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PubMed1990

Systolic blood pressure and cardiovascular mortality among 13,740 Dutch women.

Prospective data of cardiovascular mortality in relation to the systolic blood pressure of women are scarce, especially when combined with other risk factors. The association between systolic blood pressure and cardiovascular mortality was therefore studied in a 10-year follow-up of a population of 13,740 Dutch women, born between 1911 and 1925 who participated in a population-based breast cancer screening project (the DOM Project). Age-adjusted mortality rates over the 10-year follow-up period suggest a J-shaped pattern of cardiovascular mortality according to level of systolic blood pressure. Age-adjusted total cardiovascular, coronary, and cerebrovascular mortality rate ratios were significantly greater than 1.0 among women with elevated systolic blood pressure. Within categories of other risk factors (obesity index, diabetes mellitus, current smoking, and use of antihypertensive medicines) the age-adjusted cardiovascular rate ratios did not show confounding by any of these variables. A very high increase in cardiovascular mortality was observed among hypertensive diabetic women. This study shows that elevated systolic blood pressure is associated with increased rates of cardiovascular mortality for women in this age group.

Body Mass Index↗

PubMed1994

Binding sites for 5-hydroxytryptamine-2 receptor agonists are predominantly located in striosomes in the human basal ganglia.

Previous autoradiographic studies have shown that serotonin 5-HT2 receptors are homogeneously distributed in the human striatum. While these studies were done using antagonist radioligands such as [3H]ketanserin, we describe here a heterogeneous distribution of 5-HT2 binding sites in the human striatum, using [3H]LSD and [125I]DOI as ligands. Beside their agonist properties, these compounds belong to the family of psychedelic drugs. The localization of their binding sites in the dorsal striatum is very similar to that of striosomes, as visualized by acetylcholinesterase histochemistry or [3H]flunitrazepam labelling. This heterogeneous distribution seems to be a peculiarity of the human and guinea-pig brain, for it is not found in the monkey, cat, pig, and cow. In the rat striatum, a weak patchniness was seen, but corresponded to 5-HT1C binding sites. The density of [125I]DOI binding sites over striosomes presents large variations, which can neither be correlated with parameters such as age, gender and post-mortem delay nor with the effects of neurodegenerative disorders, with the exception of Huntington's disease, at late stages of the disease. The drug binding profile of [125I]DOI binding sites in the striosomes is identical to that of matrix binding sites. It is also fully comparable to the pharmacological profile of cortical 5-HT2 sites reported using [3H]ketanserin as a radioligand, with the exception of the higher affinity displayed by agonists for [125I]DOI binding sites. Interestingly, biphasic displacement curves yield a better fit for spiperone, cinanserin and ketanserin competitions. This biphasic profile can probably neither be accounted for by the presence of 5-HT1C sites nor by the existence of multiple affinity states. Taken together, these data suggest that a heterogeneous population of 5-HT2 receptors is present on the cell bodies or dendrites of striosomal neurons. These receptors provide an additional anatomical substrate to explain the psychedelic action of indoleamine (LSD) and phenylethylamine (DOI, DOM) drugs.

Adult↗

PubMed1989

LSD and other related hallucinogens elicit myoclonic jumping behavior in the guinea pig.

1. We evaluated the behavioral response of guinea pigs to hallucinogenic agents in order to characterize the response of this species to a variety of known hallucinogenic drugs. 2. The systemic injection of LSD in the guinea pig elicited a "myoclonic-like" response the frequency of which was dose-dependent. This behavior exhibited rapid tolerance which was more prominent at higher doses. 3. Subacute mescaline pretreatment reduced the myoclonic response to LSD suggesting cross-tolerance. 4. Mescaline, DOM, TMA, DMA and 5 Me-ODMT also elicited myoclonus in a dose-dependent manner and in potency ratios which approximate the human experience for hallucinogenic activity. 5. Brom-LSD failed to induce myoclonus. 6. Since the myoclonic response of the guinea pig shares a number of pharmacologic characteristics with the human hallucinogenic event, this species may be useful in the study of hallucinogenic compounds.

Animals↗

PubMed1996

Actions of methoxylated amphetamine hallucinogens on serotonergic neurons of the brain.

