Heparin disaccharides inhibit tumor necrosis factor-alpha production by macrophages and arrest immune inflammation in rodents

Inflammation is the clinical expression of chemical mediators such as the pro-inflammatory cytokine tumor necrosis factor (TNF-)-alpha produced by macrophages and other cells activated in the immune response. Hence, agents that can inhibit TNF-alpha may be useful in treating arthritis and other diseases resulting from uncontrolled inflammation. We now report that the cleavage of heparin by the enzyme heparinase I generates sulfated disaccharide (DS) molecules that can inhibit the production of TNF-alpha. Administration of nanogram amounts of the sulfated DS molecules to experimental animals inhibited delayed- type hypersensitivity to a skin sensitizer and arrested the joint swelling of immunologically induced adjuvant arthritis. Notably, the sulfated DS molecules showed a bell-shaped dose-response curve in vitro and in vivo: decreased effects were seen using amounts of the DS molecules higher than optimal. Thus, molecular regulators of inflammation can be released from the natural molecule heparin by the action of an enzyme.      

Effects of work organization on the mental health of nursing staff

A survey was carried out among a sample of 973 nurses in hospitals in the Valencian Community (Spain). The aim was to study the relation between work organization, sociodemographic and professional factors and the mental health of nursing staff. The information was collected by means of a questionnaire. Three indicators were used to study mental health: fatigue, sleep disturbance and psychological or psychosomatic indicators of mental suffering. Work organization affected the mental health of workers with varying impact according to the mental health indicator under consideration. Dissatisfaction due to work schedule, psychological and mental load increased the risk of showing signs of fatigue, with a prevalence odds ratio (POR) of 2.15, 2.00, 1.86, respectively, along with the risk of psychological symptoms with a POR of 2.36, 1.80, 2.10, respectively. Permanent night shifts or rotating night shifts increased the risk of sleep disturbance with a POR of 2.00 and 1.34 respectively.     

Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology

Summary— There are now more than 50 studies concerning neuroleptic blood levels and clinical outcome relationships. Haloperidol, the most studied, is the only antipsychotic permitting some conclusions. A number of authors suggest that the striking lack of agreement between different studies results from heterogeneity of their quality. Here, we have used a scoring system for assessing the quality of those studies. According to this system, none (0/14) of the studies having a score <0.60 was able to show a therapeutic window, as compared to 53% (10/19) of those having a score ≥0.60 (p = 0.002, Fisher exact test). Also, the studies able to identify the presence of a therapeutic window during haloperidol treatment were those having sample sizes >20 ( p = 0.06) and those whose patients were treated with fixed doses ( p = 0.02). The diagnosis of schizophrenia in the studies seems not to be an exclusive condition, as compared with those also including schizophreniform and schizoaffective disorders (p = 0.12). Our qualitative analysis of haloperidol blood level publications seem to indicate that an upper limit may exist for haloperidol efficacy; values above this limit seem not to provide any supplementary clinical improvement and may even reduce therapeutic effect.     

FS06.7The new fragrance mix II – test results of a multicentre European Study

A new fragrance mix (FM II) with 6 frequently used chemicals was evaluated in consecutive patients patch tested in 6 dermatological centres in Europe. 28% FM II contained 5% Lyral, 1% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10% alpha‐hexyl cinnamic aldehyde (AHCA); in 14% FM II the single constituents’ concentrations was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable and none. The frequency of positive reactions to the currently used 8% fragrance mix (FM I) and the new mix in 1703 patients was as follows: FM I, 6.6%; 2.8% FM II, 1.3%; 14% FM II, 2.9%; 28% FM II, 4.1%. The number of doubtful/irritant reactions was 7.2% for FM I and ranged from 1.8% to 10.6% for FM II. 8.7% of tested patients had a certain fragrance history. Of these 25.2% were positive to FM I, reactivity to FM II was dose‐dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history – certain and none – values for sensitivity (sens) and specificity (spec) were calculated. Sens: FM I, 27.2%; 2.8% FM II, 8.7%; 14% FM II, 15.9%; 28% FM II, 21.5%. Spec: FM I, 96.3%; 2.8% FM II, 99.5%; 14% FM II, 98.7%; 28% FM II, 97.9%. 31/70 (44.3%) patients positive to 28% FM II were negative to FM I. In the group of patients with a certain history a total of 6 patients was found reacting only to FM II. Simultaneous break‐down testing with the single constituents produced positive reactions in 54.3% for 28% FM II and 48% for 14% FM II. Lyral was the dominating single constituent with positive reactions (37.1% for 28% FM II, 36% for 14% FM II), followed by citral, farnesol, citronellol, AHCA and coumarin. Chemical analysis for the 6 constituents of FM II was performed on 25 products used by 12 patients being patch test positive to FM II. Lyral was detected in 76% of these products, citral in 16% and AHCA in 8%. In conclusion, the new FM II detects additional patients with contact allergy to fragrances missed by the currently used FM I. The medium concentration, 14% FM II, is probably the most useful one for diagnostic screening.     

In silico molecular docking of niloticin with acetylcholinesterase 1 (AChE1) of <Emphasis Type="Italic">Aedes aegypti</Emphasis> L. (Diptera: Culicidae): a promising molecular target

Synthetic insecticides used in mosquito control program are harmful to environment and also affect other associated organisms. As a choice, plant-based natural compounds proved to be a good alternative to synthetic insecticides. In a study, we had reported niloticin (C₃₀H₄₈O₃) from the plant Limonia acidissima L. was effective and disturbed the larval growth of A. aegypti. The main molecular target for many commercially available synthetic mosquitocides is acetylcholinesterase (AChE), which plays a major role in larval knockdown/resistant mechanisms. AChE1 is a serine protease, which fulfills the physiological function of neurotransmitter hydrolysis at synapses. In the present study, we performed molecular docking studies with acetylcholinesterase 1 (AChE1) of A. aegypti with niloticin (C₃₀H₄₈O₃) and compared with commercially available chemical larvicidal compound temephos (C₁₆H₂₀O₆P₂S₃). The docking results revealed that the binding affinities and energy values of niloticin (?8.4 kcal/mol) were found to be significantly higher than temephos (?4.75 kcal/mol). Both niloticin (C₃₀H₄₈O₃) and temephos (C₁₆H₂₀O₆P₂S₃) showed the same binding residues (THR’58 and HIS’62) on AChE1. Further, niloticin produced least binding energy (?8.4 kcal/mol), good inhibition constant value (695.18 μM) and high ligand efficiency (0.25) than temephos, suggesting that niloticin (C₃₀H₄₈O₃) could be used against the larvae of A. aegypti as an effective AChE1 inhibitor.