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Increased Vulnerability (increased + vulnerability)
Selected AbstractsComorbidity and mixed anxiety-depressive disorder: clinical curiosity or pathophysiological need?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2001Hans-Ulrich Wittchen Abstract The paper reviews available epidemiological evidence for the existence of and the implications of comorbidity of anxiety and depressive disorders and mixed anxiety,depressive (MAD) disorders. Using epidemiolological evidence of prevalence and incidence and data relating to time-course of illness, risk factor and outcome, it is concluded: (1) that anxiety,depression comorbidity is quite frequent in epidemiological and clinical settings throughout the world; (2) this comorbidity is diagnosis-specific and is associated with increased vulnerabilities and risks as well as poorer outcome and marked disabilities; and (3) no such evidence was found for MAD disorders. Contrary to what was predicted, the prevalence of MAD disorders was quite low even when using the more recent criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. (4) Furthermore, there was quite a heterogeneous pattern in terms of risk, severity and outcome making it questionable whether this disorder, as currently defined, is a clinical entity. These findings are discussed in terms of two perspectives, the ,lumpers' with their dimensional view and the ,splitters' with their categorical view. It is concluded that although comorbidity of threshold anxiety and depressive disorders seems to be an important phenomenon, no such evidence is provided for MAD disorders. Copyright © 2001 John Wiley & Sons, Ltd. [source] Age Differences in the Responses to Adult and Juvenile Alarm Calls by Bonnet Macaques (Macaca radiata)ETHOLOGY, Issue 2 2000Uma Ramakrishnan This study examined the differential responses to alarm calls from juvenile and adult wild bonnet macaques (Macaca radiata) in two parks in southern India. Field studies of several mammalian species have reported that the alarm vocalizations of immature individuals are often treated by perceivers as less provocative than those of adults. This study documents such differences in response using field-recorded playbacks of juvenile and adult alarm vocalizations. To validate the use of playback vocalizations as proxies of natural calls, we compared the responses of bonnet macaques to playbacks of alarm vocalizations with responses engendered by natural alarm vocalizations. We found that the frequency of flight, latency to flee, and the frequency of scanning to vocalization playbacks and natural vocalizations were comparable, thus supporting the use of playbacks to compare the effects of adult and juvenile calls. Our results showed that adult alarm calls were more provocative than juvenile alarm calls, inducing greater frequencies of flight with faster reaction times. Conversely, juvenile alarm calls were more likely to engender scanning by adults, a result interpreted as reflecting the lack of reliability of juvenile calls. Finally, we found age differences in flight behavior to juvenile alarm calls and to playbacks of motorcycle engine sounds, with juveniles and subadults more likely to flee than adults after hearing such sounds. These findings might reflect an increased vulnerability to predators or a lack of experience in young bonnet macaques. [source] PRECLINICAL STUDY: Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthoodADDICTION BIOLOGY, Issue 3 2009Gabriela C. Santos ABSTRACT Nicotine and psychostimulants are often abused in combination and drug abuse often begins during adolescence and can have long-term consequences. Behavioral sensitization has been suggested as an animal model of neuroplasticity implicated in the development of drug addiction. We evaluated whether the pretreatment with nicotine (0.4 mg/kg; s.c.) or amphetamine (5.0 mg/kg; i.p.) in adolescent rats [from postnatal day (P) 28 to P34] could induce cross-sensitization to nicotine and amphetamine when animals were challenged during both adolescence (P37) and adulthood (P70), in separate groups of animals. Adolescent animals pretreated with amphetamine displayed behavioral sensitization to nicotine, which persisted until adulthood. Moreover, adolescent animals pretreated with nicotine showed sensitized locomotor response to amphetamine in the adulthood. These data suggest that adolescents who abuse nicotine may be particularly susceptible to the effects of amphetamine and vice versa. Moreover, this increased vulnerability may persist through their development until adulthood. [source] Prenatal restraint stress differentially modifies basal and stimulated dopamine and noradrenaline release in the nucleus accumbens shell: an ,in vivo' microdialysis study in adolescent and young adult ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Alessandra Silvagni Abstract Gestational stress [prenatal stress (PNS)] has been associated with low birth weight, preterm delivery, and higher vulnerability to psychiatric disorders such as schizophrenia, depression or attention deficit with hyperactivity