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HAD
Selected AbstractsRole of the pro-inflammatory cytokines TNF-, and IL-1, in HIV-associated dementiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2006N. A. C. H. Brabers Abstract Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,), which are thought to play a major role in inducing neuronal death. Both TNF-, and IL-1, increase the permeability of the blood,brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca2+ levels. Additionally, TNF-, co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-, and IL-1, in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-, and IL-1, on neuronal life and death in HAD is discussed. [source] PRECLINICAL STUDY: Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of high-alcohol-drinking (HAD) ratsADDICTION BIOLOGY, Issue 2 2009Zachary A. Rodd ABSTRACT High-alcohol-drinking rats, given access to 10% ethanol, expressed an alcohol deprivation effect (ADE) only after multiple deprivations. In alcohol-preferring (P) rats, concurrent access to multiple ethanol concentrations combined with repeated cycles of EtOH access and deprivation produced excessive ethanol drinking. The current study was undertaken to examine the effects of repeated alcohol deprivations with concurrent access to multiple concentrations of ethanol on ethanol intake of HAD replicate lines of rats. HAD-1 and HAD-2 rats received access to 10, 20 and 30% (v/v) ethanol for 6 weeks. Rats from each replicate line were assigned to: (1) a non-deprived group; (2) a group initially deprived of ethanol for 2 weeks; or (3) a group initially deprived for 8 weeks. Following the restoration of the ethanol solutions, cycle of 2 weeks of ethanol exposure and 2 weeks of alcohol deprivation was repeated three times for a total of four deprivations. Following the initial ethanol deprivation period, deprived groups significantly increased ethanol intakes during the initial 24-hour re-exposure period. Multiple deprivations increased ethanol intakes, shifted preference to higher ethanol concentrations and prolonged the duration of the elevated ethanol intakes for up to 5 days. In addition, repeated deprivations increased ethanol intake in the first 2-hour re-exposure period as high as 5,7 g/kg (which are equivalent to amounts consumed in 24 hours by HAD rats), and produced blood ethanol levels in excess of 150 mg%. The results indicate that HAD rats exhibit ,loss-of-control' of alcohol drinking with repeated deprivations when multiple ethanol concentrations are available. [source] Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystoniaEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007I. M. Skogseid The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a ,good effect' of long-term BTX treatment (n = 47), had significantly lower median TWSTRS total score, and a 3× lower frequency of high HAD-D scores, than those evaluated to an ,unsatisfactory effect' (n = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms. [source] Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomesGENES, BRAIN AND BEHAVIOR, Issue 7 2008C. J. Wilhelm Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess ,choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals. [source] Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brainGLIA, Issue 2 2006Huanyu Dou Abstract The balance between astrocyte and microglia neuroprotection and neurotoxicity defines the tempo of neuronal dysfunction during HIV-1-associated dementia (HAD). Astrocytes maintain brain homeostasis and respond actively to brain damage by providing functional and nutritive neuronal support. In HAD, low-level, continuous infection of astrocytes occurs, but the functional consequences of thisinfection are poorly understood. To this end, human fetal astrocytes (HFA) and monocyte-derived macrophages (MDM) were infected with HIV-1DJV and HIV-1NL4-3 (neurotropic and lymphotropic strains respectively) and a pseudotyped Vesicular Stomatitis Virus (VSV/HIV-1NL4-3) prior to intracranial injection into the basal ganglia of severe combined immunodeficient mice. Neuropathological and immunohistochemical comparisons for inflammatory and neurotoxic activities were performed amongst the infected cell types at 7 or 14 days. HIV-1-infected MDM induced significant increases in Mac-1, glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, and proinflammatory cytokine RNA and/or protein expression when compared with HSV/HIV-1- and HIV-1-infected HFA and sham-operated mice. Levels of neuron-specific nuclear protein, microtubule-associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV-1DJV or VSV/HIV-1. We conclude that HIV-1 infection of astrocytes leads to limited neurodegeneration, underscoring the early and active role of macrophage-driven neurotoxicity in disease. © 2006 Wiley-Liss, Inc. [source] Modeling the effects of fire and climate change on carbon and nitrogen storage in lodgepole pine (Pinus contorta) standsGLOBAL CHANGE BIOLOGY, Issue 3 2009E. A. H. SMITHWICK Abstract The interaction between disturbance and climate change and resultant effects on ecosystem carbon (C) and nitrogen (N) fluxes are poorly understood. Here, we model (using CENTURY version 4.5) how climate change may affect C and N fluxes among mature and regenerating lodgepole pine (Pinus contorta var. latifolia Engelm. ex S. Wats.) stands that vary in postfire tree density following stand-replacing fire. Both young (postfire) and mature stands had elevated forest production and net N mineralization under future climate scenarios relative to current climate. Forest production increased 25% [Hadley (HAD)] to 