Biomedical subjects

C Beyer

Publications and source records attributed to C Beyer.

At least 19 recordsLinked to original sources

PubMed2005

Xenon reduces glutamate-, AMPA-, and kainate-induced membrane currents in cortical neurones.

BACKGROUND: The anaesthetic, analgesic, and neuroprotective effects of xenon (Xe) are believed to be mediated by a block of the NMDA (N-methyl-D-aspartate) receptor channel. Interestingly, the clinical profile of the noble gas differs markedly from that of specific NMDA receptor antagonists. The aim of this study was, therefore, to investigate whether Xe might be less specific, also inhibiting the two other subtypes of glutamate receptor channels, such as the alpha-amino-3-hydroxy-5-methyl-4-isoxazolole propionate (AMPA) and kainate receptors. METHODS: The study was performed on voltage-clamped cortical neurones from embryonic mice and SH-SY5Y cells expressing GluR6 kainate receptors. Drugs were applied by a multi-barreled fast perfusion system. RESULTS: Xe, dissolved at approximately 3.45 mM in aqueous solution, diminished the peak and even more the plateau of AMPA and glutamate induced currents. At the control EC(50) value for AMPA (29 microM) these reductions were by about 40 and 56% and at 3 mM glutamate the reductions were by 45 and 66%, respectively. Currents activated at the control EC(50) value for kainate (57 microM) were inhibited by 42%. Likewise, Xe showed an inhibitory effect on kainate-induced membrane currents of SH-SY5Y cells transfected with the GluR6 subunit of the kainate receptor. Xe reduced kainate-induced currents by between 35 and 60%, depending on the kainate concentration. CONCLUSIONS: Xe blocks not only NMDA receptors, but also AMPA and kainate receptors in cortical neurones as well as GluR6-type receptors expressed in SH-SY5Y cells. Thus, Xe seems to be rather non-specific as a channel blocker and this may contribute to the analgesic and anaesthetic potency of Xe.

Anesthetics, Inhalation↗

PubMed2003

Xenon incorporated in a lipid emulsion inhibits NMDA receptor channels.

BACKGROUND: Over the past decade hyperpolarized (129)xenon incorporated in lipid emulsions has been studied for the purpose of imaging enhancement in radiology. Xenon (Xe), a NMDA (N-methyl-D-aspartate)-receptor antagonist, has neuroprotective properties even at subanesthetic concentrations. Thus, its intravenous administration for this purpose deserves further evaluation. In this study, we investigated in an in vitro model the effect of Xe, incorporated in a lipid emulsion (Lipofundin MCT(R) 20%), on the NMDA receptor channel of cortical neurons of the mouse. METHODS: Pulses of 50 micro M of NMDA solution were extracellularly applied to the cells for 10 s, and the elicited membrane currents (I) were recorded while the membrane potential (V) was clamped at -80 mV. Either Lipofundin MCT(R) 20% or aqueous solution was loaded with Xe and applied simultaneously with the NMDA pulses by means of a multibarreled pipette attached to a battery of infusion-pumps. RESULTS: Xenon equilibrated in Lipofundin(R) caused a concentration-dependent and reversible inhibition of NMDA-induced currents (maximal Xe content [Xemax]: 190 micro l ml-1). The inhibitory effect was equivalent compared with the effect of Xe dissolved in aqueous solution (Xemax: 89 micro l ml-1) even though the Xe content of the lipid solution was almost doubled. Further enhancement of the Xe content by saturating both the lipid emulsion and the aqueous solutions with Xe (Xemax: 256 micro l ml-1) did not increase the inhibitory action on NMDA-receptors. CONCLUSION: The data demonstrate that Xe dissolved in Lipofundin MCT(R) 20% inhibits NMDA-receptors. Lipid emulsions enriched with Xe may serve as a carrier and a reservoir for Xe.

Animals↗

PubMed2003

Immunocytochemical detection of progesterone receptor in the female rabbit forebrain: distribution and regulation by oestradiol and progesterone.

