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Present Review (present + review)
Selected AbstractsHyperbranched macromolecules through donor-acceptor type copolymerization of allyl,vinylene bifunctional monomers,POLYMER INTERNATIONAL, Issue 10 2002O Rzaev, Zakir M Abstract Present review is an attempt to generalize and systematize the results accumulated in synthesis of cyclolinear and hyperbranched reactive macromolecules via radical alternating copolymerization of various bifunctional monomers containing donor and acceptor type double bonds. Synthesis of hyperbranched reactive macromolecules was carried out using complex-radical cyclocopolymerization of donor-acceptor type bifunctional monomers such as monoallyl ester of maleic acid (MAM), allyl acrylate (AA), allyl methacrylate (AM), allyl trans -cinnamate (AC), methylallylmaleate (MeAM), methylallylfumarate (MAF) and allyl-,-(N-maleimido)acetate (AMI), and maleic anhydride (MA) and styrene (St) as typical acceptor and donor comonomers, respectively. The kinetic parameters of these reactions, constants of cyclization, complex-formation and copolymerization, as well as the ratios of chain growth rates for the participation of monomeric charge transfer complexes and free monomers, were all determined. It was demonstrated that in the studied systems, copolymerizations predominantly proceed according to alternating mechanism with formation of macromolecules having cyclolinear structure in the steady-state and hyperbranched structure in the high conversion conditions. It was shown that formation of linear and hyperbranched macromolecules containing allyl or vinylene groups in the side chain occurs selectively carry out and depends on the nature of used comonomer. General schemes and proposed mechanism of hyperbranching and crosslinking reactions were also described. Some useful properties of synthesized reactive copolymers were discussed. © 2002 Society of Chemical Industry. [source] Birth defects caused by mutations in human GLI3 and mouse Gli3 genesCONGENITAL ANOMALIES, Issue 1 2010Ichiro Naruse ABSTRACT GLI3 is the gene responsible for Greig cephalopolysyndactyly syndrome (GCPS), Pallister,Hall syndrome (PHS) and Postaxial polydactyly type-A (PAP-A). Genetic polydactyly mice such as Pdn/Pdn (Polydactyly Nagoya), XtH/XtH (Extra toes) and XtJ/XtJ (Extra toes Jackson) are the mouse homolog of GCPS, and Gli3tmlUrtt/Gli3tmlUrt is produced as the mouse homolog of PHS. In the present review, relationships between mutation points of GLI3 and Gli3, and resulting phenotypes in humans and mice are described. It has been confirmed that mutation in the upstream or within the zinc finger domain of the GLI3 gene induces GCPS; that in the post-zinc finger region including the protease cleavage site induces PHS; and that in the downstream of the GLI3 gene induces PAP-A. A mimicking phenomenon was observed in the mouse homolog. Therefore, human GLI3 and mouse Gli3 genes have a common structure, and it is suggested here that mutations in the same functional regions produce similar phenotypes in human and mice. The most important issue might be that GCPS and PHS exhibit an autosomal dominant trait, but mouse homologs, such as Pdn/Pdn, XtH/XtH, XtJ/XtJ and Gli3tmlUrt/Gli3tmlUrt, are autosomal recessive traits in the manifestation of similar phenotypes to human diseases. It is discussed here how the reduced amounts of the GLI3 protein, or truncated mutant GLI3 protein, disrupt development of the limbs, head and face. [source] Cnidarians and the evolutionary origin of the nervous systemDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2009Hiroshi Watanabe Cnidarians are widely regarded as one of the first organisms in animal evolution possessing a nervous system. Conventional histological and electrophysiological studies have revealed a considerable degree of complexity of the cnidarian nervous system. Thanks to expressed sequence tags and genome projects and the availability of functional assay systems in cnidarians, this simple nervous system is now genetically accessible and becomes particularly valuable for understanding the origin and evolution of the genetic control mechanisms underlying its development. In the present review, the anatomical and physiological features of the cnidarian nervous system and the interesting parallels in neurodevelopmental mechanisms between Cnidaria and Bilateria are discussed. [source] The effect of prenatal hypoxia on brain development: short- and long-term consequences demonstrated in rodent modelsDEVELOPMENTAL SCIENCE, Issue 4 2006Hava Golan Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent models. Delayed development of sensory and motor reflexes during the first postnatal month of rodent life was observed by various groups. Impairment of motor function, learning and memory was evident in the adult animals. Activation of the signaling leading to cell death was detected as early as three hours following H/HI. An