Formation of free choline in brain tissue during in vitro energy deprivation

Free choline and ATP contents were measured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and anoxia, and 11-fold increase during ischemia). Media (extracellular) choline was particularly affected and increased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell to about 2.5 nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca2+ independent. These findings suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indicator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell.     

Bilateral naevus of Ota: a rare manifestation in a Caucasian

The naevus of Ota (naevus fusculocoeruleus ophthalmomaxillaris) was first described by the Japanese dermatologist M. T. Ota in 1939. It has a reported incidence of 0.2% to 1% in the Japanese population. It usually occurs in the skin innervated by the first or second branch of the trigeminal nerve. The naevus comprises dermal melanocytes and is congenital or acquired during adolescence. Commonly associated lesions include scleral melanocytosis and other ocular manifestations as well as lesions of the tympanic membrane, oral and intranasal mucosa and leptomeninges. Diseases associated with Ota's naevus in rare cases are open-angle glaucomas and melanoma. The naevus of Ota in Europeans is a rare manifestation. We report the very rare case of a bilateral naevus of Ota associated with enoral melanocytosis in a white European person.     

Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile: Pharmacodynamic implications

The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels) that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude of pharmacologic response is commonly described by the sigmoidalE _max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN ^*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN ^*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters of the effector subunits the apparentN will always have a lower value thanN ^*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic interpretation can be deduced from the apparentN value. If in the futureN ^* can be determined by theoretical or experimental methods, the distribution function relatingN ^* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques which may enable us to determine the concentration-effect relationship at the level of the individual effector unit.     

Tumor necrosis factor (TNF alpha) in lymphadenopathy and bone marrow involvement: histopathological and serological study.

Serum samples were collected from 40 patients with enlarged lymph nodes. Lymph node and bone marrow biopsies were performed and processed as usual. Tumor necrosis factor-alpha (TNF alpha) was determined in the sera by factor test human TNF alpha ELISA kit. Histopathological studies of lymph node and bone marrow biopsies were evaluated. The data obtained from this study showed that bone marrow was involved in only 5 patients and their TNF showed the lowest level in this study with a mean level 50 pg/ml. The highest level of TNF occurred in cases with granulomatous lymphadenitis (124 pg/ml) followed by reactive lymphadenitis (105 pg/ml). It can be considered that TNF reflects the immune status of the patient and its study in the serum can be of help in evaluating the progress of the disease. An extended study is need to evaluate the role of TNF-alpha as a prognostic marker in malignancy.     

Hyperglycemia potentiates H(2)O(2) production in adipocytes and enhances insulin signal transduction: potential role for oxidative inhibition of thiol-sensitive protein-tyrosine phosphatases

Insulin signal transduction in adipocytes is accompanied by a burst of cellular hydrogen peroxide (H(2)O(2)) that facilitates insulin signaling by inhibiting thiol-dependent protein-tyrosine phosphatases (PTPs) that are negative regulators of insulin action. As hyperglycemia is associated with increased cellular reactive oxygen species, we postulated that high glucose conditions might potentiate the H(2)O(2) generated by insulin and modulate insulin-stimulated protein phosphorylation. Basal H(2)O(2) generation was increased threefold in differentiated 3T3-L1 adipocytes by growth in 25 mM glucose versus 5 mM glucose. High glucose increased the sensitivity of the insulin-stimulated H(2)O(2) signal to lower concentrations of insulin. Basal endogenous total PTP activity and the activity of PTP1B, a PTP implicated in the negative regulation of insulin signaling, were reduced in high glucose conditions, and their further reduction by insulin stimulation was more enhanced in high versus low glucose medium. Phosphorylation of the insulin receptor, IRS-1, and Akt in response to insulin was also significantly enhanced in high glucose conditions, especially at submaximal insulin concentrations. In primary rat adipocytes, high glucose increased insulin-stimulated H(2)O(2) production and potentiated the oxidative inhibition of total PTP and PTP1B activity; however, insulin signaling was not enhanced in the primary cells in high glucose apparently due to cross-regulation of insulin-stimulated protein phosphorylation by activation of protein kinase C (PKC). These studies indicate that high glucose can enhance insulin stimulated H(2)O(2) generation and augment oxidative PTP inhibition in cultured and primary adipocytes, but the overall balance of insulin signal transduction is determined by additional signal effects in high glucose, including the activation of PKC.     

The role of a raphe serotonin system in the control of septal unit activity and hippocampal desynchronization.

The effects of electrical stimulation of the median raphe nucleus on neuronal discharges in the medial septal area and electrical activity of the hippocampus were examined in urethane-anaesthetized rats. Two cell populations in the medial septal area were differentiated on the basis of their spontaneous discharge pattern, response to median raphe nucleus stimulation and whether or not they were antidromically activated following hippocampal stimulation. Medial septal area cells classified as I-neurones discharge in an irregular pattern which was unrelated to hippocampal activity. In contrast, B-neurones discharge in either rhythmic bursts or in an irregular manner which were related to hippocampal ‘theta’ or ‘desynchronization’, respectively. Single pulse stimulation of the median raphe nucleus inhibited the spontaneous discharge of I-neurones but did not influence the firing of B-neurones or hippocampal activity. Repetitive stimulation of the median raphe nucleus resulted in a prolonged inhibition of I-neurones, a disruption of the bursting discharge of B-neurones, and desynchronization of the hippocampal ‘theta’. The effects of median raphe nucleus stimulation were blocked by pretreatment with parachlorophenylalanine suggesting that a serotonin-containing system originating in the median raphe nucleus may be involved in mediating these responses.     

A community education monitoring system: methods from the Stanford Five-City Project, the Minnesota Heart Health Program and the Pawtucket Heart Health Program

Understanding the process of behavior change interventions is critical to achieving campaign effectiveness and successful program replication. The present article presents a community education monitoring system (CEMS) using data from the Stanford Five-City Project (FCP), the Minnesota Heart Health Program (MHHP) and the Pawtucket Heart Health Program (PHHP). CEMS records the number and type of intervention activities, outcome objectives, targets of change (individual, organizational or environmental), channel(s) of dissemination and proportion of programs funded by the community. These data illustrate (1) the application of theory for each project, (2) data-based program administration, (3) feedback for revising programs and (4) type of reach or 'dose' information obtained from intervention monitoring. Process evaluations such as CEMS provide critical links between field realities and evaluation outcomes. This type of evaluation develops standards for measuring program reach and allows comparisons with other programs. CEMS also illustrates how programs enact theory. Validation studies are critical to the continued successful use of CEMS. The first step, however, is to develop a uniform way of describing complex multichannel behavior change programs. CEMS in a refined form should prove invaluable to health promotion program planners whether in research or service settings.