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1.
Neuroimage ; 225: 117480, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33099009

ABSTRACT

The brain can be modelled as a network with nodes and edges derived from a range of imaging modalities: the nodes correspond to spatially distinct regions and the edges to the interactions between them. Whole-brain connectivity studies typically seek to determine how network properties change with a given categorical phenotype such as age-group, disease condition or mental state. To do so reliably, it is necessary to determine the features of the connectivity structure that are common across a group of brain scans. Given the complex interdependencies inherent in network data, this is not a straightforward task. Some studies construct a group-representative network (GRN), ignoring individual differences, while other studies analyse networks for each individual independently, ignoring information that is shared across individuals. We propose a Bayesian framework based on exponential random graph models (ERGM) extended to multiple networks to characterise the distribution of an entire population of networks. Using resting-state fMRI data from the Cam-CAN project, a study on healthy ageing, we demonstrate how our method can be used to characterise and compare the brain's functional connectivity structure across a group of young individuals and a group of old individuals.


Subject(s)
Bayes Theorem , Brain/physiology , Models, Neurological , Nerve Net/physiology , Brain Mapping/methods , Humans , Individuality , Magnetic Resonance Imaging , Models, Statistical , Neural Pathways
2.
Neuroimage ; 157: 635-647, 2017 08 15.
Article in English | MEDLINE | ID: mdl-28578129

ABSTRACT

Several methods have been developed to measure dynamic functional connectivity (dFC) in fMRI data. These methods are often based on a sliding-window analysis, which aims to capture how the brain's functional organization varies over the course of a scan. The aim of many studies is to compare dFC across groups, such as younger versus older people. However, spurious group differences in measured dFC may be caused by other sources of heterogeneity between people. For example, the shape of the haemodynamic response function (HRF) and levels of measurement noise have been found to vary with age. We use a generic simulation framework for fMRI data to investigate the effect of such heterogeneity on estimates of dFC. Our findings show that, despite no differences in true dFC, individual differences in measured dFC can result from other (non-dynamic) features of the data, such as differences in neural autocorrelation, HRF shape, connectivity strength and measurement noise. We also find that common dFC methods such as k-means and multilayer modularity approaches can detect spurious group differences in dynamic connectivity due to inappropriate setting of their hyperparameters. fMRI studies therefore need to consider alternative sources of heterogeneity across individuals before concluding differences in dFC.


Subject(s)
Connectome/standards , Data Interpretation, Statistical , Image Processing, Computer-Assisted/standards , Magnetic Resonance Imaging/standards , Neurovascular Coupling/physiology , Computer Simulation , Connectome/methods , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods
3.
Burns ; 42(4): 919-25, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27061890

ABSTRACT

BACKGROUND: Burns in Switzerland are frequent and lead to high economic and social costs. However, little is known about the aetiology of burns suffered by patients seeking treatment in hospital emergency departments. This knowledge could be used to develop preventive measures. METHODS: This retrospective analysis included all patients (≥16 years old) with acute thermal injuries of known cause admitted to the adult emergency department in Bern University Hospital (Switzerland, not a specialised burns unit) between 2000 and 2012. Clinical and sociodemographic data were extracted from medical records, i.e. the environment in which the burn occurred, as well as details of burn severity and aetiology. RESULTS: Seven hundred and one (701) patients with a mean age of 35.0±14.5 years (56% men) were included in the analysis. The winter season and the days around Christmas, turn of the year and Swiss National Day were identified as times with high risk of burns. Household (45%) and workplace (31%) were the most common locations/settings in which the burns occurred. Approximately every second burn was caused by scald, every fourth by flame and every seventh by hot objects. The analysis identified cooking, tar and electricity in workplace accidents, barbecues and the use of gasoline as aetiological factors in burns in leisure time, together with water in domestic thermal injuries. Burns occurred predominantly on non-protected skin on the hand and arms. The most severe burns were seen in electrical and flame burns. Men suffered more severe burns than women in all settings except psychopathology. CONCLUSIONS: The data suggest that the incidence and severity of burns in Switzerland could be reduced by preventive strategies and public campaigns, including education on fire protection systems, raising awareness about the times and locations where the risks of burns are greater, further improvement in workplace safety, particularly with cooking facilities and electrical equipment, and the development of innovative safety devices (i.e. machines, protective gloves). These findings have to be interpreted carefully, as this study includes only adult patients who presented in our ED and, in most cases, the burns covered less than 20% of the body surface.


