Green synthesis and characterization of nontoxic L-methionine capped silver and gold nanoparticles.

The simple green method for synthesis of stable L-Methionine (L-Met) capped silver (Ag@LM NPs) and gold (Au@LM NPs) nanoparticles (NPs) without adding any additional reduction agent or stabilizer was developed. Colloidal dispersions were characterized by UV-Vis spectrophotometry. The size and spherical shape of NPs were evaluated by transmission electron microscopy. Their surface covering was confirmed by atomic force microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential measurements. Density functional theory calculations pointed that the preferential adsorption mode of L-Met on both Ag and Au surfaces was a vertical binding geometry via -NH2 group, while horizontal binding mode via S and -NH2 groups is also possible. The genotoxicity (evaluated by the micronucleus assay) of NPs, as well as their effects on some oxidative stress parameters (catalase activity, malondialdehyde level), were assessed in vitro using human peripheral blood cells as a model system. The influence of NPs on the morphology of lymphocyte cells studied using atomic force microscopy revealed that the membrane of cells remained unaffected after the treatment with NPs. When considering the effects of NPs on catalase activity and malondialdehyde level, neither particle type promoted oxidative stress. However, the treatment of lymphocytes with Ag@LM NPs induced a concentration-dependent enhancement of the micronuclei incidence and suppression of the cell proliferation while Au@LM NPs promoted cell proliferation, with no significant effects on micronuclei formation. The Ag@LM NPs were more prone to induce DNA damage than Au@LM NPs, which makes the latter type more suitable for further studies in nano-medicine.

Do health care workforce, population, and service provision significantly contribute to the total health expenditure? An econometric analysis of Serbia.

BACKGROUND: In times of austerity, the availability of econometric health knowledge assists policy-makers in understanding and balancing health expenditure with health care plans within fiscal constraints. The objective of this study is to explore whether the health workforce supply of the public health care sector, population number, and utilization of inpatient care significantly contribute to total health expenditure. METHODS: The dependent variable is the total health expenditure (THE) in Serbia from the years 2003 to 2011. The independent variables are the number of health workers employed in the public health care sector, population number, and inpatient care discharges per 100 population. The statistical analyses include the quadratic interpolation method, natural logarithm and differentiation, and multiple linear regression analyses. The level of significance is set at P < 0.05. RESULTS: The regression model captures 90 % of all variations of observed dependent variables (adjusted R square), and the model is significant (P < 0.001). Total health expenditure increased by 1.21 standard deviations, with an increase in health workforce growth rate by 1 standard deviation. Furthermore, this rate decreased by 1.12 standard deviations, with an increase in (negative) population growth rate by 1 standard deviation. Finally, the growth rate increased by 0.38 standard deviation, with an increase of the growth rate of inpatient care discharges per 100 population by 1 standard deviation (P < 0.001). CONCLUSIONS: Study results demonstrate that the government has been making an effort to control strongly health budget growth. Exploring causality relationships between health expenditure and health workforce is important for countries that are trying to consolidate their public health finances and achieve universal health coverage at the same time.

Determinants of intention to work abroad of college and specialist nursing graduates in Serbia.

BACKGROUND: In a country with a poor economy and limited job opportunities, the outmigration of students is not commonly perceived as a problem but rather is perceived as a solution to the high unemployment facing young health professionals. OBJECTIVES: Study objectives were to identify the prevalence of intention to work abroad of nursing graduates to point to the predictors of intention to work abroad and predictors of having a firm plan to work in a foreign country. DESIGN: Descriptive study, a survey. SETTINGS: College and specialist nursing schools, Serbia. PARTICIPANTS: 719 nursing graduates from the 2012/2013 school year. METHODS: Voluntarily completed a questionnaire that was designed with regard to similar surveys administered in EU-candidate countries during the pre-accession period. Data were analysed with descriptive and multivariate regression analyses. RESULTS: Almost 70% (501) of respondents indicated an intention to work abroad. Of the nurses, 13% already had established a firm plan to work abroad. Single graduates and those with a friend or relative living abroad were more likely to consider working abroad than were their counterparts (odds ratios were 2.3 and 1.7, respectively). The likelihood of considering working abroad decreased by 29% when the individuals' financial situation was improved. Factors associated with having a firm plan were previous professional experience in a foreign country, having someone abroad and financial improvement (5.4 times, 4.8 times and 2 times greater likelihood, respectively). CONCLUSIONS: The high prevalence of intention to work abroad suggests the need to place the issue of the out-migration of nursing graduates on the policy agenda. College and specialty nursing graduates and health technicians are prepared to work abroad in search of a better quality of life, better working conditions and higher salaries.

