Regulatory Actions (regulatory + action)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Extemporaneous (magistral) preparation of oral medicines for children in European hospitals

ACTA PAEDIATRICA, Issue 4 2003
S Conroy
The lack of availability of licensed paediatric medicines forces pharmacists to compound drugs into a form that children can tolerate. There is a lack of information to support much of this practice and standards tend to vary. Suitable licensed alternatives are often available in other countries but importing restrictions complicate obtaining them. Conclusion: Regulatory action is needed to simplify licensing and importation processes to facilitate universal access to suitable paediatric medicines. [source]


Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005
Robert J. Cluxton Jr PharmD
Abstract Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n,=,7226) or rosiglitazone (n,=,1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two ,Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth ,Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright © 2004 John Wiley & Sons, Ltd. [source]


No Smoking Gun: Findings From a National Survey of Office-Based Cosmetic Surgery Adverse Event Reporting

DERMATOLOGIC SURGERY, Issue 11 2003
Rajesh Balkrishnan PhD
Background. Because of recent press reports of adverse outcomes, office-based cosmetic surgery has come under intense scrutiny and associated legislative regulatory action. Objective. To assess the safety of office-based cosmetic surgery through a national survey of state agencies that collect information on adverse patient outcomes. Methods. Medical boards or other responsible authorities were contacted in 48 states to obtain records on adverse outcomes from cosmetic surgery procedures performed in an office-based setting. Results. Five states were able to provide complete information regarding 13 cases of adverse outcomes that resulted from office-based cosmetic surgery procedures. Thirteen states had incomplete information or were unable to provide information. The remaining states reported no adverse outcomes. Information collected by state agencies varies greatly and is inadequate to define the safety of office-based cosmetic surgery practice. Conclusions. The need to regulate physician office surgery on the basis of hospital privileges and office certification is not supported by current data. Mandatory reporting of adverse outcomes from office-based surgery is warranted to identify modifiable risk factors and to reduce the risk of adverse outcomes. [source]


Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index

EXPERIMENTAL DERMATOLOGY, Issue 8 2006
Heike Schäcke
Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source]


The potential role for economic instruments in drought management,

IRRIGATION AND DRAINAGE, Issue 4 2004
Stephen Merrett
changement du climat; gestion des sécheresses; irrigation; prix de l'eau Abstract Climate change in the twenty-first century will likely reduce the return period of drought events, indicating that drought management will be even more important in the future than it is already. In the case of England's Anglian region it is shown that two principal institutions are responsible for drought management,the Environment Agency and Anglian Water Services (AWS). The region has a fast-growing population of more than 5 million people, it has 58% of the most productive agricultural land in England and Wales, and in some summers irrigation can make up 50% of water use. An examination of the drought plans of the Agency and AWS demonstrates that in both cases the policy instruments that they deploy to manage drought are informational, infrastructural and regulatory. In neither case would they use water pricing as a management tool. Moreover, the government's drought plan guidelines for the water utilities make no reference to economic instruments of drought management nor do they suggest that utilities should review the economic impact on their customers of regulatory action. The principal issues that would arise if water charging were to be deployed as a drought management instrument are then reviewed. The paper concludes by proposing that national government should evaluate the feasibility, costs, benefits and risks of replacing the regulatory instruments of drought management by economic instruments. Copyright © 2004 John Wiley & Sons, Ltd. Avec les changements climatiques prévus au vingt-et-unième siècle les périodes de sècheresse deviendront probablement plus fréquentes et la gestion de ces sécheresses deviendra plus problématique. Cet article indique que dans la région Anglian de l'Angleterre deux institutions ont la responsabilité de cette gestion: "the Environment Agency" et "Anglian Water Services". Un examen des plans d'action pour la sécheresse de ces deux institutions montre que, dans les deux cas, les instruments qui seront déployés seront soit informationels soit infrastructurels soit règlementaires. Il n'y a pas dans ces plans une seule référence au prix de l'eau comme instrument de gestion. De même les conseils du gouvernement national pour la préparation de ces plans ignorent les instruments économiques. L'article conclut que le gouvernement doit réviser la faisabilité des instruments de gestion des sécheresses, et d'estimation de leurs coûts et bénéfices pour introduire davantage d'instruments économiques. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005
Robert J. Cluxton Jr PharmD
Abstract Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n,=,7226) or rosiglitazone (n,=,1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two ,Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth ,Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Role of WRINKLED1 in the transcriptional regulation of glycolytic and fatty acid biosynthetic genes in Arabidopsis