36% [Canadian Climate Center (CCC)], compared with 2% under current climate, among stands that varied in stand age and postfire density. Net N mineralization increased under both climate scenarios, e.g., +19% to 37% (HAD) and +11% to 23% (CCC), with greatest increases for young stands with sparse tree regeneration. By 2100, total ecosystem carbon (live+dead+soils) in mature stands was higher than prefire levels, e.g., +16% to 19% (HAD) and +24% to 28% (CCC). For stands regenerating following fire in 1988, total C storage was 0,9% higher under the CCC climate model, but 5,6% lower under the HAD model and 20,37% lower under the Control. These patterns, which reflect variation in stand age, postfire tree density, and climate model, suggest that although there were strong positive responses of lodgepole pine productivity to future changes in climate, C flux over the next century will reflect complex relationships between climate, age structure, and disturbance-recovery patterns of the landscape. [source] Spatial and genetic structure of host-associated differentiation in the parasitoid Copidosoma gelechiaeJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 6 2009C. R. KOLACZAN Abstract Host-associated differentiation (HAD) appears to be an important driver of diversification in the hyperdiverse phytophagous and parasitoid insects. The gallmaking moth Gnorimoschema gallaesolidaginis has undergone HAD on two sympatric goldenrods (Solidago), and HAD has also been documented in its parasitoid Copidosoma gelechiae, with the intriguing suggestion that differentiation has proceeded independently in multiple populations. We tested this suggestion with analysis of Amplified Fragment Length Polymorphism (AFLP) markers for C. gelechiae collections from the midwestern and northeastern United States and eastern Canada. AFLP data were consistent with the existence of HAD, with between-host FST significant before Bonferroni correction in two of seven sympatric populations. amova analysis strongly rejected a model of HAD with a single historical origin, and thus supported the repeated-HAD hypothesis. Copidosoma gelechiae shows significant host-associated divergence at a number of allozyme loci (Stireman et al., 2006), but only weak evidence via AFLPs for genome-wide differentiation, suggesting that this species is at a very early stage of HAD. [source] Novel role of TGF-, in differential astrocyte-TIMP-1 regulation: Implications for HIV-1-dementia and neuroinflammationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Alok Dhar Abstract Astrocyte production of tissue inhibitor of metalloproteinase (TIMP)-1 is important in central nervous system (CNS) homeostasis and inflammatory diseases such as HIV-1-associated dementia (HAD). TIMPs and matrix metalloproteinases (MMPs) regulate the remodeling of the extracellular matrix. An imbalance between TIMPs and MMPs is associated with many pathologic conditions. Our recently published studies uniquely demonstrate that HAD patients have reduced levels of TIMP-1 in the brain. Astrocyte-TIMP-1 expression is differentially regulated in acute and chronic inflammatory conditions. In this and the adjoining report (Gardner et al., 2006), we investigate the mechanisms that may be involved in differential TIMP-1 regulation. One mechanism for TIMP-1 downregulation is the production of anti-inflammatory molecules, which can activate signaling pathways during chronic inflammation. We investigated the contribution of transforming growth factor (TGF)-signaling in astrocyte-MMP/TIMP-1-astrocyte regulation. TGF-,1 and ,2 levels were upregulated in HAD brain tissues. Co-stimulation of astrocytes with IL-1, and TGF-, mimicked the TIMP-1 downregulation observed with IL-1, chronic activation. Measurement of astrocyte-MMP protein levels showed that TGF-, combined with IL-1, increased MMP-2 and decreased proMMP-1 expression compared to IL-1, alone. We propose that one of the mechanisms involved in TIMP-1 downregulation may be through TGF-signaling in chronic immune activation. These studies show a novel extracellular regulatory loop in astrocyte-TIMP-1 regulation. © 2006 Wiley-Liss, Inc. [source] Involvement of ,1,1 integrin in insulin-like growth factor-1-mediated protection of PC12 neuronal processes from tumor necrosis factor-,-induced injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Jin Ying Wang Abstract Insulin-like growth factor 1 receptor (IGF-1R) supports neuronal survival against a wide variety of insults. This includes tumor necrosis factor-, (TNF,)-mediated neuronal damage, which represents one of the factors suspected to play a role in HIV-associated dementia (HAD). PC12 neurons engineered to express human IGF-1R (PC12/IGF-1R) maintain neuronal processes on collagen IV for several weeks. However, prolonged treatment with TNF, caused degeneration of neuronal processes, with no apparent signs of apoptosis. In this process, TNF, did not affect IGF-1-mediated phosphorylation of IRS-1, IRS-2, Akt, or Erks. In addition, PC12/IGF-1R cells were found to express predominantly ,1,1 integrin, which has high affinity to collagen IV. The treatment of PC12/IGF-1R neurons with a specific ,1,1 integrin inhibitor, obtustatin, also caused loss of neuronal processes, accompanied by a quick cell detachment and extensive apoptosis. In the presence of IGF-1, both TNF,-induced and obtustatin-induced degeneration of neuronal processes were effectively inhibited. Furthermore, TNF,-mediated neuronal degeneration correlated with decreased attachment of PC12/IGF-1R cells to collagen IV and with a reduced level of ,1,1 integrin, consistent with a role for this surface