Prevalence,Cognitive and Socio-Demographic Determinants of Prostate Cancer Screening

Screening may be effective for reducing deaths due to prostate cancer. The aim of this study was determine the prevalenceand determinants influencing prostate cancer early detection behaviors based on the theory planned behavior (TPB).In this cross-sectional study, conducted in the west of Iran, a total of 250 men aged 50 to 70 years old were randomlyselected to participate. Of these, 200 (80%) signed the consent form and voluntarily agreed to take part. A structuredquestionnaire based on TPB constructs was applied for collecting data by interview. Analyses were conducted withSPSS version 16 using bivariate correlations, and logistic and linear regression. Some 26.5% of the participantsdemonstrated prostate cancer early detection behavior. Age higher than 60 (OR: 5.969), academic education (OR: 2.904),number of family members more than four (OR: 3.144), and knowledge about prostate cancer (OR: 3.693) were themost influential predictive factors for early detection behavior. Furthermore, among the TPB constructs, attitude(OR=1.090) and subjective norms (OR=1.280) were the most influential predictors. Attitude, subjective norms, andperceived behavioral control accounted for 43% of the variation in the outcome measure of the intention to screenfor prostate cancer (adjusted R squared= 0.43, F= 49.270 and P < 0.001). Designing and implementation programs toincrease positive attitudes and encourage subjective norms towards prostate cancer screening behavior may be usefulfor promotion of early detection.     

l-Deprenyl (selegiline) limits the repetitive firing of action potentials in rat hippocampal CA1 neurons via a dopaminergic mechanism

The effects of l-deprenyl (selegiline), a highly selective monoamine oxidase type B (MAO-B) inhibitor, on cell excitability of rat hippocampal CA1 neurons were examined in slice preparations using intracellular recording techniques. Superfusion of l-deprenyl (10 and 20 μM) reversibly limited the repetitive firing (RF) of action potentials elicited by injection of depolarizing current pulses (100 ms) into the pyramidal cells. At a concentration of 1–50 μM, l-deprenyl did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons. The limitation of RF by l-deprenyl (20 μM) was accompanied by the reduction of the maximal rate of rise (V?_max) of the action potentials in a non-voltage-dependent manner. In 80% of recorded cells, application of l-deprenyl (20 μM) produced an increase in the amplitude and duration of afterhyperpolarization (AHP). The limitation of l-deprenyl on RF was mimicked by other MAO-B inhibitors, pargyline and 4-phenylpyridine. In addition, the ability of l-deprenyl to limit RF was not observed in the hippocampal CA1 neurons taken from dopamine (DA)-depleted rats. Moreover, we also observed that the l-deprenyl-induced limitation of RF was specifically antagonized by (±)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF-83566, 5 μM), a selective D₁ dopaminergic receptor antagonist. However, the D₂ dopaminergic receptor antagonist, sulpiride (5 μM), had no effect on l-deprenyl's action. These results indicate that the MAO-B inhibitory ability leading to an increase of the dopaminergic tone in the hippocampus is involved, at least in part, in the l-deprenyl-induced reduction of neuronal excitability in the CA1 region of rat hippocampus and that the D₁ dopaminergic receptor is involved in l-deprenyl's action. © 1997 Elsevier Science B.V. All rights reserved.     

Distribution of glutamate receptor subunits in the primate temporal cortex and hippocampus

