In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria.

BACKGROUND: Antimicrobial peptides are components of the innate immunity that play an important role in systemic and oral health. OBJECTIVES: The antibacterial activity of the amphibian-derived K4 -S4(1-15)a antimicrobial peptide was tested against oral pathogens associated with caries and periodontitis and compared with the activities of the human-derived antimicrobial peptides LL-37 and dhvar4a. METHODS: Growth inhibition of planktonic bacteria was tested using standard microdilution assays. Live/Dead staining followed by confocal scanning laser microscopy (CSLM) was used to determine the bactericidal effect of K4 -S4(1-15)a on Streptococcus mutans attached to a glass surface or grown as biofilm. RESULTS: The cariogenic species S. mutans, Streptococcus sobrinus, Lactobacillus paracasei and Actinomyces viscosus were resistant to LL-37 found in the oral cavity. Porphyromonas gingivalis was the species most resistant to the three tested peptides. K4 -S4(1-15)a demonstrated the highest activity against the tested planktonic bacteria. In addition, K4 -S4(1-15)a was bactericidal to surface-attached S. mutans as well as to S. mutans biofilms grown in vitro. However, surface attachment increased S. mutans resistance to the antimicrobial peptide. CONCLUSIONS: Our results support growing evidence suggesting the use of antimicrobial peptides for prevention and treatment of oral disease.

CZT gamma camera for scintimammography.

A high performance prototype gamma camera based on the semiconductor radiation detector Cd(Zn)Te is described. The camera features high spatial resolution, high-energy resolution, a reduced dead space on the edge of the field of view, and a compact format. The camera performance was first examined by comparison of small field of view examinations with those from an Elscint SP6HR standard clinical gamma camera. The new camera was found to give equal or improved image quality. The camera was then used for a systematic phantom study of small lesions in a background as would be found in breast cancer imaging. In this study the camera was able to systematically detect smaller, deeper, and fainter lesions. The camera is presently being used in a clinical trial aimed to assess its value in scintimammography where previous limitations of image quality and detector size have restricted the use of the functional imaging techniques. Preliminary results from 40 patients show high sensitivity and specificity with respect to X-ray mammography and surgery.

Food-drug interaction: grapefruit juice augments drug bioavailability--mechanism, extent and relevance.

More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

Recommended micronutrient supplementation for institutionalized elderly.

A committee nominated by the Israel Ministry of Health examined the relevant literature and the local recommendations as well as the recommendations from other countries and suggested a daily micronutrient supplementation for institutionalized elderly living in institutions supervised by the Ministry of Health. The micronutrient preparatory, tailored for this population, is designed to contain about half the RDA for most of the vitamins and some microelements. Biotin and vitamins C, D and B12 as well as zinc, copper, chromium and molybdenum are suggested at a level higher than half the RDA, whereas fluorine, at a lower level. Major elements (calcium, magnesium and phosphorus) are excluded and should be supplied separately. Vitamin K and iron are also excluded. Fat-soluble vitamins should be microencapsulated. Micronutrient supplementation for institutionalized elderly is part of the Ministry of Health s balanced nutrition policy. The committee s recommendations are also applicable to the free-living elderly population.

[Micronutrient (vitamins and minerals) supplementation for the elderly, suggested by a special committee nominated by Ministry of Health].

The elderly tend to be at a higher risk for nutritional deficiencies and in particular for micronutrient deficiencies. A committee nominated by Ministry of Health examined the relevant literature and the local recommendations as well as the recommendations from other countries and suggested a daily special micronutrient supplementation for institutionalized elderly. The preparatory will contain about half the RDA for most of the micronutrients, except for fluorine that is recommended at a lower level and biotin, vitamins D, C, B12 as well as zinc, copper and molybdenum at a level higher than half the RDA. Major elements such as calcium, are not included in the preparatory and would be supplied separately when needed. Vitamin K and iron are excluded as well. The suggested preparatory composition, mg: vitamin A, 0.450; vitamin D, 0.015; vitamin E, 10; thiamin, 0.6 Pound riboflavin, 0.7; biotin, 0.030; pantothenic acid, 3; niacin, 8; vitamin C, 60; vitamin B6, 0.8; folic acid, 0.120; vitamin B12, 0.0024; choline up to 275; zinc, 8; copper, 0.9; fluorine, 0.5; manganese, 1.2; chromium 0.020; molybdenum, 0.045; selenium, 0.030; and iodine, 0.075. Fat-soluble vitamins should be microencapsulated. Micronutrient supplementation is part of Ministry of Health balanced nutrition policy. The committees recommendations are also applicable for the free-living elderly.

