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Biological Basis (biological + basis)
Selected AbstractsSustained attention as a potential endophenotype for bipolar disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010I. Ancín Ancín I, Santos JL, Teijeira C, Sánchez-Morla EM, Bescós MJ, Argudo I, Torrijos S, Vázquez-Álvarez B, De La Vega I, López-Ibor JJ, Barabash A, Cabranes-Díaz JA. Sustained attention as a potential endophenotype for bipolar disorder. Objective:, Nowadays, it is accepted that to identify the biological basis of psychiatric illnesses it would be useful to deconstruct them into the most basic manifestations, such as cognitive deficits. The aim of this study was to set attention deficit as a stable vulnerability marker of bipolar disorder. Method:, Sustained attention was evaluated by the Continuous Performance Test (DS-CPT) in 143 euthymic bipolar patients and 105 controls. To estimate the influence of clinical profile in attention, patients completed a semi-structured interview. Results:, Bipolar patients showed a deficit in attention during euthymic periods. This disturbance correlated with years of evolution, age of onset and age of first hospitalisation; and was not influenced by other clinical data. Conclusion:, Sustained attention may be considered as an endophenotype of the illness. [source] Gender-specific disruptions in emotion processing in younger adults with depression,DEPRESSION AND ANXIETY, Issue 2 2009Sara L. Wright Ph.D. Abstract Background: One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. Methods: This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). Results: For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). Conclusions: These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc. [source] Epidemiology and Biology of Menstrual MigraineHEADACHE, Issue 2008Vincent T. Martin MD Migraine is frequently associated with menstruation in female migraineurs, and consequently it is commonly referred to as menstrually associated migraine. The trigger thought to be partially responsible for menstrually associated migraine is a significant drop in circulating estrogen that is noted during 2-3 days prior to onset of menses. It is estimated that approximately 50% of women have an increased risk of experiencing migraine during the premenstrual phase of decreasing estrogen levels. Understanding the biological basis of migraine associated with menses will facilitate an accurate diagnosis and help patients recognize time susceptible to migraine exacerbations. This paper will review the biological bases for the hormonal changes that occur during the menstrual cycle and review the prevalence and burden of menstrual migraine among female headache sufferers. [source] From Migraine To Chronic Daily Headache: The Biological Basis of Headache TransformationHEADACHE, Issue 8 2007Ian D. Meng PhD Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH. [source] Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer diseaseHIPPOCAMPUS, Issue 10 2009Sebastian Mirochnic Abstract An active lifestyle is to some degree protective against Alzheimer's disease (AD), but the biological basis for this benefit is still far from clear. We hypothesize that physical and cognitive activity increase a reserve for plasticity by increasing adult neurogenesis in the hippocampal dentate gyrus (DG). We thus assessed how age affects the response to activity in the murine APP23 model of AD compared with wild type (WT) controls and studied the effects of physical exercise (RUN) and environmental enrichment (ENR) in comparison with standard housing (CTR) at two different ages (6 months and 18 months) and in both genotypes. At 18 months, both activity paradigms reduced the hippocampal human A,1-42/A,1-40 ratio when compared with CTR, despite a stable plaque load in the hippocampus. At this age, both RUN and ENR increased the number of newborn granule cells in the DG of APP23 mice when compared with CTR, whereas the levels of regulation were equivalent to those in WT mice under the same housing conditions. At 6 months, however, neurogenesis in ENR but not RUN mice responded like the WT. Quantifying the number of cells at the doublecortin-positive stage in relation to the number of cells on postmitotic stages we found that ENR overproportionally increased the number of the DCX-positive "late" progenitor cells, indicative of an increased potential to recruit even more new neurons. In summary, the biological substrates for activity-dependent regulation of adult hippocampal neurogenesis were preserved in the APP23 mice. We thus propose that in this model, ENR even more than RUN might contribute to a "neurogenic reserve" despite a stable plaque load and that age affects the outcome of an interaction based on "activity." © 2009 