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Biomedical subjects

R Stange

Publications and source records attributed to R Stange.

9 recordsLinked to original sources

Quantification, localization, and expression of IGF-I and TGF-beta1 during growth factor-stimulated fracture healing.

Because of the increasing interest on stimulating fracture healing, knowledge about the role and chronology of growth factors during the healing process is important. The purpose of this study was to quantify the protein concentration of IGF-I and TGF-beta1 during rat tibial fracture healing 5, 10, and 15 days after fracture using ELISA methods and to analyze the distribution of the proteins and the related mRNA expression in the fracture callus by immunohistochemistry and in situ hybridization. The following three groups were analyzed: Fractured tibiae intramedullary stabilized with K-wires coated with IGF-I and TGF-beta1 compared with fractures stabilized with uncoated K-wires and unfractured tibiae. The weight of the callus increased during the healing process in both experimental groups. The protein concentration of IGF-I and TGF-beta1 in the fracture callus showed significant changes between the investigated time points and treatment groups compared with the unfractured tibia. IGF-I increased with healing time whereas TGF-beta1 revealed a constantly elevated level at the investigated time points. Mesenchymal cells, osteoblasts, osteocytes, proliferating and immature chondrocytes, and osteoclasts expressed both growth factors. No differences in the expression and localization pattern of the growth factors were detectable among the groups. Using the different methods for quantification and visualization of the growth factors, no differences (except the increased IGF-I concentration at day 15 in the growth factor group) were seen between the normal and the growth factor-stimulated fracture healing as an indication for physiological healing after exogenous growth factor treatment.

Absorbable Implants↗

Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-beta1: comparison of two proliferation markers, PCNA and BrdU.

Growth factors IGF-I and TGF-beta1 are known to stimulate fracture healing. The purpose of this study was to investigate the role of locally applied IGF-I and TGF-beta1 during the early phase of fracture healing (Days 5, 10, and 15 after fracture) on cellular processes like proliferation and differentiation in a rat model. Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation (e.g., r(s): 0.887 and p < 0.001 at day 10 in the control group without growth factors). Comparison of the callus morphology and the proliferation rate showed differences during fracture healing due to the local application of IGF-I and TGF-beta1 from coated implants. At Day 5 the callus of the group treated with growth factors displayed an earlier appearance of cartilage compared to the control group. This was accompanied by an onset of cell proliferation in chondrocytes. Likewise, at the later time points an enhanced maturation of the callus tissue and the proliferation pattern were detectable in the growth-factor group. These results indicate that local application of IGF-I and TGF-beta1 accelerates early cellular processes during fracture healing.

Animals↗

A new electrochemically graded hydroxyapatite coating for osteosynthetic implants promotes implant osteointegration in a rat model.

Hydroxyapatite (HAP) is widely used as an osteoconductive coating for orthopedic implants. So far standard coating methods like plasma spraying produce a relatively thick coating layer (>30 microm). In addition, the chemical structure of the HAP may be altered because of the heating throughout the coating process. This may have negative effects on the coating stability, implant fixation, and induction of bone formation. The relatively thick layer may detach from the implant with the risk of wear debris. In the present study the potential of a newly developed HAP coating of implants on osteointegration was investigated in a rat model. The coating method, based on an electrochemical process, is applied in a graded manner and results in a biodegradable HAP coating with a thickness of approximately 2 mum. Coated versus uncoated titanium Kirschner wires (1.4-mm diameter) were inserted into the medullary cavity of the right femora of 5-month old female Sprague Dawley rats (n=36) in a retrograde fashion. Throughout an experimental period of 2 months the osteointegration was traced radiologically. After this time the animals were sacrificed and the implant integration was tested biomechanically with the use of a push-out test. To analyze the bone-implant interface, histological sections (80 mum) were investigated with an image analyzing system. The biomechanical testing revealed a significantly higher implant fixation in the group treated with the HAP-coated implant (shear strength: 27.8 +/- 6.7 MPa) compared to control (shear strength: 8.08 +/- 3.4 MPa). The histological analyses demonstrated a better ingrowth of the implants in the HAP group with significantly more direct bone-implant contacts compared to the control group. The results demonstrate that the HAP coating promotes implant osteointegration in a rat model.

