Prevalence of medically induced psychological trauma and its influence on women's health.

OBJECTIVE: The aim of the present study was three-fold. One, to assess the prevalence of medical traumatization in outpatients of a gynecologic department; two, to analyze the relationship of medical traumatization with adverse childhood events; and three, to investigate the extent to which medical traumatization affects the health outcomes of woman. METHODS: Between January and September 2022, a prospective cross-sectional study recruited patients of a gynecologic outpatient clinic at St. Gallen Cantonal Hospital in Switzerland. Medical trauma was a self-reported item. The presence of adverse childhood events was assessed using the Childhood Trauma Questionnaire. The severity of post-traumatic stress was evaluated using the Impact of Event Scale Revised questionnaire. RESULTS: In total, 227 patients were recruited. Medical trauma was reported by 20% of the interviewees and it was strongly associated with obesity (A = 0.005). Undergoing surgery was most commonly the source of psychological distress (5.7%) followed by delivery (4.8%), pregnancy loss (4.8%), and cancer diagnosis (4.0%). Yet, fewer than 1% of the patients reached the threshold suggesting post-traumatic stress disorder. CONCLUSIONS: We found no relationship between the medical trauma, adverse childhood events, cardiovascular disease, or substance abuse. The presence of medical trauma was associated with the patient's body mass index (calculated as weight in kilograms divided by the square of height in meters).

Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Results of a Prospective Multicenter Cohort.

BACKGROUND: The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed. METHODS: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. RESULTS: Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. CONCLUSIONS: Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Mass spectrometric base composition profiling: Implications for forensic mtDNA databasing.

In forensic genetics mitochondrial DNA (mtDNA) is usually analyzed by direct Sanger-type sequencing (STS). This method is known to be laborious and sometimes prone to human error. Alternative methods have been proposed that lead to faster results. Among these are methods that involve mass-spectrometry resulting in base composition profiles that are, by definition, less informative than the full nucleotide sequence. Here, we applied a highly automated electrospray ionization mass spectrometry (ESI-MS) system (PLEX-ID) to an mtDNA population study to compare its performance with respect to throughput and concordance to STS. We found that the loss of information power was relatively low compared to the gain in speed and analytical standardization. The detection of point and length heteroplasmy turned out to be roughly comparable between the technologies with some individual differences related to the processes. We confirm that ESI-MS provides a valuable platform for analyzing mtDNA variation that can also be applied in the forensic context.

Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment.

Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range) 2.37 ng/mg (0.76-4.9) versus 1.11 ng/mg (0.02-7.20) (P = 0.02). Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7) in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2) in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4) (P < 0.05). Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes.

DNA adducts of ortho-toluidine in human bladder.

BACKGROUND: 4-Aminobiphenyl (4-ABP) and o-toluidine are known human bladder carcinogens, but only 4-ABP-releasing DNA adducts are known. METHODS: Determination of 4-ABP and o-toluidine-releasing DNA adducts in epithelial and submucosal bladder tissues of sudden death victims (SDV: n=46), and bladder tumours (n=12) by gas chromatography/mass spectrometry. RESULTS: Above background, 4 and 11 of 12 tumour samples contained adducts of 4-ABP (0.057 ± 0.125 fmol/µg DNA) and o-toluidine (8.72 ± 4.49 fmol/µg DNA), respectively. Lower adduct levels were present in both epithelial and submucosal bladder tissues of SDV (4-ABP: 0.011 ± 0.022 and 0.019 ± 0.047 fmol/µg DNA; o-toluidine: 0.24 ± 0.63 and 0.27 ± 0.70 fmol/µg DNA). CONCLUSION: Detection of o-toluidine-releasing DNA adducts support the carcinogenicity of o-toluidine in the human bladder.

Ghrelin plasma levels are not altered in major depression.

BACKGROUND: In patients with major depression, the function of most endocrine axes is altered compared to healthy subjects. The orexigenic hormone ghrelin, which shows higher plasma levels in females than males, interacts with several of these endocrine axes. In addition, ghrelin levels in depressed patients decrease with psychopathological improvement. Therefore, we hypothesized that ghrelin levels in patients with major depression would be higher than in healthy subjects. METHODS: Nocturnal (20:00-07:00 h) secretion patterns of ghrelin in 20 patients with major depression [11 females, age 39.4 +/- 10.2 years (mean +/- standard deviation); 9 males, age 38.3 +/- 10.4 years] with a total score on the Hamilton Depression Rating Scale, 21-item version, of 24.8 +/- 5.2 and 20 healthy subjects [11 females, age 38.7 +/- 10.8 years; 9 males, age 39.1 +/- 11.2 years] were determined following an adaptation night. RESULTS: Ghrelin plasma levels of depressed patients and matched healthy subjects did not differ at any point in time when stratified for sex. Accordingly, the area under the curve was comparable: depressed females, 423.3 +/- 103.4; healthy females, 398.0 +/- 94.6; depressed males, 266.3 +/- 56.9, and healthy males, 228.4 +/- 41.3. CONCLUSION: This is the first comparison of ghrelin secretion patterns in patients with major depression and healthy controls. Surprisingly, no relevant differences were ascertained between the two groups.