increase in the counts of apoptotic cells appeared approximately three days after the insult and peaked about seven days later. Around 14,20 days following the H/HI, the amount of cell death observed in the tissue returned to its basal levels and cell loss was apparent in the brain tissue. The study of the molecular mechanism leading to brain damage in animal models following prenatal hypoxia adds valuable insight to our knowledge of the central events that account for the morphological and functional outcomes. This understanding provides the starting point for the development and improvement of efficient treatment and intervention strategies. [source] The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature reviewDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2010Saima Ali Abstract The relationships between co-morbid depression in people with diabetes and adverse outcomes including poor HbA1c control, adherence to medication and mortality have been examined and confirmed. However, as the awareness of the decrement to health-related quality of life (HRQOL) in people with diabetes and its clinical consequences grows, investigators have become increasingly interested in measuring HRQOL in clinical trials. Given that the psychological factors such as depression may contribute to diminished HRQOL, the present review sought to summarize the association between these variables in people with type 2 diabetes. Articles for a systematic review were obtained via a search performed using MEDLINE, EMBASE and PsycINFO (1980,2007). Fourteen articles fulfilled the inclusion criteria. Studies indicated that self-reported depressive symptoms markedly impaired HRQOL on several domains. However, depression was not related to all sub-domains of HRQOL in all studies, suggesting that the effects of depression on certain aspects of HRQOL may vary between clinical and demographic subgroups. Although a number of shortcomings identified in the current literature should be taken into account for future research, the importance of this review lies in the possibility it raises that the improvements in HRQOL and clinical practice may potentially be achieved by placing greater attention on the identification and management of depression. Copyright © 2010 John Wiley & Sons, Ltd. [source] A quantitative approach to probe the dependence and correlation of food-effect with aqueous solubility, dose/solubility ratio, and partition coefficient (Log P) for orally active drugs administered as immediate-release formulationsDRUG DEVELOPMENT RESEARCH, Issue 2 2005Brahma N. Singh Abstract The purpose of the present review was to systematically evaluate if aqueous solubility, dose/solubility ratio, and partition coefficient (Log P) could be used as useful parameters to quantitatively probe the dependence and correlation of in vivo food effects with these physicochemical properties of orally active drugs administered as immediate-release (IR) formulations. Mean AUC data obtained under fasted and fed states of over 100 structurally diverse orally active drugs with different physicochemical properties were obtained from the primary literature. Correlations of AUC ratio (Fed/Fasted) with aqueous solubility, dose/solubility ratio, and Log P were derived and statistically evaluated by Pearson's correlation test (two-tailed). A negative correlation was obtained between the logarithm of the aqueous solubility and the AUC ratio (r=,0.5982, N=93), whereas a positive correlation existed between AUC ratio and Log P (r=0.5147, N=110) and between AUC ratio and dose/solubility ratio (r=0.5511, N=87). All these correlations were significant (P<0.0001). Based on this study, the estimated range within which a drug is not expected to be significantly affected by food falls between 0.148,89.39 mg/ml for aqueous solubility and between 0.23,624 ml for the dose:solubility ratio. The corresponding range of Log P for expecting a lack of food-effect lies between ,1.13 and 2.98. Quantitatively, the effect of food was most pronounced for lipophilic, poorly water-soluble drugs (with only a few exceptions), irrespective of whether the drug is acidic, basic, or neutral. It is concluded that aqueous solubility, dose/solubility ratio, and partition coefficient can be used as useful parameters to probe the dependence and correlation of food-effect with these physicochemical parameters for immediate-release formulations. Drug Dev. Res. 65:55,75, 2005. © 2005 Wiley-Liss, Inc. [source] Hippocampal structure and the action of cholinomimetic drugsDRUG DEVELOPMENT RESEARCH, Issue 3 2002John G. Csernansky Abstract Cholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531,540, 2002. © 2002 Wiley-Liss, Inc. [source] Polyunsaturated fatty acids and epilepsyEPILEPSIA, Issue 8 2010Ameer Y. Taha Summary Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are dietary fatty acids that are involved in a myriad of physiologic processes in the brain. There is some evidence