS were not different from animals receiving treatment with placebo.CONCLUSIONS: The present study indicates that IVIG reduces the symptoms of EAE by suppression of the CNS inflammation that characterizes CNS pathology in these animals. Taking into account data from clinical trials of IVIG in MS, the results further suggest that IVIG acts primarily during the induction phase of the immune response thus preventing the development of relapses in MS.     

Depletion of mucosal substance P in acute otitis media

OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve fiber release of SP. MATERIAL AND METHODS: To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was measured using a radioimmunoassay. RESULTS: Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. CONCLUSION: SP seems to be depleted in the rat middle ear mucosa in the hyperacute phase of AOM. This depletion is followed by replenishment and the concentration of SP approaches its normal level 6 days post-inoculation. The release of SP may be the trigger of the concurrent bone resorption and may further augment the inflammatory response to the bacterial colonization.     

High intakes of skimmed milk, but not meat, increase serum IGF-I and IGFBP-3 in eight-year-old boys

OBJECTIVE: To examine whether a high protein intake (PI) from either milk or meat, at a level often seen in late infancy, could increase s-IGF-I and s-IGF-I/s-IGFBP-3 in healthy, prepubertal children. IGF-I levels are positively associated with growth velocity in children and some studies suggest that a high animal PI can stimulate growth. During protein deprivation IGF-I decrease, but it is unknown whether a high PI can increase s-IGF-I in well-nourished children. DESIGN: In all, 24 8-y-old boys were asked to take either 1.5 l of skimmed milk (n = 12) or the same amount of protein as 250 g low fat meat (n = 12) daily for 7 days. The remaining diet they could choose freely. At baseline and after 7 days, anthropometrical variables were measured, diet was registered (3-day weighed records), and s-IGF-I and s-IGFBP-3 (RIA) were determined after fast. RESULTS: PI increased by 61% in the milk group to 4.0 g/kg/day (P < 0.0001) and by 54% in the meat group to 3.8 g/kg/day (P = 0.001). The high milk intake increased s-IGF-I by 19% (P = 0.001) and s-IGF-I/s-IGFBP-3 by 13% (P < 0.0001). There were no increases in the meat group. CONCLUSIONS: High intake of milk and not meat, increased concentrations of s-IGF-I and s-IGF-I/s-IGFBP-3 significantly. Compounds in milk and not a high PI as such seem to stimulate IGF-I. This might explain the positive effect of milk intake on growth seen in some studies.