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PubMed1998

Expression of the SOX10 gene during human development.

SOX10, a new member of the SOX gene family, is a transcription factor defective in the Dom (Dominant megacolon) mouse and in the human Shah-Waardenburg syndrome. To help unravel its physiological role during human development, we studied SOX10 gene expression in embryonic, fetal, and adult human tissues by Northern blot and in situ hybridization. As in mice, the human SOX10 gene was essentially expressed in the neural crest derivatives that contribute to the formation of the peripheral nervous system, and in the adult central nervous system. Nevertheless, it was more widely expressed in humans than in rodents. The spatial and temporal pattern of SOX10 expression supports an important function in neural crest development.

Blotting, Northern↗

PubMed1997

Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors.

OBJECTIVE: To verify whether a population-based hypothesis (age at menarche and age at natural menopause have an inverse relationship) also applies at the level of the individual and to investigate what other factors predict age at natural menopause. DESIGN: Prospective cohort study (the Doorlopend Onderzoek Morbiditeit/Mortaliteit [DOM] project). SETTING: Prevention Breast Cancer Screening Centre, Utrecht, The Netherlands. PATIENT(S): A cohort of 3,756 Dutch women, born between 1911 and 1925, participating in a population-based breast cancer screening program, who experienced a natural menopause. Three samples of women were studied: a sample who did not use oral contraceptives (OCs) (n = 3,347), a sample of OC users (n = 409), and a combined sample of OC users and nonusers (n = 3,756). MAIN OUTCOME MEASURE(S): Age at menopause and menarche, fertility patterns, OC use, height, weight, smoking, and demographic variables. RESULT(S): No relation was found between age at menarche and age at natural menopause. The total percentage of variance in age at natural menopause explained by multiple regression including all factors was minimal, ranging from 1.3% to 9.7% in OC users. Linear regression analysis indicated a slight secular trend in age at menopause. CONCLUSION(S): Frisch's hypothesis could not be corroborated at the individual level. These results suggest that age at menarche and menopause should be treated as independent risk factors for breast cancer. Modification of age at menopause by lifestyle factors (except possibly for OC use) appears minimal.

Age Factors↗

PubMed2002

Aquatic phototransformation study of the antifouling agent Sea-Nine 211: identification of byproducts and the reaction pathway by gas chromatography-mass spectroscopy.

The photochemical behaviour of the biocide Sea-Nine 211 was carried out in order to investigate several transformation products formed in different environmental matrices and under different conditions. Sea-Nine 211 photodecomposition was performed under laboratory conditions using a xenon light source and under natural sunlight conditions in sea, river, lake as well as in distilled water. In order to examine the effect of dissolved organic matter (DOM), the phototransformation of the tested biocide was studied also in the presence of various concentrations of humic and fulvic acids. The phototransformation was shown to proceed via pseudo-first-order reaction in all cases and the presence of humic and fulvic acids enhanced the photolysis reaction. Kinetic experiments were monitored with GC-ECD and the half-lives (t(1/2)) varied between 6 and 433 h. Irradiation of the aqueous Sea-Nine 211 solutions gave rise to a great number of transformation products that were isolated by means of SPE using SDB extraction disks while six of them were tentatively identified using GC-MS techniques. Based on this byproduct identification a possible transformation pathway is proposed for the decomposition of Sea-Nine 211 in aqueous media.

Gas Chromatography-Mass Spectrometry↗

PubMed2003

Aqueous photolysis of the sunscreen agent octyl-dimethyl-p-aminobenzoic acid. Formation of disinfection byproducts in chlorinated swimming pool water.

