| 1. |
- Kövesdi, Erzsébet, et al.
(författare)
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A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury : an immunohistochemical and behavioral study
- 2010
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 11:4, s. 1253-1268
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Tidskriftsartikel (refereegranskat)abstract
- We examined the neuro/axono-protective potential of a novel poly (ADP-ribose) polymerase (PARP) inhibitor L-2286 in a rat impact acceleration brain injury model. Male Wistar rats (n = 70) weighing 300-350 grams were used to determine the most effective intracerebroventricular (i.c.v.) dose of L-2286 administered 30 min after injury, and to test the neuroprotective effect at two time points (immediately, and 30 min after injury). The neuroprotective effect of L-2286 was tested using immunohistochemical (amyloid precursor protein and mid-sized mouse anti-neurofilament clone RMO-14.9 antibody) and behavioral tests (beam-balance, open-field and elevated plus maze). At both time-points, a 100 microg/rat dose of i.c.v. L-2286 significantly (p < 0.05) reduced the density of damaged axons in the corticospinal tract and medial longitudinal fascicle compared to controls. In the behavioral tests, treatment 30 min post-injury improved motor function, while the level of anxiety was reduced in both treatment protocols.
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| 2. |
- Bukovics, Peter, et al.
(författare)
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Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury
- 2014
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 60, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- PACAP has well-known neuroprotective potential including traumatic brain injury (TBI). Its level is up-regulated following various insults of the CNS in animal models. A few studies have documented alterations of PACAP levels in human serum. The time course of post-ictal PACAP levels, for example, show correlation with migraine severity. Very little is known about the course of PACAP levels following CNS injury in humans and the presence of PACAP has not yet been detected in cerebrospinal fluid (CSF) of subjects with severe TBI (sTBI). The aim of the present study was to determine whether PACAP occurs in the CSF and plasma (Pl) of patients that suffered sTBI and to establish a time course of PACAP levels in the CSF and Pl. Thirty eight subjects with sTBI were enrolled with a Glasgow Coma Scale ≤8 on admission. Samples were taken daily, until the time of death or for maximum 10 days. Our results demonstrated that PACAP was detectable in the CSF, with higher concentrations in patients with TBI. PACAP concentrations markedly increased in both Pl and CSF in the majority of patients 24-48h after the injury stayed high thereafter. In cases of surviving patients, Pl and CSF levels displayed parallel patterns, which may imply the damage of the blood-brain barrier. However, in patients, who died within the first week, Pl levels were markedly higher than CSF levels, possibly indicating the prognostic value of high Pl PACAP levels.
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| 3. |
- Czobor, Pal, et al.
(författare)
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The European Adolescent Assessment Dialogue (EuroADAD) : A Psychometric Evaluation
- 2011
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Ingår i: European Addiction Research. - : S. Karger AG. - 1022-6877 .- 1421-9891. ; 17:6, s. 302-315
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Adolescent Drug Abuse Diagnosis (ADAD) has been a gold standard for assessing drug use and associated problems in adolescents. Criticism of the instrument has been increasing. A new instrument, the European Adolescent Assessment Dialogue (EuroADAD) that builds on ADAD's strengths but seeks to address its limitations is now available, but has not been subjected to comprehensive psychometric evaluation. Objective: To examine the psychometric properties of the EuroADAD across various settings in adolescent populations who developed or were at a high risk of developing substance use and psychosocial adaptation problems. Participants and Settings: Three of the samples were collected in Hungary, including: institutionalized youths from juvenile residential facility (n = 295); adolescents from outpatient psychiatry facility (n = 278), and controls (n = 59). An additional sample was collected in the Netherlands, and consisted of adolescent boys from an independent residential institution for youth with severe behavioral problems (n = 51). Procedure: The EuroADAD was administered by trained interviewers. Data were collected through face-to-face interviews and self-report questionnaires. Results: Reliability: the intraclass correlation was high for all domains of the EuroADAD; reliability analyses indicated good test-retest reliability, and internal consistency. Validity: difference among study samples was significant (p < 0.05) for the majority of the domains, with juvenile institution and psychiatric outpatient subjects exhibiting higher severity in most areas compared to controls. The Hungarian and Dutch samples were comparable, expect for the legal domain, due to the higher severity of behavioral problems in the Dutch sample. Several domains of the instrument, including 'alcohol', 'drugs' and 'legal' showed an association with trait aggression as measured by the Buss-Perry Aggression Questionnaire and with Novelty Seeking on the Cloninger Temperament and Character Inventory. Conclusion: Based on the pattern and significance of group differences, and correlations with other measures, the scale has good criterion, and convergent and discriminant construct validity. The EuroADAD is a reliable and valid tool for the assessment of alcohol and drug use, and related psychosocial problems in adolescents.