1. Previous studies of phenethylamine hallucinogenic drugs have reported that intravenous injection of DOI or similar compounds produce an inhibition of the firing rate of serotonergic dorsal raphe neurons of the rat; potentially lowering levels of 5-HT throughout the brain. 2. Direct application by iontophoresis demonstrated only weak non-specific effects, but injection into the nucleus produced slowing of cell firing possibly due to the reduction of on-going synaptic excitation. 3. The literature concerning phenethylamine hallucinogens is discussed in the context of new results obtained from acutely isolated raphe neurons. The effect of DOI (10 microM) was tested on isolated DR neurons that responded to 5-HT with the activation of an inwardly rectifying K+ current but it was without effect. Under conditions that isolated inward Ca2+ current in raphe neurons that was inhibited by 5-HT, DOI was similarly without effect, neither blocking nor mimicking the action of 5-HT. Brief applications of glutamate produced an inward current similar to those produced by synaptic excitation in a slice preparation, but DOI failed to influence the size or duration of these responses. 4. These results suggest that DOI does not directly influence the cell bodies of DR neurons. 5. Further studies using raphe slices subject to synaptic influences will be required to reveal any indirectly mediated mechanism that may underlie the effects of DOI on DR neurons. Alternative indirect mechanisms of DR neuronal inhibition by i.v. DOI and DOM are suggested.

Amphetamine↗

PubMed1986

Modulatory role for prolactin in the elevation of striatal dopamine receptor density induced by chronic treatment with dopamine receptor antagonists.

The chronic administration of haloperidol (HAL), domperidone (DOM), or sulpiride (SUL) increased the density of striatal dopamine (DA) receptors in intact but not in hypophysectomized (Hypox) male rats. This effect was independent of changes in body weight of the rats and of the drugs' abilities to produce cataleptic behavior. All treatments of intact rats increased serum rat prolactin (rPRL) concentrations, while Hypox rats had rPRL levels equivalent to zero. At the doses used in these studies, the striatal DA receptor densities were increased only if the rPRL levels were also increased. Chronic cysteamine (CYS) treatment decreased body weight gain, acutely decreased cataleptic behavior to HAL, decreased serum rPRL levels, and prevented the increase in serum rPRL levels due to HAL administration. While CYS itself did not alter striatal DA receptor density, it prevented the increase in density associated with the chronic administration of HAL (1 mg/kg). Since CYS decreased rPRL levels, these results lend further support to the hypothesis that rPRL (and prolactin in general) is a pituitary hormone with modulatory action on the increase in striatal DA receptor density.

Animals↗

PubMed1978

The identification of LSD-like hallucinogens using the chronic spinal dog.

The effects of several indoleamines and phenethylamines were studied in the chronic spinal dog and compared with two standard drugs, LSD and amphetamine. In the nontolerant chronic spinal dog, their effects on a variety of physiologic and behavioral functions were measured in untreated dogs, as well as dogs treated with certain antagonists. The effects of the antagonists phenoxybenzamine and cyproheptadine on the various physiologic effects were studied for all drugs. For some idoleamines and phenethylamines, the effects of chlorpromazine and pimozide were also studied. Indoleamines and phenethylamines in the LSD-tolerant chronic spinal dog and their anorexigenic effects in the intact dog were also studied. The results of these studies indicate that psilocin, mescaline, dimethyltryptamine and tryptamine are LSD-like drugs. DOM, DOB, DMA, and TMA are predominantly LSD-like drugs but do have some amphetamine-like action. PMA and PEA are predominantly amphetamine-like drugs with some LSD-like activity. MMDA and MDA have a more complicated pharmacology showing proerties that resemble LSD and amphetamine, but they have other actions which are not shared by either LSD or amphetamine, which suggests they have yet other modes of action.

Animals↗

PubMed2004

Heavy metal toxicity and bioavailability of dissolved nutrients to a bacterivorous flagellate are linked to suspended particle physical properties.

Many dissolved substances attach easily to sediment particles. In the presence of suspended sediments bioavailability of dissolved substances is therefore, usually reduced and clays are even applied to "wash" natural waters upon pollution. In organisms which feed on food organisms in the size range of these suspended sediment particles, however, bioavailability of such substances may even increase. For microorganisms the interaction with dissolved substances and suspended sediment particles so far has hardly been investigated. We specifically tested: (1) the importance of suspended particles as an uptake route for dissolved substances; and (2) the significance of particle surface properties, i.e. surface load and mineralogy. As a model system we used an axenically cultured strain of a widespread and often abundant flagellate ("Spumella-like" flagellate strain JBM10). We tested the toxicity of cadmium (II) and mercury (II) as well as availability of dissolved organic matter (DOM) in the absence as well as in the presence of different natural clays, i.e. a kaolinite, a montmorillonite, and a mixed clay, and of artificial silicate particles of different surface charge. When applied separately the presence of the heavy metals cadmium and mercury as well as of suspended particles negatively affected the investigated flagellate but nutritive organics supported growth of the investigated flagellate. Toxic stress response comprises behavioral changes including enhanced swimming activity and stress egestion of ingested particles and was generally similar for a variety of different flagellate species. In combination with suspended particles, the respective effect of trace metals and nutritive substances decreased. Regarding the particle quality, cadmium toxicity increased with increasingly negative surface charge, i.e. increasing surface density of silanol groups (Pearson's product moment, P = 0.005). For mercury particle mineralogy still had a significant effect (P < 0.001) but surface load seems to play a minor role and for nutritive organics no significant effect of the investigated particle properties was found. We conclude that: (i) flagellates are as sensitive as higher animals to heavy metal pollution; (ii) suspended particles decrease bioavailability of dissolved substances and ingestion of suspended particles probably play a minor role as uptake route for dissolved substances; and (iii) suspended sediment particle properties, i.e. surface charge and mineralogy, are key factors for the interaction between microorganisms and dissolved substances in the presence of suspended sediments.

