Nikos Antonakis

In vitro differential effects of the antiglucocorticoid RU486 on the release of lymphokines from mitogen-activated normal human lymphocytes

The synthetic antiglucocorticoid RU486 has multiple effects on the immune system. We have recently reported that RU486 suppresses normal lymphocyte proliferation and downregulates interleukin-2 receptors (IL-2R) by decreasing the accumulation of the beta-chain IL-2R mRNA in normal human lymphocytes in culture. To further explore the mechanism of the immunoregulatory actions of RU486, in the present study, we investigated the effects of this molecule on the release of lymphokines from phytohemagglutinin (PHA)-activated normal human peripheral blood lymphocytes (NPBL) in culture. We have found that RU486 differentially regulates the release of lymphokines from PHA-activated NPB lymphocytes. Specifically, RU486 (at concentrations of 1-100 nM) exerts pure antagonist actions by almost completely reversing the inhibitory effects of the glucocorticoid dexamethasone (Dex) on the release of monocyte/macrophages-derived lymphokines, such as IL-1, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Dex decreased in a dose-dependent manner the release of the above four lymphokines, with an ID50 of 0.9 +/- 0.1, 4.76 +/- 0.4, 9.8 +/- 1.8, and 1.16 +/- 0.2 nM for IL-1, IL-6, IL-8 and TNF-alpha, respectively. Conversely, RU486 exhibits both agonist and antagonist effects on the release of T-lymphocyte-derived lymphokines. RU486 given alone, exerts agonist/glucocorticoid effects, by decreasing in a dose-dependent manner the release of IL-2 and -3. The maximal inhibitory effect of RU486 was observed at 10 nM and was 64.5 +/- 4.3% of the control value, (n = 6, P < 0.02) for IL-2 and 59.2 +/- 6.3% (n = 6, P < 0.02) for IL-3. The ID50 of RU486 for the release of IL-2 and -3 were 14.6 +/- 2.0 and 11.6 +/- 1.9 nM, respectively, i.e. almost similar with those of Dex. Interestingly, when high doses of RU486 (1 microM) were combined with Dex RU486 exhibited antagonist actions by significantly counteracting the inhibitory effects of Dex on IL-2 and -3 release. In conclusion, the antiglucocorticoid RU486 exhibits complex regulatory actions on lymphokine secretion, dependent upon the type of the lymphokine-producing cell. A pure antagonist effect was observed on the release of monocyte-derived IL-1, IL-6, IL-8 and TNF-alpha. However, when RU486 was given alone it acted as a glucocorticoid agonist on the secretion of T-lymphocyte-derived IL-2 and -3, while combined with the agonist (Dex) it exhibits antagonist effects on the release of the above lymphokines.(ABSTRACT TRUNCATED AT 400 WORDS)

The antiglucocorticoid RU486 downregulates the expression of interleukin-2 receptors in normal human lymphocytes

The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 microM (28 +/- 2% of control, P less than 0.001) and on the high affinity IL-2R at 1 microM (from 2938 +/- 74 to 437 +/- 108 binding sites per cell, P less than 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of beta-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppressive effects.

Exploring training needs of nursing staff in rural Cretan primary care settings

The purpose of this exploratory study was to assess occupational profile, level of performance, and on-the-job training needs of nursing staff employed in all government primary health care centers in rural Crete, Greece. The translated, culturally adapted, and validated Greek version of the Training Needs Assessment questionnaire was used. There were no significant differences between 2-year degree graduates (LPNs) and 3- or 4-year degree graduates (RNs, midwives, and health visitors) in terms of importance for 28 of 30 assigned tasks, whereas level of performance did not differ in any tasks. Significant training needs were reported by all staff, mainly in research/audit and clinical skills. Systematic overview of skill deficits in relation to skill requirements should be implemented by regional health authorities to enhance delivery of on-the-job training targeting group-specific, local needs.

Translation and standardisation into Greek of the standardised general Nordic questionnaire for the musculoskeletal symptoms

Musculoskeletal disorders represent a common reason for the general population to seek care from the health services.1,2 Standardised questionnaires are among the widely accepted methods for collection and analysis of relevant data. The standardised questionnaires for the analysis of musculoskeletal symptoms (Nordic Musculoskeletal Questionnaires, NMQs),3 the general form and the specific low back and neck/shoulder questionnaires, have been extensively used as a screening instrument in epidemiological studies across Europe and all over the world.4,5 The lack of specific questionnaires that are validated in the Greek language was the main reason for this study of translation and validation of the general NMQ into Greek.

Diagnosing a popliteal venous aneurysm in a primary care setting: a case report.

IntroductionPopliteal venous aneurysms are uncommon but potentially fatal vascular disorders. They can be symptomatic or asymptomatic, mimicking different conditions. Popliteal venous aneurysms are possible sources of embolism.Case presentationA 68-year-old woman presented at a rural primary health care unit in Crete, Greece, reporting local symptoms of discomfort in the right popliteal fossa with pain during palpation. Colour Doppler ultrasonography revealed local widening and saccular dilatation in the right distal popliteal vein. The diagnosis of a popliteal venous aneurysm was formulated.ConclusionPopliteal venous aneurysms are rare conditions, but are potentially more common than usually thought in daily practice. Physician awareness and access to ultrasound examination may allow for early diagnosis, before the occurrence of any thromboembolic or other major complication.