Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases.

The authors examined the hypothesis that perinatal factors influence the onset of puberty. Children born as singletons in Uppsala, Sweden, in 1973-1977 were followed for height development before and during their school years (through 16 years of age). In all, 62 children born after preeclampsia, 129 born prematurely, 90 born small for gestational age, 175 born large for gestational age, 49 born short for gestational age, and 38 born tall for gestational age were compared with 688 "normal" children. Differences in age and height at puberty onset and age at menarche were analyzed using the t test and analyses of covariance. For boys, the mean age at puberty onset did not differ between normal boys and those with perinatal factors. Boys born small or short for gestational age were 4 cm shorter than normal boys, and those born large for gestational age were 3 cm taller than normal boys. Among girls, patterns for differences in height were similar. Girls born small for gestational age were 5 months younger than normal girls at the onset of puberty and menarche. Patterns of early childhood growth seemed to explain the relations between these perinatal factors and height and age at puberty. The authors conclude that body size at birth affects stature at puberty; in girls, smallness for gestational age is associated with earlier puberty. Associations between intrauterine exposures and disease risk may be confounded by, or mediated through, effects on adolescence.     

Parasite communities of the Salzhaff (Northwest Mecklenburg, Baltic Sea). I. Structure and dynamics of communities of littoral fish, especially small-sized fish

The parasites of ten fish species, including four Gobiidae, three Gasterosteidae, two Syngnathidae, and one Zoarcidae from the Salzhaff region, Northwest Mecklenburg, Baltic Sea, were investigated in 1995 and 1996. As many as 36 parasite species, represented by diverse groups of helminths and protozoans as well as annelids and copepods, are found during 4 seasons in these hosts. By far the most abundant group is represented by digeneans, comprising 15 species, followed by 7 cestodans and 6 nematodes. With regard to component communities, 8 host-parasite combinations are core and secondary species with more than 40% prevalence in which generalists such as the digeneans Podocotyle atomon and Cryptocotyle concavum (in 3 hosts). C. lingua, Diplostomum spathaceum, and Acanthostomum balthicum, and the nematode Hysterothylacium are involved. Also, specialists such as Aphalloides timmi in Pomatoschistus microps as well as Magnibursatus caudofilamentosa and Thersitina gasterostei in Gasterosteus aculeatus attain high levels of prevalence. A comparison of different investigations reveals greater prevalence of allogenic and autogenic parasite species with 3 host cycles in the Rerik-Riff (free Baltic) and higher levels of prevalence of autogenic parasite species with 1 or 2 host cycles in the entire Salzhaff. The component communities of gobies from Dahmeshöved, Lübeck Bight, attain generally lower degrees of prevalence than those of the Salzhaff region. The infracommunities consist mostly of 1–3 parasite species per host specimen; this value is surpassed on occasion in P. microps (maximum 7 species) and in G. aculeatus (maximum 9 species, which may compete for 5 microhabitats in a host specimen). In this context the theory of empty niches propagated by some parasitologists is critically discussed and substituted by the assumption of variable niche widths. The seasonality of the more abundant parasites is either unclear – as in the case of C. concavum– or evident – as in the case of P. atomon, which prevail in early spring and summer, or A. timmi, which dominate in late summer, as do M. caudofilamentosa, which is absent in spring. The main causes of the infestation of fish hosts may be their ages and the availability of parasites due to the presence of intermediate hosts.     