THE PLANT JOURNAL, Issue 6 2009
Sébastien Baud
Summary The WRINKLED1 (WRI1) protein is an important regulator of oil accumulation in maturing Arabidopsis seeds. WRI1 is a member of a plant-specific family of transcription factors (AP2/EREBP) that share either one or two copies of a DNA-binding domain called the AP2 domain. Here, it is shown that WRI1 acts as a transcriptional enhancer of genes involved in carbon metabolism in transgenic seeds overexpressing this transcription factor. PKp-,1 and BCCP2, two genes encoding enzymes of the glycolysis and fatty acid biosynthetic pathway, respectively, have been chosen to investigate the regulatory action exerted by WRI1 over these pathways. Using the reporter gene uidA, it was possible to demonstrate in planta that WRI1 regulates the activity of both PKp-,1 and BCCP2 promoters. Electrophoretic mobility-shift assays and yeast one-hybrid experiments showed that WRI1 was able to interact with the BCCP2 promoter. To further elucidate the regulatory mechanism controlling the transcription of these genes, functional dissections of PKp-,1 and BCCP2 promoters were performed. Two enhancers, of 54 and 79 bp, respectively, have thus been isolated that are essential to direct the activity of these promoters in oil-accumulating tissues of the embryo. A consensus site is present in these enhancers as well as in other putative target promoters of WRI1. Loss of this consensus sequence in the BCPP2 promoter decreases both the strength of the interaction between WRI1 and this promoter in yeast and the activity of the promoter in planta. [source]


Pubertal maturation modifies the regulation of insulin-like growth factor-I receptor signaling by estradiol in the rat prefrontal cortex

DEVELOPMENTAL NEUROBIOLOGY, Issue 8 2008
Amaya Sanz
Abstract The transition from adolescence to adulthood is accompanied by substantial plastic modifications in the cerebral cortex, including changes in the growth and retraction of neuronal processes and in the rate of synaptic formation and neuronal loss. Some of these plastic changes are prevented in female rats by prepubertal ovariectomy. The ovarian hormone estradiol modulates neuronal differentiation and survival and these effects are in part mediated by the interaction with insulin-like growth factor-I (IGF-I). In this study, we have explored whether the activation by estradiol of some components of IGF-I receptor signaling is altered in the prefrontal cortex during puberty. Estradiol administration to rats ovariectomized after puberty resulted, 24 h after the hormonal administration, in a sustained phosphorylation of Akt and glycogen synthase kinase 3, in the prefrontal cortex. However, this hormonal effect was not observed in animals ovariectomized before puberty. These findings suggest that during pubertal maturation there is a programming by ovarian hormones of the future regulatory actions of estradiol on IGF-I receptor signaling in the prefrontal cortex. The modification in the regulation of IGF-I receptor signaling by estradiol during pubertal maturation may have implications for the developmental changes occurring in the prefrontal cortex in the transition from adolescence to adulthood. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source]


Regulated cross-border transmission investment in Europe

EUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 6 2006
Leonardo Meeus
Abstract In a liberalized market, generation and transmission investment decisions are decoupled, so that a more elaborated grid is necessary. The European transmission grid has to ensure security of supply, facilitate the market and integrate renewables. Transmission grid investments are clearly needed, especially to increase the scarcely available cross-border transfer capacities. The regulatory framework in which these investments have to take place is discussed in this paper. It is stated that this framework does not ensure that congestion revenues are used for transmission investments that are in the long-term benefit of the market, because regulators are biased towards a short-term tariff reduction. The authors conclude that more coordination is clearly necessary, either pushed by European regulation or driven by coordinated regulatory actions. Copyright © 2006 John Wiley & Sons, Ltd. [source]


The Endocannabinoid System and Energy Metabolism

JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008
L. Bellocchio
Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors [cannabinoid receptor type 1 (CB1) and CB2] participate in the physiological modulation of many central and peripheral functions. The ability of the endocannabinoid system to control appetite, food intake and energy balance has recently received considerable attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptors and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control several metabolic functions by acting on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. The relevance of the system is further strengthened by the notion that visceral obesity seems to be a condition in which an overactivation of the endocannabinoid system occurs, and therefore drugs interfering with this overactivation by blocking CB1 receptors are considered as potentially valuable candidates for the treatment of obesity and related cardiometabolic risk factors. [source]


Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005
Robert J. Cluxton Jr PharmD
Abstract Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n,=,7226) or rosiglitazone (n,=,1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two ,Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth ,Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Estuarine eutrophication in the UK: current incidence and future trends

AQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 1 2009
Gerald Maier
Abstract 1.Increased inputs of nutrients to estuaries can lead to undesirable effects associated with eutrophication, including algal blooms, changes in species composition and bottom anoxia. Several estuaries and coastal areas around the UK have increased nitrogen (N) and phosphorus (P) concentrations, elevated concentrations of chlorophyll a and changes in algal community composition and abundance. This paper reviews the pressures that lead to high nutrient concentrations in estuaries and considers the likely effectiveness of current and proposed regulatory actions. 2.The main sources of nutrients to estuaries are river runoff, sewage discharges, atmospheric inputs and possibly submarine groundwater discharges, although little is known about the latter. Significant reductions in N and P inputs have been realized following application of the EU's Urban Waste Water Treatment Directive. Atmospheric NOx and NHx emissions have also decreased and are expected to decrease further in the next decade as implementation of existing legislation continues, and new controls are introduced for activities such as shipping. 3.Agricultural inputs reach estuaries principally through diffuse sources, either in surface water (and in some areas possibly groundwater) or, for N, via the atmosphere. Over 10 years ago the Nitrates Directive was introduced to tackle the problem of N discharges from agriculture but little change in N loads to estuaries has been recorded. 4.To meet the aims of the EU Water Framework Directive, for at least ,good' ecological status, more rigorous application and implementation of the Nitrates Directive, together with changes in the Common Agriculture Policy and farming practice are likely to be needed. Even then, the slow response of the natural environment to change and the inherent variability of estuaries means that their responses may not be as predicted. Research is needed into the relationship between policy drivers and environmental responses to ensure actions taken will achieve the planned results. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1)

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000
A D Taylor
Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3,5,-monophosphate (8-Br-cyclic AMP) and an L-Ca2+ channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca2+ entry. British Journal of Pharmacology (2000) 131, 1309,1316; doi:10.1038/sj.bjp.0703694 [source]


Sphingosine kinase signalling in immune cells

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2005
Tay Hwee Kee
SUMMARY 1.,Sphingolipids are potent second messengers modulating biochemical intracellular events and acting as ligands to mediate extracellular systems. Sphingosine kinase (SPHK) is the enzyme that phosphorylates sphingosine into sphingosine-1-phosphate (S1P), a potent bioactive sphingolipid. 2.,The fact that SPHK is highly conserved from protozoa to mammals and is ubiquitous in living tissues reveals important roles of the SPHK pathway for the maintenance of health maintenance. This is also supported by comprehensive reviews on features of its main product, S1P, as having intracellular as well as extracellular roles, inducing a wide range of physiological responses from triggering Ca2+ release from internal stores to promoting growth and cell motility. 3.,Immune cell activities have been shown to be modulated by the dynamic balance between ceramide, sphingosine and S1P, conceptualized as a rheostat. Cell proliferation, differentiation, motility and survival have been attributed to the regulatory actions of S1P. The properties of SPHK activity in immune cells are linked to the functions of triggered growth and survival factors, phorbol esters, hormones, cytokines and chemokines, as well as antigen receptors, such as Fc,RI and Fc,RI. 4.,Mechanisms of the SPHK signalling pathway are explored as new targets for drug development to suppress inflammation and other pathological conditions. [source]


Dopamine, Morphine, and Nitric Oxide: An Evolutionary Signaling Triad

CNS: NEUROSCIENCE AND THERAPEUTICS, Issue 3 2010
George B. Stefano
Morphine biosynthesis in relatively simple and complex integrated animal systems has been demonstrated. Key enzymes in the biosynthetic pathway have also been identified, that is, CYP2D6 and COMT. Endogenous morphine appears to exert highly selective actions via novel mu opiate receptor subtypes, that is, mu3,-4, which are coupled to constitutive nitric oxide release, exerting general yet specific down regulatory actions in various animal tissues. The pivotal role of dopamine as a chemical intermediate in the morphine biosynthetic pathway in plants establishes a functional basis for its expansion into an essential role as the progenitor catecholamine signaling molecule underlying neural and neuroendocrine transmission across diverse animal phyla. In invertebrate neural systems, dopamine serves as the preeminent catecholamine signaling molecule, with the emergence and limited utilization of norepinephrine in newly defined adaptational chemical circuits required by a rapidly expanding set of physiological demands, that is, motor and motivational networks. In vertebrates epinephrine, emerges as the major end of the catecholamine synthetic pathway consistent with a newly incorporated regulatory modification. Given the striking similarities between the enzymatic steps in the morphine biosynthetic pathway and those driving the evolutionary adaptation of catecholamine chemical species to accommodate an expansion of interactive but distinct signaling systems, it is our overall contention that the evolutionary emergence of catecholamine systems required conservation and selective "retrofit" of specific enzyme activities, that is, COMT, drawn from cellular morphine expression. Our compelling hypothesis promises to initiate the reexamination of clinical studies, adding new information and treatment modalities in biomedicine. [source]