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Biomedical subjects

A Wenzel

Publications and source records attributed to A Wenzel.

At least 19 recordsLinked to original sources

Hypoxic preconditioning and erythropoietin protect retinal neurons from degeneration.

Reduced tissue oxygenation stabilizes the alpha-subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1). This leads to the induction of a number of hypoxia responsive genes. One of the best known HIF-1 targets is erythropoietin that exerts neuroprotective effects on ischemia-related injury in the brain. Thus, pre-exposure to low environmental oxygen concentrations might be exploited as a preconditioning procedure to protect tissues against a variety of harmful conditions. We present recent work on neuroprotection of retinal photoreceptors induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.

Animals↗

Longitudinal study of periapical and endodontic status in a Danish population.

AIM: To describe and discuss changes in periapical and endodontic status in a general Danish population. METHODOLOGY: In 1997, 616 randomly selected individuals had a full-mouth radiographic survey taken. In 2003, 77% of the participants attended for a new full-mouth radiographic examination. Information on endodontic treatment and periapical status was obtained. The periapical index (PAI) was used to assess apical periodontitis (AP). RESULTS: More participants had root filling(s) and AP in 2003 than in 1997. More teeth had AP and/or root fillings in 2003. Fewer of the root-filled teeth (RFT) had AP in 2003. Less than 3% of the teeth without root fillings (NRFT) that in 1997 had no AP, developed AP and/or received a root filling. Of the NRFT which in 1997 had AP, more than 35% still had AP and no root filling in 2003. Approximately, 30% of the NRFT with AP in 1997 received a root filling. Of the teeth that received a root filling, 40% had healed, whereas 60% had not. Approximately, 25% of the NRFT that in 1997 had AP had been extracted. In 1997 there were 618 RFT, 314 of the RFT had no AP in 1997. Almost 20% of the RFT that in 1997 were periapically sound, developed AP. Of the 304 RFT with AP in 1997, approximately 30% had healed, in 60% AP persisted, and 10% were extracted. CONCLUSIONS: The present study indicates that caution must be exercised when statements on the outcome of root canal treatment are made based on the cross-sectional studies.

Adult↗

Rpe65 as a modifier gene for inherited retinal degeneration.

Light accelerates progression of retinal degeneration in many animal models of retinitis pigmentosa (RP). A sequence variant in the Rpe65 gene (Rpe65(450Leu) or Rpe65(450Met)) can act as a modulator of light-damage susceptibility in mice by influencing the kinetics of rhodopsin regeneration and thus by modulating the photon absorption. Depending on exposure duration and light intensity applied, white fluorescent light induces photoreceptor apoptosis and retinal degeneration in wild-type mice by the activation of one of two known molecular pathways. These pathways depend, respectively, on activation of the transcription factor c-Fos/AP-1 and on phototransduction activity. Here we tested Rpe65 as a genetic modifier for inherited retinal degeneration and analysed which degenerative pathway is activated in a transgenic mouse model of autosomal dominant RP. We show that retinal degeneration was reduced in mice expressing the Rpe65(450Met) variant and that these mice retained more visual pigment rhodopsin than did transgenic mice expressing the Rpe65(450Leu) variant. In addition, lack of phototransduction slowed retinal degeneration whereas ablation of c-Fos had no effect. We conclude that sequence variations in the Rpe65 gene can act as genetic modifiers in inherited retinal degeneration, presumably by regulating the daily rate of photon absorption through the modulation of rhodopsin regeneration kinetics. Increased absorption of photons and/or light sensitivity appear to accelerate retinal degeneration via an apoptotic cascade which involves phototransduction but not c-Fos.

Age Factors↗

Influence of autologous platelet concentrate on healing in intra-bony defects following guided tissue regeneration therapy: a randomized prospective clinical split-mouth study.

OBJECTIVES: To investigate the influence of autologous platelet concentrate (APC) on early wound healing and regeneration outcomes following guided tissue regeneration (GTR) therapy. MATERIAL AND METHODS: In 25 patients, two contralateral deep intra-bony defects were treated with beta-TCP and a bioresorbable GTR membrane. They were randomly assigned to test and control procedure. In test defects, APC was additionally applied. After 3, 6, and 12 months, healing results were assessed by clinical parameters and quantitative digital subtraction radiography. RESULTS: Post-operative membrane exposures occurred in 48% of the test sites and 80% of the control sites. Both groups revealed a significant clinical attachment level (CAL) gain of 5 mm after 12 months. Eighty-eight per cent of test and control sites showed a CAL gain of > or =4 mm. No clinical parameter revealed significant differences between test and control sites. A significant bone density gain was found in both groups after 3, 6, and 12 months. Only after 6 months, the bone density gain was significantly greater in the test defects. CONCLUSION: Within the limits of this study, autologous platelet concentrate did not seem to have a noticeable influence on the clinical and most of the radiographic outcomes following GTR. However, APC might reduce the occurrence of post-operative membrane exposures and accelerate bone density gain.

