Biomedical subjects
Publications and source records attributed to S Rabinovitz.
The postinfancy period is crucial for normal brain development, providing subsequent optimal conditions for learning and cognition. Both iron deficiency and essential fatty acids deficiency may impair normal neurological development. This review examines the limited number of studies that have been performed in preschool children and offers a broader view of the relationships among nutrition, nutrients and cognition.
The major effects of essential fatty acids (EFA) on brain structure and functions are reviewed. EFA determine the fluidity of neuronal membrane and control the physiological functions of the brain. EFA is also involved in synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Since they must be supplied from the diet, a decreased bioavailability is bound to induce major disturbances. While the brain needs a continuous supply during the life span, there are two particularly sensitive periods-infancy and aging. EFA deficiency during infancy delays brain development, and in aging will accelerate deterioration of brain functions. In discussing the role of EFA two issues must be considered-the blood-brain barrier, which determines the bioavailability, and the myelination process, which determines the efficiency of brain and retinal functions.
BACKGROUND: Within the literature on quality of life (QoL), life satisfaction (LS) has emerged as a key variable by which to measure perceived well-being, which is referred to as subjective QoL. The LS self-reports of 93 residents with intellectual disability (ID) living in community-based residences were compared with reports about their LS completed by their staff and parents. METHOD: The residents were interviewed on their LS by social workers who did not belong to the staff of the interviewee's residence. The instrument used was the Life Satisfaction Scale (LSS). Staff and parents completed the short version of the LSS. RESULTS: Residents and staff's LS reports were positively correlated. However, significant differences were found between these two groups of informants when the residents were characterized as high functioning, had a low score in challenging behaviour, worked in an integrative employment setting and lived in an apartment. As opposed to staff/resident discrepancies, no differences were found between parents' and residents' LS reports. CONCLUSIONS: If residents cannot to be interviewed about their LS, then the parent is the preferred person to respond on behalf of the resident. The current study highlights the importance of including both objective measures (e.g. functional assessment characteristics) and subjective measures (e.g. LS) in order to get a better understanding of the QoL of people with ID.
The role of Cholecystokinin (CCK), a gut hormone and neuropeptide, in early learning was examined. Pairing a novel odor (presented away from the nest) with exogenously administered CCK (0.25 & 0.5 microg/kg IP) has been shown to produce a conditioned-odor preference in infant rats (Weller, A.; Blass, E.M. Behav. Neurosci. 104:199-206; 1990). This suggests that CCK can act as a positive unconditioned stimulus (UCS). In the present study the possibility that CCK mediates learning was examined in 12-day-old rats, using rewards that represent aspects of the dam and the nest. In Experiments 1 and 2, pups received the selective CCK1 receptor antagonist devazepide (600 microg/kg), the selective CCK2 receptor antagonist L365,260 (600 microg/kg), or vehicle. In a series of training trials, choosing a particular floor texture was rewarded by 20 sec. on a rug texture (experiment 1) or with maternal (feces) odor (experiment 2). In experiment 3, after administering devazepide (0, 600, or 1000 microg/kg) a novel odor was paired once with reunion of the pup with its dam. The dependent measure in all studies was the pup's relative preference toward the (tactile or olfactory) conditioned stimulus (CS), determined in preference tests. Conditioned preferences were evident in all experiments. The CCK receptor antagonists did not increase conditioned preference levels. L365, 260 (experiment 2) and devazepide (experiment 1) clearly blocked the appearance of the conditioned effect in one of the experiments. In addition, devazepide treatment eliminated the conditioned effect in the two other experiments, by increasing preference levels in the control groups. In summary, the results suggest that endogenous CCK mediates some aspects of the infant's acquisition of new associations. The role of the two receptor-subtypes appears to be different, depending on the context and the nature of the rewarding stimulus.
Dopamine depletion induced by administration of Ro4-1284 produces a condition of rapid and repeated eye blinking in rats. This condition mimics the human disorder, blepharospasm, which often accompanies parkinsonism and other dopamine deficiency disorders. When given a 3-week course of a compound (SR-3) developed from a specific ratio of two free polyunsaturated fatty acids - linoleic acid and alpha-linolenic acid - the eye blinking rate following administration of Ro4-1284 is reduced to saline and no drug control levels. These results suggest a favorable prospect for essential fatty acids in general, and SR-3 in particular, to provide an improved therapeutic option for the clinical management of benign essential blepharospasm.
