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Biomedical subjects

Horst L Fehm

Publications and source records attributed to Horst L Fehm.

32 records · Page 2Linked to original sources
PubMed2004

Elevated resting and exercise-induced cortisol levels after mineralocorticoid receptor blockade with canrenoate in healthy humans.

Activation of central nervous mineralocorticoid receptors (MRs) has been shown to inhibit the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis in animals. Here, we examined whether MRs in humans likewise regulate HPA activity in response to a physiological stressor. In a balanced, randomized, double-blind, cross-over trial, 12 healthy men were treated with either two injections of 200 mg canrenoate or placebo 24 and 8 h before an intense physical exercise taking place between 1600 and 1700 h. Exercising was preceded by a 60-min rest period and followed by another 90-min rest. Blood was collected in regular intervals to determine ACTH, cortisol, and human GH (hGH). Exercise induced a significant rise in cortisol, ACTH, and hGH. Cortisol levels, however, were significantly higher after canrenoate, compared with placebo, whereas ACTH and hGH concentrations did not differ. The increase in cortisol was already significant during rest before exercise and continued to be elevated throughout the whole experiment. We conclude that MR blockade leads to a tonically increased cortisol secretion both during rest and under stimulation. The undiminished concentration of ACTH in the presence of elevated cortisol levels suggests that blockade of MR shifts the set point for cortisol feedback inhibition of the HPA axis toward higher cortisol levels.

Adrenocorticotropic Hormone↗
PubMed2004

Transcortical direct current potential shift reflects immediate signaling of systemic insulin to the human brain.

Circulating insulin is thought to provide a major feedback signal for the hypothalamic regulation of energy homeostasis and food intake, although this signaling appears to be slowed by a time-consuming blood-to-brain transport. Here we show, by recording direct current potentials, a rapid onset of the effects of circulating insulin on human brain activity. Recordings were obtained from 27 men who were intravenously injected with insulin (0.1 mU/kg body wt as bolus) and placebo. In a euglycemic condition, hypoglycemia was prevented, while in the hypoglycemic condition, plasma glucose reached a postinjection nadir of 43 mg/dl. Insulin injection induced a marked negative direct current (DC) potential shift starting within 7 min in all subjects. With euglycemic conditions, the DC potential at 10-60 min postinsulin injection averaged -621.3 microV (compared with preinjection baseline). Hypoglycemia reduced this potential to an average of -331.2 microV. While insulin per se did not affect oscillatory electroencephalographic activity, hypoglycemia peaking 25 min after insulin injection was accompanied by an immediate increase in theta activity. The rapid emergence of the DC potential shift, reflecting gross ionic changes in brain tissues, indicates that systemic insulin can serve as an immediate feedback signal in the control of hypothalamic and higher brain functions.

Adult↗
PubMed2003

Acute influences of estrogen and testosterone on divergent and convergent thinking in postmenopausal women.

Previous studies indicated an enhanced capability of divergent creative thinking in young women during the ovulatory phase, which expressed itself also by an increased dimensional complexity of ongoing electroencephalographic (EEG) activity. Considering the enhanced plasma levels of estrogen and testosterone characterizing the ovulatory phase, we tested whether short-term administration of estrogen or testosterone in postmenopausal women with constantly low levels of gonadal steroids induces similar changes in divergent thinking. In two placebo-controlled cross-over studies, healthy postmenopausal women (n=12, in each study, mean age 58 years, range 47-65 years) were treated transdermally over 3 days with estrogen and testosterone, respectively, at doses inducing plasma hormone concentrations comparable with those observed in young women around ovulation. Capabilities of divergent thought and convergent analytical thought, performance on motor perseveration, and verbal memory were examined. EEG activity was recorded while subjects performed on tasks of thinking and during mental relaxation. Estrogen impaired divergent thinking (p <0.01) and enhanced convergent thinking, motor perseveration, and memory for the initial word list (p <0.05 for all tests). In parallel, EEG dimensional complexity was reduced (p <0.05). Overall, these changes indicate an estrogen-induced shift from a "divergent" towards a more "convergent" mode of processing. However, overall less consistent, effects of testosterone were opposite to those of estrogen. It increased performance on some of the divergent thinking tasks (p <0.05), and tended to increase EEG dimensional complexity during divergent thinking. Data indicate a differential sensitivity of modes of thinking to short-term treatment with estrogen and testosterone in postmenopausal women.

