Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

The accommodative response,refractive error and mental effort: 1. The sympathetic nervous system

The accommodative response of 12 emmetropic subjects was measured for an array of numbers located at -1,-3 and -5 dioptres using an objective infra-red optometer. Responses were compared for passive (reading numbers) and active (adding numbers) conditions. The imposition of mental effort induced a significant increase in mean response for the -1 D stimulus, a response equivalent to the passive condition at -3 D and a reduction in response at -5 D. Mental effort induced similar responses for the -1 D and -3 D locations when sympathetic innervation to the ciliary muscle was blocked with the beta-receptor antagonist timolol maleate. Responses for the -5 D location were, however, significantly increased. It is proposed that sympathetic inhibition can modify the effect of mental effort on near accommodative responses.     

The major cicatricial pemphigoid antigen is a 180-kD protein that shows immunologic cross-reactivities with the bullous pemphigoid antigen.

Recent studies have shown that sera from patients with cicatricial pemphigoid (CP) contained autoantibodies against epidermal antigens of molecular weight 230 kD and/or 180 kD by immunoblotting, similar to those recognized by bullous pemphigoid (BP) sera. Previous immunoprecipitation studies have shown that BP sera only precipitated the 230-kD antigen. To characterize the CP antigen(s) we tested 10 CP sera, 10 BP sera, and four controls by both immunoprecipitation of radiolabeled cells and immunoblotting of epidermal extracts. For immunoprecipitation, we used 0.5% NP-40 extracts of both normal human keratinocytes and Pam cells. All CP sera precipitated a 180-kD protein that co-migrated with the BP180 antigen precipitated by some individual BP sera. Two of these CP sera also faintly bound a 230-kD protein of similar molecular weight as the major BP230 antigen. CP and BP sera with an immunoblotting pattern of 180 kD immunoprecipitated a co-migrating 180-kD protein. CP sera reacting by immunoblotting with the 230-kD antigen precipitated the 180-kD and/or the 230-kD antigen. In contrast, BP sera reacting with the 230-kD antigen only precipitated this antigen. In further experiments, labeled 0.5% NP-40 extracts from Pam cells were first preabsorbed with a reference BP serum and then immunoprecipitated with CP sera. Under these conditions, CP sera that immunoprecipitated both 180-kD and 230-kD proteins with the standard procedure no longer precipitated these proteins. Our results suggest that a 180-kD protein is the major CP target-antigen that demonstrated immunologic cross-reactivities with the BP180 and the BP230 antigens.     

Evaluation of filling materials in membrane‐protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.     

On Not Traumatising the Traumatised: The Contribution of Psychodynamic Psychotherapy to Work with People with HIV and AIDS

The incidence of HIV and AIDS is increasing in Britain. Many of those affected are subjected to, and subject others to, powerful psychological pressures. Hitherto, the psychological care of such patients has been much influenced by cognitive-behavioural approaches and only more recently have psychodynamic insights been brought into focus. This paper reports psychotherapeutic work undertaken both directly with HIV and AIDS patients, their partners and families and with clinical teams providing medical care.
The paper attempts to begin to sketch out a map of the psychodynamics of HIV and AIDS to encourage a better understanding of how clinicians can be helped to understand how psychosocial attitudes can be passed on to patients in the form of unconscious attacks and how patients can cause severe acting out on the part of clinicians as they try to resolve their own unconscious conflicts over their illness.     

Posterior Cervical-Thoracic Thermograms: Pattern Persistence and Correlation with Chronic Headache Syndromes

SYNOPSIS
These experiments investigate thermographic patterns in the posterior cervical/thoracic (PCT) region of 530headache patients and 30 headache/injury-free volunteers. The study examines: The longitudinal persistence ofProximal and Distal patterns; three distinct midline patterns (PCT I, II, and III); and their correlation with diagnosis,injury, and pain.
Twenty-four (80%) of 30 randomly selected subjects displayed unchanged Proximal patterns at the meanobservation period of 5.5 months. PCT pattern fluctuations occurred in 13/30 (43.3%) subjects. The distinctivenessof each subject's Proximal and Distal patterns was verified by blind calling of thermogram pairs. Patternpersistence was validated with alcohol spray-Patterns were identical regardless of using a 0.5°C or 1.0°Ctemperature setting. Temperature settings of 1.0°C yielded more distinct Proximal and Distal patterns.
Chi square analysis determined that there was no significant difference in the number of PCT III patterns in theexperimental or control groups.
In conclusion, it appears that Proximal and Distal Patterns may be consistent over time and individually unique,but that PCT patterns fluctuate and, therefore, do not correlate with chronic headaches.     

Efficacy of subinhibitory concentration of pefloxacin in preventing experimental Staphylococcus aureus foreign body infection in mice.

Adhesion is the first step leading to colonization and infection of a foreign body (FBI). To assess the ability of a subinhibitory concentration (subMIC) of pefloxacin (P) to prevent such infection, an experimental model was developed in Swiss albino mice. Subcuts of polyurethane catheters (Vygon) were placed in the peritoneal cavity of animals and 24 hours later, different inocula of an adherent strain of Staphylococcus aureus (SA) (MIC of P:0.8 mg/l) were injected i.p. Unexposed SA served as controls. Two days later the removed catheters, blood and spleen specimens were quantitatively cultured for bacterial content and identity. Infection was defined as more than 10 CFU/ml of SA recovered. Significant protection of mice, with lower dissemination, was found with inoculum sizes of 10(5) and 10(6). These results suggest that subMICs of P may confer protection against foreign body infection.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997