There is no information on the neuroanatomical distribution of the progesterone receptor (PR) in the rabbit. Therefore, we mapped the distribution of PR-immunoreactive cells in the forebrain of ovariectomized female rabbits. Vehicle-injected ovariectomized rabbits showed PR-immunoreactive cells only in the infundibular nucleus (IN) and nucleus X (lateral to the ventromedial hypothalamic nucleus). The injection of oestradiol benzoate (EB; 5 micro g/day for 5 days) increased the number of PR-immunoreactive cells in the IN and in three nuclei of the preoptic region (periventricular, medial, and principal). Abundant PR were also found in the paraventricular nucleus and nucleus X. Administration of progesterone (10 mg/day) for 3 days to EB-treated rabbits (a treatment that induces digging behaviour for the maternal nest and suppresses sexual receptivity and scent-marking) eliminated PR-immunoreactivity from all brain areas analysed except the IN. Thus, one-third of the number of cells seen in the ovariectomized + EB condition persisted in this region despite progesterone injections. Withdrawal of progesterone (and continuation of EB) for 5 (but not for 2) days (in a schedule similar to the one that induces straw-carrying and hair-pulling for the maternal nest) increased the number of PR-immunoreactive cells in all regions analysed. These results show that restricted regions of the female rabbit forebrain express abundant PR which are either: (i). up-regulated by oestradiol and down-regulated by progesterone; (ii). oestradiol-insensitive and down-regulated by progesterone; or (iii). insensitive to both oestradiol and progesterone.

Animals↗

PubMed2003

Non-ligand activation of estrous behavior in rodents: cross-talk at the progesterone receptor.

Estrous behavior in rodents is triggered by the binding of progesterone (P) to its intracellular receptor (PR). Non-steroidal agents (i.e., gonadotropin-releasing hormone, noradrenaline, dopamine and others), acting at the membrane, can facilitate estrous behavior in estrogen-primed rats. This action is mediated through the generation of second messengers (cyclic AMP, cyclic GMP, calcium) which, in turn, phosphorylate through diverse kinase systems (protein kinases A, G or C) either the PR or associated effector proteins linking the PR to the trans-activation machinery. P or its metabolites also activate cyclic AMP-signaling pathways by acting directly on the membrane or by modulating neurotransmitter release. Molecular processes resulting from second messenger signaling pathways and those from the progesterone-RP interaction synergize to elicit a full behavioral response.

Animals↗

PubMed2002

Application of infrared spectroscopy to monitoring gas insulated high-voltage equipment: electrode material-dependent SF(6) decomposition.

Sulfur hexafluoride is a chemically inert gas which is used in gas insulated substations (GIS) and other high-voltage equipment, leading to a significant enhancement of apparatus lifetime and reductions in installation size and maintenance requirements compared to conventional air insulated substations. However, component failures due to aging of the gas through electrical discharges may occur, and on-site monitoring for risk assessment is needed. Infrared spectroscopy was used for the analysis of gaseous by-products generated from electrical discharges in sulfur hexafluoride gas. An infrared monitoring system was developed using a micro-cell coupled to an FTIR spectrometer by silver halide fibers. Partial least-squares calibration was applied by using a limited number of optimally selected spectral variables. Emphasis was placed on the determination of main decomposition products, such as SOF(2), SOF(4), and SO(2)F(2). Besides the different electrical conditions, the material of the plane counter electrode of the discharge chamber was also varied between silver, aluminum, copper, tungsten, or tungsten/copper alloy. For the spark experiments the point electrode was the same material as chosen for the plane electrode, whereas for partial discharges a stainless steel needle was employed. Complementary investigations on the chemical composition within the solid counter electrode material by secondary neutral mass spectrometry (SNMS) were also carried out. Under sparking conditions, the electrode material plays an important role in the decomposition rates of the gas-phase, but no relevant material dependence could be observed under partial discharge conditions.

Journal Article↗

PubMed2002

Properties of a chimeric simian-human immunodeficiency virus expressing an hybrid HIV-1 Nef/SIVmac Nef protein.