Aged↗
PubMed2003

Hypoglycemia counterregulation during sleep.

STUDY OBJECTIVES: In insulin-treated patients with diabetes, episodes of severe hypoglycemia often occur during sleep, which might reflect an altered counterregulation and reduced awareness. This study examined the influence of sleep on the counterregulatory response to hypoglycemia in healthy subjects. DESIGN: Subjects participated in two experimental conditions; statistical tests relied on within subject comparisons. SETTING: University hospital sleep laboratory. PARTICIPANTS: 15 healthy young men. INTERVENTIONS: Hypoglycemia (2.8 mmol/l) was induced for 45 min by insulin infusion once during sleep and once at the same time of night while being awake. MEASUREMENTS AND RESULTS: Counterregulatory hormone concentrations (epinephrine, norepinephrine, ACTH and cortisol) and sleep recordings were obtained. Differences in the hormonal responses to hypoglycemia between sleep and wake conditions remained non-significant, indicating that sleep does not exert a primary influence on the strength of counterregulation. However, the glycemic threshold for the onset of counterregulation was significantly changed during sleep: The average onset threshold for epinephrine and norepinephrine counterregulation was 3.3 +/- 0.1 mmol/l for the wake condition and 2.7 +/- 0.1 mmol/l for the sleep condition (P < 0.001). A decrease in sleep depth coincided with the onset of the counterregulatory response, with most subjects showing signs of awakening. CONCLUSIONS: During sleep, the organism is less sensitive to hypoglycemia. Hypoglycemia per se has an awakening effect.

Adolescent↗
PubMed2003

Influence of captopril on symptomatic and hormonal responses to hypoglycaemia in humans.

AIMS: Hypoglycaemic symptoms and hormonal counter-regulation are of high importance to avoid the risk of severe hypoglycaemia in patients with diabetes mellitus. Various antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors, have been suspected for a long time to reduce this response to hypoglycaemia in diabetic subjects. Although ACE inhibitors are approved for controlling diabetic complications, previous investigations regarding this putative side-effect are controversial. METHODS: We performed clamp experiments in 16 healthy men lasting for 6 h each. The subjects were pretreated for 7 days with captopril 3 x 25 mg day-1 vs placebo in a randomized, double-blind, crossover study. Plasma glucose was decreased in a stepwise manner during a hypoglycaemic clamp session and counter-regulatory hormones [epinephrine (adrenaline), norepinephrine (adrenaline), ACTH, cortisol, glucagon], symptoms, and haemodynamic parameters (blood pressure, heart rate] were measured. RESULTS: Counter-regulatory hormone concentrations significantly increased in both sessions (ACE inhibitor vs placebo) during hypoglycaemia. The rise of counter-regulatory hormones as well as symptom scores were equal under both ACE inhibitor and placebo treatment. Systolic blood pressure and heart rate increased (from 110 +/- 3 vs 115 +/- 3 mmHg to 132 +/- 4 vs 133 +/- 4 mmHg) whereas diastolic blood pressure slightly decreased (from 63 +/- 2 vs 70 +/- 3 mmHg to 61 +/- 2 vs 64 +/- 2 mmHg) independent of pretreatment. Systolic and diastolic blood pressure were significantly lower in the captopril session vs placebo (P < 0.05). CONCLUSIONS: Our results demonstrate that subchronic treatment with captopril does not attenuate symptomatic and hormonal response to hypoglycaemia. Thus, to patients at risk of hypoglycaemia who require antihypertensive or nephroprotective treatment, we would continue giving an ACE inhibitor.