protein in the maintenance of neuronal processes. Thus the neuroprotective effects of IGF-1 are not restricted to its antiapoptotic properties but also involve an additional neuroprotective mechanism, by which IGF-1 counteracts the negative effect of TNF, on ,1,1 integrin-mediated attachment to collagen IV. © 2005 Wiley-Liss, Inc. [source] Effects of Long-Term Episodic Access to Ethanol on the Expression of an Alcohol Deprivation Effect in Low Alcohol,Consuming RatsALCOHOLISM, Issue 12 2004Richard L. Bell Background: The alcohol-preferring (P) and -nonpreferring (NP) and high alcohol,drinking (HAD) and low alcohol,drinking (LAD) rats have been selectively bred for divergent preference for ethanol over water. In addition, both P and HAD rats display an alcohol deprivation effect (ADE). This study was undertaken to test whether the NP, LAD-1, and LAD-2 lines of rats could display an ADE as well. Method: Adult female NP, LAD-1, and LAD-2 rats were given concurrent access to multiple concentrations of ethanol [5, 10, 15% (v/v)] and water in an ADE paradigm involving an initial 6 weeks of 24-hr access to ethanol, followed by four cycles of 2 weeks of deprivation from and 2 weeks of re-exposure to ethanol (5, 10, and 15%). A control group had continuous access to the ethanol concentrations (5, 10, and 15%) and water through the end of the fourth re-exposure period. Results: For NP rats, a preference for the highest ethanol concentration (15%) was evident by the end of the fifth week of access (,60% of total ethanol fluid intake). Contrarily, LAD rats did not display a marked preference for any one concentration of ethanol. All three lines displayed an ADE after repeated cycles of re-exposure to ethanol, with the general ranking of intake being LAD-1 > NP > LAD-2 (e.g., for the first day of reinstatement of the third re-exposure cycle, intakes were 6.5, 2.9, and 2.4 g/kg/day compared with baseline values of 3.1, 2.0, and 1.3 g/kg/day for each line, respectively). By the 13th week, rats from all three lines, with a ranking of LAD-1 > NP > LAD-2, were drinking more ethanol (3.3, 2.2, and 2.0 g/kg/day, respectively) compared with their consumption during the first week of access (,1.1 g/kg/day for all three lines). Conclusion: These data indicate that access to multiple concentrations of ethanol and exposure to multiple deprivation cycles can partially overcome a genetic predisposition of NP, LAD-1, and LAD-2 rats for low alcohol consumption. In addition, the findings suggest that genetic control of low alcohol consumption in rats is not associated with the inability to display an ADE. [source] Acoustic Startle Reactivity During Acute Alcohol Withdrawal in Rats That Differ in Genetic Predisposition Toward Alcohol Drinking: Effect of Stimulus CharacteristicsALCOHOLISM, Issue 5 2004Julia A. Chester Abstract: Background: We have previously reported an association between greater alcohol withdrawal magnitude after a single alcohol exposure and a genetic predisposition toward low alcohol drinking in rats selectively bred for differences in alcohol intake when acoustic startle reactivity to a tone stimulus was used to index acute alcohol withdrawal. The purpose of this study was to examine whether the quality of the acoustic startle stimulus (noise versus tone) is important for detecting a genetic relationship between alcohol withdrawal magnitude and alcohol drinking behavior. Methods: Alcohol-naive male rats selectively bred for high alcohol intake [alcohol-preferring (P), high-alcohol-drinking (HAD)1, and HAD2] or low alcohol intake [alcohol-nonpreferring (NP), low-alcohol-drinking (LAD)1, and LAD2] received a single intragastric infusion of water or alcohol (4.0 g/20.3 ml/kg; 25% v/v), and acoustic startle test sessions were given at 14, 16, 18, 20, and 24 hr after infusion. Each test session consisted of a 5-min acclimation period followed by random presentation of various white noise stimuli (90, 100, 110, and 120 dB.) Results: Line differences in acoustic startle magnitude under control conditions were present in all three pairs of selectively bred lines; P rats showed a greater startle magnitude relative to NP rats, whereas both LAD lines showed a greater startle magnitude relative to both HAD lines. During alcohol withdrawal, the P, HAD1, and HAD2 lines showed enhanced startle magnitude compared with their water-treated controls. No change in startle magnitude during alcohol withdrawal was found in the NP, LAD1, or LAD2 lines. Conclusions: In contrast to our prior findings, these results showed a genetic association between high alcohol drinking and a greater startle response magnitude to a noise stimulus during alcohol withdrawal. It seems that the genetic association between alcohol drinking and alcohol withdrawal, as assessed by the acoustic startle response, depends on the quality of the acoustic startle stimulus. [source] The Expression of an Alcohol Deprivation Effect in the High,Alcohol-Drinking Replicate Rat Lines Is Dependent On Repeated DeprivationsALCOHOLISM, Issue 6 2000Zachary A. Rodd-Henricks Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high,alcohol-drinking (HAD) rats. Methods: Adult male HAD-1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations. Results: After the initial EtOH deprivation period, EtOH consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6 week groups) and in all deprived groups for the HAD-2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation. Conclusions: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE. [source] Norepinephrine Uptake Sites in the Locus Coeruleus of Rat Lines Selectively Bred for High