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Biomedical subjects

R Bauer

Publications and source records attributed to R Bauer.

At least 37 records · Page 2Linked to original sources

Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.

Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.

Consumer Product Safety↗

Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells.

Rhizomes of butterbur, Petasites hybridus L. (Asteraceae), have been used since ancient times for the treatment of inflammatory diseases. In the present study, the effects of lipophilic extracts from rhizomes of Petasites hybridus on the formation and release of prostaglandin E2 were investigated. The extracts had different contents of petasin and isopetasin: A: 2.1 % and 0.4 %, B: 0.2 % and 0.1 %, C: 12.1 % and 6.1 % and D: 21.9 % and 9.4 %, respectively. Direct inhibition of cyclooxygenase (COX) -1 and -2 isoenzymes and inhibition of the expression of COX-2 and p42/44 MAP kinase in rat primary microglial cells were tested. All extracts were found to be only weak direct inhibitors of COX-1 (IC50> 400 microg/mL). However, most extracts revealed a strong inhibitory activity against the inducible isoform COX-2 ( A: IC50=30.4 microg/mL; B: IC50=60.6 microg/mL; C: IC50=22.6 microg/mL; D: IC50=20.0 microg/mL). This activity was not correlated to the content of petasin and isopetasin. Pure petasin and isopetasin neither inhibited COX-1 nor COX-2 (IC50 > 400 microM for both compounds and enzymes). Petasites extracts dose-dependently inhibited LPS-induced and thus COX-2-mediated PGE2 release in primary rat microglial cells (A: IC50= 2.4 microg/mL; C: IC50=5.8 microg/mL and D: IC50=4.6 microg/mL). Also this effect was independent from the petasin and isopetasin content. COX-2 synthesis in microglia was totally blocked with 5 microg/mL of C whereas COX-1 synthesis was not influenced. C and D did not affect the LPS-induced activation of p38 MAPK and IkappaBalpha, but they prevented the LPS-induced activation of p42/44 MAPK. Therefore, these Petasites hybridus extracts can be regarded as natural selective inhibitors of COX-2 and its expression, an effect which is independent from the petasin content.

Animals↗

Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients.

BACKGROUND: The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE. OBJECTIVES: To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE. METHODS: One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student's t-test using SPSS 11 software. RESULTS: MTX led to a highly significant (P < 0.01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia (< 1.0 x 10(9) cells L(-1)) prior to MTX treatment. CONCLUSIONS: Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention to side-effects and contraindications.

Adult↗

Characterization of thoeniicin 447, a bacteriocin isolated from Propionibacterium thoenii strain 447.

Fifteen strains of propionibacteria, isolated from dairy products, were screened for the production of bacteriocins. Propionibacterium thoenii 447 produced an antimicrobial peptide, thoeniicin 447, which acted bactericidal against Lactobacillus delbrueckii subsp. bulgaricus and bacteriostatic against Propionibacterium acnes. Thoeniicin 447 remained active after 15 min at 100 degrees C and after 30 min of incubation at pH 1-10. The peptide was inactivated when treated with pepsin, pronase, alpha-chymotrypsin, trypsin and proteinase K. Optimal bacteriocin production was detected during late exponential growth. The peptide was partially purified by ammonium sulfate precipitation, followed by SP-Sepharose cation exchange chromatography. The estimated size of thoeniicin 447, according to tricine-SDS-PAGE, is 6 kDa. Based on DNA sequencing, the mature peptide is 7130.20 Da in size and homologous to propionicin T1, produced by P. thoenii strain 419 (=NCFB 568(T)). Strain 447 is phenotypically different from strain 419 and belongs to a separate ribotype cluster. To our knowledge, this is the first report of a bacteriocin from a Propionibacterium species active against P. acnes.

Amino Acid Sequence↗

Potential stem cell therapy and application in neurotrauma.

Traumatic brain injury results from a sudden and external physical insult to the head, which is often accompanied by motor and cognitive impairment. Neurotrauma is characterized not only by focal abnormalities, but rather by multifocal, or even global structural and functional disturbances of the brain network. The impact initially causes necrotic cell death in the underlying tissue, followed by apoptotic cell death in the surrounding tissue due to multiple subsequent events, such as ischemia, excitotoxicity and altered gene expression. These pathological conditions are associated with high morbidity and mortality. Despite the high medical and economical relevance of neurotrauma there are currently no sufficient treatments. Supplementary therapeutic strategies have to be established. Many types of stem cells have the ability to engraft diffusely and become integral members of structures throughout the host CNS. Intrinsic factors appear to derive spontaneously from stem cells and seem to be capable of neuroprotective and/or neuroregenerative functions. Furthermore stem cells can be readily engineered to express specific genes. Such observations suggest that stem cells might participate in reconstructing the molecular and cellular milieu of traumatized brains. In this paper, the state of stem cell research is reviewed and its possible application in neurotrauma will be discussed.