Subject(s)
Burns/etiology , Accidents, Home/statistics & numerical data , Accidents, Occupational/statistics & numerical data , Adult , Burn Units/statistics & numerical data , Burns/epidemiology , Burns, Electric/epidemiology , Emergency Service, Hospital/statistics & numerical data , Female , Fires/statistics & numerical data , Hospitals, University/statistics & numerical data , Humans , Incidence , Leisure Activities , Length of Stay , Male , Middle Aged , Retrospective Studies , Switzerland/epidemiology , Young Adult
4.
J Vet Intern Med ; 29(1): 286-93, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25619520

ABSTRACT

BACKGROUND: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results. OBJECTIVES: The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment. ANIMALS AND METHODS: Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III). RESULTS: At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure. CONCLUSION AND CLINICAL IMPORTANCE: Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans.


Subject(s)
Horse Diseases/drug therapy , Lung Diseases, Obstructive/veterinary , Nanoparticles/therapeutic use , Oligodeoxyribonucleotides/therapeutic use , Animals , Auscultation , Female , Horses , Lung/pathology , Lung Diseases, Obstructive/drug therapy , Male , Mucus , Nanoparticles/adverse effects , Oligodeoxyribonucleotides/adverse effects , Oxygen/blood , Partial Pressure , Respiration/drug effects
5.
J Hosp Infect ; 89(3): 202-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25586987

ABSTRACT

BACKGROUND: Influenza vaccination of healthcare workers (HCWs) is recommended to prevent the transmission of influenza to vulnerable patients. Nevertheless, vaccination coverage rates of HCWs in European countries have been low. AIM: To investigate the relative and combined strength of sociocognitive variables, from past research, theory and a qualitative study, in explaining the motivation of HCWs to receive the influenza vaccine. METHODS: An anonymous, online questionnaire was distributed among HCWs in hospital settings in Belgium, Germany and the Netherlands between February and April 2013. FINDINGS: Attitude and past vaccination uptake explained a considerable amount of variance in the intention of HCWs to receive the influenza vaccine. Moreover, low perceived social norms, omission bias, low moral norms, being older, having no patient contact, and being Belgian or Dutch (compared with German) increased the probability of having no intention to receive the influenza vaccine compared with being undecided about vaccination. High intention to receive the influenza vaccine was shown to be more likely than being undecided about vaccination when HCWs had high perceived susceptibility of contracting influenza, low naturalistic views, and lower motivation to receive the vaccine solely for self-protection. CONCLUSION: Country-specific interventions and a focus on different sociocognitive variables depending on the intention/lack of intention of HCWs to receive the influenza vaccine may be beneficial to promote vaccination uptake.


Subject(s)
Health Personnel/psychology , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Vaccination/psychology , Adult , Attitude of Health Personnel , Belgium , Cognition , Cross-Sectional Studies , Female , Germany , Health Knowledge, Attitudes, Practice , Hospitals , Humans , Influenza, Human/psychology , Intention , Male , Middle Aged , Netherlands , Surveys and Questionnaires , Young Adult
6.
Gesundheitswesen ; 77(1): 16-23, 2015 Jan.
Article in German | MEDLINE | ID: mdl-24566836

ABSTRACT

INTRODUCTION: After the hospital discharge of older patients with multiple morbidities, GPs are often faced with the task of prioritising the patients' drug regimens so as to reduce the risk of overmedication. AIM: How do GPs prioritise such medications in multimorbid elderly patients at the transition between inpatient and home care? The experience by the GPs is documented in typical case vignettes. METHOD: 44 GPs in Sachsen-Anhalt were recruited--they were engaged in focus group discussions and interviewed using semi-standardised questionnaires. Typical case vignettes were developed, relevant to the everyday care that elderly patients would typically receive from their GPs with respect to their drug optimisation. RESULTS: According to the results of the focus groups, the following issues affect GPs' decisions: drug and patient safety, their own competence in the health system, patient health literacy, evidence base, communication between secondary and primary care (and their respective influences on each other). When considering individual cases, patient safety, patient wishes, and quality of life were central. This is demonstrated by the drug dispositions of one exemplary case vignette. CONCLUSIONS: GPs do prioritise drug regimens with rational criteria. Initial problem delineation, process documentation and the design of a transferable product are interlinking steps in the development of case vignettes. Care issues of drug therapy in elderly patients with multiple morbidities should be investigated further with larger representative samples in order to clarify whether the criteria used here are applied contextually or consistently. Embedding case vignettes into further education concepts is also likely to be useful.


