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Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 19 recordsLinked to original sources
PubMed2006

Cellular effects and metabolic stability of N1-cyclic inosine diphosphoribose and its derivatives.

BACKGROUND AND PURPOSE: Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues. EXPERIMENTAL APPROACH: cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells. KEY RESULTS: Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5'-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds. CONCLUSIONS AND IMPLICATIONS: The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.

ADP-ribosyl Cyclase↗
PubMed2005

Assessing the working memory network: studies with functional magnetic resonance imaging and structural equation modeling.

A considerable body of evidence supports the notion that the neurofunctional substrate of working memory is not only related to the integrity of the prefrontal cortex, but also to the concerted interplay of widespread interacting networks including the parietal cortex, subcortical regions and cerebellar areas. Modern functional brain imaging techniques such as functional magnetic resonance imaging (fMRI) have provided a detailed picture of functional neuroanatomy subserving working memory functions. Most of the earlier functional studies were directed toward the identification of brain areas subserving specific cognitive domains in terms of a functional segregation. More recently, different multivariate techniques were employed to specifically address measures of functional or effective connectivity. Structural equation modeling (SEM) or path analysis is one of the most often used methods to model interactions among covarying brain areas in an explicitly model-based approach. The present review will focus on basic methodological issues of SEM for the analysis of fMRI datasets in studies of working memory. Aside from a discussion of previous studies and their essential findings, advanced methodological issues and caveats as well as future perspectives of the method will be addressed.

Brain↗
PubMed2005

Loss of efferent vagal activity in acute schizophrenia.

An increased heart rate has been reported in schizophrenia. It is unclear whether this is due to disease-related autonomic nervous system changes or a side effect of antipsychotic medication. Altered cardiac autonomic function might to some extent account for the elevated cardiovascular mortality rate of schizophrenic patients. We assessed heart rate variability (HRV) in 30 acute unmedicated schizophrenic patients and matched controls. Patients were re-investigated 2--4 days after initiation of treatment to assess effects of medication. Our study demonstrates that non-medicated schizophrenic patients were significantly different in heart rate (increase) and parasympathetic parameters (loss of efferent vagal activity) at rest and during deep respiration. No significant effect was found after initiation of neuroleptic therapy. We found a correlation between duration of disease and parasympathetic parameters as well as very low frequency power (VLF) and delusion (SAPS subscale). These data suggest that schizophrenia is accompanied by a loss of vagal efferent activity, probably due to disturbed cortical-subcortical circuits modulating the autonomic nervous system in acute psychosis. The definite mechanisms by which vagal activity might be suppressed in schizophrenia are unknown. Parasympathetic hypoactivity might increase the risk for sudden cardiac death and arrhythmias in this disease. Future studies are warranted to investigate the interaction between cardiac autonomic function and schizophrenia and to identify patients on risk.

Acute Disease↗
PubMed2005

[Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling].

Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of "cognitive dysmetria" in schizophrenia.

Antipsychotic Agents↗
PubMed2005

Sexual medicine in the medical curriculum.

The new field of Sexual Medicine has now changed to the primary care physician because of the new symptom-treating pharmacological possibilities, a fact not to be foreseen 10 years ago. The future, therefore, is to create the platform for the 'basic doctor' to identify and correctly treat male and female sexual dysfunction on the basis of a sufficient knowledge (obtained through formalized, pre-graduate education) within the field of Sexual Medicine. All this will need positive support and good strategies, as well as evidence-based new knowledge created by endocrinology, gynaecology, andrology, genetics, neurology, angiology, but also psychology, sociology, anthropology and related disciplines to help the medical clinician to fulfil his Hippocratic Oath: to assist the individual who needs help - in sexual dilemmas as well.

Curriculum↗
PubMed2004

Hybrid computations with flux exchange.

We discuss a hybrid scheme that is based on flux exchange between a particle and a continuum system which reside in two slightly overlapping volumes in space. The scheme ensures conservation of mass, momentum and energy between a system of Lennard-Jones particles and a continuum description given by the compressible Navier-Stokes equations. An implementation in two dimensions employing the compressible Navier-Stokes equations to describe the continuum, and the Lennard-Jones potential to describe the particles, is discussed. The accuracy of the coupling scheme is tested successfully for the case of homogeneous flow and discussed for the more general case.

Journal Article↗
PubMed2004

Combined family trio and case-control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa.

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample.

Alleles↗
PubMed2004

The methodology of corpus cavernosum electromyography revisited.

