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Biomedical subjects

D Wedekind

Publications and source records attributed to D Wedekind.

At least 19 recordsLinked to original sources
PubMed2003

5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.

Blunted neuroendocrine and physiological responses to the selective 5-HT(1A) receptor agonist, ipsapirone, have been observed in patients with panic disorder and/or agoraphobia (PDA). In order to examine whether this hyporesponsiveness to ipsapirone is modified by pharmacological or non-pharmacological therapeutic interventions, challenges with an oral dose of ipsapirone (0.3 mg/kg) and placebo were performed in patients with PDA before and after 10 weeks of treatment with clomipramine, aerobic exercise and placebo. Before treatment, administration of ipsapirone was followed by significant increases of cortisol, anxiety and other psychopathological symptoms in comparison to the placebo challenge. In addition, a significant decrease of body temperature was observed. After the 10-week treatment period, the psychological responses to ipsapirone were significantly reduced in the clomipramine and the exercise group. In contrast, there was a non-significant trend towards higher cortisol responses after clomipramine and exercise treatment. The hypothermic response to ipsapirone was significantly reduced by clomipramine treatment. In conclusion, our results demonstrate that effective treatment of panic disorder has divergent effects on the psychological, neuroendocrine and temperature responses to ipsapirone.

Adolescent↗
PubMed2001

Genetic identification of multiple susceptibility genes involved in the development of endometrial carcinoma in a rat model.

There are clear indications that inheritance plays an essential role in certain cases of human endometrial cancer, and there are at least 2 forms of early-onset heritable endometrial adenocarcinomas (EACs). Females of the BDII inbred rat strain are known to be genetically predisposed to endometrial carcinoma, and we have performed a genetic analysis of susceptibility to endometrial cancer in this strain. F(2) populations were generated by crossing BDII females with males from 2 different strains with a low incidence of EAC, and the occurrence of endometrial cancer was studied. Three chromosome regions associated to EAC susceptibility were identified, and the susceptibility genes in these regions were designated Ecs1, Ecs2 and Ecs3. Our results indicate that the genes affecting susceptibility to EAC are different in the 2 crosses, suggesting that the genes behind the susceptibility in BDII animals may interact with different genes in different genetic backgrounds.

Adenocarcinoma↗
PubMed2001

The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus.

AIMS/HYPOTHESIS: We describe a new Type I (insulin-dependent) diabetes mellitus rat model (LEW.1AR1/Ztm-iddm) which arose through a spontaneous mutation in a congenic Lewis rat strain with a defined MHC haplotype (RT1.Aa B/Du Cu). METHODS: The development of diabetes was characterised using biochemical, immunological and morphological methods. RESULTS: Diabetes appeared in the rats with an incidence of 20 % without major sex preference at 58+/-2 days. The disease was characterised by hyperglycaemia, glycosuria, ketonuria and polyuria. In peripheral blood, the proportion of T lymphocytes was in the normal range expressing the RT6.1 differentiation antigen. Islets were heavily infiltrated with B and T lymphocytes, macrophages and NK cells with beta cells rapidly destroyed through apoptosis in areas of insulitis. CONCLUSION/INTERPRETATION: This Type I diabetic rat develops a spontaneous insulin-dependent autoimmune diabetes through beta cell apoptosis. It could prove to be a valuable new animal model for clarifying the mechanisms involved in the development of autoimmune diabetes.

Animals↗
PubMed2001

A novel black-hooded mutant rat (ci3) with spontaneous circling behavior but normal auditory and vestibular functions.

