The neurophysiology and pathology of brain zinc

Our understanding of the roles played by zinc in the physiological and pathological functioning of the brain is rapidly expanding. The increased availability of genetically modified animal models, selective zinc-sensitive fluorescent probes, and novel chelators is producing a remarkable body of exciting new data that clearly establishes this metal ion as a key modulator of intracellular and intercellular neuronal signaling. In this Mini-Symposium, we will review and discuss the most recent findings that link zinc to synaptic function as well as the injurious effects of zinc dyshomeostasis within the context of neuronal death associated with major human neurological disorders, including stroke, epilepsy, and Alzheimer's disease.     

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression

Background

Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD.

Objectives

To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch.

Methods

Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up.

Results

A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch.

Conclusions

Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.     

Ultrasound Measurements at the Proximal Phalanges in Male Patients with Psoriatic Arthritis

Bone ultrasound parameters at the proximal phalanges of the hands were measured in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic involvement and 16 with axial involvement), comparing the findings with those in 16 rheumatoid arthritis (RA) patients, 20 ankylosing spondylitis (AS) patients and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were significantly lower in RA (p<0.001 and p<1×10^–5) and PA (p<0.03 and p<1×10^–6) patients than in controls, while there was no statistically significant difference between AS patients and healthy subjects. Ultrasound parameters showed a significant negative correlation with age in all groups. In each patient group ultrasound values were unrelated either to disease duration or to inflammatory indices such as erythrocyte sedimentation rate and C-reactive protein. Moreover no significant differences were observed between ultrasound parameters of the dominant and the nondominant hand. PA patients with and without axial radiologic changes did not show any differences in ultrasound parameters. However, PA subjects with peripheral involvement only had significantly higher Ad-SoS (p<0.04) and UBPS (p<0.04) values than RA patients. PA patients with axial lesions had significantly lower (p<0.04 and p<0.01) ultrasound values than AS patients. These findings suggest that PA ultrasound techniques performed at the peripheral level are of value to speculate on bone involvement, although we think that ultrasound measurements cannot yet be recommended for monitoring bone involvement in these patients. Received: March 2000 / Accepted: October 2000     

Rotational Position of Femoral and Tibial Components in TKA Using the Femoral Transepicondylar Axis

Proper femoral and tibial component rotational positioning in TKA is critical for outcomes. Several rotational landmarks are frequently used with different advantages and limitations. We wondered whether coronal axes in the tibia and femur based on the transepicondylar axis in the femur would correlate with anteroposterior deformity. We obtained computed tomography scans of 100 patients with arthritis before they underwent TKA. We measured the posterior condylar angle on the femoral side and the angle between Akagi’s line and perpendicular to the projection of the femoral transepicondylar axis on the tibial side. On the femoral side, we found a linear relationship between the posterior condylar angle and coronal deformity with valgus knees having a larger angle than varus knees, ie, gradual external rotation increased with increased coronal deformity from varus to valgus. On the tibial side, the angle between Akagi’s line and the perpendicular line to the femoral transepicondylar axis was on average approximately 0°, but we observed substantial interindividual variability without any relationship to gender or deformity. A preoperative computed tomography scan was a useful, simple, and relatively inexpensive tool to identify relevant anatomy and to adjust rotational positioning. We do not, however, recommend routine use because on the femoral side, we found a relationship between rotational landmarks and coronal deformity. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Inhibition of the receptor for interleukin-2 induced by carbimazole: relevance for the therapy of autoimmune thyroid disease.

Evidence has been accumulated that the anti-thyroid drugs used in the treatment of Graves' disease may have immunosuppressive properties but the exact mechanism of action is still unclear. In the present study, we have investigated the in vitro effect of carbimazole (CBZ) on the expression of lymphocyte differentiation antigens and on suppressor cell activity. The incorporation of radiolabelled methimazole (35S-MMI, the active metabolite of CBZ) by resting and mitogen stimulated lymphocytes was also investigated. CBZ at concentrations of 60 microM significantly inhibited the expression of the receptor for interleukin-2 (as defined by the anti-TAC monoclonal antibody [MoAb]) by lymphocytes stimulated with phytohaemagglutinin. The expression of an early activation antigen (as characterized by the 4F2 MoAb) was not affected. Twenty-four hour pre-incubation of cells with different concentrations of CBZ or medium alone did not change the lymphocyte response to mitogenic stimulation, thus suggesting no effect of the compound on suppressor cell function. Finally, there were no significant differences in the uptake of 35S-MMI between resting and stimulated lymphocytes. These data suggest that the immunosuppressive effect of CBZ may be due to its effect of reducing the expression of the receptor for interleukin-2 on lymphocytes undergoing full activation. This property of CBZ could be of relevance in the therapy of autoimmune thyroid diseases (not only Graves' disease) which are characterised by the presence of activated T cells in the thyroid and in circulation.     