Aluminum Silicates↗

PubMed2006

Photolytic degradation of quinalphos in natural waters and on soil matrices under simulated solar irradiation.

The photochemical persistence of quinalphos, one of the most widely used organophosphorous insecticides, was investigated in a variety of environmental matrices such as natural waters and soils of different composition. Simulated solar irradiation was obtained using a xenon arc lamp (Suntest CPS+ apparatus) giving an irradiation intensity of 750 W m(-2) equivalent to a light dose per hour of irradiation of 2,700 kJ m(-2). The phototransformation rates were determined using solid-phase microextraction (SPME) and ultrasonic extraction (USE) coupled to GC-FTD, while the identification of photoproducts was carried out by GC-MS. In water samples, the degradation kinetics followed a pseudo-first-order reaction and photolysis half-lives ranged between 11.6 and 19.0 h depending on the constitution of the irradiated media. Dissolved organic matter (DOM) has a predominant retarding effect, while nitrate ions accelerated the photodegradation kinetics. In soil samples, the degradation kinetics was monitored on 1mm soil layer prepared on glass TLC plates. The kinetic behaviour of quinalphos was complex and characterized by a double step photoreaction, fast in the first 4h of irradiation followed by a slow degradation rate up to 64 h. The photolysis half-life of quinalphos was shorter in sandy soil compared to the rest of the soil samples, varying between 16.9 and 47.5 h, and showing a strong dependence on the composition of the irradiated media. Among the transformation products formed mainly through photohydrolysis and photoisomerization processes, some photoproduct structures were proposed according to their mass spectral information.

Chromatography, Gas↗

PubMed2005

Reproductive emergencies.

The emergency clinician is frequently called on to manage problems relating to the female reproductive tract. Because owners sel-dom have the medical knowledge needed to differentiate normal from abnormal reproductive behaviors, they frequently look to the emergency veterinarian for guidance and information during and after parturition. For this reason, it is essential that the veterinarian have a good understanding of the normal reproductive cycle as well as the common emergencies that may occur. This article reviews the events surrounding normal parturition in the dog and cat and the reproductive emergencies seen most commonly in practice.

Animals↗

PubMed2006

The effects of muscle damage following eccentric exercise on gait biomechanics.

To examine the effects of knee extensors muscle damage on walking and running biomechanics in healthy males. Muscle damage was caused by 60 (6x10) maximal eccentric knee flexions of both legs, selected in a random order, at an angular velocity of 1.05rad/s in 10 volunteers (mean age 20+/-1.0 years). Muscle damage indicators (creatine kinase (CK), lactate dehydrogenase (LDH), delayed onset muscle soreness (DOMS), eccentric and isometric (110 degrees knee flexion) peak torque), pelvic three dimensional (3D) orientation, as well as hip, knee and ankle-joint flexion/extension angles during gait (walking at 1.2m/s and running at 2.8m/s) were assessed pre- and 48h post-eccentric exercise. All muscle damage indicators revealed significant changes post- compared to pre-exercise data (P<0.05) confirming that muscle damage did occur. Kinematic analysis revealed that muscle damage significantly decreased the knee-joint angle range of movement at the stance and swing phases during walking (P<0.05) and running (P<0.05), respectively. These changes were accompanied by corresponding increases of pelvic rotation (P<0.05) and decrease of pelvic tilt (P<0.05). The present data demonstrate that damage of knee extensors result in changes of treadmill walking and running kinematics at both knee joint and pelvis. The fact that these alterations occur at different gait phases could be attributed to the speed of movement and to a self-protection mechanism to prevent further damage.

