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Stimulant
Terms modified by Stimulant Selected AbstractsHeteropterys aphrodisiaca Infusion Reduces the Collateral Effects of Cyclosporine A on the TestisTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2008Juliana C. Monteiro Abstract Cyclosporine A (CsA) is known to have testicular toxicity, leading to male infertility. Stimulant and aphrodisiac properties have been attributed to the plant, Heteropterys aphrodisiaca. Thus, the present work was undertaken to evaluate the association of the drug and the medicinal herb in Wistar rats, applying testicular morphometry and ultrastructure. Twenty-four rats were used, divided into four groups: I, control; II, CsA; III, simultaneous use of CsA and H. aphrodisiaca; IV, H. aphrodisiaca. Daily administration by gavage was carried out, during 56 days, of water (sham), CsA in a dose of 15 mg/kg per day and/or H. aphrodisiaca in a dose of 0.5 ml of the infusion prepared with 25 g of roots/100 ml of boiling water. Increased body weight was observed for all groups, but the animals that received only CsA showed the smallest body weight gain. Morphometry showed increased connective tissue volumetric proportion and decreased Leydig cell volumetric proportion in CsA-treated rats. Using transmission electron microscopy, it was possible to ascertain that CsA caused seminiferous epithelium degeneration, resulting in Sertoli cell vacuolization, abnormal round and elongated spermatids and large accumulation of residual cytoplasm at the epithelium border next to the lumen. Expanded intercellular spaces between germ cells were still observed in H. aphrodisiaca -treated rat testes. The administration of H. aphrodisiaca infusion to CsA-treated rats diminished nearly all the CsA-induced damage to the testis ultrastructure, suggesting that H. aphrodisiaca infusion may be used combined with CsA to reduce CsA-induced injuries in the testis. Anat Rec, 291:809-817, 2008. © 2008 Wiley-Liss, Inc. [source] Creating Research Questions from Strategies and Perspectives of Contemporary ArtCURRICULUM INQUIRY, Issue 1 2001G. Thomas Fox This essay considers how strategies and perspectives from contemporary art can suggest new questions for educational research. Although arts-based research has become more prominent lately, the concern of this paper is that the arts have become used primarily as decorative features to educational research (to further illuminate, depict, and explain the ambiguities and complexities of educational practices, see Donmoyer 1997), rather than deeply moving or disorientating perspectives on education. Another stimulant for looking into contemporary art is the concern that education must focus more on the edges of what is understood, rather than on the centers (see, for example, Fox 1995). The essay uses examples to demonstrate how a number of themes from contemporary art can be interpreted to redirect our curiosity about educational practices, policies, and theories. The paper concludes that further consideration of contemporary art can move researchers to ask more varied questions, especially about the wisdom of our progressive, critical, or humanistic views of students and learning that we have built over this century. [source] The prevalence of methamphetamine and amphetamine abuse in North America: a review of the indicators, 1992,2007DRUG AND ALCOHOL REVIEW, Issue 3 2008JANE CARLISLE MAXWELL PhD Senior Research Scientist Abstract Introduction. This paper reviews epidemiological information about methamphetamine production and use in North America. Methods. Information is drawn from a range of sources, including, but not limited to, historical accounts, peer-reviewed papers, population surveys and large national databases. Results. Methamphetamine and amphetamine use in North America is characterised by geographic variations, with different types of the drug, different routes of administration and different types of users at various times. Unlike some other drug use patterns in North America, the nature of methamphetamine use in Canada, Mexico and the United States has been linked closely in terms of production and supply of the drug. According to their national household surveys, the annual prevalence for ,speed' use in Canada was 0.8% in 2004, 0.3% for ,anfetaminas' and 0.1% for ,metanfetaminas' in Mexico in 2002, and 1.4% for ,stimulants' in the United States in 2006. Discussion. Although the data sources in the three North American countries are not consistent in methodology, terminology or frequency of reporting, all show similar trends. The type of stimulant most used has shifted from non-medical use of pharmaceutical amphetamine to use of powder methamphetamine and then to use of ,ice'. The indicators show the problem is greatest in the western parts of the countries and is moving eastward, but the decreased availability of pseudoephedrine may have a significant impact on the nature of the epidemic in the future. Nevertheless, use of methamphetamine poses a number of risks for users and specialised treatment resources for these various populations are needed. [source] ,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] Genetic toxicity of methamphetamine in vitro and in human abusersENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2003Jih-Heng Li Abstract Methamphetamine (METH) is a widely abused psychomotor stimulant. Although numerous studies have examined METH-induced neurotoxicity, its ability to produce genotoxic effects has not been evaluated. In this article, we report on the genotoxicity of METH in vitro and in human METH abusers. METH induced his+ revertants in Salmonella typhimurium strains TA98 and TA100, and increased the frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic effects were eliminated if METH exposure was conducted in the presence of rat liver S9, indicating that the genotoxicity was caused by METH, and not by metabolites of METH. In addition, reactive oxygen species (ROS) scavengers inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation with 76 human long-term METH abusers and 98 unexposed controls demonstrated that total METH exposure correlated with micronucleus and SCE frequencies in cultured lymphocytes. The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH-induced genotoxicity. Environ. Mol. Mutagen. 