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Selected AbstractsProtein kinase C beta inhibitor prevents diabetic peripheral neuropathy, but not histopathological abnormalities of retina in Spontaneously Diabetic Torii ratDIABETES OBESITY & METABOLISM, Issue 11 2009T. Sasase Spontaneously Diabetic Torii (SDT) rat shows severe ocular complications such as tractional retinal detachment. In the present study, effect of protein kinase C beta (PKC,) inhibitor JTT-010 was evaluated to clarify the involvement of PKC, in complications of SDT rat. SDT rats were administered JTT-010 (10 or 50 mg/kg/day) for 48 weeks. SDT rats showed delayed oscillatory potentials in electroretinogram. Delayed motor nerve conduction velocity, decreased coefficients of variation of R,R intervals in electrocardiogram and thermal hypoalgesia were also observed. These functional disorders were prevented by administration of JTT-010. Abnormal retinal vascular was formed and the optic disc was protruded in SDT rat; however, JTT-010 did not prevent these hyperglycaemia-induced retinal abnormalities. These findings indicate that PKC, is intimately involved in diabetic complications; however, it seems that other factor(s) are primary contributors to histopathological abnormalities in retina. Therefore, PKC, inhibitors require concurrent administration of antihyperglycaemic drugs to achieve maximum effect on diabetic complications. [source] The early identification of dyslexia: Children with English as an additional languageDYSLEXIA, Issue 3 2004Jane M. Hutchinson Abstract It is generally accepted that dyslexia should be identified early for interventions to have maximum effect. However, when children speak English as an additional language (EAL), diagnosis is more complex and there is concern that these children tend to be under-identified. This paper reports a longitudinal study following the development of phonological awareness skills in relation to progress in learning to read with a cohort of British Asian children learning EAL and their monolingual peers. It also sought to determine the usefulness of a measure of phonological skills for the identification of dyslexic-type difficulties in children learning EAL. Analysis revealed that both cohorts achieved similar levels of reading accuracy in school Years 2, 4 and 6, with higher levels of reading comprehension for the monolingual children and faster reading fluency for children learning EAL in each school year. There was a similar pattern of relationships between the reading measures and measures of phonological awareness for both groups of children. However, monolingual children achieved higher levels of rhyme detection and alliteration fluency whilst the children learning EAL achieved faster number naming times. Overall, a phonological assessment battery was useful in identifying reading accuracy related difficulties in both groups of children. However, concerns are raised about the sensitivity of such measures following the introduction of the Literacy Hour. Copyright © 2004 John Wiley & Sons, Ltd. [source] Management of Fruit Flies (Diptera: Tephritidae) of the Most Perishable FruitsENTOMOLOGICAL RESEARCH, Issue 2 2005Muhammad Ahsan KHAN ABSTRACT We investigated to minimize the dependency on the use of chemicals and thus develop safe and environmental friendly control program for the most perishable fruits i.e., apple,,ber', guava and mango. Our findings on the composition of fruit fly species reveal that Bactrocera dorsalis was dominant on apple (33.96% existence), Corpomya incompleta on,ber'(51.91% existence) and Bactrocera zonata on guava (49.62% existence) and mango (74.66% existence). The correlation between population and infestation percentage was non-significant in apple orchards, whereas positive and highly significant in between population and infestation, as well as on the cumulative basis in,ber', guava and mango orchards during 1998-1999. Hoeing, baiting and methyl eugenol were statistically equal resulting about 77% decrease in infestation. The maximum control of 91.68% was observed where all four-control operations including Dipterex® were integrated together. Weather factors, when computed together, had maximum effect on population fluctuation and infestation with rainfall contributing the major role. For guava fruits, the months of August (14.06A individuals/trap/day) and September (13.81A individuals/trap/day) were