Silver nanoparticles, a promising treatment against clinically important fluconazole-resistant Candida glabrata.

Resistance to azole antifungal agents is a challenging limitation in Candida glabrata treatment. It is associated with decreased intracellular concentrations of antifungal agents as a result of overexpression of efflux pumps on the cellular plasma membranes. This work evaluates the potential of silver nanoparticles (AgNPs) to reverse the resistance of fungal cells to fluconazole. Silver nanoparticles were prepared using wet chemical method and characterised by UV-Vis spectrophotometry, dynamic light scattering, and zeta potential. Broth microdilution and pour plates methods were used to study the anticandidal activity using two C. glabrata fluconazole-resistant strains (DSY565 and CBS138) known to overexpress active efflux pumps, and a standard fluconazole sensitive strain ATCC 22553. Silver nanoparticles-fluconazole combinations decreased concentrations of fluconazole substantially without compromising the activity. These findings suggest that AgNPs enhance the efficacy of fluconazole and offer a promising application in therapy of C. glabrata infections.

Characterization of staphylococci sampled from diabetic foot ulcer of Jordanian patients.

AIMS: The aim of this study was to isolate and characterize staphylococcal isolates from diabetic foot ulcers (DFU) in Jordanian patients. METHODS AND RESULTS: Selected aerobic pathogens recovered from DFU specimens and patients' nares with a focus on staphylococci were investigated. Antimicrobial susceptibilities and the prevalence of methicillin-resistant staphylococci (MRS) were determined. SCCmec types and toxigenic characteristics were analysed and spa typing was performed for methicillin-resistant Staphylococcus aureus (MRSA) isolates. The relationship between toxigenic characteristics of MRSA and the Wagner ulcer grading system was statistically analysed. A total number of 87 DFU patients were recruited for the study. The DFU cultures were polymicrobial. Members of the genus Staphylococcus were the most common among DFU-associated isolates found in 48·3% (n = 42) of all patients enrolled. Coagulase-negative staphylococci (CoNS) comprised 63·3% of staphylococci isolated from DFUs predominated by Staphylococcus epidermidis in both DFU (7·6%) and nares (39·2%). Staphylococcus aureus was isolated from DFUs and nares in 14·2 and 9·8%, respectively, while 93 and 70% of these isolates were MRSA. Most of MRSA carried SCCmec type IV (76·2%) while SCCmec elements were non-typeable in most methicillin resistant coagulase negative staphylococci (MR-CoNS) (61·9%). The most frequent MRSA spa type was t386 (23·8%). Most MRSA and MR-CoNS exhibited resistance towards aminoglycosides, fluoroquinolones and macrolides and susceptibility towards vancomycin, mupirocin and linezolid. No association was found between the possession of pvl, tst, sea and hlg toxins and Wagner ulcer grading system (P value >0·05). CONCLUSIONS: This analysis of Jordanian DFU culture demonstrated its polymicrobial nature with predominance of Staphylococcus sp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first of its type to assess the microbiology of DFU among Jordanian patients. The results will help in the appropriate application of antimicrobial chemotherapy in the management of DFU.

Smoking behaviour modulates pharmacokinetics of orally administered clopidogrel.

BACKGROUND AND OBJECTIVES: Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. METHODS: Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t(1/2e)), and area under the curve (AUC(0-->infinity)). RESULTS: One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC(0-->infinity) (smokers: 6.24 +/- 2.32 microg/h/mL vs. non-smokers: 8.93 +/- 3.80 microg/h/mL, P < 0.001) and shorter half-life (smokers: 5.46 +/- 2.99 vs. non-smokers: 8.43 +/- 4.26, P = 0.001). Smoking behaviour had no influence on C(max) (P = 0.3) and T(max) (P = 0.7). There was no statistically significant difference in C(max), AUC(0-->infinity), T(max) and t(1/2e) between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean +/- SE; 26.93 +/- 0.16 vs. 23.11 +/- 0.27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (C(max) = 3.09 +/- 0.99 microg/mL, CV = 32%), (T(max) =0.76 +/- 0.24 h, CV = 31.6%), (AUC(0-->infinity) = 7.98 +/- 3.58 microg/h/mL, CV = 44.8%), and (t(1/2e) = 7.38 +/- 4.10 h, CV = 55.6%). CONCLUSION: Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed.