42:233,242, 2003. © 2003 Wiley-Liss, Inc. [source] Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ,heaves'EQUINE VETERINARY JOURNAL, Issue 6 2006F. C. CAMARGO Summary Reason for performing study: Trimetoquinol (TMQ) is a potent ,-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with ,heaves'. Objectives: To assess the pharmacodynamics of TMQ in horses with ,heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with ,heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001,0.2 ,g/kg bwt i.v. and 0.01,2 ,g/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (,Pplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 ,g/kg bwt) and i.t. (2 ,g/kg bwt) TMQ was evaluated over 6 h. Results: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 ,g/kg bwt, and was still increasing after administration of highest dose, 0.2 ,g/kg bwt. Airway bronchodilation, measured as a decrease in ,Pplmax, also commenced at 0.01 ,g/kg bwt. By the i.t. route, TMQ was 50,100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. Conclusion: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with ,heaves'. Further studies of TMQ by oral and aerosol routes are necessary. Potential relevance: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of ,heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other ,-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of ,heaves'. [source] REVIEW: Human and laboratory rodent low response to alcohol: is better consilience possible?ADDICTION BIOLOGY, Issue 2 2010John C. Crabbe ABSTRACT If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of ,low level of responses to alcohol' determined by observing post-drinking-related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low level of response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and the rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: (1) behavioral measures of subjective intoxication; (2) body sway; (3) endocrine responses; and (4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively valenced and/or positively valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather sparse and unsystematic. Therefore, we suggest that more effort is still needed to collect data using refined measures designed to be more directly comparable in humans and animals. Additionally, the genetically mediated mechanisms underlying this endophenotype need to be characterized further across species. [source] REVIEW: Norepinephrine and stimulant addictionADDICTION BIOLOGY, Issue 2 2009Mehmet Sofuoglu ABSTRACT No pharmacotherapies are approved for stimulant use disorders, which are an important public health problem. Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin and norepinephrine (NE). Stimulant reward is attributable mostly to increased DA in the reward circuitry, although DA stimulation alone cannot explain the rewarding effects of stimulants. The noradrenergic system, which uses NE as the main chemical messenger, serves multiple brain functions including arousal, attention, mood, learning, memory and stress response. In pre-clinical models of addiction, NE is critically involved in mediating stimulant effects including sensitization, drug discrimination and reinstatement of drug seeking. In clinical studies, adrenergic blockers have shown promise as treatments for cocaine abuse and dependence, especially in patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE synthesis, increased the number of cocaine-negative urines in five randomized clinical trials. Lofexidine, an ,2 -adrenergic agonist, reduces the craving induced by stress and drug cues in drug users. In addition, the NE transporter (NET) inhibitor atomoxetine attenuates some of d-amphetamine's subjective and physiological effects in humans. These findings warrant further studies evaluating noradrenergic medications as treatments for stimulant addiction. [source] PRECLINICAL STUDY: Pavlovian drug discrimination with bupropion as a feature positive occasion setter: substitution by methamphetamine and nicotine, but not cocaineADDICTION BIOLOGY, Issue 2 2009Jamie L. Wilkinson ABSTRACT Bupropion can serve as a discriminative stimulus (SD) in an operant drug discrimination task, and a variety of stimulants substitute for the bupropion SD. There are no reports, however, of bupropion functioning as a Pavlovian occasion setter (i.e. feature positive modulator). The present experiment seeks to fill this gap in the literature by training bupropion in rats as a feature positive modulator that disambiguates when a light will be paired with sucrose. Specifically, on bupropion (10 mg/kg intraperitoneal) sessions, offset of 15-second cue lights were followed by brief delivery of liquid sucrose; saline sessions were similar except no sucrose was available. Rats readily acquired the discrimination with more conditioned responding to the light on bupropion sessions. Bupropion is approved for use as a smoking cessation aid, and more recently has drawn attention as a potential pharmacotherapy for cocaine and methamphetamine abuse. Accordingly, after discrimination training, we tested the ability of cocaine (1,10 mg/kg), methamphetamine (0.1 to 1 mg/kg) and nicotine (0.00625 to 0.2 mg/kg) to substitute for the bupropion feature. Nicotine (0.05 mg/kg) and methamphetamine (0.3 mg/kg) substituted fully for bupropion; cocaine did not substitute. These results extend previous research on shared stimulus properties between bupropion and other stimulants to a Pavlovian occasion setting function. Further, this is the first report of nicotine and methamphetamine substitution for bupropion. The overlap in stimulus properties might explain the effectiveness of bupropion as a smoking cessation aid and highlight the possible utility of bupropion for treatment of stimulant use disorder. [source] PRECLINICAL STUDY: Proteomic analysis of methamphetamine-induced reinforcement processes within the mesolimbic dopamine systemADDICTION