suggesting that PUFAs,and particularly omega-3 PUFAs,may have anticonvulsant effects, both in humans and in animals. In the present review, we assess the evidence related to the antiseizure properties of the n-3 PUFAs, discuss their possible mechanism(s) of action, and make recommendations for future clinical trials. In general, the available data from cell cultures and whole animal studies support the idea that the n-3 PUFAs have antiseizure properties. Future clinical trials involving the n-3 PUFAs should involve higher doses and longer periods of administration in order to definitively assess their possible antiseizure effects. [source] Vitamin D and calcium deficits predispose for multiple chronic diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005M. Peterlik Abstract There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-dihydroxyvitamin D3 and extracellular Ca++ are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1,-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D3. Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine. [source] Emerging topics in Reelin functionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2010Eckart Förster Abstract Reelin signalling in the early developing cortex regulates radial migration of cortical neurons. Later in development, Reelin promotes maturation of dendrites and dendritic spines. Finally, in the mature brain, it is involved in modulating synaptic function. In recent years, efforts to identify downstream signalling events induced by binding of Reelin to lipoprotein receptors led to the characterization of novel components of the Reelin signalling cascade. In the present review, we first address distinct functions of the Reelin receptors Apoer2 and Vldlr in cortical layer formation, followed by a discussion on the recently identified downstream effector molecule n-cofilin, involved in regulating actin cytoskeletal dynamics required for coordinated neuronal migration. Next, we discuss possible functions of the recently identified Reelin,Notch signalling crosstalk, and new aspects of the role of Reelin in the formation of the dentate radial glial scaffold. Finally, progress in characterizing the function of Reelin in modulating synaptic function in the adult brain is summarized. The present review has been inspired by a session entitled ,Functions of Reelin in the developing and adult hippocampus', held at the Spring Hippocampal Research Conference in Verona/Italy, June 2009. [source] Effects of ,-aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010Karima Begriche Abstract ,-Aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this ,-amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin-independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti-inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals. [source] Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolismFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2007Costas Giaginis Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that regulate the storage and catabolism of dietary fats. PPARs constitute molecular targets for the treatment of human metabolic disorders, and also play a crucial role in inflammatory-related disease and cancer. Recent evidence has revealed the presence of three different PPAR isotypes (,, ,/,, and ,) in different cells of the bone tissue, as well as the possible role of PPAR ligands in bone turnover. In the present review, the latest knowledge of the expression of PPARs in bone tissue and the diverse effects of PPAR ligands on bone metabolism is summarized. PPARs, especially of the , isotype, could be targets for the treatment of diverse bone diseases such as osteoporosis and osteopenia related to either diabetes or aging. [source] Multiple pathology and tails of disability: Space,time structure of disability in longevityGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2003Satoru Matsushita Disability and the resulting lowered quality of life are serious issues accompanying increased longevity. Curiously, despite its potential contribution to aging theory, complete statistical and etiological structures of this common and unwelcome aging phenotype before death have not been well identified. Another neglected issue in aging and disability is the principles of phylogenesis and morphogenesis, which contemporary life science invariably starts with. In the present review these two related subjects are addressed, with an introduction of an analysis on patients and published data. Statistically rigorous log,normal and normal distributions distinguish disability for its duration and age-wise distribution, respectively. Multiple pathology and diverse effects of various endogenous diseases on disability are confirmed. The robust long-tailed log,normal distribution for various phases of disability validates the fact that patients in disability undergo series of stochastic subprocesses of many independent endogenous diseases until