Absorbable Implants↗

Comparison of simulated periodontal bone defect depth measured in digital radiographs in dedicated and non-dedicated software systems.

OBJECTIVES: To compare simulated periodontal bone defect depth measured in digital radiographs with dedicated and non-dedicated software systems and to compare the depth measurements from each program with the measurements in dry mandibles. METHODS: Forty periodontal bone defects were created at the proximal area of the first premolar in dry pig mandibles. Measurements of the defects were performed with a periodontal probe in the dry mandible. Periapical digital radiographs of the defects were recorded using the Schick sensor in a standardized exposure setting. All images were read using a Schick dedicated software system (CDR DICOM for Windows v.3.5), and three commonly available non-dedicated software systems (Vix Win 2000 v.1.2; Adobe Photoshop 7.0 and Image Tool 3.0). The defects were measured three times in each image and a consensus was reached among three examiners using the four software systems. The difference between the radiographic measurements was analysed using analysis of variance (ANOVA) and by comparing the measurements from each software system with the dry mandibles measurements using Student's t-test. RESULTS: The mean values of the bone defects measured in the radiographs were 5.07 mm, 5.06 mm, 5.01 mm and 5.11 mm for CDR Digital Image and Communication in Medicine (DICOM) for Windows, Vix Win, Adobe Photoshop, and Image Tool, respectively, and 6.67 mm for the dry mandible. The means of the measurements performed in the four software systems were not significantly different, ANOVA (P = 0.958). A significant underestimation of defect depth was obtained when we compared the mean depths from each software system with the dry mandible measurements (t-test; P approximately equal to 0.000). CONCLUSIONS: The periodontal bone defect measurements in dedicated and in three non-dedicated software systems were not significantly different, but they all underestimated the measurements when compared with the measurements obtained in the dry mandibles.

Alveolar Bone Loss↗

A review of dentists' use of digital radiography and caries diagnosis with digital systems.

OBJECTIVES: To investigate the evidence for (1) dentists' use of digital radiography and (2) the outcome of caries diagnosis with digital systems. METHODS: A literature search with the software search package PubMed was used to get internet-based access to Medline through the website www.ncbi.nlm.nih.gov/pubmed. The search was limited to the years 1999-2005 since most papers dealing with the diagnostic value of digital radiography systems published before 1999 will hold little interest for today's users due to changes in the systems. The search strategies resulted in 123 articles (Table 1, #4 and #5). Original research articles (not reviews) were selected by the following inclusion criteria: (1) questionnaire studies on the use of direct digital intraoral radiography systems (not digitized film), (2) studies which used human teeth and natural caries lesions, and further in laboratory studies, the sectioned tooth was the gold standard for validating the presence or depth of a lesion. RESULTS: The search resulted in 42 articles fulfilling the above criteria, which could be grouped into three types of studies: (a) questionnaire studies, (b) clinical (in vivo) studies, and (c) laboratory (in vitro) studies. Nine questionnaire studies, five clinical studies and 28 laboratory studies were found. These studies and their results are summarized in Tables 2-5. CONCLUSIONS: The number of studies was limited, and some of the digital systems were evaluated in only one or two studies. A conclusive judgment may therefore not be possible for the majority of the digital systems selected for this review. There is a continuous need for the evaluation of new digital intraoral radiography systems that appear on the market, first and foremost for their image quality and diagnostic accuracy, but certainly also for their performance in the clinic, a clear deficiency observed after the literature search for the present review.

Dental Caries↗

Modulation of iodide uptake by dialkyl phthalate plasticisers in FRTL-5 rat thyroid follicular cells.

Plasticisers imparting flexibility to plastics are man-made chemicals abundantly present in the environment. Effects of six different dialkyl phthalates were studied in vitro in the rat thyroid cell line FRTL-5 on their ability to modulate basal iodide uptake mediated by the sodium/iodide symporter (NIS). The present study shows that diisodecyl phthalate (DIDP), dioctyl phthalate (DOP), diisononyl phthalate (DINP) and bis (2-ethylhexyl) phthalate (DEHP) significantly enhance iodide uptake when concentrations in the magnitude between 10(-4) M and 10(-3) M were applied. In this range, these phthalates do not assess toxicity on the cells. Specific inhibiton of NIS demonstrated that enhancement of iodide uptake is due to NIS. In contrast, benzyl butyl phthalate (BBP) also augments iodide uptake at 1mM but this concentration has just exceeded the toxicity threshold and dibutyl phthalate (DBP), the most toxic compound did not modulate iodide uptake at any concentration applied. As we can deduce from our results, plasticisers are capable of significantly modulating NIS mediated iodide uptake activity.

