Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status.

BACKGROUND: African-American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men. METHODS: Participants included 90 AA men with PCa undergoing treatment at Howard University Hospital (HUH) and 62 controls participating in HUH's free PCa screening program. We measured serum 25-hydroxy vitD [25(OH)D] and used the 98.2 item Block Brief 2000 Food Frequency Questionnaires to measure dietary intake of quercetin and other nutrients. Case and control groups were compared using a two-sample t-test for continuous risk factors and a Fisher exact test for categorical factors. Associations between risk factors and PCa risk were examined via age-adjusted logistic regression models. RESULTS: Interaction effects of dietary quercetin and serum vitD on PCa status were observed. AA men (age 40-70) with normal levels of serum vitD (>30 ng/ml) had a 71% lower risk of PCa compared to AA men with vitD deficiency (OR = 0.29, 95%CI: 0.08-1.03; P = 0.055). In individuals with vitD deficiency, increased dietary quercetin showed a tendency toward lower risk of PCa (OR = 0.91, 95%CI: 0.82-1.00; P = 0.054, age-adjusted) while men with normal vitD were at elevated risk (OR = 1.23, 95%CI: 1.04-1.45). CONCLUSION: These findings suggest that AA men who are at a higher risk of PCa may benefit more from vitD intake, and supplementation with dietary quercetin may increase the risk of PCa in AA men with normal vitD levels. Further studies with larger populations are needed to better understand the impact of the interaction between sera vitD levels and supplementation with quercetin on PCa in AA men.

Nicotine blocks quinpirole-induced behavior in rats: psychiatric implications.

RATIONALE AND OBJECTIVES: Because of known and imputed roles of dopaminergic and nicotinic cholinergic systems in a variety of neurological and neuropsychiatric disorders, combined neurochemical and behavioral methods assessments were made to study the intermodulatory roles of these neurochemical systems. METHODS: Rats were treated daily during postnatal ontogeny with the dopamine D2/D) agonist, quinpirole (QNP) HCl (1.0 mg/kg/day), for the first 3 weeks from birth. This priming process replicated previous findings of behavioral sensitization, manifested as hyperlocomotion, increased paw treading with jumping, and increased yawning. RESULTS: All effects were partially or totally blocked by acute treatment with nicotine (0.3 mg/kg, i.p.). The effects of nicotine, in turn, were partially or totally blocked by the nicotinic antagonist, mecamylamine (1.0 mg/kg, i.p.). In concert with these behavioral actions, QNP-primed rats displayed greater binding of [3H]cytisine in midbrain and cerebellum and greater [125I]alpha-bungarotoxin binding in hippocampus and striatum. CONCLUSIONS: Accordingly, these selective ligands for alpha4beta2 and alpha7 nicotinic receptors, respectively, demonstrate that nicotinic receptors are altered by dopamine D2/D3 agonist treatment of rats with primed dopamine receptors. We propose that nicotinic agonists may have a therapeutic benefit in behavioral disorders brought about by central dopaminergic imbalance.

Recurrent Meesmann's corneal epithelial dystrophy after penetrating keratoplasty.

PURPOSE: To characterize the histopathology of recurrent Meesmann's corneal epithelial dystrophy after penetrating keratoplasty. METHODS: Postmortem examination by light and electron microscopy of the eyes of an 84-year-old patient with Meesmann's dystrophy who underwent a penetrating keratoplasty in the right eye at age 74 years and a lamellar keratoplasty in the left eye at age 51 years. RESULTS: In the right eye, the characteristic features of Meesmann's dystrophy were demonstrated in both the donor and recipient corneas. The pathologic findings were limited to the corneal epithelium and included increased thickness, architectural disorganization, loss of cell polarity, increased amounts of intracellular glycogen, presence of intraepithelial microcysts containing degenerated cells, and in some cells, the presence of an electron-dense fibrillogranular material associated with disrupted cytoplasmic filaments. In the left eye, the corneal findings were consistent with but not specific for Meesmann's dystrophy. These included architectural disorganization, loss of cell polarity, presence of intraepithelial microcysts, and irregular thickening of the basement membrane in the donor cornea. CONCLUSION: Meesmann's corneal epithelial dystrophy is demonstrated to recur after penetrating keratoplasty. This finding suggests that the abnormalities that lead to the disease are localized to the corneal epithelial cells and not in the stroma, as previously proposed.

Adolescents' misinterpretation of health risk probability expressions.

