Search PubMed⌕ Search

Biomedical subjects

M Graf

Publications and source records attributed to M Graf.

At least 19 recordsLinked to original sources
PubMed2007

[Risk assessment of sex offenders in a German-speaking sample. Applicability of PCL-SV, HCR-20+3, and SVR-20].

Regarding the relatively high relapse rates of sex offenders, an increasing need for forensic prognosis reports, doubts about their validity, and a continued lack of qualified forensic experts makes the supposedly simple application of instruments such as the Psychopathy Check List Screening Version (PCL-SV), HCR-20+3, or the Sexual Violence Risk 20 (SVR-20) very tempting. Those tools supply numeric values for quantifying assumed risk and have begun appearing more frequently in forensic reports. Their use for specific collectives without prior examination of accuracy, admissibility, and accountability may lead to serious mistakes and risks. This study by the Forensic Department of the Psychiatric University Hospital in Basel, Switzerland, is part of a larger cohort study on forensic risk assessment. It investigates among others the differential indication for PCL-SV, HCR-20+3, and SVR-20. In the present study, 64 sex offenders were retrospectively rated with these three instruments based on their respective reports for prior risk assessment, including criminal reports. Those ratings were then compared with prior results from the Structured Risk Assessment of Basel, as performed by the experts. Results of this study confirm the utility of PCL-SV, HCR-20+3 and SVR-20 in a German-speaking sample of sex offenders primarily as a scientific instrument. Beyond that, these instruments may also be used literally as a checklist. Their use for risk quantification should be limited primarily to the subgroup of antisocial and physically aggressive sex offenders.

Adult↗
PubMed2006

Micro hot plate-based sensor array system for the detection of environmentally relevant gases.

A monolithic stand-alone gas sensor system is presented, which includes on a single chip an array of three metal oxide-coated micro hot plates with integrated MOS-transistor heaters, as well as a specifically designed digital system architecture. An octagonal-shaped micro hot plate design with MOS-transistor heaters has been adopted for the three gas sensors. The integrated circuitry includes a programmable digital temperature regulation, digital sensor readout units, and a standard serial interface. The programmable digital temperature controllers enable individual regulation of the micro hot plate temperatures in constant or dynamic mode. Nanocrystalline tin oxide thick films with different Pd dopings (undoped, 0.2 and 3 wt %) were used. Gas test measurements for environmentally relevant gases were carried out and evidenced detection limits of less than 1 ppm for carbon monoxide, or 100 ppm for methane, both at 40% relative humidity. Temperature modulation techniques were successfully applied for improved analyte discrimination.

Journal Article↗
PubMed2006

[Bipolar dislocation injury of the forearm].

Bipolar dislocation injury of the forearm is rarely documented. It is a combined forearm injury with trauma on the elbow side and on the side of the wrist joint. We describe two different cases of this complex dislocation. The first patient suffered from a Monteggia-like dislocation fracture with transscaphoid dislocation of the wrist. The second person had an acute longitudinal radioulnar membrane dissociation after elbow dislocation with an additional scapholunate tendon rupture. The difficult management of these injuries is illustrated by these cases.

Elbow Joint↗
PubMed2005

Orientation congruency effects for familiar objects: coordinate transformations in object recognition.

How do observers recognize objects after spatial transformations? Recent neurocomputational models have proposed that object recognition is based on coordinate transformations that align memory and stimulus representations. If the recognition of a misoriented object is achieved by adjusting a coordinate system (or reference frame), then recognition should be facilitated when the object is preceded by a different object in the same orientation. In the two experiments reported here, two objects were presented in brief masked displays that were in close temporal contiguity; the objects were in either congruent or incongruent picture-plane orientations. Results showed that naming accuracy was higher for congruent than for incongruent orientations. The congruency effect was independent of superordinate category membership (Experiment 1) and was found for objects with different main axes of elongation (Experiment 2). The results indicate congruency effects for common familiar objects even when they have dissimilar shapes. These findings are compatible with models in which object recognition is achieved by an adjustment of a perceptual coordinate system.

Adult↗
PubMed2005

Expression of poliovirus receptor-related proteins PRR1 and PRR2 in acute myeloid leukemia: first report of surface marker analysis, contribution to diagnosis, prognosis and implications for future therapeutical strategies.

