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Sökning: db:Swepub > (2010-2011) > Umeå universitet > Forskningsöversikt

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1.
  • Andersen, Peter M., et al. (författare)
  • Clinical genetics of amyotrophic lateral sclerosis : what do we really know?
  • 2011
  • Ingår i: Nature Reviews Neurology. - : Nature Publishing Group. - 1759-4758 .- 1759-4766. ; 7:11, s. 603-615
  • Forskningsöversikt (refereegranskat)abstract
    • Hereditary amyotrophic lateral sclerosis (ALS) encompasses a group of genetic disorders characterized by adult-onset loss of the lower and upper motor neuron systems, often with involvement of other parts of the nervous system. Cases of hereditary ALS have been attributed to mutations in 12 different genes, the most common being SOD1, FUS and TARDBP-mutations in the other genes are rare. The identified genes explain 25-35% of cases of familial ALS, but identifying the remaining genes has proved difficult. Only a few genes seem to account for significant numbers of ALS cases, with many others causing a few cases each. Hereditary ALS can be inherited in an autosomal dominant, autosomal recessive or X-linked manner, and families with low disease penetrance are frequently observed. In such families, the genetic predisposition may remain unnoticed, so many patients carry a diagnosis of isolated or sporadic ALS. The only clinical feature that distinguishes recognized hereditary from apparently sporadic ALS is a lower mean age of onset in the former. All the clinical features reported in hereditary cases (including signs of extrapyramidal, cerebellar or cognitive involvement) have also been observed in sporadic cases. Genetic counseling and risk assessment in relatives depend on establishing the specific gene defect and the disease penetrance in the particular family.
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2.
  • Bangdiwala, Shrikant I., et al. (författare)
  • Workforce resources for health in developing countries
  • 2010
  • Ingår i: Public Health Reviews. - : BioMed Central (BMC). - 0301-0422 .- 2107-6952. ; 32:1, s. 296-318
  • Forskningsöversikt (refereegranskat)abstract
    • With increased globalization and interdependence among countries, sustained health worker migration and the complex threats of rapidly spreading infectious diseases, as well as changing lifestyles, a strong health workforce is essential. Building the human resources for health should not only include healthcare professionals like physicians and nurses, but must take into consideration community health workers, mid-level workers and strengthened primary healthcare systems to increase coverage and address the basic health needs of societies. This is especially true in low and middle-income countries where healthcare access is a critical challenge. There is a global crisis in the health workforce, expressed in acute shortages and maldistribution of health workers, geographically and professionally. This massive global shortage, though imprecise quantitatively, is estimated at more than 4 million workers. To respond to this crisis, policies and actions are needed to address the dynamics of the health labour market and the production and management of the health workforce, and to strengthen the performance of existing health systems. Schools of public health need to develop the range of capacity and leadership in addition to the traditional training of healthcare managers and researchers. Countries should first identify their health problems in order to properly address their health worker needs, retention, recruitment and training, if they are to come close to reaching the Millennium Development Goals (MDGs) for health.
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3.
  • Behnam-Motlagh, Parviz, et al. (författare)
  • Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy
  • 2010
  • Ingår i: Toxins. - Basel : MDPI. - 2072-6651. ; 2:10, s. 2467-2477
  • Forskningsöversikt (refereegranskat)abstract
    • A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.
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5.
  • Birkholtz, Lyn-Marie, et al. (författare)
  • Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities
  • 2011
  • Ingår i: Biochemical Journal. - London : The Biochemical Society. - 0264-6021 .- 1470-8728. ; 438, s. 229-244
  • Forskningsöversikt (refereegranskat)abstract
    • New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness. Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies.
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7.
  • Blomstedt, Patric, et al. (författare)
  • Deep brain stimulation in the treatment of depression
  • 2011
  • Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 123:1, s. 4-11
  • Forskningsöversikt (refereegranskat)abstract
    • Objective: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD). Method: A review of the literature on DBS in the treatment of MDD was conducted. Results: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. Conclusion: DBS is a promising treatment for therapy-refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.
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8.
  • Bäckman, Lars, et al. (författare)
  • Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues
  • 2010
  • Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 34:5, s. 670-677
  • Forskningsöversikt (refereegranskat)abstract
    • Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.
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9.
  • Bäckström, Torbjörn, et al. (författare)
  • Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
  • 2011
  • Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
  • Forskningsöversikt (refereegranskat)abstract
    • Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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10.
  • Carlborg, Andreas, et al. (författare)
  • Suicide in schizophrenia
  • 2010
  • Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 10:7, s. 1153-64
  • Forskningsöversikt (refereegranskat)abstract
    • Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.
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