Judith Haffmans - Academia.edu (original) (raw)

Papers by Judith Haffmans

Annual Review of Medicine, 1997

▪ Mineralocorticoid and glucocorticoid receptors act as homodimers via canonical pentadecamer h... more ▪ Mineralocorticoid and glucocorticoid receptors act as homodimers via canonical pentadecamer hormone response elements to regulate transcription. Glucocorticoid, but as yet not mineralocorticoid, receptors have been shown also to modulate AP-1- and NFκB-induced transcription by direct protein-protein interactions. The role of 11β-hydroxysteroid dehydrogenase in conferring aldosterone specificity on epithelial mineralocorticoid receptors has been proven by the demonstration of sequence mutations in all cases of apparent mineralocorticoid excess examined to date. The autosomal form of aldosterone resistance (pseudohypoaldosteronism) has been shown to reflect loss-of-function mutations in epithelial sodium channel subunit sequence. (Patho)physiological roles for aldosterone and glucocorticoid membrane receptors, and for the recently described nuclear receptors for 11–ketosteroids in 11β–hydroxysteroid dehydrogenase–protected epithelia, remain to be established.

Drug Metabolism and Drug Interactions, 1991

beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (4... more beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (48 h) exposure of rats to N2O. However, a significant decrease of beta-endorphin was found in the whole brain, brain stem and subcortex during the withdrawal from chronic exposure to N2O. It has been suggested that decrease of beta-endorphin levels during N2O withdrawal could be ascribed to unspecific stress accompanying drug withdrawal. Decrease of central beta-endorphin during N2O withdrawal might have a significant modulatory effect on transmitter balance, neuronal excitability and corresponding withdrawal behaviour. Furthermore, the decrease of beta-endorphin levels in the whole brain during N2O withdrawal might contribute to the postanaesthesia N2O-excitatory syndrome in humans. This might explain the known therapeutic effect of the opioid drug, meperidine on the excitatory N2O withdrawal phenomena during recovery from N2O anaesthesia in man.

Psychiatry Research, 2016

Negative symptoms and episodes of major depressive disorder in patients with schizophrenia are co... more Negative symptoms and episodes of major depressive disorder in patients with schizophrenia are common and there is an overlap in symptoms. Unfortunately, there is no effective primary treatment for negative symptoms yet. Depressive disorder in patients with schizophrenia is associated with a decreased quality of life and an increased risk of psychotic relapses. Previous research has shown that Bright Light Therapy (BLT) has a positive impact on negative symptoms of patients with schizophrenia. Our aim was to investigate the feasibility and the effect of Bright Light

