A randomized, double-blind placebo-controlled add-on trial to assess the efficacy, safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus.

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three-month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.

Development and Evaluation of Vaginal Suppository Containing Althaea officinalis L. Polysaccharide Extract

Abstract Intrauterine adhesions cause several gynecological problems. Althaea officinalis L. roots known as marshmallows contain polysaccharides (M.P.) which possess anti-inflammatory and anti-ulcerogenic activities also can form a bio-adhesive layer on damaged epithelial membranes prompting healing processes. Vaginal formulations of herbal origin are commonly applied to relieve cervico-uterine inflammation. Herein, we aim to develop and evaluate vaginal suppositories containing polysaccharides isolated from the A. officinalis root. Six formulations (four P.E.G.-based and two lipid-based suppositories containing 25% and 50% M.P.) met standard requirements, which were then subjected to qualitative and quantitative evaluation. All suppositories exhibited acceptable weights, hardness, content uniformity, melting point, and disintegration time, which fall within the acceptable recommended limits. Higher concentrations of M.P. in PEG-bases moderately increased the hardness (p<0.05). PEG-formulations showed content uniformity>90% of the average content while it was 75-83% for suppocire formulations. All formulations disintegrated in<30minutes. In-vitro release test revealed that M.P. release from 25%-MP formulations was higher than that of 50%-M.P. suppositories. Overall, results revealed the feasibility of preparing P.E.G.-or lipid-based suppositories containing M.P., which met the B.P. quality requirement

pH-sensitive soluble soybean polysaccharide/SiO2 incorporated with curcumin for intelligent packaging applications.

In the present work, the effect of various concentrations of SiO2 nanoparticles (5, 10, and 15%) on physicochemical and antimicrobial properties of soluble soybean polysaccharide (SSPS)-based film was investigated. Then, the migration of SiO2 nanoparticles to ethanol as a food simulant was evaluated. Subsequently, curcumin was added to the nanocomposite formulation to sense the pH changes. Finally, the cytotoxicity of the developed packaging system was investigated. With increasing nanoparticle concentration, the film thickness, water solubility, and water vapor permeability decreased and mechanical performance of the films improved. SSPS/SiO2 nanocomposite did not show antibacterial activity. SEM analysis showed that SiO2 nanoparticles are uniformly distributed in the SSPS matrix; however, some outstanding spots can be observed in the matrix. A very homogeneous surface was observed for neat SSPS film with R a and R q values of 3.48 and 4.26, respectively. With the incorporation of SiO2 (15%) into SSPS film, R a and R q values increased to 5.67 and 5.98, respectively. Small amount of SiO2 nanoparticles was released in food simulant. The nanocomposite incorporated with curcumin showed good physical properties and antibacterial activity. A strong positive correlation was observed between TVBN content of shrimp and a* values of the films during storage time (Pearson's correlation = 0.985).

Evaluation of wound healing efficiency of vancomycin-loaded electrospun chitosan/poly ethylene oxide nanofibers in full thickness wound model of rat.

Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent.

Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review.

Nowadays, due to spreading antibiotic resistance among clinically relevant pathogens, the requirement of novel therapeutic approaches is felt more than ever. One of the alternative strategies is anti-virulence therapy without affecting bacterial growth or viability. In Pseudomonas aeruginosa, an opportunistic human pathogen that exhibits intrinsic multi-drug resistance, both virulence factors' production and biofilm formation depends on its quorum sensing (QS) network. Therefore, targeting the key proteins involved in QS system is an attractive method to overcome P. aeruginosa pathogenicity and resistance. The transcriptional regulator PqsR, also called MvfR, is one of these major proteins which employs 3,4-dihydroxy-2-heptylquinoline (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signaling molecules. Reviewing the advances in development of small molecules inhibit this protein, assist to open a new window to smart molecule design that may revolutionize treatment of P. aeruginosa infections.

Effects of Omeprazole and Caffeine Alone and in Combination with Gentamicin and Ciprofloxacin Against Antibiotic Resistant Staphylococcus Aureus and Escherichia Coli Strains.