A mixture of linoleic and alpha-linolenic acids (free non-esterified unsaturated fatty acids) administered for 3 weeks prior to injection of cortisol (10 mg/kg), or prior to immersion of rats in a 10 degree C saline bath, prevented elevation of blood levels of cortisol and cholesterol and deficits in Morris water maze spatial learning that usually accompany such stressful conditions. Differences from controls on all behavioural and biochemical measures were statistically significant (P < .05). It is proposed that induction of intense stress, and the associated increase in cortisol, cholesterol and other corticosteroids may damage hippocampal structures and help account for the cognitive decline witnessed in Alzheimer's disease and other age-related conditions. The modulation of these consequences by the fatty acid mixture may provide an alternative strategy for the study of stress markers and for the development of other intervention options in humans.
Major advances have been made in understanding the biochemistry of essential fatty acids (FA) and their interactions with metabolic pathways leading to the production of longer and more complex fatty acids and lipids. Less understood are the roles played by FA which are known to affect neurotransmitters, peptides, releasing factors, hormones, and a variety of physiological and cognitive processes. Based on empirical findings we propose that (a) FA exert a controlling function in the modulation of neuronal membrane fluidity, and (b) the critical factor in FA action and efficacy is not absolute level but rather the ratio between various groups of FA. This approach unifies the biochemical and cognitive results obtained from many different and unrelated fields of research.
Ro4-1284 (2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo[a] quinolizin-2-ol hydrochloride), a benzoquinolizine, is a potent dopamine depletion agent whose acute and chronic administration results in a (1) deterioration of learning in the Morris Water Maze and passive avoidance tasks, (2) decrease in locomotion and rearing, (3) intense hypothermia, and (4) decrease in the percentage of polyunsaturated fatty acids and an increase in the level of cholesterol in neuronal membranes. Pretreatment with a specific mixture of free polyunsaturated fatty acids prevents most of the behavioral, physiological, and biochemical effects of Ro4-1284 except for rearing. We propose that the dopamine-mediated functions tested in this study are dependent on the interaction of intact dopamine D1 and D2 receptors. Rearing, which is controlled only by dopamine D1 receptors, remained, therefore, unaffected. Our hypothesis is that SR-3 exerts its beneficial effects by normalizing the structure and function of the neuronal membrane and by restoring dopamine D2 receptor functions.
The role of fatty acids (FA) as a mediator and modulator of central nervous system activity in general, and peptides in particular, is only recently becoming understood. This paper reviews numerous findings concerned with the activity of fatty acids, particularly with their interaction with diverse neurochemical systems and their consequences for better understanding neurotransmitters, hormones and peptides. The effects include FA as precursors in the manufacture of neurochemical elements, including enzymes, neurotransmitters, and hormones. Of particular interest is the important changes in neuronal membrane composition that have been attributed to FA. Such changes may account for the changes in thermoregulation, learning, and other functions that accompany dietary manipulation of FA intake. While the total level of FA has been the object of many investigations, this report addresses the need to focus on the ratio of FA, especially alpha-linolenic/linoleic acid, which has been shown to be a critical factor in a number of research studies.
The neurochemical basis of sleep mechanisms (onset and maintenance) is still controversial although the phenomenon itself is known to be mediated by more than a single molecule. The list of suggested endogenous sleep substances is rather long, and there is no single 'sleep center' identified in the brain. The role of fatty acids, and essential fatty acids in particular, has been ignored in sleep research. This review proposes an integration of the current knowledge about the effects of fatty acids in sleep neurochemistry, wherein fatty acids are seen to exert a direct effect on neuronal membrane structure or indirectly on the dynamics of biochemical compounds (complex lipids, prostaglandins, neurotransmitters, amino acids, interleukins) necessary for the initiation and maintenance of sleep.
Previous studies have shown that chronic administration of SR-3 (a 1:4 mixture of alpha-linolenic and linoleic acid) affects spatial learning, thermoregulation, pain threshold and protection from seizures. The mode of action is unknown. One possible explanation is that the preparation induces changes in the fatty acids profile and in the cholesterol level in the neuronal membrane. This study used 15 independent groups of rats (n = 12) which were given either saline, mineral oil (vehicle) or SR-3 (25 mg/kg) for 0, 1, 2, 3, or 4 weeks. The learning performance was measured in the Morris Water tank and the fatty acids profile and the cholesterol level were examined by the GC method in synaptosomes obtained from the frontal cortex of the rats. SR-3 improved the learning performance and induced major changes in the neuronal membrane composition, such as an increase in the total level of fatty acids, an increase in the level of essential fatty acids and a decrease in the cholesterol level. Those changes occurred after 3 weeks of treatment. The biochemical variables can predict the behavioral variables but not vice versa. The changes in the neuronal membrane may result in a modification of the membrane fluidity, which may, in turn, enhance cognitive and neuropharmacological effects.