important, resulting in maximum infestation percentage of 10.76 to 14.74%, respectively. [source] Antiepileptic Effect of Gap-junction Blockers in a Rat Model of Refractory Focal Cortical EpilepsyEPILEPSIA, Issue 7 2006Karen E. Nilsen Summary:,Purpose: Epilepsy is the most common serious neurologic disease, and current treatments are ineffective for ,30% of patients. Gap junctions have been implicated in seizure generation and propagation, and as such, may represent a novel therapeutic target but have been little investigated in vivo. We set out to assess the efficacy and tolerability of gap-junction blockers delivered to the seizure focus in a well-characterized model of refractory cortical epilepsy in rats. Methods: A chronic epilepsy focus was induced in the cortex of rats by using tetanus toxin, and subsequent studies were conducted in freely moving unanesthetized animals with frequent spontaneous seizures, as we previously described. Carbenoxolone, meclofenamic acid, and saline were applied directly to the seizure focus. EEG, electromyogram (EMG), and behavioral parameters were measured for ,1 h before drug infusion and for ,3 h afterward. No ill effects were observed. Results: An immediate and marked reduction in percentage of seizure time was seen in rats receiving carbenoxolone (baseline, 69.4%± 7.0% (SEM); maximum effect, 9.3%± 3.5%, p ,0.001) and meclofenamic acid (baseline, 58.3%± 3.7%; maximum effect, 0.92%± 0.92%, p < 0.001). No effect was seen after saline infusion. Conclusions: Gap-junction blockers applied focally are effective at suppressing seizures and, as such, represent a potential new treatment for epilepsy. Development of focal treatment strategies is essential in this regard. [source] Direct and Indirect Actions of Fibroblast Growth Factor 2 on Osteoclastic Bone Resorption in CulturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2000Hiroshi Kawaguchi M.D., Ph.D. Abstract Fibroblast growth factor 2 (FGF-2 or basic FGF) is known to show variable actions on bone formation and bone resorption. This study was undertaken to elucidate the mechanisms whereby FGF-2 affects bone metabolism, especially bone resorption, using three different culture systems. FGF-2 at 10,9 M and higher concentrations induced osteoclastic cell formation in the coculture system of mouse osteoblastic cells and bone marrow cells, and this induction was abrogated by nonsteroidal anti-inflammatory drugs (NSAIDs). 45Ca release from prelabeled cultured mouse calvariae stimulated by FGF-2 (10,8 M) was also inhibited by NSAIDs, and the inhibition was stronger by NSAIDs, which are more selective for inhibition of cyclooxygenase 2 (COX-2) than COX-1, suggesting the mediation of COX-2 induction. COX-2 was highly expressed and its messenger RNA (mRNA) level was stimulated by FGF-2 in osteoblastic cells whereas it was undetectable or not stimulated by FGF-2 in cells of osteoclast lineage. To further investigate the direct actions of FGF-2 on osteoclasts, resorbed pit formation was compared between cultures of purified osteoclasts and unfractionated bone cells from rabbit long bones. FGF-2 (,10,12 M) stimulated resorbed pit formation by purified osteoclasts with a maximum effect of 2.0-fold at 10,11 M, and no further stimulation was observed at higher concentrations. However, FGF-2 at 10,9 M , 10,8 M stimulated resorbed pit formation by unfractionated bone cells up to 9.7-fold. NS-398, a specific COX-2 inhibitor, did not affect the FGF-2 stimulation on purified osteoclasts but inhibited that on unfractionated bone cells. We conclude that FGF-2 at low concentrations (,10,12 M) acts directly on mature osteoclasts to resorb bone moderately, whereas at high concentrations (,10,9 M) it acts on osteoblastic cells to induce COX-2 and stimulates bone resorption potently. [source] Prospective evaluation of the time to peak effect of propofol to target the effect site in childrenACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009H. R. MUŃOZ Background: The plasma-effect site equilibration rate constant (ke0) of propofol has been determined in children with the use of the time to maximum effect (tpeak), however, it has not been validated. The objective was to measure the tpeak; of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target-controlled infusion (TCI) system. Methods: Unpremedicated, ASA I children from 3 to 11 years were studied. In Part 1, children were monitored