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Dose-response Relationships (dose-response + relationships)
Selected AbstractsLeaf surfaces and the bioavailability of pesticide residuesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 5 2001M Nasir U Chowdhury Abstract Laboratory bioassays were carried out to determine the toxicity to Folsomia candida Willem (Collembola: Isotomidae) of residues of a pyrethroid insecticide, deltamethrin, and an organophosphorus insecticide, dimethoate, on different leaf surfaces. The test leaves included a range of species and leaves of different ages. Dose-response relationships were estimated for F candida walking over the various treated leaf substrates. Probit analysis was used to estimate the means and standard deviations of the associated tolerance distributions expressed as g,AI,ha,1. Parallelism tests were undertaken to compare the susceptibilities of F candida to the two compounds applied to the different leaf surfaces. On deltamethrin-treated leaf surfaces, the LD50 values for F candida varied from 6.36 to 77.14,g,AI,ha,1. F candida was least susceptible to deltamethrin residues when applied to leaves of dwarf bean (Phaseolus vulgarus L) and the highest susceptibility was observed following application to leaves of seedlings of barley (Hordeum vulgare L). In contrast, the LD50 values observed for dimethoate treatments did not differ significantly between leaf types, ranging from 1.35 to 8.69,g,AI,ha,1. The laboratory data on susceptibility of F candida on different leaf types for different pesticides can be used to investigate the role of leaf surface properties in modifying the toxicity of applied pesticides to exposed invertebrates. © 2001 Society of Chemical Industry [source] The molecular receptive range of an olfactory receptor in vivo (Drosophila melanogaster Or22a)DEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Daniela Pelz Abstract Understanding how odors are coded within an olfactory system requires knowledge about its input. This is constituted by the molecular receptive ranges (MRR) of olfactory sensory neurons that converge in the glomeruli of the olfactory bulb (vertebrates) or the antennal lobe (AL, insects). Aiming at a comprehensive characterization of MRRs in Drosophila melanogaster we measured odor-evoked calcium responses in olfactory sensory neurons that express the olfactory receptor Or22a. We used an automated stimulus application system to screen [Ca2+] responses to 104 odors both in the antenna (sensory transduction) and in the AL (neuronal transmission). At 10,2 (vol/vol) dilution, 39 odors elicited at least a half-maximal response. For these odorants we established dose-response relationships over their entire dynamic range. We tested 15 additional chemicals that are structurally related to the most efficient odors. Ethyl hexanoate and methyl hexanoate were the best stimuli, eliciting consistent responses at dilutions as low as 10,9. Two substances led to calcium decrease, suggesting that Or22a might be constitutively active, and that these substances might act as inverse agonists, reminiscent of G-protein coupled receptors. There was no difference between the antennal and the AL MRR. Furthermore we show that Or22a has a broad yet selective MRR, and must be functionally described both as a specialist and a generalist. Both these descriptions are ecologically relevant. Given that adult Drosophila use approximately 43 ORs, a complete description of all MRRs appears now in reach. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Association of the metabolic syndrome with depression and anxiety in Japanese men: A 1-year cohort studyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2009Takeaki Takeuchi Abstract Background Recent studies on the association between the metabolic syndrome (MetS) and depression have reported conflicting findings. This 1-year cohort study aims to evaluate the association of MetS with the development of both depression and anxiety. Methods The cohort comprised 956 Japanese male employees of an enterprise (mean age, 42.7 years; SD, 10.2 years). MetS was diagnosed according to the International Diabetes Federation criteria. The psychological conditions of depression and anxiety were assessed in 2 successive years by using the profile of mood states (POMS) questionnaire and by conducting clinical interviews as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We evaluated the temporal and dose-response relationships between MetS and the development of depression and anxiety, controlling for potential confounding factors like age and lifestyle-related factors. Results We identified a positive relationship between MetS at baseline and new-onset depression in the subsequent year (OR 2.14, 95% CI 1.10,4.17). Of the five MetS components examined, only waist circumference was significantly related to new-onset depression (OR 2.08, 1.23,3.50). Trend analysis revealed a significant positive trend of association between the number of MetS components identified and new-onset depression (Ptrend < 0.01), but not between Mets and new-onset anxiety. Conclusions Our results suggest that MetS is a predictive factor for the development of depression, and that waist circumference largely contributes to the association between MetS and depression. Copyright © 2009 John