and Low Alcohol Preference: A Quantitative Autoradiographic Binding Study Using [3H]-TomoxetineALCOHOLISM, Issue 5 2000Bang H. Hwang Background: The locus coeruleus (LC) is the largest norepinephrinergic cell group in the central nervous system and contains a high density of norepinephrine (NE) uptake sites. Alcohol-preferring (AP) rats and high,alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, whereas alcohol-nonpreferring (NP) rats and low,alcohol-drinking (LAD) rats are bred for low alcohol preference. However, it is unknown whether NE uptake sites in the LC are associated with alcohol preference in AP and HAD rats when compared with their respective control rats, NP and LAD rats. This study was designed to examine this question. Methods: Animals were decapitated and brains were removed, frozen with dry ice powder, and stored in a deep freezer. The LC tissue blocks were cut into 14 , cryostat sections, collected on glass slides, and incubated with 0.6 nM [3H]-tomoxetine in 50 mM Tris-HCl buffer system. For nonspecific binding, 1 ,M desipramine was added to the radioactive ligand. Sections were rinsed, quickly dried, and processed for quantitative autoradiography. In addition, galanin content in the LC was also studied. Results: The LC possessed a high density of [3H]-tomoxetine binding sites. There were fewer tomoxetine binding sites (fmol/mg protein) in the AP rats (433.0 ± 8.1) than in the NP rats (495.6 ± 3.7). HAD rats (386.5 ± 13.2) also possessed fewer tomoxetine binding sites than LAD rats (458.7 ± 10.1). Galanin content in the LC was similar between AP and NP rats and between HAD and LAD rats. Conclusions: Because both AP rats and HAD rats were selectively bred for alcohol preference, the finding of consistently low levels of [3H]-tomoxetine binding in the LC of these two lines of rats with high alcohol preference suggests that down-regulation of NE transporters in the LC of AP and HAD rats may be associated with alcohol-seeking behavior. A possible involvement of the coerulear NE uptake sites in depression is also discussed. Galanin in the LC may not relate to alcohol preference. [source] The Patient Health Questionnaire 12 Somatic Symptom scale as a predictor of symptom severity and consulting behaviour in patients with irritable bowel syndrome and symptomatic diverticular diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010R. C. Spiller Summary Background, Anxiety, depression and nongastrointestinal symptoms are often prominent in irritable bowel syndrome (IBS), but their relative value in patient management has not been quantitatively assessed. We modified the Patient Health Questionnaire 15 (PHQ-15) by excluding three gastrointestinal items to create the PHQ-12 Somatic Symptom (PHQ-12 SS) scale. Aims, To compare the value of the PHQ-12 SS scale with the Hospital Anxiety and Depression (HAD) scale in predicting symptoms and patient behaviour in IBS and diverticular disease. Methods, We compared 151 healthy volunteers (HV), 319 IBS patients and 296 patients with diverticular disease (DD), 113 asymptomatic [ASYMPDD] and 173 symptomatic DD (SYMPDD). Results, Patient Health Questionnaire 12 SS scores for IBS and SYMPDD were significantly higher than HV. Receiver,operator curves showed a PHQ-12 SS >6, gave a sensitivity for IBS of 66.4% with a specificity of 94.7% and a positive likelihood ratio (PLR) = 13.2, significantly better than that associated with an HAD anxiety score >7, PLR = 3.0 and depression score >7 PLR = 6.5. PHQ-12 SS correlated strongly with IBS severity scale and GP visits in both IBS and DD. Conclusion, The PHQ-12 SS scale is a useful clinical tool which correlates with patient behaviour in both IBS and symptomatic DD. [source] Depression and Anxiety Status of Patients with Implantable Cardioverter Defibrillator and Precipitating FactorsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2006AHMET KAYA BILGE Background: Implantable cardioverter defibrillators (ICDs) are life-saving devices in treatment of life-threatening arrhythmia. We evaluate the emotional status of Turkish patients with ICD and try to explain factors that affect emotional status of the patients. Methods: Ninety-one patients with previously implanted ICD were included in the study. Follow-up periods, presence of ICD shock, shock frequency, time of the recent shock, age, and gender were noted. Depression and anxiety scores were evaluated according to Hospital Anxiety and Depression (HAD) chart. Results: Mean anxiety and depression scores were found as 9.1 ± 5.3 and 7.2 ± 5.1, respectively. According to HAD charts, 42 patients (46%) had anxiety and 37 patients (41%) had depression. Depression scores indicated significant difference between subgroups divided on the basis of follow-up periods (P = 0.026) and on the basis of time of recent shock (P = 0.028). There was significant difference in anxiety scores (P = 0.016) between patients with ICD shocks and patients with no shocks. When the patients were divided into subgroups according to shock frequency, both depression (P = 0.024) and anxiety (P = 0.016) scores presented significant difference. In female patients, depression and anxiety scores were found significantly higher compared to male patients (P = 0.046 and P = 0.016, respectively). In multivariate analysis, gender and shock frequency were found as predictors for anxiety scores (P = 0.019 and P = 0.044, respectively). However same analysis revealed no predictive factor for depression score. Conclusion: Our study indicates presence of depression and anxiety in nearly half of the patients with ICD. Consultation with psychiatry should be a part of