The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression - an MR spectroscopy study.

Rapid improvement of depressive symptoms occurs after the administration of the NMDA antagonist ketamine. Ketamine administration is accompanied by an increase in GLX (sum-peak of glutamate, glutamine (GLN) and GABA) and GLN in the brain, as measured by magnetic-resonance (MR) spectroscopy. In healthy subjects, we observed an increase in GLX and GLN levels after total sleep deprivation (TSD), which has a rapid antidepressant effects. We examined, if an increase in GLX or GLN is related to the therapeutic effect of TSD. We examined 13 patients with major depression by means of proton MR spectroscopy (field strength: 1.5T) before and after 24h of TSD. Two anatomical areas (dorsolateral prefrontal cortex (DLPC) and parieto-occipital cortex (POC)) were studied. In the DLPC TSD did not change GLX or its elements, whereas the total creatine and choline signal increased marginally. No change could be observed in the POC. For further exploration we took gender and the presence of vegetative characteristics of melancholic depression into account, i.e. the presence of early morning awakening, appetite and weight loss was taken into account, to define vegetative melancholia (VM). TSD led to an increase in GLX and GLN in the DLPC only of male patients. In patients with VM an increase in GLN occurred in this area. The low field strength limits the accuracy for GLX and GLN estimates. Despite the exploratory nature of the study, it nevertheless supports earlier data on the importance of glutamatergic neurotransmission and furthermore of gender and/or vegetative features in depression.

Challenging sleep homeostasis in narcolepsy-cataplexy: implications for non-REM and REM sleep regulation.

STUDY OBJECTIVES: We recently proposed insufficient non-rapid eye movement sleep (NREMS) intensity to contribute to disturbed nocturnal sleep in patients with narcolepsy-cataplexy (NC). To test this hypothesis, we investigated the effect of physiologically intensified NREMS in recovery sleep following sleep deprivation. DESIGN: Nocturnal baseline and recovery sleep architecture, and the sleep electroencephalogram (EEG) before and after 40 hours of sustained wakefulness were compared between 6 drug-free patients with NC (age range: 19-37 years) and 6 individually matched, healthy control subjects (18-43 years). MEASUREMENTS: Sleep and sleep EEG power spectra (C3A2 derivation). The dynamics of the homeostatic Process S were estimated from the time course of slow-wave activity (SWA, spectral power within 0.75-4.5 Hz) across consecutive NREMS episodes. SETTINGS: Sleep research laboratory. RESULTS: In baseline, SWA decreased across consecutive NREMS episodes in patients with NC and control subjects. The build-up of SWA, however, was attenuated in NC in the second episode (P = 0.01) due to a higher number of short wake periods (P = 0.02). Prolonged wakefulness increased initial SWA in both groups (P = 0.003) and normalized the baseline differences between patients and control subjects in the time course of SWA in NREMS. The changed dynamics of SWA in the patients in recovery sleep when compared with baseline were associated with reduced numbers of intermittent wake periods in the first (P = 0.01) and second (P = 0.04) NREMS episodes. All patients, but no control subjects, showed a sleep-onset rapid eye movement period (SOREMP) in both baseline and recovery sleep. Sleep deprivation increased SOREMP duration (P = 0.03). CONCLUSIONS: Increased SWA after sleep deprivation indicates that sleep homeostasis is functional in NC. Increased NREMS intensity in recovery sleep postpones sleep fragmentation, supporting our concept that sleep fragmentation is directly related to insufficient NREMS intensity in NC. The persistence of SOREMP despite enhanced NREMS pressure suggests an abnormal interaction between NREMS and REMS regulatory processes.

Dex/CRH-test response and sleep in depressed patients and healthy controls with and without vulnerability for affective disorders.

