| 1. |
- Bauer, Brigitte, 1978, et al.
(författare)
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Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro.
- 2011
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Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:5, s. 737-43
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis is the most prevalent form of human immunotoxicity. It is caused by reactive low molecular weight chemicals, that is, haptens, coming in contact with the skin where hapten-peptide complexes are formed, activating the immune system. By using sensitizing fluorescent thiol-reactive haptens, that is, bromobimanes, we show how keratinocytes respond to hapten exposure in vitro and reveal, for the first time in a living system, an exact site of haptenation. Rapid internalization and reaction of haptens with keratin filaments were visualized. Subsequently, keratinocytes respond in vitro to hapten exposure by release of membrane blebs, which contain haptenated keratins 5 and 14. Particularly, cysteine 54 of K5 was found to be a specific target. A mechanism is proposed where neoepitopes, otherwise hidden from the immune system, are released after hapten exposure via keratinocyte blebbing. The observed expulsion of modified keratins by keratinocytes in vitro might play a role during hapten sensitization in vivo and should be subject to further investigations.
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| 2. |
- Bender, Johanna, 1975, et al.
(författare)
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Lipid cubic phases in topical drug delivery: Visualization of skin distribution using two-photon microscopy
- 2008
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 129:3, s. 163-169
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of sulphorhodamine B (SRB), a fluorescent hydrophilic model drug, was investigated in human skin after passive diffusion using four different topical delivery systems. The delivery vehicles applied were two bicontinuous lipid cubic systems, a commercial ointment and water. The lipid cubic systems consisted of either monoolein (MO) or phytantriol (PT) and water. The formulations were applied on full-thickness human skin during 24 h. Thereafter the samples were investigated using two-photon microscopy (TPM). The TPM system consisted of an inverted microscope with a 40× water-immersion objective, laser scan-box, and a pulsed femtosecond titanium:sapphire laser operating at 780 nm. The fluorescence was detected using a 560 nm long-pass filter. Sequential optical sectioning was performed, resulting in images obtained at different tissue depths. TPM revealed that SRB mainly penetrates the skin via the intercellular lipid matrix. Samples exposed to the cubic phases showed a higher accumulation of SRB in micro-fissures, from which a fluorescent network of threadlike structures spread laterally in the tissue. These structures were also detected in some of the ointment samples, but not as frequent. The penetration of SRB into the stratum granulosum was deduced from the fluorescence of SRB present inside polygonal keratinocytes with cell nuclei. Higher SRB fluorescence was obtained in the outermost layer of the epidermis using the bicontinuous cubic phases, compared to when using the reference formulations. Thus, our results suggest that the dominating delivery route using the cubic phases is via micro-fissures caused by microscopic clustering of the keratinocytes in the skin. From these micro--fissures hydrophilic compounds, here modeled by SRB, can diffuse into the surrounding intercellular lipid matrix acting like a source for sustained release.
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| 3. |
- Ericson, Marica B, 1974, et al.
(författare)
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Two-photon laser-scanning fluorescence microscopy applied for studies of human skin
- 2008
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Ingår i: Journal of Biophotonics. - : Wiley. - 1864-0648 .- 1864-063X. ; 1:4, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon laser scanning fluorescence microscopy (TPM) has been shown to be advantageous for imaging optically turbid media such as human skin. The ability of performing three-dimensional imaging without presectioning of the samples makes the technique not only suitable for noninvasive diagnostics but also for studies of topical delivery of xenobiotics. Here, TPM is used as a method to visualize both autofluorescent and exogenous fluorophores in skin. Samples exposed to sulforhodamine B have been scanned from two directions to investigate attenuation effects. It is shown that optical effects play a major role. Thus, TPM is excellent for visualizing the localization and distribution of fluorophores in human skin, although quantification might be difficult. Furthermore, an image-analysis algorithm has been implemented to facilitate interpretation of TPM images of autofluorescent features of nonmelanoma skin cancer obtained ex vivo. The algorithm was designed to detect cell nuclei and currently has a sensitivity and specificity of 82% and 78% to single cell nuclei. However, in order to detect multinucleated cells, the algorithm needs further development. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
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| 4. |
- Frykholm, Erik, 1985-, et al.