Adult↗
PubMed2003

Modulation of hunger by plasma glucose and metformin.

The plasma glucose concentration is a major short-term regulator of hunger and food intake. In patients with diabetes, therapies lowering plasma glucose are frequently associated with body weight gain, suggesting that lowered plasma glucose leads to increased feelings of hunger and food intake. However, as many physiological and symptomatic responses to low plasma glucose are attenuated after repeated episodes of hypoglycemia, this may also pertain to feelings of hunger. Here we tested whether the stimulatory effect of low plasma glucose on feelings of hunger is likewise reduced by repeated episodes of hypoglycemia. As metformin has been shown to reduce plasma glucose levels without increasing body weight and also to decrease food intake, we tested for possible interacting effects of this substance with hypoglycemia-induced hunger. Feelings of hunger were assessed by rating scales during 3 consecutive hypoglycemic clamps performed on 2 consecutive d in 15 normal weight men. Subjects were tested once while being treated with 850 mg metformin twice daily and once while receiving placebo. Treatment was started 14 d before the clamp experiments and was performed in a random order and double-blind fashion. Hypoglycemia markedly enhanced feelings of hunger (P < 0.001). However, rated feelings of hunger on the first and last hypoglycemic clamps were comparable (P = 0.304). Compared with placebo, metformin decreased feelings of hunger during hypoglycemia (P = 0.015). This reduction was not associated with a decrease in posthypoglycemic food intake as measured by the number of cookies consumed after the last clamp (P = 0.676). Data indicate that the stimulatory effect of low plasma glucose on hunger is not attenuated after repeated episodes of hypoglycemia, which implies that, in contrast to other symptoms, hunger is not subject to adaptive attenuation upon repeated hypoglycemia. Metformin attenuates hypoglycemia-induced hunger, but does not appear to influence posthypoglycemic food intake.

Adult↗
PubMed2003

Melatonin acutely improves the neuroendocrine architecture of sleep in blind individuals.

In blind individuals, the absence of light cues results in disturbances of sleep and sleep-related neuroendocrine patterns. The Zeitgeber influence of light on the timing of sleep is assumed to be mediated by melatonin, a hormone of the pineal gland, whose secretion is inhibited by light and enhanced during darkness. Here, we investigated whether a single administration of melatonin improves sleep and associated neuroendocrine patterns in blind individuals. In a double-blind crossover study, 12 totally blind subjects received 5 mg melatonin and placebo orally 1 h before bedtime starting at 2300 h. The dose used enhanced blood melatonin concentrations to clearly supraphysiological levels. Melatonin increased total sleep time and sleep efficiency (P < 0.05, respectively) and reduced time awake (P < 0.05). The increment in total sleep time was primarily due to an increase in stage 2 sleep (P < 0.01) and a slight increase in rapid eye movement sleep (P < 0.06). Most important, melatonin normalized in parallel the temporal pattern of ACTH and cortisol plasma concentration. While after placebo, ACTH and cortisol levels did not differ between early and late sleep, melatonin induced the typical suppression of pituitary-adrenal activity during early sleep and a distinct rise during late sleep (P < 0.01, respectively). Cortisol nadir values were also decreased after melatonin (P < 0.05). We conclude from these data that in totally blind individuals the single administration of a clearly pharmacological dose of melatonin can improve sleep function by synchronizing in time the inhibition of pituitary-adrenal activity with central nervous sleep processes.

Adjuvants, Immunologic↗
PubMed2002

EEG theta synchronization conjoined with alpha desynchronization indicate intentional encoding.

