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.     

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.     

New Insights into Lamellar Twisting in Transcrystalline Polyethylene

Summary: The morphology of the transcrystalline layer grown by nucleating high density polyethylene on fibers of ultra high molecular weight polyethylene was investigated by microbeam synchrotron X‐ray diffraction. Scanning with a 2 micron step size, it was possible to determine that near the fiber surface, the polymer chains of the transcrystalline layer are oriented at an angle of approx. 41° with respect to the fiber axis. This is consistent with the lamellar fold surface (the {201} plane) being close to perpendicular to the fiber axis. The X‐ray data support gradual twisting of the lamellae about the growth direction (the orthorhombic crystallite b‐axis) at a rate of ～0.85° per micron of radial distance from the fiber surface.

Polarized light micrograph of the transcrystalline layer in a PE/PE composite. The width of the fiber is approximately 20 μm.     

Local Suppression of Epileptiform Activity by Electrical Stimulation in Rat Hippocampus In Vitro

High frequency electrical stimulation of deep brain structures (DBS) has been effective at controlling abnormal neuronal activity in Parkinson's patients and is now being applied for the treatment of pharmacologically intractable epilepsy. The mechanisms underlying the therapeutic effects of DBS are unknown. In particular, the effect of the electrical stimulation on neuronal firing remains poorly understood. Previous reports have showed that uniform electric fields with both AC (continuous sinusoidal) or DC waveforms could suppress epileptiform activity in vitro . In the present study, we tested the effects of monopolar electrode stimulation and low-duty cycle AC stimulation protocols, which more closely approximate those used clinically, on three in vitro epilepsy models. Continuous sinusoidal stimulation, 50 % duty-cycle sinusoidal stimulation, and low (1.68 %) duty-cycle pulsed stimulation (120 μs, 140 Hz) could completely suppress spontaneous low-Ca²⁺ epileptiform activity with average thresholds of 71.11 ± 26.16 μA, 93.33 ± 12.58 μA and 300 ± 100 μA, respectively. Continuous sinusoidal stimulation could also completely suppress picrotoxin- and high-K⁺-induced epileptiform activity with either uniform or localized fields. The suppression generated by the monopolar electrode was localized to a region surrounding the stimulation electrode. Potassium concentration and transmembrane potential recordings showed that AC stimulation was associated with an increase in extracellular potassium concentration and neuronal depolarization block; AC stimulation efficacy was not orientation-selective. In contrast, DC stimulation blocked activity by membrane hyperpolarization and was orientation-selective, but had a lower threshold for suppression.     

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.     

Original papers: Large bimedial rectus recession (6.5 mm or more) in the management of large-angle esotropia

A total of 101 patients (total group) with primary large angle esotropia who had primary bimedial rectus recession (BMR) of 6.5 mm or more were reviewed in a retrospective study. The average pre-operative size of the deviation was 63.5 prism diopters (PD) for near and 58.2 PD for distance. Of these, 26 patients (group I) attended for one post-operative visit only. The remaining 75 patients (group II) were followed for an average period of 17.7 months. Among group II patients there was an average shift in the post-operative deviation towards divergence consisting of-6.4 PD for near and-5.5 PD for distance. The alignment (deviation of 10 PD or below) rate in the first postoperative visit was 31.7%; undercorrection was 60.4% and overcorrection was 7.9%. At the end of the period of follow-up the above rates were 40%, 42.7%, and 17.3% respectively without further surgery. This increase in the overcorrection rate was solely derived from the initially aligned patients. Amblyopia and/or poor fixation were found to be of significance in the production of overcorrection. There was no direct relationship between the age of surgery, duration of follow-up or the degree of the BMR and the rate of correction. Among group II patients, post-operative ocular movements analysis revealed limitation of adduction of-0.5 to-0.75 (out of scale 0 to-4.00) in 22.7% (17/75) and-1.00 to-1.50 in 6.7% (5/75). None had more than-1.5 limitation of adduction. Large BMR is an acceptable surgical modality for the management of large angle esotropia. It has approximately 50% alignment rate. Slight undercorrection is recommended especially in the presence of significant amblyopia and/or poor fixation. No significant limitation of adduction was encountered.