BIOLOGY, Issue 3-4 2008Moon Hee Yang ABSTRACT Methamphetamine (MAP) is a commonly used, addictive drug, and a powerful stimulant that dramatically affects the central nervous system. In this study, we used the conditioned place preference (CPP) paradigm in order to study the reinforcing properties of MAP and the herewith associated changes in proteins within the mesolimbic dopamine system. A CPP was induced by MAP after three intermittent intraperitoneal injections (1 mg/kg) in rats and protein profiles in the nucleus accumbens, striatum, prefrontal cortex, cingulate cortex and hippocampus were compared with a saline-treated control group. In addition, a group of animals was run through extinction and protein profiles were compared with a non-extinguished group. Protein screening was conducted using two-dimensional electrophoresis analysis which identified 27 proteins in the group that showed MAP-induced CPP. Some of the proteins were confirmed by Western lot analysis. Identified proteins had functions related to the cytoskeleton, transport/endocytosis or exocytosis (e.g. profilin-2 and syntaxin-binding protein), and signal transduction, among others. [source] Effects of prolonged gum chewing on pain and fatigue in human jaw musclesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2001Mauro Farella Gum chewing has been accepted as an adjunct to oral hygiene, as salivary stimulant and vehicle for various agents, as well as for jaw muscle training. The aim of this study was to investigate the effects of prolonged gum chewing on pain, fatigue and pressure tenderness of the masticatory muscles. Fifteen women without temporomandibular disorders (TMD) were requested to perform one of the following chewing tasks in three separate sessions: chewing a very hard gum, chewing a soft gum, and empty-chewing with no bolus. Unilateral chewing of gum or empty chewing was performed for 40 min at a constant rate of 80 cycles/min. In each session, perceived muscle pain and masticatory fatigue were rated on visual analog scales (VAS) before, throughout, and after the chewing task. Pressure pain thresholds (PPTs) of masseter and anterior temporalis muscles were assessed before and immediately after the chewing tasks, and again after 24 h. The VAS scores for pain and fatigue significantly increased only during the hard gum chewing, and after 10 min of recovery VAS scores had decreased again, almost to their baseline values. No significant changes were found for PPTs either after hard or soft gum chewing. The findings indicate that the jaw muscles recover quickly from prolonged chewing activity in subjects without TMD. [source] Attack and defence in the gastric epithelium , a delicate balanceEXPERIMENTAL PHYSIOLOGY, Issue 4 2007Rod Dimaline The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin. [source] Effects of some bacteria (Pseudomonas spp. and Erwinia herbicola) on in vitro growth of Piptoporus betulinusFOREST PATHOLOGY, Issue 6 2000K. Przyby Summary Bacteria including Pseudomonas putida, Pseudomonas fluorescens biovar I, Pseudomonas fluorescens biovar V, Pseudomonas aureofaciens and Erwinia herbicola were isolated from discoloured zones in birch trunks. Antagonistic effects of these bacteria to growth of Piptoporus betulinus mycelium were tested in vitro, both in dual culture and using bacterial cell-free culture filtrates. In dual cultures, P. putida was most effective at inhibiting mycelial growth of Piptoporus betulinus. Filtrates of P. putida inhibited growth of P. betulinus mycelium irrespective of filtrate concentration, incubation time of bacteria and timing of recording mycelium growth. The strongest antagonistic effect (inhibition of fungal growth) was observed on a medium containing 80% of sterile filtrate obtained from 15-day-old bacterial cultures. The highest stimulating effect on mycelium growth was noted on medium containing 80% filtrate obtained from 7-day-old E. herbicola cultures. Résumé Des bactéries, Pseudomonas putida, Pseudomonas fluorescens biovar I, Pseudomonas fluorescens biovar V, Pseudomonas aureofaciens et Erwinia herbicola, ont été isolées de zones colorées de troncs de bouleau. Les effets antagonistes de ces bactéries sur la croissance mycélienne de Piptoporus betulinus ont étéévalués in vitro, en cultures doubles et à partir de filtrats bactériens. En cultures doubles, P. putida a été le plus inhibiteur de la croissance du P. betulinus. Les filtrats de P. putida inhibaient la croissance quel que soit la concentration du filtrat, la durée d'incubation de la bactérie, et le délai dans lequel la croissance mycélienne était mesurée. L'effet inhibiteur le plus fort a été observé sur un milieu contenant 80% de filtrat stérile obtenu de cultures bactériennes de 15 jours. L'effet stimulant le plus fort a été noté sur un milieu contenant 80% d'un filtrat obtenu de cultures de 7 jours de E. herbicola. Zusammenfassung Verschiedene Bakterienarten (Pseudomonas putida, Pseudomonas fluorescens Biovar I, Pseudomonas fluorescens Biovar V, Pseudomonas aureofaciens und E. herbicola) wurden aus verfärbtem Holz in Birkenstämmen isoliert. Antagonistische Effekte dieser Bakterien gegenüber Myzel von Piptoporus betulinus wurden in vitroüberprüft (Dualkulturen und bakterienzellfreie Kulturfiltrate). In Dualkulturen zeigte P. putida den stärksten Hemmeffekt auf das Myzelwachstum von P. betulinus. Filtrate von P. putida hemmten das Wachstum von P. betulinus, unabhängig von der Filtratkonzentration, der Inkubationszeit der Bakterien und dem Zeitpunkt der Messung des Myzelwachstums. Der antagonistische Effekt (Hemmung des Myzelwachstums) war am ausgeprägtesten auf einem Medium, das 80% Sterilfiltrat von 15 Tage alten Bakterienkulturen enthielt. Der stärkste Stimulationseffekt auf das Myzelwachstum wurde auf einem Medium beobachtet, welches 80% Filtrat von sieben Tage alten E. herbicola -Kulturen enthielt. [source] Caffeine as a promoter of analgesic-associated nephropathy , where is the evidence?