The nef genes of human and simian immunodeficiency viruses code for a membrane associated protein critical for AIDS development. SIVmac Nef presents C-terminal a 27 amino acid extension absent of HIV-1 Nef. To estimate the influence of this C-terminal domain on virus properties, we constructed viruses derived from SIVmac239 by replacing SIV nef with HIV-1 Lai nef gene (SHIV NefLai4) or with a sequence encoding a Nef fusion protein: HIV-1 Lai Nef/SIV Nef-Cterm (SHIV-Cterm). The recombinant viruses replicated efficiently in vitro in CEMx174 cells and in activated macaque PBMCs. The addition of SIV Nef C-terminal domain to HIV-1 Nef in SHIVNefLai4 did not change the in vitro properties of the chimeric virus, both viruses being more infectious than a nef deleted virus. Although the half-life of Nef fusion protein was augmented, SHIV-Cterm remained slightly less infectious than SIVmac239.

Amino Acid Sequence↗

PubMed2002

Rapid stimulation of the PI3-kinase/Akt signalling pathway in developing midbrain neurones by oestrogen.

Oestrogen promotes the differentiation of neurones in the central nervous system. In the rodent midbrain, the maturation of dopaminergic neurones appears to be under oestrogen control. This is supported by the fact that dopaminergic cells contain nuclear oestrogen receptors-alpha/beta (ER). Second, aromatase is transiently expressed in the developing midbrain. In previous studies, we have shown that oestrogen increases dopamine synthesis and plasticity of dopamine cells. These effects are transmitted through classical nuclear ER but require also the stimulation of nonclassical signalling pathways involving the activation of membrane receptors. This study attempted to identify nonclassical oestrogen-dependent signalling cascades which might be stimulated downstream of membrane ERs. Using cultured mouse midbrain cells, we could demonstrate by Western blotting, that oestrogen rapidly phosphorylates Akt, a kinase which is implicated in the phosphatidylinositol 3 (PI3)-kinase pathway. This effect was only seen in midbrain neurones but not astrocytes. Oestrogen-induced Akt phosphorylation was time- and dose-dependent, showing highest responses after 30 min and at a steroid concentration of 10(-8) and 10(-6) M. Immunocytochemistry for phosphorylated Akt (pAkt) demonstrated that pAkt is predominantly found in a nuclear/perinuclear position and that oestrogen exposure increased the number of pAkt-positive cells. To investigate the mechanisms which are involved in transmitting oestrogen effects on the cellular level, cells were treated with antagonists for distinct signalling pathways. The application of the nuclear ER antagonist ICI 182 780 did not abolish the oestrogen-induced Akt phosphorylation. In contrast, interrupting intracellular calcium signalling with BAPTA completely prevented this effect. The PI3-kinase inhibitor LY294002 also inhibited the activation of Akt by oestrogen. Our study clearly indicates that oestrogen can rapidly stimulate the PI3-kinase/Akt signalling cascade in differentiating midbrain neurones. This effect requires the intermediate activation of calcium-dependent signalling pathways. In conclusion, oestrogen effects in the developing midbrain appear to be connected with the PI3-kinase/Akt signalling mechanism.

Animals↗

PubMed2002

Development of an experimental ovarian tumor: immunocytochemical analysis.