Animals↗

Neuroprotection by hypoxic preconditioning: HIF-1 and erythropoietin protect from retinal degeneration.

Hypoxic exposure of cells or organisms induces expression of a number of hypoxia responsive genes through the activation of the hypoxia-inducible factor-1 (HIF-1). One of the most prominent HIF-1 targets is erythropoietin that has beneficial effects on ischemia-related injury in the brain. Exposure to low environmental oxygen concentrations can be used as a preconditioning paradigm to protect cells or tissues against a variety of harmful conditions. Here, we summarize recent work on neuroprotection of retinal photoreceptors and ganglion cells induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.

Animals↗

[Survival factors in the treatment of hereditary retinal degeneration].

Hereditary retinal degeneration is characterized by apoptotic photoreceptor loss, a process governed by intricate molecular interplay and initiated when proapoptotic signals predominate in the individual cell. Identification of molecules involved and their actions has paved the way for testing the ones with anti-apoptotic functions in models of inherited retinal degeneration. Many of these factors are able to slow the course of the degeneration. However, to date no such treatment has been able to stop or even prevent the devolution of the disorder. Moreover, preservation of morphology does not necessarily correlate with preservation of ERG function. Deepened understanding of the pro- and anti-apoptotic networks is clearly needed for survival factors to be feasible for therapy in humans. In comparison, in a dog model of Leber's congenital amaurosis gene therapy could establish retinal function, thus supplying proof of efficacy of the method.

Animals↗

Noise in subtraction images made from pairs of bitewing radiographs: a comparison between two subtraction programs.

OBJECTIVES: To compare noise in subtraction images produced by two subtraction programs. METHODS: Twenty-five pairs of bitewing radiographs exposed under clinical conditions were subtracted using two digital subtraction programs: X-PoseIt (XP) software and EMAGO/Advanced 3.43 (EM) software. Four reference points were located between the mesial surface of the upper first premolar and the distal surface of the upper first molar (the region of interest) on the same anatomical structures using XP and EM. The standard deviation (SD) of the histogram defining the distribution of the shades of grey in the region of interest was used as the statistical parameter for comparing noise in the subtraction images created by the two subtraction programs. RESULTS: The mean and median grey shade value was lower with EM software (126.9, 126) than with XP software (128.3, 128) (P < 0.05). For the SD, the mean value was significantly lower with XP (6.2) than with EM (7.8) (P < 0.05). The range of the SD values was larger for EM (3.6-12.8) than XP (3.3-9.9). CONCLUSIONS: The standard deviation of the grey shade histogram showed that subtraction images produced with X-PoseIt software were statistically less noisy than images produced with EMAGO/Advanced 3.43 software.

Humans↗

Audit for extraoral radiographic examinations in a digital department.

OBJECTIVES: To investigate whether extraoral radiographs requested by clinicians were actually viewed by the clinicians after recording. METHODS: Digital extraoral images recorded at the radiology department were tracked over a 1-year period. Digital images are communicated to the clinical departments through our Picture Archiving and Communication System and may be viewed at any computer which houses the image display and enhancement software "DigiView". DigiView keeps track of user actions, among others where and when an image is opened. An image was defined as viewed if it had been opened in DigiView within 3 months after it had been recorded. The number of opened and non-opened images was calculated in relation to the referring clinical departments/units in the dental school. RESULTS: 2374 digital extraoral images were requested by the clinical departments. Two-thirds of these images were requested from the orthodontic department. Twenty-two percent (n=346) of their requested images were not opened. The distribution of non-opened images for the other clinical departments was: oral surgery=3% (18 images); periodontology=17% (1 image); treatment planning=33% (1 image); prosthetic=5% (6 images); county=21% (8 images) and oral physiology=23% (6 images). Panoramic images constituted the majority (58%) of non-opened images. Twenty-six percent of the images were opened once, 15% were opened twice and 41% were opened three times or more. CONCLUSIONS: Digital imaging offers new possibilities for audit compared with conventional film radiography. It seems that custom in some disciplines rules the referral of patients to radiographic examination and that this may lead to over-prescription.

Dental Audit↗

Students' attitudes to digital radiography and measurement accuracy of two digital systems in connection with root canal treatment.