Wiley-Liss, Inc. [source] Assessment of pulp vitality: a reviewINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2009VELAYUTHAM GOPIKRISHNA Background., One of the greatest diagnostic challenges in clinical practice is the accurate assessment of pulp status. This may be further complicated in paediatric dentistry where the practitioner is faced with a developing dentition, traumatized teeth, or young children who have a limited ability to recall a pain history for the tooth in question. A variety of pulp testing approaches exist, and there may be confusion as to their validity or appropriateness in different clinical situations. Aim., The aim of this paper is to provide the clinician with a comprehensive review of current pulp testing methods. A key objective is to highlight the difference between sensitivity testing and vitality testing. A biological basis for pulp testing is also provided to allow greater insight into the interpretation of pulp testing results. The rationale for, and methods of, assessing pulpal blood flow are described. [source] Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats,JAPANESE PSYCHOLOGICAL RESEARCH, Issue 1 2008SHUICHI YANAI Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5-bromo-2,-deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed-matching-to-place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction. [source] Underarm cosmetics and breast cancerJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2003P. D. Darbre Abstract Although risk factors are known to include the loss of function of the susceptibility genes BRCA1/BRCA2 and lifetime exposure to oestrogen, the main causative agents in breast cancer remain unaccounted for. It has been suggested recently that underarm cosmetics might be a cause of breast cancer, because these cosmetics contain a variety of chemicals that are applied frequently to an area directly adjacent to the breast. The strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells. Multidisciplinary research is now needed to study the effect of long-term use of the constituent chemicals of underarm cosmetics, because if there proves to be any link between these cosmetics and breast cancer then there might be options for the prevention of breast cancer. Copyright © 2003 John Wiley & Sons, Ltd. [source] RNAi-mediated inhibition of MSP58 decreases tumour growth, migration and invasion in a human glioma cell lineJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Wei Lin Abstract MSP58, a 58-kD nuclear microspherule protein, is an evolutionarily conserved nuclear protein implicated in the regulation of gene transcription as well as in malignant transformation. An analysis of mRNA expression by real-time PCR revealed that MSP58 was significantly up-regulated in 29% of high-grade glioblastoma tissues as well as in four glioblastoma cell lines. In the present study, we further evaluated the biological functions of MSP58 in U251 glioma cell proliferation, migration, invasion and tumour growth in vivo by specific MSP58 knockdown using short hairpin RNA (shRNA). We found that MSP58 depletion inhibited glioma cell growth, primarily by inducing cell cycle arrest rather than apoptosis. MSP58 depletion also decreased the invasive capability of glioma cells and anchorage-independent colony formation in soft agar. Moreover, suppression of MSP58 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, a cell cycle-associated gene array revealed potential molecular mechanisms contributing to cell cycle arrest in MSP58-depleted glioma cells. In summary, our data highlight the importance of MSP58 in glioma progression and provided a biological basis for MSP58 as a novel candidate target for treatment of glioma. [source] Innate Differences in the Expression of Brain-Derived Neurotrophic Factor in the Regions Within the Extended Amygdala Between Alcohol Preferring and Nonpreferring RatsALCOHOLISM, Issue 6 2008Anand Prakash Background:, Animal lines such as alcohol-preferring (P) and nonpreferring (NP) rats appear to be suitable animal models to investigate the biological basis of alcohol-drinking behaviors. The extended amygdala serves as a neuroanatomical substrate for alcohol-drinking behaviors. Brain-derived neurotrophic factor (BDNF) in the amygdala has been implicated in alcohol-drinking behaviors; however, its expression in the extended amygdala of P and NP rats is unknown. Therefore, we examined the basal expression of BDNF in the extended amygdala of alcohol naïve P and NP rats. Methods:, We determined the basal mRNA and protein levels of BDNF by in situ RT-PCR and immuno-histochemical procedure, respectively, in the amygdaloid [central nucleus of amygdala (CeA), medial nucleus of amygdala (MeA), and basolateral amygdala (BLA)], nucleus accumbal (NAc shell and core), and bed