OBJECTIVE: The aim of the present work was to study whether immunocytochemical parameters present in the normal ovary were altered after tumor development under high gonadotropin levels. METHODS: Ovarian tumors (luteoma): castrated female rats had an ovary grafted into the spleen; tumors were left to develop for 1, 2, 3 or 7 months. The presence of apoptotic cells (TUNEL method) and the expression of proliferating cell nuclear antigen (PCNA), gap junction protein (Cx43), steroidogenic acute regulatory protein (StAR), aromatase and synaptosome-associated protein of 25 kDa (SNAP-25) were determined by immunocytochemistry. Some of these findings were confirmed by RT-PCR (Cx43, StAR, SNAP-25). Inhibin subunit mRNAs were investigated by Northern blot. RESULTS: PCNA staining of tumors was mainly found in granulosa cells of transforming follicles and was absent from luteinized follicles. A nearly complete absence of apoptosis was observed. Cx43 was mainly found in follicles, while it was very weakly expressed or absent in luteinized follicles. StAR protein expression, indicating active steroidogenesis, was demonstrated only in luteinized follicles and in thecal cells, but was absent from granulosa cells. Aromatase immunoreactivity was very intense in granulosa and also present in luteal cells. Membrane-associated and cytoplasmic SNAP-25 immunostaining was determined in patches of endocrine cells in the follicles, as well as in the luteinized follicles. The expression of mRNAs for Cx43, StAR and SNAP-25 (RT-PCR) and inhibin subunits (Northern blots) were confirmed in 1-, 3- and 7-month-old tumors. CONCLUSIONS: These results indicated that luteoma most likely develop from unruptured follicles by hypertrophy and proliferation of follicular cells. Circulating gonadotropins seem to play a fundamental role in maintaining the expression of proteins typically expressed in normal ovary, while avoiding apoptosis in this tissue.

Animals↗

PubMed2001

Estrogen stimulates brain-derived neurotrophic factor expression in embryonic mouse midbrain neurons through a membrane-mediated and calcium-dependent mechanism.

We have provided evidence that 17beta-estradiol (E) synthesized in the midbrain promotes the differentiation of midbrain dopamine neurons through nonclassical steroid action. Because these developmental effects resemble those reported for brain-derived neurotrophic factor (BDNF), we hypothesized that E influences dopaminergic cell differentiation through a BDNF-dependent mechanism. Competitive RT-PCR and ELISA techniques were employed to study first the developmental pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein/mRNA levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure reduced midbrain BDNF mRNA/protein levels. The coapplication of CGS 16949A and E abolished this effect. Midbrain cultures from mouse fetuses were used to investigate intracellular signaling mechanisms involved in transmitting E effects. Estrogen increased expression of BDNF but not of other neurotrophins. As concerns the related signaling mechanism, these effects were antagonized by interrupting intracellular Ca(2+) signaling with BAPTA and thapsigargin but not by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF mRNA expression were inhibited by cycloheximide, it appears likely that other, not yet characterized intermediate proteins take part in the estrogenic regulation of BDNF expression. We conclude that E exerts its stimulatory effect on the differentiation of dopaminergic neurons by coordinating BDNF expression. This particular E effect appears to be transmitted through Ca(2+)-dependent signaling cascades upon activation of putative membrane estrogen receptors.

Animals↗

PubMed2001

Pre- and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippocampus.

Brain-derived neurotrophic factor (BDNF) is implicated in the control of hippocampal development. In this study, we have analyzed the developmental expression of BDNF mRNA/protein and its receptor tyrosine protein kinase receptor (trk) B mRNA in the mouse hippocampus by competitive reverse transcription/polymerase chain reaction and enzyme-linked immunoassay. Cell-type specificity of BDNF/trkB expression was studied in primary hippocampal cultures. BDNF levels increased stepwise from embryonic day 15 until the second postnatal week, whereas trkB expression was stable throughout development. Neurons and astrocytes expressed both BDNF and trkB. Our data suggest that developmental BDNF action mainly occurs postnatally and indicates that hippocampal neurons and astroglia not only produce BDNF but also appear to be targets for BDNF.

Aging↗

PubMed2001

Dopamine regulates brain-derived neurotrophic factor (BDNF) expression in cultured embryonic mouse striatal cells.

The differentiation of striatal GABAergic neurons coincides with the perinatal establishment of nigrostriatal dopaminergic synaptic connections. We have shown previously that dopamine stimulates the maturation of striatal GABAergic neurons. Since BDNF also regulates the development of GABAergic cells, we hypothesized that dopamine might affect striatal BDNF expression. The influence of dopamine on BDNF protein/mRNA and trkB mRNA levels was studied in neuronal and astroglia cultures of the mouse striatum. Stimulation with dopamine and a dopamine D1 receptor agonist increased BDNF mRNA and protein but not trkB mRNA in neuronal cultures. Our data indicate a potential role for dopamine in the developmental regulation of striatal BDNF expression and suggest that dopamine effects on GABAergic cells may be intertwined with BDNF action.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2001

Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms.

