PubMed HealthSearch

Biomedical subjects

J Jolles

Publications and source records attributed to J Jolles.

At least 19 recordsLinked to original sources

Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine.

Treatment of rats with i.c.v. injected streptozotocin (STREP) may provide a relevant model of neurodegeneration that is induced by a decrease in the central metabolism of glucose. Acetyl-L-carnitine (ALCAR) enhances the utilization of alternative energy sources and by such a mechanism of action ALCAR could antagonize the effects of STREP treatment. In this study the effects of chronic treatment with ALCAR were evaluated on spatial discrimination learning in the Morris task and choline acetyltransferase (ChAT) activity of middle-aged STREP-treated rats. Chronic treatment with ALCAR attenuated both the STREP-induced impairment in spatial bias and the decrease in hippocampal ChAT activity. These findings indicate that ALCAR treatment has a neuroprotective effect, although further studies are needed to characterize the mechanism of action of ALCAR in this model.

Acetylcarnitine

Problems of caregiving spouses of patients with dementia.

Twenty-six caregiving spouses of patients with dementia in the Netherlands were interviewed to better understand their problems and needs. Special attention was paid to the information the caregivers received from their general practitioner. Nineteen caregivers indicated that they received little or no information about the disease and its possible consequences. Furthermore, they experienced many problems, because of the disease and the daily care they provided; eleven caregivers indicated a decrease in social contact, which resulted in further problems. Caregivers who sought professional help at an early stage experienced fewer problems in providing daily care. The results of this project suggest that in future health education policy special attention should be paid to the role of the general practitioner and to the importance of a caregiver's social network.

Activities of Daily Living

Primitive reflexes in Alzheimer's disease and vascular dementia.

Data on the prevalence and clinical value of primitive reflexes (PRs) in dementia are controversial, mainly due to a lack of standardization of the methods by which these signs are elicited and scored. A standardized protocol was used to investigate eight PRs in 20 patients with Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 20 control subjects for each group. Both patient groups showed considerably more PRs than the control groups. The prevalence of PRs was related to the severity of dementia. No single reflex or combination of PR pathognomonic for dementia could be distinguished. The PR profile of AD and VD patients were similar.

Aged

Late neurobehavioural symptoms after mild head injury.

The present study examined whether patients (n = 11) with post-concussional symptoms (PCS) 12-34 months after mild head injury (MHI) performed less well on selected neuropsychological tests than patients with MHI without PCS (n = 11) and healthy controls (n = 11). Patients with PCS were individually matched with controls for the time elapsed after the injury, age, sex, education and IQ. There were no overall gross differences between the groups in cognitive functioning, except for an isolated deficit on a sustained attention task. Post-hoc analysis of results obtained with two behavioural rating scales showed that patients with higher ratings on a post-concussive/cognitive complaints scale performed less well on a sustained attention task than subjects with lower ratings.

Adolescent

Depression, insight, and personality changes in Alzheimer's disease and vascular dementia.

Although it is generally believed that depression, retained insight, and preserved personality occur more frequently in vascular dementia than in Alzheimer's disease, there is little empiric evidence for this presumption. Most studies on this subject have been carried out with severely demented inpatients, and confounding factors such as age, sex, and severity of dementia have not been sufficiently taken into account. We compared 48 patients with relatively mild vascular dementia with 48 patients with Alzheimer's disease, matched for age, sex, and stage of dementia, to investigate if depression, lack of insight, and personality changes were related to the cause of dementia. The two groups did not differ regarding the incidence of major depression, the mean depression score, the awareness score, or the sum of scores on the items of the Blessed Dementia Scale concerning personality changes. We conclude that depression, lack of insight, and personality changes do not favor an etiology of vascular dementia over that of Alzheimer's disease. The present findings underscore the notion that the severity of the dementia should be considered in studies on the differences between vascular dementia and Alzheimer's disease.

Aged

Phosphoinositide kinase activities in synaptosomes prepared from brains of patients with Alzheimer's disease and controls.