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003Johannes M. Fox Abstract Individual groups of nephrologists , in their responsibility for their patients , initiated a most controversial discussion whether or not caffeine , coformulated to analgesics , might initiate or sustain analgesic overdosing. The original sources (data) of such suspicion have got lost during the debate of the last two decades. Therefore, it seemed to be appropriate to investigate the original data background and the reasons why nephrologists started to suspect caffeine as a stimulant of analgesic overdosing by employing a systematic and exhaustive review of primary nephrological publications. Their selection followed a precise selection plan, including all epidemiological studies on analgesic-associated nephropathy, the original papers of all groups having been involved in those studies, further originals from the mainly involved countries (academically, politically), and any literature thereof cited as a proof. The following results emerged from the investigation: (i) The epidemiological studies warranted no conclusion about a role of caffeine in prompting excessive analgesic use. (ii) The identified groups of nephrologists provided not substantial data to advocate the said suspicion, except for the observation of a preferential choice of phenacetin-containing combinations, especially powder preparations. (iii) Only two cited original data sources revealed drug-seeking behaviour with phenacetin-containing preparations which subsided, after phenacetin was banned from the respective markets. Conclusively, it appears that there is no substantial data to support a pivotal role of caffeine in initiating or sustaining analgesic overdosing. However, there is strong data that phenacetin, by its psychotropic properties, may have caused drug-seeking behaviour and thus led to analgesic overdosing. This conclusion is convincingly supported by thorough pharmacokinetic investigations. Note: All caffeine-related statements within the reviewed literature have been collected in tables (referred to as Table SX) which are provided in full text for check on the following website: http://www.blackwellpublishing.com/products/journals/suppmat/FCP/FCP174/FCP174sm.htm [source] Lipopolysaccharide is a frequent and significant contaminant in microglia-activating factorsGLIA, Issue 1 2008Jonathan R. Weinstein Abstract Lipopolysaccharide (LPS/endotoxin) is a potent immunologic stimulant. Many commercial-grade reagents used in research are not screened for LPS contamination. LPS induces a wide spectrum of proinflammatory responses in microglia, the immune cells of the brain. Recent studies have demonstrated that a broad range of endogenous factors including plasma-derived proteins and bioactive phospholipids can also activate microglia. However, few of these studies have reported either the LPS levels found in the preparations used or the effect of LPS inhibitors such as polymyxin B (PMX) on factor-induced responses. Here, we used the Limulus amoebocyte lysate assay to screen a broad range of commercial- and pharmaceutical-grade proteins, peptides, lipids, and inhibitors commonly used in microglia research for contamination with LPS. We then characterized the ability of PMX to alter a representative set of factor-induced microglial activation parameters including surface antigen expression, metabolic activity/proliferation, and NO/cytokine/chemokine release in both the N9 microglial cell line and primary microglia. Significant levels of LPS contamination were detected in a number of commercial-grade plasma/serum- and nonplasma/serum-derived proteins, phospholipids, and synthetic peptide preparations, but not in pharmaceutical-grade recombinant proteins or pharmacological inhibitors. PMX had a significant inhibitory effect on the microglia-activating potential of a number of commercial-, but not pharmaceutical-grade, protein preparations. Novel PMX-resistant responses to ,2 -macroglobulin and albumin were incidentally observed. Our results indicate that LPS is a frequent and significant contaminant in commercial-grade preparations of previously reported microglia-activating factors. Careful attention to LPS levels and appropriate controls are necessary for future studies in the neuroinflammation field. © 2007 Wiley-Liss, Inc. [source] Relationship between the cardiac response to acute intoxication and alcohol-induced subjective effects throughout the blood alcohol concentration curveHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2007Caroline Brunelle Abstract Rationale There is evidence to suggest that individual differences in the subjective response to alcohol exist and exaggerated cardiac response to alcohol has been suggested to be a marker of increased sensitivity to the stimulant properties of alcohol. Objectives The present investigation examines the relationship between cardiac reactivity to alcohol measured on the ascending limb of the Blood Alcohol Concentration (BAC) curve and the subjective stimulant and sedative effects of alcohol throughout the BAC curve. Methods The stimulant and sedative effects of alcohol anticipatory to alcohol and during the ascending and descending limbs of the BAC curve were evaluated using the Biphasic Alcohol Effects Scale in 39 male social drinkers. Results Cardiac response to ethanol measured on the ascending limb of the BAC curve was positively correlated with intoxicated stimulant effects at numerous time points during the ascending and descending limbs of the BAC curve (ps,<,0.01). No associations were found between cardiac change following alcohol and alcohol-related sedative effects at any time point. Conclusions Objective and subjective reports of stimulation post-alcohol ingestion may increase risk for problematic drinking. Copyright © 2007 John Wiley & Sons, Ltd. [source] Mechanisms of natural tolerance in the intestine.INFLAMMATORY BOWEL DISEASES, Issue 4 2004Implications for inflammatory bowel disease Abstract Tolerance, the regulated inability to respond to a specific immunologic stimulant, is a physiological event important to normal immune function. Just as loss of tolerance to self-proteins results in autoimmune diseases, we assert that loss of tolerance to commensal flora in the intestinal