Delta-opioid receptor immunoreactivity on astrocytes is upregulated during mitosis

Endogenous opioid peptides and opioid receptors are expressed by brain cells early during normal development, and exogenous opiate exposure in this period is known to affect brain cell proliferation and maturation. Despite the abundant evidence that opioids affect brain development, little is known about the mechanisms involved. In this study cortical astrocytes in primary culture were examined immunohistochemically by using antibodies against the opioid receptors. The immunoreactivity for delta-opioid receptors was strongly upregulated during mitosis with an increase in immunostaining that started in early prophase and lasted through the M-phase to cytokinesis. Similar effects could not be observed when antibodies against the mu- or kappa-opioid receptor subtypes were used. Cultured neurons and microglia presented a strong and homogenous immunostaining for the delta-opioid receptor and no further upregulation of immunoreactivity could be detected in these cells. The presence of functional delta-opioid receptors on the mitotic astrocytes was verified by using microspectrofluorometry for detection of delta-opioid agonist induced changes in intracellular free calcium concentrations ([Ca2+]i). In these experiments fluo-3/AM incubated cells showed a rapidly induced delta-opioid agonist (DPDPE, 10(-6) M) evoked increase in [Ca2+]i. These results suggest an upregulation of the delta-opioid receptors that could represent a mechanism involved in the response to opioids in the developing brain.     

Interaction between voluntary and postural motor commands during perturbed lifting

STUDY DESIGN: An experimental study was conducted to evaluate the effect of an unexpected postural perturbation during a lifting task. OBJECTIVES: To investigate electromyographic responses in the erector spinae to a postural perturbation, simulating slipping, during an ongoing voluntary lifting movement. It was hypothesized that specific combinations of voluntary movement and postural perturbation present a situation in which injury caused by a rapid switch between conflicting motor commands can occur. SUMMARY OF BACKGROUND DATA: Studies of postural perturbations have mainly focused on behavior during static tasks such as quiet, upright standing. To date, there are no published studies of the effect of a perturbation during an ongoing voluntary lifting movement. METHODS: Subjects standing on a movable platform were exposed to random perturbations while lifting a 20-kg load. Muscle activity was recorded from flexor and extensor muscles of the trunk and hip. Trunk flexion angle in the sagittal plane was recorded with a video system. RESULTS: Perturbations forward were followed by an increased activity in erector spinae superimposed on the background activation present during the lift, indicating that both the voluntary and postural motor programs caused an activation of erector spinae. During backward perturbation, however, there was a sudden cessation of erector spinae activity followed by an extended period of rapid electromyographic amplitude fluctuations while the trunk was flexing, indicating an eccentric contraction of the erector spinae. CONCLUSIONS: This erratic behavior with large electromyographic amplitude fluctuations in the erector spinae after a backward slip during lifting may indicate a rapid switch between voluntary and postural motor programs that require conflicting functions of the back muscles. This may cause rapid force changes in load-carrying tissue, particularly in those surrounding the spine, thus increasing the risk of slip-and-fall-related back injuries.     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions

In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of -MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the -MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptors (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptors, but may also be 5-HT- or LSD-sensitive receptors.The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.     

Involvement of central GABA receptors in the regulation of the urinary bladder function of anaesthetized rats

Summary Cystometric recordings were performed in pentobaribitone anaesthetized rats and the effects of gammaaminobutyric acid (GABA) mechanisms on urinary bladder function were evaluated as their influence on a bladder hyperactivity induced by 1-dihydroxyphenylalanine (l-DOPA) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricular (i.c.v., 4th ventricle) injections of GABA (250 g), muscimol (0.2 g) and glycine (1,000 g) as well as by systemically administered muscimol (4 mg/kg) and diazepam (2 mg/kg). Intravenous (i.v.) bicuculline, but not i.v. strychnine, antagonized the inhibitory actions of intraperitoneal (i.p.) and i.c.v. muscimol and i.v. diazepam while the opposite was true for the inhibitory action of i.c.v. glycine. In rats not pretreated with l-DOPA, i.p. administration of bicuculline (4 mg/kg) after 15 min caused prominent detrusor contractions that were prevented by an infracollicular brain transection.It is suggested that GABA synapses in the pontinemesencephalic brain region may be involved in the modulation of urinary bladder function.     

Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers

Summary The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg · kg^–1.Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and IS min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (V_ss) was 741, (range 26 to 1271). Only 0.5 to 1 % of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 1171. h^–1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1 % of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of the ₂-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man.