The photochemical behavior of the sunscreen agent octyl-dimethyl-p-aminobenzoic acid (ODPABA) was studied in different aqueous solutions and under different conditions. ODPABA photolysis was performed under laboratory conditions using a xenon light source and under natural sunlight conditions in sea, swimming pool as well as in distilled water. The influence of dissolved organic matter (DOM) on the degradation kinetics was also studied in the presence of various concentrations of humic acids (HA). The phototransformation was shown to proceed via pseudo-first-order reaction in all cases and the reaction rates followed the order: distilled water > swimming pool water > seawater, depending mainly on the presence of dissolved organic matter that retarded the photolysis reaction. Kinetic experiments were monitored with HPLC/UV-DAD and the half-lives (t 1/2) varied between 1.6 and 39 h in simulated solar irradiation and between 27 and 39 h in natural sunlight conditions. The product distribution during illumination was strongly dependent on the constitution of the irradiated media. Irradiation of the aqueous ODPABA solutions gave rise to several transformation products that were isolated by means of solid-phase extraction (SPE) and identified using GC-MS techniques. These were formed mainly through dealkylation and hydroxylation reactions and were detected in all aqueous solutions investigated. In the case of swimming pool water some additional byproducts were isolated and were tentatively identified as chlorinated intermediates, formed by the subsequent chlorination of the parent molecule as well as other intermediates.

4-Aminobenzoic Acid↗

PubMed2000

Effects of strain and serotonergic agents on prepulse inhibition and habituation in mice.

Neural sensorimotor gating mechanisms prevent the interruption of ongoing information processing routines by ensuing stimuli to permit mental integration and adaptive behavior. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is now being investigated using murine models to exploit transgenic and "knockout" technology. The present studies were undertaken to evaluate potential murine strain differences in the effects of serotonergic drugs on PPI and habituation. Two strains used most often as a genetic background for transgenic or knockout manipulations, C57BL/6 and 129Sv, and the outbred ICR strain were used. We assessed the effects of the 5-HT(1A/1B) agonist 5-methoxy-3(1,2,3,6)tetrahydropyridin-4-yl-1H-indole (RU24969), the 5-HT(1A) agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT(2A/2C) agonist (+/-)2,5-dimethoxy-4-methylamphetamine (DOM), and the serotonin releaser (+)3, 4-methylenedioxy-N-methylamphetamine (MDMA) on PPI and habituation of acoustic startle in the three strains. C57BL/6 mice exhibited lower baseline PPI levels than 129Sv and ICR mice, and 129Sv mice habituated less than C57BL/6 and ICR mice. MDMA decreased PPI in C57BL/6 and ICR, but not 129Sv mice, and RU24969 disrupted habituation in C57BL/6 and 129Sv, but not ICR mice. Lastly, RU24969 decreased and 8-OH-DPAT increased PPI across all strains, although qualitative differences were observed. Thus, both baseline and serotonergic drug-induced effects on murine PPI and habituation are strain-dependent.

Animals↗

PubMed2002

Characterization, differentiation and classification of aquatic humic matter separated with different sorbents: synchronous scanning fluorescence spectroscopy.

Aquatic humic solutes were separated by the non-ionic macroporous XAD-8 and DAX-8 resins and a weakly basic DEAE cellulose anion exchanger from seven different fresh water sources. Synchronous fluorescence spectroscopy was applied for characterization, differentiation and classification of the different humic-solute aggregates. Fluorescence properties verified that humic-solute fractions isolated parallelly with the non-ionic XAD-8 and DAX-8 resins resembled very closely each other speaking strongly for their structural similarities. DAX-8 resin separated ca. 19% more aquatic humic matter than did the analogous XAD-8 resin. It was possible to tentatively differentiate the untreated water samples according to their fluorescent materials. Several distinct classes of chromophores were detected in both DOM and isolated humic fractions by the synchronous technique: lambda(ex)/lambda(em) 280/298, 330/348, 355/373, 400/418, 427/445, 460/478, 492/510 and 516/534 nm.

Environmental Monitoring↗

PubMed2001

Characterization of mucilage aggregates in Adriatic and Tyrrhenian Sea: structure similarities between mucilage samples and the insoluble fractions of marine humic substance.