Poliovirus receptor-related (PRR) proteins belong to the Nectin-adhesion molecules' group, are expressed on endothelial cells and on CD34(+) stem cells and mediate the organization of endothelial and epithelial junctions. There is evidence to suggest, that those receptors could have a role in leukemia. We have studied the expression of PRR molecules PRR1 and PRR2 on mononuclear bone marrow (BM) cells of 55 patients with acute myeloid leukemia (AML) at first diagnosis by FACS-analysis using directly Phycoerythrin-labeled markers (PRR1 clone R1.302.12; PRR2 clone R2.477.1) in combination with other Fluorescein conjugated antibodies to evaluate the blast phenotype in AML. The leukemic gate included blasts and residual monocytes and lymphocytes. A case was defined as positive, if more than 20% of the gated cells expressed the regarding receptor. We could demonstrate, that on average 35% PRR1(+) or 45% PRR2(+) cells in AML were found. Within FAB-types we observed a high PRR1 expression in cases with M3 and M4 and lowest expressions in M0 and M5; a high PRR2 expression was found in cases with M3, M4, M5 and M1 and lowest expressions in M0 and M2. Separating our patients' cohorts in cytogenetic risk groups we could detect a significant higher proportion of PRR1(+) cases (73% vs. 25% of cases, P = 0.009) or PRR1(+) cells (57% vs. 18% of cases, P = 0.001) in the cytogenetic favorable risk vs. poor risk group (75% vs. 32% PRR2(+) cases). Moreover cut-off-values with a maximum probability for a significant differentiation between cases with higher or lower levels of these markers could be found: cases with >78% PRR1(+) and cases with >77% PRR2(+) cells were characterized by a tendency for longer relapse free survival times. Qui-square analyses showed, that 3 of 4 cases with FAB-type M3 (P = 0.03) or a favorable karyotype (P = 0.04) were found in the group with >7% PRR1(+) cells, due to only few cases available a similar correlation, however, could not be found in cases with >78% PRR2(+) cells. We can conclude, that blasts in AML regularly express PRR1 and PRR2. Cases with a high expression of PRR1 or PRR2 are characterized by a more favorable prognosis. With respect to the individual PRR-status the benefit of biological response modifiers as priming agents, differentiation mediators or factors influencing cellular metabolisms inducing factors can be discussed under a new point of view.

Antigens, CD34↗
PubMed2004

High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML).

Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80 proportions and lower CD86 proportions compared to the "nonresponder" group. Whereas cases with more than 15% CD80(+) cells had a significantly lower probability for relapse-free survival, only cases with more than 65% CD86(+) were characterized by a significantly lower probability for relapse-free survival. Expression profiles of CD11a and CD58 were not associated with specific FAB types or prognostically relevant groups. We can conclude: (1) Expression of costimulatory molecules in AML is very variable. This reflects the great diversity of immunophenotypes in AML. (2) CD56 is mainly expressed in monocytic subtypes of AML. CD56(+) subtypes of AML seem to be a separate entity with a worse prognosis independent of the karyotype. (3) High expression of some costimulatory molecules correlates with a worse prognosis concerning relapse-free survival times.

Antigens, CD↗
PubMed2004

High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study.

UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Low L-selectin (CD62L) expression in acute myeloid leukemia correlates with a bad cytogenetic risk.