Animals↗

Lymphocytopenia in lupus erythematosus: close in vivo association to autoantibodies targeting nuclear antigens.

BACKGROUND: Leukopenia and lymphopenia are typical features of lupus erythematosus (LE) and correlate with elevated disease activity and higher grades of systemic involvement. Antilymphocyte antibodies are regarded as the most likely rationale for the decreased cell numbers; however, their relevance has not been confirmed so far. OBJECTIVES: Previous investigations at our department have shown a significant correlation between diminished lymphocyte numbers and the presence of antinuclear antibodies (ANA). We wanted to achieve a better understanding of this phenomenon. METHODS: We performed a detailed analysis of autoantibodies and peripheral leucocyte subsets in 82 patients with different subtypes of LE. Leucocyte subsets were measured using flow cytometry (FACScan; Becton Dickinson, Franklin Lakes, NJ, USA.); autoantibodies were detected by indirect immunofluorescence and by enzyme-linked immunosorbent assay. RESULTS: A significant association (P < 0.05) between specific antibodies targeting nuclear antigens (SSA/Ro-52, SSB/La, snRNPs) and lymphocytopenia was found. CONCLUSIONS: We suppose that some of these autoantibodies might have an antilymphocyte effect. Apoptosis induction by specific antinuclear antibodies has already been described earlier, but to the best of our knowledge this is the first study presenting a strong indication of a possible interaction between these antibodies and lymphocyte subsets in vivo.

Adolescent↗

Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Recently, echinacea has regained popularity as one of the treatments chosen most commonly by consumers with the expectation that it will reduce the severity and duration of the common cold. However, the results from a limited number of clinical trials for this application have thus far been inconclusive. This incongruity may be the result of investigators utilizing poorly standardized echinacea products, likely devoid of sufficient quantities of active constituents necessary to exert a definitive clinical effect. Therefore, a formulation containing alkamides, cichoric acid, and polysaccharides at concentrations of 0.25, 2.5, and 25 mg/mL, respectively, was prepared from freshly harvested Echinacea purpurea plants (commercially available as Echinilin, Natural Factors Nutritional Products, Inc., Vancouver, BC, Canada). The objective of this study was to test the efficacy of this highly standardized formulation in reducing the severity and duration of symptoms of a naturally acquired common cold. METHODS: In a randomized, double-blind, placebo-controlled trial, 282 subjects aged 18-65 years with a history of two or more colds in the previous year, but otherwise in good health, were recruited. The subjects were randomized to receive either echinacea or placebo. They were instructed to start the echinacea or placebo at the onset of the first symptom related to a cold, consuming 10 doses the first day and four doses per day on subsequent days for 7 days. Severity of symptoms (10-point scale: 0, minimum; 9, maximum) and dosing were recorded daily. A nurse examined the subjects on the mornings of days 3 and 8 of their cold. RESULTS: A total of 128 subjects contracted a common cold (59 echinacea, 69 placebo). The total daily symptom scores were found to be 23.1% lower in the echinacea group than in placebo in those who followed all elements of the study protocol (P<0.01). Throughout the treatment period, the response rate to treatments was greater in the echinacea group. A few adverse event profiles were observed in both groups. CONCLUSIONS: Early intervention with a standardized formulation of echinacea resulted in reduced symptom severity in subjects with naturally acquired upper respiratory tract infection. Further studies with larger patient populations appear to be warranted.

Adult↗

CD45RA+ ICAM-3+ lymphocytes in interferon-beta1b-treated and -untreated patients with relapsing-remitting multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is believed to be an autoimmune disease of the human central nervous system mediated by autoreactive T cells. Interferon-beta1b (IFN-beta1b) has been shown to be effective in reducing disease activity defined by clinical and magnetic resonance imaging (MRI) criteria in relapsing-remitting MS (RRMS). Yet, the exact mechanisms by which these benefits are achieved remain unknown. CD45RA is a marker for naive T lymphocytes and intercellular adhesion molecule-3 (ICAM-3) is expressed on resting lymphocytes. MATERIAL AND METHODS: Forty-eight patients with RRMS, 24 of them treated with recombinant IFN-beta1b and 24 untreated, were enrolled in this prospective study over 18 months. We investigated the percentage of CD45RA+ ICAM-3+ cells within the total lymphocyte subset in the peripheral blood serially every 3 months and in CSF once at baseline. Detailed clinical examination including Expanded Disability Status Scale (EDSS) score was performed every 3 months and cranial MRI scans were assessed every 6 months. RESULTS: We found a temporary increase in the CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood of both untreated and IFN-beta1b-treated RRMS patients. Moreover, we determined a significant negative correlation (r = -0.5874; P < 0.01) between age as well as the EDSS score (r = -0.3629; P < 0.05) and the percentages of CD45RA+ ICAM-3+ lymphocytes in peripheral blood but a positive correlation between EDSS score and the CD45RA+ ICAM-3+ ratio (r = 0.3913; P < 0.05) in the CSF at baseline. CONCLUSION: CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood might indicate immunosenescence in MS. However, from our data it cannot be finally concluded whether it is also influenced by IFN-beta1b treatment.

