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Biomedical subjects

S Hoyer

Publications and source records attributed to S Hoyer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?

Lead is known to be a potent inhibitor of many enzymes working in the brain, thus possibly inducing functional problems in the brain under pathophysiological conditions. Among such enzymes are those involved in glucose metabolism and energy production. We investigated the inhibitory effects of low-level lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) with rat brain homogenate. PDHc was distinctively inhibited when low-dose lead acetate was added last of all (IC50 = 5 microM) to the reaction mixture. The other enzymes were completely resistant to 5 microM of lead acetate. When the homogenate was preincubated with lead acetate HK was dramatically inhibited by low-level lead acetate (1-5 microM), in a manner dependent on both preincubation time and lead concentration. However, the inhibitory effect was abolished by coincubation with its substrates, glucose or ATP. The results suggest that exposure to low levels of lead may increase the risk of cerebral hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the abnormal glucose metabolism seen in some kinds of neurodegenerative disorders such as sporadic Alzheimer's disease.

Adenosine Triphosphate↗
PubMed2000

Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update.

It is discussed that Alzheimer disease does not form a nosologic entity. 5 to 10% of all Alzheimer cases are due to inherited abnormalities on chromosomes 1, or 14, or 21, whereas the majority of 90-95% is sporadic in origin. Age-related changes in the composition of membranes and in glucose/energy metabolism along with a sympathetic tone in the brain are assumed to be cellular/molecular risk factors for this disease. In its pathogenesis, the desensitization of the neuronal insulin receptor similar to non-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in insulin concentration is assumed to induce a cascade-like process of disturbances including decreases in cellular glucose, acetylcholine, cholesterol, and ATP, associated with changes in the metabolism of amino acids and fatty acids. There is evidence that the reductions in the availability of both glucose/energy and insulin contribute to the formation of amyloidogenic derivatives and hyperphosphorylated tau protein. This may indicate that the amyloid cascade hypothesis in not valid for sporadic Alzheimer disease but that the formation of both, amyloidogenic derivatives and hyperphosphorylated tau protein is downstream the origin of this neurodegenerative disease.

Alzheimer Disease↗
PubMed2000

Successful breast-feeding as a result of a health education programme for mothers.

The present study aims to prove an improvement in breast-feeding practices in mothers who received written instructions for successful breast-feeding and had individual counselling at the time of taking this questionnaire. The instructions were based on the results of a study carried out in Slovenia in 1993 and published in the Journal of Advanced Nursing (1998), 27, 1250-1256 (Hoyer & Pokorn 1998). The variables that were then found statistically significant in the initial and continued breast-feeding became the basis of written instructions for breast-feeding. The results obtained in the new current study were compared with that basic study which included 881 mothers. This was possible because the conditions of breast-feeding between 1993 and 1995 (when the new study was launched) had not changed. The idea of baby-friendly hospital initiative (BFHI) had not yet come into force in Slovenia. The current study comprised 203 pregnant women who were first visited during their 8th month of pregnancy. In order to collect data on breast-feeding and deliver instructions, a field nurse visited each mother eight times until the completion of first year and continued to visit them every third month and for all those who were still breast-feeding after that time, until the end of the lactation period. Statistical analysis was carried out by means of SPSS statistical package and survival analysis. All mothers in the study started breast-feeding. By the end of the first month 84.7% of them were still breast-feeding, while by the end of the third month it dropped to 74.9%, and by the end of the sixth month to 45.8%. Among these, breast-feeding alone was practised in the first week by 25.7%, by the end of the first month by 16.4%, and by the end of the third month by 9.5%. All the observed parameters were better than in the basic study. The mean duration of breast-feeding was 217 days, while the longest duration was 852 days. The survival analysis showed a statistically significant difference in the duration of breast-feeding. In the current study group, mothers weaned their infants at a slower rate than in the group from the year 1993. It has been found that the written instructions as well as personal encouragement by the field nurse exerted a favourable influence on breast-feeding practices, which was taken as a guideline for our further professional work and change of standards in the field of breast-feeding promotion.

Adult↗
PubMed2000

Linear relation between cerebral phosphocreatine concentration and memory capacities during permanent brain vessel occlusions in rats.

