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D Schäfer

Publications and source records attributed to D Schäfer.

At least 19 recordsLinked to original sources

The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison.

Glutamatergic neurotransmission in the CNS plays a predominant role in learning and memory. While NMDA receptors have been extensively studied, less is known about the involvement of group I metabotropic glutamate receptors in this area. The purpose of the present study was to evaluate the contribution of mGluR1 and mGluR5 to both acquisition and expression of behaviours in contextual and auditory fear conditioning models. The effects of both receptor types were tested using selective antagonists: (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) for mGluR1, and [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) for mGluR5. Their effects on acquisition were compared to those of the NMDA receptor antagonist (+)MK-801, and the unselective muscarinic antagonist scopolamine, while diazepam and citalopram served as reference compounds in the expression experiments. EMQMCM (1.25 to 5mg/kg) impaired acquisition of contextual fear conditioning (CFC), but not auditory fear conditioning (AFC). Similarly, administration of MTEP during the acquisition phase impaired learning in CFC at doses of 2.5 to 10mg/kg, but was ineffective in AFC. When given before the retention test, both EMQMCM (1 and 3mg/kg) and MTEP (3mg/kg) impaired expression of CFC. In contrast, MTEP (2.5 and 5mg/kg) blocked the expression of AFC, while EMQMCM was ineffective. In conclusion, group I mGlu receptors are shown to be involved in the acquisition of hippocampus-dependent CFC, but not hippocampus-independent AFC. Unlike mGluR5, mGluR1 does not seem be involved in expression of AFC.

Acoustic Stimulation↗

The role of group I metabotropic glutamate receptors in schizophrenia.

It has been proposed that glutamatergic transmission, in particular NMDA receptor function, might be altered in schizophrenia. This hypothesis is mainly based on the observation that uncompetitive NMDA receptor antagonists, e.g. phencyclidine, evoke psychotic symptoms in healthy subjects, whereas agonists interacting at the glycine site of the NMDA receptor complex, e.g. glycine or D-serine, administered jointly with typical neuroleptics, can alleviate schizophrenic symptoms. The function of NMDA receptors may be modulated by group I mGluRs (mGluR1 and mGluR5), which have also been shown to be altered in schizophrenia. In rodents, mGluR5 antagonists, but not mGluR1 ones, potentiate the locomotor activity and the deficit of prepulse inhibition (PPI) induced by uncompetitive NMDA receptor antagonists. These antagonists (of either type) administered alone are not active in the above tests. Hence, antagonists of mGluR1 and mGluR5 may evoke different effects on the NMDA receptor antagonists-induced behavior and, possibly, on schizophrenic symptoms.

Animals↗

[CT assisted mandibular osteodistraction with reconstruction of the temporomandibular joint and two piece maxilla].

BACKGROUND: The possibilities for computer assisted planning and its surgical conversion with stereolithographic templates are shown for complex maxillofacial surgical interventions. CASE REPORT: We describe the case of a patient with extreme micrognathia due to an ankylosis of the temporomandibular joint. In addition to the exact determination of the osteotomy lines on the mandibular angle and the segment osteotomy of the maxilla, vectors of the bidirectional osteodistraction were also predictable. CONCLUSION: In comparison with the conventional procedures, computer assisted planning achieved a much higher degree of precision and safety with reduced complication rates. The CMF module is a component of the SimPlant software which enables the precise planning of osteotomies and osteodistractions.

Adult↗

[Gerocomy -- gerontology -- geriatrics. The naming of a modern medical discipline].

300 years ago, the lawyer Theodosius Schöpffer coined the notion gerontology. On this occasion, this paper offers terms and corresponding concepts of gerontology which arose in the western tradition: 1. From the Graeco-Roman antiquity until 1750, gerocomy (the care for the elderly) was defined as a branch of medicine, but in practice almost did not exist. Basically, it provided instructions for a way of life in conformity with the physiological circumstances of elderly people. Its implementation was left to the patient. Furthermore, in the early modern times medical treatises dealt more frequently with diseases of the elderly and their therapy. The gerokomia succeeded in evolving a specific technical literature. Yet it failed to get institutionalized. 2. At the beginning of the 20th century, Ignaz Nascher interpreted geriatrics as a counterpart to pediatrics and opposed it to a clinical-pathological consideration of old age before 1900. He aimed at the exploration and treatment of old age as an autonomous physiological entity. Under the influence of the demographic transformation the institutionalization of geriatrics as a interdisciplinary branch within medicine could be realized relatively soon. 3. Around 1930, we experience the recreation of the notion gerontology, initially restricted to medical gerontology. However, with the integration of the non-medical sciences of old age the spectrum and the objectives changed. Today gerontology signifies on a international level a generic term or independent scientific discipline beside medicine. This evolution corresponds with the intentions pursued 300 years ago.