disorder. The alteration of catecholamine transmission has been attributed a major role in the etiology of psychiatric disturbances. We investigated the effect of PNS on basal and stimulated dopamine and noradrenaline output in the nucleus accumbens of freely moving adolescent and young adult rats (30,35 and 60,70 postnatal days respectively) because of the importance of this area in drug dependence and possibly in psychiatric disorders that are treated with drugs that act on dopamine and noradrenaline transmission. Stimulation was obtained with intraperitoneal amphetamine (0.25 mg/kg) or subcutaneous nicotine (0.4 mg/kg). The results showed the following: (i) basal and amphetamine-stimulated dopamine output in adolescent and adult PNS rats is higher than in controls; (ii) nicotine-stimulated dopamine output is lower than in controls in adolescent but not in adult PNS rats; (iii) basal noradrenaline output is lower than in controls in adolescent but not in adult PNS rats; (iv) amphetamine-stimulated noradrenaline output is higher than in controls in adult but not in adolescent PNS rats; (v) nicotine-stimulated noradrenaline output in PNS rats is higher than in controls, although only in adults. These results show that PNS may produce a complex change in accumbal dopamine and noradrenaline transmission. We discuss the possibility that these changes might be correlated with the development of psychiatric disorders or with an increased vulnerability to drug addiction. [source] Differential responses to NMDA receptor activation in rat hippocampal interneurons and pyramidal cells may underlie enhanced pyramidal cell vulnerabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005E. Avignone Abstract Hippocampal interneurons are generally more resistant than pyramidal cells to excitotoxic insults. Because NMDA receptors play a crucial role in neurodegeneration, we have compared the response to exogenous NMDA in CA1 pyramidal cells and interneurons of the stratum oriens using combined whole-cell patch-clamp recording and ratiometric Ca2+ imaging. In voltage-clamp, current-clamp or in nominally Mg2+ -free medium, NMDA (10 µm; 3,5 min exposure in the presence of tetrodotoxin) induced a markedly larger inward current and Ca2+ rise in pyramidal cells than in interneurons. Pyramidal cells also showed a more pronounced voltage dependence in their response to NMDA. We hypothesized that this enhanced response to NMDA receptor activation in pyramidal cells could underlie their increased vulnerability to excitotoxicity. Using loss of dye as an indicator of degenerative membrane disruption, interneurons tolerated continuous exposure to a high concentration of NMDA (30 µm) for longer periods than pyramidal cells. This acute neurodegeneration in pyramidal cells was independent of intracellular Ca2+, because high intracellular BAPTA (20 mm) did not prolong survival time. Thus, a plausible explanation for the enhanced sensitivity of pyramidal neurons to excitotoxic insults associated with cerebral ischemia is their greater response to NMDA receptor activation, which may reflect differences in NMDA receptor expression and/or subunit composition. [source] The acute-phase response impairs host defence against Enterococcus faecium peritonitisIMMUNOLOGY, Issue 1pt2 2009Masja Leendertse Summary Enterococcus faecium is an emerging pathogen that causes infections in hospitalized patients with various co-morbid diseases. These underlying diseases are often associated with an acute-phase response that renders patients vulnerable to nosocomial infections. To study the influence of the acute-phase response induced by sterile tissue injury on host defence against E. faecium, mice were injected subcutaneously with either turpentine or casein 1 day before intraperitoneal infection with E. faecium. Control mice were subcutaneously injected with saline or sodium bicarbonate, respectively. Turpentine and casein induced an acute-phase response as reflected by increases in the plasma concentrations of interleukin-6, serum amyloid P and C3. A pre-existent acute-phase response in mice was associated with a strongly reduced capacity to clear E. faecium, resulting in prolonged bacteraemia for several days. The inflammatory response to E. faecium was impaired in mice with an acute-phase response, as shown by reduced capacity to mount a neutrophilic leucocytosis in peripheral blood and by decreased local cytokine concentrations. These data indicate that the acute-phase response impairs host defence against E. faecium, suggesting that this condition may contribute to the increased vulnerability of critically ill patients to enterococcal infections. [source] Attenuated apoptosis response to Fas-ligand in active ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 12 2008Jakob B. Seidelin MD Abstract Background: From mainly carcinoma cell line studies, apoptosis has been thought to play a major role in the pathogenesis of ulcerative colitis (UC). Apoptosis has been suggested to be due to a Fas ligand / Fas receptor interaction, but has never been studied in cells from patients with active UC. The aim was to