The present study investigates the interrelation between cerebral energy state and memory capacities in a rat model of stepwise cerebral vessel occlusions. After acute and subchronic permanent vessel occlusions, cortical energy metabolites (ATP, phosphocreatine, ADP, AMP) were detected by high-pressure liquid chromatography (HPLC) analysis, and the effects on learning, memory, and cognitive behavior were evaluated using a hole-board test. The results of the study demonstrated a drastic decrease in energy-rich phosphates by 33% for phosphocreatine and by 44% for ATP after acute vessel occlusions. In addition, rat working and reference memories were strikingly decreased to about 5% of controls. In contrast, two weeks after four-vessel occlusion, the energy state was almost completely restored to control levels. However, a significant decrease in memory capacities was observed in subchronic state. In summary, this study has demonstrated a close linear relationship (p < 0.001) between an impaired cerebral energy state and brain memory dysfunction after acute and permanent cerebral four-vessel occlusion. Thus, this animal model of stepwise reduction of the cerebral blood supply may reflect some clinically relevant processes occurring during cerebrovascular and neurodegenerative diseases.

Adenosine Diphosphate↗
PubMed2000

Inhibition of the neuronal insulin receptor. An in vivo model for sporadic Alzheimer disease?

It has been hypothesized that a central even in the early pathogenesis of sporadic Alzheimer disease (SAD) is the dysfunction of the neuronal insulin receptor signal transduction. To prove this, this receptor was inhibited by a triplicate icv application of STZ. Insulin binding sites were upregulated as in SAD. With respect to glucose transport proteins, detailed investigations are necessary.

ATP-Binding Cassette Transporters↗
PubMed1999

Interrelation between cerebral energy metabolism and behaviour in a rat model of permanent brain vessel occlusion.

The present study investigates the interrelation between cerebral energy metabolism and memory capacities after acute and permanent occlusions of carotid and vertebral arteries in adult Wistar rats (n=60). Tissue ATP, phosphocreatine, ADP, AMP and adenosine concentrations were determined in rat brain by high-pressure liquid chromatography (HPLC) analysis. Lactate and pyruvate were measured spectrophotometrically. Rats underwent psychometric testing by means of a holeboard test, closed field activity, and passive avoidance behaviour. Acute cerebral ischaemia was associated with a substantial deficit in energy load (-50%). Cortical adenosine and lactate exhibited a 7- and a 10-fold increase, respectively, in concentration. After 2 weeks of four-vessel occlusion, cortical ATP and phosphocreatine showed a partial enhancement in their concentrations if compared with acute ischaemia. Consequently, energy load (micromol/g) increased from 0.59 to 1.42 in cerebral cortex and from 0.58 to 1.14 in hippocampus under conditions of acute and permanent ischaemia, respectively. While lactate was normalized, adenosine showed a 2-fold increase in its cortical concentration. All animals improved their abilities in learning, memory and cognition after a 7-day training period. Acute vessel occlusion severely decreased working memory (WM), reference memory (RM) and locomotor activity. Simultaneously, the passive avoidance test showed a significant reduction in latency time from 247+/-85 s (sham) to 145+/-132 s. The partial improvement in brain energy state was accompanied by a relative improvement in WM and RM, although both memory capacities remained significantly lower than in controls. The data of the present study demonstrate a linear relationship between cerebral energy metabolism and brain memory capacities after acute and permanent vessel occlusions in rats.

Animals↗
PubMed1999

Brain-derived neurotrophic factor improves long-term potentiation and cognitive functions after transient forebrain ischemia in the rat.

We investigated the effect of brain-derived neurotrophic factor (BDNF) on hippocampal long-term potentiation (LTP) and cognitive functions after global cerebral ischemia in the rat. After four-vessel occlusion, BDNF was administered via an osmotic minipump continuously over 14 days intracerebroventricularly. Electrophysiological experiments were performed 14 days after cerebral ischemia. Test stimuli and tetanization were delivered to the Schaffer collaterals of the hippocampus and field excitatory postsynaptic potentials (fEPSP) were recorded in the CA1 region. Cognitive impairment was analyzed repeatedly with a passive avoidance test, a hole-board test, and with an activity center on the same animal. In sham-operated animals, LTP was consistantly induced after delivering a tetanus (increase of initial slope of fEPSP to 173 +/- 12% of baseline; n = 6). After transient forebrain ischemia LTP could not be induced (117 +/- 4% of baseline; n = 7). In ischemic animals treated with BDNF, LTP could be induced (168 +/- 28% of baseline; n = 8). Transient forebrain ischemia resulted in a significant decrease in spatial discrimination performance but not of associative memory. The ratios for working memory (WM) and reference memory (RM) 15 days after ischemia were lower in the ischemic rats (n = 10) than in the sham-operated control animals (n = 10; WM: 22 +/- 6 vs 72 +/- 7; RM: 30 +/- 7 vs 72 +/- 5). Postischemic intracerebroventricular BDNF infusion increased both WM (63 +/- 4; n = 10) and RM (58 +/- 5; n = 10). The spontaneous locomotor activity did not differ significantly in the three groups. These data indicate a protective effect of BDNF for synaptic transmission and cognitive functions after transient forebrain ischemia.

