Delta9 -tetrahydrocannabinol increases brain temperature and inverts circadian rhythms.

Delta9-tetrahydrocannabinol (THC) has been shown to protect against focal and global ischemia. Hypothermia is thought to be one mechanism for this protection. These observations are important since brain hyperthermia is known to increase ischemic damage while hypothermia is protective. To establish the effect of THC on brain and body core temperature, brain and body temperature probes were inserted for chronic temperature monitoring (n = 20). THC treated groups were administered THC at either low (0.1 mg/kg) or high (10 mg/kg) dose for 1 week. Brain temperature was recorded during this period and for 1 week following the discontinuation of THC. Chronic administration of THC at either dose increased brain temperature (p < 0.0001) but did not significantly change body core temperature (p = 0.4767) in the freely moving rat.

6-Aminonicotinamide inhibition of the pentose phosphate pathway in rat neocortex.

6-Aminonicotinamide (6-AN) is thought to inhibit the pentose phosphate pathway (PPP) since large increases in 6-phosphogluconate are observed following its administration. Immediately following 45 min i.v. infusion of [2-(13)C]glucose to controls and 6-AN-treated (50 mg/kg i.p. given 4 h previously) Sprague-Dawley rats (n = 5 for both groups), metabolism was arrested using freeze-funnel fixation. Chloroform-methanol-water neocortical extracts from animals administered with 6-AN demonstrated elevated levels of 6-phosphogluconate and 6-phosphoglucono-delta-lactone, both of which demonstrated labeling through metabolism of [2-(13)C]glucose. Comparison of the C-2 and C-3 lactate positions using 1H NMR spectroscopy showed that the fraction of glucose metabolized through the PPP is unchanged by 6-AN (14+/-0.6% vs 14+/-0.3% in control animals). It is hypothesized that as the PPP is inhibited by metabolites of 6-AN in the neocortex, glycolysis is inhibited in a proportionate manner through an inhibitory effect on phosphoglucose isomerase by 6-phosphogluconate and/or 6-phosphoglucono-delta-lactone.

Maintenance of tricarboxylic acid cycle kinetics in Brown-Norway Fischer 344 rats may translate to longevity.

Glucose metabolism and tricarboxylic acid cycle (TCA) kinetics have been shown to decline in brain with age in various animal species. This study examined TCA cycle kinetics and age in Brown-Norway Fischer 344 rats. Using [1-(13)C]glucose infused over 10, 30, 60 or 100 min, and following the label through the TCA cycle using (1)H¿(13)C¿ spin-echo difference magnetic resonance spectroscopy, groups of 2 (n=18), 12 (n=16), and 24 (n=16) month old rats were evaluated. Unexpectedly, TCA cycle kinetics did not change with age. Observed decreases in glutamate, glutamine and N-acetyl aspartate levels are consistent with an age-related decrease in neuronal numbers. The possible link between this observation and increased longevity, together with a decreased incidence of neoplasia in the Brown-Norway Fischer 344 rat is discussed.

Hypothermia: depression of tricarboxylic acid cycle flux and evidence for pentose phosphate shunt upregulation.

OBJECT: Hypothermia is used in neurosurgery and other surgical disciplines to reduce tissue injury, but the mechanism of such protection remains elusive. The authors have endeavored to delineate the mechanism of neural protection afforded by hypothermia through a study of glucose metabolism. METHODS: Nuclear magnetic resonance spectroscopy was used to follow the carbon-13 label from [1-13C]glucose as it was metabolized through the glycolytic and tricarboxylic acid pathways. Male Sprague-Dawley rats were maintained at either 37.5 degrees C or 31 degrees C and infused with labeled glucose for 10, 30, 60, 100, or 200 minutes (five rats were used for each time point and for each temperature). At the end of the infusion period, the rats' brains were subjected to rapid freeze-funnel fixation. Water-soluble metabolites were extracted from samples of the neocortex and hippocampus by using perchloric acid extraction. The fractional enrichment of these metabolites was used to calculate the reaction rate constant of formation and steady-state enrichment for a number of metabolites. Hypothermia resulted in a 30 to 40% depression of metabolism (p < 0.0001) in both the neocortex and hippocampus. Steady-state fractional enrichment of metabolites was also decreased by 20 to 25% with hypothermia (p < 0.0001), implying a loss of label during metabolism. CONCLUSIONS: The results of this study suggest that an increased fraction of glucose metabolism was shunted through the pentose phosphate pathway in the presence of hypothermia.