Adult↗

PubMed2004

A multi-layered application for the gross description using Semantic Web technology.

OBJECTIVE: Development of a Semantic Web technology based system for the formalization of the gross description. METHOD: A system is developed using the Java-2 platform. It is based on a light-weight version of the Galen top level ontology. Web technologies like XML, SAX en DOM have been used. RESULT: Three system components have been developed to support the semantic, the object and the syntax layers of the PathOnt architecture. CONCLUSION: The PathOnt approach provides a tool for the communication among clinicians and technicians involved in pathology examinations. This tool also provides a foundation for linking the specimen-specific data with the controlled medical ontology so that the stored information can be used in different circumstances.

Internet↗

PubMed2004

Increase in breast size after menopause: prevalence and determinants.

OBJECTIVES: To determine the prevalence and determinants of increases in breast size after menopause. METHODS: Subjects were 1130 postmenopausal women, aged 54-71, participating in a population based breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Questionnaire data on changes in breast size, parity, age at first childbirth, breast feeding, age at menarche, age at menopause, HRT use and usual weight between age 30 years and age at questionnaire were used. Weight and height were measured at three screening rounds and waist and hip circumference was measured once. RESULTS: 18.6% of the women reported that they had to buy a larger bra because of changes in breast size, whereas 1.7% reported that they had to buy a smaller bra. Weight gain, waist circumference, hip circumference, Quetelet's index at third screening, Quetelet's index at first screening, waist-to-hip ratio and years since menopause were significantly associated with increased breast size (odds ratios between 2.5 and 1.4) (all tests for trend P < 0.05), whereas age at menopause, HRT use, parity and age at menarche were modestly, though not significantly associated with increased breast size. Age, usual Quetelet's index, age at first childbirth and number of months of full breast feeding were not associated with increased breast size. CONCLUSION: About one in five women experienced an increase in breast size after menopause. The most important factor associated with such an increase was found to be weight gain.

Adipose Tissue↗

PubMed2005

The stimulus properties of LSD in C57BL/6 mice.

RATIONALE: Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Although a variety of species has been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice. OBJECTIVE: To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species. METHODS: Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, s.c.; 15 min pretreatment] or vehicle. RESULTS: Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed. CONCLUSIONS: The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well.

Animals↗

PubMed2006

Differential induction of apoptosis by type A and B trichothecenes in Jurkat T-lymphocytes.

Several studies have shown that the mycotoxins T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and nivalenol (NIV) affect lymphocyte functioning. However, the molecular mechanisms underlying the immunomodulatory effects of these trichothecenes are not defined yet. In this study, the potency of the type A trichothecenes T-2 toxin and DAS, and the type B trichothecenes DON (and its metabolite de-epoxy-deoxynivalenol; DOM-1) and NIV to reduce mitochondrial activity and to induce apoptosis of Jurkat T cells (human T lymphocytes) were examined. T-2 toxin and DAS are much more cytotoxic at low concentrations than DON and NIV as shown by the AlamarBlue cytotoxicity assay. In addition, the mechanism whereby DON and NIV induced cytotoxicity is mainly via apoptosis as we observed phosphatidylserine externalization, mitochondrial release of cytochrome c, procaspase-3 degradation and Bcl-2 degradation. In contrast, type A trichothecenes reduce the mitochondrial activity at approximately 1000-fold lower concentrations than the type B trichothecenes, resulting in necrosis. These data suggest that the mechanisms resulting in cytotoxic effects are different for type A and type B trichothecenes.

Apoptosis↗

PubMed2004

Measurement of protein-like fluorescence in river and waste water using a handheld spectrophotometer.

Protein-like fluorescence intensity in rivers increases with increasing anthropogenic DOM inputs from sewerage and farm wastes. Here, a portable luminescence spectrophotometer was used to investigate if this technology could be used to provide both field scientists with a rapid pollution monitoring tool and process control engineers with a portable waste water monitoring device, through the measurement of river and waste water tryptophan-like fluorescence from a range of rivers in NE England and from effluents from within two waste water treatment plants. The portable spectrophotometer determined that waste waters and sewerage effluents had the highest tryptophan-like fluorescence intensity, urban streams had an intermediate tryptophan-like fluorescence intensity, and the upstream river samples of good water quality the lowest tryptophan-like fluorescence intensity. Replicate samples demonstrated that fluorescence intensity is reproducible to +/- 20% for low fluorescence, 'clean' river water samples and +/- 5% for urban water and waste waters. Correlations between fluorescence measured by the portable spectrophotometer with a conventional bench machine were 0.91; (Spearman's rho, n = 143), demonstrating that the portable spectrophotometer does correlate with tryptophan-like fluorescence intensity measured using the bench spectrophotometer.

