Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 181 records · Page 10Linked to original sources

PubMed1997

Effect of metrifonate on extracellular brain acetylcholine and object recognition in aged rats.

The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats. Extracellular acetylcholine levels were measured by transversal microdialysis in vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old rats did not discriminate between familiar and novel objects. In old rats, metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase activity in the cortex and hippocampus, a 4-fold increase in extracellular acetylcholine levels in the cortex only, and restored object recognition. In young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral cortex and hippocampus, a 2-fold increase in cortical and hippocampal extracellular acetylcholine levels, and no effect on object recognition. The slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats had no effect on cortical acetylcholine levels and object recognition. In conclusion, metrifonate may improve the age-associated cholinergic hypofunction and cognitive impairment.

Acetylcholine↗

PubMed1997

Behavioral characterization of metrifonate-improved acquisition of spatial information in medial septum-lesioned rats.

We investigated the effects of acute oral pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation in medial septum-lesioned rats. We observed that metrifonate (30 mg/kg, orally) (1) does not alter the pattern of exploration of lesioned rats at the water maze pool or retrieval of spatial memory, (2) effectively reverses the acquisition defect, (3) enhances reversal learning, and (4) improves acquisition of water maze navigation by facilitating the encoding of the spatial representation of a specific environment. These results indicate that metrifonate does not improve escape performance to the hidden platform by modulating exploration strategy, but that metrifonate enhances the speed and accuracy of development and durability of spatial memory engrams, and facilitates learning capacity that depends on activity of the septo-hippocampal projection.

Acetylcholinesterase↗

PubMed1997

Design, synthesis, and biological activities of four angiotensin II receptor ligands with gamma-turn mimetics replacing amino acid residues 3-5.

Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy3,5]-Ang II, c[Cys3,5]-Ang II, and c[Pen 3,5]-Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and 1H-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys3,5]-Ang II and c[Pen3,5]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT1 receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen3,5]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.

Angiotensin II↗

PubMed1997

Effects of combined chronic nimodipine and acute metrifonate treatment on spatial and avoidance behavior.

The present experiment was designed to elucidate whether chronic dietary treatment with nimodipine (3 months, 1000 ppm) enhances water maze spatial navigation, passive avoidance behavior and locomotor activity, and whether such a treatment with nimodipine would interact with the therapeutic effect of acute metrifonate treatment. In young medial septum-lesioned rats, nimodipine had no effect by its own on cognitive or motor behavior, and did not enhance the water maze and passive avoidance behavior improving action of metrifonate (3 and 10 mg/kg. p.o.). Nimodipine treatment of aged rats did not markedly affect the deficit in motor performance. Single and combined nimodipine and metrifonate (3 and 10 mg/kg, p.o.) treatment of aged rats resulted in shorter escape distance values to the hidden water maze escape platform compared to those of control aged rats. The passive avoidance performance of aged rats was more effectively facilitated by a combined nimodipine and metrifonate treatment than by either of the drugs on their own. Following a washout period of 2.5 months the rats that were treated previously with nimodipine no longer performed better than aged controls in the water maze test. Furthermore, after the washout period metrifonate 10 mg/kg was no longer effective in improving the water maze behavior of the now 26-month-old rats irrespective of their chronic pretreatment. Taken together, these findings indicate that chronic nimodipine and acute metrifonate treatment may more effectively stimulate cognitive functioning than either of the treatments on their own.

Animals↗

PubMed1997

Nd:YAG laser and tracheobronchial metallic stents: an experimental in vitro study.

STUDY DESIGN/MATERIALS AND METHODS: The aim of this experimental study was to investigate the effect of Nd:YAG laser on metallic tracheobronchial stents, because Nd:YAG laser could be used for resection of tumourous tissue growing through stent meshes (Strecker-, Palmaz-, Wallstent). STUDY DESIGN/MATERIALS AND METHODS: An in vitro worst-case-model was used to investigate the effects of different types of laser application on metallic stents: non-contact application, and contact application with bare fibres and with hemispherical sapphires. RESULTS: In the non-contact method and with bare fibres stent destruction occurred at power settings exceeding 10 W, whereas in the contact method with hemispherical sapphires power settings of 20 W were possible without stent damage.

Animals↗

PubMed1997

Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity.

