| 1. |
- Morin, Maxim, et al.
(author)
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Skin hydration dynamics investigated by electrical impedance techniques in vivo and in vitro
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 17218-
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Journal article (peer-reviewed)abstract
- Skin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.
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| 2. |
- Götrick, Bengt, et al.
(author)
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The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats.
- 2004
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In: Archives of oral biology. - : Elsevier BV. - 0003-9969 .- 1879-1506. ; 49:12, s. 969-73
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Journal article (peer-reviewed)abstract
- Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. Currently it was examined by which principal mechanism tramadol induces oral dryness. The effects of intravenous administration (+/-)-tramadol were studied in rats on the flow of saliva in response to a peripheral cholinergic stimulus or to reflex activation involving the relay of impulses in the central nervous system. In pentobarbitone-anaesthetized rats, the salivary secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The administration alpha- and beta-adrenoceptor antagonists resulted in almost identical acetylcholine-evoked responses as in the absence of tramadol. The secretory response to the application of citric acid on the tongue of the rat was reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p < 0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating inhibitory pathways in the central nervous system and has no anticholinergic effect on the salivary glands at dosages that may be clinically relevant. Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion occurred at a glandular level and depended most likely on a release of noradrenaline from glandular nerve terminals.
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| 3. |
- Lavant, Ewa H., et al.
(author)
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HLA DR-DQ genotyping by capillary electrophoresis for risk assessment for celiac disease.
- 2013
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In: Clinical Applications of Capillary Electrophoresis. - Totowa, NJ : Humana Press. - 9781627030281 - 9781627030298 ; 919, s. 297-307
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Book chapter (other academic/artistic)abstract
- The risk for celiac disease (CD) is clearly related to specific HLA DQA1 and DQB1 alleles, but HLA -typing is often considered too costly for frequent use.Here we present a method using sequence-specific primed PCR (PCR-SSP) for HLA-DR-DQ genotyping optimized for capillary electrophoresis on Applied Biosystems 3130xl Genetic Analyzer. Requiring a total of three PCR reactions and a single electrophoretic step, this method reduces the reagent expenses and technical time for directed HLA typing to distinguish risk alleles for CD, with a sufficient throughput for large-scale screening projects.
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| 4. |
- Shahgaldi, Kambiz, et al.
(author)
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Flow-volume loops derived from three-dimensional echocardiography : a novel approach to the assessment of left ventricular hemodynamics
- 2008
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In: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 6
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Journal article (peer-reviewed)abstract
- Background: This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities. Methods: Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post-processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group. Results: Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume. Conclusion: Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities.
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| 5. |
- Tobin, Gunnar, 1954, et al.
(author)
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Studies of muscarinic receptor subtypes in salivary gland function in anaesthetized rats.
- 2002
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In: Autonomic neuroscience : basic & clinical. - 1566-0702 .- 1872-7484. ; 100:1-2, s. 1-9
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Journal article (peer-reviewed)abstract
- The in vivo study aimed to examine whether muscarinic receptor subtypes other than muscarinic M3 receptors exert exocrine functional roles in the rat salivary glands. The effects of pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were examined on secretion from the major salivary glands evoked by acetylcholine (0.001-10 micromol kg(-1) i.v.) in pentobarbitone-anaesthetized rats. Observations were occasionally made on glandular blood flow. 4-DAMP (0.1-100 nmol kg(-1) i.v.) markedly and equipotently inhibited the acetylcholine-evoked fluid responses in all glands. Pirenzepine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) showed significantly lower inhibitory potency than 4-DAMP, most conspicuously in the parotid, while methoctramine (0.1 micromol kg(-1) i.v.-10 mmol kg(-1) i.v.) exerted an even lesser inhibitory effect. Also against acetylcholine-evoked blood flow increases, 4-DAMP showed a conspicuous potency. At 1 and 10 micromol kg(-1) i.v. of pirenzepine, the antagonist reduced the protein concentration in the submandibular saliva, but not in the parotid saliva. While 4-DAMP (1 and 10 nmol kg(-1) i.v.) significantly inhibited acetylcholine-evoked protein secretory responses in the submandibular glands, methoctramine (below 10 micromol kg(-1) i.v.) affected the responses in neither gland. The reduction of the protein concentration in submandibular saliva caused by 4-DAMP and pirenzepine was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg(-1) i.p.), while L-NAME had no or only minute effects on the parotid protein secretion. Thus, in addition to muscarinic M3 receptors, other muscarinic receptors contribute to in vivo functional responses in rat submandibular and sublingual glands. While these other receptors are muscarinic M1 receptors in the sublingual gland, they may be a different subtype, possibly muscarinic M5 receptors, in the submandibular gland. However, muscarinic M1 receptors may induce indirect effects via nitric oxide in the submandibular gland.
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| 6. |
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| 7. |
- Ellervall, E, et al.