The aim of this study was to evaluate students' attitudes towards digital radiography and measurement accuracy in digital images recorded with a CCD-sensor and a photostimulable phosphor (PSP) plate radiography system in connection with root canal treatment. Thirty-one dental students participated in an endodontic course. Two single-rooted teeth were assigned at random to two receptors for digital radiographic examination, either (i) the RVG-ui CCD sensor or (ii) the Digora PSP plate system. After the endodontic treatment had been completed for the first tooth, the student filled in a questionnaire on their use of the digital system. Thereafter, the students switched radiography system and repeated the procedure for the second tooth. Eventually, the students completed the questionnaire by answering questions that directly compared the two digital systems. The gutta-percha filled tooth was measured using the system's own software. Two measurements of each tooth were performed: total tooth length (TTL) and root filling length (RFL). The teeth were dismounted from the plaster blocks and the true TTL and RFL was measured with an electronic slide calliper. The majority of the students had used the contrast enhancement facility (CCD sensor = 52%, PSP = 71%) and the zoom facility (65-68%) whilst some had used the density enhancement facility (CCD sensor = 39%, PSP = 55%). The students stated that they saved more time when they used the CCD sensor than when they used the PSP system (P < 0.001), and that it was easier to position the tooth with the PSP plate than with the sensor (P < 0.01). The lengths measured on the digital images from both digital systems were marginally larger than the true tooth lengths (P < 0.05). However, there was no difference between the two digital systems for the TTL/RFL ratio (P > 0.05).

Dental Pulp Cavity↗

Bitewing and digital bitewing radiography for detection of caries lesions.

When radiography is applied in the clinic for caries detection, the recommended technique is bitewing projection (Gröndahl, 1994). This technique was introduced by Raper (1925) and has continued with only minor alterations. The aims of this report are to provide evidence for (1) optimal bitewing recording for individual examinations and clinical trials, (2) advantages and disadvantages of digital receptors for bitewing examinations, (3) the diagnostic outcomes and limitations of bitewing radiography, and (4) computer-automated detection of caries.

Clinical Trials as Topic↗

Prevalence of generalized anxiety at eight weeks postpartum.

OBJECTIVE: This study investigated the prevalence and nature of generalized anxiety symptoms in women who were eight weeks postpartum. METHOD: A community-based sample of 68 postpartum women completed an interview assessing generalized anxiety disorder and depression and a self-report measure of worry associated with concerns relevant to postpartum women. RESULTS: Three women (4.4%) met DSM-IV criteria for generalized anxiety disorder, and an additional 19 women (27.9%) endorsed subsyndromal difficulties with generalized anxiety. Approximately one third of these women endorsed symptoms of depression. In contrast, only two woman met criteria for major depressive disorder. CONCLUSION: Postpartum generalized anxiety has a higher prevalence than postpartum depression.

Adult↗

Increased light damage susceptibility at night does not correlate with RPE65 levels and rhodopsin regeneration in rats.

The susceptibility of rats to light-induced retinal degeneration is increased at night. In mice, an important determinant of light damage susceptibility is the efficacy of rhodopsin regeneration after bleaching. The rate of rhodopsin regeneration is at least partly controlled by RPE65, a protein expressed in the retinal pigment epithelium. We therefore tested a potential involvement of RPE65 and rhodopsin regeneration in the increased light damage susceptibility of rats at night. For this purpose, rats were exposed to visible light at noon or at midnight and extent of light damage was determined by retinal morphology and TUNEL staining. Rpe65 gene expression was analyzed by semiquantitative RT-PCR and levels of RPE65 protein were determined by Western blotting. Rhodopsin regeneration kinetics was determined by measuring rhodopsin content immediately after a strong bleach and after different times of recovery in darkness. Rats were more susceptible to light damage at night as described by Organisciak and collegues [Invest. Ophthalmol. Vis. Sci. 41 (2000) 3694]. Rpe65 gene expression followed a day-night rhythm with highest steady-state mRNA levels at the beginning and lowest levels at the end of the day period. However, RPE65 protein levels remained constant. Rhodopsin regeneration kinetics did not differ during day and night. We conclude that levels of RPE65 protein and rhodopsin regeneration kinetics do not correlate with the increased light damage susceptibility observed in rats at night. Additional genetic or physiologic modifiers may exist in rats that regulate the retinal responsiveness to acute light exposure.

Acute Disease↗

Identification of endocrine-disrupting effects in aquatic vertebrates and invertebrates: report from the European IDEA project.