Subject(s)
Ambulatory Care/statistics & numerical data , General Practitioners/statistics & numerical data , Health Care Rationing/statistics & numerical data , Health Priorities/statistics & numerical data , Health Services Misuse/prevention & control , Prescriptions/statistics & numerical data , Adult , Aged , Aged, 80 and over , Case-Control Studies , Data Collection , Decision Making , Drug-Related Side Effects and Adverse Reactions/prevention & control , Female , Germany , Health Care Rationing/methods , Health Services for the Aged/statistics & numerical data , Home Care Services , Humans , Male , Medication Therapy Management/statistics & numerical data , Middle Aged , Patient Discharge/statistics & numerical data , Patient Transfer/statistics & numerical data
7.
Ophthalmologe ; 112(1): 49-56, 2015 Jan.
Article in German | MEDLINE | ID: mdl-25033948

ABSTRACT

PURPOSE: Are there any morphological parameters in pigment epithelial detachment (PED) in eyes with age-related macular degeneration (AMD), which could identify the development of tears (RIP) in the retinal pigment epithelium (RPE) before initiation of anti-vascular endothelial growth factor (VEGF) therapy? METHODS: Retrospectively, the spectral domain optical coherence tomography (SD-OCT), FLA and near infrared (NIR) images of 98 eyes with PED in exudative AMD before treatment (ranibizumab or bevacizumab) were analyzed. Eyes in which a tear in the RPE (RIP group) could be observed during treatment were compared to eyes without the development of RIP (PED group) in the following morphological parameters of PED: height, number of peaks, presence of hyporeflective fissures at the base of the PED, structure of the RPE, presence of floating structures in the PED with maximum hyperreflectivity, amount and localization of hyperreflectivity in the PED and hyperreflectivity in the NIR images. RESULTS: In the 80 eyes of the PED group the mean PED height was 373.7± 197 µm and in the 18 eyes of the RIP group the mean PED height was higher (694.2± 284.3 µm, p < 0.0001). A difference was also seen in the number of peaks per PED (PED group 43%, RIP group 72%, p = 0.039) and in the hyperreflectivity in NIR images (PED group 68%, RIP group 94%, p = 0.033). There were no significant differences in the other morphological parameters. A classification into four types of PED was found by the parameters height and number of peaks. The PED type with a height > 350 µm and one peak (RIP 43%) developed tears more often (p = 0.001) than the PED type < 350 µm with one peak (RIP 0%, p = 0.001). A trend in the visual acuity over 156 weeks was seen: in PED types with heights > 350 µm there was a lower increase in the visual acuity than in PED types < 350 µm (rm ANOVA p = 0.18; ɛ HH = 0.88). Furthermore, in PED types > 350 µm with multiple peaks the total number of injections necessary was higher than in the other PED types (p = 0.032). CONCLUSION: Morphological parameters, such as PED height, number of peaks per PED in OCT images and hyperreflectivity in NIR images are prognostic factors for RPE tears in exudative AMD. The PED height and number of peaks per PED are useful for classification of PED in the daily routine.


Subject(s)
Neovascularization, Pathologic/pathology , Retinal Detachment/pathology , Retinal Detachment/therapy , Retinal Pigment Epithelium/injuries , Wet Macular Degeneration/pathology , Wet Macular Degeneration/therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Central Serous Chorioretinopathy/drug therapy , Central Serous Chorioretinopathy/pathology , Central Serous Chorioretinopathy/prevention & control , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/therapy , Retinal Detachment/complications , Rupture , Tomography, Optical Coherence/methods , Wet Macular Degeneration/drug therapy
8.
Internist (Berl) ; 54(6): 765-8, 2013 Jun.
Article in German | MEDLINE | ID: mdl-23677566

ABSTRACT

A 62-year-old woman presented with severe, isolated thrombocytopenia. Due to the positive family history and normal thrombocyte morphology ANKRD26-associated thrombocytopenia 2 (THC2) was suspected. The diagnosis was confirmed by DNA sequencing. Although this is the first case report on THC2 in Germany, we anticipate that THC2 might be a frequent cause of hereditary thrombocytopenia. A specific therapy was not necessary, but would consist of platelet supplementation.