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumorigenesis is complex. On the one hand, GM-CSF can promote tumor cell growth, survival, and even metastasis. On the other hand, it can stimulate tumor cell rejection. In skin, it is early expressed after topic application of tumor-promoting agents and therefore may be responsible for changes that correlate with skin tumor promotion (e.g., epidermal hyperproliferation and inflammation). To analyze GM-CSF function in skin tumorigenesis, we generated transgenic mice epidermally overexpressing either GM-CSF or a GM-CSF antagonist. Both types of transgenic mice exhibited significantly increased numbers of benign tumors in a two-step skin carcinogenesis experiment using 7',12'-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-CSF displayed a significantly elevated carcinoma burden following a single-step carcinogenesis protocol consisting of tumor initiation only. Therefore, endogenous promotion is responsible for elevated tumor development in GM-CSF-overexpressing mice. In antagonist transgenic animals, an increased tumorigenicity of modified B16 tumor cells after cutaneous transplantation as compared with nontransgenic or GM-CSF transgenic mice was observed. Thus, the antitumor activity leading to the repression of tumor cell growth in control mice is GM-CSF dependent and is compromised in mice expressing the antagonist. We suggest that both, up-regulation and down-regulation of GM-CSF activity in skin, increase the incidence and growth of tumors via two independent mechanisms: endogenous tumor promotion in the case of increased GM-CSF activity and compromised tumor cell rejection in the case of decreased GM-CSF activity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Estrogen stimulates the mitogen-activated protein kinase pathway in midbrain astroglia.

Estrogen stimulates the development of midbrain dopamine neurons predominantly by acting through membrane receptors coupled to Ca(2+)-signaling. In this report, we describe that estrogen activates extracellular signal-regulated kinases (ERK1/2) in midbrain astrocytes but not neurons. This effect was inhibited by BAPTA which interrupts Ca(2+)-signaling but not by antagonists specific for other signaling pathways. The activation of the MAP kinase pathway suggests a potential role for astrocytes in mediating estrogen effects in the midbrain.

Animals↗

PubMed2001

Classical and nonclassical estrogen action in the developing midbrain.

There is widespread acceptance that estrogen is involved in various steps of cellular differentiation during brain development. In the past years, we have demonstrated such a developmental role for estrogen in the rodent midbrain. Precisely, estrogen affects midbrain dopamine neurons with respect to functional and morphological maturation. On the cellular level, estrogen may act classically by binding and activating its respective nuclear receptors, thereby controlling the transcription of target genes. On the other hand, many estrogen effects in the CNS are transmitted nonclassically by interactions with putative membrane receptors and by stimulating distinct intracellular signaling cascades. In the midbrain, classical and nonclassical estrogen signaling routes operate side by side to ensure the proper development of dopaminergic cells. In the present report, we detail some of the cellular and molecular events which are activated by estrogen and are thought to take part in the estrogen-mediated stimulation of dopamine neuron differentiation.

Animals↗

PubMed2001

Role of facet joints in chronic low back pain in the elderly: a controlled comparative prevalence study.

Evaluation of the age related prevalence of persistent low back pain has been estimated to be consistently higher in the elderly compared to the younger population. Facet joints have been shown to be the cause of chronic low back pain in 15% to 45% of the patients in controlled studies. Prevalence of facet joint mediated pain has not been studied in the elderly. The study population consisted of 100 patients. Group I consisted of 50 patients that were 64 years of age or younger. Group II consisted of 50 patients 65 years of age or older. The patients were randomly allocated into 1 of the 2 groups. Facet joints were investigated with diagnostic blocks initially using lidocaine 1% followed by bupivacaine 0.25%, usually 2 weeks apart. The prevalence of facet joint mediated pain was determined to be 30% in the adults and 52% in the elderly, which was significantly higher with a false positive rate of 26% in adults and 33% in the elderly. In conclusion, the results of this study show that facet joint mediated pain is a significant problem in all patients suffering with chronic low back pain with the prevalence of 52% in the elderly and 30% in adults.

