1.
Lundberg, Stefan, et al.
(författare)
Nicotine treatment of obsessive-compulsive disorder
2004
Ingår i: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. - : Elsevier BV. - 0278-5846. ; 28:7, s. 1195-1199
Forskningsöversikt (refereegranskat)
2.
Regland, Björn, 1947
(författare)
Schizophrenia and single-carbon metabolism
2005
Ingår i: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. - : Elsevier BV. - 0278-5846. ; 29:7, s. 1124-1132
Forskningsöversikt (refereegranskat)
3.
4.
Andersson, Karl-Erik, et al.
(författare)
CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention.
2003
Ingår i: Drugs. - 0012-6667. ; 63:23, s. 2595-2611
Forskningsöversikt (refereegranskat) abstract
The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson’s disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may be found in the CNS. Several CNS transmitters/transmitter systems are known to be involved in micturition control, but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and duloxetine) have been used for the treatment of voiding disorders. GABA, glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine receptors and mechanisms are known to influence micturition, and drugs influencing these systems could potentially be developed for the treatment of OAB. Preclinical studies in different animal models have shown that modulation of normal micturition and detrusor overactivity by drugs acting within the spinal cord or supraspinally is possible. Promising results have been obtained in such models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering the limited predictability of existing animal models for efficacy in humans, positive proof of concept studies in humans are mandatory. Such studies are scarce and further investigations are needed.
5.
Björklund, L., et al.
(författare)
Aspirin in cardiology - benefits and risks
2009
Ingår i: INTERNATIONAL JOURNAL OF CLINICAL PRACTICE. - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 63:3, s. 468-477
Forskningsöversikt (refereegranskat)
6.
Björkman, Sven
(författare)
Prediction of cytochrome p450-mediated hepatic drug clearance in neonates, infants and children : how accurate are available scaling methods?
2006
Ingår i: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 45:1, s. 1-11
Forskningsöversikt (övrigt vetenskapligt/konstnärligt) abstract
Correct dosing of drugs in neonates, infants and children is hampered by a general lack of knowledge about drug disposition in this population. Suggested methods to improve our knowledge without performing conventional full-scale investigations include population pharmacokinetic studies, allometric scaling of drug disposition according to bodyweight and in silico prediction of pharmacokinetics. The last method entails scaling of pharmacokinetic parameters according to age-dependent changes in drug absorption and elimination capacity, plasma protein binding and physiological characteristics of the subjects. Maturation (or ontogeny) of the drug-metabolising part of the cytochrome P450 (CYP) enzyme system is thus an important factor in the calculations for most drugs. The aim of this commentary is to test and critically examine the proposed methods to estimate hepatic clearance (CL) as a function of age (0-20 years), with CYP3A-mediated metabolism as the case in point. Midazolam and alfentanil were used as model drugs.Allometric scaling failed to predict the CL of midazolam and alfentanil in neonates. Calculations using in vitro findings on CYP maturation gave better estimates for neonates but very divergent ones for older infants and children. This was chiefly due to very different data on CYP3A4/5 ontogeny in three published studies. In the age range where full adult CYP activity per gram of liver could be assumed, allometric scaling and in silico predictions gave similar results. These predictions were also in approximate agreement with clinical data.The findings with the two model drugs can very probably be generalised to most drugs cleared by CYP-dependent hepatic metabolism. Allometric scaling accounts for development of body size and function but not for the fact that the drug-metabolising capacity of the liver is generally low at birth. The crucial question in the prediction of CL is thus when the activity of the applicable CYP isoform(s) attains adult levels. There are still not enough data on this, particularly when different studies even on the same CYP isoform have given very divergent results. It may also be pointed out that CYP ontogeny is an area where we have at least some information. There are several other important developmental changes about which we know practically nothing. Thus, while allometric scaling is generally unreliable for prediction in neonates and infants, the alternative method of in silico prediction can at present be used only to obtain tentative initial estimates of drug CL. Neither of the methods can be used as a substitute for actual clinical studies.
7.
Blomgren, Bo, et al.
(författare)
A novel method for quantification of the folding of elastic laminae in elastic arteries
2008
Ingår i: Micron. - : Elsevier BV. - 0968-4328 .- 1878-4291. ; 39:5, s. 623-630
Forskningsöversikt (refereegranskat) abstract
A transgenic mouse overexpressing the human form of semicarbazide-sensitive amine oxidase (SSAO) is known to have an abnormal structure of the elastic laminae and the elastic fibres in the aorta. Compared to the non-transgenic littermates, the elastic laminae are less folded. In order to quantify the undulation of this structure, an image analysis program that identified the elastic laminae was developed. The program measures the area fraction in different sectors from a plane parallel to the aorta wall. Images were taken from unstained aorta specimens where the elastic laminae were visualised with phase contrast microscopy. A contextual operation of the images produced a local orientation estimation for every linear structure. The image was then thresholded in eight sectors from 0 degrees to 180 degrees, with different orientation angles. The results show that the area fraction of the elastic laminae was significantly lower for the transgenic mouse in all sectors measured except for two. At 0-25 degrees, no difference was seen. In the sector at 160-180 degrees, parallel to the aorta wall, the area fraction of elastic laminae was instead significantly higher in the transgenic mouse. A novel method is presented, developed for detection and quantification of pathological changes in the elastic laminae in the aorta wall. The method gave reliable results and is considered to be a useful tool for morphometric studies of aorta with this kind of altered morphology concerning the elastic laminae. When compared with tangent count, the control group had a significantly larger mean curvature.
8.
Borrebaeck, Carl, et al.
(författare)
Progress in miniaturisation of proteon arrays - a step closer to high-density nanoarrays
2007
Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 12:19-20, s. 813-819
Forskningsöversikt (refereegranskat) abstract
Protein microarrays is a technology with great promise for high-throughput proteomics. Designing high-performance protein microarrays for global proteome analysis has, however, turned out to be challenging. To this end, major efforts are under way to design novel array formats capable of harboring the tremendous range of probes required to target complex proteomes composed of more than 10 000 analytes. By adopting nanotechnology, the first generation of miniaturized nanoarrays has recently emerged, which opens up new avenues for global proteome analysis and disease proteomics. This review describes the progress and key issues in designing miniaturized protein arrays.
9.
Bramer, Tobias, et al.
(författare)
Pharmaceutical applications for catanionic mixtures
2007
Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 59:10, s. 1319-1334
Forskningsöversikt (refereegranskat) abstract
Mixtures of oppositely charged surfactants, so called catanionic mixtures, are a growing area of research. These mixtures have been shown to form several different types of surfactant aggregates, such as micelles of various forms and sizes, and lamellar structures, such as vesicles. In this review, a short introduction to the field of catanionic mixtures is presented and the pharmaceutical possibilities offered by such mixtures are reviewed. There are several interesting ideas on how to apply catanionic mixtures to improve the delivery of, for example, drug compounds and DNA, or for HIV treatment.
10.