lumen leads to inflammatory bowel disease (IBD). Mechanisms through which the mucosal immune system establishes and remains hyporesponsive toward the presence of food proteins and commensal flora, which we define as natural tolerance, are discussed. In addition to the contributions by commensal flora, the innate host defense and the adaptive immune systems promote natural tolerance to sustain normal mucosal homeostasis. Understanding the molecular and cellular events that mediate natural tolerance will lead to more advanced insights into IBD pathogenesis and improved therapeutic options. [source] Interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders in an HIV-infected cohort: experience of the National NeuroAIDS Tissue ConsortiumINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2006S. Morgello Abstract The interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was assessed in a multicentre study. Four sites of the National NeuroAIDS Tissue Consortium performed blinded reratings of audiotaped PRISM interviews of 63 HIV-infected patients. Diagnostic modules for substance-use disorders and major depression were evaluated. Seventy-six per cent of the patient sample displayed one or more substance-use disorder diagnoses and 54% had major depression. Kappa coefficients for lifetime histories of substance abuse or dependence (cocaine, opiates, alcohol, cannabis, sedative, stimulant, hallucinogen) and major depression ranged from 0.66 to 1.00. Overall the PRISM was reliable in assessing both past and current disorders except for current cannabis disorders when patients had concomitant cannabinoid prescriptions for medical therapy. The reliability of substance-induced depression was poor to fair although there was a low prevalence of this diagnosis in our group. We conclude that the PRISM yields reliable diagnoses in a multicentre study of substance-experienced, HIV-infected individuals. Copyright © 2006 John Wiley & Sons, Ltd. [source] Differences in woody vegetation are unrelated to use by African elephants (Loxodonta africana) in Mkhuze Game Reserve, South AfricaAFRICAN JOURNAL OF ECOLOGY, Issue 1 2010Angela M. White Abstract The reintroduction of African elephants into fenced game reserves throughout South Africa has presented managers with several challenges. Although elephants are a natural part of southern African ecosystems, their confinement to fenced protected areas in South Africa has exacerbated their potential to impact their habitats negatively. However, many studies investigating the impact of elephants have failed to control for the effects of other browsers on the vegetative community. In this study, we used location data on an elephant herd to delineate high-use and low-use areas. This paired design allowed us to minimize confounding factors that could explain differences in the structure, diversity and utilization of woody species. We found little evidence to suggest elephant-mediated change in, or selection for, the structure or diversity of woody species; however, our results suggest that elephants may be altering the composition of species by preferentially using areas with higher canopy diversity and by enhancing sapling recruitment. Although stripping of bark was higher in high-use areas, there was no evidence of differential mortality of tree species. Therefore, in our study area, and over the current time scale, elephants are having a negligible impact on the vegetative community. Résumé La réintroduction d'éléphants africains dans des réserves de faune clôturées dans toute l'Afrique du Sud représente plusieurs défis pour les gestionnaires. Bien que les éléphants fassent naturellement partie des écosystèmes d'Afrique australe, leur confinement dans des aires protégées clôturées en Afrique du Sud a exacerbé leur capacité d'avoir des impacts négatifs sur leurs habitats. Pourtant, les nombreuses études qui ont recherché l'impact des éléphants ont omis de contrôler l'effet des autres herbivores sur la communauté végétale. Dans cette étude, nous avons utilisé des données sur la localisation des hardes d'éléphants pour délimiter les zones plus ou moins fréquentées. Cette étude couplée nous a permis de minimiser les facteurs prêtant à confusion qui pouvaient expliquer des différences de structure, de diversité et d'utilisation des espèces ligneuses. Nous avons trouvé peu de preuves qui auraient indiqué que les éléphants changeaient ou sélectionnaient la structure ou la diversité des espèces ligneuses; cependant, nos résultats suggèrent que les éléphants pourraient modifier la composition des espèces en choisissant de préférence les zones où la diversité de la canopée est plus élevée et en stimulant le recrutement de jeunes plants. Même si les arrachages d'écorces étaient plus nombreux dans les zones très fréquentées, il n'y avait aucune preuve d'une mortalité différentielle selon les espèces d'arbres. C'est pourquoi, dans l'aire où nous avons travaillé, et pour le moment, on peut dire que les éléphants n'ont qu'un impact négligeable sur la communauté végétale. [source] Caffeine Content of Prepackaged National-Brand and Private-Label Carbonated BeveragesJOURNAL OF FOOD SCIENCE, Issue 6 2007K.-H. Chou ABSTRACT:, Caffeine is a well-known stimulant that is added as an ingredient to various carbonated soft drinks. Due to its stimulatory and other physiological effects, individuals desire to know the exact amount of caffeine consumed from these beverages. This study analyzed the caffeine contents of 56 national-brand and 75 private-label store-brand carbonated beverages using high-performance liquid chromatography. Caffeine contents ranged from 4.9 mg/12 oz (IGA Cola) to 74 mg/12 oz (Vault Zero). Some of the more common national-brand carbonated beverages analyzed in this study with their caffeine contents were Coca-Cola (33.9 mg/12 oz), Diet Coke (46.3 mg/12 oz), Pepsi (38.9 mg/12 oz), Diet Pepsi (36.7 mg/12 oz), Dr Pepper (42.6 mg/12 oz), Diet Dr Pepper (44.1 mg/12 oz), Mountain Dew (54.8 mg/12 oz), and Diet Mountain Dew (55.2 mg/12 oz). The Wal-Mart store-brand beverages with their caffeine contents were Sam's Cola (12.7 