nucleus of stria terminalis (BNST) [lateral BNST (lBNST), medial BNST (mBNST), and ventral BNST (vBNST)] brain structures of P and NP rats. In addition, we examined the localization of BDNF in neurons using double-immunofluorescence labeling of BDNF with neuron-specific nuclear protein (NeuN) and also determined the number of NeuN-positive neurons in the amygdaloid structures of P and NP rats. Results:, The mRNA and protein levels of BDNF were found to be significantly lower in both the CeA and MeA, but not in the BLA, of P compared with NP rats. We also found that BDNF was expressed in neurons in the amygdaloid structures of P and NP rats. In addition, we found that the number of NeuN-positive neurons was similar in the amygdaloid structures of P and NP rats. Interestingly, the mRNA and protein levels of BDNF were also significantly lower in the lBNST, mBNST, and vBNST of P compared with NP rats. On the other hand, mRNA and protein levels of BDNF were similar in the NAc shell and core structures of P and NP rats. Conclusions:, P and NP rats are selectively bred for higher and lower alcohol preference, respectively; therefore it is possible that lower BDNF levels in the amygdaloid and BNST structures may be associated with the excessive alcohol-drinking behaviors of P rats. [source] Induction and Maintenance of Ethanol Self-Administration in Cynomolgus Monkeys (Macaca fascicularis): Long-Term Characterization of Sex and Individual DifferencesALCOHOLISM, Issue 8 2001J. A. Vivian Background: Investigations of oral ethanol self-administration in nonhuman primates have revealed important parallels with human alcohol use and abuse, yet many fundamental questions concerning the individual risk to, and the biological basis of, excessive ethanol consumption remain unanswered. Moreover, many conditions of access to ethanol in nonhuman primate research are largely unexplored. This set of experiments extends within- and across-session exposure to ethanol to more fully characterize individual differences in oral ethanol self-administration. Methods: Eight male and eight female adult cynomolgus monkeys (Macaca fascicularis) were exposed to daily oral ethanol self-administration sessions for approximately 9 months. During the first 3 months, a fixed-time (FT) schedule of food delivery was used to induce the consumption of an allotted dose of ethanol in 16-hr sessions. Subsequently, the FT schedule was suspended, and ethanol was available ad libitum for 6 months in 16- or 22-hr sessions. Results: Cynomolgus monkeys varied greatly in their propensity to self-administer ethanol, with sex and individual differences apparent within 10 days of ethanol exposure. Over the last 3 months of ethanol access, individual average ethanol intakes ranged from 0.6 to 4.0 g/kg/day, resulting in blood ethanol concentrations from 5 to 235 mg/dl. Males drank approximately 1.5-fold more than females. In addition, heavy-, moderate-, and light-drinking phenotypes were identified by using daily ethanol intake and the percentage of daily calories obtained from ethanol as criteria. Conclusions: Cynomolgus monkeys displayed a wide intersubject range of oral ethanol self-administration with a procedure that used a uniform and prolonged induction that restricted early exposure to ethanol and subsequently allowed unlimited access to ethanol. There were sex and stable individual differences in the propensity of monkeys to consume ethanol, indicating that this species will be important in characterizing risk factors associated with heavy-drinking phenotypes. [source] Instream Flow Science For Sustainable River Management,JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 5 2009Geoffrey E Petts Abstract:, Concerns for water resources have inspired research developments to determine the ecological effects of water withdrawals from rivers and flow regulation below dams, and to advance tools for determining the flows required to sustain healthy riverine ecosystems. This paper reviews the advances of this environmental flows science over the past 30 years since the introduction of the Instream Flow Incremental Methodology. Its central component, Physical HABitat SIMulation, has had a global impact, internationalizing the e-flows agenda and promoting new science. A global imperative to set e-flows, including an emerging trend to set standards at the regional scale, has led to developments of hydrological and hydraulic approaches but expert judgment remains a critical element of the complex decision-making process around water allocations. It is widely accepted that river ecosystems are dependent upon the natural variability of flow (the flow regime) that is typical of each hydro-climatic region and upon the range of habitats found within each channel type within each region. But as the