death. For 60% of patients, the log,normal distribution is mimicked by a random walk model. Diseases of core organs are major causes of the long tails. A declining force of natural selection after reproduction and trade-off of life history through pleiotropy of the genes are considered to be the roots of aging. The attenuated selection pressure and the resulting decrease of genetic constraints produce an increased opportunity for chance and stochastics. Elucidated stochastic behaviors of disability underscore the key role of chance in aging. Evolutionary modifications in the development of the structure tend to favor developmentally later stages first. Distal parts are developmentally last, therefore most subject to modification. The rate of molecular evolution of the genes is also found to be relatively slow at the core and rapid at the edge of cells and organs. Therefore, systems at the core must be relatively slow and inactive to comply with pleiotropy and trade-offs in comparison with systems at the edge. Hence, against flat and probabilistic aging, the core organs must be moulded to be more robust with a lower threshold for dysfunction, to age relatively slowly, and should have less of a disease quota in aging. The principle of core protective aging assures possibilities not only to reduce disability but also to accomplish the Third Age as well. Finally, it must also be acknowledged that the principle is a double-edged sword. Paradoxically, the developed biological and societal organization provides protection for the injured core, and so develops long tails of disability. The principle of core protective aging re-emphasizes the key role of prevention in order to reduce the amount of disability. [source] Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic optionsHEMATOLOGICAL ONCOLOGY, Issue 2 2009Andrés J. M. Ferreri Abstract Central nervous system (CNS) dissemination is a rare (4,5%) but usually fatal complication of aggressive lymphomas. Prophylaxis modalities to prevent CNS dissemination in aggressive lymphomas cannot be widely applied to every lymphoma patient since it is associated with increased risk of neurotoxicity. Therefore, identification of high-risk patients as the best candidates to receive CNS prophylaxis constitutes a major endpoint in the management of these malignancies. Various risk factors and models for CNS recurrence have been described. Parameters reflecting the extent and proliferation of the disease, like elevated serum lactate dehydrogenase levels, involvement of multiple extranodal sites, advanced stage and high age-adjusted International Prognostic Index (IPI) score, as well as the involvement of specific anatomic sites, like testes, orbit, paranasal sinuses, have been identified and confirmed as important to predict CNS dissemination. Management of this complication in aggressive lymphomas with conventional-dose chemotherapy is associated with disappointing results, while some preliminary but encouraging experiences suggest a potential role of high-dose chemotherapy and stem cell transplantation. The analysis of recent clinical studies could lead to advancement in the prognosis of aggressive lymphomas, but several questions regarding the optimum chemotherapy combination, the best conditioning regimen and the role of radiation therapy and intrathecal chemotherapy remain still unanswered. The purposes of the present review are to critically analyse current data on the risk of CNS dissemination in aggressive lymphomas, the clinical presentation of secondary CNS lymphomas and the efficacy of CNS prophylaxis as well as to discuss the available therapeutic options for this devastating event. Copyright © 2009 John Wiley & Sons, Ltd. [source] Genetic background of Japanese patients with adult-onset storage diseases in the liverHEPATOLOGY RESEARCH, Issue 10 2007Hisao Hayashi In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with hemochromatosis of unknown etiology, Wilson disease of primary copper toxicosis, and the black liver of Dubin,Johnson syndrome. Three patients with middle-age onset hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and iron complex. Six patients with Dubin,Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices. [source] Laparoscopic pancreatic surgery: a review of present results and future prospectsHPB, Issue 4 2010Omer S. Al-Taan Abstract Pancreatic surgery is still associated with a relatively high morbidity and mortality compared with other specialties. This is a result of the complex nature of the organ, the difficult access as a result of the retroperitoneal position and the number of technically challenging anastomoses required. Nevertheless, the past two decades have witnessed a steady improvement in morbidity and a decrease in mortality achieved through alterations of technique (particularly relating to the pancreatic anastomoses) together with hormonal manipulation to decrease pancreatic secretions. Recently minimally