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• Sol-gel approach was used to synthesize Fe 3 O 4 stabilized zirconia nanoparticles. • XRD results showed mixed phases (i.e. monoclinic and tetragonal) for all wt% using acidic (pH 2) value while pure tetragonal phase of zirconia was observed with 6 wt% basic (pH 9) iron oxide. • Maximum value of dielectric constant and minimum value of tangent loss was observed for 6 wt% basic iron oxide stabilized zirconia nanoparticles. • Maximum value of hardness along with high fracture toughness was observed for basic 6% Fe 3 O 4 stabilized zirconia. • Optimized nanoparticles exhibited very weak hemolytic activity. • Optimized nanoparticles showed maximum scavenging value (~76) for antioxidant activity. Zirconia ceramics have attained much consideration owing to the amazing mechanical strength and white color. These properties provide an opportunity for the use in biomedical applications. In the present study, an application oriented sol-gel route was adapted for synthesis of zirconia nanoparticles. ZrOCl 2 ·8H 2 O was used as a precursor, iron oxide (Fe 3 O 4) nanoparticles (pH 2 & pH 9) as a stabilizer and de-ionized water was used as a solvent. Sol-gel synthesized iron oxide stabilized zirconia nanoparticles were prepared by varying concentrations of iron oxide nanoparticles in the range of 2–10 wt%. X-ray diffraction results showed mixed phases at all wt% with acidic pH value, while pure tetragonal phase of zirconia was observed for stabilization with 6 wt% basic iron oxide. Maximum value of dielectric constant (~80 at log f = 4) and minimum value of tangent loss (~0.66 at log f = 4) were observed for zirconia stabilized with basic 6 wt% iron oxide. Maximum value of hardness (1410 ± 10 HV) along with high fracture toughness were observed with optimized stabilization. Very weak hemolytic activity and maximum scavenging (~76) antioxidant activity was observed under optimized conditions. Thus, it can be suggested that optimized nanoparticles, i.e. tetragonal zirconia stabilized with 6 wt% of basic Fe 3 O 4 , can be further useful for therapeutical and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

The bioactive molecules in greener material act as effective bio-reductants and surfactants to form the nanoparticles. This study, hence, focused to synthesize the MgO nanoparticles using grains extract of Oryza sativa L. indica (black rice). The synthesized nanoparticles were subjected to various analytical and biomedical analyses. High-resolution transmission electron microscopic (HRTEM) analysis exposed the rectangular and rice-grain architecture shaped morphology of nanoparticles with the average length and diameter in between 50-90 nm and 5–25 nm respectively. The antioxidant, anti-inflammatory and anti-diabetic activities explicated the higher activity of 91.36, 89.92 and 90.43% in the concentration of 80 μg/mL. The anticancer activity revealed the competent drug activity with 89.66% of toxicity towards cancer cells. The biocompatibility and hemolytic analyses showed no toxicity of nanoparticles towards normal cells and RBC's. The results of analyses suggest that the biosynthesized MgO nanoparticles can be used as therapeutic drugs in biomedical and pharmaceutical sectors. [Display omitted] • Rectangular and rice-grain shape of MgO nanoparticles was attained. • High toxicity of nanoparticles was observed against HT-29 cancer cells. • MgO nanoparticles revealed no toxicity towards HEK293 normal cells. • MgO nanoparticles showed zero hemolytic effect at high concentrations. [ABSTRACT FROM AUTHOR]

Anoplin (GLLKRIKTLL-NH 2 ) is of current interest due to its short sequence and specificity towards bacteria. Recent studies on anoplin have shown that truncation and acylation compromises its antimicrobial activity and specificity, respectively. In this study, truncated analogues (pal-ano-9 to pal-ano-5) of palmitoylated anoplin (pal-anoplin) were synthesized to determine the effects of C -truncation on its bioactivities. Moreover, secondary structure of each analogue using circular dichroism (CD) spectroscopy was determined to correlate with bioactivities. Interestingly, pal-anoplin, pal-ano-9 and pal-ano-6 were helical in water, unlike anoplin. In contrast, pal-ano-8, pal-ano-7 and pal-ano-5, with polar amino acid residues at the C -terminus, were random coil in water. Nevertheless, all the peptides folded into helical structures in 30% trifluoroethanol/water (TFE/H 2 O) except for the shortest analogue pal-ano-5. Hydrophobicity played a significant role in the enhancement of activity against bacteria E. coli and S. aureus as all lipopeptides including the random coil pal-ano-5 were more active than the parent anoplin. Meanwhile, the greatest improvement in activity against the fungus C. albicans was observed for pal-anoplin analogues (pal-ano-9 and pal-ano-6) that were helical in water. Although, hydrophobicity is a major factor in the secondary structure and antimicrobial activity, it appears that the nature of amino acids at the C -terminus also influence folding of lipopeptides in water and its antifungal activity. Moreover, the hemolytic activity of the analogues was found to correlate with hydrophobicity, except for the least hemolytic, pal-ano-5. Since most of the analogues are more potent and shorter than anoplin, they are promising drug candidates for further development. [ABSTRACT FROM AUTHOR]