The cellular function of the prion protein (PrPc), a cell surface glycoprotein expressed in neurones and astrocytes, has not been elucidated. Cell culture experiments reveal that cerebellar cells lacking PrPc are more sensitive to oxidative stress and undergo cell death more readily than wild-type cells. This effect is reversible by treatment with vitamin E. In vivo studies show that the activity of Cu/Zn superoxide dismutase is reduced in Prnp gene-ablated (Prnp0/0) mice. Constitutively high Mn superoxide dismutase activity in these animals may compensate for this loss of responsiveness to oxidative stress. These findings suggest that PrPc may influence the activity of Cu/Zn superoxide dismutase and may be important for cellular resistance to oxidative stress.

Amino Acid Sequence↗

PubMed1997

Cell death in prion disease.

Prion diseases are neurodegenerative transmissible diseases. The infectious agent, termed prion, is thought to consist of an altered host-encoded protein. The pathogenesis of these diseases which typically in a very short time lead to rampant nerve cell death and astrocytic gliosis is poorly understood. Investigations using the in situ endlabeling technique and electron microscopy in a scrapie model in the mouse (79A strain) show that nerve cell death is due to apoptosis. A cell culture model using a synthetic peptide of the prion protein (PrP106-126) shows that this peptide is toxic only to normal neurons whereas nerve cells derived from PrP knock-out (PrP0/0) mice are unaffected by this neurotoxic effect. In addition, microglia play a crucial part in this process by secreting reactive oxygen species. Experiments in animals will have to show whether these cell culture findings adequately reflect the in vivo pathogenesis.

Amino Acid Sequence↗

PubMed1997

Chronic nimodipine and acute metrifonate treatment decreases age-related cortical high voltage spindles in rats.

We studied the effect of nimodipine (1000 ppm mixed in food), an L-type calcium-channel antagonist, administered for 4 months, on the cortical EEG activity in young and aged rats. Nimodipine treatment decreased cortical high voltage spindles (HVSs) in aged rats, but did not prevent the diminution of spontaneous locomotor activity. The threshold dose of metrifonate, a cholinesterase inhibitor, for suppression of HVSs was lower in nimodipine compared to placebo treated aged rats (30 mg/kg versus 60 mg/kg; p.o.). In young rats, nimodipine did not decrease HVSs, protect from scopolamine (0.1 or 0.8 mg/kg, i.p.) induced EEG slowing or augment the effect of metrifonate to suppress slow waves induced by scopolamine. The present results suggest that a chronic nimodipine treatment modulates thalamocortical arousal and thereby adds to the therapeutic effects of metrifonate to restore normal cortical electrical arousal in aged rats.

Aging↗

PubMed1997

Long-term follow up of children with head injuries-classified as "good recovery" using the Glasgow Outcome Scale: neurological, neuropsychological and magnetic resonance imaging results.

UNLABELLED: The primary issues addressed in this study were: (1) determination of the significance of the classification "good outcome" utilizing the Glasgow Outcome Scale (GOS) in children at least 1 year after brain injury; (2) detection of residual lesions of brain parenchyma in these children upon follow up MRI scans; and (3) detection of relationships between neuropsychological test performance and MRI results. Selection criteria included children 6-15 years of age at the time of testing who received an initial CT scan at the time of their head injury and who had been injured at least 12 months prior to the follow up test. Only children who did not demonstrate neurological disability at the time of follow up examination were selected. The children showed a status of "good outcome" as defined by the GOS. Neurological examination, neuropsychological tests and an MRI were done. The test results of 59 patients were compared to those of a matched control group. Children, after receiving head injuries, showed significantly poorer results with respect to cognitive, motor and fine motor skills. Of all MRI-scans 66% revealed pathological findings. Cortical lesions were detected on MRI in 14% of cases; subcortical injuries were detected in 12% and, deep white matter lesions in 31%. Furthermore, corpus callosum damage was observed in 26% of cases. Pathological MRI findings were also observed in children with mild head injuries. All of the children with normal MRI findings showed abilities comparable to those of children in the control group. Patients with cortical lesions exhibited only motor deficits, whereas motor and cognitive deficits were seen in patients with deep white matter lesions. Children with multiple lesions demonstrated test results in all variables 1 to 2 standard deviations below those of the control group. CONCLUSION: Children suffering a brain injury who 1 year later are classified within the "good outcome" group according to the Glasgow Outcome Scale often have significant morphological and functional brain deficits.

