| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Westin, J. E., et al.
(author)
-
Persistent changes in striatal gene expression induced by long-term L-DOPA treatment in a rat model of Parkinson's disease
- 2001
-
In: European Journal of Neuroscience. - 0953-816X .- 1460-9568. ; 14:7, s. 1171-1176
-
Journal article (peer-reviewed)abstract
- Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with L-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained L-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and L-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/DFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of L-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion-induced up-regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. L-DOPA, but not bromocriptine, induced high striatal levels of FosB/DFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short-term and long-term L-DOPA-treated rats. The present data provide the first demonstration that L-DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short-treatment paradigms studied thus far.
|
|
| 5. |
|
|
| 6. |
- Fuqua, Joshua L, et al.
(author)
-
Dynamic changes in dopamine neuron function after DNSP-11 treatment: Effects in vivo and increased ERK 1/2 phosphorylation in vitro.
- 2014
-
In: Peptides. - : Elsevier BV. - 1873-5169 .- 0196-9781. ; 54:Jan 7, s. 1-8
-
Journal article (peer-reviewed)abstract
- Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and d-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function.
|
|
| 7. |
- Gudelis, M., et al.
(author)
-
Epidemiology of hamstring injuries in 538 cases from an FC Barcelona multi sports club
- 2024
-
In: Physician and Sportsmedicine. - : Informa UK Limited. - 0091-3847 .- 2326-3660. ; 52:1, s. 57-64
-
Journal article (peer-reviewed)abstract
- ObjectivesHamstring injuries are the most common muscle injuries in team sports. The aims of this study were to describe the epidemiology of hamstring muscle injuries in the professional and amateur sport sections of a multi-sport club Football Club Barcelona (FCB) and to determine any potential correlation between return-to-play (RTP) and injury location, severity of connective tissue damage, age, sex, and athlete's level of competition.MethodsThis descriptive epidemiological study with data collected from September 2007 to September 2017 stored in the FCB database. The study included non-contact hamstring injuries sustained during training or competition.ResultsA total of 538 hamstring injuries were reported in the club's database, of which 240 were structurally verified by imaging as hamstring injuries. The overall incidence for the 17 sports studied was 1.29 structurally verified hamstring injuries per 100 athletes per year. The muscle most commonly involved in hamstring injuries was the biceps femoris, and the connective tissue most frequently involved was the myofascial. There was no evidence of a statistically significant association between age and RTP after injury, and no statistically significant difference between sex and RTP. However, the time loss by professionals was shorter than for amateurs, and proximal hamstring injuries took longer RTP than distal ones.ConclusionIn the 17 sports practiced at multi-sport club, the incidence of hamstring injury was 1.29 per 100 athletes per year. Players from sports in which high-speed sprinting and kicking are necessary, and amateurs, were at higher risk of suffering a hamstring injury. In addition, proximally located hamstring injuries involving tendinous connective tissue showed the longest RTP time. Age did not seem to have any influence on RTP. Documenting location and the exact tissue involved in hamstring injuries may be beneficial for determining the prognosis and RTP.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Lundblad, Matilda, 1982, et al.
(author)
-
Epidemiological Data on LCL and PCL Injuries Over 17 Seasons in Men's Professional Soccer: The UEFA Elite Club Injury Study
- 2020
-
In: Open Access Journal of Sports Medicine. - 1179-1543. ; 11, s. 105-112
-
Journal article (peer-reviewed)abstract
- Background: There is limited epidemiological information on injury rates and injury mechanisms for lateral collateral ligament (LCL) and posterior cruciate ligament (PCL) injuries in male professional soccer. In addition, time trends and lay-off times for these injuries have not yet been determined. Aim: To determine injury rates and circumstances of LCL and PCL injuries over 17 seasons in men's professional soccer. Methods: A prospective cohort study, in which 68 professional European soccer teams were followed over 17 consecutive seasons (2001/2002 to 2017/2018). The teams' medical staff recorded player exposure and time-loss injuries. Lay-off time was reported as the median and the first and third quartile. Injury rate was defined as the number of injuries per 1000 playerhours. Results: One hundred and twenty-eight LCL and 28 PCL injuries occurred during 2,554,686 h of exposure (rate 0.05 and 0.01/1000 h, respectively). The median lay-off time for LCL injuries was 15 (Q(1)=7, Q(3)=32) days, while it was 31 days for PCL injuries (Q(1)=15, Q(3)=74). The match injury rate for LCL injuries was 11 times higher than the training injury rate (0.21 vs 0.02/1000 h, rate ratio [RR] 10.5, 95% CI 7.3 to 15.1 p<0.001) and the match injury rate for PCL injuries was 20 times higher than the training injury rate (0.056 vs 0.003/1000 h, RR 20.1, 95% CI 8.2 to 49.6, p<0.001). LCL injuries saw a significant annual decrease of approximately 3.5% (p=0.006). In total, 58% (63/108) of all LCL injuries and 54% (14/26) of all PCL injuries were related to contact mechanism. Conclusion: This study with prospectively registered data on LCL and PCL injuries in men's professional soccer shows that the median lay-off from soccer for LCL and PCL injuries is approximately 2 and 4 weeks respectively. These rare knee ligament injuries typically occur during matches and are associated with a contact injury mechanism.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Wasserman, D, et al.