Inhibition of AChE by single and simultaneous exposure to malathion and its degradation products.

In vitro inhibition of bovine erythrocytes acetylcholinesterase (AchE) by separate and simultaneous exposure to organophosphorous insecticide malathion and the transformation products, which are generally formed during the storage or natural as well as photochemical degradation pathways of malathion, was investigated. The increasing concentration of malathion, its oxidation product - malaoxon and isomerisation product - isomalathion inhibited AChE activity in a concentration-dependent manner. The half-maximum inhibitory concentrations (IC(50) values): (3.2 +/- 0.1) x 10(-5) mol/l, (4.7 +/- 0.8) x 10(-7) mol/l and (6.0 +/- 0.5) x 10(-7)mol/l were obtained from the inhibition curves induced by malathion, malaoxon and isomalathion, respectively. However, the products formed due to photoinduced degradation, phosphorodithioic O,O,S-trimethyl phosphorodithioic ester (OOS(S)) and O,O-dimethyl thiophosphate did not noticeably affect the enzyme activity at all investigated concentrations, while diethyl maleate inhibited the AChE activity at concentrations >10 mmol/l. By simultaneous exposure of the enzyme to malaoxon and isomalathion in various concentration combinations the additive effect was achieved by low concentration of inhibitors, while the antagonistic effect was obtained at high concentration (>or= 3 x 10(-7) mol/l) of inhibitors. Inhibitory power of irradiated samples of 1 +/- 10(-5) mol/l malathion can be attributed to the formation of malaoxon and isomalathion, organophosphates about 100 times more toxic than their parent compound, while the presence of non-inhibiting degradation product OOS(S) did not affect the inhibitor efficiency of inhibiting malathion by-products, malaoxon and isomalathion.

Epidemiology of end-stage renal disease and current status of hemodialysis in Yugoslavia.

Maintenance hemodialysis (HD) in Yugoslavia started in the sixties and followed the dialysis trends in the Western Europe. However, in the last decade the development of renal replacement therapy (RRT) slowed down. In this report the epidemiology of ESRD from 1997-1999 and the survey of the status of HD treatment in Yugoslavia in 1999 are presented. Epidemiological data are obtained by the annual center questionnaires (response rate: 92.6 -94.2%). The survey of HD status is based on a specific questionnaire and covered 2108 patients (65%). At the end of 1999 there were 56 RRT centers in Yugoslavia treating 3939 patients: 3232 (82%) patients by HD, 248 (6.3%) by peritoneal dialysis, and 459 (11.7%) living with transplanted kidney. In a three year period, incidence of ESRD ranged from 108-128 pmp, point prevalence from 435-463 pmp and mortality rate from 20.7-17.9. Numerous refugee patients were treated over the last 10 years. Main causes of ESRD were glomerulonephritis (30%); Balkan nephropathy represented 11% and diabetic nephropathy 7% of all primary renal diseases. Cardiovascular and cerebrovascular diseases were the most common causes of death of RRT patients. Most centers are overcrowded and HD machines are worn out. Mean Kt/V was 1.19+/-0.08, mean URR% 58.8+/-7.4. The shortage of drugs prevented adequate management: 83% of HD patients had hemoglobin level less than 100 g/L but only 10.3 -17.8% were treated with rHuEpo; 64.5% of patients had phosphate levels higher than 1.7 mmol/L but only 33.5% used phosphate binders; 47% of patients had hypertension despite the antihypertensive therapy. The prevalence of hepatitis B remained unchanged (about 14%) in HD population during the last three years, but the prevalence of anti-HCV positive patients decreased (31-23%). In conclusion, there is a well developed dialysis service in Yugoslavia but insufficient conditions for adequate treatment.