invasive pancreatic surgery has been attempted by several centres around the world which has stimulated considerable interest in this approach. The majority of the cases attempted have been distal pancreatectomies, because of the more straightforward nature of the resection and the lack of a pancreatic ductal anastomosis, but more recently reports of laparoscopic pancreaticoduodenectomy have started to appear. The reports of the series to date have been difficult to interpret and although the results are claimed to be equivalent or better than those associated with a traditional approach a careful examination of the literature and comparison with the best results previously reported does not presently support this. In the present review we examined all the reports of pancreatic procedures performed laparoscopically and compared the results with those previously achieved at open surgery. [source] Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype,phenotype relationshipHUMAN MUTATION, Issue 3 2001Niels Gregersen Abstract Mutation analysis of metabolic disorders, such as the fatty acid oxidation defects, offers an additional, and often superior, tool for specific diagnosis compared to traditional enzymatic assays. With the advancement of the structural part of the Human Genome Project and the creation of mutation databases, procedures for convenient and reliable genetic analyses are being developed. The most straightforward application of mutation analysis is to specific diagnoses in suspected patients, particularly in the context of family studies and for prenatal/preimplantation analysis. In addition, from these practical uses emerges the possibility to study genotype,phenotype relationships and investigate the molecular pathogenesis resulting from specific mutations or groups of mutations. In the present review we summarize current knowledge regarding genotype,phenotype relationships in three disorders of mitochondrial fatty acid oxidation: very-long chain acyl-CoA dehydrogenase (VLCAD, also ACADVL), medium-chain acyl-CoA dehydrogenase (MCAD, also ACADM), and short-chain acyl-CoA dehydrogenase (SCAD, also ACADS) deficiencies. On the basis of this knowledge we discuss current understanding of the structural implications of mutation type, as well as the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. We propose that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation. The realization that the effect of the monogene, such as disease-causing mutations in the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. The rapid development of mutation detection systems, such as the chip technologies, makes such profile analyses feasible. However, it remains to be seen to what extent mutation analysis will be used for diagnosis of fatty acid oxidation defects and other metabolic disorders. Hum Mutat 18:169,189, 2001. © 2001 Wiley-Liss, Inc. [source] Approaches to measuring the effects of wake-promoting drugs: a focus on cognitive functionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2009Christopher J. Edgar Abstract Objectives In clinical drug development, wakefulness and wake-promotion may be assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake-promoting drugs may have nootropic properties (and vice versa). Clinical trials of wake-promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake-promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have underexplored or unknown wake promoting properties. Copyright © 2009 John Wiley & Sons, Ltd. [source] Sedation and antihistamines: an update.HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2008Review of inter-drug differences using proportional impairment ratios Abstract Background The use of antihistamines (AHs) has been associated with cognitive and psychomotor impairments, largely caused by the sedative properties of many of these drugs. Due to the ambulant nature of the population using AHs, it is important to evaluate these effects using standardised methodology and psychometric tests. A previous extensive review of the literature collated the results of studies of H1 receptor antagonists to determine the extent to which a particular AH produced impairments on a battery of psychometric tests by calculating a proportional impairment ratio for each AH. Objective In light of a number of major studies published following the previous review, and the development of the second and new-generation AHs, the present review aims to add to the database and update the review, using the same methodology. Results and Conclusion The newer generation AHs appear to be the least impairing, and the first generation, as expected, appear to be the most impairing. There are also differences within the AH drug generations. The review highlights the necessity to consider the sedating potential of AHs, along with other factors such as efficacy, when prescribing AHs to ambulant patients. Copyright © 2008 John Wiley & Sons, Ltd. [source] Interleukin-10 