The distribution of subunits for the N-methyl-d-aspartate (NR1, NR2A/B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (GluR1, GluR2/3, GluR4) and low affinity kainate (GluR5/6/7) ionotropic glutamate receptors was examined by immunocytochemistry in the temporal cortex and hippocampus of the rhesus macaque (Macaca mulatta). Neurons expressing NR1, NR2A/B, GluR2/3, and GluR4 subunits were widely distributed in all of the cortical layers but the overall density of the GluR4-immunopositive neurons was very low. Neurons expressing the GluR1 subunit were found predominantly in cortical layers V and VI while those expressing the GluR5/6/7 subunits were concentrated in layer V and were readily distinguishable by the thick elongate shape of their primary apical dendrites. Subcellular differences in the immunostaining pattern were also noted between the different glutamate receptor subunits. NR1 and NR2A/B immunoreactivity was most pronounced in somatic and primary dendritic compartments and to a lesser extent in cortical and hippocampal molecular layers. GluR1 immunoreactivity was more intense than GluR2/3 in the hippocampal molecular layers whereas GluR4 was undetectable. GluR5/6/7 immunoreactivity was very intense in the dentate molecular layer, and the CA1 pyramidal cells had a subcellular distribution of GluR5/6/7 that was similar to the cortical neurons. Overall, the distribution patterns of the different glutamate receptor subunits was identical in animals that had been ovariectomized and in ovariectomized animals that had subsequently undergone estradiol or estradiol/progesterone hormone replacement. Taken together, these findings demonstrate a differential spatial arrangement of glutamate receptor subunits in the primate temporal cortex and hippocampus, which may have functional significance for the integration of excitatory inputs to these areas. Furthermore, they show that in adult macaques, sex steroids do not play a major role in determining the distribution patterns of these receptor subunits.     

Whole-body kinetics and dosimetry ofl-3-[123I]iodo-α-methyltyrosine

The synthetic amino acidl-3-[¹²³I]iodo--methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370–550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%±11.5% at 1.5 h p.i., 63.0%±15.7% at 3 h p.i. and 74.6%±9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.     

Involvement of nitric oxide in human transient lower esophageal sphincter relaxations and esophageal primary peristalsis

Background & Aims: Nitric oxide (NO) is well accepted as an inhibitory neurotransmitter in the gastrointestinal tract; however, its role in the triggering of transient lower esophageal sphincter relaxations (TLESRs) in humans remains to be determined. Therefore, the effect of N^G-monomethyl-L-arginine (L-NMMA), a specific NO synthase blocker, on gastric distention–induced TLESRs was investigated. Methods: Esophageal manometry was performed using a perfused sleeve assembly. The effect of L-NMMA was evaluated on water swallow–evoked primary peristalsis (n = 8; single-blind, placebo-controlled) and on the rate of TLESRs during gastric distention (n = 8; double-blind, placebo-controlled). Results:L-NMMA increased the amplitude of peristaltic pressure waves in the distal esophagus and increased peristaltic velocity in the proximal esophagus. In contrast, L-NMMA had no effect on basal lower esophageal sphincter pressure, nadir pressure, duration, and area under the curve of lower esophageal sphincter relaxation. L-NMMA significantly inhibited the increase in TLESRs during gastric distention. L-NMMA also increased the intraballoon pressure during distention. Conclusions: NO is one of the neurotransmitters involved in the reflex arc mediating the triggering of TLESRs. NO is involved in the timing of human esophageal peristalsis and may exert a tonic inhibition on the proximal stomach.GASTROENTEROLOGY 1998;115:1374-1380     

Trihexyphenidyl Potentiation ofl-DOPA: Reduced Effectiveness Three Years Later in MPTP-Induced Chronic Hemiparkinsonian Monkeys

The effects of a combination of trihexyphenidyl andl-DOPA methyl ester given i.m. were studied 3–5 years after MPTP induced hemiparkinsonism in five female adultMacaca nemistrinamonkeys. Three years later, these studies were repeated to determine if the drug combination was equally effective. Although the combination of trihexyphenidyl andl-DOPA produced potentiation in both studies, 3 years later it was quantitatively less. This was due primarily to the reduced effectiveness ofl-DOPA methyl ester in a dose of 12.5 mg/kg i.m. Even though the combination was less effective in subsequent years, the animals continued to show the same clinical signs of hemiparkinsonism. Reduced effectiveness of the drug combination does not appear to be due to a lessening of MPTP-induced hemiparkinsonism, but rather to the reduced effectiveness ofl-DOPA.     