Subclinical hallucinations and delusions in nonpsychotic adolescents.

A number of studies have suggested that clinical populations of adolescents may report hallucinations and/or delusions without meeting criteria for a psychotic disorder. The purpose of this study was to provide information about the prevalence and symptom correlates of these subclinical hallucinations and delusions that occur in a nonpsychotic population of adolescents. Thirty-eight adolescents from a residential program and day treatment center were assessed with respect to hallucinatory experiences, ideas of reference, paranoid ideation, dissociative experiences, depressive symptomatology, and schizotypal cognitions. Results of this study indicated that 33% of the participants reported having experienced auditory hallucinations, and 24% reported having had delusional ideas. In addition, the results suggest that subclinical auditory hallucinations may have an especially strong relation with dissociative processes, whereas subclinical delusions appeared to be most strongly correlated with schizotypal thought processes. The results of this study begin to clarify the phenomenon of hallucinatory and delusional experiences in a nonpsychotic population.

Prenatal exposure to alcohol in adult rats: relationships between sleep and memory deficits, and effects of glucose administration on memory.

Previous studies show that prenatal exposure to alcohol results in sleep deficits in rats, including reductions in paradoxical sleep. Little is known, however, about the extent or duration of sleep impairments beyond the neonatal period. The present experiment examined effects of prenatal exposure on sleep in young adulthood. Three-hour, daytime sleep EEGs were obtained in 6-month-old female rats prenatally exposed to alcohol. Compared to isocaloric pair-fed and ad libitum control groups, the alcohol-exposed group showed reduced paradoxical sleep. Non-paradoxical sleep did not differ between groups. Concurrent deficits were obtained in radial arm maze, but not inhibitory (passive) avoidance, performance. One year later, at the age of 18 months, alcohol-exposed rats showed deficits in spontaneous alternation behavior which were reversed by administration of glucose (100 mg/kg). Deficits in paradoxical sleep at 6 months of age were highly correlated with deficits in spontaneous alternation behavior at 18 months of age, in individual, alcohol-exposed animals. These results provide the first evidence that prenatal exposure to alcohol results in selective and persistent deficits in sleep. They also show that measures of paradoxical sleep can predict impaired memory over a large portion of the life span, and suggest that glucose can attenuate memory deficits in this population.

Anxiety-like and depression-like behavior in Maudsley reactive (MR) and non-reactive (NMRA) rats.

1. Female MR ("anxious") and MNRA ("non-anxious") Maudsley rats were tested in the CSD behavioral conflict paradigm (anxiety-like measure) and also in the FST paradigm (depression-like measure). 2. As expected, MNRA rats accepted significantly more shocks in the CSD paradigm than did MR rats (i.e., MNRA rats were less "anxious"), MNRA rats also exhibited significantly less immobility in the FST procedure (i.e., MNRA rats were less easily made "depressed"). 3. When the data were pooled across the two strains, there was a significant correlation between CSD and FST behavioral scores; however, there was no significant correlation between these measures when the data from the two strains were evaluated separately. Multiple regression (independent variables of rat strain and CSD score, dependent variable of FST score) revealed a significant effect of rat strain, but not CSD score, on FST behavior. 4. The relationship of these findings to the apparent relationship between anxiety and depression in humans is discussed.

Electrophysiological characteristics of locus coeruleus neurons in the Maudsley reactive (MR) and non-reactive (MNRA) rat strains.