investigate both the spontaneous and the cell death receptor ligand-induced apoptosis in UC. Methods: Twenty patients with UC and 16 control subjects who underwent routine colonoscopy either for the control or surveillance of their disease or where the diagnosis of irritable bowel syndrome was subsequently reached were included. Cultures of isolated colonic crypts were obtained from biopsies and cultured for 4 to 16 hours with Fas ligand or Fas ligand and costimulation with interferon-, (IFN-,). Control experiments were performed on HT29 cells. Apoptosis was assessed by independent methods. Results: Isolated colonocytes from healthy subjects or patients with remission in UC had a dose-dependent response to Fas ligand. This response was abolished in patients with active UC (P < 0.002), and costimulation with IFN-, did not alter this response. Patients with active UC had an increased apoptosis rate of 9.5% compared with controls (P < 0.05). Conclusions: The current study indicates that colonocytes do not respond to cytokine exposure and inflammation by an increased vulnerability, as previously thought. Colonocytes seem to activate cytoprotective programs in response to inflammation. Apart from supporting the regeneration process during inflammation, this response could additionally cause an increased susceptibility to neoplastic transformation. (Inflamm Bowel Dis 2008) [source] What are the high risk periods for incident substance use and transitions to abuse and dependence?INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue S1 2008Implications for early intervention, prevention Abstract Background: For a better understanding of the evolution of addictive disorders and the timely initiation of early intervention and prevention, we have to learn when and how quickly the critical transitions from first substance use (SU) to regular use and from first SU and regular SU to abuse and dependence occur. Little data are currently available on the transitions to substance use disorders (SUDs) across the spectrum of legal and illegal drugs taking into account gender differences. It is the aim of this paper to describe the high density incidence and transition periods of SU and SUD for alcohol, nicotine, cannabis and other illicit drugs for young males and females. Methods: A sample of (N = 3021) community subjects aged 14,24 at baseline were followed-up prospectively over 10-years. SU and SUD were assessed using the DSM-IV/M-CIDI. Results: Ages 10,16 are the high risk period for first alcohol and nicotine use (up to 38% of subjects start before age 14). Onset of illegal SU occurs later. Substantial proportions of transitions to regular SU and SUD occur in the first three years after SU onset. Only few gender differences were found for time patterns of SU/SUD incidence and transition. Conclusion: Except for alcohol the time windows for targeted intervention to prevent progression to malignant patterns in adolescence are critically small, leaving little time for targeted intervention to prevent transition. The fast transitions to abuse and dependence in adolescence may be indicative for the increased vulnerability to substance effects in this time period. Basic research on the determinants of transitions should thus target this period in adolescence. Copyright © 2008 John Wiley & Sons, Ltd. [source] Characterization of the Electroanatomical Substrate in Human Atrial Fibrillation: The Relationship between Changes in Atrial Volume, Refractoriness, Wavefront Propagation Velocities, and AF BurdenJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2007PIPIN KOJODJOJO M.R.C.P. Introduction: Progressive remodeling occurs in experimental models of AF whereby slowing of conduction, shortening of refractoriness, and atrial dilatation are associated with an increased vulnerability to atrial fibrillation (AF). This study investigates the relative changes in atrial geometry and electrophysiology with increasing AF burden in humans. Methods and Results: Patients undergoing ablation of AF or left-sided accessory pathways were recruited. Atrial volumes were determined by echocardiography. Wavefront propagation velocities (WPV), specifically in the direction of activation, were calculated from pre-ablation activation (CartoŌ) maps of both atria. Dispersion, adaptation of, and effective refractoriness (ERP) were measured at 3 sites. A composite arrhythmogenic index (Atrial Volume/WPV × ERP) was derived to compare the degree of electroanatomical remodeling with AF burden. Fifty-nine patients (22 paroxysmal AF, 19 recurrent persistent AF, and 18 controls) were recruited. AF subjects had slower right atrial WPV (P = 0.01), but no difference in left atrial WPV compared with controls. ERP was reduced globally (P < 0.05), with increased dispersion (P < 0.05). WPV and ERP did not distinguish between patients with paroxysmal or persistent AF. Biatrial volumes were greater only in patients with persistent AF (P < 0.01). There was a stepwise increase in the AI with increasing AF burden (P < 0.0001). Conclusion: An arrhythmogenic substrate exists in human AF, characterized by globally decreased refractoriness