Adjuvants, Immunologic↗

Optimization of the microbial synthesis of dihydroxyacetone from glycerol with Gluconobacter oxydans.

An optimized repeated-fed-batch fermentation process for the synthesis of dihydroxyacetone (DHA) from glycerol utilizing Gluconobacter oxydans is presented. Cleaning, sterilization, and inoculation procedures could be reduced significantly compared to the conventional fed-batch process. A stringent requirement was that the product concentration was kept below a critical threshold level at all times in order to avoid irreversible product inhibition of the cells. On the basis of experimentally validated model calculations, a threshold value of about 60 kg x m(-3) DHA was obtained. The innovative bioreactor system consisted of a stirred tank reactor combined with a packed trickle-bed column. In the packed column, active cells could be retained by in situ immobilization on a hydrophilized Ralu-ring carrier material. Within 17 days, the productivity of the process could be increased by 75% to about 2.8 kg x m(-3) h(-1). However, it was observed that the maximum achievable productivity had not been reached yet.

Bioreactors↗

Photoelectrocatalytic degradation of 4-chlorophenol and oxalic acid on titanium dioxide electrodes.

Photocatalytically active thin TiO(2) films were produced by spin-coating or dip-coating an alkoxy precursor onto a transparent conducting electrode substrate and by thermal oxidation of titanium metal. The thin films were used to study the photoelectrocatalytic or photoelectrochemical degradation of oxalic acid and 4-chlorophenol (4-CP) under near UV (monochromatic, 365 nm) light irradiation. Degradation was monitored by a variety of methods. In the course of oxalic acid degradation, CO(2) formation accounted for up to 100% of the total organic carbon degradation for medium starting concentrations; for the degradation of 4-CP, less CO(2) was detected due to the higher number of oxidation steps, i.e. intermediates. Incident-photon-to-current conversion efficiency, educt degradation and product formation as well as Faradaic efficiencies were calculated for the degradation experiments. Quantum yields and Faradaic efficiencies were found to be strongly dependent on concentration, with maximum values (quantum yield) around 1 for the highest concentrations of oxalic acid.

Catalysis↗

Optimization of codon usage is required for effective genetic immunization against Art v 1, the major allergen of mugwort pollen.

BACKGROUND: As the major allergen of mugwort pollen, Art v 1 is an important target for specific immunotherapy. However, both recombinant protein as well as a gene vaccine for Art v 1 failed to be immunogenic in mice. In order to improve immunogenicity we focused on genetic immunization because interspecific differences of codon usage have been shown as an obstacle for effective induction of immune responses with gene vaccines encoding infectious pathogens. OBJECTIVE: In order to find out, whether codon usage might also be used to improve genetic immunization with allergen genes, the response against a gene vaccine expressing the wild-type gene of Art v 1 (pCMV-wtArt) was compared with a synthetic codon-optimized vector with human codon usage (pCMV-humArt). METHODS: Balb/c mice were injected intradermally with pCMV-wtArt or pCMV-humArt. In vitro expression levels of both constructs were compared in transfection experiments. Total immunoglobulin G (IgG), IgG1, IgG2a and IgE antibodies were analyzed by enzyme-linked immunosorbent assay and the anaphylactic activity of the sera was determined by allergen-specific degranulation of rat basophil leukemia-2H3 cells. RESULTS: No immune response was detectable with the gene vaccine expressing the wildtype Art v 1, but immunization with pCMV-humArt revealed a strong and allergen-specific induction of antibody responses. The antibodies recognized both the recombinant as well as the purified natural (glycosylated) Art v 1 molecule. The response type was Th1-biased, as indicated by high levels of IgG2a antibodies. Expression analysis with B16 mouse melanoma cells transfected with pCMV-humArt or pCMV-wtArt revealed an impaired expression of the wild-type vector but normal translation after recoding. CONCLUSION: The results demonstrate that optimization of codon usage offers a simple way to improve immunogenicity and therefore should be routinely considered in the development of gene vaccines for the treatment of allergy.

Allergens↗

Safety of rush insect venom immunotherapy. The results of a retrospective study in 178 patients.