OBJECTIVE: To determine if differences exist between adolescents and physicians in their numerical translation of 13 commonly used probability expressions (eg, possibly, might). DESIGN: Cross-sectional. SETTING: Adolescent medicine and pediatric orthopedic outpatient units. PARTICIPANTS: 150 adolescents and 51 pediatricians, pediatric orthopedic surgeons, and nurses. MEASUREMENT: Numerical ratings of the degree of certainty implied by 13 probability expressions (eg, possibly, probably). RESULTS: Adolescents were significantly more likely than physicians to display comprehension errors, reversing or equating the meaning of terms such as probably/possibly and likely/possibly. Numerical expressions of uncertainty (eg, 30% chance) elicited less variability in ratings than lexical expressions of uncertainty (eg, possibly). CONCLUSION: Physicians should avoid using probability expressions such as probably, possibly, and likely when communicating health risks to children and adolescents. Numerical expressions of uncertainty may be more effective for conveying the likelihood of an illness than lexical expressions of uncertainty (eg, probably).

Induction of Apoptosis and c-myc in L1210 Lymphocytic Leukemia Cells by Adenosine.

High concentrations of adenosine (Ado), when added to L1210 lymphocytic leukemia cells, resulted in apoptosis or programmed cell death. The apoptotic process was accompanied by distinct morphological changes including chromatin condensation and blebbing of plasma membranes. Extensive DNA fragmentation was correlated with Ado concentrations. Furthermore, apoptosis in these cells was preceded by an early but transient expression of c-myc proto-oncogene, and was not influenced by homocysteine thiolactone added to the cells. Since severe combined immunodeficiency (SCID) is associated with a deficiency of adenosine deaminase, leading to defects in both cellular and humoral immunity, Ado-induced apoptosis may thus be a contributing factor in the pathology of SCID. Copyright 1994 S. Karger AG, Basel

The shortened advanced course for Army physicians.

The Army uses a series of career courses to prepare officers for progressive assignments. These courses have not been widely utilized by Army physicians. To improve the military education of physicians, an abbreviated Advanced Course was developed by the Academy of Health Science. A study of this course by the physicians attending its first offering showed that 8 weeks was an appropriate length. Information is provided to help improve the course and encourage attendance by Army physicians. This course will likely become mandatory and will be a key element in the training of all Army physicians.

Behavioral effects of ethanol inhalation in rats.

Behavioral effects of ethanol inhalation were studied on two fixed-ratio (FR) liquid-reinforced schedules and a continuous reinforcement (CRF) schedule intracranial self-stimulation (SS) in rats using the inhalational behavioral chamber designed in our laboratory. In the FR-24 schedule ethanol caused a decrease of reinforcement rate at 161 ppm and higher concentrations. In the FR-50 schedule decreases of the rate were observed at 102 ppm and 203 ppm. In the SS behavior ethanol produced a decrease in the rate of reinforcement at 603 ppm and higher concentrations. In rats of this schedule, blood ethanol concentrations were measured to be 393 micrograms/ml and 545 micrograms/ml after exposure to 600 ppm and 1200 ppm of ethanol respectively. Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule. Thus ethanol inhalation could produce adequate blood concentrations so as to produce behavioral effects.

Effects of ethanol inhalation on EEG in rats.

Effects of ethanol on duration of stages of sleep-wake cycle and EEG power spectra were measured during a 2-h exposure in a dynamic inhalational chamber in rats. Rats were exposed to one of four graded concentrations (approx. 100, 400, 800 and 1600 ppm) of ethanol on different days. Ethanol was found to increase the duration of waking (W) with a decrease in duration of rapid eye movement (REM) sleep at 100 and 400 ppm. No effect was observed at 800 and 1600 ppm on the stages of sleep-wake cycle or at 100-1600 ppm on EEG power spectra from the somatosensory or visual cortices. Results indicate that ethanol administered by inhalation could produce arousal action at low doses, but did not have any effect on EEG power spectrum at the concentrations used.

Sensitivity of EEG in young rats to toluene exposure.

Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in young rats (30-53 days old) and compared to those in adult rats (63-77 days old). Rats were exposed to one of the three concentrations [low (108-111 ppm), medium (160-163 ppm), and high (407-432 ppm)] of toluene on different days. In tests on sleep-wake cycle, in the young animals the duration of the wake stage (W) was increased with decreases of rapid eye movement (REM) and non-REM (NREM) sleep during hr 1 and hr 2 of exposure to the low concentration. These effects were marked at the medium and the high concentrations. In adult rats, at the low concentration the increase of W and the decrease of REM were observed only at hr 1; however, at medium and high concentrations these changes of W and REM sleep were marked along with a decrease of NREM. Comparison of the changes of duration of different states in rats of two age groups showed that there was a significant difference in the increase of W and the decrease of NREM sleep in young rats at hr 2 of exposure to low concentrations only compared to those in adult rats. Tested on power spectrum in young rats during REM sleep recorded from the visual cortex, the power of delta waves increased at the medium and high concentrations and that of theta wave decreased at the high concentration during hr 2 of exposure compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of toluene exposure on the spontaneous cortical activity in rats.

Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in rats. Rats were exposed to one of six graded concentrations (110.6, 162.5, 432, 676, 1558, 2730 ppm) of toluene on different days. It was found that the duration of waking (W) was increased with a decrease in duration of rapid eye movement (REM) sleep even at 110.6 ppm. Duration of nonrapid eye movement (NREM) sleep was decreased with an increase of W and a decrease of REM sleep at 162.5 ppm. Dose-related effects were noted in higher concentrations. The power of delta frequency band was increased with a decrease of theta frequency band power at hr 1 of exposure to 676 ppm during REM sleep recorded from the visual cortex. The power of theta frequency band was also decreased at hr 2 of exposure at 432 ppm. During W and NREM sleep power spectra were not changed significantly. Results indicate that the changes of EEG are a sensitive measure of the effects of toluene on the central nervous system (CNS).

Rebound increase of basal cAMP level in NG108-15 cells during chronic morphine treatment: effects of naloxone and chloramphenicol.

The effects of morphine on the basal cAMP level in the neuroblastoma X glioma NG108-15 hybrid cell line have been studied. Morphine (10 microM) added to the incubation media at hr 0 caused a rapid and significant decrease in the cAMP level up to hr 1; the level then slowly returned to the control at hr 6, and gradually increased to its peak at hr 36, returning to the control at hr 60. These results provide the first evidence for a delayed rebound increase of cAMP during morphine treatment. Naloxone (10 microM) added at hr 0 concomitantly with morphine blocked the morphine-induced decrease in cAMP level at hr 1 and attenuated its increase at hr 36. However, when naloxone was added at hr 5.5, the cAMP level significantly increased at hr 6, and at hr 36 the cAMP level increase was the same as in the case of morphine alone. Furthermore when naloxone was added 0.5 hr prior to harvesting the cells at hr 6, 12, 24 and 36, the cAMP level showed an immediate increase at each time point up to about the same level as observed with morphine alone at hr 36. Chloramphenicol, a protein synthesis inhibitor (100 microM) itself caused little or no change in the cAMP level. Added 30 min before morphine, chloramphenicol decreased the morphine-induced rebound increase at hr 36 in a concentration-dependent manner without any significant effect on cAMP decrease at hr 1. However when chloramphenicol was added at hr 5.5, the morphine-induced rebound increase at hr 36 was also attenuated, thereby suggesting an involvement of macromolecular synthesis in the rebound increase of cAMP which may be used as a model for the development of morphine dependence.

Effect of morphine on self-stimulation in rats and its modification by chloramphenicol.

The effect of morphine was studied on self-stimulation (SS) behavior in rats implanted with bipolar electrodes in the posterior hypothalamus. A single dose (10 mg/kg) of morphine decreased SS responding within 10-20 min, reaching a minimum level between 20-40 min after which the responding gradually returned to normal. The SS responding then increased above the control level at 120-180 min postdrug, then slowly returned to normal, thus showing a rebound effect. The combination treatment with morphine (10 mg/kg) and chloramphenicol (50 mg/kg) on SS behavior produced an accentuation of the initial decrease in responding, which was prolonged before gradually returning to the control levels without showing any rebound effect. The data suggest that alterations in protein synthesis may underlie the suppressed excitatory effect of a high dose of morphine on SS behavior.

Effect of inhalation of xylene on intracranial self-stimulation behavior in rat.