The different classes of the opioid peptides the endorphins and the dynorphins may function as ne... more The different classes of the opioid peptides the endorphins and the dynorphins may function as neuromodulators or ho~nes. The receptor-mediated enkephalins, the neurotransmitters, actions of these opioids show a considerable overLap, not surpris1ngly in view of their close structural relationships (Table 1.). 'rhus in order to understand the roles of these peptides in physiological or pathological events, it is necessary to elucidate the mechanisms underlying and controlling their biogenesis, inactivation and release. 2.1.. ~osyn~hes~s Peptide hormones are derived from the enzymatic cleavage o£ Larger, and generally inactive prohormones which are synthesized under the direction of mRNA on membrane-bound pol.yrihosomes. The nascent protein characteristically contains a 1.8-25 residue hydrophobic amino acid sequence at its N-termi.nus, termed the "signal sequence••. The cleavage of this pre-prohormone in its entry into the Golgi apparatus yields the prohormone. Sequential cleavage of the prohormone then results in one or more biologically active peptides that are available for secretion (Mal:x, 1983). The use of modern techniques, including ~ cloning, has revealed the total sequences of the following prohormones: L Proopiomelanocortin (POMC) (Smyth, 1983); 2. Proenkephalin (Noda et al., 1982); 3. Prodynorphi.n (Kak.idani et al., 1982). These proteins provide the basis for three separate opioid peptide families. 2.1.1. Proopiomelanocortin (POMC) POMC was the first of the precursors to be identified. The sequence of amino acids in the complete POMC molecule results after cleavage in at least seven active peptides including 13-lipotropi.n (13-LPH), ,6-endorphin, adrenocorticotropic hormone (ACTII), and a-, {!r-, and y-melanocyte stimulating hormones (a-, (3-, and y-MSEI) (Pig. la) (Ma:rx, 1983). The individual pepti.des in the precursor are bound on both ends by pairs of amino acid residues, usually containing one lysine and one arginine residue. These pairs are the sites,-13-.1.. 2. Proerikephali.n A D~fferent groups of investigators (Noda et al. 1 1982; GUbler et al.., 1982) cloned the gene coding for the polypepti.de now cal.l.ed proenkephalin A. The proenkephal.in A and not POMC is the precursor of Met-and Leu-enkephalin and also of some larger enkephalin-containing pepti.des, some of them more active than the enkepbalins themselves (GUbler et al., 1982). Proenkephal:in A contai.ns six copi.es of the Met-enkephal.i.n sequence (Tyr-Gl.y-Gl.y-Phe-Met) and one of Leu-enkepha1in (Tyr-Gly-Gly-Phe-Leu) (Fig. 1.b). 2 .1.. 3. Prodynorphin I<aki.dani et al. (1982) have identified a sequence from a DNA cl.one of porcine hypothalamic RNA which encodes the complete sequences of dynorphin and a-neoendorphin but which contains no Met-enkephalin sequence (F:i.g. l.c). Analysis of the DNA structure indicates that the precursor protein consists of 256 amino acids including a signal sequence. 2.2. Me"taboZ.tsm The final products produced and stored within a given neuron depend not only on the genetic code for the precursor, but also on the program that directs the enzymes to process the precursor in certain ways. The action of cutting specific peptides out of the precursor protein, and modifying these products by acetylation, amidati.on, phosphorylation, methylation, glycosylati.on or further cleavage is part of the biological program of a given ceU.. 'l'hese events are capable of determining the exact mix of peptides in a given neuron. They appear to va:ry from one tissue to the next, in spite of the existence of a common gene for the precursor. Since these changes result in peptides of widely differing potencies, pharmacological profiles and receptor selectivities, they are critical in determining function and may constitute a critical step in the regulation and homeostasis of a given opi.oid system in a particular region in the CNS. Detailed studies on the biosynthesis of these pepti.des are lacking, (Bambrook et al.., 1.976; Meek et al., 1977; Vogel and Altstein, 1.980). bestatin. The best inhibitor presently available is 2. Dtpept;tdyl,-anri.nopept:t.aase ("enkephalinase B") hydrolyses the Gly 2-Gly 3 amide bond of enkephalin. No selective inhibitor for this enzyme is available as yet (Gorenstein and Snyder, 1979). 3. Angtot.enst.nwconvert.t,ng enzyme (ACE) hydrolyses the enkephalin 3 4 at the level o£ the Gly-Phe bond (Erdos et al., 1975). This enzyme can be inhibited by captopril. 4. Df...pep"tt.dy1wcarbcxcypepti.dase termed "enkephaJ.inase" (Malfroy et al., J.97S) or "enkephal.i.nase A'' (Gorenstei.n and Snyder 1 l. 979) , which cleaves the enkephali.n al.so at the Gly 3-Phe 4 bond, can be inhibited by phosphoramidon or thiorphan. Recently, kelatorphan has been descr~ as the first complete inhibitor of enkephal.in metabolism. This substance inhibits the activity of ••enkephal.:inase A" 1 dipeptidylaminopeptidase and-23-REPERENCES 1\k.il a, Richardson DE, HUghes J, Barchas JD, Enkephali.n-like material. elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimuLation, Science 201: 463-465, 197Sa.

Pharmacopsychiatry, 1995

The narcolepsy syndrome consists of excessive daytime somnolence, cataplexy, hallucinations, and ... more The narcolepsy syndrome consists of excessive daytime somnolence, cataplexy, hallucinations, and sleep paralysis. Data on the effects of tranylcypromine are scant. We report on a patient with severe narcolepsy in whom administration of tranylcypromine led to freedom from hallucinations, nightmares, sleep paralysis, and rapid eye movements (REM), with considerable amelioration of cataplexy and increased daytime alertness. Muscle atonia and low-voltage desynchronized cortical activity during REM sleep did not change. Tranylcypromine warrants further study in narcolepsy.

Neuropharmacology, 1983

The correlation between the distribution of the intraventricularly (i.v.t.) administered delta ag... more The correlation between the distribution of the intraventricularly (i.v.t.) administered delta agonist [3H](D-ala2,D-leu5)-enkephalin ([3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 microns. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of delta opiate receptors, localized within the first 100 microns of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.

Journal of Substance Abuse Treatment, 1999

After 12 months of inpatient treatment, 16 opiate-addicted patients were exposed to drugrelated s... more After 12 months of inpatient treatment, 16 opiate-addicted patients were exposed to drugrelated stimuli. The results of this study indicate that cue reactivity in opiate-addicted subjects is still present after 12 months of intensive inpatient treatment. After exposing subjects to drug-related stimuli, there is an increase in craving, feelings of depression, and anger. Because posttreatment subjects are likely to be confronted with these stimuli following discharge, a reduction of this reactivity is desirable. In the present study, cue reactivity (feelings of depression, anger, tension, craving, and physical symptoms) reduced after protocolized cue exposure treatment.