simultaneously with the bispectral index (BIS) and the A-Line ARX-index (AAI) from the Alaris A-Line auditory-evoked potential monitor/2. The tpeak after a bolus dose of propofol was measured. In Part 2, the tpeak measured was used to target the effect site with a TCI system. The median (MD) and the absolute median (MDA) difference between the predicted time of peak concentration at the effect site (Ce) and the measured time of peak effect in the index of depth of anesthesia (terror) was used to evaluate the performance of the system. Results: The BIS recordings were of a better quality than the AAI. The mean ± standard deviation tpeak was 65 ± 14 s with the BIS (n=25) and 201 ± 74 s with the AAI (n=10)(P<0.001). Validation was only performed with the BIS monitor in 40 children, yielding an MD terror of ,9.5 s and an MDA terror of 10.0 s. Conclusions: The small delay between the evolution of Ce of propofol and the observed effect suggests that this can be a useful model to target the effect site in children. [source] A novel artificial habitat collection device for studying resettlement patterns in anguillid glass eelsJOURNAL OF FISH BIOLOGY, Issue 5 2001V. Silberschneider The number of glass eels Anguilla australis and A. reinhardtii caught in artificial habitat collectors, made from a PVC base and polyethylene split rope fibres, was related to the number of rope fibre tufts attached to each collector rather than collector area directly. Ageing of collectors in situ to promote algal growth enhanced the catch of glass eels. Glass eels entered the collectors at night primarily during the flood tide, and did not move into the collectors during daylight hours. Glass eel abundance increased with increasing distance from the freshwater drain located in the causeway. The artificial habitat collectors are effective for assessing relative numbers of resettling glass eels and may be useful for studying recruitment and settlement patterns of other anguillid eel species, as well as identifying areas and habitats within a catchment that provide important shelter for glass eels. Sampling glass eels can be carried out with maximum effect and minimum effort using compact, aged artificial habitat collectors on the night time flood tide when low tide coincides with dusk. [source] Neuropeptide Y Cotransmission with Norepinephrine in the Sympathetic Nerve,Macrophage InterplayJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Rainer H. Straub Abstract: The CNS modulates immune cells by direct synaptic-likecontacts in the brain and at peripheral sites, such as lymphoid organs. Tostudy the nerve-macrophage communication, a superfusion method was used toinvestigate cotransmission of neuropeptide Y (NPY) with norepinephrine (NE),with interleukin (IL)-6 secretion used as the macrophage read-out parameter.Spleen tissue slices spontaneously released NE, NPY, and IL-6 leading to asuperfusate concentration at 3-4 h of 1 nM, 10 pM, and 120pg/ml, respectively. Under these conditions, NPY dose-dependently inhibitedIL-6 secretion with a maximum effect at 10 -10M(p = 0.012) and 10 -9M (p < 0.001).Simultaneous addition of NPY at 10 -9M and the,-2-adrenergic agonist p -aminoclonidine further inhibited IL-6secretion (p < 0.05). However, simultaneous administration of NPYat 10 -9M and the ,-adrenergic agonist isoproterenolat 10 -6M or NE at 10 -6Msignificantly increased IL-6 secretion (p < 0.005). To objectifythese differential effects of NPY, electrical field stimulation of spleenslices was applied to release endogenous NPY and NE. Electrical fieldstimulation markedly reduced IL-6 secretion, which was attenuated by the NPYY1 receptor antagonist BIBP 3226 (10 -7M, p = 0.039;10 -8M, p = 0.035). This indicates that NPY increases theinhibitory effect of endogenous NE, which is mediated at low NE concentrationsvia ,-adrenoceptors. Blockade of ,-adrenoceptors attenuatedelectrically induced inhibition of IL-6 secretion (p < 0.001),which was dose-dependently abrogated by BIBP 3226. This indicates that underblockade of ,-adrenoceptors endogenous NPY supports the stimulatingeffect of endogenous NE via ,-adrenoceptors. These experimentsdemonstrate the ambiguity of NPY, which functions as a cotransmitter of NE inthe nerve-macrophage interplay. [source] The anti-diabetic effects and pharmacokinetic profiles of bis(maltolato)oxovanadium in non-diabetic and diabetic ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2008Shuang-Qing