The appearance of gelatinous aggregates called mucilages causes serious damages to tourism and fishery industries of the Adriatic Sea. So, many studies have been planned and some of them are still in progress to clarify the origin and causes of the phenomenon. The scientific research has showed that mucilages are produced by several marine organisms when peculiar climatic and trophic conditions occur. Moreover, as far as the mucilage composition is concerned, although it is well known that polysaccharides give a high contribution, knowledge of the structural characteristics of mucilages and their relationship with the natural organic matter of the marine environment has not been clarified yet. In this paper a study on the characterization of the marine mucilage samples collected in the Adriatic and Tyrrhenian Seas is described. The study was performed by spectroscopic (infrared and colorimetric) techniques, and elemental analysis. The results showed that mucilage samples have chemical and structural similarities with the insoluble fraction of the marine humic substance (humin). According to experimental evidences it is possible to establish the relationship between mucilages and the dissolved organic matter (DOM) in the marine environment in order to identify the most likely pathways of mucilage formation.

Adhesives↗

PubMed2003

Improvement of DOC removal by multi-stage AOP-biological treatment.

The single and multi-stages advanced oxidation process (AOP)-biological treatments were evaluated to apply for drinking water treatment, especially for the water containing less susceptible dissolved organic carbon (DOC) to ozone, comparing with the ozonation-biological treatment. Minaga reservoir water and the secondary effluent from a Municipal wastewater treatment plant were used as dissolved organic matter (DOM) solutions. DOC removals after 60 min AOP-biological treatment were 62% and 41% in the Minaga reservoir water and the secondary effluent, respectively, whereas those in the ozonation-biological treatment only 40% and 15% of DOC were removed, respectively. The result indicated that the single-stage AOP-biological treatment could improve DOC removal in comparison with the single-stage ozonation-biological treatment. This is because the AOP mineralized both biodegradable dissolved organic carbon (BDOC) produced in the early stage of oxidation and non-biodegradable dissolved organic carbon (NBDOC), whereas only BDOC was mineralized by further ozonation and NBDOC was not oxidized in the ozonation-biological treatment. The multi-stage treatment could not improve DOC removal in comparison with the single-stage treatment in the ozonation-biological treatment for the secondary effluent containing less susceptible DOC to ozone. However, the multi-stage AOP-biological treatment significantly reduced DOC and achieved 71% of DOC removal by 4 times repetition of 15 min oxidation, whereas DOC removal was 41% in the single-stage AOP-biological treatment for the same oxidation time. The improvement of DOC removal by the multi-stage AOP-biological treatment was due to BDOC removal as a radical scavenger by subsequent biological treatment in the early stage of oxidation and direct mineralization in the latter stage of oxidation.

Biodegradation, Environmental↗

PubMed2001

Partitioning of copper onto suspended particulate matter in river waters.

Suspended particles and river water from the Susquehanna River, White Clay Creek and the Delaware River were collected to experimentally study the partitioning of copper. The effects of many factors that may influence the partitioning coefficient (Kd) including pH, total suspended solids (TSS), total copper concentration ([Cu]T), dissolved organic matter (DOM), particulate organic matter (POM), hardness, and ionic strength were investigated by performing batch adsorption experiments. The results implied that organic matter binding sites in both the aqueous and solid phases play the most important role in controlling copper partitioning. Other major factors governing the partitioning are pH and TSS. Kd increases with pH in the pH range 3-8. TSS increases caused decreases in Kd values, which may be attributed to the decrease in the quantity of available binding sites caused by interparticle interactions, rather than by the redistribution of organic matter between solid and solution phases with the variation of TSS. Kd decreases slightly when total Cu concentration increases; however, Kd can be considered to be independent of Cu concentration when TSS is high. The effects of calcium competition and ionic strength on partitioning are small.

Binding Sites↗

PubMed2002

The influence of soluble organic matter from municipal solid waste compost on trace metal leaching in calcareous soils.

