| 1. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors
- 2010
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an L-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed K-i values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 mu M and 0.33 mu M respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M461, V82F, and 184V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.
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| 2. |
- Alterman, Mathias, et al.
(författare)
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P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 13:2, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.
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| 3. |
- Andersson, Pia, et al.
(författare)
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Comparison of oral health status on admission and at discharge in a group of geriatric rehabilitation patients
- 2003
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Ingår i: Oral health & preventive dentistry. - : Quintessence. - 1757-9996 .- 1602-1622. ; 1:3, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to compare oral health status on a geriatric rehabilitation ward among patients who were assessed using the Revised Oral Assessment Guide (ROAG) on admission and at discharge; and to investigate in what respect the oral health procedures (OHP) suggested in ROAG were applied when oral health problems were detected. MATERIALS AND METHODS: Registered nurses on the ward performed oral health assessments using ROAG with 107 patients on admission and at discharge. When oral health problems were detected measures to be taken were suggested using ROAG. RESULTS: Oral health problems were common among the patients on admission (86%), as well as at discharge (51%). The frequency of the problems was significantly lower at discharge compared to admission. The OHP that were recommended in ROAG were completely followed when saliva flow-related problems were detected. Regarding other oral health problems, measures other than the recommended ones were often performed. CONCLUSION: This study demonstrated that the oral health was better at the end of the hospital stay compared to admission.
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| 4. |
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| 5. |
- Andersson, Pia, et al.
(författare)
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Inter-rater reliability of an oral assessment guide for elderly patients residing in a rehabilitation ward
- 2002
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Ingår i: Special Care in Dentistry. - : Wiley. - 0275-1879 .- 1754-4505. ; 22:5, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to test the inter-rater reliability of a revised oral assessment guide (ROAG) for patients residing in a geriatric rehabilitation ward. A consecutive sample of 140 patients was recruited for the study. Oral assessments were performed for 133 newly admitted patients by one registered nurse (RN) during a period of six months. A dental hygienist (DH) carried out 103 oral assessments during the same half-year. For 66 patients, the RN and the DH performed independent assessments. There was an agreement between the RN and the DH in the majority of the independent assessments, except for tongue and teeth/dentures. The percentage agreement exceeded 80 percent. Inter-rater agreement measured by Cohen's Kappa coefficient ranged from moderate to very good and percentage agreement had a range of 58 to 91 percent. The agreement was highest in assessment of voice and swallowing (91%). Assessments of teeth and dentures seemed to be most difficult for the RN to evaluate. ROAG was found to be a clinically useful assessment tool. Additional education and training is needed to improve the reliability of the oral assessments and should include continuous support from a dental hygienist as well as a pictorial manual on how to use the ROAG.
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| 6. |
- Andersson, P, et al.
(författare)
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Oral health and nutritional status in a group of geriatric rehabilitation patients
- 2002
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 16:3, s. 311-318
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to evaluate the oral health status and nutritional status in a group of geriatric rehabilitation patients, and to analyse the relationship between these two parameters. Nurses at the ward performed structured assessments of oral and nutritional status using the Revised Oral Assessment Guide and the Subjective Global Assessment form in 223 newly admitted patients. Most oral health problems were found among patients who stayed longer at the hospital and were more dependent on help as compared with the healthier patients. Thirty-four per cent of the patients were either severely undernourished, at risk or suspected to be undernourished (UN). Oral health problems were more common among UN patients (p < 0.0005) compared with well-nourished patients. The most frequent oral health problem was found on teeth or dentures (48%). Problems related to the tongue and lips were also common among UN patients (56 and 44%, respectively). Oral health status was correlated (r = 0.32) to nutritional status. Problems with swallowing had the strongest association to the nutritional status (OR 6.05; 95% CI 2.41-15.18). This study demonstrated that poor oral health status was related to undernourishment.
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| 7. |
- Andersson, P, et al.