The EU-funded project IDEA aimed to evaluate (a) what parameters and endpoints allow the detection of endocrine-mediated developmental and reproductive effects of (xeno)estrogens in life cycle- and life stage-specific toxicity tests with the zebrafish Danio rerio, a small laboratory fish used in many ecotoxicity test guidelines, and (b) whether substances that act as estrogens in vertebrates may also adversely affect the development, differentiation, and reproduction of aquatic invertebrates. The invertebrate species investigated included Hydra vulgaris, Gammarus pulex, Chironomus riparius, Hyalella azteca, and Lymnaea stagnalis. The animals were exposed to the model estrogenic chemicals ethynylestradiol (EE2), bisphenol A (BPA), and octylphenol (OP), which exert their endocrine activity in vertebrates through the estrogen receptor. As endpoints, developmental and reproductive parameters at the organism level as well as molecular and cellular parameters were measured. Life cycle exposure of zebrafish to (xeno)estrogens induced a specific, partly irreversible response pattern, consisting mainly of (a) induction of vitellogenin (VTG), (b) alterations of gonad differentiation, (c) delay of first spawning, and (d) reduced fertilization success. The effects of EE2 on zebrafish were expressed at environmentally realistic concentrations, while BPA and OP became effective at concentrations higher than those usually found in the environment. The vitellogenic response was equally sensitive as the reproductive parameters in the case of EE2, but VTG was more sensitive in the case of BPA. Partial life cycle exposure of zebrafish had lasting effects on fish development and reproduction only when the fish were exposed during the stage of juvenile bisexual gonad differentiation. In (partial) life cycle and multigeneration studies with invertebrates, (xeno)estrogenic impact was assessed by a range of developmental and reproductive parameters including hatching, growth, moulting, mating behavior, and egg number. Several parameters were found to be responsive to (xeno)estrogens; however, most effects were induced only at higher, probably nonphysiological concentrations. Low-dose effects were observed in full life cycle experiments, particularly in the second generation. It remains to be established whether the estrogen-induced alterations in the invertebrate species indeed do result from disturbances of the endocrine system. The findings of the present research project support the development of appropriate testing methodologies for substances with estrogenic activity.

Animals↗

Potencies of estrogenic compounds in in vitro screening assays and in life cycle tests with zebrafish in vivo.

The objective of this study was to compare the estrogenic potency of environmental estrogens at two testing tiers: at the initial level of in vitro screening assays, and at the level of definitive fish reproduction tests in vivo. The in vitro tests included a recombinant yeast estrogen receptor (ER) assay, a competitive radioreceptor assay using the hepatic ER of carp (Cyprinus carpio), and assays on vitellogenin induction in cultured hepatocytes of rainbow trout (Oncorhynchus mykiss) and carp. In vivo, full life cycle tests with zebrafish (Danio rerio) were performed, using fertilization success as estrogen-sensitive reproductive endpoint. The test compounds included the natural estrogen 17beta-estradiol (E2) (only applied in the in vitro assays); the synthetic estrogen ethynylestradiol (EE2); and two xenoestrogens, 4-tert-octylphenol (OP) and bisphenol A (BPA). Among the in vitro assays, differences were observed in the relative ranking of the test substances, and in the absolute sensitivity (EC50 values), although the interassay differences of EC50 values were within one order of magnitude. The in vivo activity of the test compounds was not accurately predicted by the in vitro assays, with respect to neither sensitivity nor ranking. The in vitro assays tended to overestimate the relative potency of the xenoestrogens; i.e. the ratio between the activity of the reference compound, EE2, and that of the test compound. The best prediction of the in vivo fish test results was obtained from the recombinant yeast assay.

Animals↗

Why study rod cell death in retinal degenerations and how?

Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease. Recent anatomical studies using elegant innovative techniques reveal that there is a 30% rod loss in normal ageing, which is increased in early AMD. Those and other observations by Curcio and co-workers indicate that early rod loss is an important denominator of AMD (Curcio CA. Eye 2001; 15:376). As in retinitis pigmentosa (RP), rods appear to die by apoptosis. Thus it seems mandatory to study the regulation of rod cell death in animal models to unravel possible mechanisms of rod loss in AMD. Our laboratory investigates signal transduction pathways and gene regulation of rod death in our model of light-induced apoptosis. The transcription factor AP1 is essential, whereas other classical pro- and antiapoptotic genes appear to be less important in our model system. Caspase-1 gene expression is distinctly upregulated after light exposure and there are several factors which completely protect against light-induced cell death, such as the anesthetic halothane, dexamethasone and the absence of bleachable rhodopsin during light exposure. A fast rhodopsin regeneration rate increased damage susceptibility. Our data indicate that rhodopsin is essential for the initiation of light-induced rod loss. Following photon absorption, there may be the generation of photochemically active molecules wich then induce the apoptotic death cascade.

Animals↗