sophistication of physical (hydrological and hydraulic) models has advanced emerging biological evidence to support those assumptions has been limited. Empirical studies have been important to validate instream flow recommendations but they have not generated transferable relationships because of the complex nature of biological responses to hydrological change that must be evaluated over decadal time-scales. New models are needed to incorporate our evolving knowledge of climate cycles and morphological sequences of channel development but most importantly we need long-term research involving both physical scientists and biologists to develop new models of population dynamics that will advance the biological basis for 21st Century e-flow science. [source] Major depression: emerging therapeuticsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2008Srijan Sen MD Abstract The first effective antidepressants, monoamine oxidase inhibitors and tricyclic antidepressants, were identified 50 years ago, largely through serendipity. These medications were found to improve mood in a little more than half of depressed patients after a few weeks of chronic use. Almost all antidepressants prescribed today were developed through minor modifications of these original antidepressants and, like monoamine oxidase inhibitors and tricyclic antidepressants, act primarily through monoaminergic mechanisms. Although there have been improvements in side-effect profiles and overdose toxicity, these newer medications have not provided substantial advances in the efficacy and speed of the antidepressant effect for patients. Over the last 2 decades, our understanding of the neurobiology underlying depression has expanded exponentially. Given this expansion, we may be nearing an inflection point in antidepressant drug development, at which useful medicines will be designed through a rational understanding of the biological systems. In this review, we discuss the biological basis and preclinical and clinical evidence for a series of promising classes of antidepressants developed primarily out of a pathophysiologically informed approach. Mt Sinai J Med 75:203,224, 2008. © 2008 Mount Sinai School of Medicine [source] HARVESTING AN AGE-STRUCTURED POPULATION AS BIOMASS: DOES IT WORK?NATURAL RESOURCE MODELING, Issue 4 2008OLLI TAHVONEN Abstract The economics of fisheries is based heavily on describing fish populations by the surplus production model. Both economists and ecologists have different opinions on whether this approach provides an adequate biological basis for economic analysis. This study takes an age-structured population model and shows how, under equilibrium conditions, it determines the surplus production model. The surplus production model is then used to solve an optimal feedback policy for a generic optimal harvesting problem. Next, it is assumed that the fishery manager applies this feedback policy even though the fish population actually evolves according to the age-structured model. This framework is applied to the widow rockfish, Atlantic menhaden, and Pacific halibut fisheries. Population age-structure contains information on future harvest possibilities. The surplus production model neglects this information and may lead to major deviations between the expected and actual outcomes especially under multiple steady states and nonlinearities. [source] Multicomponent attention deficits in attention deficit hyperactivity disorderPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2007M GÜNAY KILIÇ md Abstract The aim of this study was to examine the specific aspects of attention, such as selective attention, sustained attention, and short-term memory in children with attention deficit hyperactivity disorder, combined subtype (ADHD-C). A total of 40 children with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual, aged 6,11 years old were compared with 40 controls matched for age and gender on a battery of tests. Short-term memory span and attention was measured by Visual Aural Digit Span Test,Revised. Stroop test and the Turkish version of Cancellation Test were used to assess selective and sustained attention, respectively. In order to check for factor structure in two groups on the test scores, principal component analysis was conducted for both groups separately. Relative to the comparison children, children with ADHD showed significant deficits on tests that are related to different aspects of attention. The results are consistent with the theories explaining the biological basis of ADHD by scattered attention networks in the brain, which have reciprocal dynamic interactions. Further comparative studies are needed to elucidate whether the cognitive processes that are known to be assessed by these tests are specific to ADHD. [source] Genetic and