(author)
-
Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
- 2020
-
In: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
-
Journal article (peer-reviewed)abstract
- Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Bimpisidis, Zisis, et al.
(author)
-
Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease
- 2017
-
In: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 292, s. 113-124
-
Journal article (peer-reviewed)abstract
- Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease.
|
|
| 20. |
|
|
| 21. |
- Cardell, L O, et al.
(author)
-
Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.
- 2009
-
In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1301-8
-
Journal article (peer-reviewed)abstract
- Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Cohen, JC, et al.
(author)
-
The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse
- 2004
-
In: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 5
-
Journal article (peer-reviewed)abstract
- Background: Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results: Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. Conclusions: In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung.
|
|
| 25. |
|
|
| 26. |
- Grenback, E, et al.
(author)
-
Galanin in pituitary adenomas
- 2004
-
In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 117:2, s. 127-139
-
Journal article (peer-reviewed)
|
|
| 27. |
- Hatta, Fazleen H M, et al.
(author)
-
Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine : Role of Ethnicity, Genotype, Smoking, Age, and Sex
- 2015
-
In: Omics. - : Mary Ann Liebert Inc. - 1536-2310 .- 1557-8100. ; 19:6, s. 346-353
-
Journal article (peer-reviewed)abstract
- Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors. CYP2C9 genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity. CYP2C9 genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assessed using urinary losartan/metabolite E-3174 ratio. The frequency of CYP2C9 defective variant alleles (*2 and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (p<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations, CYP2C9 genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to CYP2C9 pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.
|
|
| 28. |
|
|
| 29. |
- Kaminsky, DA, et al.
(author)
-
Oscillation mechanics of the human lung periphery in asthma
- 2004
-
In: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 97:5, s. 1849-1858
-
Journal article (peer-reviewed)abstract
- To more precisely measure the mechanical properties of the lung periphery in asthma, we have developed a forced oscillation technique that applies a broad-band flow signal through a wedged bronchoscope. We interpreted the data from four healthy and eight mildly asthmatic subjects in terms of an anatomically accurate computer model of the wedged segment. There was substantial overlap in impedance between the two groups, with resistance ( R) showing minimal frequency dependence and elastance (E) showing positive and negative frequency dependence across subjects. After direct instillation of methacholine, R rose in both groups, but compared with healthy subjects, the asthmatic subjects displayed upward, parallel shifts in their dose-response curves. The baseline frequency-response patterns of E were enhanced after methacholine. Frequency dependencies of R and E were well reproduced in two normal subjects by a computational model that employed rigid airways connected to constant-phase tissue units but were better reproduced in the other two normal and three asthmatic subjects when the model employed heterogeneous, peripheral airway narrowing and compliant airways. To capture the frequency dependencies of R and E in the remaining five asthmatic subjects, the model was modified by increasing airway wall stiffness. These results indicate that the lung periphery of mildly asthmatic subjects is not well distinguished from that of healthy subjects by measurement of mechanical impedance at baseline, but group differences are seen after challenge with methacholine. Modeling of the response suggests that variable contributions of airway narrowing and wall compliance are operative in determining overall mechanical impedance of the lung periphery in humans with asthma, likely reflecting the functional consequences of airway inflammation and remodeling.
|
|
| 30. |
- Lagergren, Fredrik, et al.
(author)
-
Net primary production and light use efficiency in a mixed coniferous forest in Sweden
- 2005
-
In: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 28:3, s. 412-423
-
Journal article (peer-reviewed)abstract
- Simple light use efficiency (epsilon) models of net primary production (NPP) have recently been given great attention (NPP = epsilon x absorbed photosynthetically active radiation). The underlying relationships have, however, not been much studied on a time step less than a month. In this study daily NPP was estimated as the sum of net ecosystem exchange (NEE) and heterotrophic respiration (R-h) of a mixed pine and spruce forest in Sweden. NEE was measured by eddy correlation technique and R-h was estimated from measurements of forest floor respiration (R-f) and the root share of R-f. The total yearly NPP was on average 810 g C m(-2) year(-1) for 3 years and yearly epsilon was between 0.58 and 0.71 g C MJ(-1), which is high in comparison with other studies. There was a seasonal trend in epsilon with a relatively constant level of approximately 0.90 g C MJ(-1) from April to September Daily NPP did not increase for daily intercepted radiation above 6 MJ m(-2) d(-1), indicating that between-years variation in NPP is not directly dependent on total Q(i). The light was most efficiently used at an average daytime temperature of around 15 degreesC. At daytime vapour pressure deficit above 1400 Pa epsilon was reduced by approximately 50%.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Liljencrantz, Jaquette, et al.