Wiley & Sons, Ltd. [source] Lung, liver and bone cancer mortality in Mayak workers,INTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Mikhail E. Sokolnikov Abstract Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment. Published 2008 Wiley-Liss, Inc. [source] Effect of temperature and pH on the toxicity of aluminium towards two new, soil born species of Arthrobacter sp.JOURNAL OF BASIC MICROBIOLOGY, Issue 2 2004Paul Illmer Dr. Two coryneform bacteria Arthrobacter sp. PI/1,95 (Arth1) and Arthrobacter sp. PI/3-95 (Arth3) were isolated from forest soil characterized and investigated with respect to their reaction towards aluminium (Al). Sigmoid functions were used to describe dose-response relationships between Al concentration and microbial growth and to calculate EC-values. EC100 , indicating a complete inhibition of microbial growth , varied between 185 ,M Al for Arth1 and 11 mM Al for Arth3. A pure pH effect seems probable in connection with the sensitive Arth1 but not with the tolerant species Arth3. Temperature was shown to distinctly increase the toxic effects of Al towards Arth3 whereas only a moderate modification in Al-toxicity was observed with Arth1. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusionMAGNETIC RESONANCE IN MEDICINE, Issue 5 2001Patrick M. Kochanek Abstract Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-response, and timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2,4 ,L). CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of interest (ROI) around the injection and in ipsilateral hemispheric ROIs at ,90 min and ,180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle) were seen in the circular ROI at ,90 min and ,180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at ,90 min and ,180 min, respectively, after injection of 12 nmoles. Linear dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2-chloroadenosine produces potent, dose-dependent, and sustained vasodilation over large areas of brain. This treatment and imaging paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury. Magn Reson Med 45:924,929, 2001. © 2001 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 5 2007Article first published online: 16 MAY 200 OFT wants PPRS reform The Office of Fair Trading (www.oft.gov.uk) says reform of the Pharmaceutical Price Regulatory Scheme (PPRS) would allow the NHS to re- invest £500 million in drugs it needs. Its investigation of the 50- year-old PPRS concludes that the scheme does not reflect the therapeutic value of drugs and, while providing a financial safety net for the industry, it mitigates against innovation. The OFT believes drugs should be priced according to their therapeutic value based on their cost effectiveness. Analyses would be fast- tracked for new drugs or, if there are insufficient data, a risk-sharing scheme should be adopted. The ABPI insists that its medicines offer the NHS value for money and believes the OFT's proposal for drug- by-drug pricing would delay access to new medicines. Switching saves money and is problem free Switching to cheaper alternatives within a drug class does not affect the quality of care and offers substantial savings, say UK researchers (Int J Clin Pract 2007;61:15-23). They switched selected patients from atorvastatin (Lipitor) to simvastatin and from losartan (Cozaar) to candesartan (Amias). Exclusion criteria included previous unsuccessful use, poor control of lipids or blood pressure, contraindications and potential drug interactions. In 70 patients switched to simvastatin, there was no change in mean total cholesterol after four months; one patient reverted to atorvastatin due to adverse effects. Of 115 switched to candesartan, seven reverted to losartan; in the remainder, blood pressure was slightly reduced after four months. The switch was not associated with adverse effects. Savings for the year 2005/06 were estimated at £12 716 for statins and £13 374 for antihypertensive drugs. Scotland gets donepezil for mild to moderate AD The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved the use of orodispersible donepezil (Aricept Evess) for the treatment of mild to moderate Alzheimer's disease in NHS Scotland. The decision conflicts with NICE advice that the drug is not appropriate for patients with mild disease. The SMC has not approved rimonabant (Acomplia) as adjunctive treatment for obese patients. Adherence threatens anticoagulation Patients find it difficult to adhere to anticoagulant treatment ,significantly impairing the quality of anticoagulation, US investigators have shown (Arch Intern Med 2007;167:229-35). Using electronic containers to monitor dose adherence over 32 weeks in 136 patients, they found that 92 per cent opened the container at least once too often or too little and one-third missed 20 per cent of scheduled openings. Patients with less than 20 per cent adherence were twice as likely to be undercoagulated compared with adherent patients. Those with overadherence were overcoagulated. Hypo risk greatest with glibenclamide Glibenclamide is associated with a significantly greater risk of hypoglycaemic events than other secretagogues, a new systematic review has concluded (Diabetes Care 2007;30:389-94). The review of 21 randomised trials found that the risk of experiencing at least one hypoglycaemic event was 52 per cent