(författare)
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Applicability of a supramaximal high-intensity interval training program for older adults previously not engaged in regular exercise : analyses of secondary outcomes from the Umeå HIT Study
- 2024
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Ingår i: Psychology of Sport And Exercise. - : Elsevier. - 1469-0292 .- 1878-5476. ; 73
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Tidskriftsartikel (refereegranskat)abstract
- This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults.
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| 5. |
- Guldbrand, Stina, 1970, et al.
(författare)
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Measuring the diffusion of fluorophores in human skin by two-photon fluorescence correlation spectroscopy combined with measurements of point spread function
- 2011
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Ingår i: MULTIPHOTON MICROSCOPY scigloo.IN THE BIOMEDICAL SCIENCES XI Book Series: Proceedings of SPIE. ; 7903, s. 7903291-7903296
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon excitation fluorescence correlation spectroscopy (TPFCS) has been used in combination with measurements of the point spread function (PSF), for quantitative analysis of fluorophores in excised human skin. Measurements have been performed at depths between 0 and 40 μm. The PSF, measured as full width at half maximum, was found not to depend on the depth. Measurements revealed difference in diffusion coefficient depending on extra- or intracellular location of fluorophore. The number of molecules was accumulating close to the surface and then decreased by the depth. The results from our study show that TPFCS can be used for quantitative analyses of fluorescent compounds in human skin.
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| 6. |
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| 7. |
- Guldbrand, Stina, 1970, et al.
(författare)
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Two-photon fluorescence correlation microscopy combined with measurements of point spread function; investigations made in human skin
- 2010
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Ingår i: Optics Express. - 1094-4087. ; 18:15, s. 15289-15302
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Tidskriftsartikel (refereegranskat)abstract
- Two-photon excitation fluorescence correlation spectroscopy (TPFCS) has been applied in connection to measurements of the point spread function (PSF) for quantitative analysis of sulphorhodamine B (SRB) in excised human skin. The PSF was measured using subresolution fluorescent beads embedded in the skin specimen. The PSF, measured as full width at half maximum (FWHM) was found to be 0.41 ± 0.05 μm in the lateral direction, and 1.2 ± 0.4 μm in the axial direction. The molecular diffusion of SRB inside the skin ranged between 0.5 and 15.0 × 10 −8 cm2/s. The diffusion coefficient is not dependent on depths down to 40 μm. The fluorophores were found to accumulate on the upper layers of the skin. This work is the first TPFCS study in human skin. The results show that TPFCS can be used for quantitative analyses of fluorescent compounds in human skin.
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| 8. |
- Guldbrand, Stina, 1970, et al.
(författare)
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Two-photon fluorescence correlation spectroscopy as a tool for measuring molecular diffusion within human skin
- 2013
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411. ; 84:2, s. 430-436
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for tools enabling quantitative imaging of biological tissue for pharmaceutical applications. In this study, two-photon fluorescence microscopy (TPM) has been combined with fluorescence correlation spectroscopy (FCS), demonstrating proof-of-principle providing quantitative data of fluorophore concentration and diffusion in human skin. Measurements were performed on excised skin exposed to either rhodamine B (RB) or rhodamine B isothiocyanate (RBITC), chosen based on their similarity in fluorescence yield and molecular weight, but difference in chemical reactivity. The measurements were performed at tissue depths in the range 0 and 20 pm, and the diffusion coefficients at skin depths 5 and 10 mu m were found to be significantly different (P < 0.05). Overall median values for the diffusion coefficients were found to be 4.0 x 10(-13) m(2)/s and 2.0 x 10(-13) m(2)/s for RB and RBITC, respectively. These values correspond to the diffusion of a hard sphere with a volume eight times larger for RBITC compared to RB. This indicates that the RBITC have bound to biomolecules in the skin, and the measured signal is obtained from the RBITC-biomolecule complexes, demonstrating the potential of the TPM-FCS method to track molecular interactions in an intricate biological matrix such as human skin.
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| 9. |
- Karlsson, Isabella, et al.
(författare)
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The Fate of a Hapten - From the Skin to Modification of Macrophage Migration Inhibitory Factor (MIF) in Lymph Nodes
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by flow cytometry. Identification of the most abundant TRITC-modified protein in lymph nodes by tandem mass spectrometry revealed TRITC-modification of the N-terminal proline of macrophage migration inhibitory factor (MIF) - an evolutionary well-conserved protein involved in cell-mediated immunity and inflammation. This is the first time a hapten-modified protein has been identified in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modification of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions.