(author)
-
Slow brushing reduces heat pain in humans
- 2017
-
In: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 21:7, s. 1173-1185
-
Journal article (peer-reviewed)abstract
- Background: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. Methods: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Results: Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Conclusions: Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms.
|
|
| 34. |
- Lundblad, Barbro, 1947, et al.
(author)
-
Continuing nursing care needs of children at time of discharge from one regional medical center in Sweden.
- 2001
-
In: Journal of pediatric nursing. - 0882-5963. ; 16:1, s. 73-8
-
Journal article (peer-reviewed)abstract
- Hospital nurses used an investigator designed survey instrument to record demographics and anticipated nursing needs of 29 children discharged from 7 units during a 1 month period. The median age of the children was 18 months and 77% of the sick children had one or more siblings. Parental leave enabled most parents to participate in the child's hospital care. Over three quarters of the families reported no support person available to assist them at home. At time of discharge 42% of the children required long-term nursing interventions related to chronic illness. Nurses trained parents visiting in the hospital for an average of 3 hours and 40 minutes per family before discharge. Nurses also arranged an informal system of follow-up telephone contact but few community referrals. With decreasing length of hospital stay, parents need a formal system of nursing support before and after the discharge of their child from a hospital.
|
|
| 35. |
- Lundblad, Dan, et al.
(author)
-
Low level of tissue plasminogen activator activity innon-diabetic patients with a first myocardial infarction
- 2005
-
In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 258:1, s. 13-20
-
Journal article (peer-reviewed)abstract
- Objective. To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. Design. Case-control study in northern Sweden. Subjects. A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex matched with control subjects drawn from the local cohort in the MONICA population survey 1994. Main outcome measures. We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR). Results. PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not. Conclusion. Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables
|
|
| 36. |
|
|
| 37. |
- Lundblad, Martin, et al.
(author)
-
Chronic intermittent L-DOPA treatment induces changes in dopamine release
- 2009
-
In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 108:4, s. 998-1008
-
Journal article (peer-reviewed)abstract
- 3,4-Dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia often develops as a side effect of chronic l-DOPA therapy. This study was undertaken to investigate dopamine (DA) release upon l-DOPA treatment. Chronoamperometric measurements were performed in unilaterally DA-depleted rats, chronically treated with l-DOPA, resulting in dyskinetic and non-dyskinetic animals. Normal and lesioned l-DOPA naïve animals were used as controls. Potassium-evoked DA releases were significantly reduced in intact sides of animals undertaken chronic l-DOPA treatment, independent on dyskinetic behavior. Acute l-DOPA further attenuated the amplitude of the DA release in the control sides. In DA-depleted striata, no difference was found in potassium-evoked DA releases, and acute l-DOPA did not affect the amplitude. While immunoreactivity to serotonin uptake transporter was higher in lesioned striata of animals displaying dyskinetic behavior, no correlation could be documented between serotonin transporter-positive nerve fiber density and the amplitude of released DA. In conclusions, the amplitude of potassium-evoked DA release is attenuated in intact striatum after chronic intermittent l-DOPA treatment. No change in amplitude was found in DA-denervated sides of either dyskinetic or non-dyskinetic animals, while release kinetics were changed. This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects of l-DOPA replacement therapy.
|
|
| 38. |
|
|
| 39. |
- Lundblad, Martin, et al.
(author)
-
Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease.
- 2002
-
In: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 15:1, s. 120-132
-
Journal article (peer-reviewed)abstract
- In an attempt to define clinically relevant models of akinesia and dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, we have examined the effects of drugs with high (L-DOPA) vs. low (bromocriptine) dyskinesiogenic potential in Parkinson's disease on three types of motor performance, namely: (i) abnormal involuntary movements (AIMs) (ii) rotational behaviour, and (iii) spontaneous forelimb use (cylinder test). Rats with unilateral 6-OHDA lesions received single daily i.p. injections of L-DOPA or bromocriptine at therapeutic doses. During 3 weeks of treatment, L-DOPA but not bromocriptine induced increasingly severe AIMs affecting the limb, trunk and orofacial region. Rotational behaviour was induced to a much higher extent by bromocriptine than L-DOPA. In the cylinder test, the two drugs initially improved the performance of the parkinsonian limb to a similar extent. However, L-DOPA-treated animals showed declining levels of performance in this test because the drug-induced AIMs interfered with physiological limb use, and gradually replaced all normal motor activities. L-DOPA-induced axial, limb and orolingual AIM scores were significantly reduced by the acute administration of compounds that have antidyskinetic efficacy in parkinsonian patients and/or nonhuman primates (-91%, yohimbine 10 mg/kg; -19%, naloxone 4-8 mg/kg; -37%, 5-methoxy 5-N,N-dimethyl-tryptamine 2 mg/kg; -30%, clozapine 8 mg/kg; -50%, amantadine 40 mg/kg). L-DOPA-induced rotation was, however, not affected. The present results demonstrate that 6-OHDA-lesioned rats do exhibit motor deficits that share essential functional similarities with parkinsonian akinesia or dyskinesia. Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Lundblad, M, et al.