Animals↗

Validation of questionnaires from several medical fields regarding the constitution of patients.

INTRODUCTION: To consider or determine an individual's 'warm and cold' constitution is common part of traditional Chinese medicine (TCM), Indian medicine (Ayurveda), anthroposophic medicine and classical natural medicine. OBJECTIVE: Common psychometric characteristics of 4 questionnaires should be examined. METHODS: 110 cancer patients and 110 non-cancer patients were asked to answer these questionnaires twice 4 weeks apart. Subsequent validation of the questionnaires included psychometrical qualities of item acceptability, sensitivity to change, construct validity (homogeneity), re-test reliability and group comparison. RESULTS: The Ayurveda questionnaire was considered suitable after reducing the questions from 22 to 8 (internal construct validity kappa = 0.64). The TCM questionnaire was considered unsuitable in our model because of the absence of construct validity. The questionnaire on anthroposophic medicine was considered a suitable and reliable tool with alpha = 0.57 (Cronbach's alpha) and r = 0.61 (re-test reliability) after reducing the questions from 6 to 4. The questionnaire on sensitivity to temperatures based on classical natural medicine was considered suitable after reducing the questions from 10 to 8 (alpha = 0.58; r = 0.73). Cancer and non-cancer patients differ in only one item, i.e. in their sensitivities to cold. CONCLUSION: The questionnaires for anthroposophic medicine, Ayurveda medicine and sensitivity to temperatures are in part suitable and reliable for determining individual constitutions according to their medical philosophy. The questionnaire based on traditional Chinese medicine failed these criteria. A difference between patients with or without malignant disease was only observed for sensitivity to temperatures. The anthroposophic hypothesis that cancer either changes an individual's thermic constitution or is caused by such a change could not be confirmed in this study.

Body Temperature↗

[Scatter tomography - dosimetry and radiographic technique with diagnostic x-rays (author's transl)].

Scatter tomography (ST) is a method to acquire information about biological structures using Compton scattered photons. In contrast to previously published methods high resolution in ST is achieved by using conventional x-ray energies. From a general model for the calculation of the radiation exposure, a minimum of the x-ray dosis relative to the spatial resolution is predicted at 60 keV. A simple experimental set-up for recording scatter tomograms is described. First measurements on bovine lungs seem to confirm the expected advantages of the proposed method.

Dose-Response Relationship, Radiation↗

Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients.

The protease bromelain from pineapple was suggested for adjuvant therapy of malignant diseases. We studied immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors. Bromelain was applied for 10 days with a daily dose of 3000 F.I.P. units and the immunocytotoxicity of blood monocytes and lymphocytes against the leukemic K562 and MDA-MB-231 mammary carcinoma target cells was determined in vitro. In addition, the expression of the cell surface markers CD44, CD16, CD11a and CD62L on lymphocytes and the secretion of IL-2 and IL-1beta from monocytes was measured. Patients leukocytes expressed lower bMAK-, MAK-, NK- and LAK-cell activities, compared with those from healthy donors. Orally applied bromelain increased the reduced bMAK- and MAK-cell activity of patients monocytes about 2-fold. When the patients were classified on the basis of bromelain effects on the monocytic cytotoxicity into bromelain responders and nonresponders, about 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity) and from 16% to 47% (MAK-cell activity). Bromelain was less effective on the higher cytotoxicity of monocytes from healthy donors, but stimulated the secretion of IL-1beta from monocytes. In contrast, patient monocytes secreted no detectable IL-1beta, before, during and after bromelain treatment. Bromelain had no effects on the impaired patients NK- and LAK-cell activity, but reduced the LAK-cell activity of healthy donors. No IL-2 was found in the supernatants of untreated and treated lymphocytes from healthy donors. Bromelain reduced the expression of CD44, but weakly increased CD11a and CD62L expression on patient lymphocytes, whereas CD16 remained unchanged. In vitro bromelain application to lymphocytes had similar effects, with greater reduction rates of CD44 and CD16 expression. As to coagulation parameters in plasma of healthy donors, the activated partial thromboplastin time was increased from 38 to 46 sec, leaving prothrombin time and plasminogen unchanged. These data suggest, that orally applied bromelain stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity.

Administration, Oral↗