mg/12 oz), Sam's Diet Cola (13.3 mg/12 oz), Dr Thunder (30.6 mg/12 oz), Diet Dr Thunder (29.9 mg/12 oz), and Mountain Lightning (46.5 mg/12 oz). Beverages from 14 other stores were also analyzed. Most store-brand carbonated beverages were found to contain less caffeine than their national-brand counterparts. The wide range of caffeine contents in carbonated beverages indicates that consumers would benefit from the placement of caffeine values on food labels. [source] Suppression of the Febrile Response in Late Gestation: Evidence, Mechanisms and OutcomesJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2008A. Mouihate Fever is a beneficial host defence response. However, fever caused by the immune stimulant, lipopolysaccharide (LPS), are attenuated in many species during pregnancy, particularly near term. A number of parallel mechanisms may be responsible, and these vary in magnitude according to the time of gestation, type of inflammatory stimulus and species of animal. Some studies report a reduction in the plasma levels of circulating pro-inflammatory cytokines such as tumour necrosis factor-,, interleukin-1, and interleukin-6 along with increased levels of anti-inflammatory cytokines such as interleukin-1 receptor antagonist. Associated with the attenuated febrile response to LPS is a reduction in the activation of the prostaglandin synthesising enzyme, cyclo-oxygenase 2, resulting in reduced levels of the obligatory prostaglandin mediators of the febrile response in the brain. There is also a reduction in the sensitivity of the brain to the pyrogenic action of prostaglandins, which does not appear to be due to a change in the levels of hypothalamic EP3 prostaglandin receptors. The suppression of fever at term may be important for the health of the neonate because fever in pregnant mothers may be harmful to the late-term foetus and neonate. [source] Investigation of ,2 -adrenoceptor subtype selectivity and organ specificity for bedoradrine (KUR-1246), a novel tocolytic beta-adrenergic receptor stimulantJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2009Yoshihito Inoue Abstract Objectives:, The aim of this study was to evaluate the beta-adrenergic receptor (,-AR) selectivity, organ specificity and efficacy of delaying the onset of spontaneous delivery of bedoradrine (KUR-1246), a novel uterine relaxant. Methods:, ,-AR selectivity was evaluated in terms of the amount of cyclic adenosine monophosphate produced by bedoradrine, ritodrine and isoprenaline in Chinese hamster ovary cells expressing human ,1 -, ,2 -AR or ,3 -AR. Inhibition of contractions of the atrium, trachea and proximal colon by bedoradrine were compared with those of the uterus in pregnant rats using an organ bath method. Finally, the delaying effect of bedoradrine on spontaneous labor was evaluated by an in vivo study using term pregnant rats. Results:, EC50 values of bedoradrine for cyclic adenosine monophosphate production in Chinese hamster ovary cells via ,1 -, ,2 - and ,3 -AR were 2400 ± 30, 2.9 ± 0.10 and 363 ± 3 nmol/L, respectively, indicating that bedoradrine had 832- and 126-fold higher selectivity for ,2 -AR than for ,1 - and ,3 -AR. EC50 values of bedoradrine for the uterus, atrium, trachea and proximal colon were 1.01 ± 0.27, 2300 ± 356, 1610 ± 299 and 219 ± 23.5 nmol/L, respectively. Thus, bedoradrine was 2280-, 1590- and 217-fold more specific for the uterus than for the atrium, trachea and proximal colon, respectively. Bedoradrine delayed the spontaneous delivery of 21-day-pregnant rats in a dose-dependent manner. Conclusions:, Bedoradrine is a promising drug for the treatment of preterm labor in obstetrical practice because it has better selectivity for ,2 -AR and specificity for the uterus than currently used agents and may effectively delay spontaneous delivery. [source] Porphyromonas gingivalis stimulates the release of nitric oxide by inducing expression of inducible nitric oxide synthases and inhibiting endothelial nitric oxide synthasesJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2010W. Sun Sun W, Wu J, Lin L, Huang Y, Chen Q, Ji Y. Porphyromonas gingivalis stimulates the release of nitric oxide by inducing expression of inducible nitric oxide synthases and inhibiting endothelial nitric oxide synthases. J Periodont Res 2010; 45: 381,388. © 2010 The Authors. Journal compilation © 2010 Blackwell Munksgaard Background and Objective:, The purpose of this study was to examine the ability of Porphyromonas gingivalis to invade human umbilical vein endothelial cells (HUVECs) and to study the effects of P. gingivalis ATCC 33277 on the production of nitric oxide (NO) and on the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in HUVECs. We attempted to throw light on the pathway of damage to endothelial function induced by P. gingivalis ATCC 33277. Material and Methods:,P. gingivalis ATCC 33277 was cultured anaerobically, and HUVECs were treated with P. gingivalis ATCC 33277 at multiplicities of infection of 1:10 or 1:100 for 4, 8, 12 and 24 h. HUVECs were observed using an inverted microscope and transmission electron microscopy. NO production was assayed through measuring the accumulation of nitrite in culture supernatants. Expression of both iNOS and eNOS proteins was investigated through western blotting. Results:, It was found that P. gingivalis ATCC 33277 can adhere to HUVECs by fimbriae, invade into HUVECs and exist in the cytoplasm and vacuoles. P. gingivalis ATCC 33277 can induce iNOS and inhibit eNOS expression, and stimulate the release of NO without any additional stimulant. Conclusion:, Our study provides evidence that P. gingivalis ATCC 33277 can invade HUVECs, and the ability of P. gingivalis ATCC 33277 to promote the production of NO may be important in endothelial dysfunction, suggesting that P. gingivalis ATCC 33277may be one of the pathogens responsible for atherosclerosis. [source] Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretionJOURNAL OF PINEAL RESEARCH, Issue 4 2003Markus Sjöblom Abstract: Melatonin, originating from intestinal enterochromaffin cells, mediates vagal and sympathetic neural stimulation of the HCO