(författare)
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Oral health problems in elderly rehabilitation patients
- 2004
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Ingår i: International Journal of Dental Hygiene. - : Wiley. - 1601-5029 .- 1601-5037. ; 2:2, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- A combination of poor oral hygiene and dry mouth may be hazardous to the oral health status. However, systematic assessments in order to detect oral health problems are seldom performed in the nursing care of the elderly. The aims of this study were to investigate the occurrence of oral health problems measured using the Revised Oral Assessment Guide (ROAG) and to analyse associations between oral health problems and age, gender, living conditions, cohabitation, reason for admission, number of drugs, and functional and nutritional status. One registered nurse performed oral health assessments using ROAG in 161 newly admitted elderly patients in rehabilitation care. Oral health problems were found in 71% of the patients. Thirty per cent of these patients had between four and eight problems. Low saliva flow and problems related to lips were the most frequent oral health problems. Problems in oral health status were significantly associated with presence of respiratory diseases (problems with gums, lips, alterations on the tongue and mucous membranes), living in special accommodation (low saliva flow, problems with teeth/dentures and alterations on the tongue), being undernourished (alterations on the tongue and low saliva flow) and being a woman (low saliva flow). The highest Odds ratio (OR) was found in problems with gums in relation with prevalence of respiratory diseases (OR 8.9; confidence interval (CI) 2.8-27.8; P < 0.0005). This study indicates the importance of standardised oral health assessments in order to detect oral health problems which can otherwise be hidden when the patients are admitted to the hospital ward.
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| 8. |
- Andersson, P, et al.
(författare)
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Testing an oral assessment guide during chemotherapy treatment in a Swedish care setting: a pilot study
- 1999
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 1365-2702 .- 0962-1067. ; 8:2, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- Oral complications are common in patients with haematological malignancies who undergo chemotherapy treatment. A pilot study including 16 haematological patients was carried out to evaluate the oral status using an Oral Assessment Guide (OAG) and to test the reliability of the OAG. The oral assessments were made daily by registered nurses at a Department of Internal Medicine in Sweden. Once a week a dental hygienist made the oral assessments independent of the registered nurses in order to provide data for calculations of inter-rater reliability. All patients had varying degrees of alterations in the oral cavity, especially in the mucous membranes, teeth/dentures and gums. The inter-rater agreement between the nurses and the dental hygienist was good for saliva and swallow, and moderate for voice and gums. Assessments to detect alterations in the oral cavity afford the opportunity for early and individualized interventions and may decrease the risk of oral infections. It is necessary to train the nurses to ensure high levels of reliability in the oral assessments. The OAG seems to be a reliable and clinical useful tool for assessing the oral cavity status and determining changes.
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| 9. |
- Balciunas, Darius, et al.
(författare)
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Functional interactions within yeast mediator and evidence of differential subunit modifications
- 2003
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 278:6, s. 3831-3839
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Tidskriftsartikel (refereegranskat)abstract
- It is possible to recruit RNA polymerase II to a target promoter and, thus, activate transcription by fusing Mediator subunits to a DNA binding domain. To investigate functional interactions within Mediator, we have tested such fusions of the lexA DNA binding domain to Med1, Med2, Gal11, Srb7, and Srb10 in wild type, med1, med2, gal11, sin4, srb8, srb10, and srb11 strains. We found that lexA-Med2 and lexA-Gal11 are strong activators that are independent of all Mediator subunits tested. lexA-Srb10 is a weak activator that depends on Srb8 and Srb11. lexA-Med1 and lexA-Srb7 are both cryptic activators that become active in the absence of Srb8, Srb10, Srb11, or Sin4. An unexpected finding was that lexA-VP16 differs from Gal4-VP16 in that it is independent of the activator binding Mediator module. Both lexA-Med1 and lexA-Srb7 are stably associated with Med4 and Med8, which suggests that they are incorporated into Mediator. Med4 and Med8 exist in two mobility forms that differ in their association with lexA-Med1 and lexA-Srb7. Within purified Mediator, Med4 is present as a phosphorylated lower mobility form. Taken together, these results suggest that assembly of Mediator is a multistep process that involves conversion of both Med4 and Med8 to their low mobility forms.
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