the treatment for patients with ICD, especially for those who constitute high-risk groups. [source] Pessimism as a predictor of emotional morbidity one year following breast cancer surgeryPSYCHO-ONCOLOGY, Issue 5 2004I. Schou The prevalence of and predictive factors for emotional morbidity (measured by the Hospital Anxiety and Depression Scale (HAD)) one year following surgery, with special focus on dispositional optimism/pessimism (measured by the Life Orientation Test (LOT-R), was examined in 165 women, newly diagnosed with breast cancer. Patients characteristics, appraisal of cancer diagnosis, beliefs about treatment efficacy, treatment decision-making participation, coping and emotional morbidity was assessed by self-rating questionnaires. Prevalence of anxiety and depression cases at time of diagnosis was 34 and 12%, respectively, and 26 and 9% after one year. Prevalence of emotional morbidity was significantly enlarged among pessimists at all assessments. Pessimism was the strongest predictor for anxiety (OR: 0.86 C.I. 95% 0.77 , 0.95) and depression (OR: 0.83, C.I. 95% 0.73 , 0.95) one year following breast cancer surgery. Optimists and pessimists differed not only in regard to coping styles, but also in regards to predictors of emotional morbidity. Optimists experiencing anxiety at time of breast cancer diagnosis had about six times higher risk of experiencing anxiety after one year, compared to optimists without preoperative anxiety. For pessimists, the more pessimistic one was about one's overall future the higher risk for developing anxiety following one year of breast cancer surgery. Pessimists, who endorse helpless/hopeless coping style when receiving a diagnosis of breast cancer, had three times greater risk for experiencing depression one year after breast cancer surgery, than pessimists who did not. Health care professionals should therefore provide intervention for pessimists, as well as for patients with high anxiety scores at time of diagnosis. Copyright © 2003 John Wiley & Sons, Ltd. [source] Daily assessment of coping in patients with gastrointestinal cancerPSYCHO-ONCOLOGY, Issue 1 2002Elisabet Wasteson Ninety-five patients with gastrointestinal (GI) cancer participated in a study concerning stressful events, coping and emotional well-being. Participants were either potentially cured (n=62) after radical surgery or non-cured (n=33). For a period of 1 week, close to being informed about their diagnosis, they performed daily recordings of stressful events, the distress occasioned by these events and their perception of control over them, coping, worry and happiness/sadness. Anxiety and depression were assessed by a single retrospective assessment at the end of the week (Hospital Anxiety and Depression (HAD) scale). The most commonly recorded stressful events were ,Somatic aspects' and ,Everyday concerns'. ,Somatic aspects', ,Social aspects' and ,Other consequences of the disease' were rated as most bothersome. Patients perceived that they had the highest degree of control over ,Returning home after hospital stay', whereas ,Contact with the medical services' was assigned low control. The most commonly used coping strategies were ,Acceptance' and ,Relaxation', and the least used was ,Religion'. Significant positive correlations between the occurrence of stressful events and the use of coping strategies were demonstrated between ,Somatic Aspects' and ,Acceptance'/,Direct Action', and between ,Social Aspects' and ,Seeking Social Support'. Daily assessment of stress-coping relationships represents a promising approach to the understanding of adaptation among cancer patients. Copyright © 2002 John Wiley & Sons, Ltd. [source] Bacterial hydrolytic dehalogenases and related enzymes: Occurrences, reaction mechanisms, and applicationsTHE CHEMICAL RECORD, Issue 2 2008Tatsuo Kurihara Abstract Dehalogenases catalyze the cleavage of the carbon,halogen bond of organohalogen compounds. They have been attracting a great deal of attention partly because of their potential applications in the chemical industry and bioremediation. In this personal account, we describe occurrences, reaction mechanisms, and applications of bacterial hydrolytic dehalogenases and related enzymes, particularly L -2-haloacid dehalogenase, DL -2-haloacid dehalogenase, fluoroacetate dehalogenase, and 2-haloacrylate reductase. L -2-Haloacid dehalogenase is a representative enzyme of the haloacid dehalogenase (HAD) superfamily, which includes the P-type ATPases and other hydrolases. Structural and mechanistic analyses of this enzyme have yielded important insights into the mode of action of the HAD superfamily proteins. Fluoroacetate dehalogenase is unique in that it catalyzes the cleavage of the highly stable CF bond of a fluorinated aliphatic compound. In the reactions of L -2-haloacid dehalogenase and fluoroacetate dehalogenase, the carboxylate group of Asp performs a nucleophilic attack on the ,-carbon atom of the substrate, displacing the halogen atom. This mechanism is common to haloalkane dehalogenase and 4-chlorobenzoyl-CoA dehalogenase. DL -2-Haloacid dehalogenase is unique in that a water molecule directly attacks the substrate, displacing the halogen atom. The occurrence of 2-haloacrylate reductase was recently reported, revealing a new pathway for the degradation of unsaturated aliphatic organohalogen compounds. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 67,74; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20141 [source] Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondriaTHE JOURNAL OF PHYSIOLOGY, Issue 6 2008Carley R. Benton Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPAR, agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day,1) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and ,-hydroxyacyl CoA dehydrogenase (,-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle (P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities (P > 0.05) were not altered. Similarly, citrate synthase (CS) and ,-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria (P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria. [source] The prevalence and related risk factors of anxiety and depression symptoms among Chinese pregnant women in ShanghaiAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Yong-Xia QIAO Objective: To investigate the prevalence of anxiety and depression of the pregnant women during the prenatal period, and provide information for further epidemiological study. Methods: With ethics committee approval, a total of 527 recruited pregnant women from the Department of Obstetrics and Gynecology, Tongji University Medical School were selected at four hospitals that affiliated to the University. By applying a self-designed questionnaire for hospital anxiety and depression (HAD) scale, we evaluated anxious and depressive symptoms in these women. Results: The prevalence rates of anxiety and depression in these Chinese pregnant women during prenatal period were 6.8% and 4.8%, respectively, whereas the co-prevalence rate of both anxiety and depression was 3.4%, and anxiety and/or depression 15.0%. The relationship between the prevalence rate of anxiety/depression and the age distribution was proven negatively correlated (,2 = 1.478, P = 0.016) by the trend chi-squared test. Among all three groups, the prevalence rate of anxiety and depression was highest in the group of below 20 years old, lowest in the group of over 30 years old, and in-between in the group of 20 to 30 years old. Logistic regression analysis showed that lower age was a risk factor (odds ratio (OR) = 10.094, 95% confidence interval (CI): 1.418~71.838). Meanwhile, poor educational background (OR = 1.929, 95%CI: 1.101~3.379) was a relevant risk factor as well. Conclusions: We suggest that introduction of psychological health instruction programs for pregnant women, especially the younger ones, should be strengthened. Besides, the essential intervention measures may be applied if necessary. [source] Structure of a putative ,-phosphoglucomutase (TM1254) from Thermotoga maritimaACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 12 2009Richard W. Strange The structure of TM1254, a putative ,-phosphoglucomutase from T. maritima, was determined to 1.74,Å resolution in a high-throughput structural genomics programme. Diffraction data were obtained from crystals belonging to space group P22121, with unit-cell parameters a = 48.16, b = 66.70, c = 83.80,Å, and were refined to an R factor of 19.2%. The asymmetric unit contained one protein molecule which is comprised of two domains. Structural homologues were found from protein databases that confirmed a strong resemblance between TM1254 and members of the haloacid dehalogenase (HAD) hydrolase family. [source] Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjectsCLINICAL ENDOCRINOLOGY, Issue 1 2003I. A. Malik Summary objective There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. patients and methods A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). results Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36·0 ± 26·4 (range 13,159) months. Mean age was 43·9 ± 15·8 years (37 males) in treated GHD patients compared to a mean age 41·7 ± 10·5 years (32 males) in the controls. Mean IGF-1 levels were 22·5 ± 13·6 nmol/l in the GHD patients and the mean dose of GH replacement was 1·2 ± 0·4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P , 0·0001, except life fulfilment-material, P = 0·33) compared to the control population. conclusions This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes). [source] Synthesis,Structure,Property Relationships for Hyperbranched Aminosilica CO2 AdsorbentsADVANCED FUNCTIONAL MATERIALS, Issue 23 2009Jeffrey H. Drese Abstract Hyperbranched aminosilica (HAS) adsorbents are prepared via the ring-opening polymerization of aziridine in the presence of mesoporous silica SBA-15 support. The aminopolymers are covalently bound to the silica support and capture CO2 reversibly in a temperature swing process. Here, a range of HAS materials are prepared with different organic loadings. The effects of organic loading on the structural properties and CO2 adsorption properties of the resultant hybrid materials are examined. The residual porosity in the HAS adsorbents after organic loading, as well as the molecular weights and degrees of branching for the separated aminopolymers, are determined to draw a relationship between adsorbent structure and performance. Humid adsorption working capacities and apparent adsorption kinetics are determined from experiments in a packed-bed flow system monitored by mass spectrometry. Dry adsorption isotherms are presented for one HAS adsorbent with a high amine loading at 35 and 75,°C. These combined results establish the relationships between adsorbent synthesis, structure, and CO2 adsorption properties of the family of HAS materials. [source] Effect of recombinant factor VIIa variant (NN1731) on platelet function, clot structure and force onset time in whole blood from healthy volunteers and haemophilia patientsHAEMOPHILIA, Issue 5 2007D. F. BROPHY Summary., NN1731 is a novel variant of recombinant factor VIIa (rFVIIa) that binds to activated platelets, but has greater enzymatic activity than rFVIIa in generating