OBJECTIVES: Interactions between hemopoietic cells and the stromal microenvironment or immunoreactive cells are mediated by specific cell surface receptors. The expression of those molecules may alter the adhesive qualities (mobility and homing) as well as immune response behavior of leukemic blasts. L-Selectin (CD62L) is suggested to play a role in the redistribution and homing of hemopoietic progenitor cells to the bone marrow (BM). Down-regulation of L-selectin is responsible for mobilization of blasts from the BM into the circulation and ligation of L-selectin stimulates proliferation of progenitor cells. This could have an influence on the process of leukemia. METHOD: We have studied the expression of L-selectin on mononuclear BM cells of 36 acute myeloid leukemia (AML) patients at first diagnosis by FACS analysis using a directly fluorescein isothiocyanate conjugated antibody (clone DRE G56). RESULTS: On average the patients presented with 88% blasts in the BM. The expression tended to be higher in primary (p) AML compared with secondary (s) AML. L-Selectin was very heterogenously expressed in all FAB groups. Highest expression was found in cases with AML-M4 with four of nine cases presenting with an inv(16) karyotype. Separating our patient cohort in cytogenetic risk groups we could detect a significantly higher expression of L-selectin in cases with a 'good risk' karyotype and a very low expression in cases with a 'bad risk' karyotype (P = 0.037). Comparing patients who achieved remission after double induction therapy (responders) with patients who showed persisting disease (non-responders) we found a higher percentage of L-selectin+ cases or cells in the responder group than in the non-responder group, although the differences were not significant because of only five cases in the 'non-responder' group. Evaluating cut-off points greatest differences in relapse-free survival probabilities were found in patients who presented with > or = 30% L-selectin+ BM cells compared with cases with < 30%: 86% of cases with > or = 30% L-selectin+ cells were still in remission after a mean follow up time of only 8 months compared with only 46% in the group with < 30% L-selectin+ cells. CONCLUSIONS: We can conclude that (i) expression of L-selectin on AML blasts is variable. This reveals the great diversitiy of immunophenotypes in AML and might contribute to identify individual blast phenotypes in order to detect minimal residual disease in remission. (ii) Low L-selectin expression correlates with a bad cytogenetic risk, with a lower probability to achieve remission and with a shorter relapse-free survival time. This might reflect a decreased homing of the blasts to the BM as well as an impaired cytotoxic T-cell reaction against leukemic cells. The expression of L-selectin on leukemic blasts might be influenced by different cytokine therapies (e.g. with interferon alpha) and this might result in an altered hematologic reconstitution after cytotoxic therapies as well as in an altered immunologic recognition of blasts.

Acute Disease↗
PubMed2003

[Direct MR arthrography of the wrist- value in detecting complete and partial defects of intrinsic ligaments and the TFCC in comparison with arthroscopy].

PURPOSE: To assess the value of two-compartment magnetic resonance (MR) wrist arthrography in comparison with diagnostic arthroscopy for the evaluation of defects of the triangular fibrocartilage complex (TFCC) and intrinsic ligaments in patients with refractory wrist pain. The direct MR arthrographies were evaluated following arthroscopic classification with consideration of complete and partial defects. The distinction between these types of lesions has clinical implications for treatment procedures such as cast immobilization, arthroscopic debridement, surgical repair or partial intercarpal arthrodesis. MATERIALS AND METHODS: Seventy-five patients (25 female, 50 males, mean age 38.3 years) who suffered from refractory wrist pain without radiography evidence of carpal instability underwent two-compartment wrist MR arthrography. Under aseptic conditions a solution of gadopentate dimeglumine and iodinated contrast agent (concentration 2.5 mmol/l) was injected into the radiocarpal and midcarpal joints under fluoroscopy guidance. Using a scanner of 1.5 T field strength and a wrist-coil following sequences were acquired: coronary and sagittal T (1)-weighted spin-echo (SE) sequences (TR 500 ms, TE 25 ms, matrix 512 x 512.3 mm) and coronary fast low angle shot (FLASH) 3D sequences (TR 24 ms, TE 11 ms, matrix 256 x 256, 1.5 mm, flip angle 50 degrees). All patients underwent subsequent arthroscopy of the wrist. The direct MR arthrographies were evaluated retrospectively by two observers experienced in the diagnosis of wrist pathology. They were not aware of the clinicial, arthrographic and arthroscopic findings. Pathology of the scapholunate ligament was classified according to the guidelines of the German Society of Hand Surgery (DGH), lesions of the lunotriquetral ligament according to Hempfling and lesions of the TFCC according to Palmer. RESULTS: Twenty-five complete and 47 partial defects were detected arthroscopically (TFCC: 21/20, scapholunate ligament: 3/18, lunotriquetral ligament: 1/9). The TFCC showed a higher prevalence for degenerative lesions (11 type 2C-lesions and 20 type 2A/B lesions) than for traumatic lesions (5 type 1A lesions, 5 type 1D lesions). For direct MR arthrography, the obtained sensitivities and specificities in assessing complete defects were 96 % and 99.6 % (T (1)-weighted SE) and 92 % and 100 % (FLASH 3D), respectively. For all partial defects, sensitivities and specificities were 68.1 % and 93.3 % (T (1)-weighted SE) and 63 % and 96.1 % (FLASH 3D), respectively. For depicting partial defects of the scapholunate ligament the T (1)-weighted SE sequence (83.3/95.5 %) was superior to the FLASH 3D sequence (64.7/96.6 %), p < 0.05. For the evaluation of the TFCC (T (1)-weighted SE: 65/94.4 %, FLASH 3D: 70/94.6 %) and the lunotriquetral ligament (T (1)-weighted SE: 44/89.4 %, FLASH 3D: 44 /96.7 %), direct MR arthrography showed an insufficient correlation with arthroscopy. CONCLUSION: Direct MR arthrography proved to be of equal value compared with diagnostic arthroscopy in detecting complete defects of the intrinsic ligaments and the TFCC. The method has the potential of replacing diagnostic arthroscopy for the evaluation of the intrinsic ligaments and the TFCC. The T (1)-weighted SE sequence appeared to be superior to the FLASH 3D sequence in evaluating partial defects of the scapholunate ligament. Direct MR arthrography did not reliably detect partial defects of the TFCC and the lunotriquetral ligament.