The effect of the inhalation of xylene on intracranial self-stimulation behavior was studied in rats in a flow-through (dynamic) inhalational behavioral chamber. Rats were exposed successively to four graded concentrations (102, 192, 419 and 623 ppm) of xylene vapor during 2-hr sessions on different days. The rate of lever-pressing showed a dose-dependent decrease during exposure to 192, 419 and 623 ppm of xylene. The 4-hr exposure to the smallest concentration (106 ppm) of xylene failed to show any effect on self-stimulation behavior. During a 5-day 2 hr/day exposure, the decrease in response observed on the 1st day was further accentuated with a nadir on the 3rd day; from the 4th day onwards, the depressant effect was attenuated showing the development of tolerance.

Effect of xylene inhalation on fixed-ratio responding in rats.

The effect of xylene inhalation was studied on operant behavior under a fixed-ratio (FR24) schedule in rats. Experiments were performed while rats were being exposed to xylene vapor in an inhalational (flow-through) behavioral chamber. Rats were exposed successively to three graded concentrations (113, 216 and 430 ppm) of xylene vapor each for 2 hr in range-finding studies during 6 1/4-hr sessions. The reinforcement rate which is correlated with FR responding was shown to be decreased at hr 1, hr 3 and hr 5. However at hr 2, hr 4 and hr 6 the reinforcement rate in rats increased approaching the control levels, thereby indicating development of tolerance. When rats were exposed to one of the three graded concentrations of xylene for 2 hr on separate days, they also showed a decrease in the reinforcement rate at hr 1; development of acute tolerance was also noted in this schedule. Exposure to the lowest (98.5 ppm) level of xylene used during 5-hr sessions caused no significant decrease in the reinforcement rate. This study thus attempts to identify a minimum effective concentration of xylene and indicates the development of acute tolerance to behavioral effect of xylene.

An inhalational behavioral chamber.

An inhalational (flow-through) behavioral chamber has been designed and prepared in order to facilitate recording of the behavioral performance of a small experimental animal (e.g., rat and mouse) while the subject is being exposed to an inhalant (vapor or gas). The animal can be clearly viewed during behavioral performance inside the chamber, which consists of a cylindrical glass jar. The apparatus is made up of easily available materials (e.g., glass, metal, Teflon, etc.) that are not affected by usual industrial solvents. At the present stage of its development, three types of behavioral schedules can be performed within the chamber: schedules involving brain stimulation (e.g., self-stimulation, avoidance of aversive stimulations); liquid-reinforced schedules (e.g., fixed ratio, fixed interval, variable ratio, variable interval, differential reinforcement of low rates); shock avoidance (classical or continuous). The schedules can be microcomputer assisted. The device is suitable for study of behavioral pharmacology and toxicology of inhalants.

Behavioral and neurochemical effects of hydergine in rats.

Effects of various (20, 40 or 80 mg/kg; intragastric instillation) doses of Hydergine (dihydroergotoxine) were studied on the self-stimulation (SS) behavior (in young and old rats with electrodes implanted in the A10 area) and also on spontaneous motor activity (SMA) and stereotypy (ST) as well as on the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and gamma-aminobutyric acid (GABA) in discrete brain areas, such as caudate nucleus (CN), pons-medulla (PM) and diencephalon-midbrain (DM) in adult rats. Following Hydergine administration, SS and SMA showed a dose-dependent increase with peak effects occurring between 80-120 min and then decreased. ST was not induced at any dose. DA and NE levels in the DM also showed a dose-dependent increase at 90 min and then sharply decreased up to 120 min after drug administration. NE in the PM and DA in the CN showed a similar pattern, but to a smaller degree. GABA in the DM and CN showed marked increases up to 120 min, while 5-HT in the PM and DM showed steady declines during the same period. Thus it appears that the behavioral stimulant effects of Hydergine may be correlated to increase in NE and DA levels, particularly in the DM.

Nanosecond response ''gasket-type'' magnetic loop current monitor for relativistic electron beam current measurements.

A fast response magnetic loop current monitor has been developed to measure relativistic electron beam return currents. The monitor has a rise time of about a nanosecond and a high degree of symmetry with moderate sensitivity, variable from about 1 to 10 V/kA. This simple monitor, with a thickness of 0.254 mm or less, is thin enough to be placed between segments of return current path in the diode or drift tube regions, is insensitive to flashover, beam and plasma bombardment, and radiation effects, and measures net current, thus offering some advantages over conventional magnetic probes, since the main components are outside of the vacuum region. Design criteria, an equivalent circuit analysis, and typical calibration waveforms are presented. Experimental current measurements for a pinched electron beam diode configuration using both conventional magnetic probes and ''gasket-type''current monitors with the FX-75 relativistic electron beam accelerator are presented.