environmental influences on emotion-modulated startle reflex: A twin studyPSYCHOPHYSIOLOGY, Issue 1 2007Andrey P. Anokhin Abstract Emotion-modulated startle reflex is an important indicator of traitlike differences in affective processing implicated in the biological basis of personality and psychopathology. This study examined heritability of startle modulation by affective pictures in 66 pairs of monozygotic and 57 pairs of dizygotic female twins. Consistent with previous studies, startle magnitude was significantly influenced by emotional valence of the picture (positive Research Review: Crossing syndrome boundaries in the search for brain endophenotypesTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 6 2009Yonata Levy The inherent imprecision of behavioral phenotyping is the single most important factor contributing to the failure to discover the biological factors that are involved in psychiatric and neurodevelopmental disorders (e.g., Bearden & Freimer, 2006). In this review article we argue that in addition to an appreciation of the inherent complexity at the biological level, a rather urgent task facing behavioral scientists involves a reconsideration of the role that clinical syndromes play in psychological theorizing, as well as in research into the biological basis of cognition and personality. Syndrome heterogeneity, cross-syndrome similarities and syndrome comorbidities question the relevance of syndromes to biological research. It is suggested that the search for brain endophenotypes, intermediate between genes and behavior, should be based on cross-syndrome, trait classification. Cohort selection should rest on behavioral homogeneity, enabling, when necessary, syndrome heterogeneity. [source] Reproductive ageing in women,THE JOURNAL OF PATHOLOGY, Issue 2 2007O Djahanbakhch Abstract The traditional view in respect to female reproduction is that the number of oocytes at birth is fixed and continuously declines towards the point when no more oocytes are available after menopause. In this review we briefly discuss the embryonic development of female germ cells and ovarian follicles. The ontogeny of the hypothalamic-pituitary-gonadal axis is then discussed, with a focus on pubertal transition and normal ovulatory menstrual cycles during female adult life. Biochemical markers of menopausal transition are briefly examined. We also examine the effects of age on female fertility, the contribution of chromosomal abnormalities of the oocyte to the observed decline in female fertility with age and the possible biological basis for the occurrence of such abnormalities. Finally, we consider the effects of maternal age on obstetric complications and perinatal outcome. New data that have the potential to revolutionize our understanding of mammalian oogenesis and follicular formation, and of the female reproductive ageing process, are also briefly considered. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Human motor associative plasticity induced by paired bihemispheric stimulationTHE JOURNAL OF PHYSIOLOGY, Issue 19 2009Satoko Koganemaru Paired associative stimulation (PAS) is an effective non-invasive method to induce human motor plasticity by the repetitive pairing of peripheral nerve stimulation and transcranial magnetic stimulation (TMS) at the primary motor cortex (M1) with a specific time interval. Although the repetitive pairing of two types of afferent stimulation might be a biological basis of neural plasticity and memory, other types of paired stimulation of the human brain have rarely been studied. We hypothesized that the repetitive pairing of TMS and interhemispheric cortico-cortical projection or paired bihemispheric stimulation (PBS), in which the right and left M1 were serially stimulated with a time interval of 15 ms, would produce an associative long-term potentiation (LTP)-like effect. In this study, 23 right-handed healthy volunteers were subjected to a 0.1 Hz repetition of 180 pairings of bihemispheric TMS, and physiological and behavioural measures of the motor system were compared before, immediately after, 20 min after and 40 min after PBS intervention. The amplitude of the motor evoked potential (MEP) induced by the left M1 stimulation and its input,output function increased for up to ,20 min post-PBS. Fine finger movements were also facilitated by PBS. Spinal excitability measured by the H-reflex was insensitive to PBS, suggesting a cortical mechanism. The associative LTP-like effect induced by PBS was timing dependent, occurring only when the interstimulus interval was 5,25 ms. These findings demonstrate that using PBS in PAS can induce motor cortical plasticity, and this approach might be applicable to the rehabilitation of patients with motor disorders. [source] The theoretical basis of cancer-stem-cell-based