Subject(s)
Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Hemorrhagic Disorders/diagnosis , Hemorrhagic Disorders/genetics , Polymorphism, Single Nucleotide/genetics , Thrombocytopenia/congenital , Chromosome Breakage , Diagnosis, Differential , Female , Genetic Testing , Humans , Middle Aged , Thrombocytopenia/diagnosis , Thrombocytopenia/genetics
9.
J Intellect Disabil Res ; 57(11): 1068-78, 2013 Nov.
Article in English | MEDLINE | ID: mdl-22974110

ABSTRACT

BACKGROUND: The population of ageing people with mild and moderate intellectual disabilities (ID) is growing rapidly. This study examines how personal resources (physical health, mental health and social networks) impact the well-being of ageing people with ID. METHODS: Longitudinal survey data on 667 people with a mild or moderate ID were acquired via interviews in 2006 and 2010. Indicators of personal resources (physical health, mental health and social networks) were assessed, as were indicators of well-being (satisfaction with life, happiness and loneliness). Additionally, data on background characteristics and autonomy were gathered. RESULTS: The results show that age is positively related to decreased mobility and auditory disabilities and negatively related to independent living, autonomy in how one spends one's leisure time and autonomy in decision-making. Longitudinal analyses demonstrated that, with the exception of health that deteriorated, and social satisfaction that improved, almost all variables remained stable over the 4-year period. Further, good physical health in 2006 predicted happiness in 2010. CONCLUSION: Despite the fact that age is associated with poorer physical and mental health and a smaller social network, this study showed that older people with ID have relatively high levels of well-being. Findings are discussed in the light of coping with ageing and impact of life events.


Subject(s)
Aging/psychology , Cost of Illness , Intellectual Disability/psychology , Mental Health , Social Support , Adolescent , Adult , Aged , Aged, 80 and over , Data Collection , Family Characteristics , Female , Happiness , Hearing Disorders/psychology , Humans , Independent Living , Loneliness , Longitudinal Studies , Male , Middle Aged , Personal Satisfaction , Young Adult
10.
Article in German | MEDLINE | ID: mdl-19266173

ABSTRACT

Regulation (EC) No. 1901/2006 of the European Parliament and the Council dated 12 December 2008 on medicinal products for paediatric use is the result of a survey by the European Commission, concluding that children in the European Union are inadequately treated with medicinal products. The Regulation is addressed to the pharmaceutical industry with the intention to place medicinal products on the market and to the Member States to register all information on medicinal products for the treatment of children. The pharmaceutical industry will be obliged to conduct clinical trials in children for new medicinal products and medicinal products still under patent. This will be supported by incentives and rewards. As a consequence of the requirement to conduct clinical trials in children the framework and conditions have to be defined and ethical considerations have to be respected.


Subject(s)
Clinical Trials as Topic/legislation & jurisprudence , Patient Selection/ethics , Adolescent , Child , Clinical Trials as Topic/ethics , Drug Approval/legislation & jurisprudence , Drug Industry/ethics , Drug Industry/legislation & jurisprudence , Ethics, Research , Germany , Humans , Informed Consent/ethics , Informed Consent/legislation & jurisprudence , Patents as Topic/ethics , Patents as Topic/legislation & jurisprudence , Therapeutic Human Experimentation/ethics , Therapeutic Human Experimentation/legislation & jurisprudence
11.
Oncogene ; 27(29): 4086-95, 2008 Jul 03.
Article in English | MEDLINE | ID: mdl-18332865

ABSTRACT

Ectopic expression of mutant forms of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) lacking lipid (G129E) or lipid and protein (C124S) phosphatase activity decreased sensitivity of MCF-7 breast cancer cells, which have wild-type PTEN, to doxorubicin and increased sensitivity to the mammalian target of rapamycin (mTOR) inhibitor rapamycin. Cells transfected with a mutant PTEN gene lacking both lipid and protein phosphatase activities were more resistant to doxorubicin than cells transfected with the PTEN mutant lacking lipid phosphatase activity indicating that the protein phosphatase activity of PTEN was also important in controlling the sensitivity to doxorubicin, while no difference was observed between the lipid (G129E) and lipid and protein (C124S) phosphatase PTEN mutants in terms of sensitivity to rapamycin. A synergistic inhibitory interaction was observed when doxorubicin was combined with rapamycin in the phosphatase-deficient PTEN-transfected cells. Interference with the lipid phosphatase activity of PTEN was sufficient to activate Akt/mTOR/p70S6K signaling. These studies indicate that disruption of the normal activity of the PTEN phosphatase can have dramatic effects on the therapeutic sensitivity of breast cancer cells. Mutations in the key residues which control PTEN lipid and protein phosphatase may act as dominant-negative mutants to suppress endogenous PTEN and alter the sensitivity of breast cancer patients to chemo- and targeted therapies.