Journal Article↗

PubMed2001

Provocative discography in low back pain patients with or without somatization disorder: a randomized prospective evaluation.

Recent reports of provocative discography not only instill confusion, but also create numerous questions about its value in evaluating low back pain. It was reported that provocative discography produced pain in patients who were not suffering with low back pain but suffering with somatization disorder and depression. This study was designed to evaluate 50 randomly assigned patients, with 25 patients in Group I without somatization disorder and 25 patients in Group II with diagnosis of somatization disorder. In addition, depression, generalized anxiety disorder and combinations thereof were also evaluated. All patients underwent discography, investigating two to three discs in each patient. All studies included a control level with a disc that did not produce the patient's pain upon injection of contrast medium. Provocation with exact pain reproduction concordant with the symptom complex upon injection of contrast into the disc was considered positive. Any other response, with or without pain, was considered negative. Results showed positive provocative discography in 46% of the patients in the somatization group compared to 54% in the non-somatization group; in 46% of patients with depression compared to 54% of patients without depression; in 15 of 30 patients with generalized anxiety disorder; in 11 of 20 patients without generalized anxiety disorder; and in 42% of patients with combined somatization and depression, with negative discography in 58% of the patients. It is concluded that provocative discography provides similar results in patients with or without somatization, with or without depression, with somatization but with or without depression or with other combinations of the psychological triad of somatization disorder, depression, and generalized anxiety disorder.

Journal Article↗

PubMed2001

Evaluation of the role of facet joints in persistent low back pain in obesity: a controlled, prospective, comparative evaluation.

Chronic low back pain and obesity are two common medical conditions. Obesity has been associated with symptoms such as adverse fat distribution and multiple secondary disorders, including low back pain. Obesity is defined as being 30% over ideal weight, which influences normal body mechanics as well as recovery from an injury. Facet joints have been described as contributing to a significant proportion of patients suffering with persistent or chronic low back pain, variably from 15% to 45%. Since an obese patient is at a higher risk of disability compared to a patient with normal weight, obesity has been described as a confounding factor in persistent low back pain. This study included 100 patients, with 50 patients in Group I who were of normal weight and 50 patients in group II who were obese, by random allocation. Facet joints were investigated with diagnostic blocks using lidocaine 1% initially, followed by bupivacaine 0.25%. The results showed that the prevalence rate of facet joint pain in chronic low back pain in Group I or nonobese patients was 36%, in contrast to 40% in Group II, or the obese patient group, with no significant differences among the two groups. The study also showed a false-positive rate of 39% in the total sample, or 44% in Group I nonobese patients and 33% in Group II, or obese patients. It is concluded that the prevalence of lumbar facet joint mediated pain of 40% in obese patients and 36% in patients of normal weight with a false-positive rate of 33% in obese patients and 44% in nonobese patients is similar to the results of multiple previous studies concluding that facet joint mediated pain is a common occurrence in obese patients; however, the incidence of facet joint mediated pain is similar in obese patients and nonobese patients.

Journal Article↗

PubMed2001

Evaluation of the relative contributions of various structures in chronic low back pain.

An attempt was made to determine the relative contribution of various structures to chronic low back pain, including facet joint(s), disc(s), and sacroiliac joint(s) in a prospective evaluation. Precision diagnostic blocks, including disc injections, facet joint blocks, and sacroiliac joint injections, are frequently used. In contrast, selective nerve root blocks or transforaminal epidural injections are used occasionally to evaluate persistent or recurrent low back pain in patients without appropriate radiologic or neurophysiologic diagnosis. One hundred and twenty patients with a chief complaint of low back pain were evaluated with precision diagnostic injections, which included medial branch blocks, provocative discography and sacroiliac joint injections. In 40% (95% CL, 31%, 49%), of the patients, facet joint pain was diagnosed; and in 26% (95% CL, 18%, 34%) of the patients discogenic pain was diagnosed; and 2% of the patients were diagnosed with sacroiliac joint pain.

Journal Article↗