secretion by the duodenal mucosa. This alkaline secretion is considered the first line of mucosal defense against hydrochloric acid discharged from the stomach. We have studied whether luminally applied melatonin stimulates the protective secretion and whether a melatonin pathway is involved in acid-induced stimulation of the secretion. Rats were anaesthetized (Inactin®) and a 12-mm segment of proximal duodenum with an intact blood supply was cannulated in situ. Mucosal HCO secretion (pH-stat) and the mean arterial blood pressure were continuously recorded. Luminal melatonin at a concentration of 1.0 ,m increased (P < 0.05) the secretion from 7.20 ± 1.35 to 13.20 ± 1.51 ,Eq/cm/hr. The MT2 selective antagonist luzindole (600 nmol/kg, i.v.) had no effect on basal HCO secretion, but inhibited (P < 0.05) secretion stimulated by luminal melatonin. Hexamethonium (10 mg/kg i.v. followed by continuous i.v. infusion at a rate of 10 mg/kg/hr), abolishes neurally mediated rises in secretion and also inhibited (P < 0.05) the stimulation by luminal melatonin. Exposure of the lumen to acid containing perfusate (pH 2.0) for 5 min increased (P < 0.05) the HCO secretion from 5.85 ± 0.82 to 12.35 ± 1.51 ,Eq/cm/hr, and luzindole significantly inhibited (P < 0.05) this rise in secretion. The study thus demonstrates that luminal melatonin is a potent stimulant of duodenal HCO secretion and, furthermore, strongly suggests melatonin as an important mediator of acid-induced secretion. [source] Expanding the Utility of the Biphasic Alcohol Effects Scale (BAES) and Initial Psychometric Support for the Brief-BAES (B-BAES)ALCOHOLISM, Issue 5 2009Sandra Y. Rueger Background:, The utility of one of the most widely used subjective alcohol assessment tools, the Biphasic Alcohol Effects Scale (BAES) has been somewhat limited based on lack of psychometric studies in large and diverse samples, a range of alcohol doses, the length of the measure, and the original instructional set which precluded baseline measurement and disclosed to subjects that they received alcohol. Methods:, The current study investigated the factor structure of the BAES with a modified instructional set at pre-drink baseline and after consumption of various doses of alcohol, in a sample of 190 men and women, heavy and light social drinkers. This study tested the psychometric properties of a brief version of the BAES (Brief-BAES or B-BAES). Results:, Results demonstrated robust support of the stimulant and sedative constructs across all conditions, and demonstrated strong psychometric support for the 6-item B-BAES. Discussion:, This is the first comprehensive study to expand the utility of the BAES by instructional set, baseline measurement, at various alcohol doses, and by drinking history and sex. In addition, the introduction of the B-BAES may further increase the utility of this scale, particularly in paradigms with repeated measurement or time constraints. [source] Multi-residue method for the analysis of pharmaceutical compounds in sewage sludge, compost and sediments by sonication-assisted extraction and LC determinationJOURNAL OF SEPARATION SCIENCE, JSS, Issue 12 2010Julia Martín Abstract A method for the simultaneous determination of 16 pharmaceutical compounds in three types of sewage sludge (primary, secondary and anaerobically digested dehydrated sludge), compost and sediment samples is described. Pharmaceutical compounds evaluated were nonsteroidal anti-inflammatory drugs (acetaminophen, diclofenac, ibuprofen, ketoprofen, naproxen and salicylic acid), antibiotics (sulfamethoxazole and trimethoprim), an anti-epileptic drug (carbamazepine), a ,-blocker (propranolol), a nervous stimulant (caffeine), estrogens (17,-ethinylestradiol, 17,-estradiol, estriol and estrone) and lipid regulators (clofibric acid, metabolite of clofibrate and gemfibrozil). The method is based on the ultrasonic-assisted extraction, clean-up by SPE and analytical determination by HPLC with diode array and fluorescence detectors. The best extraction recoveries were achieved in a three-step extraction procedure with methanol and acetone as extraction solvents. Extraction recoveries of several pharmaceutical compounds as caffeine were highly dependent on the type of sample evaluated. The applicability of the method was tested by analyzing primary, secondary and anaerobically digested dehydrated sludge, compost and sediment samples from Seville (Southern Spain). Ten of the sixteen pharmaceutical compounds were detected in sludge samples and five in compost and sediment samples. The highest concentration levels were recorded for ibuprofen in sewage samples, whereas salicylic acid and 17,-ethinylestradiol were detected in all of the samples analyzed. [source] Cognitive Efficiency in Stimulant Abusers With and Without Alcohol DependenceALCOHOLISM, Issue 3 2003Andrea Lawton-Craddock Background: Although previous studies have found stimulant (i.e., cocaine, methamphetamine) abusers and alcoholics to have neuropsychological deficits, research examining which cognitive abilities are most affected by concurrent exposure to these substances is lacking. To address this issue, detoxified men and women who met criteria for dependence of (a) alcohol only (ALC) (n= 15); (b) stimulants only (STIM) (n= 15); and (c) both alcohol and stimulants (A/STIM) (n= 15) were compared with age- and education-matched community controls (n= 15). Methods: Tasks that measured visual spatial skills, problem-solving and abstraction, short-term memory, cognitive flexibility, and gross motor speed were administered to participants. For each test, both speed and accuracy were assessed and an efficiency ratio (accuracy/time) was derived. Based on an average of these efficiency ratios, an overall performance index of cognitive efficiency was obtained. Results: Overall, controls performed more efficiently than all other groups. However, they were statistically significantly better only in relation to the A/STIM and STIM groups (p < 0.01). Individual comparisons revealed that the ALC group performed significantly better than the STIM group, although the ALC group did not