Abnormal circling behavior in rodents is usually attributed to vestibular dysfunction. In rats, all circling mutants described previously have inner ear defects resulting in auditory and vestibular dysfunctions. Here, we describe a new mutant rat with abnormal spontaneous circling behavior but normal auditory and vestibular functions. The new circling mutant rat was discovered in progeny of an apparently normal black-hooded (BH) rat inbred line [BH.7A(LEW)/Won] and was termed ci3, because we recently found two other mutant circling rats (ci1 and ci2) in a Lewis (LEW) inbred rat strain. The ci3 mutant is characterized by circling behavior and locomotor hyperactivity, which occur in phases or bursts either spontaneously or in response to stress, e.g., when rats are transferred to a new environment. Video monitoring of undisturbed rats in their home cage during the light and dark periods showed that circling behavior is much more intense during the dark period, i.e., during the active phase of the animals. Most ci3 rats show a lateral preference in their rotational behavior, i.e., they either rotate to the left or to the right. Brainstem auditory evoked potential testing and different tests of vestibular function did not disclose any auditory or marked vestibular defects in ci3 rats. Furthermore, no morphological abnormalities were seen during histological examination of the cochlear and vestibular nuclei in the brainstem. Neurochemical determination of dopamine and dopamine metabolite levels in striatum, nucleus accumbens and substantia nigra showed that ci3 rats have a significant asymmetry in striatal dopamine in that dopamine levels were significantly lower in the hemisphere contralateral to the preferred direction of turning. Consistent with this finding, immunohistological examination of dopaminergic neurons in substantia nigra and ventral tegmental area yielded a significant laterality in the medial part of substantia nigra pars compacta with a lower density of tyrosine hydroxylase-positive neurons in the contralateral hemisphere of mutant circling rats, while no laterality was seen in unaffected rats of the background strain [BH.7A(LEW)/Won].Thus, the novel mutant ci3 rat exhibits several features which clearly differ from previously described circling rat or mouse mutants. The behavioral phenotype occurs in the absence of auditory or obvious vestibular defects and is most likely a consequence of lateralized abnormalities found in the nigrostriatal circuit. Apart from the use of ci3 rats for studying the functional lateralization of brain functions, the ci3 mutant may serve as a new model for movement disorders with abnormal lateralization.

Animals↗
PubMed2001

Auditory and vestibular defects in the circling (ci2) rat mutant.

The circling rat is an autosomal recessive mutant (homozygous ci2/ci2) that displays lateralized circling behaviour, locomotor hyperactivity, ataxia and stereotypic head-movement. These abnormal behaviours occur in phases or bursts either spontaneously or in response to stress. Heterozygous (ci2/+) littermates display normal spontaneous behaviours. We have previously found that ci2/ci2 rats of both genders have a lower tissue content of dopamine in the striatum ipsilateral to the preferred direction of rotation, indicating that the rats turn away from the brain hemisphere with higher striatal dopaminergic activity. In view of the similarities of the motor syndrome of the ci2/ci2 mutant rat to that of mouse deafness mutants, the present study evaluated the hearing ability of the circling rat mutant by recording brainstem auditory-evoked potentials. To test for vestibular dysfunction, a swimming test was conducted. Histological methods were used to examine the cochlear and vestibular parts of the inner ear and the cochlear and vestibular brainstem nuclei for defects. The absence of auditory-evoked potentials demonstrated a complete hearing loss in the adult ci2/ci2 mutant rat, whereas heterozygous littermates exhibited auditory-evoked potentials with thresholds resembling those of other laboratory strains. Furthermore, the mutant rats were unable to swim. Histological analysis of the inner ear of adult mutants revealed virtually complete loss of the cochlear neuroepithelium, while no such hair cell degeneration was seen in the vestibular parts of the inner ear. However, part of the vestibular hair cells showed protrusions into the endolymphatic space, suggesting alterations in the cytoskeletal architecture. The histological findings in mutant circling rats strongly indicate that the hearing loss of the mutants is of the sensory neural type, the most prevalent type of hearing loss. In the cochlear nuclei of the brain stem of mutant rats, neurons exhibited an abnormal shape, reduced size and increased density compared to controls. In contrast, no abnormal neuronal morphology was seen in the vestibular nuclei, but a significantly reduced neuronal density was found in the medial vestibular nucleus. Abnormal vestibular function would be a likely explanation for the disturbed balance of mutant rats as exemplified by the ataxia and the inability to swim, whereas the previous data on these rats strongly indicate an involvement of the basal ganglia in the abnormal circling behaviour. The genetic defect in the mutant rats, thus, results in a clinical syndrome with features also seen in human genetic disorders with deafness and hyperkinesia, making the ci2/ci2 rat an excellent model for investigating both cochlear/vestibular dysfunction and hyperkinetic movement disorders.

Animals↗
PubMed2001

[Cortisol in night-urine: Introduction of a research method in psychoneuroendocrinology].