with greater dispersion, slower right atrial conduction, and atrial dilatation. Persistence of AF is not accompanied by any further electrical remodeling, but only atrial dilatation. The degree of electroanatomical remodeling is associated with the clinical pattern of AF. [source] Chronic exposure to sub-lethal beta-amyloid (A,) inhibits the import of nuclear-encoded proteins to mitochondria in differentiated PC12 cells*JOURNAL OF NEUROCHEMISTRY, Issue 5 2007Daniel Sirk Abstract Studies on amyloid beta (A,|), the peptide thought to play a crucial role in the pathogenesis of Alzheimer's disease, have implicated mitochondria in A,-mediated neurotoxicity. We used differentiated PC12 cells stably transfected with an inducible green fluorescent protein (GFP) fusion protein containing an N,-terminal mitochondrial targeting sequence (mtGFP), to examine the effects of sub-lethal A, on the import of nuclear-encoded proteins to mitochondria. Exposure to sub-lethal A,25,35 (10 ,mol/L) for 48 h inhibited mtGFP import to mitochondria; average rates decreased by 20 ± 4%. Concomitant with the decline in mtGFP, cytoplasmic mtGFP increased significantly while mtGFP expression and intramitochondrial mtGFP turnover were unchanged. Sub-lethal A,1,42 inhibited mtGFP import and increased cytoplasmic mtGFP but only after 96 h. The import of two endogenous nuclear-encoded mitochondrial proteins, mortalin/mtHsp70 and Tom20 also declined. Prior to the decline in import, mitochondrial membrane potential (mmp), and reactive oxygen species levels were unchanged in A,-treated cells versus reverse phase controls. Sustained periods of decreased import were associated with decreased mmp, increased reactive oxygen species, increased vulnerability to oxygen-glucose deprivation and altered mitochondrial morphology. These findings suggest that an A,-mediated inhibition of mitochondrial protein import, and the consequent mitochondrial impairment, may contribute to Alzheimer's disease. [source] Delay Discounting Behavior and White Matter Microstructure Abnormalities in Youth With a Family History of AlcoholismALCOHOLISM, Issue 9 2010Megan M. Herting Background:, Youth with family history of alcohol abuse have a greater risk of developing an alcohol use disorder (AUD). Brain and behavior differences may underlie this increased vulnerability. The current study examined delay discounting behavior and white matter microstructure in youth at high risk for alcohol abuse, as determined by a family history of alcoholism (FH+), and youth without such family history (FH,). Methods:, Thirty-three healthy youth (FH+ = 15, FH, = 18), ages 11 to 15 years, completed a delay discounting task and underwent diffusion tensor imaging. Tract-based spatial statistics (Smith et al., 2006), as well as follow-up region-of-interest analyses, were performed to compare fractional anisotropy (FA) between FH+ and FH, youth. Results:, FH+ youth showed a trend toward increased discounting behavior and had significantly slower reaction times (RTs) on the delay discounting paradigm compared to FH, youth. Group differences in FA were seen in several white matter tracts. Furthermore, lower FA in the left inferior longitudinal fasciculus and the right optic radiation statistically mediated the relationship between FH status and slower RTs on the delay discounting task. Conclusions:, Youth with a family history of substance abuse have disrupted white matter microstructure, which likely contributes to less efficient cortical processing and may act as an intrinsic risk factor contributing to an increased susceptibility of developing AUD. In addition, FHP youth showed a trend toward greater impulsive decision making, possibly representing an inherent personal characteristic that may facilitate substance use onset and abuse in high-risk youth. [source] Prenatal Alcohol Exposure and Chronic Mild Stress Differentially Alter Depressive- and Anxiety-Like Behaviors in Male and Female OffspringALCOHOLISM, Issue 4 2010Kim G. C. Hellemans Background:, Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neurobehavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods:, Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitum-fed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and/or anxiety-like behaviors. Results:, We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of "behavioral despair" in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions:, These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. [source] Individual Differences in Alcohol Drinking Frequency Are Associated With Electrophysiological Responses to Unexpected NonrewardsALCOHOLISM, Issue 4 2010Ingmar H. A. Franken Background:, It has been suggested that alcohol use is related to sensitivity of the reward system. Although there are several studies using self-reported measures supportive of this notion, objective biological data in humans on this issue are lacking. Aims:, This study is designed to test whether alcohol drinking frequency is associated with electrophysiological indices of reward processing. Materials and Methods:, In a passive gambling task, stimuli