OBJECTIVE: The methodology of corpus cavernosum electromyography (CC-EMG) was revisited, in order to overcome current methodological difficulties that hinder its clinical application. MATERIALS AND METHODS: Using an 8-channel device, CC-EMG was performed in 12 healthy volunteers. Surface electrodes were placed bilaterally on the penile shaft and the kneecap (reference electrode), the pubis region and the anterior superior iliac spine (ASIS). A band pass filter with cut-off frequencies of 0.1 and 20 Hz was used. At least 2 sessions of recordings were performed in each subject. RESULTS: Thirty-five of 46 recordings were interpretable. Significant time delays between potentials recorded from different sites of the CC were detected. Clear spatial voltage gradients related to CC-potentials were observed on the pubis region. No voltage changes related to CC-potentials, but electrical activity from other sources were recorded from the ASIS. In contrast to frequency, a clear correlation could be demonstrated between amplitude, duration and polyphasity of CC-potentials recorded in 2 different sessions in the same individual. CONCLUSIONS: Multichannel monopolar recording of CC-EMG with surface electrodes is practical and has several advantages compared with bipolar recording. The results provide evidence that the recorded signals indeed reflect electrical activity of the CC and therefore offer a basis to pursue further clinical validation studies.

Adult↗
PubMed2004

Resolution and sensitivity of high field nuclear magnetic resonance spectroscopy.

The arrival of very high field magnets and cryogenic circuitries, and the development of relaxation-optimized pulse sequences have added powerful tools for increasing sensitivity and resolution in NMR studies of biomacromolecules. The potential of these advances is not fully realized in practice, however, since current experimental protocols do not permit sufficient data sampling for optimal resolution in the indirect dimensions. Here we analyze quantitatively how increasing resolution in indirect dimensions affects the S/N ratio and compare this with currently used sampling routines. Optimal resolution would require sampling up to approximately 3 R (2)(-1), and the S/N reaches a maximum at approximately 1.2 R (2)(-1). Currently used data acquisition protocols rarely sample beyond 0.4 R (2)(-1), and extending evolution times would result in prohibitively long experiments. We show that a general solution to this problem is to use non-uniform sampling, where only a small subset of data points in the indirect sampling space are measured, and possibly different numbers of transients are collected for different evolution times. Coupled with modern methods of spectrum analysis, this strategy delivers substantially improved resolution and/or reduced measuring times compared to uniform sampling, without compromising sensitivity. Higher resolution in the indirect dimensions will facilitate the use of automated assignment programs.

Entropy↗
PubMed2004

The effect of management factors on the seroprevalence of Anaplasma marginale in Bos indicus cattle in the Mexican tropics.

A cross-sectional study with a two-stage design and proportional distribution was carried out to determine the effect of management factors on the seroprevalence of Anaplasma marginale in Bos indicus cattle in the Mexican tropics. Serum was obtained from 384 cattle aged 1-2 years on 92 farms. The number of samples was proportionally distributed according to the number of farms in eastern Yucatan. Antibody activity against A. marginale was assessed using the card agglutination test. A primary screening using a 2 x K contingency table of the exposed variables with the outcomes was performed. All variables for which p < 0.20 were included in a fixed-effects log regression. The seroprevalence in the cattle was 69.75% (SE +/- 0.02). Sixty-four per cent of the farms had a seroprevalence > or = 75%. The risks related to managemental factors were stocking density ( > or = 1 animal/ha, OR = 10.94), type of acaricide (pyrethroids, OR = 3.8), dipping interval ( > 60 days, OR = 0.13) and type of veterinary instruments used (needles, scalpels, ear tattoos, and dehorners, OR = 0.17).

Agglutination Tests↗
PubMed2004

Severe and uncommon involuntary movement disorders due to psychotropic drugs.

Disorders of involuntary movement due to psychotropic drugs pose a major problem when treating mentally ill patients. These adverse drug reactions (ADR) frequently undermine the patients' compliance and may have serious consequences as well. The drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) surveyed a population of 122,562 patients between 1993 and 2000, and documented 129 especially severe or uncommon involuntary movement disorders (IMD): 9 episodes of severe acute dyskinesia, 32 of severe Parkinsonism, 5 of especially severe akathisia, 16 of 'atypical dyskinesia', 38 of Pisa syndrome, 6 of catatonic neuroleptic syndrome, 15 of neuroleptic malignant syndrome, and 8 of tardive dyskinesia. The epidemiological data for this population were systematically analyzed as regards the patient's history of medication, comedication, and clinical course. In those cases, in which a certain drug was imputed to cause an ADR alone and the causal relationship was rated as definite or probable, typical neuroleptics with mainly antipsychotic effects showed a relatively high incidence of 0.1047 %, those with hypnotic-sedative effect a lower incidence of 0.0198 %, and the atypical neuroleptics an incidence of 0.0567 %. This difference was highly significant in an chi (2)-analysis (chi (2) = 18.81, df = 2, p < 0.0001). Our data provide important information on the frequency, severity, and the consequences of ARD for the patients' compliance, and thus are of clinical interest.

Adult↗
PubMed2004

Blood dyscrasias induced by psychotropic drugs.

Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions.

Adult↗
PubMed2004

Time course of ECG depolarization and repolarization changes during ischemia in PTCA recordings.