greater with glibenclamide compared with other secretagogues and 83 per cent greater than with other sulphonylureas. In three comparative trials with insulin, there was no significant difference in the risk of hypoglycaemia (though this could not be excluded) but only insulin was associated with weight gain. Glibenclamide was not associated with significantly increased risks of cardiovascular events, weight gain or death. Few major hypoglycaemic events were reported in these trials. Drug groups implicated in ADR admissions Four classes of drugs account for half of hospital admissions for adverse reactions, according to a new systematic review (Br J Clin Pharmacol 2007;63:136-47). Antiplatelet agents (16 per cent of admissions), diuretics (16 per cent), NSAIDs (11 per cent) and anticoagulants (8 per cent) were implicated in drug- related admissions according to a review of nine studies. Analysis of five studies also showed that adherence problems were associated with one-third of drug-related admissions. The authors suggest that focussing resources in these areas could substantially reduce admissions. Value of pharmacist MUR questioned Pharmacist medicines use review (MUR) for older patients does not reduce hospital readmission and is not cost effective by current standards, according to a study from Norfolk (Pharmacoeconomics 2007;25:171-80). A total of 872 patients aged over 80 who had been admitted as an emergency and discharged taking two or more drugs were randomised to MUR by a pharmacist or usual care. The pharmacist visited twice, providing education, removing out-of-date drugs and checking for adverse effects, interactions and the need for compliance aids. After six months, the admissions rate was not reduced among patients who received MUR and quality of life was not significantly improved. The estimated cost per QALY gained was £54 454 , above the conventional threshold for cost effectiveness of £30 000. MHRA review of LABAs The MHRA has clarified which aspects of long-acting beta-agonists (LABAs) are being addressed in its current review. This full review of salmeterol (Serevent) and formoterol, following advice issued in December last year, will consider recent research, whether the two agents differ significantly, dose-response relationships, the effect of concurrent treatment with inhaled steroid and how they are used in practice. Manufacturers have been asked to provide data by the end of March. Interventions for weight gain in schizophrenia There is not enough evidence to support the use of drugs to reduce weight gain associated with schizophrenia, a new Cochrane review has found (Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005148. DOI: 10.1002/14651858. CD005148.pub2). Noting a lack of adequate trials, the review found that cognitive/behavioural interventions effectively prevented weight gain by a mean of 3.4kg and reduced established weight gain by a mean of 1.7kg. Drugs prevented weight gain by about 1.2kg. Switching anti-TNFs An analysis of a UK rheumatoid arthritis (RA) registry has shown that patients who stop treatment with their first anti-TNF agent should be switched to a second (Arthr Rheum 2007;56:13-20). Every UK patient with RA who receives an anti-TNF agent is included in the British Society for Rheumatology Biologics Register. Analysis of this database identified 6739 patients who started treatment, of whom 841 stopped within 15 months due to lack of efficacy and 1023 due to toxicity. Of these, 503 and 353 respectively were switched to another anti- TNF agent. Overall, 73 per cent of patients remained on their second drug by the end of follow-up, but patients were two to three times more likely to stop their second treatment for the same reason they discontinued their first. Copyright © 2007 Wiley Interface Ltd [source] IgE-Mediated Asthma and Rhinitis I: A Role of Allergen Exposure?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2002Gunnar D. Nielsen The IgE antibodies and associated cellular responses are responsible for the allergic airway diseases, allergic rhinitis and allergic asthma, which are increasing in societies with Western life style. Aeroallergens may have different potential to sensitize exposed subjects. Thus, there are only a limited number of important groups of aeroallergens, which are those from house dust mites, cockroaches, pets, pollens, and moulds. Allergy follows to a certain extent the pharmacological/toxicological paradigm of dose-response relationship. Unlike effects of pharmacologically and toxicologically active substances, allergens elicit their adverse effects in a two-stage process. In the first stage the immunologically naïve individual is sensitized to the allergen. In the second stage renewed exposure to the allergen elicits the disease response. Also, high concentrations of aeroallergens may induce immunological tolerance. The scientific literature suggests that many environmental factors contribute to the increase in sensitization and development of airway allergies. Nevertheless, the dose-response relationships apply (within certain limits) both to the sensitization itself and to the exacerbation of the diseases. This suggest that exposure reduction may be one of the methods for reduction of risk, in relation to control of the allergic airway diseases. [source] | |||||||||||||