Labeling of N-acetylaspartate and N-acetylaspartylglutamate in rat neocortex, hippocampus and cerebellum from [1-13C]glucose.

Both N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are localized almost exclusively to neurons, and have become important markers of neuronal viability in a number of cerebral pathological conditions. Using nuclear magnetic resonance spectroscopy combined with [1-13C]glucose administration (200 min infusion) we show that the synthesis of both NAA and NAAG can be observed. Label was incorporated into NAA from labeled acetate and from labeled aspartate, while NAAG was labeled from labeled glutamate. The low fractional enrichment of NAA (ca. 3%) relative to aspartate (20%) suggests a slow turnover rate, while NAAG (20.0%) and glutamate (25.2%) labeling were nearly equal, suggesting that NAAG labeling is near steady state. The rapid turnover of NAAG suggests an important role in glutamate delivery, while the slow rate of NAA turnover implies that its major role is as substrate for the formation of NAAG.

Human cerebral neoplasms studied using MR spectroscopy: a review.

Of primary central nervous system tumors treated each year, the majority are glioma, followed by meningioma and then pituitary adenoma. While the use of magnetic resonance (MR) and computed tomographic imaging is well established in the diagnosis and management of such tumors, these techniques have a limited role in determining the metabolic state, either prior to or following therapy. Multinuclear MR spectroscopy, on the other hand, provides information on tumor metabolism and the effect of therapy on tumor viability. This paper reviews MR spectroscopic studies performed on patients with central nervous system tumors and discusses the impact that such studies have had on tumor diagnosis and management.

23Na nuclear magnetic resonance spectral changes during and after forebrain ischemia in hypoglycemic, normoglycemic, and hyperglycemic rats.

BACKGROUND AND PURPOSE: The severity of brain injury in animal models of forebrain ischemia increases with blood glucose level. During ischemia, energy failure is slower and maintenance of ion gradients is prolonged as the level of glycemia increases. It is not clear how the level of glycemia influences recovery of ion homeostasis on reperfusion. It has been shown that changes in the intensity of the multiple-quantum 23Na nuclear magnetic resonance (NMR) signals reflect changes in intracellular Na+ levels. We have used 23Na NMR spectroscopy to evaluate the influence of the level of glycemia on changes in Na+ concentration during and after forebrain ischemia in rats. METHODS: Single-quantum (SQ) and double-quantum (DQ) 23Na NMR spectra were measured before and during 10-minute forebrain ischemia and during reperfusion in hypoglycemic, normoglycemic, and hyperglycemic rats. RESULTS: The DQ 23Na NMR signal increased to 210% of preischemia intensity in all rats, but a delay in this increase was observed in normoglycemic and hyperglycemic animals. The rate of the DQ 23Na NMR signal increase was fastest in hypoglycemic (apparent first-order rate constant 0.673 +/- 0.046 min-1, P < .002 compared with normoglycemic animals) and slowest in hyperglycemic (0.285 +/- 0.024 min-1, P < .03) rats. During reperfusion, the signal intensity recovered rapidly in hypoglycemic (0.385 +/- 0.050 min-1) and normoglycemic (0.464 +/- 0.047 min-1) rats, whereas in hyperglycemic animals recovery was slow (0.108 +/- 0.044 min-1, P < .0001 compared with normoglycemic animals). The SQ 23Na NMR signal intensity increased to 117% of preischemia level in hypoglycemic (P < .05 compared with normoglycemic animals) and to 107% in normoglycemic and hyperglycemic animals during reperfusion. CONCLUSIONS: The slower increase in the 23Na DQ NMR signal intensity during forebrain ischemia in rats with higher blood glucose levels suggests that Na+ homeostasis is maintained longer in these animals. On reperfusion, the slower recovery of the DQ 23Na NMR signal intensity in hyperglycemic animals likely indicates a slower recovery of Na+ homeostasis, perhaps contributing to the increased neuronal injury after cerebral ischemia in hyperglycemic animals.