differ from either the control or A/STIM groups (p, 0.05). This pattern of results was relatively consistent across the individual subtests of problem-solving/abstraction, short-term memory, and cognitive flexibility. Conclusions: As expected, substance abuse was associated with cognitive inefficiency. More importantly, these findings suggest that the cognitive effects of chronic stimulant abuse are not additive with those of alcohol abuse. That is, singly addicted stimulant abusers demonstrated similar or greater neurocognitive impairments than individuals who abuse alcohol and stimulants concurrently. The reason for this pattern is speculative but may be attributed to alcohol's opposing actions on cerebrovascular effects brought on by stimulant abuse. [source] Validation of a Feeding Stimulant Bioassay Using Fish Hydrolysates for the Pacific White Shrimp, Litopenaeus vannameiJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 4 2009Michael Grey A protocol for testing feeding stimulants on Pacific white shrimp, Litopenaeus vannamei, is described. Thirty-five rectangular tanks (55 L volume) served as the test system into which ten 5,6 g shrimp were stocked. Every tank contained two bowls, each of which contained either 25 feed pellets of a Reference Diet or Test Diet (consisting of the Reference Diet with one test ingredient added). After 1 h, the difference between the number of pellets consumed of the Test Diet and the Reference Diet was used as the Response. Each of the four Test Diets contained a different salmon hydrolysate made from by-products of the Alaska fish processing industry (included at 50 g/kg). A fifth commercial shrimp diet was also tested. Each Test Diet was tested against the Reference Diet over a 4-d period in seven replicate tanks. The data were subjected to a one-way ANOVA and a confidence interval for each treatment response was calculated. The confidence interval was used to assess the test ingredient as a feeding stimulant. Treatment means were compared using Tukey's test (, = 5%). All the hydrolysates tested were found to act as feeding stimulants. [source] A Methodology for Evaluation of Dietary Feeding Stimulants for the Pacific White Shrimp, Litopenaeus vannameiJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 1 2005Dagoberto R. Sanchez A simple and practical method for quantification of feeding stimulation of shrimp Litopenaeus vannamei was developed using feed preference as an index of comparison. Feed preference was defined as the percentage of shrimp observed in each feeding tray. Preliminary trials were undertaken with two commercial feeds (45% protein with 5% squid meal and 40% protein without squid meal). Results indicated the following criteria were suitable for use as methodology for evaluating feeding stimulation in 5-m diameter static flow tanks: shrimp density (2.5 shrimp/m2); observational period (1 or 2 h post-addition of feed to trays), feed rate (2%), and between-trial feed rate (2%). A further investigation was undertaken to evaluate the influence of protein level and source on feed preference using a basal diet consisting of wheat flour, casein, carboxymethyl cellulose binder, and limestone, with or without krill meal as a feeding stimulant. A significant difference was shown in feeding preference for the 16% protein/4% krill meal vs. one without krill meal; however, this relationship was not shown in 45% protein feed comparisons. A second trial comparing 0, 16,30, and 45 % protein/casein-based feeds showed similar results. From these findings, it was postulated that casein, itself, also serves as a feeding stimulant at high dietary inclusion levels. A third trial comparing 16% protein/casein or wheat gluten-based feeds Indicated a delay of at least 2 h in maximum feeding preference response in feeds in which 4% krill meal was added as a feeding stimulant. It was postulated that chemical stimulants from krill meal were more slowly released in wheat gluten-based feeds. Our methodology appears suitable for evaluation of potential feeding stimulants when incorporated into low-protein casein-based or wheat-gluten-based feeds. [source] Early Mesozoic evolution of alivincular bivalve ligaments and its implications for the timing of the ,Mesozoic marine revolution'LETHAIA, Issue 2 2004MICHAEL HAUTMANN The early Mesozoic radiation of the Pteriomorphia was accompanied and furthered by the development of several new types of alivincular ligaments. These new types evolved as modifications of the primitive alivincular-areate (new term) ligament, which is characterized by an ontogenetic shift of both the central resilium and the straight lateral ligament in the direction of main shell growth. Arching of the attachment surface of the ligament led to the alivincular-arcuate (new term) ligament type, which has been realized by the Ostreidae only. By contrast, a replacement of the lateral ligament by hinge teeth, limiting the (primary) ligament to a central groove (alivincular-fossate, new term), has evolved independently in three families (Dimyidae, Plicatulidae and Spondylidae). Functionally, both kinds of modification effectively impede shearing of the valves and are interpreted as an antipredatory adaptation advantageous in the cemented habit of these families. The alivincular-alate (new term) ligament of the Entoliidae and Pectinidae differs from the other types of alivincular ligaments by different growth directions of resilium and lateral ligament, which result in an internal position of the resilium suitable for fast and powerful opening of the valves. This arrangement is an important prerequisite for effective swimming, which, in its turn, is a behaviour chiefly used to escape from predator attacks. The simultaneous early Mesozoic appearance of different antipredatory adaptations within independent clades hints at increased predator pressure as a stimulant and may therefore point to a contemporaneous proliferation of durophagous predators. Hence, an important aspect of the ,Mesozoic marine revolution' might have started earlier than previously thought. [source] | ||||||||||||||||||||||||||||||||||||||||