Adolescent↗

PubMed1997

Cerebral complications in Schimke immuno-osseous dysplasia.

UNLABELLED: Schimke immuno-osseous dysplasia is a multisystem disorder consisting of spondylo-epiphysial dysplasia, progressive renal insufficiency due to focal segmental glomerulosclerosis, and immunodeficiency. Cerebrovascular complications have only been described in five patients. Here we report a patient with prominent neurological symptoms most likely caused by transient ischaemic attacks. CONCLUSION: Neurological symptoms consisted of repeated brief spells of hemiparaesthesia, motoric aphasia and diplopia. MRI studies of the CNS revealed progressive white matter lesions. Morphological changes as well as neurological deficits are compatible with cerebral ischaemia.

Brain↗

PubMed1997

Does vitamin C cause hemolysis in premature newborn infants? Results of a multicenter double-blind, randomized, controlled trial.

OBJECTIVE: We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis. STUDY DESIGN: A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10). RESULTS: Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09). CONCLUSION: Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.

Anemia, Hemolytic↗

PubMed1997

Alterations of the metastasis suppressor gene nm23 and the proto-oncogene c-myc in human testicular germ cell tumors.

The putative metastasis suppressor genes nm23-H1, nm23-H2 and the c-myc proto-oncogene were investigated in testicular germ cell tumors (GCTs) using Southern and Northern blotting as well as semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analysis. When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases. A 2 to 7 fold nm23 mRNA overexpression was found in 22/34 (64.7%) tumors examined. RT-PCR revealed that this phenomenon is mainly a consequence of nm23-H2 overexpression. Overexpression of both the H1 and the H2 gene was predominantly found in the seminoma subtype and was not associated with tumor stage. Only 1/25 tumors, a seminoma with distant metastases, had a point mutation in the coding region of the nm23-H2 gene as demonstrated by SSCP analysis. None of the 8 seminomas and only 1/13 non-seminomas had c-myc overexpression. No abnormalities of the c-myc gene could be detected on the DNA level. Despite the fact that in previous investigations nm23-H2 was demonstrated to be a putative transcription factor for c-myc, no coexpression of c-myc and nm23-H2 was found by quantitative RT-PCR in this study.

Chromosome Aberrations↗

PubMed1997

Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits.

The cholinergic system is known to show deterioration during aging and Alzheimer's disease. In response, a therapeutic approach to Alzheimer's disease has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase inhibitors. In this study treatment with the long-lasting cholinesterase inhibitor metrifonate enhanced acquisition of eyeblink conditioning in aging rabbits without producing interfering side effects. The effects of metrifonate on central and peripheral cholinesterase activity were evaluated, as was the involvement of plasma atropine esterase activity on the central and peripheral response to metrifonate. Results demonstrate that metrifonate can produce predictable, dose-dependent ChE inhibition. Associative learning in the aging rabbit was improved by metrifonate-induced steady state ChE inhibition within a range of 30-80%. Metrifonate was behaviorally effective in the absence of the severe side effects which typically plague cholinesterase inhibitors, suggesting that metrifonate is a possible treatment for the cognitive deficits resulting from normal aging and Alzheimer's disease.

Aging↗

PubMed1997

The etiology, diagnosis and treatment of thrombotic disorders in newborn infants: a call for international and multi-institutional studies.

OBJECTIVE: To examine the present state of knowledge on the etiology, diagnosis, and treatment of neonatal thrombosis. METHODS: A Medline search (exp infant, newborn, and exp thrombosis, and prospective studies) was performed to identify high-quality articles that have been published during the last 30 years. RESULTS: The retrieval rate increased from less than one citation per year to an average of three per year in the current Medline file. An intravascular catheter is the most common risk factor for the development of neonatal thrombosis (excluding strokes). Little is known about the precision and accuracy of noninvasive imaging techniques, which are commonly used to make the diagnosis. The efficacy and safety of anticoagulant or thrombolytic therapy remain uncertain. CONCLUSIONS: The published literature on neonatal thrombotic disorders continues to show a shortage of well-designed international and multi-institutional studies. The latter are urgently needed to rationalize the management of affected infants.

Humans↗

PubMed1997

Effects of oxidative stress on prion protein expression in PC12 cells.