(author)
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Antibiotic prophylaxis in oral healthcare - the agreement between Swedish recommendations and evidence.
- 2010
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In: British Dental Journal. - : Springer Science and Business Media LLC. - 1476-5373 .- 0007-0610. ; 208:3, s. 5-115
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Journal article (peer-reviewed)abstract
- BACKGROUND: Almost all (17/20) Swedish counties have pharmaceutical committees that establish recommendations for the use of antibiotic prophylaxis in oral healthcare.Objective To evaluate the evidence for the use of antibiotic prophylaxis in oral healthcare and the agreement between Swedish recommendations and evidence. MATERIAL AND METHODS: We conducted a systematic literature search in PubMed and the Cochrane Controlled Trials Register. The MeSH terms 'antibiotic prophylaxis' and 'dentistry' were used in the database search. Abstracts were reviewed according to specific inclusion and exclusion criteria. A total of 186 articles were read in full text by the four authors independently. Data extraction and interpretation of data was carried out using a pre-defined protocol. In the end, one case-control study was included for evaluation of evidence. RESULTS: The case-control study included patients with specific cardiac conditions. The study reported a 49% protective efficacy (odds ratio: 0.51) of antibiotic prophylaxis for first-time episodes of endocarditis within 30 days of procedure. This result was not statistically significant. The quality of the evidence was low. No studies were evaluated on patients with other medical conditions. The recommendations included several cardiac and other medical conditions for which there is a lack of evidence or no evidence to support the use of antibiotic prophylaxis.CONCLUSIONS: There is a lack of evidence to support the use of antibiotic prophylaxis. To avoid the risk of adverse events from antibiotics and the risk of developing resistant bacterial strains, the use of antibiotic prophylaxis should be minimised and recommendations in Sweden should be revised to be more evidence-based.
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| 8. |
- Liedberg, Birgitta, et al.
(author)
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'Inadequate' dietary habits and mastication in elderly men
- 2007
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In: Gerodontology. - : Wiley. - 0734-0664 .- 1741-2358. ; 24:1, s. 41-46
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Journal article (peer-reviewed)abstract
- Objective: the aim of this study was to re-evaluate data about oral status, mastication and nutrition in elderly men in Malmö, Sweden, recorded in 1985-1987, to assess associations between inadequate dietary habits, oral conditions and masticatory function. Material and methods: Four hundred and eighty-one med, aged 67-68, participated in a comprehensive health examination, including tooth and denture status and masticatory tests. A separate study of dietary habits and nutritional status was made. Ninety-five men had inadequate dietary habits. The databases of dental/denture status, mastication, nutritional status and social network factors were re-evaluated for assessment of associations. Results: No significant differences between those with adequate or inadequate nutrition were found with regard to the number of teeth, occlusal contracts or removable dentures. Also self-assessed chewing did not show any differences. Conclusion: Inadequate dietary habits were independent of teeth and denture status. Some correlations to social network conditions could be identified. Overweight, obesity, low physical activity and high alcohol intake were more common among those with inadequate nutritional intake.
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| 9. |
- Lönn, Johanna, et al.
(author)
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Lipoprotein modifications by gingipains of Porphyromonas gingivalis
- 2018
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In: Journal of Periodontal Research. - : Wiley-Blackwell Publishing Inc.. - 0022-3484 .- 1600-0765. ; 53:3, s. 403-413
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVE: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro.MATERIAL AND METHODS: Plasma lipoproteins were isolated from whole blood treated with wild-type and gingipain-mutant (lacking either the Rgp- or Kgp gingipains) P. gingivalis by density/gradient-ultracentrifugation and were studied using 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid-reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation.RESULTS: Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high-density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation.CONCLUSIONS: Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.
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| 10. |
- Petruk, Ganna, et al.
(author)
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Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs
- 2023
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In: Nature Communications. - : Springer. - 2041-1723. ; 14, s. 1-20
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Journal article (peer-reviewed)abstract
- There is a clinical need for conceptually new treatments that target the excessive activation of inflammatory pathways during systemic infection. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators interfering with CD14-mediated TLR-dependent immune responses. Here we describe the development of a peptide-based compound for systemic use, sHVF18, expressing the evolutionarily conserved innate structural fold of natural TCPs. Using a combination of structure- and in silico-based design, nuclear magnetic resonance spectroscopy, biophysics, mass spectrometry, cellular, and in vivo studies, we here elucidate the structure, CD14 interactions, protease stability, transcriptome profiling, and therapeutic efficacy of sHVF18. The designed peptide displays a conformationally stabilized, protease resistant active innate fold and targets the LPS-binding groove of CD14. In vivo, it shows therapeutic efficacy in experimental models of endotoxin shock in mice and pigs and increases survival in mouse models of systemic polymicrobial infection. The results provide a drug class based on Nature´s own anti-infective principles.
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