BACKGROUND: Venom immunotherapy (VIT) is regarded as an established and efficient treatment of Hymenoptera venom allergy. Different frequencies of side-effects have been reported in the literature, depending on the hyposensitization regimen (conventional outpatient programme, rush immunotherapy, ultra rush immunotherapy) and the venom preparation. Aim of this study was to evaluate safety and tolerance of rush VIT in patients treated with a 7-day protocol in our department. METHODS: VIT protocols of 178 patients treated at the Department of Dermatology and Allergy of the University of Bonn were analysed retrospectively. All patients had been treated with a standardized venom preparations (ALK-SQ). We used a modified VIT-protocol with a 2-day break to reduce systemic side-effects. RESULTS: During the course of VIT in 15 patients (8.4%) systemic reactions grade I (Mueller scale) were observed, in seven (3.9%) grade II, in six (3.4%) grade III and in four (2.2%) grade IV. A total of 146 patients (82.1%) had no or only local reactions. CONCLUSIONS: The rate of systemic adverse reactions Mueller Grade I-IV of 17.9% of the 'Bonn rush VIT protocol' appears to be relatively low compared with the data in the literature.

Adolescent↗

Regional alterations in fiber type distribution, capillary density, and blood flow after lower jaw sagittal advancement in pig masticatory muscles.

Muscular remodeling is known to be a prerequisite for permanent correction of mandibular-maxillary malocclusion. The objective of this study was to clarify if an increase in type I fiber number is accompanied by an increased capillary density and improved muscular blood flow. Juvenile pigs received build-ups on the molars, which induced a protrusion of 7.6 + 1.5 mm. After 4 weeks of treatment, chronic lower jaw protrusion induced a marked muscle blood flow increase in the anterior and medial regions of the superficial part of the masseter and in the medial pterygoid muscle (P < 0.05). Furthermore, an increase in capillary density and in the amount of type I fibers was found in all regions of masticatory muscles with an increased muscle blood flow (P < 0.05). Finally, the capillary-to-fiber ratio increased (P < 0.05). Muscle blood flow and capillary density showed a strong linear correlation (r = 0.89, P < 0.01). These changes suggest a complex muscle adaptation for long-term, fatigue-resistant activity during the early corrective period of mandibular-maxillary malocclusion treatment.

Animals↗

Simultaneous measurement of local cortical blood flow and tissue oxygen saturation by Near infra-red Laser Doppler flowmetry and remission spectroscopy in the pig brain.

In the current study we evaluated the combined use of Near-infrared Laser-Doppler flowmetry (NiLDF) and Remission Spectroscopy (RS) for measurement of regional perfusion and oxygen saturation of the cerebral cortex. An epidural probe for combined measurements of NiLDF and RS was placed above the parietal or frontal cortex of nine anesthetized juvenile pigs. Cerebral perfusion pressure (CPP) was stepwise decreased by intracisternal infusion of artificial CSF at clamped arterial blood pressure (baseline, CPP50, CPP40, CPP30 mmHg, ischemia). Subsequent reperfusion was followed for 3 h. Regional cerebral blood flow (rCBF) was measured with colored microspheres (CMS) and compared with corresponding NiLDF values during CMS injection. Cerebral venous oxygen saturation was measured in blood samples withdrawn from the sagittal sinus and compared with simultaneous recordings of tissue oxygenation during blood withdrawal. Linear regression analysis resulted in a significant correlation (p < 0.001) for changes in regional perfusion during CPP decrease and reperfusion, as measured with CMS and NiLDF (r = 0.92, n = 39). A significant correlation was also found for tissue oxygen saturation--as measured with RS--and cerebral venous oxygen saturation (r = 0.85, n = 67). Although the problem of spatial variability remains to be solved, the combined use of NiLDF and RS allows continuous and non-invasive monitoring of changes of key parameters of oxygen metabolism within the cerebral cortex.

Animals↗

[Retrograde tibial intramedullary nailing with the Flex Nail--treatment of tibial fracture in an unusual case].

We report a case by a 75 year old female patient suffering a third-degree open fracture of the shinbone with a severe damage of the soft tissue. Primary operation was a temporary fixation with a fixateur externe and a radical debridement of the soft tissue with vacuum-sealing. Ten days later we did the definitive surgery. Osteosynthesis was done by a retrograd nailing with the flexible unreamed humerus nail (Flex-Nail) through the medial ankle. The defect of the soft tissue was treated by a muscle flap and meshgraft transplantation. Healing of the soft tissue and beginning consolidation of the fracture comes after 4 months. In our opinion the retrograd inserted Flex-Nail is a good option for treatment of compound fractures of the lower leg in special cases.

Aged↗

Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity.

BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS.

Adult↗