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| 10. |
- Kirejev, Vladimir, 1984, et al.
(författare)
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Multiphoton microscopy – a powerful tool in skin research and topical drug delivery science
- 2012
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Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 22:3, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- Multiphoton microscopy (MPM) has become a powerful complementary tool in biomedical research, enabling non-invasive three-dimensional imaging of tissue with high resolution. The major advantage is that investigations and visualization can be performed without mechanical destruction of the sample through tissue sectioning. This review will give a brief introduction to the technology, accompanied by examples of how the technique can be implemented within the field of skin research. Specifically, MPM has already made it possible to visualize cellular morphology and the cutaneous distribution of topically applied compounds applied to intact skin. MPM provides information that can be used to assess the bioavailability of drugs and to visualize drug penetration pathways into skin. MPM has also been implemented as a tool for obtaining non-invasive tissue biopsy based on skin autofluorescence in connection to diagnostics of skin cancer. We will also briefly present some recent results where MPM has been used to track cyclodextrin based drugs applied topically. Finally, we will discuss some future challenges of the technology, including label-free imaging, multimodal techniques, and quantitative imaging.
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| 11. |
- Madsen, Jakob Torp, et al.
(författare)
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Ethosome formulation of contact allergens may enhance patch test reactions in patients*
- 2010
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Ingår i: CONTACT DERMATITIS. - 0105-1873. ; 63:4, s. 209-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ethosomes and liposomes are ultra-small vesicles capable of encapsulating drugs and cosmetic ingredients for topical use, thereby potentially increasing bioavailability and clinical efficacy. So far, few reports have suggested that formulation of cosmetic ingredients in vesicular carrier systems may increase the allergenicity potential. Objectives: To investigate the effect of ethosome formulation of isoeugenol and methyldibromo glutaronitrile on the elicitation response under patch test conditions and by repeated open applications. Patients/Materials/Methods: A total of 27 volunteer patients with a previous positive patch test reaction to either isoeugenol or methyldibromo glutaronitrile were included in the study. In all patients, a serial dilution patch test was performed with the allergen in question formulated in ethosomes and in an ethanol/water solution. In addition, a repeated open application test (ROAT) was performed in a subset of 16 patients, and lag time until a positive response was recorded. Results: Both contact allergens encapsulated in ethosomes showed significantly enhanced patch test reactions as compared with the allergen preparation in ethanol/water without ethosomes. No significant difference in the median lag time was recorded between preparations in the ROAT. Conclusions: Encapsulating potential contact allergens in ethosomes may increase the challenge response as compared with the same concentrations in an ethanol/water base without ethosomes. © 2010 John Wiley & Sons A/S.
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| 12. |
- Madsen, Jacob Torp, et al.
(författare)
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Ethosome Formulations of Known Contact Allergens can Increase their Sensitizing Capacity
- 2010
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 90:4, s. 374-378
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Tidskriftsartikel (refereegranskat)abstract
- Vesicular systems, such as liposomes and ethosomes, are used in cosmetic and pharmaceutical products to encapsulate ingredients, to protect ingredients from degradation, to increase bioavailability, and to improve cosmetic performance. Some reports have suggested that formulation of cosmetic ingredients in vesicular carrier systems may increase their contact allergy elicitation potential in humans. However, no sensitization studies have been published. We formulated two model contact allergens (isoeugenol and dinitrochlorobenzene) in ethosomes and investigated the sensitization response using a modified local lymph node assay (LLNA). The results were compared with those for the same allergens in similar concentrations and vehicles without ethosomes. Both allergens encapsulated in 200–300 nm ethosomes showed increased sensitizing potency in the murine assay compared with the allergens in solution without ethosomes. Empty ethosomes were non-sensitizing according to LLNA. The clinical implications are so far uncertain, but increased allergenicity from ethosome-encapsulated topical product ingredients cannot be excluded.
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| 13. |
- Samuelsson, Kristin, 1979, et al.