Journal of Affective Disorders, 2008

International Psychogeriatrics, 1997

The effects of a daily program of various activities on disturbed behavior were studied prospecti... more The effects of a daily program of various activities on disturbed behavior were studied prospectively in three patients with severe dementia. Prior to the study, patients had not responded to treatment with benzodiazepines and/or neuroleptics. The study consisted of three periods, each lasting for 4 weeks: i.e., baseline, intervention, and follow-up. During each period, behavior was assessed by means of observation scales: GIP, SDAS, and CGI. Psychotropic medication was held as constant as possible. During intervention, the patients took part in a program of activities, including group, musical, physical, and social activities. During baseline and follow-up, patients followed the regular ward activities. The patients showed different responses, probably related to personal interests. Possible implications for the treatment of patients with dementia, complicated by disturbed behavior, and suggestions for future research are discussed. The enthusiasm of the nursing staff dealing with ...

International Journal of Group Psychotherapy, 2013

The reader will be able to: 1. Assess the indications and contraindications for adjunct (group) I... more The reader will be able to: 1. Assess the indications and contraindications for adjunct (group) IPSRT in patients with bipolar disorder. 2. Communicate to a patient with bipolar disorder the importance of improving social rhythm and interpersonal issues in achieving and maintaining mood stability. 3. Identify factors in a patient's life underlying circadian and social rhythm instability, and help the patient, in individual or group sessions, to realize improvements in these areas. 4. Describe the phases of an IP(SR)T group and the working method and objectives of each phase.

European Neuropsychopharmacology, 1995

European Neuropsychopharmacology, 1998

Dementia is characterized by progressive function deficits including concentration, attention and... more Dementia is characterized by progressive function deficits including concentration, attention and social behaviour. These functions are often associated with affective disorders, insomnia and disturbed behaviour. Disturbed behaviour includes physi-cally nonaggressive ...

BASIC/TRANSLATIONAL - Glucocorticoid Disease & Physiology, 2011

Community mental health journal, Jan 18, 2016

Referral to collaborative mental health care within the primary care setting is a service concept... more Referral to collaborative mental health care within the primary care setting is a service concept that has shown to be as effective as direct referral to specialized mental health care for patients with common mental disorders. Additionally it is more efficient in terms of lower mental health services use. This post-hoc analysis examines if treatment intensity during 1-year of follow-up can be predicted prospectively by baseline characteristics. With multilevel multivariate regression analyses baseline characteristics were examined as potential predictors of visit counts. Results showed that only the enabling factors service concept and referral delay for treatment had a significant association with mental health visit counts, when outcome was dichotomized in five or more visits. Inclusion of the outcome variable as a count variable confirmed the predictive value of service concept and referral delay, but added marital status as a significant predictor. Overall, enabling factors (se...

Psychiatry Research, 1991

Psychiatry research, Jan 15, 2014

A relatively small number of studies have been dedicated to the differential effects of the curre... more A relatively small number of studies have been dedicated to the differential effects of the current mood state on cognition in patients with a bipolar disorder (BD). The aim of the current study was to investigate the effect of current mood state on divided attention (DA) performance, and specifically examine possible beneficial effects of the (hypo-) manic state. Over a maximum period of 24 months, medication use, divided attention test (a subtest of the Test for Attentional Performance (TAP)) was assessed every 6 months in 189 outpatients with BD. Data were analyzed with multilevel regression analysis (i.e. linear mixed models). DA performance varied considerable over time within patients. Corrected for psychotropic medication a significant quadratic relationship between manic symptoms and DA performance was found, with mild hypomanic symptoms having a positive influence on divided attention scores and moderate to severe manic symptoms having a negative influence. No association b...

Transcultural psychiatry, 2010

This article presents the results of a large efficacy study comparing different forms of therapy ... more This article presents the results of a large efficacy study comparing different forms of therapy for major depressive disorder (MDD), including interpersonal psychotherapy (IPT) and pharmacotherapy. Patients were randomized to either IPT, IPT in combination with anti-depressant medication, IPT in combination with pill-placebo or medication only. The primary outcome measure was the Hamilton Rating Scale for Depression (HAMD). Patients were treated for 12 to 16 weeks. Ratings were performed at baseline, after 6 weeks of treatment and at the end of treatment. Ethnic minority patients (EMP) had higher scores on the HAMD than non-EMP for every rating period. However, the rate of improvement was the same for EMP and non-EMP. The higher mean scores of EMP on the HAMD could not be explained as solely due to higher scores on somatic items of the rating scales. The attrition rate in EMP (45.9%) was significantly higher than in non-EMP (24.4%), even in the structured treatment format studied. ...

Schizophrenia Research, 2000

Psychotherapy and Psychosomatics, 2007

primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) t... more primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. Results: Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. Conclusions: The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.