Previously, phosphatidylinositol (PI) kinase activity in cytosolic fractions prepared from postmortem tissue of the cerebral cortex from patients with Alzheimer's disease (AD) appeared to be lower than that of age-matched controls [Jolles et al., J. Neurochem., 58 (1992) 2326-2329]. In the study presented here, PI and PIP (phosphatidylinositol phosphate) kinase activities were studied in synaptosomes prepared from postmortem brain tissue of AD patients and age-matched controls. Firstly, PI kinase activity in synaptosomes prepared from the frontal superior gyrus of AD brain was 30% lower than in synaptosomes prepared from postmortem tissue of control brain. PIP kinase activity was the same in AD and control synaptosomes. Secondly, the yield of synaptosomal protein (micrograms protein per mg tissue wet weight) was lower in preparations from AD brain than in preparations from control brain, which could be a manifestation of a loss of presynaptic terminals in the frontal cortex. These results suggest that the difference in PI kinase activity between AD and control brain tissue may originate from differences in intact neurons in view of the fact that synaptosomes can originate only from intact neurons.

1-Phosphatidylinositol 4-Kinase

Behavioral and biochemical effects of an ICV injection of streptozotocin in old Lewis rats.

Intracerebroventricularly (ICV) injected streptozotocin (STREP) decreases central glucose metabolism and energy metabolism, which has also been observed in patients with dementia. In the present study we examined the behavioral (open-field behavior and two-way active avoidance learning) and biochemical (hippocampal ChAT activity) effects of STREP treatment in old Lewis rats. The results suggest that hippocampal function was affected by STREP. STREP-treated rats acquired the two-way active avoidance task faster than the control rats, which indicates that STREP treatment does not lead to a general learning deficit. Hippocampal ChAT activity was decreased in STREP-treated rats. The present results suggest also that susceptibility to STREP may not be related to age in Lewis rats.

Aging

Public education about normal forgetfulness and dementia: importance and effects.

In the Netherlands considerable attention has been given to dementia, but hardly any is paid to normal forgetfulness. Two information meetings about the differences between normal forgetfulness and dementia were organized in order to meet current information needs. Evaluation of those meetings gave more insight into the characteristics of people who are worried about their diminishing memory and provided the opportunity of measuring changes in knowledge and anxiety. Almost 50% of the 450 participants indicated that they were worried about their memory; 66% of these people reported being more or less reassured afterwards. Although the level of knowledge increased, no correlation was found between increased knowledge and decreased anxiety. Because of people's anxiety about possible dementia, it is important to provide the general public with more information about this subject. More research, with a control group, is necessary to draw conclusions about the effectiveness of health education in this area.

Adult

The relationship between plasma osmolality and plasma vasopressin concentration is altered in old male Lewis rats.

Kidney dysfunction has been observed in aged humans and rats, the primary cause of which may reside in the kidney itself or in the hypothalamus. The latter possibility is suggested by the increased release of AVP in response to salt infusion in humans. The effect of age on the relationship between plasma osmolality and plasma AVP concentration has never been verified in an animal model. Therefore, in the present study, 9% salt solution was infused into adult and aged Lewis rats, and plasma AVP concentration and osmolality were measured. Basal plasma AVP concentration, osmolality and total water intake were not altered in aged Lewis rats as compared with adult animals, indicating the absence of overt disturbances in water homeostasis. Infusion of 9% salt solution resulted in a linear increase in plasma osmolality in both adult and aged rats. Plasma osmolality increased more with time in aged animals than in adult animals, suggesting an age-related difference in kidney function during salt infusion. Plasma AVP concentration increased 50% less with osmolality at relatively low osmolalities, but not at relatively high osmolalities. The altered relationship between plasma osmolality and plasma AVP concentration in rats with age may be related to changes in neurons monitoring osmolality or to changes in baroreflex regulation. The data suggest that reduced kidney function with age does not result from an altered relationship between plasma osmolality and plasma AVP concentration.

Aging

The effect of age on phosphatidylinositol kinase, phosphatidylinositol phosphate kinase and diacylglycerol kinase activities in rat brain cortex.