Sleep electroencephalographic (EEG) abnormalities and increased hypothalamo-pituitary-adrenal (HPA) axis activity are the most prominent neurobiological findings in depression and were suggested as potential biomarker for depression. In particular, increased rapid eye movement sleep (REM) density, deficit in slow wave sleep and excessive stress hormone response are associated with an unfavorable long-term outcome of depression. Recent studies indicate that the sleep and endocrine parameters are related to each other. This study investigated the association of sleep structure including a quantitative EEG analysis with the results of the combined dexamethasone (Dex)/corticotropin-releasing hormone (CRH)-test in 14 patients with a severe major depression, 21 healthy probands with a positive family history of depression (HRPs) and 12 healthy control subjects without personal and family history for psychiatric disorders. As expected patients with depression showed an overactivity of the HPA axis, disturbed sleep continuity and prolonged latency until slow wave sleep in the first sleep cycle. Differences in microarchitecture of sleep were less prominent and restricted to a higher NonREM sigma power in the HRP group. Dexamethasone suppressed cortisol levels were positively associated with higher NonREM sigma power after merging the three groups. We also observed an inverse association between the ACTH response to the Dex/CRH-test and rapid eye movement sleep (REM) density in HRPs, with suggestive evidence also in patients, but not in controls. This contra-intuitive finding might be a result of the subject selection (unaffected HRPs, severely depressed patients) and the complementarity of the two markers. HRPs and patients with high disease vulnerability, indicated by an elevated REM density, seem to have a lower threshold until an actual disease process affecting the HPA axis translates into depression, and vice versa. To summarize, our findings provide further evidence that the HPA axis is involved in the sleep regulation in depression. These associations, however, are not unidimensional, but dependent on the kind of sleep parameters as well as on the selection of the subjects.

Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression.

Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW). Cortisol increased duration and intensity of non-REM sleep in particular in male patients and stimulated GH release. The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. Stimulation of delta sleep was less pronounced in patients with dexamethasone nonsuppression. In contrast, REM sleep parameters were not affected by the treatment. These data demonstrate that the non-REM sleep-promoting effects of acute cortisol injections observed in healthy controls could be replicated in patients with depression. Our results suggest that non-REM and REM sleep abnormalities during the acute state of the disease are differentially linked to the activity of the HPA axis.

Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms.

The metabolite ratio of amitriptyline (AT), nortriptyline (NT) and its 10-hydroxy metabolites (E10-OHAT, Z10-OHAT, E10-OHNT and Z10-OHNT) was examined by liquid chromatography-mass spectrometry in hair samples of 23 white infants after long-term administration of AT. High inter-individual variation of the metabolite ratios were observed (e.g. NT/AT = 0.8-8.1, E10-OHNT/Z10-OHNT = 1.6-10.3). The significance of these variations was proven by confirmation of the temporary stability of these ratios within a hair fibre. Moreover, an association of the metabolic phenotype with genetic disposition was observed. The genotypes of CYP2C19 (alleles *2, *3 and *4) and of CYP2D6 (*3, *4, and *6) were examined by conventional polymerase chain reaction genotyping experiments. The relative amount of demethylation (NT/AT) is clearly affected by the number of functional alleles of CYP2C19. The demethylation capacity of CYP2C19 poor metabolizers (3 individuals, compared to 15 extensive metabolizers) was 4.3 times depleted. Moreover, the selectivity of hydroxylation (e.g. E10-OHNT/Z10-OHNT) is significantly correlated with CYP2C19.

Proof of a 1-(3-chlorophenyl)piperazine (mCPP) intake: use as adulterant of cocaine resulting in drug-drug interactions?

Since 2005, increasing numbers of seizures of the designer drug of abuse 1-(3-chlorophenyl)piperazine (mCPP) have been reported. This paper describes the unequivocal proof of a mCPP intake. Differentiation from the intake of its precursor drugs trazodone and nefazodone was performed by a systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation. The found mCPP/hydroxy-mCPP ratio indicated altered metabolism of this cytochrome (CYP) 2D6 catalyzed reaction compared to published studies using the same procedure. Although this might be ascribed to a poor metabolizer (PM) phenotype, genotyping revealed no PM genotype but indications for an intermediate metabolizer genotype. However, a PM phenotype could also be caused by drug-drug interactions with CYP2D6 inhibitors or substrates such as the co-consumed cocaine and diltiazem and/or diltiazem metabolites, respectively. In conclusion, the presented data indicate a possible relevance of CYP2D6 polymorphism and/or drug interactions to mCPP toxicokinetics, which is important for risk assessment of this new designer drug of abuse, in particular if it is used as adulterant of CYP2D6 substrates such as cocaine.

Individual variations of amitriptyline biotransformation examined in scalp hair samples.