OBJECTIVE: Antibiotic resistance is a global health problem and threatens health of societies. These problems have led to a search for alternative approaches such as combination therapy. The aim of the present study was to investigate the effect of caffeine and omeprazole in combination with gentamicin or ciprofloxacin against standard and clinically resistant isolates of Staphylococcus aureus and Escherichia coli. METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interaction of non- antibiotic drugs with gentamicin and ciprofloxacin was studied in vitro using a checkerboard method and calculating fraction inhibitory concentration index (FICI). Verapamil as efflux pump inhibitor was used to evaluate the possible mechanism of bacterial resistance to antibiotics. RESULTS: The MIC and MBC values of gentamicin against bacterial strains were in the range of 20- 80 µg/ml and 40-200 µg/ml, respectively. Caffeine and omeprazole had no intrinsic inhibitory activity against tested microorganisms. However, upon combination of caffeine with antibiotics, the synergistic effects were observed. Verapamil was able to reduce the MIC values of gentamicin (4 folds) only in some bacterial strains. CONCLUSION: These findings indicated that caffeine was effective in removing bacterial infection caused by S. aureus and E. coli. The relevant mechanisms of antibiotic resistance were not related to the drug efflux.

Characterization of a green nanocomposite prepared from soluble soy bean polysaccharide/Cloisite 30B and evaluation of its toxicity.

The present paper aims to elucidate the structural, thermal and mechanical properties of soybean polysaccharide (SSPS)/Cloisite 30B. Tensile strength of the nanocomposite films improved with incorporation of nanoparticles, whereas elongation at break decreased. Surface roughness of the samples increased with the addition of nanoclay. Neat SSPS film and SSPS-1% Cloisite 30B had a relatively smooth surface with no irregularities, while for the samples containing 3 and 7% Cloisite 30B, the surface was rough. DSC analysis demonstrated that following an increase in nanoparticles content, the melting temperature of the nanocomposite elevated, whereas, glass transition temperature decreased. The results of antibacterial activity indicated that Cloisite 30B could inhibit the growth of Salmonella typhi PTCC 1609, Staphylococcus epidermis PTCC 1114 (ATCC 12228) and Listeria monocytogenes PTCC 1165. SSPS-Cloisite 30B nanocomposite could not inhibit the growth of Aspergillus niger. The results demonstrated that the migration of nanoparticles might happen into deionized water as a food simulant, but they could not migrate into bread as a food model. Furthermore, it was found that Cloisite 30B nanoparticles had cytotoxicity effect, and thus, it is recommended that Cloisite 30B/SSPS nanocomposites be used only for the packaging of solids foods such as bread.

Soluble soybean polysaccharide/TiO2 bionanocomposite film for food application.

In the current study, a set of biodegradable soybean polysaccharide (SSPS) nanocomposites containing different ratios of TiO2 nanoparticles was characterized as new packaging system. X-ray diffraction (XRD) measurement showed that the crystalline structure of the TiO2 nanoparticles remained intact in the polysaccharide matrix and the surface of nanocomposites containing 1-3% TiO2 was observed morphologically uniform under scanning electron microscopy (SEM). Dynamic mechanical thermal analysis revealed that the magnitude of storage modulus was 3.62-fold higher in SPSS/TiO2 nanocomposites containing 7 wt.% of TiO2 than control SSPS indicating improvement in the physical properties of the film supposed to be utilized for food packaging. With respect to the concern over the safety of these nanocomposites, inductively coupled plasma-optical emission spectroscopy (ICP-OES) showed that no TiO2 was detected in bread samples covered by SSPS/TiO2 film and stored for 6 months. Similarly, the nanocomposite films only released a minuscule amount (21.05 ±â€¯0.054 ppm) of TiO2 in water. TiO2 nanoparticles were found in the plasma membrane of epithelial cell line after long-term exposure (10-day) of these cells to large amounts of the free nanoparticles. SSPS/TiO2 nanocomposites showed excellent antimicrobial activity against Staphylococcus aureus PTCC 1431 (ATCC 25923), while neither anti-cancerous nor pro-cancerous activity was observed for these nanocomposites denoting their neutrality with respect to cancer suppression or progression in gastrointestinal tract. In conclusion, SSPS/TiO2 nanocomposites could be a promising packaging system for food industries' objective regarding their physical characteristics, low rate of Ti transition, and low health risk.