(author)
-
Stand transpiration and sapflow density in relation to weather, soil moisture and stand characteristics
- 2002
-
In: Basic and Applied Ecology. - : Elsevier BV. - 1618-0089 .- 1439-1791. ; 3:3, s. 229-243
-
Journal article (peer-reviewed)abstract
- Sapflow density was measured in six stands in a boreal forest in central Sweden, to assess its dependence on soil moisture and stand characteristics. The stands were mixed and pure Scots pine and Norway spruce stands, which were between 34 and 105 years old. Sapflow was measured in 12 trees per stand using the Granier method during two contrasting growing seasons; one warm and dry and one wet and cool. The canopy conductance of the stands was estimated by the inverse of the Penman-Monteith equation, using time-lag-adjusted sapflow as input. Maximum canopy conductance varied between 8 mm s(-1) and 88 mm s(-1) for the stand with the lowest and highest conductance, respectively. Transpiration was higher in the dry, warm season, mean values for the different stands ranging between 1.30 to 4.64 mm day(-1) during July to September. The corresponding range in the wet, cool season was 0.95 to 2.65 mm day(-1). Besides climatic factors, stand age, stem density and diameter explained most of the variation in sapflow density. By use of multiple regression analysis for 5-day periods it was possible to estimate sapflow density and transpiration for a larger area of the forest. This upscaled area) transpiration was compared with evaporation measured by an eddy-correlation system located centrally in the area. It was shown that areal transpiration constituted 78% of total evaporation in the warm, dry season and 52% in the wet, cool season. It was not possible to establish with confidence a critical limit for soil water at which transpiration began to be reduced, mainly because of wide scatter in the relationship between potential and actual transpiration.
|
|
| 45. |
|
|
| 46. |
- Noponen, M., et al.
(author)
-
Current distribution measurements in a PEFC with net flow geometry
- 2004
-
In: Journal of Applied Electrochemistry. - 0021-891X .- 1572-8838. ; 34:3, s. 255-262
-
Journal article (peer-reviewed)abstract
- A measurement system for current distribution mapping for a PEFC has been developed. The segmented anode is constructed so as to have high thermal conductivity in order to prevent the formation of large temperature gradients between the electrodes. The construction is therefore feasible for use at high current densities. Both segmented and unsegmented gas diffusion layers are used. The effect of inlet humidification and gas composition at the cathode side is studied. In addition, two different flow geometries are studied. The results show that the measurement system is able to distinguish between current distribution originating from differences in proton conductivity, species concentration and gas diffusion layer properties.
|
|
| 47. |
|
|
| 48. |
- Pereira, Maria J M, et al.
(author)
-
Highly efficient generation of induced neurons from human fibroblasts that survive transplantation into the adult rat brain.
- 2014
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
-
Journal article (peer-reviewed)abstract
- Induced neurons (iNs) offer a novel source of human neurons that can be explored for applications of disease modelling, diagnostics, drug screening and cell replacement therapy. Here we present a protocol for highly efficient generation of functional iNs from fetal human fibroblasts, and also demonstrate the ability of these converted human iNs (hiNs) to survive transplantation and maintain their phenotype in the adult rat brain. The protocol encompasses a delay in transgene activation after viral transduction that resulted in a significant increase in conversion efficiency. Combining this approach with treatment of small molecules that inhibit SMAD signalling and activate WNT signalling provides a further increase in the conversion efficiency and neuronal purity, resulting in a protocol that provides a highly efficient method for the generation of large numbers of functional and transplantable iNs from human fibroblasts without the use of a selection step. When transplanting the converted neurons from different stages of in vitro culture into the brain of adult rats, we observed robust survival and maintenance of neuronal identity four weeks post-transplantation. Interestingly, the positive effect of small molecule treatment observed in vitro did not result in a higher yield of iNs surviving transplantation.
|
|
| 49. |
|
|
| 50. |
- Suneson, Klara, et al.
(author)
-
Omega-3 fatty acids for inflamed depression - A match/mismatch study
- 2024
-
In: Brain, Behavior, and Immunity. - 1090-2139. ; 118, s. 192-201
-
Journal article (peer-reviewed)abstract
- Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.
|
|