The identification of amitriptyline, nortriptyline and its hydroxy-metabolites including a subsequent measurement of concentration profiles in hair samples was carried out to evaluate the administration history of amitriptyline. Analyses were carried out using liquid chromatography-tandem mass spectrometry, which permits simultaneous identification of all relevant substances in hair at low target concentrations (limit of detection better than 0.5 pg/mg). Standard hair sample preparation was applied for the estimation of average substance concentration in a hair bundle, while segmentation of individual hairs was utilised to examine accurate concentration profiles. Replication of analyses demonstrated a good reproducibility of individual hair concentration profiles, which proved to coincide for all relevant compounds. Significant variations of metabolite ratios (e.g. nortriptyline to amitriptyline and E10- to Z10-hydroxynortriptyline) between individuals suggest a correlation between hair concentration and metabolic phenotype. Different concentration ratios of certain metabolites in hair are highly correlated, indicating a systematic association between demethylation and stereo-specificity of hydroxylation. The trans isomers of hydroxy-metabolites become significantly more prevalent with increasing degree of demethylation of amitriptyline or hydroxylation of amitriptyline.

Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine.

The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.9+/-4.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days -3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day -3. The Hamilton Depression score decreased from 32.1+/-7.3 to 15.5+/-6.7 between days -1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin.

Nocturnal ghrelin levels--relationship to sleep EEG, the levels of growth hormone, ACTH and cortisol--and gender differences.

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue receptor, stimulates sleep, appetite and weight gain as well as the secretion of GH, adrenocorticotropic hormone (ACTH), cortisol in humans and rodents. The interaction between nocturnal ghrelin levels, sleep EEG and the secretion of these hormones was not investigated systematically so far. Furthermore conflicting data exist on gender differences in nocturnal ghrelin secretion. We examined simultaneously sleep EEG and the nocturnal levels of ghrelin, GH, ACTH and cortisol in young and middle-aged normal human subjects (eight males, eight females). A significant interaction between gender and the course of ghrelin concentration was observed to the interval between 20:00 and 23:00 hours. In males a continuous increase of ghrelin levels before sleep onset was found. In females, however, a rise of ghrelin during the night was missed. We found a trend suggesting a lower time spent in stage I sleep in subjects with high nocturnal ghrelin levels. Other systematic interactions between plasma ghrelin, sleep EEG and other hormones were not found. No peak in plasma ghrelin levels resembling the GH surge was observed. We suggest that under naturalistic conditions plasma ghrelin levels show no distinct interaction with sleep.

Allele frequencies of the ACTBP2 (=SE33), D18S51, D8S1132, D12S391, D2S1360, D3S1744, D5S2500, D7S1517, D10S2325 and D21S2055 loci in a German population sample.

A population study on 10 tetrameric STR loci (ACTBP2 (=SE33), D18S51, D8S1132, D12S391, D2S1360, D3S1744, D5S2500, D7S1517, D10S2325, D21S2055) was performed with Germans from Bavaria.

Significant genetic differentiation between Poland and Germany follows present-day political borders, as revealed by Y-chromosome analysis.

To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r = 0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmonier's algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies.

Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls.

Ghrelin, a growth hormone (GH) secretagogue receptor ligand was isolated from the stomach and hypothalamus of rats and humans. In rodents, ghrelin exerts distinct orexigenic action, probably as counterpart of the anorexigenic leptin. In humans, ghrelin infusion enhances appetite. It is unknown whether single intravenous (i.v.) injections of ghrelin affect human eating behavior. Therefore, we investigated the influence of a single i.v. bolus injection of 100 microg ghrelin on appetite, ideas about food, hormone levels, and glucose concentration in young control subjects. In order to test gender differences, we included five women and four men. After ghrelin administration, appetite was enhanced in eight of nine subjects. Seven probands reported a vivid, plastic image of their preferred meal. Furthermore, ghrelin stimulated an immediate increase in plasma levels of GH (area under the curve, mean+/-SEM 35+/-16 ng/ml x min after placebo [P] to 2808+/-533 ng/ml x min after ghrelin [G]; p<0.001), cortisol (5908+/-984 ng/ml x min [P] to 10179+/-1293 ng/ml x min [G]; p<0.001), and ACTH (922+/-103 pg/ml x min [P] to 3030+/-763 pg/ml x min [G]; p<0.02), whereas leptin levels remained unchanged. Contrary to placebo, glucose concentration did not decrease markedly after administration of ghrelin. Our data suggest that i.v. ghrelin stimulates appetite and images of food in young women and men. Obviously, leptin is not involved in these effects.