The use of municipal solid waste (MSW) compost as fertilizer may cause increased leaching due to its high content of trace metals and thus pose a threat to groundwater quality. The effect of MSW compost application on trace metal leaching in calcareous soils has been studied in soil column experiments under laboratory conditions using three soils from the study area in the Gaza Strip and Israel. Higher levels of organic matter in solution (TOMS), nitrate, and the trace metals Cu, Ni and Zn were found in the leachates of a sandy soil and, to a lesser extent, a loamy soil, to which MSW compost had been applied at a rate of 65 Mg ha(-1) (dry weight basis). Nevertheless, the majority of water-soluble trace metal species from compost accumulated in the topsoil rather than washing out, with the exception of aqueous Ni species. Ni concentrations exceeded the maximum allowable limits for drinking water (in Germany: 50 microg l(-1)) at peak times in the leachates from sandy soil, while all other trace metals remained far below the corresponding limits. The highest absolute concentrations of trace metals were found for the leaching of Cu from compost-amended sandy soil (100 microg l(-1)). For Cd, Pb and Hg no evidence of downward movement was found in any assay. Gel filtration studies of the collected soil leachates showed that all trace metals encountered in the leachates existed mostly as organic complexes. In sandy soil most of the water-soluble organic matter added with the compost had leached from the rootzone after a year's equivalent of rainfall, while TOMS mobility was greatly reduced in the loamy soil. The makeup of the TOMS in the sandy soil and its metal-binding capacity was strongly influenced by compost-derived dissolved organic matter (DOM) as observed by FTIR spectrometry. Hence the vertical displacement of trace metals (Cu, Ni, Zn) in these calcareous soils seemed to result primarily from the presence of mobile metal-organic complexes in the soil solution after compost addition. Further studies are required to validate these findings in the field, especially to assess the risk of Cu and Ni leaching in sandy soil.

Calcium Compounds↗

PubMed1998

The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens.

The acute effects of amphetamine derivatives on extracellular concentration of serotonin (5-HT) and dopamine in the nucleus accumbens were studied with in vivo microdialysis using conscious, freely moving rats. 5-HT, dopamine, and their major metabolites were measured by HPLC with electrochemical detection. Amphetamine (1.0-9.0 mg/kg) elevated dopamine levels considerably, but failed to affect the levels of 5-HT, except at the highest dose administered. 3,4-Methylenedioxyamphetamine (MDA, 1.0-9.0 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, 1.0-9.0 mg/kg) elevated both 5-HT and dopamine levels dose dependently. The failure of 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5-1.0 mg/kg) to affect the 5-HT levels suggests that extracellular levels of 5-HT play a minor role in hallucinogenic activity. The strong effects of MDA and MDMA on levels of 5-HT indicate that their actions on serotonergic mechanisms are different from those of the hallucinogens. In addition, methylenedioxyamphetamines may act via dopaminergic mechanisms similar to those of amphetamine.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Increasing the selectivity of drug discrimination procedures.

In an attempt to increase the selectivity of drug discrimination, rats were trained to discriminate LSD (0.08 mg/kg) from a group of "other" compounds consisting of cocaine (10 mg/kg), pentobarbital (5 mg/kg), and saline. Acquisition of this LSD-other discrimination was rapid (31 days) in chambers equipped with retractable levers and did not differ significantly from that of a group of animals trained to discriminate LSD from saline (26 days). In substitution (generalization) tests, hallucinogens such as LSD, DMT, and DOM mimicked LSD in a dose-dependent manner in both groups. The designer drug (+/-)MDMA substituted for LSD in the LSD-other group (ED50 = 1.38) but did not substitute for the training drug in the LSD-ND group; neither (+) MDMA nor PCP mimicked LSD in either group. Most importantly, lisuride, quipazine, and yohimbine, drugs that have been described as "false positives," substituted for LSD in animals trained to discriminate LSD from saline (ED50s = 0.012, 1.662, 2.344, respectively), but not in animals trained to discriminate LSD from other drugs. Thus, the LSD-other training procedure can be described as more selective than the standard drug-ND procedure.

Animals↗

PubMed2004

Preliminary exploration of the relationships between soil characteristics and PAH desorption and biodegradation.