(författare)
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Accumulation of FITC near stratum corneum-visualizing epidermal distribution of a strong sensitizer using two-photon microscopy
- 2009
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 61:2, s. 91-100
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Tidskriftsartikel (refereegranskat)abstract
- Background The allergenic potency of a hapten is related to its skin penetration properties, but little is known about the distribution of haptens in the skin following topical application. Objectives The aim of this study was to investigate the diffusion and epidermal distribution using two-photon microscopy (TPM) of two fluorescent compounds. Methods Sensitizing capacities of fluorescein isothiocyanate (FITC) and fluorescein were investigated using the local lymph node assay. Chemical reactivity of the compounds was analysed, and their distribution in human epidermis was visualized using TPM and confocal microscopy. Also the in vitro diffusion through epidermis of FITC and fluorescein has been examined. Results FITC was classified as an extreme sensitizer, whereas fluorescein was non-sensitizing. TPM and confocal microscopy showed an accumulation of FITC in stratum corneum (SC), whereas fluorescein was more evenly distributed in epidermis. The diffusion of fluorescein through epidermis was three times higher than that of FITC. Conclusions TPM, which has never been used in this context before, is a promising tool for visualizing the distribution of fluorescent compounds of varying reactivity in intact skin. The strong allergen FITC is mainly retained in or adjacent to SC, whereas most fluorescein diffused through the epidermis.
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| 14. |
- Simonsson, Carl, 1976, et al.
(författare)
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A study of the enhanced sensitizing capacity of a contact allergen in lipid vesicle formulations.
- 2011
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Ingår i: Toxicology and applied pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 252:3, s. 221-7
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Tidskriftsartikel (refereegranskat)abstract
- The growing focus on nanotechnology and the increased use of nano-sized structures, e.g. vesicles, in topical formulations has led to safety concerns. We have investigated the sensitizing capacity and penetration properties of a fluorescent model compound, rhodamine B isothiocyanate (RBITC), when administered in micro- and nano-scale vesicle formulations. The sensitizing capacity of RBITC was studied using the murine local lymph node assay (LLNA) and the skin penetration properties were compared using diffusion cells in combination with two-photon microscopy (TPM). The lymph node cell proliferation, an indicator of a compounds sensitizing capacity, increased when RBITC was applied in lipid vesicles as compared to an ethanol:water (Et:W) solution. Micro-scale vesicles showed a slightly higher cell proliferative response compared to nano-scale vesicles. TPM imaging revealed that the vesicle formulations improved the skin penetration of RBITC compared to the Et:W solution. A strong fluorescent region in the stratum corneum and upper epidermis implies elevated association of RBITC to these skin layers when formulated in lipid vesicles. In conclusion, the results indicate that there could be an elevated risk of sensitization when haptens are delivered in vehicles containing lipid vesicles. Although the size of the vesicles seems to be of minor importance, further studies are needed before a more generalized conclusion can be drawn. It is likely that the enhanced sensitizing capacity is a consequence of the improved penetration and increased formation of hapten-protein complexes in epidermis when RBITC is delivered in ethosomal formulations.
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| 15. |
- Simonsson, Carl, 1976, et al.
(författare)
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Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
- 2011
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 131:7, s. 1486-93
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis (ACD) is the most prevalent form of human immunotoxicity. It is caused by skin exposure to haptens, i.e., protein-reactive, low-molecular-weight chemical compounds, which form hapten-protein complexes (HPCs) in the skin, triggering the immune system. These immunogenic HPCs are elusive. In this study a series of thiol-reactive caged fluorescent haptens, i.e., bromobimanes, were deployed in combination with two-photon fluorescence microscopy, immunohistochemistry, and proteomics to identify possible hapten targets in proteins in human skin. Key targets found were the basal keratinocytes and the keratins K5 and K14. Particularly, cysteine 54 of K5 was found to be haptenated by the bromobimanes. In addition, elevated levels of anti-keratin antibodies were found in the sera of mice exposed to bromobimanes in vivo. The results indicate a general mechanism in which thiol-reactive haptens generate cryptic epitopes normally concealed from the immune system. In addition, keratinocytes and keratin seem to have an important role in the mechanism behind ACD, which is a subject for further investigations.
