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.     

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.     

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.     

Program evaluation strategies for community-based health promotion programs: perspectives from the cardiovascular disease community research and demonstration studies

Community-based programs are being widely adopted in the struggle to prevent chronic disease. Program evaluation of community-based programs involves a particular set of problems stemming from the variety of activities being undertaken simultaneously, the multiple intermediate goals of the programs and the rapidity with which the programs evolve. An analysis of the experience of four large community-based cardiovascular disease research and demonstration studies (Stanford Five-City Project, Minnesota Heart Health Program, Pawtucket Heart Health Program and the German Cardiovascular Prevention Project) provides valuable models, methodologies and strategies for planning and conducting evaluations of public health programs or community studies. By comparing and combining their experiences, the four programs have identified eight categories of evaluation for community studies, including formative evaluation, quality assurance, assessment of delivered dose, assessment of received dose, component program impact, intermediate outcomes, community impact and cost analysis. This paper presents information on the strategies by which each of the four programs addressed these evaluation categories.     

Effects of the superoxide dismutase-mimic compound TEMPOL on oxidant stress-mediated endothelial dysfunction

The aim of this study was to investigate the effects of oxidant stress on endothelium-dependent and endothelium-independent arterial relaxation. For this, oxidant stress was generated by preincubation of rat aortic rings (RARs) in either 25 mM glucose (mimicking hyperglycemic stress) or 0.5 mM pyrogallol (a superoxide generator) and the effects of the superoxide dismutase (SOD)-mimetic compound 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy free radical (TEMPOL) on the vasorelaxant and cGMP-producing effects of acetylcholine (ACh) and glyceryl trinitrate (GTN) in control RARs and RARs exposed to oxidant stress were examined. Pyrogallol, and to a lesser extent high glucose concentration, enhanced the contractile response of RARs to phenylephrine and markedly inhibited the vasorelaxant response to ACh. Although they existed, the inhibitory effects of high glucose and pyrogallol on the vasorelaxant response to GTN were less profound, especially with pyrogallol. Moreover, both pyrogallol and high glucose concentration inhibited the basal and the ACh-induced vascular cyclic guanosine monophosphate (cGMP) production. Treatment with TEMPOL (1-5 mM) slightly increased the ACh and GTN-induced cGMP levels in control RARs but had a significant effect in high glucose and pyrogallol-pretreated RARs. Additionally, concomitant treatment of RARs with TEMPOL (5 mM) abolished the difference in the relaxation response between control RARs and RARs exposed to either pyrogallol or high glucose concentration. These results further support the theory that reactive oxygen species (ROS), especially superoxide, play a key role in mediation of endothelial dysfunction accompanying diabetes, probably through their effects on the ability of the endothelium to synthesize, release or respond to endogenous nitric oxide (NO) or NO donated by nitrovasodilators.     

Thermostable antigens from the bone marrow of several animal species.

Studies on bone marrow extracts from ten animal species have revealed the presence of thermostable antigens. Similar antigens were found in other organs as shown by immunodiffusion and cross-reactivity was demonstrated between the thermostable proteins from horse and dog and between cow and sheep proteins. Using an immunoenzymatic reaction with glucose oxidase as the marker, the thermostable antigens were localized in the blood and bone marrow polymorphonuclear leukocytes and the myeloid cell line.     

Diagnosis of viral agents associated with neonatal calf diarrhea.

During this study, 134 samples have been examined for the detection of the viruses associated with neonatal calf diarrhea. The presence of Nebraska viruses (rotavirus and coronavirus) has been demonstrated by using the electron microscope and the fluorescent antibody techniques while the presence of other viruses has been detected by the observation of a cytopathic effect on monolayer cells of calf testis. The Nebraska viruses have been demonstrated in 107 (80%) out of 134 field case specimens. An association of rotaviruses and coronaviruses was found in 58 cases (54%) whilst the coronaviruses and the rotavirus were found singly in 34 cases (53%) and in 15 cases (14%) respectively. Four bovine virus diarrhea viruses, two infectious bovine rhinotracheitis viruses and two enteroviruses have also been isolated in the preceding 107 Nebraska positive specimens. For the detection of the Nebraska viruses, the fluorescent antibody techniques were more sensitive than the electron microscopy. However, those two techniques must be used simultaneously for a better detection of a greatest possible number of cases.