The good boy syndrome and malignant academic failure in early adolescence.

The shift into adolescence coincides with an increase in academic demands that reveals a large diagnostic range of difficulties underlying academic underachievement or failure at this developmental stage. A group of compliant boys of high intelligence and proved abilities, previously apparently well-adjusted and well-liked, unexpectedly come to attention because of sudden academic failure. Their puzzling difficulties indicate a serious underlying disorder, including depression, which requires intensive treatment. Intrasystemic superego conflicts of ideals form an intrinsic part of the psychic picture.

Neurotic negativism and negation in the psychoanalytic situation.

Negativistic phenomena in the treatment of neurotic children and adults are examined and distinctions are made among negativism, negation, and denial. Clinical vignettes exemplifying various forms of negativism are presented and viewed as expressions of developmental, defensive, or characterological aspects of the personality. Hartmann's seminal concepts of the genetic fallacy, change of function, and secondary autonomy are employed. The addition of a developmental view provides a broader context within which to view the patient's behavior and on the basis of which to formulate interpretive interventions.

The emergence of oedipal centrality comments on Michael Feldman's paper 'Common ground: the centrality of the Oedipus complex.

The Oedipus complex is indeed a central organizing focus of human development. Given the opportunity to review psychoanalytic work illustrative of how this concept influences clinical theory and technique, patches of common ground and of significant differences are described. The patient discussed was in the termination phase of a very long analysis, resulting in a concentration and telescoping of the three weeks of reported material from six months prior to termination. This facilitated the elucidation of similarities and differences in viewing and handling manifestations of resistance, transference and countertransference. In particular, differences in conceptualization of the Oedipus complex were addressed, especially the constraints imposed on the analyst's thinking and technique by an obligatory perception that all material represented oedipal themes. In an alternative view, a pre-oedipal, dyadic developmental foundation provides a framework for the elaboration and evolution of oedipal, triadic complexities as a developmental achievement. This enables a reconsideration of transference manifestations of conflictual object relations in terms of distinctions between dyadic, pre-oedipal and triadic, oedipal themes, thus enhancing the analyst's interpretive relevance.

Electron spin resonance of charge carriers in chlorophyll a/water micelles.

Chlorophyll a/water micelles (P740) prepared in hydrocarbon media have been shown by small-angle neutron scattering to consist of hollow cylinders whose surface is formed of a monolayer of chlorophyll crosslinked by water. The micelles can be reversibly oxidized or reduced to generate highly mobile holes or electrons that undergo rapid, one-dimensional transport along the chains of chlorophyll macrocycles comprising the surface of the micelles. Large pi-pi overlap within the chains facilitates the one-dimensional charge transport and is expected to do the same for energy transport. Structural defects in the micelle surface act as boundaries for charge transport, confining the spins to one-dimensional domains of approximately 200 macrocycles. The one-dimensional transport within the limited domains results in motionally narrowed electron spin resonance lines with some residual inhomogeneous broadening. Although the chlorophyll a incorporated in micelles is more easily oxidized than is monomeric chlorophyll a, it is much more resistant to chemical alteration.

Countertransference evolution in theory and practice.