predicted the presence (reward) and absence (nonreward) of rewards resulting in P2 and medial frontal negativity (MFN) indices of reward processing. Forty-seven undergraduate students were asked about their habitual drinking frequency and the P2 and MFN to stimuli predicting reward were measured. Results:, Most importantly, the MFN to unpredicted nonrewards at the frontal midline (Fz) location correlated significantly with drinking frequency, with frequent drinkers showing larger MFN amplitudes. The results did not show a significant association between frequency and alcohol drinking and P2. Discussion:, Although several studies showing increased reward-sensitivity in addictive behaviors, the present results indicate that, in frequent alcohol drinkers, electrophysiological responsiveness is particularly activated by unpredicted nonrewards. In general, this may point to the involvement of the reward system in alcohol drinking frequency. Conclusion:, More specifically, the results demonstrate an increased vulnerability of high frequency drinkers to signals of (frustrative) nonrewards. [source] Widespread dispersal of Icelandic tephra: how does the Eyjafjöll eruption of 2010 compare to past Icelandic events?,JOURNAL OF QUATERNARY SCIENCE, Issue 5 2010Siwan M. Davies Abstract The Eyjafjöll AD 2010 eruption is an extraordinary event in that it led to widespread and unprecedented disruption to air travel over Europe , a region generally considered to be free from the hazards associated with volcanic eruptions. Following the onset of the eruption, satellite imagery demonstrated the rapid transportation of ash by westerly winds over mainland Europe, eventually expanding to large swathes of the North Atlantic Ocean and the eastern seaboard of Canada. This small-to-intermediate size eruption and the dispersal pattern observed are not particularly unusual for Icelandic eruptions within a longer-term perspective. Indeed, the Eyjafjöll eruption is a relatively modest eruption in comparison to some of the 20 most voluminous eruptions that have deposited cryptotephra in sedimentary archives in mainland Europe, such as the mid Younger Dryas Vedde Ash and the mid Holocene Hekla 4 tephra. The 2010 eruption, however, highlights the critical role that weather patterns play in the distribution of a relatively small amount of ash and also highlights the spatially complex dispersal trajectories of tephra in the atmosphere. Whether or not the preservation of the Eyjafjöll 2010 tephra in European proxy archives will correspond to the extensive distributions mapped in the atmosphere remains to be seen. The Eyjafjöll 2010 event highlights our increased vulnerability to natural hazards rather than the unparalleled explosivity of the event. Copyright © 2010 John Wiley & Sons, Ltd. [source] Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantationLIVER TRANSPLANTATION, Issue 2 2005Arianeb Mehrabi Catecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 ,g/kg/minute and high dose = 10 ,g/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33,75% reduction) and microcirculation (39,58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully. (Liver Transpl 2005;11:174,187.) [source] A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease,MOVEMENT DISORDERS, Issue S1 2010C. Savio Chan PhD Abstract Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. There is no cure or proven strategy for slowing the progression of the disease. Although there are signs of pathology in many brain regions, the core symptoms of PD are attributable to the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. A potential clue to the vulnerability of these neurons is an increasing reliance with age upon L-type Ca2+ channels with a pore-forming Cav1.3 subunit to support autonomous activity. This reliance could pose a sustained stress on mitochondrial ATP generating oxidative phosphorylation, accelerating cellular aging and death. Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L-type Ca2+ channel independent mechanism to generate autonomous activity. This "rejuvenation" confers protection against toxins that produce experimental Parkinsonism, pointing to a potential neuroprotective strategy for PD. Their decades-long track record of safe use in the treatment of hypertension makes dihydropyridines particularly attractive as a therapeutic tool in PD. © 2010 Movement Disorder Society [source] Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep ModelPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2001RIK WILLEMS WILLEMS, R. et al.: Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep Model. In different animal models rapid atrial stimulation led to a shortening and maladaptation to rate of the atrial effective refractory period (AERP). This atrial electrical remodeling resulted in an increased vulnerability to atrial fibrillation (AF). These experimental findings formed the rationale for a stringent pursuit of sinus rhythm in patients with AF, since this would prevent or reverse atrial remodeling. This study tested the hypothesis that a reduction of arrhythmia burden would lead to a decreased vulnerability