Environmental Monitoring↗

PubMed2005

Efficiency of activated carbon to transform ozone into *OH radicals: influence of operational parameters.

Based on previous findings (Jans, U., Hoigné, J., 1998. Ozone Sci. Eng. 20, 67-87), the activity of activated carbon for the transformation of ozone into *OH radicals including the influence of operational parameters (carbon dose, ozone dose, carbon-type and carbon treatment time) was quantified. The ozone decomposition constant (k(D)) was increased by the presence of activated carbon in the system and depending on the type of activated carbon added, the ratio of the concentrations of *OH radicals and ozone, the R(ct) value ([*OH]/[O3]), was increased by a factor 3-5. The results obtained show that the surface chemical and textural characteristics of the activated carbon determines its activity for the transformation of ozone into *OH radicals. The most efficient carbons in this process are those with high basicity and large surface area. The obtained results show that the interaction between ozone and pyrrol groups present on the surface of activated carbon increase the concentration of O2*- radicals in the system, enhancing ozone transformation into *OH radicals. The activity of activated carbon decreases for extended ozone exposures. This may indicate that activated carbon does not really act as a catalyst but rather as a conventional initiator or promoter for the ozone transformation into *OH radicals. Ozonation of Lake Zurich water ([O3] = 1 mg/L) in presence of activated carbon (0.5 g/L) lead to an increase in the k(D) and R(ct) value by a factor of 10 and 39, respectively, thereby favouring the removal of ozone-resistant contaminants. Moreover, the presence of activated carbon during ozonation of Lake Zurich water led to a 40% reduction in the content of dissolved organic carbon during the first 60 min of treatment. The adsorption of low concentrations of dissolved organic matter (DOM) on activated carbon surfaces did not modify its capacity to initiate/promote ozone transformation into *OH radicals.

Charcoal↗

PubMed2005

Food competition and social experience effects on V1a receptor binding in the forebrain of male Long-Evans hooded rats.

The present study investigated the effect of social status in Long-Evans hooded rats established during food competition on V(1a) vasopressin receptor (V(1a)R) binding in the lateral septum (LS), medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), anterior hypothalamus (AH), and central/basolateral amygdala (CeB). Serum concentration of testosterone (T) and corticosterone (CORT) was also measured. In Experiment 1, thirty-two lever-trained weight-matched rat pairs were placed in operant chambers where a single bar press provided access to milk reinforcement. A dominant-subordinate relationship, determined by the duration of drinking, was evident in 88% of the pairs. Sixteen rats were lever-trained but did not interact and served as no-treatment (NT) controls. In the LS, V(1a)R binding in the subordinate (SUB) group was significantly higher than in the dominant (DOM) group. V(1a)R binding was significantly higher in the LS, BNST, CeB, and AH in the NT group than in the other groups. The levels of CORT and T were not affected significantly by group membership. Experiment 2 investigated whether the binding effect in the LS was related to differences in fluid consumption. The results did not indicate a significant effect of fluid consumption. In the rat, V(1a)R binding in several forebrain areas seems to be affected by brief periods of social interactions, and, in the LS, it also appears to be related to dominance status.

Aggression↗

PubMed1998

Conservation of the conformation of the porphyrin macrocycle in hemoproteins.

The out-of-plane distortions of porphyrins in hemoproteins are characterized by displacements along the lowest-frequency out-of-plane normal coordinates of the D4h-symmetric macrocycle. X-ray crystal structures are analyzed using a computational procedure developed for determining these orthogonal displacements. The x-ray crystal structures of the heme groups are described within experimental error, using the set composed of only the lowest frequency normal coordinate of each out-of-plane symmetry type. That is, the distortion is accurately simulated by a linear combination of these orthonormal deformations, which include saddling (B2u), ruffling (B1u), doming (A2u), waving (Eg), and propellering (A1u). For example, orthonormal structural decomposition of the hemes in deoxymyoglobins reveals a predominantly dom heme deformation combined with a smaller wav(y) deformation. Generally, the heme conformation is remarkably similar for proteins from different species. For cytochromes c, the conformation is conserved as long as the amino acids between the cysteine linkages to the heme are homologous. Differences occur if this short segment varies in the number or type of residues, suggesting that this small segment causes the nonplanar distortion. Some noncovalently linked hemes like those in the peroxidases also have highly conserved characteristic distortions. Conservation occurs even for some proteins with a large natural variation in the amino acid sequence.

Amino Acid Sequence↗