Desorption and biodegradation of pyrene (PYR) were investigated and their relationships to soil characteristics were addressed. The results indicated that maximum achievable desorption was 30.2, 10.4, and 1.0 mg/kg for soils that had 1.7, 2.2, and 4.4 wt.% of expandable clays (smectite and vermiculite), respectively. Neither dissolved organic matter (DOM) nor total clay amounts made a good prediction of the desorption trend. Subsequently, the ease of desorption facilitated a faster aqueous biodegradation rate. The slowest aqueous biodegradation rate, 0.02 l/h, was achieved for the soil system that had the greatest amount of expandable clays, whereas the soil containing 1.7% expandable clays only achieved 0.73 l/h. The soil with 2.2% expandable clays depicted 0.41 l/h of aqueous biodegradation rate. A good linear correlation was obtained between maximum achievable desorption and aqueous biodegradation rate (R(2)=0.92). Soil analysis revealed that the total (soil+water) biodegradation reached was 65%, 78.3%, and 81.8% of the initial concentration (100 mg/kg) for the sandy clay loam (Colombian), sandy loam (Ohio), and silty loam (New Mexico) soils, respectively. This biodegradation extent was also in good agreement of expandable clay amount. Although aqueous PYR bioavailability was limited due to the strong association with the expandable clays, microbial movement and adhesion to those clays seemed to result in a great extent of the soil-phase biodegradation.

Adsorption↗

PubMed1997

Effects of some phenylethylamines in rhesus monkeys trained to discriminate (+)-amphetamine from saline.

Although the structure-activity relationships (SAR) for the discriminative stimulus (DS) effects of phenylethylamines (PEAs) have been extensively evaluated in rats, only isolated components of the SAR have been studied in other species. Since DS effects in animals predict subjective effects in humans, it is important to establish cross-species generality of substitution results. In the present experiment, rhesus monkeys (n = 4) were trained to discriminate (+)-amphetamine (0.56 or 1.0 mg/kg, i.g.) from saline in a two-lever drug discrimination paradigm. Responding was maintained under a fixed-ratio discrete-trials schedule of shock avoidance. (+)-Amphetamine, and the N-substituted phenylethylamines (+)-methylamphetamine, and (+)-ethylamphetamine all engendered dose-dependent, full substitution for (+)-amphetamine and had no effect on rate of responding. In contrast, the ring-substituted compounds (+/-)-4-methoxyamphetamine (PMA), (+/-)-2,5-dimethoxy-4-methylamphetamine (DMA), (+/-)-2,5-dimethoxy-4-methylamphetamine (DOM), and (+/-)-3,4, 5-trimethoxyamphetamine (TMA) occasioned little or no (+)-amphetamine-appropriate response up to doses of 3.0 or 10 mg/kg. Therefore, it appears that monkeys respond to N-substituted amphetamines in the same way as rats, at least qualitatively. Considering that ring-substituted compounds have been found to partially substitute for (+)-amphetamine in rats, it is possible that the (+)-amphetamine DS may be pharmacologically more selective in monkeys. However, methodological differences may also explain differences between experiments.

Amphetamine↗

PubMed2000

Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors.

A large series of beta-carbolines was examined for their ability to bind at [3H]agonist-labeled 5-HT(2A) serotonin receptors. Selected beta-carbolines were also examined at 5-HT(2C) serotonin receptors, 5-HT(1A) serotonin receptors, dopamine D(2) receptors, and benzodiazepine receptors. Indolealkylamines and phenylisopropylamines were also evaluated in some of these binding assays. The beta-carbolines were found to bind with modest affinity at 5-HT(2A) receptors, and affinity was highly dependent upon the presence of ring substituents and ring saturation. The beta-carbolines displayed little to no affinity for 5-HT(1A) serotonin receptors, dopamine D(2) receptors and, with the exception of beta-CCM, for benzodiazepine receptors. Examples of beta-carbolines, indolealkylamines (i.e. N,N-dimethyltryptamine analogs), and phenylisopropylamines have been previously shown to produce common stimulus effects in animals trained to discriminate the phenylisopropylamine hallucinogen DOM (i.e. 1-(2, 5-dimethoxy-4-methylphenyl)-2-aminopropane) from vehicle. Although the only common receptor population that might account for this action is 5-HT(2A), on the basis of a lack of enhanced affinity for agonist-labeled 5-HT(2A) receptors, as well as on their lack of agonist action in the PI hydrolysis assay, it is difficult to conclude that the beta-carbolines behave in a manner consistent with that of other classical hallucinogens.