An innovative pharmaceutical care practical course.

The innovative practical course was developed to improve the students' ability to acquire pharmaceutical care skills. The primary components of the course were in-school training using small group discussions and hospital experience including identification, analysis, prevention and resolution of drug-therapy problems, patient counseling on their medications and diseases, and interaction with medical team. Specific objectives of the research were to (1) compare students' performance before and after the course, (2) measure students' perceptions of their pharmaceutical care skills before and after the course, (3) determine students' perception of the value of the course. Statistical comparison of pre-test and post-test grades indicated both a retention and acquiring pharmaceutical care skills. A pre-course and post-course survey instrument was designed to measure students' perception of their pharmaceutical care skills. Perception of most of the items of the survey was significantly improved at the end of the course. Overall, the majority of students were highly satisfied with the course. In conclusion, the present study demonstrates that the innovative pharmaceutical care practical course was successfully introduced.

[Effect of tuftsin and hydroxymethacil on tyrosine hydrolase of macrophages in chronic stress]. / Vliianie taftsina i oksimetatsila na tirozingidrolazu makrofagov pri khronicheskom stresse.

It has been established that rat peritoneal macrophages possess tyrosine hydroxylase activity which has been characterized by KM4, 2 microM, Vmax 30 nmole/min per mg of protein. After 15 days of electronociseptive stimulation almost all tyrosine hydroxylase activity has been established in the form which has tyrosine KM47.0 M and Vmax 18.6 nmole/min. per mg of protein. Immunostimulator hydroxymethacil++, at its intraperitoneal injections to stressed rats during 7 days induced the appearance of low-affinity form of tyrosine hydroxylase with KM270 microM and Vmax 27.8 nmole/min.per mg of protein. The same low affinity form of the enzyme has been established after injections of tuftsin which possesses immunostimulating properties.

Changes in synaptosomal membranes from cerebral cortex due to psychogenic stress in rats.

The changes in synaptosomal membranes in comparison with those of macrophages and mitochondria during repeated psychogenic stress were evaluated using a specially designed multiprobe procedure. Activity of Na,K-ATPase activity was measured as a functional marker for synaptosomal membranes. The interaction of peritoneal macrophages with nitrobluetetrazole (NBT-test) was also evaluated. Some bioenergetic parameters were measured in mitochondria using spectrophotometric techniques. The data revealed profound structural and functional changes in synaptosomal membranes on 15th day of stress. Those in macrophage membranes, present on 3rd and 6th day were not accompanied by functional ones. In conclusion the present data suggest that stress repeated for 15 days leads to a modelled psychopathology in rats and induce selective structural and functional changes in synaptosomal membranes from the cerebral cortex. This model may be used for investigations of the effects of psychotropic drugs.

[Post-stress correlation of the functional activity of macrophages by tuftsin and its derivatives]. / Poststressornaia korreliatsiia funktsional'noi aktivnosti makrofagov taftsinom i ego proizvodnymi.

The effect of 15 day programmed neurotization on the functional activity of the peritoneal macrophages has been studied. The NBT-test and the adhesion measurements were used. The experimental neurosis resulted in the decrease of the macrophage functional activity and in leukopenia. Tuftsin did not restore the stress induced depression of macrophage activity but led to additional rise of the adrenal glands weight and to pronounced granulocyte-monocytosis. Pentapeptide analog of tuftsin gave the additional inhibition of NBT-activity of the macrophage. Heptapeptide analog favoured the restoration of the macrophage activity after neurotization and stimulated lymphopoiesis.