Digestion by pepsin releases biologically active chromopeptides from C-phycocyanin, a blue-colored biliprotein of microalga Spirulina.

C-phycocyanin, the major protein of cyanobacteria Spirulina, possesses significant antioxidant, anti-cancer, anti-inflammatory and immunomodulatory effects, ascribed to covalently attached linear tetrapyrrole chromophore phycocyanobilin. There are no literature data about structure and biological activities of released peptides with bound chromophore in C-phycocyanin digest. This study aims to identify chromopeptides obtained after pepsin digestion of C-phycocyanin and to examine their bioactivities. C-phycocyanin is rapidly digested by pepsin in simulated gastric fluid. The structure of released chromopeptides was analyzed by high resolution tandem mass spectrometry and peptides varying in size from 2 to 13 amino acid residues were identified in both subunits of C-phycocyanin. Following separation by HPLC, chromopeptides were analyzed for potential bioactivities. It was shown that all five chromopeptide fractions have significant antioxidant and metal-chelating activities and show cytotoxic effect on human cervical adenocarcinoma and epithelial colonic cancer cell lines. In addition, chromopeptides protect human erythrocytes from free radical-induced hemolysis in antioxidative capacity-dependant manner. There was a positive correlation between antioxidative potency and other biological activities of chromopeptides. Digestion by pepsin releases biologically active chromopeptides from C-phycocyanin whose activity is mostly related to the antioxidative potency provided by chromophore.

Effect of Allium flavum L. and Allium melanantherum Panc. Extracts on Oxidative DNA Damage and Antioxidative Enzymes Superoxide Dismutase and Catalase.

Allium flavum L. and Allium melanantherum Panc. are wild growing plants used in traditional diet in Balkan region. While chemical composition and some biological activities of A. flavum have been reported, A. melanantherum, as an endemic in the Balkan Peninsula, has never been comprehensively examined. After chemical characterization of A. melanantherum, we examined the protective effect of methanol extracts of both species against t-butyl hydro-peroxide (t-BOOH)-induced DNA damage and mutagenesis. The bacterial reverse mutation assay was performed on Escherichia coli WP2 oxyR strain. DNA damage was monitored in human fetal lung fibroblasts (MRC-5) with alkaline comet assay. Obtained results indicated that extracts reduced t-BOOH-induced DNA damage up to 70 and 72% for A. flavum and A. melanantherum extract, respectively, and showed no effect on t-BOOH-induced mutagenesis. Since the results indicated modulatory effect on cell-mediated antioxidative defense, the effect of extracts on total protein content, and superoxide dismutase (SOD) and catalase (CAT) amounts and activities were monitored. Both extracts increased total protein content, while the increase of enzyme amount and activity was obtained only with A. melanantherum extract and restricted to CAT. The activity of CuZnSOD family was not affected, while SOD1 and SOD2 amounts were significantly decreased, indicating potential involvement of extracellular CuZnSOD. Obtained results strongly support the traditional use of A. flavum and A. melanantherum in nutrition and recommend them for further study.

Second generation steroidal 4-aminoquinolines are potent, dual-target inhibitors of the botulinum neurotoxin serotype A metalloprotease and P. falciparum malaria.

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 µM). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the Ki of compound 67 is 0.10 µM). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.

Sensitizing potential of enzymatically cross-linked peanut proteins in a mouse model of peanut allergy.

SCOPE: The cross-linking of proteins by enzymes to form high-molecular-weight protein, aggregates can be used to tailor the technological or physiological functionality of food products. Aggregation of dietary proteins by food processing may promote allergic sensitization, but the effects of enzymatic cross-linking of dietary proteins on the allergenic potential of food are not known. In this study, the bioavailability and the sensitizing or tolerizing potential of peanut proteins (PE) cross-linked with microbial tyrosinase from Trichoderma reesei and mushroom tyrosinase from Agaricus bisporus, were investigated. METHODS AND RESULTS: The impact of cross-linking of PE on the in vitro bioavailability of fluorescein isothiocyanate-labeled peanut proteins was tested in a Caco-2 cell monolayer and by competitive ELISA. The in vivo allergenicity or capacity to induce oral tolerance in mice were measured by serum levels of PE-specific antibodies and T cell cytokine production after exposure to PE and cross-linked PE. CONCLUSION: Enzymatic processing of peanut proteins by the two tyrosinases increased the bioavailability of major peanut allergen Ara h 2, but did not significantly change the allergenic or tolerizing properties of peanut. Enzymatic treatment of peanut proteins yielded cross-linked proteins with preserved molecular and immunological features of peanut allergens.

Ten years development of human resources in Serbian health system.

A key component of any healthcare reform process is to ensure that the services are delivered by the right numbers of staff with appropriate skills and training. In 2007, public health institutions in Serbia had 2% more employees than before the economic transition. Nevertheless, the trend of the total number of employees in the Serbian health care system still preserved a mild rising trend. The most prominent changes in the structure of human resources were effectuated in the total numbers of physicians, nurses and administrative and technical staff. Development of medical science and practice in Serbia is characterized by more intensive processes of specializations, resulting in increased number of specialists among medical doctors. Health care provided in in-patient institutions still employs most of the doctors. The number of unemployed physicians, dentists and pharmacists has been rising since 2000. Another aspect that explains the rise of unemployed, university educated human resources is the rising number of graduated physicians, dentist and pharmacists. Health care policy makers may recognize the need for more integrated planning of human resources in health care, in particular, making management of human resources responsive to system needs and design, instead of vice versa.

Job satisfaction among health care workers in Serbia.

According to literature review there seems to be a general agreement that job satisfaction among doctors is declining. This study's objective was to identify job satisfaction levels and their causes among health care workers, employed at the public health institutions. A job satisfaction survey of health care workers was therefore carried out in 197 public health centers in the Republic of Serbia, 157 primary health care centers and 40 general hospitals, in 2008. A satisfaction questionnaire, containing 24 items was used to investigate job satisfaction. Respondents (23.259), working in primary health care, indicated an average job satisfaction level of 3.08 +/- 0.67 on a 5-point scale. Respondents (11.302), working in general hospitals, indicated a lower average job satisfaction level of 2.96 +/- 0.63. The reported level of satisfaction was the highest for their opportunities to use their abilities, cooperation with colleagues and fellow workers, and freedom to choose their own methods of work. Doctors, working in primary health care centers, reported higher level of job satisfaction than hospital doctors. Overall, job satisfaction of doctors and nurses is relatively low. Increased pay rate and more adequate equipment, as well as possibilities for education and career improvement, would enhance their job satisfaction.

Health care managers as a crucial component of health care workforce in Serbia.

The aim of the paper was to describe and analyse health services management in Serbia, commencing with present status and projecting, as accurately as possible, future changes over the next years, skills and required competencies of the health management workforce. The study was done as a part of Ministry of Health/EU funded Project "Preparation for Health Management Training Programme in Serbia" by a desk review of current and draft legislation, related projects in the health sector and relevant local and international literature; semi-structured interviews with key local and international stakeholders and a structural analysis of the health management sector. The results of the study have shown that there was a big gap in knowledge and skills regarding Health Management in Serbia and a true need for such type of education.