Effects of buprenorphine and Ro 15-4513 on delayed death and brain beta-endorphin levels in rats treated with cocaine or cocaine-ethanol

The present study was aimed at elucidating the relationship between brain beta-endorphin, which was estimated by the immunofluorescence method, and fatal drug toxicities due to cocaine and combined cocaine-ethanol administration, including the late fatal toxicities clinically noted. beta-endorphin is an endogenous opioid peptide, and its secretion has been suggested to be influenced by physiological stresses. Furthermore, since protection against these fatal toxicities has been previously reported to be provided by buprenorphine (a ligand for opioid receptors) and Ro 15-4513 (a ligand for benzodiazepine receptors), this study also focused on the relationship between the effects of these two ligands and the changes in brain beta-endorphin immunoreactivity. In the fatal toxicity study, a toxic dose (75 mg/kg, i.p.) of cocaine combined with and without ethanol (3 g/kg, i.p.) was administered to the rats, with and without buprenorphine (0.25, 0.5, 1 mg/kg, i.p.) or Ro 15-4513 (5, 10, 15 mg/kg, i.p.). All of the deaths that occurred in these animals were divided into two groups: early deaths with early toxic symptoms in which the drugs were detected in the tissue samples, and late deaths with late toxic symptoms in which no drugs were detected in the samples. Without the administration of buprenorphine or Ro 15-4513, the frequency of late deaths was higher in the cocaine group as compared to the cocaine-ethanol group. The total mortality rate was effectively attenuated by treatment with 0.25 mg/kg buprenorphine or 10 mg/kg Ro 15-4513. Following treatment with 1 mg/kg buprenorphine or 15 mg/kg Ro 15-4513, the frequency of late deaths was significantly enhanced in the cocaine group. The brain and liver cocaethylene concentrations were also attenuated in those groups in which the total mortality rates were attenuated. In the brain beta-endorphin immunoreactivity study, the number of beta-endorphin immunoreactive nerve cells at the arcuate nucleus was counted at 3 minutes or 24 hours after the drug treatment. At 3 minutes after the drug treatment, the number of weakly immunoreactive cells with photographic light absorption values greater than 50% was enhanced in the groups in which the frequency of late deaths had been increased. In the cocaine-ethanol groups treated with buprenorphine or Ro 15-4513, this enhancement of weakly immunoreactive cells was observed when the total mortality rate was increased, regardless of the type of death. At 24 hours after the drug treatment (50 mg/kg cocaine), an enhancement of the weakly immunoreactive cells only was observed in all of the groups in which the occurrence of toxicities had been enhanced, regardless of the type of toxicity. Therefore, it can be concluded that the enhancement of total brain beta-endorphin immunoreactivity was closely correlated with the increase in the frequency of total fatal toxicities, and that the enhancement of weakly immunoreactive cells was closely correlated with the increase in the frequency of delayed fatal toxicities.     

Effects of calcium channel entry blockers on cocaine and amphetamine-induced motor activities and toxicities

The effects of calcium channel entry blockers on cocaine and amphetamine-induced behavioral responses were investigated. Cocaine and amphetamine produced dose-dependent increases in locomotor activity and stereotyped behavior with a maximum response at 40 and 1.2 mg/kg, respectively. The 1,4-dihydropyridine nimodipine and the benzothiazepine diltiazem were more effective in inhibiting cocaine (20 mg/kg)-induced responses than amphetamine (0.6 mg/kg)-induced responses. At doses of cocaine and amphetamine that caused seizures and death, nimodipine, nitrendipine and diltiazem did not offer any protection; rather, they potentiated the toxicities produced by these psychomotor stimulants.     

Self-ideal congruence as an index of adjustment.

"A test of the theoretical assumptions and the methods upon which the conventional Q sort tests was made using several criteria of adjustment. The results tended to support the theoretical assumptions underlying the Q sort as currently utilized. Although certain criticisms of the procedures involved are not thereby completely invalidated, it would appear that they are not sufficiently serious to justify abandoning either the method or the assumptions supporting the method." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiac change as an index of attention.

Conducted a study with undergraduates in which 7 experimental Ss clinically evaluated segments of a therapy protocol on the basis of specific verbal cues, and 9 controls made the same evaluation with no awareness of the clues. All Ss were monitored for heart rate while listening to the protocol and while making their judgments. All Ss showed lower and less variable heart rate during periods when they were listening to the clinical segments than during periods when they were making a clinical decision. The experimental group showed greater awareness of the verbal clues, but presence of clue was not associated with change in either mean or variability of heart rate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diastolic pressure as an index of salt sensitivity

This paper analyses the association between blood pressure and sodium excretion in 3975 individuals aged 20-74 years, selected in a probability sample survey of private households carried out in Rio Grande do Sul, Brazil. Sodium and creatinine titrations were performed in casual urine samples collected at the time of BP measurements. A subsample of 611 subjects provided 24 h urine collections. The regression slopes of systolic pressure on sodium excretion increased when diastolic level was higher. At the lowest levels of diastolic pressure the slope did not differ significantly from zero. The adjusted correlation coefficient then rose progressively to a maximum of +0.41 at diastolic pressures of 95-99 mmHg. Strikingly, at diastolic pressures of > or = 100 mmHg, there was no longer any significant association between systolic pressure and sodium excretion. These results could explain some earlier contradictory findings concerning the role of salt intake in hypertension and provide estimates of expected reduction on the prevalence of hypertension in each diastolic pressure group following a reduction on salt intake of a population.     

Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium-exposed rats following acute or chronic intraperitoneal administration of cocaine

We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracellular domain of GactRIIB contains two serine kinase consensus sequences, DFKSRN and GTRRYMAPE, in agreement with the reports in other vertebrates that serine/threonine phosphorylation is involved in activin signal transduction. The identity of GactRIIB was confirmed by transient expression in the COS cells followed by activin binding. Iodinated human activin A bound to the GactRIIB-transfected cells and the binding could be completely inhibited by unlabeled activin. Affinity labeling revealed a band of about 85 kDa, which is in agreement with the reported type II receptors in other vertebrates. Together with the fact that activin is expressed in the goldfish ovary, the cloning of activin receptors from the ovary suggests paracrine and autocrine roles for activin in the goldfish ovarian functions.     

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.     

Food preferences as an index or orality.

A self-report questionnaire dealing with food preferences (Food Preference Inventory—FPI) was proposed as a measure of Ss' contemporaneous position in respect to oral-passive vs. oral-sadistic involvement. The measure was pretested and through an item analysis found to be internally consistent enough to be utilized. The questionnaire was expanded and retested on new Ss to guarantee its stability and to increase its discriminatory potential. Finally it was subjected to validation by contrasting the scores of a group of Ss thought to be high on oral passivity (alcoholics) vs. a normal control group and by correlating it with their orality trait scores. The FPI was found to be fairly reliable and yielded data in agreement with the 2 validation predictions. It was concluded that food preferences as measured by the inventory offer a valid means of assessing an individual's position in regard to orality. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain metastases as the only manifestation of an undetected primary tumor

BACKGROUND: The prognosis of patients with brain metastasis as the only manifestation of an undetected primary tumor generally is considered to be poor. Therefore, most treatment is palliative. The authors reviewed the clinical outcomes and treatment results of patients presenting with brain metastasis from an undetected primary tumor at The University of Texas M. D. Anderson Cancer Center. METHODS: Between 1977-1996, 220 patients were referred to the study department for the treatment of brain metastasis from an undetected primary tumor. The patients' records were reviewed to identify those for whom brain metastasis was the only manifestation of the primary tumor. The majority of patients were excluded from the current analysis because extracranial metastasis also were present. Thirty-nine patients qualified for this retrospective review. The level of neurosurgical excision varied, but all patients received radiotherapy. Tumor control in the brain and survival were analyzed by various tumor-related and treatment-related factors. RESULTS: In 31 patients, the brain metastasis were adenocarcinomas, whereas the remaining patients had tumors of various other histologies. In 12 patients, the primary tumor eventually was found, most commonly in the lung. The median survival time for all patients was 13.4 months. Overall survival rates (OS) at 1, 3, and 5 years were 56%, 19%, and 15%, respectively. Intracranial disease control was 72% at 5 years. Patients who received gross total resection (GTR) and radiotherapy had significantly better OS than patients who received radiotherapy alone. The OS of patients whose primary tumor was identified was similar to that of patients in whom the primary tumor remained occult. CONCLUSIONS: Brain metastasis as the only manifestation of an unknown primary tumor is a distinct clinical entity. The prognosis for patients with this presentation is better than that of patients with brain metastasis in general. Although the majority of patients die of extracranial disease, a few will achieve long term survival. Treatment to the brain is effective in controlling local disease; aggressive treatment with GTR and radiotherapy is recommended.     

Verbal imprecision as an index of knowledge in transition.

Children can be verbally imprecise when they are learning, but this phenomenon is not well documented. Verbal imprecision, anecdotally referred to as hemming and hawing, may be indexed by restatements, comments on one's lack of knowledge, deletions of sentence constituents, and pauses. The authors examined whether they could quantify indexes of verbal imprecision and use them to predict changes in problem-solving performance. Four types of verbal imprecision were found to predict improved performance. Results were used to make inferences about processes of knowledge change. In particular, evidence suggests that adopting a new approach and rejecting an old one may be independent, and ordered, processes. Although others have drawn similar conclusions, using verbal imprecision as the data source is a relatively unique and readily accessible method for lending support to this model of knowledge change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Random number generation as an index of controlled processing.

Random number generation (RNG) is a functionally complex process that is highly controlled and therefore dependent on Baddeley's central executive. This study addresses this issue by investigating whether key predictions from this framework are compatible with empirical data. In Experiment 1, the effect of increasing task demands by increasing the rate of the paced generation was comprehensively examined. As expected, faster rates affected performance negatively because central resources were increasingly depleted. Next, the effects of participants' exposure were manipulated in Experiment 2 by providing increasing amounts of practice on the task. There was no improvement over 10 practice trials, suggesting that the high level of strategic control required by the task was constant and not amenable to any automatization gain with repeated exposure. Together, the results demonstrate that RNG performance is a highly controlled and demanding process sensitive to additional demands on central resources (Experiment 1) and is unaffected by repeated performance or practice (Experiment 2). These features render the easily administered RNG task an ideal and robust index of executive function that is highly suitable for repeated clinical use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrodermal activity as an index of arousal in schizophrenics.