FXa and thrombin. The effect of NN1731 on clot structure and platelet function was characterized ex vivo in whole blood from healthy volunteers and haemophilic patients. Blood samples from six healthy volunteers, nine haemophilia A patients with and without inhibitors and one acquired haemophilia A patient, were spiked with increasing concentrations (0.32, 0.64 and 1.28 ,g mL,1) of rFVIIa and NN1731. Platelet contractile force (PCF) or platelet function, clot elastic modulus (CEM) or clot structure, and force onset time (FOT) or the thrombin generation time (TGT) were determined using the Hemodyne Hemostasis Analysis System (HASÔ). Baseline PCF, CEM and FOT values in patients were abnormal compared to healthy volunteers' baseline values. Overall, haemophilia blood samples with or without inhibitors spiked with NN1731 had significantly greater PCF, CEM and shorter FOT values relative to samples spiked with corresponding doses of rFVIIa. The variability in response to treatment between patients was greater with rFVIIa compared to NN1731. At 1.28 ,g mL,1 (90 ,g kg,1), NN1731 normalized PCF, CEM and FOT in nine of 10 patients, while rFVIIa normalized these parameters in four of 10 patients. Increasing in vitro concentrations of NN1731 normalized platelet function, clot structure and thrombin generation consistently in haemophilia blood with or without inhibitors. NN1731 may be a promising haemostatic agent for patients with bleeding disorders. These results should be confirmed in an in vivo study. [source] Routine intraoperative Doppler sonography in the evaluation of complications after living-related donor liver transplantationJOURNAL OF CLINICAL ULTRASOUND, Issue 9 2007Jin-Young Choi MD Abstract Purpose To determine whether quantitative and qualitative analysis of intraoperative Doppler sonography data are predictive of vascular complications after living-related donor liver transplantation. Methods Intraoperative sonograms of 81 transplanted livers (right lobe in 61 patients, left lobe in 20 patients) were analyzed for the presence of blood flow, resistance index, systolic acceleration time (SAT), peak systolic velocity, and morphologic characteristics of spectral waveform of the hepatic artery. Peak velocity and spectral waveforms of portal and hepatic veins were also analyzed. Intraoperative sonography results were compared with information obtained with multidetector-row CT (MDCT) angiography or conventional angiography. The time interval between operation and angiography ranged from 1 to 23 days (mean, 8.5 days). Results Hepatic artery stenosis (HAS) was identified in 20 patients via MDCT angiography, conventional angiography, or both. The Doppler parameters found helpful for predicting HAS were tardus-parvus pattern and delayed SAT. The sensitivity, specificity, and negative predictive value (NPV) were 60.0%, 73.7%, and 84.9%, respectively, for tardus-parvus pattern and 40.0%, 83.6%, and 80.9%, respectively, for delayed SAT. Peak velocities of the portal and hepatic veins were not reliable indicators of vascular complication. Loss of triphasity of the hepatic vein had a 98.4% NPV for venous obstruction. Conclusions Delayed SAT of the hepatic artery and loss of triphasity of the hepatic vein had a >80% for specificity for predicting vascular complications. Tardus-parvus pattern, delayed SAT of the hepatic artery, and loss of triphasity of the hepatic vein showed an acceptable NPV for identifying vascular complications. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007 [source] Aqueous Colloidal Processing of ZTA CompositesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 1 2009Susana M. Olhero Two different zirconia-alumina composites, ZTA-30 (70 wt% Al2O3+30 wt% ZrO2) and ZTA-60 (40 wt% Al2O3+60 wt% ZrO2), with potential for orthopedic applications, were processed in aqueous media and consolidated by slip casting (SC), hydrolysis-assisted solidification (HAS), and gelcasting (GC) from suspensions containing 50 vol% solids loading. For comparison purposes, the same ceramic compositions were also consolidated by die pressing of freeze-dried granules (FG). In the HAS process, 5 wt% of Al2O3 in the precursor mixture was replaced by equivalent amounts of AlN to promote the consolidation of the suspensions. Ceramics consolidated via GC exhibited higher green (three-point bend) strengths (,17 MPa) than those consolidated by other techniques. Further, these ceramics also exhibited superior fracture toughness and flexural strength properties after sintering for 1 h at 1600°C in comparison with those consolidated by other techniques, including conventional die pressing (FG). [source] Analytical Electron Microscopy Study of Green Ceramics Formed from Aqueous Suspensions Using the Hydrolysis-Assisted Solidification ProcessJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 1 2002a Novak During the hydrolysis-assisted solidification (HAS) of aqueous ceramic suspensions, aluminum hydroxides are formed that bind the ceramic particles into a stiff wet body. Transmission electron microscopy investigations of HAS-processed Al2O3 and ZrO2 green parts after drying revealed that the secondary phase is amorphous and distributed uniformly around the host ceramic particles. The estimated thickness of this layer was 3,5 nm. Moreover, areas of a few tens of nanometers in size were found at three-particle junctions that contained an amorphous phase and individual nanocrystals of boehmite. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 84JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003V Donadio The aim of the study is to determine the site of autonomic lesion in a patient with Holmes-Adie Syndrome (HAS) who subsequently developed generalized anhydrosis. We describe a 38-year-old woman who from age 33 showed a right pupil larger than the left and from age 34 complained of focal and, a year later, generalized anhydrosis. Neurological examination showed absent tendon reflexes and right mydriatic pupil. Brain MRI, EEG, motor and sensory conduction studies were normal. Serologic screening for autoimmune disease was negative. To determine the site of the autonomic lesion the patient underwent the following investigations: pupillary tests with a diluted solution of pilocarpine (0.062%) and adrenaline (0.1%); cardiovascular reflexes; thermoregulatory sweat test (TST); circadian rhythm of body core temperature (CRT°); sympathetic skin response (SSR); microneurography recording of skin sympathetic activity (SSA) from median and peroneal nerves, and muscle sympathetic activity (MSA) from peroneal nerve; skin biopsy to evaluated the eccrine glands. Pupillary tests showed postganglionic parasympathetic and sympathetic denervation only of the right pupil. TST showed complete anhydrosis, SSR and SSA were absent and skin biopsy revealed normal morphology of the eccrine glands with hypotrophy of their structures. These results indicated a lesion of the postganglionic skin sympathetic fibers. Mechanisms for heat loss and conservation, cardiovascular reflexes and MSA were normal excluding a hypothalamic dysfunction or a more diffuse involvement of the autonomic nervous system. In conclusion, our patient showed a HAS associated with generalized anhydrosis and the autonomic investigations suggested underlying postganglionic parasympathetic and sympathetic autonomic lesions. [source] Exploitation of the complex chemistry of hindered amine stabilizers in effective plastics stabilization,JOURNAL OF VINYL & ADDITIVE TECHNOLOGY, Issue 3 2007J. Pospí Hindered amine stabilizers (HAS) remain a prominent class of stabilizers having a fortunate development with continuous interest in shaping the future properties of plastics: increase in polymer durability, application extension, reaching new effects. Commercial tests provided much information. Insufficient mechanistic interpretations of the complex effects of environmental factors (harshness of testing, penetration of radiation and oxygen, superposition of temperature, atmospheric impurities) and those of the microenvironment (morphology of the polymer matrix, physical relations of HAS,polymer, interference between HAS and other additives) are a drawback. Model experiments complement commercial studies and explain some phenomena. A careful transfer of information from model experiments must be done to avoid misinterpretation of mechanisms, particularly of the HAS regenerative cycle. A critical analysis of primary steps of the HAS activity mechanism in the polymer matrix based on HAS-related primary nitroxides, formation of their stationary concentration and concentration gradients influenced by polymer morphology, spatial competition between autoreactions, and oxidation of polymer-developed alkyl radicals and their scavenging by nitroxides (the key process of HAS efficiency) is outlined. Cyclic regeneration of nitroxides affected by the structure of the amino moiety in the HAS molecule, influence of acid environment, atmospheric ozone or singlet oxygen, cooperative mixtures of HAS with UV absorbers, combinations with additives increasing the thermal stabilization effect and improving color retention, assessment of the heat stabilization performance of HAS by proper testing, and influence of the molecular weight of HAS are mentioned together with examples of the chemical consumption of HAS in the final phases of their lifetime. lifetime. J. VINYL ADDIT. TECHNOL., 13:119,132, 2007. © 2007 Society of Plastics Engineers [source] Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their componentsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2006Daniela Carulli Abstract The decrease in plasticity that occurs in the central nervous system during postnatal development is accompanied by the appearance of perineuronal nets (PNNs) around the cell body and dendrites of many classes of neuron. These structures are composed of extracellular matrix molecules, such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan (HA), tenascin-R, and link proteins. To elucidate the role played by neurons and glial cells in constructing PNNs, we studied the expression of PNN components in the adult rat cerebellum by immunohistochemistry and in situ hybridization. In the deep cerebellar nuclei, only large excitatory neurons were surrounded by nets, which contained the CSPGs aggrecan, neurocan, brevican, versican, and phosphacan, along with tenascin-R and HA. Whereas both net-bearing neurons and glial cells were the sources of CSPGs and tenascin-R, only the neurons expressed the mRNA for HA synthases (HASs), cartilage link protein, and link protein Bral2. In the cerebellar cortex, Golgi neurons possessed PNNs and also synthesized HASs, cartilage link protein, and Bral2 mRNAs. To see whether HA might link PNNs to the neuronal cell surface by binding to a receptor, we investigated the expression of the HA receptors CD44, RHAMM, and LYVE-1. No immunolabelling for HA receptors on the membrane of net-bearing neurons was found. We therefore propose that HASs, which can retain HA on the cell surface, may act as a link between PNNs and neurons. Thus, HAS and link proteins might be key molecules for PNN formation and stability. J. Comp. Neurol. 494:559,577, 2006. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||