Extracellular single-unit recording techniques were used to evaluate the physiological and pharmacological characteristics of noradrenergic locus coeruleus (LC) neurons in urethane-anesthetized Maudsley reactive (MR) and non-reactive (MNRA) rat strains, a presumed genetic model for differences in 'anxiety'. LC neurons from MNRA rats were found to have a significantly higher basal discharge rate than LC neurons from either the MR or Sprague-Dawley (SD) rats. The discharge pattern of MNRA LC neurons also differed significantly from that of LC neurons from SD and MR rats, with LC neurons from MNRA rats exhibiting a burst-like pattern of discharge. Finally, MNRA LC neurons were significantly less sensitive to the inhibitory effects of i.v. clonidine on spontaneous activity.

Plasma concentrations of inorganic sulfate in Alzheimer's disease.

Recent reports have suggested that plasma concentrations of inorganic sulfate may be lower in patients with Alzheimer's disease (AD). We measured sulfate concentrations in 10 patients with AD and found an average concentration of 0.28 mM, which was not significantly different from the mean concentration in age-matched controls (0.32 mM) or young healthy controls (0.27 mM). These results indicate that plasma sulfate concentrations are not altered in AD and that previous reports suggesting altered metabolism of sulfur-containing xenobiotics in neurodegenerative diseases should be reevaluated.

Conflict behavior in Maudsley reactive and nonreactive rats: effects of noradrenergic neuronal destruction.

The present studies were designed to examine the effects of treatment with the noradrenergic neurotoxin N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine HCl (DSP4; 65 mg/kg, IP) on conflict behavior in the Maudsley reactive (MR) and nonreactive (MNRA) rat strains. In daily 10-min sessions, water-restricted rats were trained to drink water from a tube that was occasionally electrified; electrification was signaled by the presence of a tone (7-s duration; ISI = 30 s). Consistent with previous reports, the number of shocks accepted by rats of the MR and MNRA strains did not differ initially, but MNRA rats exhibited a dramatic increase in punished responding relative to their MR counterparts over the course of several weeks of conflict testing. This MR vs. MNRA strain difference in punished responding did not exhibit extinction following discontinuation of CSD conflict behavior testing for a period of 6 weeks. Whether it was administered after conflict training or before, DSP4 treatment did not reduce the MR vs. MNRA strain difference in conflict behavior; rather, DSP4 treatment tended to increase the magnitude of the MR vs. MNRA difference in conflict behavior. The effects of DSP4 on norepinephrine (NE) and 5-hydroxytrypamine (5-HT) concentrations in the pons medulla region were determined in one group of conflict-experienced MR and MNRA rats (35 weeks after administration) and in a second group of naive MR and MNRA rats (3 weeks after administration). There were no MR vs. MNRA strain differences in NE or 5-HT concentrations in vehicle-treated rats. DSP4 treatment significantly reduced NE, but not 5-HT, concentrations when compared to control values; rats that were sacrificed 3 weeks following DSP4 administration exhibited a greater NE depletion than did rats sacrificed 35 weeks after DSP4 administration. Finally, there were no significant correlations between pons medulla region NE concentrations and conflict behavior in either strain alone or when the data from the two strains were combined. The present results are not consistent with the hypothesis that the MR vs. MNRA strain difference in conflict behavior is the result of strain differences in brain NE function.

Maudsley reactive and nonreactive rats in the forced swim test: comparison in fresh water and soiled water.

Maudsley reactive (MR) and nonreactive (MNRA) and Sprague-Dawley (SD) male rats were tested for their immobility response in the forced swim test when the water was fresh or soiled by a rat of the same or other strain. For all strains, rats tested in soiled water were less immobile than rats in fresh water. The three strains did not differ as producers of soiling substance, but did differ in their response to it. The MR strain was least responsive, whereas the MNRA and SD did not differ from one another. These results support a previous study suggesting that MR rats are more immobile than MNRA rats in the forced swim test. The interpretation of these findings regarding the use of the Maudsley rat strains as an animal model for studying anxiety and/or depression is discussed.

Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats: performance in an operant conflict paradigm.