Animals↗
PubMed1999

Damaged neuronal energy metabolism and behavior are improved by Ginkgo biloba extract (EGb 761).

The standardized extract EGb 761 from the dried green leaves of Ginkgo biloba is a complex mixture of ingredients with an uniquely broad spectrum of pharmacological activities on the central nervous system e.g. in memory enhancing properties and in the regulation of cerebral glucose/energy metabolism. To test these effects on both behavioral and metabolic brain parameters, the animal model of intracerebroventricular (i.c.v.) streptozotocin (STZ) treatment was used. To quantify the experimental data more precisely, animals that were good performers were separated from poor performers by means of the holeboard test before i.c.v. administration of STZ. Good performers only were considered for the study. After a 1-week training period on the holeboard improvement was seen in all animals in learning, memory and cognition, and the improvement was maintained over the investigation period of 12 weeks in the control group. In this group, the energy pool in the cerebral parietotemporal cortex was found to be large and the energy turnover high. After triplicate i.c.v. STZ injection, working memory (WM), reference memory (RM), and passive avoidance (PA) behavior fell off and continued to deteriorate throughout the investigation period. Otherwise there were no significant differences in locomotor activity, excluding the possibility that activity per se might have contributed to the behavioral abnormalities. These were accompanied by a permanent deficit in cerebral energy metabolism. The ongoing deterioration in behavior and the maintained deficit in cerebral energy metabolism occurring after a triplicate i.c.v. STZ injection were significantly slowed down by EGb761. The deficits in learning, memory and cognition were partially compensated, and the disturbances in cerebral energy metabolism returned to almost completely normal values. These findings underscore the beneficial effect of EGb761 that had been reported in dementia disorders.

Adenosine Triphosphate↗
PubMed1999

A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease.

Disturbances of glucose and energy metabolism are hypothesized as pathogenetic factors in sporadic dementia of Alzheimer type (SDAT). Insulin and is receptors play an important role in the regulation of brain glucose metabolism and neuronal growth. In postmortem brain cortex in SDAT, the densities of brain insulin receptors were decreased compared to adult controls, but were increased in relation to aged controls. Tyrosine kinase activity, a signal transduction mechanism common to insulin and IGF-1 receptors, was reduced in SDAT in comparison to middle-aged and age-matched control groups. The data are consistent with a neurotrophic role of insulin in the human brain and an upregulation of insulin receptors is SDAT brain as a compensatory mechanism, possibly due to impaired signal transduction mechanism.

Adult↗
PubMed1998

Increased ATP production during long-term brain ischemia in rats in the presence of propentofylline.

Forty adult rats were subjected to stepwise two- and four-brain vessel occlusion and propentofylline 25 mg/day per kilogram body weight was intraperitoneally administered for 1 week or 3 weeks. Adenosine 5'-triphosphate, creatine phosphate, adenosine 5'-diphosphate and adenosine were determined in rat parietotemporal cortex by high-pressure liquid chromatography; lactate and pyruvate were measured spectrophotometrically. Stepwise and permanent long-term brain vessel occlusion gradually reduced the concentration of energy-rich phosphates and induced a marked increase in the concentration of adenosine, a parameter of ischemia. Three weeks of propentofylline treatment resulted in a significant increase in cerebral adenosine 5'-triphosphate concentration from 2.16 +/- 0.15 [(-)-propentofylline] to 2.70 +/- 0.24 nmol/mg wet weight during four-vessel occlusion (+25%). This was associated with an enhancement of the adenosine 5'-triphosphate/adenosine 5'-diphosphate ratio (+33%), mainly because of the significant reduction in adenosine 5'-diphosphate concentration. Propentofylline did not prevent the increase in lactate concentration during permanent brain vessel occlusion, but significantly reduced the tissue concentration of adenosine. In summary, the results demonstrate that continuous propentofylline administration over 3 weeks induced a striking increase in rat cortical adenosine 5'-triphosphate concentration during long-term brain vessel occlusion. Thus, propentofylline may have possible neuroprotective effects and could be used in the treatment of patients with chronic cerebrovascular disorders.

Adenosine Triphosphate↗
PubMed1998

Risk factors for Alzheimer's disease during aging. Impacts of glucose/energy metabolism.