Subject(s)
Breast Neoplasms/enzymology , Drug Resistance, Neoplasm , Mutation, Missense , PTEN Phosphohydrolase/metabolism , Protein Kinases/metabolism , Signal Transduction , Amino Acid Substitution , Antibiotics, Antineoplastic/agonists , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cell Line, Tumor , Doxorubicin/agonists , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Drug Synergism , Female , Gene Expression , Humans , PTEN Phosphohydrolase/antagonists & inhibitors , PTEN Phosphohydrolase/genetics , Protein Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/genetics , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Sirolimus/agonists , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases , Transfection
12.
Horm Metab Res ; 39(2): 71-84, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17326003

ABSTRACT

Vitamins A and D are the first group of substances that have been reported to exhibit properties of skin hormones, such as organized metabolism, activation, inactivation, and elimination in specialized cells of the tissue, exertion of biological activity, and release in the circulation. Vitamin A and its two important metabolites, retinaldehyde and retinoic acids, are fat-soluble unsaturated isoprenoids necessary for growth, differentiation and maintenance of epithelial tissues, and also for reproduction. In a reversible process, vitamin A is oxidized IN VIVO to give retinaldehyde, which is important for vision. The dramatic effects of vitamin A analogues on embryogenesis have been studied by animal experiments; the clinical malformation pattern in humans is known. Retinoic acids are major oxidative metabolites of vitamin A and can substitute for it in vitamin A-deficient animals in growth promotion and epithelial differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is not synthesized in the body and must be derived from carotenoids in the diet. On the other hand, retinoids are also hormones - with intracrine activity - because retinol is transformed in the cells into molecules that bind to and activate specific nuclear receptors, exhibit their function, and are subsequently inactivated. The mechanisms of action of natural vitamin A metabolites on human skin are based on the time- and dose-dependent influence of morphogenesis, epithelial cell proliferation and differentiation, epithelial and mesenchymal synthetic performance, immune modulation, stimulation of angiogenesis and inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites have been approved for the topical and systemic treatment of mild to moderate and severe, recalcitrant acne, photoaging and biologic skin aging, acute promyelocytic leukaemia and Kaposi's sarcoma. On the other hand, the critical importance of the skin for the human body's vitamin D endocrine system is documented by the fact that the skin is both the site of vitamin D (3)- and 1,25-dihydroxyvitamin D (3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for 1,25(OH) (2)D (3). 1,25(OH) (2)D (3) is not only essential for mineral homeostasis and bone integrity, but also for numerous further physiologic functions including regulation of growth and differentiation in a broad variety of normal and malignant tissues, including cells derived from prostate, breast and bone. In keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Other newly detected functions of vitamin D analogues include profound effects on the immune system as well as protection against cancer and other diseases, including autoimmune and infectious diseases, in various tissues. Current investigation of the biological effects of vitamin D analogues are likely to lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. This review summarizes existing knowledge on vitamins A and D, the major vitamin-hormones of the skin.


Subject(s)
Hormones/physiology , Vitamin A/physiology , Vitamin D/physiology , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation , Hormones/metabolism , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/metabolism , Models, Biological , Receptors, Calcitriol/physiology , Retinoids/pharmacokinetics , Retinoids/physiology , Retinoids/toxicity , Skin/growth & development , Skin/immunology , Skin/metabolism , Skin Diseases/drug therapy , Vitamin A/analogs & derivatives , Vitamin A/metabolism , Vitamin D/analogs & derivatives , Vitamin D/metabolism , Vitamin D/therapeutic use , Wound Healing/drug effects
14.
Hautarzt ; 55(5): 446-52, 2004 May.
Article in German | MEDLINE | ID: mdl-15069602

ABSTRACT

Epidermal keratinocytes are the site of both UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D(3) (25 OHD(3)) and the enzymatically controlled hydroxylation via 25-hydroxyvitamin D(3) to the biologically active final product 1alpha,25-dihydroxy vitamin D(3) (1alpha,25(OH)(2)D(3), calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and dermal immunocompetent cells. Calcitriol and other vitamin D-analogues are effective in the treatment of psoriasis because of their anti-proliferative and pro-differentiation effects. One mechanism for UVB-light therapy in psoriasis could be the induction of calcitriol synthesis. A better understanding of the metabolism of vitamin D(3) in the skin opens new perspectives for potential therapeutic applications of vitamin D analogues in inflammatory skin diseases. Further studies investigating the role of vitamin D(3) metabolism in the prevention of malignant skin disorders are needed.