therapeutics of cancer: can it be put into practice?BIOESSAYS, Issue 12 2007Isidro Sánchez-García In spite of the advances in our knowledge of cancer biology, most cancers remain not curable with present therapies. Current treatments consider cancer as resulting from uncontrolled proliferation and are non-specific. Although they can reduce tumour burden, relapse occurs in most cases. This was long attributed to incomplete tumour elimination, but recent developments indicate that different types of cells contribute to the tumour structure, and that the tumour's cellular organization would be analogous to that of a normal tissue, with a main mass of differentiating cells sensitive to anti proliferative agents, together with a small percentage of quiescent, resistant stem cells responsible for replenishing the tumour: the Cancer Stem Cells (CSCs). Anti-CSCs targeted therapeutic agents would prevent tumour regeneration. New mouse models tailored to exploit this novel concept will be critical to develop CSC-based anti-cancer therapies. Here we review the biological basis and the therapeutic implications of the stem-cell model of cancer. BioEssays 29:1269,1280, 2007. © 2007 Wiley Periodicals, Inc. [source] Profile of Cognitive Impairment in Parkinson's DiseaseBRAIN PATHOLOGY, Issue 3 2010G. Stennis Watson Abstract Cognitive impairment (CI) is a common nonmotor complication of Parkinson's disease (PD), and is associated with significant disability for patients and burden for caregivers. Similar to motor symptoms, the characteristics of CI in PD can be quite variable, both in terms of what cognitive domains are impaired, and the timing of onset and rate of progression. This review will examine the profile of cognitive domain impairments observed in PD, with a focus on early CI (without dementia). We will also discuss possible relationships between specific cognitive domain impairments in PD and pathological processes such as Lewy-related pathology and Alzheimer's disease. It is our hypothesis that the specific characteristics of CI observed in individual PD patients provide clues to the underlying pathological processes, and that understanding the biological basis of this clinical phenomenon will assist in directing disease-specific treatments. Given the high lifetime risk for CI in PD, it is imperative that we improve our understanding and treatments for this common and disabling problem in PD. [source] Sabiston Textbook of Surgery: the biological basis of modern surgical practice 17th Edn.BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2005No abstract is available for this article. [source] Modulation of growth hormone action by sex steroidsCLINICAL ENDOCRINOLOGY, Issue 4 2006Udo J. Meinhardt Summary Growth hormone (GH) is a major regulator of growth, somatic development and body composition. Sex steroids can act centrally by regulating GH secretion and peripherally modulating GH responsiveness. This review addresses data of potential clinical relevance on how sex steroids modulate GH secretion and action, aiming to increase the understanding of sex steroid/GH interactions and leading to improved management of patients. Sex steroids regulate GH secretion directly as well as indirectly through IGF-I modulation. Testosterone stimulates GH secretion centrally, an effect dependent on prior aromatization to oestrogen. Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback inhibition. Whether oestrogen stimulates GH secretion centrally in females is unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and protein anabolism while exhibiting similar but independent actions of its own. Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of the liver. This is a concentration-dependent phenomenon that arises invariably from oral administration of therapeutic doses of oestrogen, an effect that can be avoided by using a parenteral route. This strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biological basis of sexual dimorphism in growth, development and body composition and practical information for the clinical endocrinologist. It calls for an appraisal of the diagnostic criteria for GH deficiency of GH stimulation tests, which currently are based on arbitrary cut-offs that do not take into account the shifting baseline from the changing gonadal steroid milieu. In the management of GH deficiency in the hypopituitary female, oestrogen should be administered by a nonoral route. In hypopituitary men, androgens should be replaced concurrently to maximize the benefits of GH. In the general population, the metabolic consequences of long-term treatment of women with oral oestrogen compounds, including selective oestrogen receptor modulators, are largely unknown and warrant study. [source]
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