This study examined the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio of alpha-linolenic acids), on brain biochemistry and on learning deficits induced by injection of an agent that induces experimental allergic encephalomyelitis. Treatment with SR-3 caused a decrease in myelin and changes in the fatty acid profile of brain synaptosomes, and a learning deficit. Eighteen days of treatment with SR-3 reversed the biochemical and learning deficit significantly, but did not restore them to normal levels. We propose that, most probably, the main action of SR-3 is the modulation of the cholesterol level, which in turn causes the modulation of the fatty acid profile and enhances learning by allowing improved neuronal communication.
Because of the high prevalence of Chlamydia trachomatis in adolescent females and the high cost of chlamydia cultures, we evaluated the use of the direct fluorescein conjugated monoclonal antibody test (DFA) in diagnosing C. trachomatis in adolescent females. Chlamydia trachomatis was found in 37 (20.1%) of 184 cultures. The sensitivity of the direct smear as compared with the culture was 89% and the specificity was 99%. The results of recent studies of the DFA and chlamydiazyme tests are reviewed as well as the problems in comparing techniques.
This study was designed to compare the Ayres spatula/cytobrush combination with the Ayres spatula/cotton swab combination as to the quality of the Pap smear in adolescent females. We evaluated 111 Pap smears, of which 60 (54%) were from cotton applicators/spatula combination and 51 (46%) were from cytobrush/spatula combination. Seventy-nine percent of the specimens with the cytobrush showed good cellular yield, compared to only 50% of the specimens obtained with a cotton applicator (p less than 0.05). The adequate specimen rate for endocervical cell content was 68% for the cytobrush versus 56% for the cotton applicator (p = not significant). The adequacy rate was less for trainees than for attending physicians, but the difference was less marked for those using the cytobrush. The cytobrush does have some impact on improving adequacy rates for Pap smears. However, this study was unable to determine whether this is a cost-effective addition to the Ayres spatula or cotton swab. The problem of inadequate Pap smears deserves more scrutiny among various health care systems.
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This study evaluated the effects of an adolescent medicine rotation on paediatric residents' pelvic examination skills. Measurements were: self-evaluations pre- and post-rotation; nurse's evaluations of pelvic examination performance during the first and last week of the rotation; and patients' evaluations. The self-evaluation was also given at the start and at the end of the year to residents not taking the rotation. Twenty-four third-year residents were evaluated during the year. Eighteen subjects taking the rotation showed significant improvement post-rotation in the areas of competence, comfort, evaluation of training and importance to career, while the six residents not taking the rotation showed no change. The nurse's evaluation of the pelvic examination showed increases in comfort level, skill, awareness of adolescents' feelings, and ability to explain and reassure. Patient ratings were high at the beginning of the rotation and showed no significant change post-rotation. An adolescent medicine rotation significantly improved pelvic examination skills as assessed by self-ratings and a nurse's evaluation. A rotation in adolescent medicine can play a crucial role in developing gynaecological skills in paediatric residents.
This study evaluated the effects of an adolescent medicine rotation on the attitudes and skills in the care of adolescents of third-year pediatric residents and medical students. Competence, comfort, and prior training in four areas were assessed by a self-evaluation questionnaire. Ratings were made at the start of the year, prerotation, and post a four- to six-week rotation. Residents not taking the rotation were rated at the beginning and end of the year. In addition, pelvic-examination skills were assessed by the clinic nurse and by the patients during the first and last week of the rotation. There were no significant changes in those not taking the rotation. In those residents taking the rotation, there was no change from beginning of year to prerotation, but there were significant changes after the rotation. Only those residents taking the rotation indicated an increase in liking adolescents. Pelvic examination skills were rated significantly higher during the last week of the rotation by the nurse and patients. A one-year follow-up study continued to show significantly higher scores in those residents taking the rotation. An adolescent medicine elective may significantly improve medical students' and residents' self-assessed levels of competence, comfort, and training in adolescent health care and pelvic examination skills.
In addition to commonly advertised hazards of obesity contributed by excess dietary fat, evidence of alterations in brain chemistry and structure are well documented. This brief review examines the role of nutrients, minerals and certain lipids, primarily the essential fatty acids (FA), that are beneficial to the maintenance of good health and that may offer therapeutic options by dietary supplementation. The review also considers the damaging effects of stress, especially in pre-existing conditions of obesity and diabetes, as studied in both animals and humans. The main focus of this brief review is to examine the effects of a high fat diet on stress and the immune system with particular emphasis on brain and cognitive function.