Interfacial morphology of self-etching adhesive systems in dentin.

OBJECTIVE: To portray and assess the interfacial morphology achieved with self-etching systems in dentin under observation by scanning electron microscopy. METHOD AND MATERIALS: Ten caries-free extracted erupted human third molars were used in this study. The occlusal enamel was removed, and 10 dentin disks with a thickness of 800 +/- 200 Microm were obtained by slow-speed sectioning with a diamond saw parallel to the occlusal surface. A standard smear layer was created on the occlusal surface by wet sanding with 600-grit sandpaper for 60 seconds. The dentin disks were randomly assigned to one of the systems: AdheSE (Ivoclar Vivadent), Optibond Solo Plus-Self-Etch (Kerr), Tyrian SPE (Bisco) as self-etching primers, and Adper Prompt Self-Etch (3M Espe) and One-Up Bond F (Tokuyama) as self-etching adhesives. All systems were applied according to the manufacturers' instructions. After application of the adhesive systems, a 1.0-mm-thick layer of a flowable composite resin (Filtek Flow; 3M Espe) was applied to the treated dentin surface and light cured for 40 seconds. The specimens were then processed for observation by scanning electron microscopy. RESULTS: All self-etching systems achieved the formation of sealed interfaces and hybridized areas with variable extents except for the self-etching adhesive One-Up Bond F, which showed some gap formation and poor hybridization. Optibond Solo Plus-Self-Etch presented a more consistent adhesive interface with thicker hybrid layers, numerous resin tags, and lateral branches. CONCLUSION: Regarding the micromorphology aspect, Optibond Solo Plus-Self-Etch showed the finest result, while One-Up Bond F was not able to produce a satisfactory ultrastructural morphology.     

Delayed application of aurintricarboxylic acid reduces glutamate-induced cortical neuronal injury

The non-specific endonuclease inhibitor, aurintricarboxylic acid (ATA), attenuated glutamate-induced destruction of cultured cortical neurons. In part, this protective effect likely reflected the ability of ATA to produce a slowly developing block of N-methyl-D-aspartate receptor-mediated inward whole cell current or increase in intracellular free Ca²⁺. However, ATA also attenuated a high K⁺-induced increase in intracellular free Ca²⁺ in the presence of D-aminophosphonovalerate, suggesting that ATA may have a more general effect on Ca²⁺ homeostasis. In addition, ATA attenuated glutamate neurotoxicity even if added up to 2 hr after completion of glutamate exposure, a time when glutamate antagonists or lipid peroxidation inhibitors are no longer neuroprotective. Involvement of apoptosis in this excitotoxic death is unlikely, as Southern blotting of genomic DNA revealed no evidence of fragmentation, and death was not prevented by inhibitors of RNA or protein synthesis. Most likely, ATA interferes with some key downstream consequences of excitotoxic glutamate receptor overactivation. © 1994 Wiley-Liss, Inc.     

Hereditary hemorrhagic telangiectasy (HHT) and HLA

Linkage between HHT and 10 genetic marker systems was investigated in a family with 7 affected members. The analysis supports the previously suggested linkage between HLA and HHT (theta = .17).     

Agricultural occupational health and health education in Latin America and the Caribbean

Agricultural diseases and injuries are major sources of healthconcern in Latin America and the Caribbean. To help alleviatethis situation, health education programs directed at workersat risk have been implemented. This paper discusses the factorsinherent to agricultural work that need to be considered inthe design, planning, implementation, and evaluation of healtheducation activities, such as the characteristics of agriculturalwork and occupational health problems. In addition, it presentsa case study of health promotion for Argentine Hemorrhagic Feverdirected to agricultural workers in the endemic area of thisdisease.