Characterization of soluble soybean (SSPS) polysaccharide and development of eco-friendly SSPS/TiO2 nanoparticle bionanocomposites.

This research aims to characterization of soluble soybean polysaccharide (SSPS) and development of a biodegradable SSPS nanocomposites prepared using various concentrations of TiO2 nanoparticles. 13C NMR suggested that backbone of SSPS is rhamnogalacturonan [1→4)-α-GalAp-(1/2)-α Rhap(1→]. Weight average molecular weight, number average molecular weight (Mn) and polydispersity index (PDI) of SSPS were found to be 2.54×106g/mol, 5.54×106g/mol, and 4.5, respectively. The intrinsic viscosity of SSPS (0.33) was lower than most of hydrocolloids. With increasing TiO2 concentration, the water solubility, moisture content and water-vapor permeability (WVP) of SSPS-based nanocomposite films decreased. TiO2 addition led to an increase in the melting temperature to a maximum of 132°C for the SSPS nanocomposite with 5wt% TiO2. With increasing TiO2 concentrations from 5 to 15wt%, the melting temperature declined from 24 to 19°C. There were no significant agglomerates when the TiO2 concentrations were increased to 5wt%; however, when the concentration reached 15wt%, agglomerations were observed. With addition of TiO2 nanoparticles, tensile strength increased but elongation at break decreased. SSPS-based nanocomposite films demonstrated a promising range of antimicrobial activity. The current research clearly introduces a new antimicrobial composite which is potentially useful to prevent and treat infections.

Eco-friendly soluble soybean polysaccharide/nanoclay Na+ bionanocomposite: Properties and characterization.

The impact of montmorillonite (MMT) as a nanofiller at different concentrations (5, 10, 15wt.%) on the physicochemical and functional properties of nanocomposite film based on soluble soybean polysaccharide (SSPS) was investigated. The results showed that an increase in MMT concentration was accompanied by a decrease in water solubility, thickness, and elongation at break. Furthermore, tensile strength increased when MMT concentration was increased to 10wt.%. Atomic force and scanning electron micrographs showed a significant agglomeration at MMT 15wt.%. With added MMT, the level of whiteness, greenness, and yellowness of SSPS film increased (P<0.05). Dynamic mechanical thermal analysis indicated that the storage modulus of nanocomposites increased when the MMT was increased to 10wt.%. Furthermore, Fourier transform infrared spectrophotometry demonstrated that no considerable changes occurred in the functional groups of the SSPS when MMT was added. Antimicrobial tests revealed that antibacterial and anti-mold activities were unlikely from reinforced nanocomposites.

Evaluation, prediction and optimization the ultrasound-assisted extraction method using response surface methodology: antioxidant and biological properties of Stachys parviflora L.

OBJECTIVES: To optimize the extraction method using response surface methodology, extract the phenolic compounds, and identify the antioxidant and biological properties of Stachys parviflora L. extracts. MATERIALS AND METHODS: Maceration and ultrasound-assisted extraction (UAE) (4, 7, 10 min treatment time, 40, 70, 100 % high-intensity and 60, 80, 100 % (v v-1) methanol purity) were applied to obtain the extracts. SEM was conducted to provide the microstructure of the extracted plant. MICs (colorimetric assay), MFCs (colony diameter), total phenolic content, total flavonoid content, radical scavenging capacity and extraction efficiency were determined. HPLC analysis was applied to measure the existent phenolic compounds. RESULTS: A quadratic model (4 min treatment time, 74.5 % high-intensity and 74.2 % solvent purity) was suggested as the best (TPC: 20.89 mg GAE g-1 d.m., TFC: 6.22 mg QEs g-1 d.m., DPPH IC50: 21.86 µg ml-1 and EE: 113.65 mg g-1 d.m.) UAE extraction model. The optimized UAE extract was generally more effective against Gram-positive microorganisms (MIC: 10-20; MBC: 10-40 (mg ml-1)) than Gram-negative ones (MIC: 40; MBC: >40 (mg ml-1)). Moreover, it (MGI: 2.32-100 %) revealed more anti-mold activity than maceration (MGI: <28.77 %). Explosive disruption of the cell walls, therefore, enhanced extraction yield by acoustic cavitation, was elucidated using SEM. Caffeic acid, tannic acid, quercetin, trans ferulic acid and rosmarinic acid were determined as the phenolic compounds in the optimized extract. CONCLUSION: RSM optimization was successfully applied for UAE from S. parviflora. The considerable antioxidant and biological properties were attributed to the phenolic compounds.

Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology.

Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram-negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 µM for Meloxicam and 201.39 nM and 4.88 µM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors.

Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects.

Nigella sativa seeds have wide therapeutic effects and have been reported to have significant effects against many ailments such as skin diseases, jaundice, gastrointestinal problems, anorexia, conjunctivitis, dyspepsia, rheumatism, diabetes, hypertension, intrinsic hemorrhage, paralysis, amenorrhea, anorexia, asthma, cough, bronchitis, headache, fever, influenza and eczema. Thymoquinone (TQ) is one of the most active constituent and has different beneficial properties. Focus on antimicrobial effects, different extracts of N. sativa as well as TQ, have a broad antimicrobial spectrum including Gram-negative, Gram-positive bacteria, viruses, parasites, schistosoma and fungi. The effectiveness of N. sativa seeds and TQ is variable and depends on species of target microorganisms. The present review paper tries to describe all antimicrobial activities that have been carried out by various researchers.

New aspects of Saccharomyces cerevisiae as a novel carrier for berberine.

BACKGROUND: Berberine was encapsulated in yeast cells of Saccharomyces cerevisiae as novel carriers to be used in different food and drug industries. The microcapsules were characterized by differential scanning calorimetry (DSC), fourier transform infra red spectroscopy (FT-IR) and fluorescence microscopy. The encapsulation factors such as plasmolysis of yeast cells which affects the % encapsulation yield were studied. RESULTS: Fluorescence microscopy showed the yeast cells became fluorescent after encapsulation process. DSC diagram was representing of new peak for microcapsule which was not the same as berberine and the empty yeast cells peaks, separately. FTIR spectrums of microcapsules and yeast cells were almost the same. The plasmolysed and non plasmolysed microcapsules were loaded with berberine up to about 40.2 ± 0.2% w/w. CONCLUSION: Analytical methods proved that berberine was encapsulated in the yeast cells. Fluorescence microscopy and FTIR results showed the entrance of berberine inside the yeasts. DSC diagram indicated the appearance of new peak which is due to the synthesis of new product. Although plasmolysis caused changes in yeast cell structure and properties, it did not enhance berberine loading in the cells. The results confirmed that Saccharomyces cerevisiae could be an efficient and safe carrier for active materials.

Interaction of methylxanthines and gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa: role of phosphodiesterase inhibition.

Previous studies showed that methylxanthines increased the antimicrobial activity of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. In this study, the effect of non-selective phosphodiesterase (PDE) inhibitors (methylxanthines: aminophylline and caffeine) and partially selective PDE inhibitors, dipyridamole and sildenafil, was evaluated on the antimicrobial activity of gentamicin using checkerboard method. Aminophylline at concentrations of 0.5 and 1 mg/ml reduced the minimal inhibitory concentration (MIC) of gentamicin (2 µg/ml) 2 and 4 times against S. aureus, and at concentrations of 0.5 and 2 mg/ml reduced the MIC of gentamicin (4 µg/ml) 2 and 4 times, respectively, against P. aeruginosa. Caffeine at concentrations of 1 and 2 mg/ml reduced the MIC of gentamicin (2 µg/ml) 4 and 32 times against S. aureus, and at concentrations of 0.12 and 2 mg/ml reduced the MIC of gentamicin (4 µg/ml) 2 and 4 times, respectively, against P. aeruginosa. However, dipyridamole and sildenafil (32 µg/ml) did not show any effect on MIC of gentamicin against S. aureus and P. aeruginosa. These results suggest that methylxanthines could increase gentamicin effects against S. aureus and P. aeruginosa but this effect is not mediated by inhibition of PDE 5, 6, 8, 10 and 11.