Cortisol is one of the major parameters investigated in psychoneuroendocrinological research, but the methods employed for sample collecting are often unsatisfactory. A suitable method of sample collection should allow for the integrative assessment of long-term changes of the HPA-system, should be non-invasive, and should not exceed the subject's compliance. The assessment of cortisol in night-urine fulfils these demands; although this method has been occasionally employed, it has not yet been described systematically. For the first time a detailed description is given here that allows for a standardized replication. In ten previous studies and three investigations of our own this method has been successfully applied to detect changes in the cortisol excretion of patients with endocrinological and psychiatric disorders as well as in subjects under conditions of psychosocial stress. The determination of cortisol in night-urine represents an ideal method for the assessment of changes in the basal HPA-activity in numerous areas of psychoneuroendocrinological research, e.g. field and screening studies in natural environment, clinical studies in psychiatry and especially follow-up studies in psychotherapy research.

Adult↗
PubMed2000

Diurnal variation of cortisol in panic disorder.

In patients with panic disorder (n=23), daytime salivary cortisol levels were determined in 2-h spans on 3 consecutive days and compared with 23 age- and sex-matched healthy controls. Additionally, nocturnal urinary free cortisol levels were measured. Daytime salivary cortisol levels were numerically higher in the patients, although the difference did not reach statistical significance. In a subgroup of 14 patients with higher illness severity (as expressed by a score >/=22 on the Panic and Agoraphobia Scale), salivary cortisol levels were significantly higher than in the controls. Mean nocturnal urinary cortisol levels were significantly higher in the whole group of patients and also in the more severely ill subgroup when compared with controls. Cortisol elevations seem to be more pronounced during the night and occurred mainly in more severely ill panic patients.

Adult↗
PubMed2000

Salivary, total plasma and plasma free cortisol in panic disorder.

BACKGROUND: Research on basal HPA axis activity in patients with panic disorder showed inconsistent results. METHODS: Basal total plasma, plasma free and salivary cortisol levels were compared in patients with panic disorder (n = 47) and in healthy individuals (n = 23). Correlations between these fractions were calculated. RESULTS: All three basal cortisol fractions were significantly elevated in patients compared to controls. There were significant correlations between all three cortisol fractions. CONCLUSIONS: Nonsignificant differences between cortisol levels of patients and healthy controls in previous studies may have been due to inclusion of less severely ill patients or to small sample sizes (96 words).

Adult↗
PubMed2000

Salivary cortisol in panic attacks.

OBJECTIVE: Documentation of hypothalamic-pituitary-adrenal (HPA) axis disturbance in panic disorder has been inconsistent. Increased cortisol levels have been associated with altered HPA function due to stress. The authors examined salivary cortisol levels in spontaneously occurring, unprovoked panic attacks. METHOD: Patients with panic disorder (N=25) collected saliva samples when panic attacks occurred. Levels of cortisol in the saliva samples were determined and were compared with levels in comparison samples of saliva obtained 24 hours after the panic attack occurred. RESULTS: During spontaneous panic attacks there was a subtle but significant elevation of cortisol levels, compared with levels obtained 24 hours later. No significant correlations were found between the cortisol elevations during panic attacks and the severity of the attack as measured by using the Acute Panic Inventory or the severity of illness as measured by using the Panic and Agoraphobia Scale. CONCLUSIONS: Saliva sampling may be a useful method for investigating neuroendocrine parameters during spontaneously occurring panic attacks.

Adult↗
PubMed1999

Tumor gene therapy made easy: allogeneic major histocompatibility complex in the C6 rat glioma model.

The C6 glioma in the immune-competent rat is a frequently used model in brain tumor gene therapy research. It displays the histologic hallmarks of the human glioblastoma and has been employed to demonstrate new mechanisms of anti-tumor immunity and therapeutic strategies. We noted that C6 tumors regressed spontaneously in three of five animals and that protective anti-tumor immunity ensued without therapeutic intervention. A review of the literature revealed that different rat strains are used as "syngeneic" host for the C6 cell glioma, namely, BDIX, BDX, Sprague-Dawley, and Wistar. Allelotyping of the RT1.A (rat MHC I homolog) by a serologic technique and of the RT1.B (rat MHC II homolog) by a newly developed molecular technique showed that C6 cells express the haplotype RT1u and are allogeneic in the preceding rat strains. Expression of the gene encoding the transactivator CIITA in C6 gliomas using an EBV-based transduction system led to induction of MHC I and II and thereby mimicked therapeutic responses that could not operate in syngeneic models. These data suggest that the C6 glioma model in the immune-competent rat should no longer be used to study gene therapy strategies, that the available data obtained in this model need to be critically reinterpreted, and that findings obtained in the C6 glioma model may not be sufficient to support a clinical trial in glioblastoma patients.