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| 16. |
- Simonsson, Carl, 1976
(författare)
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New insights in contact allergy and drug delivery. A study of formulation effects and hapten targets in skin using two-photon fluorescence microscopy
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The skin is a remarkable barrier, protecting us from invasion of e.g. harmful microorganisms and UV-radiation. However, the skin is not adopted to resist repeated exposure to the multitude of xenobiotics introduced into modern society. Some of these chemicals are skin sensitizers, and exposure can lead to the development of contact allergy. Contact allergy has significant social and economic consequences, both for the individual and for society. It is therefore important to prevent sensitization. The skin also constitutes a potential route for administration of drugs, and much effort is put into the development of cutaneous and transdermal drug delivery systems. The work of this thesis aims to improve the understanding of processes related to the interactions between the skin and topically applied compounds, i.e. drugs and skin sensitizers. Specifically, two-photon microscopy has been used to study the cutaneous absorption and distribution of model drugs and a series of model skin sensitizers. Improved cutaneous absorption was demonstrated using formulations composed of lipid cubic phases. The work also showed elevated sensitization potency of haptens depending on delivery vehicles. Putative mechanistic explanations for the observed effects have been proposed. Specifically, phthalates were shown to increase the sensitization potency of isothiocyanates. The phthalate-induced effect could be linked to a PSU-targeted delivery of the haptens into the skin. It could also be shown that vehicles alter hapten reactivity to stratum corneum proteins leading to variations in sensitization potency. Moreover, hapten protein targets in skin have been identified using caged fluorescent model hapten. Specifically, basal cell keratinocytes and the keratins were identified as specific hapten targets in the skin. In conclusion, the work presented in this thesis contributes to the general understanding of the mechanisms involved in the cutaneous absorption of topically applied drugs and skin sensitizers. It also demonstrates the capabilities of using TPM when investigating the interactions between the skin and xenobiotics.
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| 17. |
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| 18. |
- Simonsson, Carl, 1976, et al.
(författare)
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The pilosebaceous unit-a phthalate-induced pathway to skin sensitization
- 2012
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 264:1, s. 114-120
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. (C) 2012 Elsevier Inc. All rights reserved.
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| 19. |
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| 20. |
- Simonsson, Emma, et al.
(författare)
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Effects of controlled supramaximal high-intensity interval training on cardiorespiratory fitness and global cognitive function in older adults : the Umeå hit study-a randomized controlled trial
- 2023
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 78:9, s. 1581-1590
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study examined the effects of regulated and controlled supramaximal high-intensity interval training (HIT) adapted for older adults, compared to moderate-intensity training (MIT), on cardiorespiratory fitness; cognitive, cardiovascular, and muscular function; and quality of life.METHODS: Sixty-eight nonexercising older adults (66-79 years, 44% males) were randomized to 3 months of twice-weekly HIT (20-minute session including 10 × 6-second intervals) or MIT (40-minute session including 3 × 8-minute intervals) on stationary bicycles in an ordinary gym setting. Individualized target intensity was watt controlled with a standardized pedaling cadence and individual adjustment of the resistance load. Primary outcomes were cardiorespiratory fitness (V̇o2peak) and global cognitive function (unit-weighted composite).RESULTS: V̇o2peak increased significantly (mean 1.38 mL/kg/min, 95% CI [0.77, 1.98]), with no between-group difference (mean difference 0.05 [-1.17, 1.25]). Global cognition did not improve (0.02 [-0.05, 0.09]), nor differed between groups (0.11 [-0.03, 0.24]). Significant between-group differences in change were observed for working memory (0.32 [0.01, 0.64]), and maximal isometric knee extensor muscle strength (0.07 N·m/kg [0.003, 0.137]), both in favor of HIT. Irrespective of the group, there was a negative change in episodic memory (-0.15 [-0.28, -0.02]), a positive change in visuospatial ability (0.26 [0.08, 0.44]), and a decrease in systolic (-2.09 mmHg [-3.54, -0.64]) and diastolic (-1.27 mmHg [-2.31, -0.25]) blood pressure.CONCLUSIONS: In nonexercising older adults, 3 months of watt-controlled supramaximal HIT improved cardiorespiratory fitness and cardiovascular function to a similar extent as MIT, despite half the training time. In favor of HIT, there was an improvement in muscular function and a potential domain-specific effect on working memory.CLINICAL TRIAL REGISTRATION: NCT03765385.
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