The majority of Alzheimer patients is of late onset and with unknown etiology. However, several risk factors have been discussed among which age is a most important one with respect to sporadic Alzheimer type dementia (SDAT). Age includes changes in brain glucose/energy metabolism, in both insulin and acetylcholine signal transduction and in membrane function to name the functionally most important ones. Variations in these parameters can form the basis for ongoing changes in terms of the principle of self-organized critically inducing catastrophic i.e. disease processes. Subsequent abnormalities at the cellular and molecular levels may develop including the formation of both amyloid plaques and neurofibrillary tangles.

Aging↗
PubMed1998

Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis.

The hypothesis is forwarded that sporadic late-onset Alzheimer disease is caused by non-insulin dependent diabetes mellitus which is confined to the brain. This hypothesis is based on the findings of Frölich and coworkers (this volume) who clearly demonstrate a perturbation of the neuronal insulin/ insulin receptor signal transduction pathway which is considered to be the pathobiochemical basis for the drastic reduction in glucose/energy metabolism in Alzheimer brain. As a consequence of this abnormality, advanced glycation end products are formed. Münch et al. (this volume) evaluate the impacts of the latter related to oxidative stress and the formation of beta-amyloid and neurofibrillary tangles.

Age of Onset↗
PubMed1998

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Adult↗
PubMed1998

Streptozotocin increases free fatty acids and decreases phospholipids in rat brain.

Streptozotocin (STZ) is a diabetogenic drug that disrupts glucose and energy metabolism in brain. To study its effect on brain lipids, tissue concentrations of free fatty acids and phospholipids were measured in the temporal cortex and the hippocampus of adult rats 3 weeks after a single intracerebroventricular (icv) injection of STZ. STZ increased concentrations of palmitic acid and stearic acid in temporal cortex and these of arachidonic acid both in the anterior part of the hippocampus and in CA1. In addition, palmitic acid and stearic acid concentrations were elevated in the anterior hippocampus. In contrast, STZ decreased brain cortex levels of phosphatidylethanolamine and phosphatidylserine. These data show that STZ alters brain lipid metabolism. They suggest that oxidative phospholipid breakdown is accelerated by STZ. These changes may be related to decreased brain glucose utilization and energy formation.

Animals↗
PubMed1998

Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats.

Drastic abnormalities have been demonstrated to occur in cerebral glucose and energy metabolism in sporadic Alzheimer's disease, pointing to a primary disturbance in neuronal insulin and insulin receptor signal transduction and contributing to the causation of dementia. The compound streptozotocin (STZ) is known to inhibit insulin receptor function. The study was designed to investigate whether intracerebroventricularly (icv) applied STZ would inhibit neuronal insulin receptor function and would induce changes in both behavior and neuronal energy metabolism. Adult rats with icv-injected STZ developed long-term and progressive deficits in learning, memory, and cognitive behavior, indicated by decreases in working and reference memory in the holeboard task and the passive avoidance paradigm, along with a permanent and ongoing cerebral energy deficit. This animal model may be appropriate for investigations related to sporadic Alzheimer's dementia.

Adenosine Diphosphate↗
PubMed1998

The influence of various factors on breast-feeding in Slovenia.

This research on breast-feeding was conducted with 881 randomly selected Slovenian mothers who gave birth in January and February 1992. At the time of the study the infants were about 15 months old. The survey was conducted in the homes of the mothers. Statistical analyses included descriptive statistics, the chi-square test, t-test and multivariate binary regression analysis. The mothers' average age was 26.2 years. Their educational level was approximately 12 years of public schooling. On average there were 1.67 children per family. Of the total surveyed, 22 mothers (2.5%) did not breast-feed their babies; 38 mothers (4.3%) were still breast-feeding at the time of the survey. The average duration of breast-feeding for mothers who stopped before or at 15 months of the infant's age was 159.1 days (about 5 months). Having adequate information about breast-feeding and failing to state problems during the breast-feeding period were found to be positive influences which induced mothers to breast-feed their infants. Characteristics of the mothers which influenced longer duration of breast-feeding were: feeding eight or more times daily in the first month of breast-feeding, the birth order of the infant, attending courses for parents, deciding before the birth to breast-feed, living in the city, living with a partner, having a secure income, having no other problems during the period of breast-feeding, spoon-feeding liquids, having a secondary level or more of education, being well informed about breast-feeding and giving the first feed within 12 hours after the birth. Breast feeding among Slovenian mothers is significantly on the rise and the period of breast-feeding is being extended to 6 months. Nevertheless, greater efforts are needed in the education of health personnel to promote and support the healthy practice of breast-feeding.

Adolescent↗