Subject(s)
Cholecalciferol/metabolism , Cholecalciferol/radiation effects , Psoriasis/metabolism , Psoriasis/radiotherapy , Ultraviolet Therapy/methods , Dermatitis/metabolism , Dermatitis/radiotherapy , Humans , Skin Diseases/metabolism , Skin Diseases/radiotherapy , Ultraviolet Rays
15.
Arch Dermatol Res ; 295(1): 24-8, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12709817

ABSTRACT

Cutaneous vitamin D(3) (VD(3)) is generated by UVB-induced photolysis of 7-dehydrocholesterol (7-DHC). VD(3) then undergoes sequential hydroxylation to calcidiol (25-OHD(3)) in the liver and to hormonally active calcitriol (1 alpha,25-(OH)(2)D(3)) in the kidney. Recently, we have described the epidermal VD(3) metabolic pathway by demonstrating the autochthonous formation of calcitriol in cultured keratinocytes. In this study we sought to determine whether photolysis of 7-DHC induced by irradiation of human skin with monochromatic UVB at 300 nm results in epidermal synthesis of calcitriol in vivo. Using a microdialysis technique we demonstrated that UVB irradiation results in a dose- and time-dependent increase in the calcitriol concentration in the extracellular fluid of UVB-irradiated skin. Topical treatment of skin with an ointment containing 2% ketoconazole immediately after irradiation suppressed UVB-induced intraepidermal calcitriol synthesis. This study demonstrates for the first time UVB-triggered synthesis of calcitriol in human skin in vivo. The link between UVB irradiation and synthesis of calcitriol in the skin may be of great importance for regulation of biological processes such as cell growth, differentiation, apoptosis and immunological reactions.


Subject(s)
Calcitriol/biosynthesis , Skin/metabolism , Skin/radiation effects , Ultraviolet Rays , Abdomen , Administration, Topical , Calcitriol/antagonists & inhibitors , Dehydrocholesterols/metabolism , Dehydrocholesterols/radiation effects , Epidermis/metabolism , Humans , Ketoconazole/administration & dosage , Microdialysis , Photolysis , Reference Values , Skin/drug effects
16.
J Clin Periodontol ; 28(12): 1145-50, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11737512

ABSTRACT

AIM: The aim of this study was to evaluate in vivo the effectiveness of scaling and root planing of new oscillating instruments (Periosonic) using a sonic handpiece compared to hand curettes with a split mouth design after 2 months. METHODS: 11 patients with adult periodontitis participated in this study. Plaque index (PII) (O'Leary), bleeding on probing (BOP), probing pocket depth (PPD), recession (REC) and clinical attachment level (CAL) were recorded at baseline and 2 months after treatment. After oral hygiene instruction, 2 randomly assigned quadrants per patient were scaled and root planed with curettes (control side) and the remaining 2 quadrants with the Periosonic instruments 1 and 2 (test side). The student t-test for paired data was used to test the significance of difference between test and control sides. RESULTS: There was no statistical difference (p>0.05) between the 2 sides for the improvement of the clinical parameters excepted for the group with initial PPD of 4-6 mm (test: 1.3+/-0.4 mm PPD reduction, control: 1.6+/-0.4 mm). For PPD > or =7 mm, the test side had better clinical improvement in attachment levels (2.2+/-0.9 mm), less recession (-0.4+/-0.5 mm) with lower PPD reduction (2.4+/-0.6 mm) than the control side (AL: 1.6+/-1.8 mm; REC: -1.3+/-0.7 mm, PPD reduction: 3.0+/-1.4 mm). CONCLUSION: This clinical study demonstrated that Periosonic(R) instruments are clinically at least as effective as curettes in PPD reduction when initial PPD is < or =6 mm and show better clinical attachment level improvement with less recession for initial PPD of > or =7 mm.