Animals↗
PubMed1999

Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy.

By using three-dimensional magnetic resonance imaging-based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinson's syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA-P, n = 12) or ataxia (MSA-C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA-C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA-P, 15 of 17 patients with MSA-C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA-P could not be separated from patients with PSP. In conclusion, total intracranial volume-normalized magnetic resonance imaging-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism.

Adult↗
PubMed1998

Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3.

Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all three SCA mutations compared with a group of 31 age- and sex-matched controls. Comparison between the SCA groups showed that cerebellar and brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three morphological criteria was defined that enabled us to assign all SCA2 and SCA3 patients correctly to the underlying genotype. In contrast, these criteria did not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a significant association between CAG repeat length and the volumes of the respective brain structures in any of the SCA mutant types. The present data provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.

Adult↗
PubMed1997

No evidence for a physiological coupling between melatonin and glucocorticoids.

Much has been speculated about the existence of a physiological coupling between melatonin and glucocorticoid secretion and about a possible anti-stress action of melatonin. We examined the relationship between melatonin and glucocorticoid secretion under close-to-physiological conditions, when the plasma concentration of either melatonin or glucocorticoids was elevated acutely or chronically in both rats and humans. Tryptophan administration caused a massive rise of plasma melatonin, but had no effect on corticosterone levels in rats or on cortisol levels in humans. The acute and long-lasting exposure of rats to uncontrollable stress resulted in a significant rise of adrenal corticosterone secretion, but had no effect on circulating melatonin levels. Orchectomy caused an initial increase in circulating corticosterone (when melatonin was unaffected) and a delayed rise in circulating melatonin (when corticosterone levels were normalized). In humans, no correlation was found between the nocturnal urinary excretion of melatonin and cortisol, either among healthy subjects, or among patients suffering from panic disorder (with an increased urinary excretion of cortisol) or among insomnia patients (with a high incidence of low melatonin secretion). Furthermore, no evidence was found for a suppressive action of melatonin on dexamethasone-mediated thymus regression in rats and on dexamethasone-mediated suppression of lymphocyte proliferation in vitro. Taken together, the results of this study provide no evidence for the existence of mutual influences between melatonin and glucocorticoid secretion, nor do they support the proposed attenuation of glucocorticoid-mediated effects on target cells or tissues by melatonin under physiological conditions.

Adult↗
PubMed1997

Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder.

Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and melatonin secretion patterns were studied in male patients with DSM IV/ICD-10 panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time urinary excretion of cortisol, norepinephrine, and epinephrine was significantly elevated in drug-free patients compared to normal individuals (n = 13). Measurements were repeated after 4 weeks, and the same differences were found again. There were high correlations between the first and the second series of measurements. Testosterone and melatonin levels did not differ between panic patients and controls.

Adult↗
PubMed1997

Endocrine correlates of personality traits: a comparison between emotionally stable and emotionally labile healthy young men.

An initial sample of 120 healthy young men was screened by a personality questionnaire and 15 subjects each with highest and lowest scores respectively on emotionality (emotionally labile, EL subjects and emotionally stable, ES subjects) were recruited for a study on the relationship between the degree of emotionality and the basal secretion of stress-sensitive hormones during night-time. The nocturnal urinary excretion of cortisol, testosterone, adrenaline, noradrenaline and melatonin was measured over a period of 5 consecutive nights. The average amounts of each hormone excreted per night were not different between the two extreme groups. The variability of the excretion during the 5 nights of cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin, was significantly higher in EL compared to ES subjects. The larger fluctuations in the nocturnal secretion of these two (and no other) hormones in EL subjects indicate that emotional lability is associated with a more labile regulation of cortisol and testosterone secretion. The observed intraindividual variability of basal stress hormone secretion may contribute to the vast interindividual variability noticed in psychoneuroendocrine stress research, especially in emotionally labile subjects.

Adolescent↗