Preventive systemic cyclosporin A in risk keratoplasty

Systemic cyclosporin A prophylaxis was applied in 18 high-risk corneal transplants. Immunoreactions occurred in three cases. They correlated with too low serum level of cyclosporin A. Two of them could be reversed by an increase of cyclosporin A dosage in combination with an intensive corticosteroid therapy. Four corneal transplants failed from persistent severe basic disease. Eleven corneal transplants remained clear during the follow-up (5-33 months). A constant trough cyclosporin A serum level of 100-120 ng/ml has been shown to exert efficient immunomodulating effects. We currently judge a postoperative prophylaxis period of 6 to 12 months with cyclosporin A to be sufficient in most high-risk cases.     

Antidepressants may not assist recovery in practice: a naturalistic prospective survey.

A total of 130 people attending psychiatric hospitals within 6 months of onset or relapse of an episode of depressive disorder were interviewed about their symptoms and treatment at the time of their initial contact. After a mean 4-month interval, 119 were reassessed to test the hypothesis that patients treated with antidepressants would be significantly more likely to be clinically improved compared with those untreated. Severity and duration of the episode emerged as the only significant clinical predictors of clinical improvement. Patients on treatment with antidepressants at the start of the study showed a nonsignificant trend for a lesser degree of clinical improvement, even when clinical severity and compliance were taken into account. Those who were not commenced on treatment until later in the study also fared no better than those who were never prescribed antidepressants. The effect of low doses of antidepressants (almost always a tricyclic) appeared to be less beneficial than either higher doses or clinical management without antidepressant drugs. The need for further experimental and naturalistic studies conducted over various periods of time and the implications for clinical practice, medical audit and the appropriate use of health outcome indicators are discussed.     

Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.

The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.     

Síndrome metabólica em trabalhadores de um hospital universitário

IntroductionMetabolic syndrome (MS) is a major health problem, and has economic effects on enterprises. The workplace is thus an important environment for primary prevention of risk factors for cardiovascular disease.ObjectiveTo determine the prevalence of MS and variables related to its development in hospital workers.MethodsWe performed a cross-sectional study of 740 workers in a large university hospital. Socioeconomic variables, anthropometric and blood pressure measurements, and laboratory exams were analyzed. MS was defined according to the criteria of the International Diabetes Federation.ResultsOf the 740 workers, 72.4% were female and mean age was 34.9±9.5 years; 27.8% worked the morning shift, 20.3% the afternoon shift, 34.1% office hours, and 17.8% the night shift. As to educational level, 86.6% had finished high school or college. Waist circumference was high in 55.4%. Overall MS prevalence was 12.8%, 16.2% in males and 11.6% in females. Logistic regression analysis showed an independent association between MS and the following variables: elementary education, period of employment >10 years, office hours shift, and age group.ConclusionA diagnosis of MS was affected by age, educational level, work shift, and prolonged period of employment. Hospital workers do not differ from other populations and also need stimuli to make preventive changes to their behavior to modify cardiovascular risk factors.     

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

BACKGROUND: Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. METHODS AND RESULTS: We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). CONCLUSION: These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.     

Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages

Objective

Tea tree oil (TTO) is an essential oil with anti-inflammatory properties, steam distilled from the plant Melaleuca alternifolia. We investigated the immunomodulatory properties of TTO and its components (terpinen-4-ol and alpha-terpineol) using lipopolysaccharide (LPS)-stimulated macrophages.

Methods

The ability of TTO, terpinen-4-ol and alpha-terpineol to modulate the macrophage response to bacterial LPS stimulation was assessed by ELISA for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 cytokine production and by western blotting for the activation of nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling, which are associated with the expression of pro-inflammatory cytokines. We used a human monocytic cell line (U937) differentiated into macrophages.

Results

LPS induced the production of all cytokines, and TTO and its components significantly reduced the production of IL-1β, IL-6 and IL-10. The production of TNF-α was not affected by either TTO or its major components. The modulation of cytokine production was not mediated by changes in NF-κB or p38 MAPK activation.

Conclusion

TTO, terpinen-4-ol and alpha-terpineol can suppress the production of inflammatory mediators in LPS-stimulated human macrophages; this inhibition was mediated by interfering with the NF-kB, p38 or ERK MAPK pathways.