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- Zygmunt, P.M., et al.
(författare)
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Effects of ω‐conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor
- 1993
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188. ; 110:4, s. 1285-1290
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Tidskriftsartikel (refereegranskat)abstract
- The effects of ω‐conotoxin GVIA (an inhibitor of N‐type voltage‐operated calcium channels; VOCCs) were compared on adrenergic, cholinergic and non‐adrenergic, non‐cholinergic (NANC) responses induced by electrical field stimulation (EFS) in the rabbit urethra and detrusor. EFS induced a relaxation in urethral smooth muscle and lamina propria precontracted by arginine vasopressin (AVP). The relaxation was abolished by tetrodotoxin (TTX) or the nitric oxide (NO) synthase inhibitor Nω‐nitro‐l‐arginine. ω‐Conotoxin inhibited the relaxation induced by EFS, but not that elicited by the NO donor 3‐morpholino‐sydnonimin. The inhibition, however, decreased with increasing frequencies of stimulation. Nimodipine, tetramethrin and nickel did not affect the ω‐conotoxin‐resistant relaxation in lamina propria, suggesting that neuronal L or T VOCCs were not involved in the response. EFS contracted urethral smooth muscle at resting tension. The contractions were virtually abolished by TTX or prazosin. ω‐Conotoxin effectively inhibited the contractile responses to EFS, but not those to exogenous noradrenaline. An ω‐conotoxin‐resistant contraction was, however, observed at high frequencies of stimulation. The detrusor responded with frequency‐dependent contractions upon EFS. A TTX‐resistant contraction less than 10% of controls remained at 30 Hz stimulation. At a stimulation frequency of 10 Hz, scopolamine reduced the EFS‐induced contraction by 71%. ω‐Conotoxin inhibited the responses in both the absence and presence of scopolamine. The inhibition decreased with increasing frequencies of stimulation (examined in the absence of scopolamine). ω‐Conotoxin did not affect the contractile responses to carbachol or adenosine 5′‐triphosphate. The adrenergic contraction (25 Hz) and NANC relaxation (10 Hz) in the urethra, and cholinergic and NANC contractions (10 Hz) in the detrusor were inhibited concentration‐dependently by ω‐conotoxin. The adrenergic contraction in the urethra was 10 times and the cholinergic contraction in the detrusor was three times more sensitive to ω‐conotoxin than the NANC responses. These results suggest that NANC neurotransmission is less inhibited by ω‐conotoxin than transmission mediated by adrenergic and cholinergic nerves in the rabbit lower urinary tract. In the urethra a marked ω‐conotoxin‐resistant component of the NANC relaxation was observed which increased with increasing stimulation frequencies and was unaffected by inhibitors of L and T type VOCCs. This raises the question whether VOCCs of a type other than L, T, and N is involved in the mediation of this response. 1993 British Pharmacological Society
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| 3. |
- Degerman, Eva, et al.
(författare)
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Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase
- 1994
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002. ; 1205:2, s. 189-198
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Tidskriftsartikel (refereegranskat)abstract
- The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using single step affinity chromatography on the isothiocyanate derivative of cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was 6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of the total protein, respectively. Limited proteolysis of the cGI-PDE with chymotrypsin produced a major fragment of approximately 47 kDa (and at least two smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911 similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of 32P/mol 110/105 and 79 kDa polypeptides; much lower and variable amounts of phosphate were incorporated into the 62 and 55/53 kDa polypeptides. After digestion of cGI-PDE with several proteinases a number of peptides were isolated and sequenced. Most of the peptide sequences obtained could be aligned within the carboxy terminal domain of the deduced sequence of the human cardiac cGI-PDE. These and other results suggest that the subunit size of the intact platelet cGI-PDE is 110 kDa and that proteolytic fragments of 79, 62 and 55/53 kDa are produced during purification. The smaller fragments (62 and 55/53 kDa) contain the catalytic domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain with phosphorylation sites for A-kinase.
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| 6. |
- Johansson, P. A., et al.
(författare)
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Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of L-DOPA-induced dyskinesia
- 2001
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 8:2, s. 220-239
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Tidskriftsartikel (refereegranskat)abstract
- Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with L-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic L-DOPA treatment affected opioid receptor binding in both the basal ganglia and the cerebral cortex, producing changes that were both structure- and receptor-type specific, and closely related to the motor response elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with L-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to L-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.
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| 7. |
- Riemsma, R., et al.
(författare)
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Can incontinence be cured? A systematic review of cure rates
- 2017
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Ingår i: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 15:63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Incontinence constitutes a major health problem affecting millions of people worldwide. The present study aims to assess cure rates from treating urinary (UI) or fecal incontinence (FI) and the number of people who may remain dependent on containment strategies. Methods: Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PEDro were searched from January 2005 to June 2015. Supplementary searches included conference abstracts and trials registers (2013-2015). Included studies had patients >= 18 years with UI or FI, reported treatment cure or success rates, had >= 50 patients treated with any intervention recognized in international guideline algorithms, a followup >= 3 months, and were published from 2005 onwards. Title and abstract screening, full paper screening, data extraction and risk-of-bias assessment were performed independently by two reviewers. Disagreements were resolved through discussion or referral to a third reviewer where necessary. A narrative summary of included studies is presented. Results: Most evidence was found for UI: Surgical interventions for stress UI showed a median cure rate of 82.3% (interquartile range (IQR), 72-89.5%); people with urgency UI were mostly treated using medications ( median cure rate for antimuscarinics = 49%; IQR, 35.6-58%). Pelvic floor muscle training and bulking agents showed lower cure rates for UI. Sacral neuromodulation for FI had a median cure rate of 38.6% (IQR, 35.6-40.6%). Conclusions: Many individuals were not cured and hence may continue to rely on containment. No studies were found assessing success of containment strategies. There was a lack of data in the disabled and in those with neurological diseases, in the elderly and those with cognitive impairment. Surgical interventions were effective for stress UI. Other interventions for UI and FI showed lower cure rates. Many individuals are likely to be reliant on containment strategies.
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| 9. |
- Andersson, A. K. E., et al.
(författare)
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Chemical Expansion Due to Hydration of Proton-Conducting Perovskite Oxide Ceramics
- 2014
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Ingår i: Journal of the American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 97:8, s. 2654-2661
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structures of proton-conducting BaZr1-xYxO3-x/2 (BZY05-BZY20) and BaCe0.8Y0.2O2.9 (BCY20) during hydration/dehydration has been studied by in situ high-temperature X-ray diffraction and thermal analysis. A contraction/expansion of the crystal lattice associated with dehydration/hydration was observed for all materials at elevated temperatures and the polymorphic phase transition temperatures of BaCe0.8Y0.2O2.9 were depressed by lowering the vapor pressure of water. A thermodynamic formalism is introduced to describe the chemical expansion associated with the hydration of oxygen vacancies in acceptor-doped oxides. A conventional point defect model was applied to describe the lattice strain associated with the hydration. The chemical expansion is discussed with respect to the available volumetric data on the hydration of proton-conducting oxide materials and its likely impact on ceramic fuel cells/hydrogen separation membranes utilizing a proton-conducting electrolyte.
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