Influence of ribavirin on the micronucleus formation and in vitro proliferation of human lymphocytes.

Cytotoxic effects of the antiviremic drug ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were evaluated in vitro measuring micronucleus formation and cell proliferation kinetics in whole blood cultures employing cytokinesis block (CB) micronucleus test. The cells were exposed to ribavirin doses ranging from 0.05 0.65 micromol/ml at three different incubation times. The frequency of micronuclei in treated samples demonstrated relatively low ability of ribavirin to induce micronuclei. However, the lowest concentration ofribavirin markedly changed the frequency of mononucleated and multinucleated cells, particularly binucleated ones, which declined significantly. The decline in the frequency ofbinucleate cells was followed with accumulation of greater number of mononucleate cells. Decreased proliferation potential of lymphocytes treated with ribavirin indicates that cells are arrested prior to metaphase. The present investigation showed that ribavirin is capable to induce a delay in cellular proliferation at all the doses assayed. The study demonstrated that CB micronucleus assay is simple and rapid method that can be used to assess toxic effect of drugs in vitro.

Prevention and recovery of CuSO4-induced inhibition of Na+/K+ -ATPase and Mg2+ -ATPase in rat brain synaptosomes by EDTA.

Enzymatic activities of Na+/K+-ATPase and Mg2+ -ATPase from rat brain synaptic plasma membrane were studied in the absence and presence of EDTA. The aim of the study was to examine the ability of this strong chelator to prevent and recover the CuSO4-induced inhibition. The influence of experimentally added CuSO4 and EDTA on MgATP2- complex and 'free' Cu2+ concentrations in the reaction mixture was calculated and discussed. CuSO4 induced dose-dependent inhibition of both enzymes in the absence and presence of 1 mM EDTA. In the absence of EDTA, the IC50 values of Cu2+, as calculated from the experimental curves, were 5.9x10(-7) M for Na+/K+ -ATPase and 3.6x10(-6) M for Mg2+ -ATPase. One millimolar EDTA prevented the enzyme inhibition induced by CuSO4, but also reversed the inhibited activity, in a concentration-dependent manner, following exposure of the enzymes to the metal ion, by lowering 'free' Cu2+ concentration. Kinetic analysis showed that CuSO4 inhibits both the Na+/K+ -ATPase and Mg2+ -ATPase, by reducing their maximum enzymatic velocities (Vmax), rather than apparent affinity for substrate MgATP2- (K0.5), implying the noncompetitive nature of enzyme inhibition induced by the metal. The kinetic analysis also confirmed two distinct Mg2+ -ATPase subtypes activated in the presence of low and high MgATP2- concentrations. K0.5 and Vmax were calculated using a computer-based program. The results of calculation showed that MgATP2- concentration in the kinetic experiments exceeded three times the apparent K0.5 value for the enzyme activation.

Spectrophotometric and electrochemical study of protolytic equilibria of some oximes-acetylcholinesterase reactivators.

Newly synthesized oximes, mono and bis imidazole derivatives, which promise to be more effective acetylcholinesterase reactivators than standard antidotes used, were investigated by spectrophotometric and electrochemical methods. The electrochemical investigations confirmed the existence of overlapping equilibria, obtained by spectrophotometric methods. Dissociation constants of those oximes were also obtained by numerical treatment of overlapping equilibria, using the Lavendberg Marquardt least square method, and when compared with the same for some similar compounds, were found to be very effective acetylcholinesterase reactivators. The distribution of ionic forms of the investigated oximes, as a dependence of pH values, was calculated from the obtained values of dissociation constants. The results indicated that many oxime anions will be available at physiological pH 7.4 and a relative increased ability to reactivate inhibited acetylcholinesterase could be expected.