for AF. Different rapid atrial pacing protocols in a sheep model were used. During 15 weeks, 13 animals were continuously rapid paced and 7 animals were intermittently burst-paced, resulting in rapid atrial activation during 100% versus 33 ± 4% of the time, respectively. In the continuously paced group, 77% of the animals developed sustained AF (i.e., >1 hour) versus only 29% in the burst-paced group (P < 0.05). However, there was no difference in mean AERP shortening over time, nor maximal AERP shortening per animal, between both protocols. Minimal AERP was 103 ± 5 ms in the continuously paced group and 107 ± 5 in the burst-paced group (P = NS). Significant changes could be identified in effect on P wave duration, AVN function, and atrial dilation. Conduction slowing was more pronounced in the continuously paced group with a maximal P wave duration of 136 ± 4 ms in this group versus 116 ± 5 in the burst-paced group (P < 0.05). In the continuously paced group, the right atrial area significantly increased from 2.5 ± 0.1 cm2 at baseline to 4.2 ± 0.2 cm2. In the burst-paced group there was no significant atrial dilatation (from 2.6 ± 0.1 to 2.8 ± 0.1 cm2). In conclusion, limiting atrial arrhythmia burden slowed the development of sustained AF in this sheep model. This was not mediated by a decreased influence on atrial refractoriness but seemed to be dependent on smaller changes in atrial conduction and dimensions. [source] Proteomic analysis of rabbit tear fluid: Defensin levels after an experimental corneal wound are correlated to wound closurePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2007Lei Zhou Abstract The cornea is the major refracting optical element of the eye and therefore critical for forming a retinal image. The exposed surface of the eye is protected from pathogens by the innate immune system whose components include defensins, naturally occurring peptides with antimicrobial properties, and the physical barrier formed by the outer epithelial layer of the cornea. The proteomic approach has revealed that tear levels of defensins are correlated with the course of healing of an experimental corneal wound. Tears were collected from New Zealand White rabbits prior to (day 0) and daily for 5 days (days 1,5) following a standard unilateral 6,mm diameter corneal epithelial abrasion. Tear protein profiles obtained from wounded and contra-lateral control eyes were compared using SELDI ProteinChip technology. Peptides and proteins of interest were purified by RP-HPLC and characterized by nanoESI-MS/MS. Mass spectra of tears on post-wound day 1, revealed 13,peaks whose level decreased and five that increased. During wound healing the tear protein profile correlated with wound closure. An important finding was that the levels of rabbit defensins (NP-1 and NP-2), which were elevated after wounding returned to normal levels by the time the corneal abrasion healed. Relative quantification of NP-2 in tear fluid prior to (day 0) and after corneal wounding (days 1, 3) was determined using iTRAQ technology. A corneal wound eliminates the barrier function of innate immunity and puts the cornea at risk from microbial attack until the epithelial cells restore the surface barrier. The increased availability of defensins in the tears during healing suggests that these peptides could protect the cornea from microbial attack during a period of increased vulnerability. [source] Risk for schizophrenia in intercountry adoptees: a Danish population-based cohort studyTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 11 2007Elizabeth Cantor-Graae Background:, Increasing numbers of intercountry adoptees are reaching adulthood, the age of onset for most serious mental disorders. Little is known about the development of schizophrenia in intercountry adoptees, a group with potentially increased vulnerability. The aim of this study was to investigate the risk of developing schizophrenia in adoptees and in non-adoptees. Methods:, Utilising data from the Danish Civil Registration System, we established a population-based cohort of 1.06 million persons resident in Denmark before the age of 15, whose legal mother lived in Denmark at the child's birth. Intercountry adoptees were identified as children born abroad. Record linkage provided information on psychiatric admissions. Results:, Intercountry adoptees had an increased relative risk (RR) (RR = 2.90, 95% CI 2.41,3.50) of developing schizophrenia compared to native Danes. The increased risk was independent of age at onset and age at, or region of, adoption, and was not attributable to mental illness in a foster parent, the foster parent's age, or to urbanisation. The foster mother's own biological offspring had also an increased risk of developing schizophrenia (1.92, 95% CI 1.23,3.02). Conclusions:, Young adult intercountry adoptees are at increased risk for schizophrenia. Although the underlying cause is unknown, a complex interplay of factors presumably may be involved, including heredity, adversity prior to adoption, and post-adoption adjustment difficulties during upbringing. [source] Electrocardiographic Transmural