The present studies were designed to characterize the behavior of Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats in a modification of the Geller-Seifter operant conflict paradigm. Food-restricted (85% of free-feeding weights) female MR/Har and MNRA/Har rats were trained to lever press for food reinforcement in a multiple-schedule operant conflict paradigm. In the absence of a tone, a fixed ratio-30 (FR-30) schedule for reinforcement only was in effect (i.e., every 30th lever press resulted in the delivery of a 45-mg food pellet). During the presence of a tone, a fixed ratio-1 (FR-1) schedule of both reinforcement (food) and punishment (0.20 mA footshock applied for 500 ms) was in effect (i.e., each lever press resulted in both food and shock delivery). The tone periods were 27 s in duration and were presented on a variable interval (VI)-120-s schedule (approximately 20 tones/40-min session). Behavioral testing was conducted 5 days/week for 35 weeks. Initially, punished responding between the MR/Har and MNRA/Har rat strains did not differ dramatically. However, over the course of many weeks of conflict testing, rats of the MNRA/Har strain came to accept significantly more shocks than did subjects of the MR/Har strain. A direct examination of footshock sensitivity in these rats revealed that this difference in conflict behavior over time was not due to strain differences in shock sensitivity. The mechanism for this time-dependent difference in conflict behavior between the MR/Har and MNRA/Har rats remains undetermined.

Effects of combined acetylcholinesterase inhibition and serotonergic receptor blockade on age-associated memory impairments in rats.

We recently reported that post-training administration of serotonergic receptor antagonists attenuated the inhibitory-avoidance memory deficits normally exhibited by aged rats. In the present study, we determined whether a subeffective dose of the serotonergic type-2 receptor antagonist, ketanserin, would augment the facilitative effects produced by the acetylcholinesterase inhibitor, physostigmine, on memory in aged rats using the same task. The drugs were injected intraperitoneally alone, or in combination, immediately following training. Retention testing occurred 24 hours following training. A dose-dependent enhancement of memory was demonstrated as a result of the two treatment conditions (physostigmine 0.01-10.0 micrograms/kg, ketanserin 1.0 mg/kg + physostigmine 0.001-0.01 micrograms/kg). The facilitation of memory produced by the combined treatment was observed at doses well below those required to produce a similar effect when each drug was administered alone. The results provide additional evidence for an interaction between the cholinergic and serotonergic neurotransmitter systems in learning and memory, and may have important implications in the treatment of age-related memory impairments.

Effects of lesions of the central nucleus of the amygdala on anxiety-like behaviors in the rat.

The effects of lesions of the central nucleus of the amygdala on anxiety-like behaviors in the rat were determined using two animal models, the conditioned suppression of drinking (CSD) and defensive burying paradigms. For CSD conflict testing, water-restricted rats were trained to drink water from a tube that was occasionally electrified (0.25 mA); electrification was signaled by a tone. CSD test sessions were 10 min in duration and were conducted 4 days per week. After at least 3 weeks of conflict testing, both punished (30-40 shocks per session) and unpunished (10-12 ml water per session) responding had stabilized. Subjects then received bilateral electrolytic lesions of the central nucleus of the amygdala or sham lesions. After a 1-week recovery period, CSD conflict testing was reinstated and continued for 20 weeks. Amygdaloid-lesioned subjects accepted significantly more shocks than did sham controls. In addition, acute challenges with the benzodiazepine chlordiazepoxide (2.5-10 mg/kg, IP, 30-min pretreatment), the barbiturate phenobarbital (20 mg/kg, IP, 10-min pretreatment), and carbamazepine (10 mg/kg, IP, 10-min pretreatment) produced an increase in punished responding in both amygdaloid-lesioned and sham-treated subjects. Analysis of covariance (ANCOVA)-based adjusted means for the change in shocks received were not significantly different between the two groups. Following completion of the CSD studies, subjects were tested in the defensive burying paradigm. Although there was no significant difference between lesioned and sham-treated subjects on the percent of animals that exhibited burying, subjects with lesions of the central nucleus of the amygdala exhibited a significantly greater latency to initiate defensive burying.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular permeability and cognition in the aging rat.