Antisense mapping of opioid receptor clones: effects upon 2-deoxy-d-glucose-induced hyperphagia

Antisense oligodeoxynucleotides (AS ODNs) directed against exons 1 and 2 of the MOR-1 clone significantly and markedly reduced (81–93%) hyperphagia induced by the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG) across a 4 h time course. AS ODNs directed against exons 3 or 4 of the MOR-1 clone had a more limited (1–2 h) duration of action upon 2DG-induced hyperphagia. 2DG-induced hyperphagia was significantly reduced by AS ODNs directed against exon 2 (44–51%), but not exons 1 or 3 of the KOR-1 clone across a 4 h time course. Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective. These data provide further converging evidence for the roles of primarily mu, but also kappa₁ and kappa₃ opioid receptors in mediating the hyperphagic effects of glucoprivation.     

Effects of Central Injection of Kyotorphin and l-Arginine on Oxytocin and Vasopressin Release and Blood Pressure in Conscious Rats

Intracerebroventricular (ICV) administration of an inhibitor of nitric oxide synthase (NOS) increases oxytocin but not vasopressin secretion, in dehydrated rats [38]. Surprisingly, central injection of l-arginine, the substrate for NOS, caused a similar effect. Kyotorphin (l-tyrosyl-l-arginine), a dipeptide formed from l-arginine by kyotorphin synthetase in the brain may mediate this magnocellular response. Therefore, the dose and time responses of hormone release were compared following ICV injection of kyotorphin and l-arginine to conscious rats that were normally hydrated or deprived of water for 24 h. In water-sated rats, both l-arginine and kyotorphin increased blood pressure and plasma glucose levels coincident with elevating circulating levels of oxytocin, but not vasopressin. In dehydrated animals, both l-arginine and kyotorphin increased plasma oxytocin levels with a similar time course but only kyotorphin decreased vasopressin release. d-arginine, like l-arginine, stimulated secretion of oxytocin, indicating a nonstereospecific effect. A kyotorphin receptor antagonist (l-leucyl-l-arginine) given ICV to dehydrated animals elevated plasma oxytocin and prevented the decrease in vasopressin levels after kyotorphin. Thus, kyotorphin, but not l-arginine, appears to attenuate release of vasopressin either directly from magnocellular neurons or indirectly via modulating compensatory reflexes activated by the pressor response. On the other hand, an excess of l-arginine and kyotorphin within the CNS may mimic the stress response by augmenting release of oxytocin and activating the sympathetic nervous system to increase blood pressure and plasma glucose levels.     

Advances in the molecular characterization of tryptophan hydroxylase

The neurotransmitter serotonin has been implicated in numerous physiological functions and pathophysiological disorders. The hydroxylation of the aromatic amino acid tryptophan is rate-limiting in the synthesis of serotonin. Tryptophan hydroxylase (TPH), as the rate-limiting enzyme, determines the concentrations of serotonin in vivo. Relative serotonin concentrations are clearly important in neural transmission, but serotonin has also been reported to function as a local antioxidant. Identification of the mechanisms regulating TPH activity has been hindered by its low levels in tissues and the instability of the enzyme. Several TPH expression systems have been developed to circumvent these problems. In addition, eukaryotic expressions systems are currently being developed and represent a new avenue of research for identifying TPH regulatory mechanisms. Recombinant DNA technology has enabled the synthesis of TPH deletions, chimeras, and point mutations that have served as tools for identifying structural and functional domains within TPH. Notably, the experiments have proven long-held hypotheses that TPH is organized intoN-terminal regulatory and C-terminal catalytic domains, that serine-58 is a site for PKA-mediated phosphorylation, and that a C-terminal leucine zipper is involved in formation of the tetrameric holoenzyme. Several new findings have also emerged regarding regulation of TPH activity by posttranslational phosphorylation, kinetic inhibition, and covalent modification. Inhibition of TPH byl-DOPA may have implications for depression in Parkinson’s disease (PD) patients. In addition, TPH inactivation by nitric oxide may be involved in amphetamine-induced toxicity. These regulatory concepts, in conjunction with new systems for studying TPH activity, are the focus of this article.