Dispersion of Repolarization in Patients with Inherited Short QT SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2008Olli Anttonen M.D. Background: Short QT syndrome (SQTS) carries an increased risk for sudden cardiac death. However, only a short QT interval does not express the risk of ventricular arrhythmias. Thus, additional evaluation of the repolarization abnormality in SQTS patients is essential. In experimental models of SQTS, increased transmural dispersion of repolarization (TDR) and its electrocardiographic counterpart T-wave peak to T-wave end interval (TPE) appeared critical for induction of polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We hypothesized that the TPE/QT ratio would be greater in SQTS patients than in control subjects. Methods and Results: We compared the behavior of the electrocardiographic TDR in three seriously symptomatic SQTS patients of unknown genotype presenting baseline QTc values <320 ms and in nine healthy age-matched control subjects. We determined QT and TPE intervals as well as TPE/QT ratio from 24-hour ECG recordings using a computer-assisted program. Diurnal average of TPE/QT ratio was 0.28 ± 0.03 in SQTS patients and 0.21 ± 0.02 in control subjects (P = 0.01). SQTS patients had also lesser capacity to change TPE intervals from steady-state conditions to abrupt maximal values than control subjects. Conclusion: SQTS patients have increased and autonomically uncontrolled electrocardiographic TDR. According to experimental SQTS models, the present results may in part explain increased vulnerability of SQTS patients to ventricular arrhythmias. [source] Bedside biochemical monitoring of the penumbra zone surrounding an evacuated acute subdural haematomaACTA NEUROLOGICA SCANDINAVICA, Issue 3 2003N. Ståhl We describe a penumbra zone with increased biochemical vulnerability in cerebral cortex underlying an evacuated acute subdural haematoma. Two microdialysis catheters were placed in this zone and one catheter was placed in the opposite, less injured hemisphere. The microdialysis perfusates were analysed bedside for glucose, pyruvate, lactate, glutamate, and glycerol. In the penumbra zone, but not in the opposite hemisphere, energy metabolism was seriously disturbed with signs of cell membrane degradation. During an adverse event (decrease in haemoglobin level, systemic blood pressure and cerebral perfusion pressure) the perturbation of energy metabolism increased in this zone. Energy metabolism recovered and the signs of cell membrane degradation disappeared after normalization of the physiological parameters. We use the term biochemical penumbra zone to describe an area with signs of energy failure and cell membrane degradation, which has a capacity to regain a normal metabolic pattern but also an increased vulnerability to secondary insults. [source] Assessment of infant physiology and neuronal development using magnetic resonance imagingCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2002B. Morgan Abstract Previous work has demonstrated both that there are substantial individual differences in the rate of physiological development, and that infants with risk factors for Sudden Infant Death Syndrome (SIDS) develop more slowly, suggesting that their increased vulnerability may be due to delayed neuronal development associated with compromised development in fetal or early neonatal life. This project aims to test the hypothesis that individual differences in the rate of physiological development of infants correlate with measurable differences in the rate of brain development as assessed by magnetic resonance imaging (MRI). Sixty infants were recruited to this study in three different groups that are known to have differing rates of physiological development. MRI was performed successfully in 49 cases at 6 weeks of age without sedation. Forty-one of these cases had full follow-up (15 normal; 19 IUGR; 11 ,high risk'). Postnatal physiological development was assessed by measuring age-related deep body temperature patterns during sleep. Neuronal development was assessed by subjective analysis of MRI images and objective measurements relating to myelination using T1 and diffusion weighted (23 cases) MRI images. As expected the normal group acquired the adult temperature pattern earlier, but this was not statistically significant. All MRI scan appearances were within normal limits. Ranking cases subjectively in order of maturity revealed no significant pattern. The normal group had a significantly higher myelination score than the IUGR and ,high risk' groups (P = 0.001). This trend was also shown by the diffusion weighted myelination score but did not reach statistical significance. No significant differences were seen in both the subjective and objective MRI measurements and development of nocturnal temperature patterns. The results suggest there may be differences in neurodevelopment between the different groups at 6 weeks of age but these are not linked to late development of temperature patterns. It is therefore unlikely that this related to a global delay in maturation. [source] | |||||||||||||||||||||||||||||||