Aged↗

Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice.

Phencyclidine and ketamine (but not other NMDA channel blockers, such as memantine) produce psychotomimetic effects. Since unlike memantine, phencyclidine-like compounds show no significant affinity at 5-HT(3) receptors, we investigated if behavioral effects of ketamine could be reduced by 5HT(3) receptor blockade. Ketamine (3-40 mg/kg) produced ataxia, stereotypes and diminished exploratory activity in mice, and reduced prepulse inhibition of acoustic startle response, lowered accuracy in fixed consecutive number and in delayed non-matching-to-sample tasks in rats. The 5HT(3) receptor antagonist MDL 72222 (0.3-3 mg/kg) administration did not reverse any of these deficits and exerted no effects on discriminative stimulus properties of ketamine. In the tail suspension test, both ketamine and MDL 72222 produced anti-immobility effects when given alone (50-66 and 3 mg/kg, respectively) and together (12.5-25 and 1 mg/kg). The present data suggest that 5-HT(3) receptor blockade does not reverse the behavioral deficits of ketamine and may even enhance its certain effects, such as the antidepressant-like action.

Animals↗

mGluR5, but not mGluR1, antagonist modifies MK-801-induced locomotor activity and deficit of prepulse inhibition.

Hypoglutamatergic theory of schizophrenia is substantiated by observation that high affinity uncompetitive antagonists of NMDA receptors such as PCP can induce psychotic symptoms in humans. Recently, metabotropic glutamate receptors of the mGluR5 type have also been discussed as possible players in this disease. However, less is known about the potential contribution of mGluR1 in schizophrenia. Therefore, the aim of the present study was to compare the effect of selective mGluR1 antagonist EMQMCM, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist (MTEP ([(2-methyl-1, 3-thiazol-4-yl) ethynyl] pyridine) either alone or in combination with (+)MK-801 in a prepulse inhibition (PPI) model and locomotor activity tests. Additionally, the effect of both mGluR1 and mGluR5 antagonists on (+)MK-801-evoked ataxia was tested. In contrast to (+)MK-801, which induced disruption of PPI, neither MTEP (1.25-5 mg/kg) nor EMQMCM (0.5-4 mg/kg) altered the PPI. However, MTEP, but not EMQMCM, enhanced disruption of PPI induced by (+)MK-801. Although neither mGluR1 nor mGluR5 antagonists given alone changed locomotor activity of rats, MTEP at 5 mg/kg potentiated the effect of (+)MK-801 while EMQMCM (up to 4 mg/kg) turned out to be ineffective. On the other hand, EMQMCM, but not MTEP, enhanced ataxia evoked by MK-801. The present results demonstrate that blockade of mGluR1 and mGluR5 evokes different effects on behavior induced by NMDA receptor antagonists.

Acoustic Stimulation↗

Effects of mGlu1 and mGlu5 receptor antagonists on negatively reinforced learning.

Effects on aversive learning of the novel highly selective mGlu5 receptor antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and mGlu1 receptor antagonist (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM) were tested, after systemic administration, in the passive avoidance (PA) and fear potentiated startle (FPS) paradigms. Both MTEP at 10 mg/kg and EMQMCM at 5 and 10 mg/kg, given 30 min before training, impaired acquisition of the passive avoidance response (PAR). Co-administration of MTEP and EMQMCM at doses ineffective when administered alone, produced anterograde amnesia when given 30 min before the acquisition phase. Neither EMQMCM (5 mg/kg) nor MTEP (10 mg/kg) impaired retention of the PAR after direct post-training injections. EMQMCM (5 mg/kg), but not MTEP (10 mg/kg) blocked the PAR when given 30 min before testing. Pre-training administration of MTEP at doses of 2.5 and 5 mg/kg inhibited fear conditioning in the FPS when tested 24 h later. In contrast, EMQMCM was ineffective. Our findings suggest diverse involvement of mGlu1 and mGlu5 receptors in negatively reinforced learning.

Amnesia, Anterograde↗

Ten-year survival of the MS-30 matt-surfaced cemented stem.