Regional cerebrovascular permeability-capillary surface area products (rPS) and brain vascular space (BVS) were measured in aging, conscious, unrestrained Sprague-Dawley rats. Three groups of animals were examined: young-mature (6 months), middle-aged (12-14 months), and old (24-26 months) rats. Complex maze learning had been previously characterized in these same animals. Maze learning declined with age. Brain vascular space did not differ significantly with age in any brain region. However, small, but significant age-dependent decreases in rPS (25-33%) were observed. These decreases occurred mainly in the old animals in the basal ganglia and parietal cortex, and in the middle-aged and old rats in the olfactory bulbs. Significant and unexpected positive average correlations between brain permeability-capillary surface area products (PS) and learning errors occurred primarily in young rats and were attributable mainly to changes in 5 of 14 brain regions; hypothalamus, hippocampus, parietal cortex, septal area and superior colliculus. The higher correlations between maze learning errors and PS in young animals may indicate dynamic regulation of this cerebrovascular parameter which is lessened with aging. Average correlations between PS and cerebral blood flow also were determined and found to be generally small and not significant for most brain regions and age groups.

Systemic lupus erythematosus in a boy with chronic granulomatous disease: case report and review of the literature.

We describe a patient with X-linked chronic granulomatous disease (CGD) who developed systemic lupus erythematosus, which was characterized by photosensitivity, malar rash, glomerulonephritis, leukopenia, hypocomplementemia, antinuclear antibodies, and anti-double-stranded DNA antibodies, at age 3. The patient's mother is an asymptomatic carrier of CGD, and her other son (the patient's half-brother) also has CGD. Neither the mother nor the brother has clinical or serologic evidence of systemic lupus erythematosus. Previous cases of discoid lupus-like skin lesions have been reported both in carriers and in patients with CGD. Our patient represents the first reported case of an individual with convincing clinical, serologic, and pathologic evidence of systemic lupus erythematosus. The association between defective host defense mechanisms and autoimmune phenomena has been described previously in patients with Job's syndrome and in patients with B cell and T cell deficiency disorders, including the acquired immunodeficiency syndrome. The relationship between the known leukocyte defects in CGD and the pathogenesis of a lupus-like illness is unclear.

Effects of combined serotonin depletion and lesions of the nucleus basalis magnocellularis on acquisition of a complex spatial discrimination task in the rat.

The purpose of the present experiment was to determine the effects of lesions of cholinergic neurons originating from the nucleus basalis magnocellularis (NBM), alone or in combination with central serotonin depletion, on learning and memory in rats trained in the Stone 14-unit T-maze--a complex, positively-reinforced spatial discrimination task. Lesion of cholinergic neurons within the NBM was accomplished by bilateral infusion of ibotenic acid. Serotonin depletion was accomplished by the systemic administration of p-chloroamphetamine (PCA). The results show that PCA-induced serotonin depletion enhanced learning. This effect was completely prevented by NBM lesions, despite the fact that NBM lesions alone did not affect the performance of rats in this task. The results of this study support the view that the cholinergic and serotonergic systems may functionally interact in learning and memory processes. The significance of this interaction in the etiology and treatment of dementia should be further investigated.

Enhanced spatial discrimination learning in rats following 5,7-DHT-induced serotonergic deafferentation of the hippocampus.

Learning in rats trained in the Stone 14-unit T-maze, a complex, positively reinforced spatial discrimination task was assessed following cytotoxic (5,7-dihydroxytryptamine; 5,7-DHT) deafferentation of the serotonergic inputs to the hippocampus. Serotonergic deafferentation was accomplished by infusing the cytotoxin in to the fornix-fimbria/cingulum bundle. Lesioned rats reached criterion (i.e. learned) in significantly fewer trials and made significantly fewer errors throughout training than either vehicle-injected or sham-operated controls. This represents the first time that the effects of selective chronic destruction of serotonergic inputs to the hippocampus have been investigated. The present results provide, therefore, evidence in support of a neuromodulatory role for serotonin (5-HT) within the rat hippocampus in the mediation of the processes underlying learning and memory for this task. Other studies are, therefore, warranted in order to determine whether hippocampal 5-HT also plays a role in the mediation of the processes underlying learning and memory in other types of tasks.