A framework is suggested for conceptualizing countertransference, based on expansion of the concept emerging subsequent to Freud's original view of the phenomenon: from Ucs to Cs, from reactions to transference to all reactions, from the analyst's neurosis to the analyst's functioning, from self-analysis to self-scrutiny, from obstacle to contribution. Particular attention is called to the advantages of maintaining the distinction between the patient's transference and the analyst's countertransference; the importance for successful psychoanalytic work of being aware of the subtleties of countertransference in work with neurotic patients, especially in contrast to the blatant countertransference experiences more disturbed patients thrust upon the analyst; the need for further investigation of the relations between the analyst's empathy, regression, and countertransference; the lack of understanding of and information about the homosexual countertransference, based on insufficient knowledge of the mechanisms of resistance to self-analysis, among other reasons; and the need for more reliable information about the limits of and indications for using countertransference responses in particular kinds of clinical situations, whether for informing the patient as to the analyst's responses to him, for informing the analyst in the interpretive process, or in formulating reconstructions. A clinical example provides an illustration of the complexity of countertransference-transference interaction and of the impact of countertransference on the transference.

Narcissism and superego development.

To elucidate the role of the superego in th maintenance of narcissistic equilibrium, we reviewed Freud's ideas about narcissism and the superego as well as the relevant theories of Kohut, Kernberg, and certain ego psychologists. These latter authors offer an alternative mode of understanding narcissism more consistent with Freud's structural theory, one in which signal affects and superego functioning play a central role in normal development and in the pathogenesis of narcissistic disturbances. Early steps in superego formation were then examined schematically to elucidate the interaction of environmental influences and emerging psychic structure. We suggested that the first step in a developmental line toward superego formation is based on the affective qualities experienced in the course of self-object differentiation. Subsequent steps examined were introject and ego-ideal formation; compliance with th object; compliance with the introject; identification with the introject and the ego ideal; and finally, with oedipal resolution, the integration of superego nuclei into a progressively structuralized autonomous superego system. This system achieves growing independence from the drives and from pressures from early introjects during the course of latency, and functions to maintain the demands of the conscience and the standards of the ego ideal; rewards or punishments result when these demands and standards are or are not met. The final stage briefly considered here was the revision, modification, and elaboration of moral codes and the ego ideal as part of the adolescent process. Narcissistic vulnerabilities at various stages were pointed out in an attempt to stress that a particular clinical picture in later phases of development or adulthood may derive from any of several development points of origin and from one or more etiological factors.

Some narcissistic consequences of object loss: a developmental view.

This paper examines the effects of object loss on narcissistic equilibrium from a developmental perspective. Such effects vary, depending on when the loss occurs in relation to the process of self-object differentiation, as well as on other characteristics in the loss situation. An effort is made to clarify the particular narcissistic elements which may be identified as involved in the experience of psychic pain following a loss. To this end, a distinction is made between feelings of omnipotence, of self-constancy, and of self-esteem, and their different developmental bases illustrated with clinical examples.

A case of 'pseudo-narcissistic' psychopathology: a re-examination of the developmental role of the superego.

In this paper we have attempted a tentative delineation of particular superego elements which may be involved in the production of 'pseudo-narcissistic' psychopathology, that is to say, a disturbance which superficially appears to be a narcissistic personality disturbance but which is fundamentally based on neurotic conflict. Using a framework of superego constituents and superego functions, aspects from the analysis of a man with profound difficulties in self-esteem regulation were examined to highlight his intrasystemic conflict--a conflict of ideals. Some possible explanations were offered, taking into account the persistence of early stages in the development of the superego and of difficulties in the resolution of oedipal conflicts. This work is offered as an example of a way in which the psychoanalytic treatment process can contribute to knowledge of early psychic structure formation and development.

Potential antitumor agents. XVII. physalin B and 25,26-epidihydrophysalin C from Witheringia coccoloboides.

An investigation of Witheringia coccoloboides (Dammer) A. T. Hunziker [Capsicum fuscoviolaceum (Cufodontis) Mort. And Standl.] roots has resulted in the isolation of two cytotoxic compounds: physalin B (1) and a novel physalin, which was characterized by spectral analysis as 25,26-epidihydrophysalin C (2). Both compounds have demonstrated cytotoxic activity in 9KB and 9PS tumor cells (in vitro). Physalin B (1) has demonstrated moderate activity against the 3PS mouse leukemia (in vivo).