in viral diseases and cancer: exiting the labyrinth?IMMUNOLOGICAL REVIEWS, Issue 1 2004Alain P. Vicari Summary:, Interleukin-10 (IL-10) is unique among cytokines, as it is considered both as a potent immunostimulatory and immunosuppressive factor. This complex biology has been particularly challenging when trying to define the useful or harmful role of IL-10 in chronic viral diseases and cancer. In the present review, we emphasize how these multiple roles define IL-10 as an adaptive molecule, constantly tuning the host response against dangerous and resourceful pathogens. [source] Nursing management of fever in children: A systematic reviewINTERNATIONAL JOURNAL OF NURSING PRACTICE, Issue 1 2003FRCNA, Robin Watts RN ABSTRACT Objectives:, The aim of the present review was to determine whether the best available evidence supports the types and timing of the various nursing interventions that are commonly used to reduce fever in non-critically-ill children, and to what extent the outcomes are influenced by these nursing actions. Methods:, Studies included were randomised or quasi-randomised controlled trials that involved non-critically-ill children with a fever aged between 3 months and 16 years. ,,The search strategy sought to identify both published and unpublished research reports in the English language and covered all major databases up to 1998. ,,The methodological quality of each study was assessed by two independent reviewers using a piloted critical appraisal checklist. ,,Despite all studies being randomised, heterogeneity precluded conduction of a meta-analysis; therefore, evidence was synthesised using narrative summaries. Results: Ten studies were assessed as being of sufficient quality to be included in the review. These studies addressed two of the intervention categories identified in the protocol: (i) administration of antipyretics (paracetamol); and (ii) direct cooling measures on the outcome measure (reduction of or prevention of increase in fever). The review found little benefit from sponging in temperate climates and usually at the expense of the child's comfort. There may be situations in high environmental temperatures and high humidity, or where there is a need for immediate temperature reduction, in which sponging may be warranted. Risks were identified when paracetamol was administered on a sustained basis over even a short period of time and above a relatively low total daily dosage. There was a lack of evidence to support the administration of antipyretics to reduce the incidence of febrile convulsions. There is a need for parental education that focuses on knowledge of the body's protective physiological responses and how to support these responses. Conclusion: The primary purpose for intervening when a child has a fever is to increase the child's comfort. This consideration should be weighed against any harm that might result from intervening. There was a lack of evidence to support the routine use of sponging. The administration of paracetamol should be used selectively and with caution. In summary, care needs to be individualised, based on current knowledge of the effectiveness and risks of interventions. [source] Administering local anaesthesia to paediatric dental patients , current status and prospects for the futureINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 2 2002D. Ram Summary .,Fear-related behaviours have long been recognized as the most difficult aspect of patient management and can be a barrier to good care. Anxiety is one of the major issues in the dental treatment of children, and the injection is the most anxiety-provoking procedure for both children and adults. There is a constant search for ways to avoid the invasive, and often painful, nature of the injection, and to find more comfortable and pleasant means for anaesthesia before dental procedures. Objective. The purpose of the present review is to summarize relevant data on topics connected with the administration of local anaesthesia. Methods. The review will survey the current available methods, viz. electronic anaesthesia, lidocaine patch, computerized anaesthesia (the Wand), and the syrijet as well as the conventional injection, used for paediatric patients. Conclusions. Usually new techniques for locally anaesthetizing dental patients are tested on adults. However, despite recent research in the field, the injection remains the method of choice. It is necessary to continue to conduct studies using new techniques on adults and children, so that a more acceptable technique can be found. [source] Evolutionary emergence of synaptic nervous systems: what can we learn from the non-synaptic, nerveless Porifera?INVERTEBRATE BIOLOGY, Issue 1 2010Michael Nickel Abstract. The Porifera represent one of the only two recent nerveless and muscleless metazoan phyla. Nevertheless, sponges provide behavioral, physiological, pharmacological, morphological, and, more recently, an increasing amount