PC12 cells are known to express the prion protein, a normal cell surface glycoprotein. This protein is upregulated in PC12 cells differentiated with nerve growth factor. A neurotoxic prion protein peptide, PrP106-126, is not toxic to PC12 cells alone. PrP106-126 is toxic to PC12 cells co-cultured with microglia and more so to NGF-differentiated PC12 cells. PC12 cells selected for resistance to either copper toxicity or oxidative stress have higher levels of PrP(C) expression. Both PC12 variants are more sensitive to the toxicity of PrP106-126. This suggests that PC12 sensitivity to PrP106-126 toxicity is related to prion protein expression and not to a state of high differentiation induced by NGF. Variants of PC12 cells that are more resistant to copper toxicity have higher levels of anti-oxidant enzymes, superoxide dismutase and glutathione peroxidase. Our results suggest that cells expressing higher levels of PrP(C) have higher resistance to oxidative stress or copper toxicity but are more sensitive to PrP106-126 toxicity. Prion protein expression may be involved in both the metabolism of copper and resistance to oxidative stress. Increased cellular resistance to copper toxicity may be partly related to increased activity of anti-oxidant enzymes.

Animals↗

PubMed1997

Temporary tracheobronchial stenting in malignant stenoses.

Endobronchial stent implantation has been successfully employed in malignant stenoses. The aim of this prospective study was to investigate the temporary use of tracheobronchial stents combined with tumour-specific therapy. All patients received stents for primary palliation of dyspnoea followed by radio- or chemotherapy with the aim of stent removal after reduction of the stenosis. In 22 patients suffering from severe malignant strictures, 34 endobronchial stents (29 Strecker-, 3 Dumon-, 1 Orlowski-, 1 Dynamic-Y-stents) were implanted (in 9 patients, 2 stents were necessary). Patients were treated by irradiation (n = 18) or chemotherapy (n = 4) after stent implantation. Significant improvement of dyspnoea (P < 0.001) and partial oxygen pressure (P < 0.01) was observed. In 11 out of 22 cases (50%), the stents could be removed after successful tumour-specific therapy which led to reduction of stenosis after a mean interval of 31.7 (6-104) days (temporary stenting). During the period of tumour-specific therapy, 9 patients died after a mean interval of 132 (13-347) days (definite stenting). In two cases, stents had to be removed after stent compression, stent dislocation and severe cough. The results suggest that temporary stenting, characterised by subsequent successful tumour-specific therapy, is a new valuable therapeutic strategy. It can "bridge the gap" before tumour-specific therapy can take effect. If tumour-specific therapy is ineffective, definite stenting is the palliative method of choice in severe dyspnoea in bronchial carcinoma.

Adult↗

PubMed1997

Metrifonate improves associative learning and retention in aging rabbits.

The cholinergic system is known to show deterioration during aging and Alzheimer's disease (AD). In response, a therapeutic approach to AD has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase (ChE) inhibitors. In this study treatment with the long-lasting ChE inhibitor metrifonate facilitated acquisition and retention of eyeblink conditioning in aging rabbits. Metrifonate treatment resulted in steady-state, dose-dependent acetylcholinesterase (AChE) inhibition in red blood cells. Maximal behavioral efficacy was achieved with AChE inhibition of approximately 40%, with no further improvements resulting from increased levels of inhibition. Metrifonate was behaviorally effective in the absence of the severe side effects that can plague ChE inhibitors, supporting metrifonate as a possible treatment for the cognitive deficits resulting from normal aging and AD.

Acetylcholinesterase↗

PubMed1997

Comparative study of the complement-activating and specific IgE-binding properties of ragweed pollen allergen.

Previous reports have defined the capacity of ragweed pollen extract (RWA) to activate human complement (C) in fluid phase through the classical pathway and have ascertained a strong correlation between the extent of complement activation and the severity of symptoms of allergic rhinoconjunctivitis during the ragweed blooming season. In the present study the complement-activating and specific IgE-binding capacities of various ragweed allergen preparations were compared. Elimination of physically adsorbed (flavonoid) pigments from the allergenic proteins had no significant effect on their complement-consuming capacity, although the process strongly diminished specific IgE binding. Removal of an IgE-binding trypsin inhibitor from RWA significantly enhanced RWA-induced complement activation, whereas it did not change IgE binding. These findings indicate that neither the physically adsorbed pigments nor the trypsin inhibitor are involved in complement activation by ragweed pollen allergens, and suggest that complement activation and specific IgE binding are distinct molecular properties of ragweed pollen allergen.

Allergens↗