Notes that previous reviews of research utilizing electrodermal activity as an index of arousal in schizophrenia have found no consistent differences between schizophrenics and normals, although other psychophysiological measures have shown chronic schizophrenics to be more aroused. A more detailed look at the electrodermal research, however, reveals that consistent results have been reported for 2 aspects of electrodermal activity: (a) habituation of responses or levels during periods of minimal stimulation (e.g., tones and lights of low intensity), and (b) frequency of spontaneous electrodermal responses regardless of stimulus conditions. Both of these measures appear to reflect arousal and yield results indicating that chronic schizophrenics are overaroused. (36 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human placental morphology as an index of features of maternal-fetal relationships

Principle possibilities of the complex evaluation of the mother-fetus exchange were studied by means of morphological investigations of the human placenta in normality, in vesicular mole, late toxicoses, hemolytic disease of newborns and malformations of the fetus. The investigation of the ratio of the villi of different size, deposition of fibrinoid on their surface, the change of the amount of cytotrophoblastic elements, cells of Kaschenko-Hofbauer and the polymerity of the basic substance are of diagnostic value. The authors propose the basal lamina of the placenta to be included into the scheme of the examination of placenta.     

Calculation of the systolic time as an index of thyroid performance

Two methods for determining some features of cardiovascular behaviour in dysthyroidism are compared: time of appearance of the femoral sphygmic wave (as an expression of the cardiovascular response to thyroid hormones); systolic times, particularly tension time (as an expression of the contractile function of the myocardium only). Results in 52 euthyroid, hyperthyroid and hypothyroid subjects showed that systolic times (especially tension time) are more accurate and more discriminating in the assessment of thyroid performance. Measurement of this interval is thus proposed as an index for the appraisal of myocardial contractility in dysthyroidism, and as an additional means of evaluating thyroid performance.     

Heart rate variability as an index of regulated emotional responding.

The study of individual differences in emotional responding can provide considerable insight into interpersonal dynamics and the etiology of psychopathology. Heart rate variability (HRV) analysis is emerging as an objective measure of regulated emotional responding (generating emotional responses of appropriate timing and magnitude). This review provides a theoretical and empirical rationale for the use of HRV as an index of individual differences in regulated emotional responding. Two major theoretical frameworks that articulate the role of HRV in emotional responding are presented, and relevant empirical literature is reviewed. The case is made that HRV is an accessible research tool that can increase the understanding of emotion in social and psychopathological processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facial EMG as an index of affective response to nicotine.

Negative affect reduction has been postulated to be a key feature of cigarette smoking. In the present study, facial electromyography (EMG), heart rate (HR), and skin conductance response (SCR) were used to evaluate the affective significance of acute nicotine administration and overnight withdrawal. Smokers (N = 115) attended four 90-min laboratory assessment sessions scheduled approximately 3 days apart. The sessions provided a complete crossing of 2 prelaboratory deprivation conditions (12-hr deprived vs. nondeprived) with 2 drug conditions (nicotine vs. placebo nasal spray). During each session, smokers viewed affective slides while facial EMG, HR, and SCR were recorded. Results indicated that for women, nicotine nasal spray resulted in lower corrugator EMG activity during both smoking-deprived and nondeprived sessions, compared with placebo. However, nondeprived women also showed an increase in zygomaticus EMG when given nicotine compared with placebo spray, whereas smoking-deprived women demonstrated a decrease in the zygomaticus response to nicotine compared with placebo. With men, nicotine also appeared to lower corrugator during deprivation, but not nondeprivation, compared with placebo spray, though the contrast only approached significance. With zygomaticus EMG, nicotine spray decreased men's zygomaticus responding during nondeprivation but not during deprivation, compared with placebo spray. The HR results reflected the stimulatory properties of the drug rather than nicotine's affective properties, whereas SCR was unresponsive to our experimental manipulations. The corrugator EMG results support negative reinforcement models of smoking that postulate that acute nicotine use reduces withdrawal-driven negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Popularity of self-help counseling tapes as an index of community needs.

Investigated whether patterns of requests for such tapes are a useful index of systematic changes in clientele needs. It is suggested, however, that requests for tapes may be a function not only of preexisting community needs but also of varying patterns of advertising. Post hoc analysis of tape requests and advertising patterns in 1 telephone counseling service operating over 2 college semesters suggested the need for extreme caution in interpreting tape-request patterns. (5 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peer play scale as an index of complexity of peer interaction.

A rating scale for interactive peer play was developed and validated on 2 independent samples of 24 and 28 young children varying in age (18–43 mo) and peer experience. Frequency scores from each sample met criteria for unidimensionality and cumulativeness. Ss with more experience with peers had higher frequencies of higher level play. (7 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)