Animals↗

PubMed1998

Menstrual cycle length preceding menopause in relation to age at menopause.

OBJECTIVES: In one of the earlier hypotheses of the etiology of breast cancer (Korenman's 'oestrogen window' hypothesis (1981)), it was assumed that women with a later age at menopause have a longer period with irregular cycles preceding menopause than women with an early menopause. This assumption was tested in a prospective study. METHODS: Subjects were 628 women, born between 1932 and 1941, who had participated in a breast cancer screening project in Utrecht, The Netherlands (the DOM-project) in 1982-1985, and who were still menstruating at that time. The women had filled out a questionnaire and a menstrual calendar every 2 years to determine their age at menopause prospectively. The women had not used oral contraceptives or medicines for menopausal complaints and had reached natural menopause by 1992. The median of the mean menstrual cycle length per woman and the median of the standard deviation of the mean menstrual cycle length per woman were plotted against number of years prior to menopause in three categories of age at menopause (44-49; 50-54; 55-59). RESULTS: During the 9 years prior to menopause, women with a late age at menopause have a somewhat higher mean menstrual cycle length than women with a younger age at menopause (P = 0.0008). Cycle length variability in the 9 years prior to menopause is not statistically significantly different between the three categories of age at menopause (P = 0.16). CONCLUSIONS: The assumption that women with a late age at menopause have a longer period with irregular cycles than women with an earlier age at menopause was not corroborated by our results.

Adult↗

PubMed2002

Translocation of the 5-alkoxy substituent of 2,5-dialkoxyarylalkylamines to the 6-position: effects on 5-HT(2A/2C) receptor affinity.

Positional modification of 2,5-dimethoxyamphetamine analogues has been studied. Specifically, the 5-alkoxy substituent was translocated to the 6-position of the phenyl nucleus. Methoxy groups were also constrained by incorporation into appended dihydrofuran and furan rings. 2,6-Dimethoxy-4-methylamphetamine had an approximately 3-fold lower affinity for the 5-HT(2A) receptor compared to the parent 2,5-dimethoxy-4-methylamphetamine (DOM). The rigid compound based on the 2,3,5,6-tetrahydrobenzo[1,2-b;5,4-b']difuran nucleus and the aromatic analogue containing the benzo[1,2-b;5,4-b']difuran nucleus possessed an approximate 7- and 27-fold increase in affinity, respectively, compared to 2,6-dimethoxy-4-methylamphetamine, the non-rigid, positional isomer.

Amphetamines↗

PubMed1997

Pressure pain tolerance at different sites on the quadriceps femoris prior to and following eccentric exercise.

Downhill running, particularly for the untrained subject, is a mode of eccentric exercise that produces delayed-onset muscle soreness (DOMS) in the quadriceps femoris muscle which is maximal between 24 and 72 h after the exercise. It is not clear whether sensitivity to pain is uniform over the surface of the muscle, or whether some locations become more sensitive following eccentric exercise. The purpose of this investigation was to compare pressure pain tolerance (PPTO) at various sites on the quadriceps femoris muscle on 2 days prior to exercise, immediately after, and at 24, 48 and 72 h following a bout of eccentric exercise. Fifteen untrained female subjects performed a 40 min downhill run on a motorized treadmill with a gradient of -12%, where running speed was adjusted to elicit a heart rate of approximately 60% of age-related maximum heart rate reserve, and were measured for PPTO at seven sites on the right thigh. Sites were visited sequentially three times and repeated on each of 6 days. Pressure pain tolerance as an index of tenderness was determined using a strain gauge algometer. Two sites were close to the distal myotendinous junction, three sites were located on the mid belly of the muscle and two sites were located at the proximal myotendinous junction. There was a significant difference (p<0.01) in PPTO between muscle sites prior to eccentric exercise (Days 1 and 2), and a significant difference between sites following eccentric exercise (p<0.01). Sites close to the distal and proximal myotendinous junction were most sensitive to pain (p<0.01). There was no difference in PPTO at any site across the belly of the muscle. These results suggest that the belly of the quadriceps femoris is the most suitable area for measurement of PPTO.

Journal Article↗