The involvement of different oscillating neuronal systems activated during intentional learning was investigated by measuring ongoing EEG activity. In 17 subjects, the EEG was recorded while learning pairs of words and faces. Subjective task difficulty was rated and a control condition of mental relaxation was also run. Spontaneous EEG activity during epochs which subsequently resulted in efficient encoding was associated with upper alpha desynchronization (10-12 Hz) and theta synchronization (4-8 Hz) when compared with spontaneous EEG activity during epochs of poor recall performance. The combined measure of theta synchronization plus upper alpha desynchronization was enhanced selectively over left frontotemporal cortical regions during efficient learning of words and over right parietal cortical regions during efficient learning of faces (P < 0.001). This striking topographical dissociation between learning materials for the combined measure of theta and upper alpha EEG activity suggests that the mode of intentional learning relies essentially on an interdependent regulation of two neuronal circuits: the thalamo-cortical circuit and the hippocampo-cortical circuit.

Action Potentials↗
PubMed2002

Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men.

A weight-reducing effect of metformin has been demonstrated in obese subjects with and without diabetes. The mechanisms of this action are unclear, which may be partly due to the fact that in obese and diabetic patients the substance's effects result from a complex interaction with the distinct endocrine and metabolic disturbances in these patients. To dissociate primary from secondary action of metformin, we examined effects of the substance in normal-weight healthy subjects. Fifteen normal-weight men were treated with metformin (850 mg twice daily) or placebo for a 15-day period in a double-blind, placebo-controlled, cross-over study. Anthropometric, psychologic, cardiovascular, endocrine, and metabolic parameters were assessed before and at the end of the treatment period. Metformin did not affect body weight (P =.838) and body fat mass (P =.916). Yet, serum leptin concentration was distinctly reduced after metformin (P <.001). Also, metformin reduced the concentration of plasma glucose (P =.011), serum insulin (P=.044), and serum insulin-like growth factor -1 (IGF-1) (P=.013), while it increased serum glucagon concentration (P <.001). There were no effects of metformin on feelings of hunger, blood pressure, heart rate, resting energy expenditure, the respiratory quotient, free fatty acids, beta-hydroxybutyrate, glycerol, triglycerides, cholesterol, and uric acid (all P >.1). Data indicate that metformin decreases the serum leptin concentration even without affecting body weight and body composition in normal-weight men.

Adipose Tissue↗
PubMed2002

Acute and prolonged effects of insulin-induced hypoglycemia on the pituitary-thyroid axis in humans.

Secretory activity of the pituitary-thyroid axis and thyroid hormone metabolism show characteristic changes in response to different stressors often referred to as the euthyroid sick syndrome. Hypoglycemia is an acute metabolic stressor inducing various neuroendocrine responses, the effects of which on pituitary-thyroid secretory activity so far have been entirely neglected. We performed stepwise hypoglycemic and euglycemic clamps each lasting 6 hours in 30 healthy men. To assess the potential influence of hyperinsulinemia on pituitary-thyroid hormone release, 2 different rates of insulin infusion were used for the clamps. During the hypoglycemic clamps, serum thyroid-stimulating hormone (TSH) concentration decreased in comparison to the euglycemic condition on average by 28% +/- 4% (P <.001), while serum concentration of free triiodothyronine (fT3), free thyroxine (fT4), and thyroxine-binding globulin (TBG) remained unchanged. The effect did not depend on the rate of insulin infusion. To assess the prolonged effect of acute hypoglycemia on pituitary-thyroid secretory activity, serum TSH and thyroid hormone concentrations were subsequently measured in another 15 healthy men before and 18 hours after 2 consecutive hypoglycemic clamps together lasting about 270 minutes. Compared with values before the hypoglycemic clamps, serum levels of TSH, fT3, and fT4 were found to be still reduced (by 44% +/- 6%, 12% +/- 2%, and 10% +/- 1%, respectively) 18 hours after the last hypoglycemic episode (P <.001 for all comparisons). The observed hormonal changes after hypoglycemia were not accompanied by any change in resting energy expenditure (REE). Data indicate acute as well as prolonged inhibitory influences of hypoglycemia on pituitary-thyroid secretory activity. The pattern of changes suggests that hypoglycemia exerts its influence primarily at a central, ie, pituitary and/or hypothalamic, site of the axis.