Zhang ABSTRACT The purpose of this study was to evaluate the anti-diabetic effects and pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic study was carried out in non-diabetic and diabetic rats by single-dose subcutaneous and intragastric administration. Pharmacokinetic investigation was performed using non-diabetic rats. Results showed that BMOV significantly decreased plasma glucose levels in diabetic rats at all given doses, and restored hyperglycaemic values to normal values after subcutaneous injections at doses of 4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14 and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non-diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma, widely distributed in various tissues and accumulated to a greater extent in the femur tissue. The average absolute bioavailability for intragastric administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%, respectively. The presence of the peak vanadium level in the plasma was not coincident with that of the maximum effect of lowering plasma glucose levels. In conclusion, at the present dosing levels and administration routes, BMOV was effective in lowering plasma glucose levels in diabetic rats. BMOV has a promising outlook as an oral glucose-lowering drug. [source] The Search for Mechanisms of Behavior Change in Evidence-Based Behavioral Treatments for Alcohol Use Disorders: OverviewALCOHOLISM, Issue 2007Robert B. Huebner Background:, Over the past three decades, the main question of interest to alcohol treatment researchers has concerned the main effects of a particular behavioral intervention or what works. Increasingly, alcohol treatment researchers are turning their attention to the underlying psychological, social, and even neurophysiologic processes or "active ingredients" that are driving therapeutic change. Method:, The articles contained in this supplement to Alcoholism: Clinical and Experimental Research grew out of invited presentations given at a one-day satellite session immediately preceding the 28th Annual Meeting of the Research Society on Alcoholism (RSA). The conference was a collaborative effort of the Center on Alcoholism, Substance Abuse, and Addiction at the University of New Mexico, the Center on Addiction and Substance Abuse at Columbia University, Brown University, and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. Results:, The conference featured a mix of full-length presentations on conceptual and methodological issues, reports of original research findings, and lively discussion among speakers and conference participants. Understanding mechanisms of behavior change will benefit the field by identifying the key aspects of therapy that must be present for maximum effect, irrespective of the specific technique being applied; provide a new way to approach patient,treatment interactions; and lay the groundwork for understanding how change is affected by social and other extratreatment factors. Conclusions:, Although not a new topic to the field, understanding mechanisms of behavior change has begun to capture the interest of an increasing number of alcohol treatment researchers. Understanding behavior change is an exceedingly complex enterprise and innovative thinking and creative research designs will be required to advance the field. [source] Role of Myocardial Contractility and Autonomic Control in the Hypotensive Response to a Limited Access Ethanol Paradigm in SHRsALCOHOLISM, Issue 6 2007Mahmoud M. El-Mas Background: Previous experimental studies that evaluated the chronic hemodynamic effect of ethanol employed the continuous exposure protocol of ethanol, which does not mimic the pattern of alcohol consumption in humans. This study dealt with the long-term hemodynamic and cardiovascular autonomic effects of ethanol, in a limited-access regimen in telemetered spontaneously hypertensive rats (SHRs). Methods: Changes in blood pressure (BP), heart rate (HR), myocardial contractility (dP/dtmax), and spectral cardiovascular autonomic profiles during the ethanol exposure period (2.5 or 5% w/v, 8 h/d, 8:30 am till 4:30 pm) were followed for 12 weeks. Results: Compared with control pair-fed SHRs, body weight and urine output, osmolality, and potassium levels were decreased in SHRs receiving 5% but not 2.5% ethanol. Blood pressure showed progressive falls during ethanol-feeding periods with a maximum effect observed