of genetic evidence for a paracrine pre-nervous integration system. Although this system might be derived, it allows us to draw conclusions, on the basis of comparative data, about the origin of the nervous system sensu stricto as found in the eumetazoan phyla. The goal of the present review is to compile recent evidence on the sponge integration systems. Based on this framework, new light is also shed on the evolutionary origin of the eumetazoan synaptic nervous systems, which can be regarded to form an evolutionary biochemical continuum with the paracrine signaling system in sponges. Thus, we can assume that the evolutionary transition from a paracrine-dominated, pre-nervous system to an electrochemically dominated, primordial nervous system resulted in part from compartmentalization effects. As intermediate evolutionary stages, regionalized synapse precursor areas might have occurred within pre-nervous cells, which foreshadowed the highly organized synaptic scaffolds present in recent nerve cells of the Eumetazoa. [source] Functional effects of mutations identified in patients with Multiminicore diseaseIUBMB LIFE, Issue 1 2007Francesco Zorzato Abstract Multiminicore disease is a recessive congenital myopathy characterized by the presence of small cores or areas lacking oxidative enzymes, in skeletal muscle fibres. From a clinical point of view, the condition is widely heterogeneous and at least four phenotypes have been identified; genetic analysis has revealed that most patients with the classical form of multiminicore characterized by rigidity of the spine, early onset and respiratory impairment harbour recessive mutations in the SEPN1 gene, whereas the majority of patients belonging to the other categories, including patients with ophthalmoplegia or patients with a phenotype similar to central core disease, carry recessive mutations in the RYR1. In the present review we discuss the most recent findings on the functional effect of mutations in SEPN1 and RYR1 and discuss how they may adversely affect muscle function and lead to the clinical phenotype. IUBMB Life, 59: 14-20, 2007 [source] The Neuropathological Spectrum of Neurodegenerative TauopathiesIUBMB LIFE, Issue 6 2003Markus Tolnay Abstract Abundant neurofibrillary lesions made of abnormal and hyperphosphorylated microtubule-associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous deposits in neurons and/or glial cells also define a heterogeneous group of neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. Thus, all these disorders are collectively grouped under the generic term of tauopathies. In the present review we outline the morphological and biochemical characteristics of some major tauopathies, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration. Finally, we will discuss the very recent finding of 'tau-deficient' tauopathy in a subset of frontotemporal dementia cases. IUBMB Life, 55: 299-305, 2003 [source] Toxicogenomics: a pivotal piece in the puzzle of toxicological researchJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2007Elisavet T. Gatzidou Abstract Toxicogenomics, resulting from the merge of conventional toxicology with functional genomics, being the scientific field studying the complex interactions between the cellular genome, toxic agents in the environment, organ dysfunction and disease state. When an organism is exposed to a toxic agent the cells respond by altering the pattern of gene expression. Genes are transcribed into mRNA, which in turn is translated into proteins that serve in a variety of cellular functions. Toxicogenomics through microarray technology, offers large-scale detection and quantification of mRNA transcripts, related to alterations in mRNA stability or gene regulation. This may prove advantageous in toxicological research. In the present review, the applications of toxicogenomics, especially to mechanistic and predictive toxicology are reported. The limitations arising from the use of this technology are also discussed. Additionally, a brief report of other approaches, using other -omic technologies (proteomics and metabonomics) that overcome limitations and give global information related to toxicity, is included. Copyright © 2007 John Wiley & Sons, Ltd. [source] Myocardial Protection in Reoperative Coronary Artery Bypass Grafting:JOURNAL OF CARDIAC SURGERY, Issue 4 2004Mortality, Toward Decreasing Morbidity Myocardial infarction and dysfunction contribute significantly to the increased risk of redo CABG. Results of reoperative coronary surgery have gradually improved, largely because of improvements in myocardial protection techniques. In the present review we will highlight the principles of myocardial protection in redo CABG patients with an emphasis on retrograde cardioplegia. [source] Chagas' disease: an update on immune mechanisms and therapeutic strategiesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Silvia Beatriz Boscardin Abstract ,,Introduction ,,Chagas' disease ,,Chemotherapy ,,Immune response in experimental T. cruzi infection ,,Immune response in human beings infected with T. cruzi ,,Immune response in the treatment of chagasic infection ,,The need for new therapeutic alternatives for Chagas' disease ,,Conclusions The final decade of the 20th century was marked by an alarming resurgence in infectious diseases caused by tropical parasites belonging to the kinetoplastid protozoan order. Among the pathogenic trypanosomatids, some species are of particular interest due to their medical importance. These species include the agent responsible for Chagas' disease, Trypanosoma cruzi. Approximately 8 to 10 million people are infected in the Americas, and approximately 40 million are at risk. In the present review, we discuss in detail the immune mechanisms elicited during infection by T. cruzi and the effects of chemotherapy in controlling parasite proliferation and on the host immune system. [source] An islet in distress: , cell failure in type 2 diabetesJOURNAL OF DIABETES INVESTIGATION, Issue 4 2010Takeshi Ogihara Abstract Over 200 million people worldwide suffer from diabetes, a disorder of glucose homeostasis. The majority of these individuals are diagnosed with type 2 diabetes. It has traditionally been thought that tissue resistance to the action of insulin is the primary defect in type 2 diabetes. However, recent longitudinal and genome-wide association studies have shown that insulin resistance is more likely to be a precondition, and that the failure of the pancreatic , cell to meet the increased insulin requirements is the triggering factor in the development of type 2 diabetes. A major emphasis in diabetes research has therefore shifted to understanding the causes of , cell failure. Collectively, these studies have implicated a complex network of triggers, which activate intersecting execution pathways leading to , cell dysfunction and death. In the present review, we discuss these triggers (glucotoxicity, lipotoxicity, amyloid and cytokines) with respect to the pathways they activate (oxidative stress, inflammation and endoplasmic reticulum stress) and propose a model for understanding , cell failure in type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00021.x, 2010) [source] Satellite DNA and chromosomes in Neotropical fishes: methods, applications and perspectivesJOURNAL OF FISH BIOLOGY, Issue 5 2010M. R. Vicari Constitutive heterochromatin represents a substantial portion of the eukaryote genome, and it is mainly composed of tandemly repeated DNA sequences, such as satellite DNAs, which are also enriched by other dispersed repeated elements, including transposons. Studies on the organization, structure, composition and in situ localization of satellite DNAs have led to consistent advances in the understanding of the genome evolution of species, with a particular focus on heterochromatic domains, the diversification of heteromorphic sex chromosomes and the origin and maintenance of B chromosomes. Satellite DNAs can be chromosome specific or species specific, or they can characterize different species from a genus, family or even representatives of a given order. In some cases, the presence of these repeated elements in members of a single clade has enabled inferences of a phylogenetic nature. Genomic DNA restriction, using specific enzymes, is the most frequently used method for isolating satellite DNAs. Recent methods such as C0t,1 DNA and chromosome microdissection, however, have proven to be efficient alternatives for the study of this class of DNA. Neotropical ichthyofauna is extremely rich and diverse enabling multiple approaches with regard to the differentiation and evolution of the genome. Genome components of some species and genera have been isolated, mapped and correlated with possible functions and structures of the chromosomes. The 5SHindIII-DNA satellite DNA, which is specific to Hoplias malabaricus of the Erythrinidae family, has an exclusively centromeric location. The As51 satellite DNA, which is closely correlated with the genome diversification of some species from the genus Astyanax, has also been used to infer relationships between species. In the Prochilodontidae family, two repetitive DNA sequences were mapped on the chromosomes, and the SATH 1 satellite DNA is associated with the origin of heterochromatic B chromosomes in Prochilodus lineatus. Among species of the genus Characidium and the Parodontidae family, amplifications of satellite DNAs have demonstrated that these sequences are related to the differentiation of heteromorphic sex chromosomes. The possible elimination of satellite DNA units could explain the genome compaction that occurs among some species of Neotropical Tetraodontiformes. These topics are discussed in the present review, showing the importance of satellite DNA analysis in the differentiation and karyotype evolution of Actinopterygii. [source] | |||||||||||||||||||||||||||||||||||||