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| 4. |
- Kövesdi, Erzsébet, et al.
(författare)
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Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics
- 2010
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 152:1, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Purpose: This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma.Methods: We performed an electronic search of the National Library of Medicine's MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-beta(1-42)) in the last 10 years, but recent data on "classical" markers (S-100B, neuron-specific enolase, etc.) were also examined.Results: We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment.Conclusions: We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.
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| 5. |
- Matuszka, Balazs, et al.
(författare)
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Psychometric Characteristics of the Drug Use Disorders Identification Test (DUDIT) and the Drug Use Disorders Identification Test-Extended (DUDIT-E) Among Young Drug Users in Hungary
- 2014
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Ingår i: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 21:3, s. 547-555
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Tidskriftsartikel (refereegranskat)abstract
- AbstractThe Drug Use Disorders Identification Test (DUDIT) was developed for problematic substance use screening, and for a more detailed assessment of problematic use, the Drug Use Disorders Identification Test-Extended (DUDIT-E) was additionally developed.Examining the psychometric properties of DUDIT and DUIT-E across diverse settings in populations of young drug users.We examined the psychometric characteristics of these instruments across various settings in populations of young substance users differing in substance use severity and treatment status. Data were collected from three clinically relevant groups (n = 259) as well as a control sample of college students (n = 109).Reliability analyses indicated good internal consistency for both instruments; high intraclass correlations further indicated good test-retest reliability. Differences among study groups were significant on the DUDIT scale and all DUDIT-E subscales (p < 0.01), with the target groups exhibiting higher scores compared to controls. A two-factor solution was identified for the factor structure of DUDIT.The Hungarian version of DUDIT and DUDIT-E can effectively identify substance use problems among young users.
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| 6. |
- Tamas, Andrea, et al.
(författare)
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Effect of PACAP in central and peripheral nerve injuries
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 13:7, s. 8430-8448
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Forskningsöversikt (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a bioactive peptide with diverse effects in the nervous system. In addition to its more classic role as a neuromodulator, PACAP functions as a neurotrophic factor. Several neurotrophic factors have been shown to play an important role in the endogenous response following both cerebral ischemia and traumatic brain injury and to be effective when given exogenously. A number of studies have shown the neuroprotective effect of PACAP in different models of ischemia, neurodegenerative diseases and retinal degeneration. The aim of this review is to summarize the findings on the neuroprotective potential of PACAP in models of different traumatic nerve injuries. Expression of endogenous PACAP and its specific PAC1 receptor is elevated in different parts of the central and peripheral nervous system after traumatic injuries. Some experiments demonstrate the protective effect of exogenous PACAP treatment in different traumatic brain injury models, in facial nerve and optic nerve trauma. The upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central and peripheral nerve injuries show the important function of PACAP in neuronal regeneration indicating that PACAP may also be a promising therapeutic agent in injuries of the nervous system.
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| 7. |
- Wahlgren, Weixiao Yuan, 1970, et al.
(författare)
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The catalytic aspartate is protonated in the Michaelis complex formed between trypsin and an in vitro evolved substrate-like inhibitor: a refined mechanism of serine protease action.
- 2011
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 286:5, s. 3587-96
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of serine proteases prominently illustrates how charged amino acid residues and proton transfer events facilitate enzyme catalysis. Here we present an ultrahigh resolution (0.93 Å) x-ray structure of a complex formed between trypsin and a canonical inhibitor acting through a substrate-like mechanism. The electron density indicates the protonation state of all catalytic residues where the catalytic histidine is, as expected, in its neutral state prior to the acylation step by the catalytic serine. The carboxyl group of the catalytic aspartate displays an asymmetric electron density so that the O(δ2)-C(γ) bond appears to be a double bond, with O(δ2) involved in a hydrogen bond to His-57 and Ser-214. Only when Asp-102 is protonated on O(δ1) atom could a density functional theory simulation reproduce the observed electron density. The presence of a putative hydrogen atom is also confirmed by a residual mF(obs) - DF(calc) density above 2.5 σ next to O(δ1). As a possible functional role for the neutral aspartate in the active site, we propose that in the substrate-bound form, the neutral aspartate residue helps to keep the pK(a) of the histidine sufficiently low, in the active neutral form. When the histidine receives a proton during the catalytic cycle, the aspartate becomes simultaneously negatively charged, providing additional stabilization for the protonated histidine and indirectly to the tetrahedral intermediate. This novel proposal unifies the seemingly conflicting experimental observations, which were previously seen as either supporting the charge relay mechanism or the neutral pK(a) histidine theory.
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