Adult↗
PubMed2002

Vascular endothelial growth factor: a novel endocrine defensive response to hypoglycemia.

Glucose, the most important fuel for the brain, is supplied by the actions of counterregulatory hormones and the sympathetic nervous system. Yet to obtain access to the brain, glucose must pass the blood-brain barrier. Here we show that vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, is a candidate hormone for facilitating glucose passage across the blood-brain barrier under critical conditions. In 16 healthy men, VEGF serum concentrations increased under 6 h of insulin-induced hypoglycemic conditions from 86.1 +/- 13.4 to 211.6 +/- 40.8 pg/ml (P = 0.002), whereas in the hyperinsulinemic euglycemic control condition, no change was observed. During hypoglycemia serum VEGF, but no other counterregulatory hormone, was associated with preserved neurocognitive function, as measured with a memory test (r = 0.539; P = 0.031) and the Stroop interference task (r = 0.569; P = 0.021). Findings show that acute hypoglycemia is accompanied by a brisk increase in circulating VEGF concentration and that VEGF could mediate rapid adaptation of the brain to neuroglycopenia.

Adult↗
PubMed2002

Food deprivation fails to affect preoccupation with thoughts of food in anorectic patients.

OBJECTIVES: Memory for food words was used to investigate effects of hunger and satiety on information processing in acute and recovered anorectics. DESIGN: In Expt 1, recall of words related to food and unrelated to food was compared between anorectics and controls. In Expt 2, the same procedure was undertaken in recovered anorectics and controls. METHODS: Tests were performed in each subject after starvation and after food intake. RESULTS: When hungry, recall of food words did not differ between anorectics and controls. During satiety, however, anorectics recalled significantly more food words than controls. Recall of food unrelated words did not differ between both groups. Recall in recovered anorectics was comparable with that in acute anorectics. CONCLUSIONS: Results indicate that cognitive processing of food stimuli does not depend on food deprivation in anorectics.

Acute Disease↗
PubMedDate not supplied

Sleep enhances the human antibody response to hepatitis A vaccination.

OBJECTIVE: The common belief that sleep supports immune defense has received surprisingly little direct experimental support. The antibody response to vaccination provides a valid tool to assess the influence of sleep on adaptive immune functioning in humans, which is also clinically relevant. METHODS: Two groups of healthy humans (N = 19) not previously infected with hepatitis A virus (HAV) were studied. On the night after primary vaccination with inactivated HAV, which took place at 0900 hours, one group had regular sleep. The other group stayed awake, and did not sleep before 2100 hours the following day. HAV antibody titers were measured repeatedly until 28 days after vaccination. Plasma hormone concentrations and white blood cell (WBC) subset counts were determined on the night and day after vaccination. RESULTS: Subjects who had regular sleep after vaccination, displayed a nearly two-fold higher HAV antibody titer after 4 weeks than subjects staying awake on this night (p=.018). Compared with wakefulness, sleep after vaccination distinctly increased release of several immune-stimulating hormones including growth hormone, prolactin, and dopamine (p <.01). Concentrations of thyrotropin, norepinephrine, and epinephrine were lowered by sleep (p <.02), whereas sleep only marginally influenced WBC subset counts. CONCLUSIONS: Data suggest that sleep compared with sleep deprivation on the night after vaccination improves the formation of antigen-specific immune defense as reflected by antibody production in humans. Sleep presumably acts by inducing a hormonal environment in secondary lymphoid tissues, enhancing lymphocyte proliferation and differentiation and finally antibody synthesis. Results underscore the importance of sleep for immunocompetence.

Adult↗