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Klaus Lieb

Publications and source records attributed to Klaus Lieb.

45 records · Page 3Linked to original sources
PubMed2002

Inhibition of LPS-induced p42/44 MAP kinase activation and iNOS/NO synthesis by parthenolide in rat primary microglial cells.

Nitric oxide (NO) has been implicated in the etiopathology of central nervous system (CNS) diseases such as multiple sclerosis (MS). Inhibition of NO synthesis has been proposed to be a possible mechanism of action of relevance in the treatment of multiple sclerosis and migraine. Here, we investigated the effect of parthenolide on inducible NO synthase (iNOS) synthesis and NO release using primary rat microglia. We found parthenolide to be an inhibitor of iNOS/NO synthesis. Investigating the molecular mechanisms by which parthenolide prevents iNOS/NO synthesis, we found that parthenolide inhibits the activation of p42/44 mitogen-activated protein kinase (MAPK), but not IkBalpha (IkappaBalpha) degradation or nuclear factor-kappaB (NF-kappaB) p65 activation. The data suggest that parthenolide might have a potential in the treatment of CNS diseases where NO is part of the pathophysiology.

Animals↗
PubMed2002

Interferon alpha (IFNalpha) and psychiatric syndromes: a review.

Interferon alpha (IFNalpha) is used for the treatment of several disorders, such as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses, or confusional states. The reasons and management of these side effects are widely unknown. Our aim is to review research evidence for the contribution of IFNalpha for the etiopathology of psychiatric syndromes. Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha treatment, the putative mechanisms underlying those syndromes, and their treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed. Finally, the question is addressed whether IFNalpha may contribute to the etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric syndromes in a subset of treated patients. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine, and neurotransmitter systems. Research data on the role of IFNalpha in the pathogenesis of endogenous psychiatric disorders are conflicting. Future research should improve our understanding of the role of IFNalpha for the etiopathology of psychiatric syndromes and has an impact on treatment of IFNalpha-induced psychiatric syndromes.

Animals↗
PubMed2002

Effects of the neuropeptide substance P on sleep, mood, and neuroendocrine measures in healthy young men.

The neuropeptide substance P (SP) has been supposed to be involved in the etiopathology of affective disorders, mainly because of the finding of increased levels of SP in the cerebrospinal fluid of depressed patients and the preliminary evidence of antidepressant effects of SP-receptor antagonists in depressed patients. We investigated whether SP may induce changes of sleep, mood and neuroendocrine measures that are similar to those in depressed patients. In a double-blind, randomized cross-over design, 12 healthy young men were investigated in two blocks of three consecutive nights, in which SP or NaCl was intravenously infused during the third night. Polysomnographic recordings were obtained during all nights and blood samples were drawn every 30 min during the third night. Infusion of SP caused a significant worsening of the mood of the subjects, led to an increase of REM latency and time awake during the SP-infusion intervals, caused increased stage 1 sleep in the first part of the night, and led to increased cortisol and thyroid stimulating hormone levels and a trend for decreased growth hormone levels. These effects can be interpreted as evidence for a central arousing effect of SP. Further studies should focus on the effects of substance P in patients with depressive or other psychiatric disorders.

Adult↗
PubMed2002

Transient total sleep loss in cerebral Whipple's disease: a longitudinal study.

A case with transient, almost complete sleep loss caused by cerebral manifestation of Whipple's disease (WD) is presented. Cerebral WD is rare and in most cases occurs after gastrointestinal infection. In our case, a progressive and finally almost complete sleep loss was the initial and predominant symptom. Polysomnographic studies in several consecutive nights and over 24 h showed a total abolition of the sleep-wake cycle with nocturnal sleep duration of less than 15 min. Endocrine tests revealed hypothalamic dysfunction with flattening of circadian rhythmicity of cortisol, TSH, growth hormone and melatonin. Cerebrospinal fluid (CSF) hypocretin was reduced. [18F]Deoxyglucose positron emission tomography (FDG-PET) revealed hypermetabolic areas in cortical and subcortical areas including the brainstem, which might explain sleep pathology and vertical gaze palsy. In the course of treatment with antibiotics and additional carbamazepine for 1 year, insomnia slowly and gradually improved. Endocrine investigations at 1-year follow-up showed persistent flattening of circadian rhythmicity. The FDG-PET indicated normalized metabolism in distinct regions of the brain stem which paralleled restoration of sleep length. The extent of sleep disruption in this case of organic insomnia was similar to cases of familial fatal insomnia, but was at least partially reversible with treatment.

Adult↗
PubMed2002

Substance P and affective disorders: new treatment opportunities by neurokinin 1 receptor antagonists?

Substance P (SP) is a neuropeptide which is abundant in the periphery and the central nervous system, where it is colocalized with other neurotransmitters such as serotonin or dopamine. SP has been proposed to play a role in the regulation of pain including migraine and fibromyalgia, asthma, inflammatory bowel disease, emesis, psoriasis as well as in central nervous system disorders. This review summarizes our current knowledge of the role of SP in the pathogenesis of neuropsychiatric disorders with special emphasis on affective disorders including bipolar disorders. It also reviews current treatment approaches with neurokinin 1 receptor antagonists which appear to be promising drugs for the future treatment of affective disorders.

Animals↗
PubMedDate not supplied

Increased diurnal salivary cortisol in women with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.

Activities of Daily Living↗
PubMedDate not supplied

Borderline personality disorder.

Borderline personality disorder is characterised by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. Clinical signs of the disorder include emotional dysregulation, impulsive aggression, repeated self-injury, and chronic suicidal tendencies, which make these patients frequent users of mental-health resources. Causal factors are only partly known, but genetic factors and adverse events during childhood, such as physical and sexual abuse, contribute to the development of the disorder. Dialectical behaviour therapy and psychodynamic partial hospital programmes are effective treatments for out-of-control patients, and drug therapy can reduce depression, anxiety, and impulsive aggression. More research is needed for the understanding and management of this disabling clinical condition. Current strategies are focusing on the neurobiological underpinnings of the disorder and the development and dissemination of better and more cost-effective treatments to clinicians.

Animals↗