at week 5. The peak hypotensive effect was maintained thereafter in SHRs receiving 5% ethanol in contrast to steady rises in BP in the 2.5% ethanol group to near-control levels by the conclusion of the study. Heart rate was slightly but significantly increased by ethanol 5% whereas dP/dtmax showed persistent reductions. Power spectral analysis showed that ethanol attenuated the baroreflex gain of HR as suggested by the reductions in index ,, the spectral index of spontaneous baroreflex sensitivity (BRS). Conclusions: It is concluded that limited access ethanol drinking in SHRs elicited hypotension that was concentration dependent and mediated, at least partly, through reductions in myocardial contractility. Baroreflex sensitivity attenuation by ethanol appeared to have limited the tachycardic response to ethanol and perhaps its capacity to offset the evoked hypotension. [source] The exposure-time-response relationship between occupational asbestos exposure and lung cancer in two German case-control studies,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2002Michael Hauptmann PhD Abstract Background Numerous studies have been carried out to evaluate the association between lung cancer and occupational asbestos exposure. However, the effects of timing of exposure have not been analyzed thoroughly. Methods Two German case-control studies with data on occupational asbestos exposure histories have been pooled. Duration of work in potentially asbestos exposed jobs and two derived weighted exposure measures are analyzed together with time since last exposure. A spline function is used to model the effect of time since exposure. Results The odds ratios (OR) and corresponding 95% confidence intervals were 1.8 (1.2, 2.7) and 2.4 (1.7, 3.4) for subjects having worked for 3 to 7 years and 8 or more years, respectively, in a job with potential asbestos exposure compared to never-exposed. Based on an evaluation of time since last exposure, the OR decreased significantly to about one-half after more than 20 years since exposure ceased. Using a spline function, applied to workers' complete exposure histories, the effect of an increment of exposure is greatest 10,15 years after that exposure was received. Conclusions In contrast to previous indications, the risk of lung cancer increases soon after asbestos exposure, with its maximum effect from 10 to 15 years after the exposure was received. Am. J. Ind. Med. 41:89,97, 2002. Published 2002 Wiley-Liss, Inc. [source] 2-Phenylmelatonin: A Partial Agonist at Enteric Melatonin ReceptorsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2000Maria Grazia Santagostino-Barbone The effect of the melatonin receptor ligand, 2-phenylmelatonin, has been assessed in isolated strips of the guinea-pig proximal colon. 2-Phenylmelatonin (0.01 nM-1 ,M) caused a concentration-dependent contractile response. The potency value (,log EC50) was 9.3±1.0. The maximum effect was 25±4% of that elicited by the maximally effective concentration (0.3 ,M) of 5-HT and 43±3% of that by the maximally effective concentration (10 ,M) of melatonin. When used as an antagonist, 2-phenylmelatonin (0.01 nM and 0.1 nM) concentration-dependently inhibited melatonin-induced contractions with depression of the maximum response by 25% and 54%, respectively. Higher (1 nM) 2-phenylmelatonin concentrations failed to antagonize melatonin-induced response. Prazosin (0.3 ,M), a selective antagonist of melatonin MT3 sites, antagonized melatonin-induced contractions to an extent similar to that induced by 0.01 nM 2-phenylmelatonin (with 30% reduction of the maximum effect to melatonin). The combination of 0.3 ,M prazosin and 0.01 nM 2-phenylmelatonin caused antagonism similar in extent to that caused by each individual antagonist. 