A previous study, in which a lysed fraction was used with endogenous phospholipids as substrate, revealed age-related changes in PA and PIP2 formation but not in PIP formation (Bothmer et al., Neurochem. Int. 21, 223-228, 1992). To rule out the influence of substrate availability in the present study, the effect of age on PI kinase, PIP kinase and DAG kinase activities was studied with exogenous phospholipids as substrate in the cerebral cortex from 8-month-old, 14-month-old and 26-month-old Brown Norway rats. PI kinase activity was predominantly located in a tight membrane-bound protein fraction, DAG kinase activity in cytosolic and loosely membrane-bound protein fractions, and PIP kinase activity was present in all three protein preparations. The effects of age were limited to a small increase in kinase activity in the tight membrane-bound protein fraction in 14-month-old and 26-month-old rats compared to 8-month-old rats, and a 10% decrease in PIP kinase activity in the cytosolic protein fraction in 14-month-old and 26-month-old rats compared to 8-month-old rats. DAG kinase activity showed no age-related changes. In conclusion, one should take care in comparing rat aging with human aging as PI kinase activity shows an age-related decline in human brain cortex (Jolles et al., J. Neurochem. 58, 2326-2329, 1992). Furthermore, previously reported decreases in PA formation rates in rat brain are probably not due to changes in DAG kinase itself but to changes in DAG availability, although further experimental evidence is needed to confirm this conclusion.

1-Phosphatidylinositol 4-Kinase

[Education about dementia and forgetfulness in daily and weekly press].

In the period March 1990-March 1991 the attention for dementia increased in the Dutch printing press in comparison with the period 1987-1990. Despite this increase, the average number of articles on dementia in daily and weekly news magazines is less than one article per two months. This is extremely little for such an enormous medical and social problem. Furthermore, there is a relative decrease in the number of articles on general aspects of dementia. As expected, the number of articles on research in the field of dementia has increased considerably. In contrast with our hypothesis, it appears that in the printing press there is still hardly attention to memory and normal forgetfulness. In future education programs more explicit information should be given not only about dementia (symptoms, progress, consequences, etc), but also about memory complaints and normal forgetfulness. The printing press could make an important contribution towards achieving these goals. An important condition for this is a better cooperation with experts on the subject.

Aged

[Psychiatric disorders in patients of a memory outpatient clinic].

OBJECTIVE: To determine whether psychiatric conditions other than depression are relevant in elder patients with memory disturbances. METHODS: 430 consecutive outpatients (242 males, 188 females; mean age 61.7 years) who visited the Maastricht Memory Clinic were examined, according to a standardised diagnostic procedure, including somatic, neurological, psychiatric and neuropsychological examination. Psychiatric disorders were diagnosed according to DSM-III(-R) criteria. RESULTS: Of 152 patients with dementia, 34 had a secondary depressive syndrome, 19 another secondary psychiatric disorder. Of the 37 patients with a psycho-organic disorder other than dementia, 16 had an organic mood disorder. Of the other 241 patients, 152 had 159 primary psychiatric diagnoses: mood disorders in 100 cases and other psychiatric disorders in 59 cases, especially adjustment disorders, anxiety disorders and personality disorders. Together, only 60% percent of all primary or secondary psychiatric disorders were mood disorders. Various ways in which organic substrate, cognitive problems and psychopathology can be interrelated are discussed. CONCLUSION: Although affective disorders were the most frequent psychiatric disorders, several other psychiatric conditions were related to memory disturbances as well. Psychiatric assessment in patients with memory complaints should not be restricted to the diagnosis of depressive symptoms.

Adolescent

Behavioural and biochemical effects of acute central metabolic inhibition: effects of acetyl-l-carnitine.

In the present study we evaluated a new method to assess the behavioural and biochemical effects of a brief period of acute hypoxia in the brain. In this method, cyanide is injected into the lateral ventricles. Spatial navigation performance in a Morris task was found to be impaired 1 and 5 min after an i.c.v. injection of 5.0 micrograms cyanide but not after 2.5 micrograms cyanide. Increased rate of phosphatidic acid formation, reflecting increased phospholipase C activity, were observed after injection of 5.0 micrograms cyanide, indicating that energy-dependent phosphoinositide metabolism was affected. Chronic treatment with acetyl-l-carnitine attenuated the cyanide-induced behavioural deficit, but had no effect on energy-dependent phosphoinositide metabolism. The results suggest that, in this model, acetyl-l-carnitine may act via free fatty acid metabolism, by increasing the reservoir of activated acyl groups which are involved in the reacylation of membrane phospholipids.