Effect of galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus aureus

Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana roots, was investigated for its potentiating effect on the antimicrobial activity of antibiotics as well as ethidium bromide, in 6 multidrug resistance (MDR) clinical isolates of Staphylococcus aureus. Galbanic acid had inhibitory effect on none of the isolated bacteria tested (up to 800 µg /ml). The MIC range of ciprofloxacin, tetracycline and ethidium bromide, against all tested S. aureus were 10-80, 10-80 and 4-16 µg/ml, respectively. These were reduced to ≤2.5-5, 2.5-5 and 0.5-2 µg/ml in the presence of galbanic acid (300 µg /ml) or verapamil (100 µg /ml). The rate of ethidium bromide (2 µg /ml) accumulation in clinical isolates was enhanced with galbanic acid (300 µg /ml). There is also a decrease in loss of ethidium bromide from bacteria in the presence of galbanic acid. Similar results were obtained when verapamil (100 µg /ml) was used as an efflux pump inhibitor. Galbanic acid, like verapamil, a typical inhibitor of efflux pump, reduced the MIC of ethidium bromide and tested antibiotics. Since efflux is the only known reported mechanism for ethidium bromide resistance, the reduction in ethidium bromide MIC and enhanced accumulation as well as decreased efflux of ethidium bromide in the presence of galbanic acid, can be attributed to this efflux inhibitory properties.

Effect of galbanic Acid, a sesquiterpene coumarin from ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus aureus.

Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana roots, was investigated for its potentiating effect on the antimicrobial activity of antibiotics as well as ethidium bromide, in 6 multidrug resistance (MDR) clinical isolates of Staphylococcus aureus. Galbanic acid had inhibitory effect on none of the isolated bacteria tested (up to 800 µg /ml). The MIC range of ciprofloxacin, tetracycline and ethidium bromide, against all tested S. aureus were 10-80, 10-80 and 4-16 µg/ml, respectively. These were reduced to ≤2.5-5, 2.5-5 and 0.5-2 µg/ml in the presence of galbanic acid (300 µg /ml) or verapamil (100 µg /ml). The rate of ethidium bromide (2 µg /ml) accumulation in clinical isolates was enhanced with galbanic acid (300 µg /ml). There is also a decrease in loss of ethidium bromide from bacteria in the presence of galbanic acid. Similar results were obtained when verapamil (100 µg /ml) was used as an efflux pump inhibitor. Galbanic acid, like verapamil, a typical inhibitor of efflux pump, reduced the MIC of ethidium bromide and tested antibiotics. Since efflux is the only known reported mechanism for ethidium bromide resistance, the reduction in ethidium bromide MIC and enhanced accumulation as well as decreased efflux of ethidium bromide in the presence of galbanic acid, can be attributed to this efflux inhibitory properties.

The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates from a general hospital in Iran.

This study was conducted at a 900+ bed general teaching hospital, from May to September 2007, in Iran. The aim of this study was to determine the prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae and their antimicrobial pattern. The Kirby-Bauer disk diffusion method and the phenotypic disk confirmatory test were performed for each isolate. The total of 206 isolates including 106 E. coli and 100 K. pneumoniae were collected of which 122 isolates (59.2%) were ESBL positive. The prevalence of ESBL-producing strains was 59.2% (122/206). All the isolates were susceptible to imipenem. Among the ESBL-producing isolates, the sensitivity was from 3.3% to 61.5% for ampicillin to aztreonam. From female isolates (136), 59.5% and from male isolates (70), 58.6% were ESBL-producers. Ratios of isolates from hospitalized patients to out-patients were 94/28 in the ESBL-producing group. The number of ESBL-producing isolates according to the isolation sites showed a significant difference between ESBL-producers and non-producers in blood samples (P < 0.05). This study shows that the prevalence of ESBL strains in Iran is high. It seems necessary for clinicians and medical community personnel to be fully aware of ESBL-producing microorganisms.

Effect of topical liposomes containing paromomycin sulfate in the course of Leishmania major infection in susceptible BALB/c mice.

The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37 degrees C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 microg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 microg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.