OBJECTIVES: In this work we studied the temporal evolution of changes in the electrocardiogram (ECG) as a consequence of the induced ischemia during prolonged coronary angioplasty, comparing the time course of indexes reflecting depolarization and those reflecting repolarization. METHODS: We considered both local (measured at specific points of the ECG) and global (obtained from the Karhunen-Loève transform) indexes. In particular, the evolution of Q, R and S wave amplitudes during ischemia was analyzed with respect to classical indexes such as ST level. As a measurement of sensitivity we used an Ischemic Changes Sensor (ICS), which reflects the capacity of an index to detect changes in the ECG. RESULTS: The results showed that, in leads with low-amplitude ST-T complexes, the S wave amplitude was more sensitive in detecting ischemia than was the commonly used index ST60. It was found that in such leads the S wave amplitude initially exhibited a delayed response to ischemia when compared to ST60, but its performance was better from the second minute of occlusion. The global indexes describing the ST-T complex were, in terms of the ICS, superior to the S wave amplitude for ischemia detection. CONCLUSIONS: Ischemic ECG changes occur both at repolarization and depolarization, with alterations in the depolarization period appearing later in time. Local indexes are less sensitive to ischemia than global ones.

Action Potentials↗
PubMed2003

The value of corpus cavernosum electromyography in erectile dysfunction: current status and future prospect.

In the last decade, several investigators have tried to develop corpus cavernosum electromyography (CC-EMG) as a direct clinical method to evaluate the state of the penile autonomic innervation and the cavernous smooth muscle. Both basic and clinical studies have shown promising results. However, its application as a diagnostic tool with clinical relevance was hindered by insufficient knowledge of cavernous smooth muscle electrophysiology, lack of standardization, technical and practical difficulties and problems in the interpretation of the results. Recently, the European Commission created the so-called COST Action B18 (corpus cavernosum EMG in erectile dysfunction), aiming to strengthen the coordination of the European research groups and give the development of CC-EMG a new impetus. This review presents an overview of the physiological background, the current status of CC-EMG, and discusses possibilities for further developments.

Electromyography↗
PubMed2003

Epidemiology of erectile dysfunction.

This review of the current epidemiological literature on erectile dysfunction (ED) suggests that approximately 5-20% of men have moderate-to-severe ED. Different definitions of ED, age distributions and concomitant medical conditions, as well as methodological differences, may explain much of the variance in reported prevalence rates. Various chronic disorders are associated with elevated rates of ED including depression, diabetes, and cardiovascular and neurological diseases. Such disorders are more common in the elderly, which may partially explain the elevated prevalence of ED in men over 60 y of age. Currently, up to 70% of men with ED are not treated. However, so many men experience considerable distress from their condition, that the increasing awareness of ED as well as the availability of noninvasive treatments may result in a greater proportion of patients seeking treatment, and eventually regaining satisfaction with their sex life.

Adolescent↗
PubMed2003

Levels and correlates of psychological distress in male couples of mixed HIV status.

Few studies have analyzed the impact of HIV infection on dyadic functioning and on the distress levels of each partner, independently, in HIV-serodiscordant relationships, particularly in same-sex dyads. The main purpose of this study was to assess levels of psychological distress in the HIV-positive and HIV-negative members of HIV-discordant male couples and to explore possible couple-related factors associated with distress. This was done within a systems theory framework. Levels of distress among the men were in the mild to moderate range, according to general population norms. Factors associated with distress in the men included dyadic satisfaction, sexual satisfaction, avoidance and self-blame coping style, and support from one's partner. Results suggest the need for 'couple-focused' clinical interventions for HIV-discordant couples.

Adaptation, Psychological↗
PubMed2003

Photoperiod affects amplitude but not duration of in vitro melatonin production in the ruin lizard (Podarcis sicula).

The pineal gland and its major output signal melatonin have been demonstrated to play a central role in the seasonal organization of the ruin lizard Podarcis sicula. Seasonal variations in the amplitude of the nocturnal melatonin signal, with high values in spring as compared to low values in summer and autumn, have been found in vivo. The authors examined whether the pineal gland of the ruin lizard contains autonomous circadian oscillators controlling melatonin synthesis and whether previously described seasonal variations of in vivo melatonin production can also be found in isolated cultured pineal glands obtained from ruin lizards in summer and winter. In vitro melatonin release from isolated pineal glands of the ruin lizard persisted for 4 days in constant conditions. Cultured explanted pineal glands obtained from animals in winter and summer showed similar circadian rhythms of melatonin release, characterized by damping of the amplitude of the melatonin rhythm. Although different photoperiodic conditions were imposed on ruin lizards before explantation of pineal glands, the authors did not find any indication for corresponding differences in the duration of elevated melatonin in vitro. Differences were found in the amplitude of in vitro melatonin production in light/dark conditions and, to a lesser degree, in constant conditions. The presence of a circadian melatonin rhythm in vitro in winter, although such a rhythm is absent in vivo in winter, suggests that pineal melatonin production is influenced by an extrapineal oscillator in the intact animal that may either positively or negatively modulate melatonin production in summer and winter, respectively.

5-Methoxytryptamine↗