Adult↗
PubMed2003

Early trans-tibial oedema control using polymer gel socks.

The aim of this investigation was to determine if early trans-tibial oedema control, by polymer gel socks prior to the fitting of a shrinker, could enhance trans-tibial stump volume reduction. Sixteen (16) adults, following unilateral trans-tibial amputation, were randomly allocated into 2 groups and baseline volume measurements taken of their stumps. The control group followed the normal removable rigid dressing programme, while the experimental group wore a polymer gel sock in conjunction with the removable rigid dressing. When wound healing permitted fitting of a shrinker, use of the polymer sock was discontinued and a stump volume measurement was taken. The shrinker was worn for a minimum of 2 days before casting for a prosthesis and a final stump volume measurement taken. Volumes were measured by water filling casts taken of the stump and calculated as a percentage of the baseline volume and the rate of volume reduction calculated. Two t-tests for unequal variance (2-tail, alpha=0.05) were used to compare the rate of percentage volume reduction between the groups, for the trial period of baseline to shrinker fitting and baseline to casting. A statistical difference was observed for the period of baseline to shrinker exceeding the 95% confidence limit (p<0.05). No significant difference was detected for the overall period of baseline to cast. It was concluded that early oedema control by polymer gel sock could enhance stump volume reduction, prior to a shrinker. It was also found that no volume advantage was carried over to the time of casting for a prosthesis.

Adult↗
PubMed2001

Dendritic hypertrophy of Stach type VI neurons within experimentally altered ileum of pigs.

Myenteric neurons were investigated morphometrically to answer the question if type-specific somal hypertrophy of type VI neurons in mechanically stressed ileum of pigs, which was known from an earlier study, is correlated with an increased dendritic arborization, that is, with dendritic hypertrophy. Muscular hypertrophy was induced in the ileum of two juvenile pigs by narrowing the gut circumference (mechanical stenosis) and by reversing a loop of ileum which results in an antiperistaltic segment (functional stenosis), respectively. After a survival time of 6 weeks, wholemounts from the pre- and poststenotic ileal regions, from the antiperistaltic segment as well as from an age matched control animal, were silver impregnated. Dendritic parameters of Stach types IV and VI neurons were recorded using a computer-aided morphometric program and analysed statistically. Type IV neurons showed no change of dendritic parameters, neither within control nor within stenosed ileal segments. In contrast, the type VI neurons displayed increased dendritic parameters within zones of muscular hypertrophy such as total dendritic length, numbers of dendrites, of dendritic branching points and of dendritic endings. We suggest that type VI neurons may participate as descending nitrergic interneurons or motorneurons in the control of muscular function, thus, undergoing plastic changes in case of experimental muscular hypertrophy. Type IV neurons which are involved in the regulation of mucosal processes were not affected by muscular hypertrophy.

Animals↗
PubMed2001

Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers.