The Morscher-Spotorno (MS-30) femoral stem is a stainless-steel, straight, three-dimensionally tapered, collarless implant for cemented fixation in total hip replacement. We report the results at ten years of a consecutive series of 124 total hip replacements in 121 patients with the matt-surfaced MS-30 stem and an alumina ceramic head of 28-mm diameter. All the stems were fixed with Palacos bone cement with gentamicin using a modern cementing technique. They were combined with an uncemented, press-fit cup. The mean period of observation was 10.2 years (8.3 to 12.1) and no patient was lost to follow-up. Twenty-seven patients (22%) died with the implant in situ. Nine could only be interviewed by telephone. We included 85 patients with 88 hips in the clinical and radiological follow-up examinations. None of the stems or cups had been revised. The Harris hip score was excellent or good in 97% (85 hips) and moderate in 3% (three hips). Radiologically, six hips (6.8%) had osteolysis adjacent to the stem, mostly in Gruen zone 7. Twenty (22.7%) showed one or more radiolucent lines. Twenty-two stems (25%) had subsided by 2 mm to 5 mm. In these cases two showed osteolysis (9.1%) with subsidence and four without (6.1%). Radiolucent lines were seen in seven with migration (31.8%) and in 13 without (19.7%). No infections and no acetabular osteolysis were observed. The clinical results were excellent with survivorship after ten years of 100% and only a slightly statistically non-significant higher rate of osteolysis and radiolucency in cases of subsidence.

Acetabulum↗

Functional eicosanoid test and typing (FET) of peripheral blood cells in eicosanoids related diseases.

Monitoring of eicosanoid synthesis in peripheral blood cells has significant potential for improving the diagnosis and therapy of many human diseases. The quantitative relation between concentrations of prostaglandins and leukotrienes is central to the physiologic function of the eicosanoid network. Here we show that this regulation, which we call the functional eicosanoid typing (FET), fluctuates dynamically in individual living blood cells from patients, thereby limiting the accuracy with which concentration circuits of eicosanoids can transfer metabolic information. Using living cells in functional cell testing, we characterised the eicosanoid pattern score (EPS). A novel technique based on binomial errors on lipid mediator partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that eicosanoid production rates fluctuate over a time scale of about twenty minutes, while intrinsic noise decays rapidly. Thus, biochemical eicosanoid parameters, noise, and slowly varying cellular states together determine the effective FET. These results can form a basis for quantitative modelling of natural eicosanoid circuits in diagnosis of eicosanoid related diseases and design of synthetic ones for the prediction other diseases.

Adult↗

Abnormal eicosanoid-pattern of peripheral white-blood cells in gastro-intestinal cancer.

COX-inhibitors promote nasal polyps or bronchial asthma in individuals susceptible to an alteration of the pattern of the eicosanoids, especially leukotrienes and prostaglandins. This is associated with an abnormal release of eicosanoids from white blood cells. Since COX-inhibitors also protect from colorectal cancer an analogous association may be suggested. The study was performed to detect abnormal patterns of eicosanoids in white blood cells of patients with intestinal cancer compared to healthy controls. Seventy patients with intestinal cancer (stomach = 5; colon = 25; sigma = 18; rectum = 22) were compared to 62 healthy controls. Blood leukocytes from patients in complete long-lasting remission were incubated with diluent, arachidonic acid or acetylsalicylic acid. The synthesis of prostaglandin E(2) and peptido-leukotrienes was quantified using competitive enzyme-immuno-assays and calculated for individual eicosanoid patterns. The mean basal and arachidonic- or acetylsalicylic acid-modulated PGE(2) synthesis in patients was significantly higher than in controls (4.8-fold, 9.4-fold, 3.7-fold, respectively) whereas pLT was generally less elevated. We conclude that the eicosanoid-pattern of white-blood-cells from patients with intestinal cancer differs significantly from that in healthy individuals. This abnormal cellular metabolism may contribute to the manifestation of cancer and help to detect individuals at risk.

Adult↗

[Engineering and characterization of functional osteochondral replacement tissue].

Extensive osteochondral lesions require repair of the cartilage and underlying bone. We generated osteochondral repair tissue by tissue engineering. Standardized defects, 7 x 5 x 5 mm, were created in femoropatellar grooves of adult rabbits. Engineered cartilage, generated in vitro starting from chondrocytes and a biodegradable scaffold, was implanted using Collagraft as subchondral support. Cell-free implants, defects left empty, and unoperated knee joints served as controls. Explants were characterized morphologically and mechanically. Engineered cartilage implants were superior to cell-free implants and to natural healing of empty defects with respect to the histologic score and Young's modulus of the 6-month repair tissue. These data suggest that engineered cartilage can provide primary stability for the treatment of critical osteochondral defects.