2-Phenylmelatonin at subnanomolar concentrations behaves as an antagonist of melatonin-induced contractile responses while at nanomolar/micromolar concentrations it behaves as a weak contractile agonist. [source] Tachykinin receptor modulation of cyclooxygenase-2 expression in human polymorphonuclear leucocytesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009M Gallicchio Mandarin translation of abstract Background and purpose:, We investigated the ability of natural and synthetic selective NK receptors agonists and antagonists to modulate cyclooxygenase-2 (COX-2) expression in human polymorphonuclear leucocytes (PMNs). Experimental approach:, The presence of all three tachykinin in PMNs was assessed by Western blot and PCR techniques. Natural and synthetic ligands selective for the tachykinin receptors were used to modulate COX-2 protein (measured with Western blotting) and activity [as prostaglandin E2 (PGE2) output]. Effects of substance P (SP) on phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-,B) activation were studied to analyse the signalling pathway involved in COX-2 up-regulation mediated by SP. Key results:, Stimulation of NK receptors with the natural ligands SP, neurokinin A (NKA) and neurokinin B, in the pmol·L,1 -µmol·L,1 concentration range, modulated COX-2 expression and PGE2 release in a concentration- and time-dependent manner. Experiments with synthetic selective agonists [Sar9, Met(O2)11]SP, [,-Ala8] NKA(4-10), senktide or selective antagonists L703,606, SR48,968 or SR142801, confirmed that COX-2 up-regulation was mediated by NK receptors. We found that mainly p38, p42 and p46 MAPKs were phosphorylated by SP and SB202190, PD98059 and SP600125, which are selective inhibitors of these kinases, blocked SP-induced COX-2 expression. SP also induced nuclear translocation of NF-,B concentration-dependently, with a maximum effect at 1 nmol·L,1. Conclusions and implications:, Human PMNs possess functional NK1, NK2 and NK3 receptors, which mediate the induction of COX-2 expression and NF-,B activation by SP. Mandarin translation of abstract [source] Modulation of insulin release by adenosine A1 receptor agonists and antagonists in INS-1 cells: The possible contribution of 86Rb+ efflux and 45Ca2+ uptakeCELL BIOCHEMISTRY AND FUNCTION, Issue 8 2008M. Töpfer Abstract Due to the lack of specific agonists and antagonists the role of adenosine receptor subtypes with respect to their effect on the insulin secretory system is not well investigated. The A1 receptor may be linked to different 2nd messenger systems, i.e. cAMP, K+ - and 45Ca2+ channel activity. Partial A1 receptor agonists are going to be developed in order to improve diabetes (increase in insulin sensitivity, lowering of FFA and triglycerides). In this study newly synthesized selective A1 receptor agonists and antagonists were investigated thereby integrating three parameters, insulin release (RIA), 45Ca2+ uptake and 86Rb+ efflux (surrogate for K+ efflux) of INS-1 cells, an insulin secretory cell line. The presence of A1 -receptors was demonstrated by Western blotting. The receptor nonselective adenosine analogue NECA (5,- N -ethylcarboxyamidoadenosine) at high concentration (10,µM) had no effect on insulin release and 45Ca2+ uptake which could be interpreted as the sum of effects mediated by mutual antagonistic adenosine receptor subtypes. However, an inhibitory effect mediated by A1 receptor agonism was detected at 10,nM NECA and could be confirmed by adding the A1 receptor antagonist PSB-36 (1-butyl-8-(3-noradamantyl)-3-(3-hydroxy-propyl)xanthine). NECA inhibited 86Rb+ efflux which, however, did not fit with the simultaneous inhibition of insulin secretion. The selective A1 receptor agonist CHA (N6 -cyclohexyladenosine) inhibited insulin release; the simultaneously increased Ca2+ uptake (nifedipine dependent) and inhibition of 86Rb+ efflux did not fit the insulin release data. The CHA effect (even the maximum effect at 50,µM) can be increased by 10,µM NECA indicating that CHA and NECA have nonspecific and physiologically non-relevant effects on 86Rb+ efflux in addition to their A1 -receptor interaction. Since PSB-36 did not influence the NECA-induced inhibition of 86Rb+ efflux, the NECA effect is not mediated by potassium channel-linked A1 receptors. The nonselective adenosine receptor antagonist caffeine increased insulin release which was reversed by CHA as expected when hypothesizing that both act via A1 receptors in this case. In conclusion, stimulation of A1 receptors by receptor selective and nonselective compounds reduced insulin release which is not coupled to opening of potassium channels (86Rb+ efflux experiments) or inhibition of calcium channels (45Ca2+ uptake experiments). It may be expected that of all pleiotropic 2nd messengers, the cAMP system (not tested here) is predominant for A1 receptor effects and the channel systems (K+ and Ca2+) are of minor importance and do not contribute to insulin release though being coupled to the receptor in other tissues. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||