OBJECTIVE AND DESIGN: To elucidate if the planar chiral paracyclophane moiety conveys pharmacological activity to arylacetic acid analogs in two animal models. MATERIAL OR SUBJECTS: Female NMRI mice (6 mice/group); female Wistar rats (8 rats/group); thrombocytes from human blood. TREATMENT: The enantiomers of [2.2]paracyclophaneacetic acid were applied locally (10(-7) and 10(-6) mol/ear) and orally (10-100 mg/kg). METHODS: (a) Phorbol myristyl acetate model of acute inflammation of the inner auricle. (b) Oxazolone model of allergic contact dermatitis. (c) Carrageenan model of acute inflammation. (d) Inhibition of cyclooxygenase-1 and 12-lipoxygenase (in vitro). RESULTS: (a) PMA model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 58% inhibition after 24 h (p < 0.05). (b) Oxazolone model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 42% inhibition after 24 h (p < 0.05). (c) Carrageenan model: pR-(-)-[2.2]paracyclophaneacetic acid (10 mg/kg): 31.4% inhibition (paw volume 0.48 +/- 0.13 ml). (d) Cyclooxygenase-1 and 12-lipoxygenase: no inhibition at concentrations up to 10 microM. CONCLUSIONS: The easily accessible [2.2]paracyclophane moiety should find its use in medicinal chemistry as it is a pharmacophoric substituent with the interesting feature of planar chirality.

Acetates↗
PubMed2001

[Subretinal microphotodiode array as replacement for degenerated photoreceptors?].

A survey is given on the status of developments, concerning a subretinal electronic microphotodiode array that aims at replacing degenerated photoreceptors. Various prototypes have been developed, tested, and implanted in various experimental animals up to 18 months. The fact that electrical responses were recorded from the visual cortex of pigs after electrical stimulation by subretinal electrodes and the fact that responses are also recorded in-vitro in degenerated rat retinae, shows the feasibility of this approach. However, there are a number of open questions concerning the biocompatibility, the long-time stability, and the type of transmitted image to be solved before application in patients can be considered.

Animals↗
PubMed2001

Molecular cloning and expression of cERG, the ether à go-go-related gene from canine myocardium.

Given the anatomical and physiological similarities to the human heart, canine in vivo heart models may facilitate the analysis of molecular mechanisms underlying cardiac repolarization abnormalities. The development of such models depends, however, on information about canine K+ channels responsible for the establishment of IK currents. In this context, we isolated and sequenced the reverse transcript of the canine ether à go-go-related gene (cERG). The complementary deoxyribonucleic acid (cDNA-derived cERG polypeptide consists of 1,158 amino acids, the sequence of which shows striking homology to human, rat and mouse ERG subunits (97%, 94% and 95% identity respectively). In highly conserved peptide domains like the PAS domain, the membrane-spanning segments S1, S3-S6 and the pore-forming region, there was 100% identity. Analysis of cERG transcription revealed abundant expression of cERG messenger ribonucleic acid (mRNA) in heart and brain and low expression in liver, spleen and kidney. Membrane currents recorded in Xenopus oocytes expressing cERG channels showed functional properties very similar to the human K+ channel hERG, which encodes the alpha-subunit of the cardiac rapidly activating, delayed rectifier (IKr) channel.

Animals↗
PubMed2001

Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment.

Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in Sprague--Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically impaired 5-HT storage and reuptake system and a putative model of depression and anxiety. In addition, the effects of 7 and 16 days treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses were studied. FH rats showed significantly higher anxiety in the social interaction test, and much lower platelet 5-HT content compared to SD rats. The efficacy of 8-OH-DPAT (15-120 microg/kg, i.v.) to induce lower lip retraction (an effect mediated by median raphe receptors) was increased in FH rats. In most FH but only a few SD rats a special neurological syndrome, clonic movement of the masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and this behaviour like other effects of 8-OH-DPAT, was completely blocked by pretreatment with the 5-HT(1A) receptor antagonist WAY-100635. In SD rats fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced hypothermia, an effect mediated most likely by hypothalamic 5-HT(1A) receptors, (-19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection, respectively). In FH rats fluoxetine caused a rapid and complete reduction in the 8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine, respectively). Fluoxetine caused no change in lower lip retraction but a reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data provide evidence that in FH rats, median raphe 5-HT(1A) receptors are hypersensitive, and the hypothalamic 5-HT(1A) receptor desensitization, caused by SSRI antidepressants, is faster and more complete. These data support the notion that chronic treatment with SSRIs induces a desensitization of some 5-HT(1A) receptor populations, and impaired 5-HT storage and reuptake may accelerate this process.

8-Hydroxy-2-(di-n-propylamino)tetralin↗