Acetylcarnitine

Primitive reflexes in healthy, adult volunteers and neurological patients: methodological issues.

A study was made to determine whether two experienced clinicians elicited and scored primitive reflexes (PR) differently and whether reliability could be improved by standardization. Three studies were carried out, using a protocol for the examination of 14 PR. In the first study with 31 healthy young subjects, two investigators found virtually no difference in the routine neurological examination. However, the interobserver agreement was very poor, indicating the need for a further improvement of the PR protocol. In the second study, 30 neurological patients were examined with an improved, more explicit and standardized protocol, in which the amplitude and the persistence of the reflex were scored separately. Interobserver agreement improved considerably, and was high for amplitude as well as persistence. In the third study, 36 neurological patients were examined twice by one investigator within 2 weeks. Good to excellent intraobserver agreement was found. No pathognomonic or strictly localizing reflex could be distinguished.

Adolescent

Platelet phosphatidylinositol kinase activity is not altered in Alzheimer disease.

We previously reported a specific decline in phosphatidylinositol (PI) kinase activity in the neocortex of patients with Alzheimer disease (AD) as compared to controls, whereas phosphatidylinositol phosphate (PIP) kinase activity appeared not to be affected (Jolles et al., 1992). In search of a possible systemic effect of AD, in the present study we investigated phosphoinositide kinase activity in platelets from patients with AD and from control subjects. The study was based on the notion that disease-specific abnormalities in the brain could be reflected in blood platelets. PI kinase activity was studied in platelet homogenates and in a salt-solubilized protein fraction of platelets, because of the difference in subcellular localization of the different types of PI kinases. In addition, NADH cytochrome-C reductase was measured in platelet homogenates as a marker for the endoplasmic reticulum, to detect a possible proliferation of the endoplasmic reticulum. AD patients and normal elderly controls showed no difference in PI kinase activity in either enzyme fraction. Furthermore, NADH cytochrome-C reductase activity and the protein/phospholipid ratio per 10(6) platelets were the same for AD patients and controls. This was taken as an indication that platelets in AD patients do not show proliferation of intracellular membranes.

1-Phosphatidylinositol 4-Kinase

Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin.

ICV injections of streptozotocin (STREP) lower the glucose utilization of the brain and affect the cholinergic system. The present study was designed to evaluate whether STREP-treated rats have an impaired spatial discrimination performance in the Morris spatial navigation task. Performance in this task is sensitive to treatment with cholinergic antagonists. In contrast to young rats, middle-aged STREP-treated rats tended to have an impaired spatial discrimination performance in the Morris task at the end of training. In middle-aged STREP-treated rats, but not in control rats, spatial discrimination performance was associated with hippocampal choline acetyltransferase (ChAT) activity. The correlation between spatial discrimination performance in the Morris task and the decrease in hippocampal ChAT activity resembles the relation between cognitive and biochemical changes observed in Alzheimer's disease. Our findings suggest that STREP treatment of middle-aged rats may provide a relevant model for dementia.

Animals

Primitive reflexes in Parkinson's disease.

A standardised protocol for the examination of 15 primitive reflexes in which the amplitude and the persistence were scored separately, was applied to 25 patients with Parkinson's disease and an equal number of healthy matched control subjects. Most reflexes were found considerably more often in the patients than in the control subjects, especially the snout, the glabellar tap, and its variant, the nasopalpebral reflex. Only the mouth open finger spread reflex was present more often in the control subjects. For all reflexes except this last, the scores for amplitude and persistence of the reflexes for the control group never exceeded the scores for the patient group. Reflexes persisted more often in the patients than in the control subjects. Parkinsonism alone can explain a large number of primitive reflexes, irrespective of the severity or duration of the disease. In contrast, the number of reflexes was related more closely to cognitive scales. It is concluded that such reflexes may be helpful in diagnosing Parkinson's disease. In addition, a standardised protocol for eliciting and scoring is essential for the study of these reflexes in parkinsonism and other neuropsychiatric conditions.

Adult