Subject(s)
Dental High-Speed Equipment , Dental Scaling/instrumentation , Periodontitis/therapy , Adult , Aged , Dental Instruments , Dental Plaque Index , Humans , Middle Aged , Patient Satisfaction , Periodontal Index , Root Planing/instrumentation , Sonication , Subgingival Curettage/instrumentation , Treatment Outcome
17.
J Clin Periodontol ; 28(11): 1058-66, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11686828

ABSTRACT

AIMS: This study investigated the loss of tooth substance (microg) by means of liquid scintillation in combination with profilometric and SEM analyses in order to evaluate the roughness and morphological changes of the root surface before and after instrumentation. METHOD: 40 polished and irradiated bovine root surfaces were scaled in vitro while covered with 50 ml distilled water using a sonic prototype (Periosonic 1/2), a magnetostrictive ultrasonic (Cavitron with Slimline inserts) scaler and a hand curette. Pressures were applied for the Periosonic, Cavitron and hand curette at 500, 500 and 30 g respectively, for 30-s intervals, up to 120 s. Loss of apatite (microg) was determined from the decays/min (32P) of the water samples using the radiochemical method of liquid scintillation. Replicas were made of the specimens for SEM and profilometric analyses. RESULTS: The least substance loss was noted significantly (p<0.01) at all time intervals after Slimline, followed by the fine sonic prototype Periosonic 2, then the Periosonic 1 and finally the hand curette. In contrast, profilometric and SEM analyses revealed the smoothest root surfaces after the hand curette, whereas Cavitron produced a less smooth surface. CONCLUSION: It can be concluded that this method can reveal very precisely small quantities of substance lost and, in combination with SEM analysis and microroughness measurements, be of considerable value in evaluating the aggressiveness and efficacy of periodontal instruments.


Subject(s)
Dental Scaling/instrumentation , Tooth Abrasion/etiology , Tooth Root/pathology , Ultrasonic Therapy/instrumentation , Animals , Apatites/chemistry , Cattle , Curettage/instrumentation , Dental Scaling/methods , Dentin/pathology , Dentin/ultrastructure , Microscopy, Electron, Scanning , Phosphorus Radioisotopes , Pressure , Radiopharmaceuticals , Replica Techniques , Scintillation Counting , Statistics as Topic , Time Factors , Tooth Abrasion/pathology , Tooth Root/ultrastructure
18.
J Invest Dermatol ; 117(5): 1179-85, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11710930

ABSTRACT

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol (1alpha,25-dihydroxyvitamin D3). This study was initiated to test whether the ultraviolet-B-induced photolysis of provitamin D3 (7-dehydrocholesterol), which results in the formation of vitamin D3, can generate calcitriol in an in vivo-like human skin equivalent model made of fibroblasts in a collagen matrix as the dermal component and keratinocytes as the epidermal component. Cultures were preincubated with increasing concentrations of 7-dehydrocholesterol (0.53-5.94 nmol per cm2 human skin equivalent) at 37 degrees C and irradiated with monochromatic ultraviolet B at wavelengths ranging from 285 to 315 nm (effective ultraviolet doses 7.5-45 mJ per cm2). In our in vitro model irradiation with ultraviolet B resulted in a sequential metabolic process with generation of previtamin D3 followed by the time-dependent formation of vitamin D3, 25-hydroxyvitamin D3, and ultimately calcitriol in the femtomolar range. Unirradiated cultures and irradiated cultures without keratinocytes generated no calcitriol. Irradiation of skin equivalents at wavelengths > 315 nm generated no or only trace amounts of calcitriol. The ultraviolet-B-triggered conversion of 7-dehydrocholesterol to calcitriol was strongly inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases. The amount of calcitriol generated was dependent on the 7-dehydrocholesterol concentration, on wavelength, and on ultraviolet B dose. Hence, keratinocytes in the presence of physiologic concentrations of 7-dehydrocholesterol and irradiated with therapeutic doses of ultraviolet B may be a potential source of biologically active calcitriol within the epidermis.