Bone Remodeling↗

Pain treatment: a historical overview.

Pain is a common experience of mankind. Pain theories and the management of pain have been modified throughout the history of mankind. This article gives a brief review on pain, pain believes and pain management from early magico-demonic and magico-religious ideas and procedures to more empiric-scientific models; from ancient times and primitive cultures to the 20th century. Due to new anatomical, physiological and biochemical insights, modern pain theories developed in the 19th and 20th century. Modern analgesics were synthesized and new invasive procedures were approved having a major impact on pain management strategies. However, older traditional beliefs and attitudes have not been replaced completely and have survived to some degree in modern patients.

Analgesics↗

ORC-GAC-Fe0 system for the remediation of trichloroethylene and monochlorobenzene contaminated aquifer: 1. Adsorption and degradation.

Activities at a former Chemistry Triangle in Bitterfeld, Germany, resulted in contamination of groundwater with a mixture of trichloroethylene(TCE) and monochlorobenzene(MCB). The objective of this study was to develop a barrier system, which includes an ORC(oxygen release compounds) and GAC(granular activated carbon) layer for adsorption of MCB and bioregeneration of GAC, a Fe0 layer for chemical reductive dechlorination of TCE and other chlorinated hydrocarbon in situ. A laboratory-scale column experiment was conducted to evaluate the feasibility of this proposed system. This experiment was performed using a series of continuous flow Teflon columns including an ORC column, a GAC column, and a Fe0 column. Simulated MCB and TCE contaminated groundwater was pumped upflow into this system at a flow rate of 1.1 ml/min. Results showed that 17%-50% of TCE and 28%-50% of MCB were dissipated in ORC column. Chloride ion, however, was not released, which suggest the dechlorination do not happen in ORC column. In GAC column, the adsorption of contaminants on activated carbon and their induced degradation by adapted microorganisms attached to the carbon surface were observed. Due to competitive exchange processes, TCE can be desorbed by MCB in GAC column and further degraded in iron column. The completely dechlorination rate of TCE was 0.16-0.18 cm(-1), 1-4 magnitudes more than the formation rate of three dichloroethene isomers. Cis-DCE is the main chlorinated product, which can be cumulated in the system, not only depending on the formation rate and its decaying rate, but also the initial concentration of TCE.

Adsorption↗

Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes.

Recent works have shown that mechanical loading can alter the metabolic activity of chondrocytes cultured in 3D scaffolds. In this study we determined whether the stage of development of engineered cartilaginous constructs (expanded adult human articular chondrocytes/Polyactive foams) regulates the effect of dynamic compression on glycosaminoglycan (GAG) metabolism. Construct maturation depended on the culture time (3-14 days) and the donor (4 individuals). When dynamic compression was subsequently applied for 3 days, changes in GAG synthesized, accumulated, and released were significantly positively correlated to the GAG content of the constructs prior to loading, and resulted in stimulation of GAG formation only in the most developed tissues. Conversely, none of these changes were correlated with the expression of collagen type II mRNA, indicating that the response of chondrocytes to dynamic compression does not depend directly upon the stage of cell differentiation, but rather on the extracellular matrix surrounding the cells.

Cartilage, Articular↗

Development and validation of a bioreactor for physical stimulation of engineered cartilage.

A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer-controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072+/-0.051 microm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74+/-0.36% for samples of 1.60-3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).

Bioreactors↗

[Early functional treatment of surgically managed Achilles tendon rupture].

40 acute traumatic ruptures of the Achilles tendon were evaluated in a prospective study after open repair using an early functional rehabilitation protocol. The age of the patients averaged 43 (23-64) years. The operation consisted of a Kessler suture and microadaptation of the tendon. A special boot was used for after treatment. The boot was used 9 (1-18) weeks and full weight bearing was reported after 7 (1-16) weeks. The sick leave time averaged 5.5 (0-18) weeks. After 1 year, length and ankle joint motion were restored. Outcome was assessed using a 100-point score described by Thermann. After 4 months it averaged 73.5 +/- 15.5 points and after 1 year 94.5 +/- 6.0 points. There were no perioperative complications. One rerupture occurred 6 weeks postoperatively and was operated successfully. The combination of surgical repair and early functional after treatment resulted in normal function after 1 year, but requires cooperation of the patient.

Achilles Tendon↗

[Estimation of accident risk in obstructive sleep apnea syndrome (OSAS) by driving simulation].

Abstract. Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

Accidents, Traffic↗