Protolytic constants of nizatidine, ranitidine and N,N'-dimethyl-2-nitro-1,1-ethenediamine; spectrophotometric and theoretical investigation.

The prototropic exchange equilibria of two drugs, nizatidine (I) and ranitidine(II), and also of structurally related the N,N'-dimethyl-2-nitro-1,1-ethenediamine molecule (III) were investigated. From the changes in electronic spectra in media of various acidity several protonation constants were determined. For pK values were -0.82, 1.95, and 6.67; for ranitidine pK values were 1.95 and 8.13; and for III was 2.60. The hydroxylation equilibrium constant in strongly alkaline media was determined too. Corresponding pK(a) values were 13.23 for I, 13.36 for II and 13.76 for III. Molecular orbital calculations of electronic spectra confirmed that pK 1.95 for I and II, and pK 2.60 for III, are associated with C-protonation of nitroethenediamine fragment, while all pK(a) values correspond to the addition of HO- anion at the same double bond.

Kinetics of the reaction of S-carboxymethyl-L-cysteine with palladium(II) chloride.

The influence of the acidity and the Cl- concentration on the kinetics of the complex formation between s-carboxymethyl-L-cysteine and Pd(II) chloride was studied with a stopped-flow technique in the pH range from 1.5 to 5.0 at 25 degrees C. The reaction mechanism involving Pd(H2O)4-nCln, LH-, LH2 and LH3+ species was proposed. Fairly good agreement between the computed and experimentally determined rate constants was found.

A secure method of repair of large ventral hernias with Marlex mesh to eliminate tension.

The use of Marlex mesh to bridge abdominal fascial defects is well known. However, its use in reinforcing securely the repair of a minority of ventral hernias which can be approximated, only under considerable tension, is described.

Specialized nutritional support and cancer.

Over a 7 1/2-year period, 94 cancer patients presenting considerable operative risk were managed by total parenteral nutrition (TPN). All were nutritionally depleted, had obstruction to the gastrointestinal tract or had postoperative complications such as enterocutaneous fistulas, evisceration or intra-abdominal sepsis, which left TPN as the only means of achieving anabolism. When TPN was started preoperatively and continued post-operatively (28 patients--Group 1), no deaths or significant complications occurred. When TPN was first started after life-threatening complications had occurred (58 patients--Group 2), the mortality was 17.2%, so that a high incidence of recovery was achieved. When TPN was used in inoperable cachectic patients (8 patients--Group 3) to enable them to tolerate radiotherapy or chemotherapy, the mortality was 37.5%. This latter group is small, but TPN is worthwhile in selected patients where significant palliation and improvement in the quality of life can occur. With careful technique, risk of sepsis with TPN was no greater than in noncancer patients.

Specialized nutritional support in the cancer patient: is it worthwhile?

Over a 7 year period, 85 cancer patients were managed by the nutrition service of St. Joseph's Hospital, Toronto. All these patients were nutritionally depleted, had obstruction to the gastrointestinal tract, or had postoperative complications such as enterocutaneous fistulas, evisceration or intraabdominal sepsis, which left total parenteral nutrition (TPN) as the only means of achieving positive nitrogen balance. A prospective study started in 1970 has found that when cancer was resectable and TPN was started preoperatively and continued postoperatively (24 patients-group 1) until the patient could take a normal diet, no deaths or significant complications occurred. When TPN was first started after life-threatening complications had occurred (53 depleted patients-group 2), the mortality was 17.0%. This mortality was only 4.5% after complications following operations for colon cancer, but was much higher with esophageal, pancreatic and bladder cancer, and especially after complications following surgery where radiotherapy had previously been given to abdomen or pelvis. When TPN was used in inoperable, cachectic patients (8 patients-group 3) to permit them to tolerate radiotherapy or chemotherapy, the mortality was 37.5%. This latter group is small, but TPN is worthwhile in selected patients where significant palliation and improvement in the quality of life can occur.