Subject(s)
Cholecalciferol/biosynthesis , Dehydrocholesterols/metabolism , Hydroxycholecalciferols/biosynthesis , Skin, Artificial , Ultraviolet Rays , Cholecalciferol/metabolism , Collagen , Dose-Response Relationship, Radiation , Fibroblasts/metabolism , Fibroblasts/radiation effects , Humans , Keratinocytes/metabolism , Keratinocytes/radiation effects
19.
J Clin Periodontol ; 28(7): 642-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11422585

ABSTRACT

BACKGROUND: The effects of magnetostrictive ultrasonic instruments and piezoelectric ultrasonic instruments on tooth surfaces seem to differ with regards to root debridement. AIM: The purpose of this study was to compare a magnetostrictive ultrasonic scaling instrument with a piezoelectric ultrasonic scaling instrument and a hand curette regarding time taken, calculus removal, tooth surface roughness (Ra), and SEM examination before and after instrumentation. METHODS: 30 extracted human teeth with subgingival calculus were assigned to one of three treatment groups (n=10). The working force was standardised for both ultrasonic instruments at 200 g and for the curette at 500 g. RESULTS: The results revealed that the time needed for instrumentation was 126.1+/-38.2 s for the curette, significantly more than for the piezoelectric ultrasonic instrument (74.1+/-27.6 s; p<0.05) and 104.9+/-25.4 s for the magnetostrictive ultrasonic instrument. Remaining calculus was similar for all three groups. The end Ra values were significantly worse for the piezoelectric instrument (2.02+/-0.41; p<0.05) compared to 1.42+/-0.48 for the curette and 1.36+/-0.41 for the magnetostrictive instrument. The SEM examination revealed the smoothest surfaces but, subjectively, the most tooth substance loss after the curette, followed by the magnetostrictive instrument, with the least substance loss, and then the piezoelectric instrument, with medium substance loss. CONCLUSION: The piezoelectric ultrasonic scaler was more efficient than the magnetostrictive ultrasonic scaler in removing calculus but left the instrumented tooth surface rougher.


Subject(s)
Dental Scaling/instrumentation , Ultrasonic Therapy/instrumentation , Analysis of Variance , Dental Calculus/pathology , Dental Calculus/therapy , Electricity , Equipment Design , Humans , Magnetics/instrumentation , Microscopy, Electron, Scanning , Pressure , Statistics as Topic , Subgingival Curettage/instrumentation , Time Factors , Tooth/ultrastructure
20.
Gesundheitswesen ; 63(1): 42-8, 2001 Jan.
Article in German | MEDLINE | ID: mdl-11272865

ABSTRACT

It is well known that fish contains high amounts of arsenic (As) compounds (mean values per wet weight [mg x kg-1] Ballin [1]: 41; Falconer et al. [2]: 14; Staveland et al. [3]: 5.2), which are mainly represented by organic As compounds, especially by arsenobetaine. It is generally assumed that arsenobetaine is rapidly eliminated via the urine and therefore seems to be non-toxic for humans. However, the kinetics of arsenobetaine in human blood are unknown to date. Therefore, the following experiments were performed: 14 women of 24 to 32 years of age voluntarily ingested 179 to 292 g of cooked plaice fillet containing 44 (minimum) to 276 (maximum) mg As x kg-1 dry weight. Hence, the volunteers ingested 2.5 (minimum) to 20 (maximum) mg As per person, equivalent to 0.04 to 0.35 mg As x kg-1 body weight. The element As was measured by atomic absorption spectrometry using the graphite furnace technique in order to detect the total amount of As including that of the stable arsenobetaine. In the blood, the highest As values of 55 +/- 5.8 micrograms x L-1 (median) were found 2 hours after fish ingestion. Subsequently the As concentrations declined reaching 16 +/- 0.69 micrograms x L-1 (median) 48 hours after fish ingestion. In respect of the As values in blood recorded between 2 and 10 hours after fish ingestion, rapid elimination could be observed leading to a half-life of 7.1 hours (first value) recorded by linear regression analysis. With regard to the As values in blood between 10 and 48 hours after fish ingestion, a lower elimination rate was estimated with a longer half-life of 63 hours (second value). The reason for this delayed elimination of As is not known. The results indicate that As mainly absorbed as arsenonetaine due to ingestion of fish is not eliminated as fast as had been expected on the basis of published data. As long as it is not known what happens to arsenobetaine remaining for longer periods in the blood with a half-life of 63 hours, caution is advised regarding the general opinion that arsenobetaine is rapidly eliminated and non-toxic for human consumption.


Subject(s)
Arsenic/pharmacokinetics , Fishes , Food Contamination/analysis , Adult , Animals , Arsenicals/pharmacokinetics , Female , Germany , Half-Life , Humans , Metabolic Clearance Rate/physiology
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