Currently, combinations of natural polymers and semi-synthetic biomolecules have gained attention for food-packaging, drug delivery, coatings, and biomedical applications. In this work, cross-linking property of two biopolymers was employed for the fabrication of hydrogel films. Sodium alginate (SAlg) and Okra gel (OkG) were used in different ratios (95:05, 75:25 and 85:15) to synthesize hydrogel films by solvent-casting method. Formation of the films was confirmed by FTIR and Raman techniques which specified the interaction between biomolecules of SAlg and OkG. XRD pattern has shown the presence of both amorphous and micro-crystalline phases in the hydrogel films and SEM studies have shown porosity, amorphousness and agglomerated morphology. TGA and DSC analyses revealed degradation of the film at 420 °C and stability studies using PBS buffer indicated stability and hydrophilic nature of hydrogel films. In-vitro degradation test was also performed for 10 weeks through the incubation of hydrogel-films in simulated body fluid and the effect of pH and temperature was also studied. Results have shown worth-some influence of okra gel on the fabricated films. Hemolytic and antioxidant activities of the gels were also determined and being non-toxic, all these ratios were found suitable for biomedical applications; especially 85:15 have shown maximum potential. [ABSTRACT FROM AUTHOR]

Metal nanoparticles have a great impact and even change the composition of soil microbial communities. This poses the risk of their accumulation in the ecosystem, which may call on health hazard. Statistical techniques such as Plackett-Burman design, Response Surface Methodology were used for optimizing medium constituents for Bacillus cereus SVK1 and other critical variables responsible for the production of biomolecules and biosynthesis of hematite nanoparticles. The effect of hematite nanoparticles on the growth of soil bacteria were tested by agar-well diffusion method and dynamic growth curve techniques. Bacterial growth inhibition was not observed with hematite nanoparticle concentration of up to 25 mg/mL. In addition, hematite nanoparticles enhanced the growth of the soil bacteria. The results show that hematite nanoparticles were non-toxic to soil bacteria indicating their scope for wide range of applications. The effective cytotoxic concentration (CTC 50 ) of hematite nanoparticles against MCF-7, A549, Hep3 B and Vero cell lines was found to be 207.58, 224.69, 193.26 and 2530 μg/mL respectively. Hematite nanoparticles didn’t cause lysis of red blood cells. [ABSTRACT FROM AUTHOR]

δ-Toxin is a 26 amino acid peptide capable of lysing several mammalian cell types and subcellular structures. Structurally, δ-toxin predominantly exhibits a α-helical secondary structure in membranes but, in aqueous solution, it adopts varying helical content. As no atomic-level data is available for this peptide in aqueous solutions and for the water-to-membrane transition, this work aims to characterize δ-toxin behavior in these conditions through molecular dynamics simulations in triplicates employing four different parameter sets. Our results, validated on previous experimental data, suggest that the peptide has from 4 to 16 residues folded as α-helix in aqueous solution, and a water-to-membrane foldamer comprising residues 14–18. Considering a previously proposed stable tetramer form in aqueous solutions, protein-protein docking and molecular dynamics studies were performed, suggesting that δ-toxin increases its α-helical content in such organization. The obtained results are expected to contribute in future studies on δ-toxin aggregation and interaction to biomembranes. [ABSTRACT FROM AUTHOR]

Six homobimetallic organotin(IV) carboxylates dithiocarboxylates of the general formula R 2 (Cl)SnSSCLCOOSn(Cl)R 2 (R = Me: 1 ; n -Bu: 2 ; Ph: 3 )/R 3 SnSSCLCOOSnR 3 (R = Me: 4 ; n -Bu: 5 ; Ph: 6 ), a trinucleartin(IV) derivative [Ph 2 (Cl)SnSSCLCOO] 2 SnPh 2 ( 7 ), three heterobimetallic (Sn, Pd) products of the type Cl 2 PdSSCLCOOSnR 3 (R = Me: 8 ; Bu: 9 ; Ph: 10 ) and a palladium complex KOOCLCSSPdSSCLCOOK ( 11 ) were synthesized from potassium 1-dithiocarboxylatopiperidine-4-carboxylate ( KSSCLCOOK ) insitu . The structures of the complexes were verified by spectroscopic techniques (FT-IR, UV–Visible, 1 H NMR, 13 C NMR, EI-MS/ESI) and TGA. FT-IR data indicated a bidentate binding mode of the carboxylate/dithiocarbamate group, with tetra and penta-coordinated arrangements around Pd(II) and Sn(IV) centers in solid state. In solution state, a trigonal bipyramidal environment around Sn(IV) and a square planar geometry of Pd(II) was justified by NMR ( 1 H and 13 C) and UV–Vis spectroscopies. In heteronuclear products ( 8 – 10 ), the ligand develops linkage through oxygen and sulfur donor sites to Sn(IV) and Pd(II), respectively. The mass fragmentation and thermal degradation patterns were excellently agreed with the molecular composition of products. Single crystal XRD analysis of the complex 6 demonstrated that the geometry of sulfur bonded tin(IV) lies between tetrahedral and trigonal bipyramidal, while a distorted trigonal bipyramidal arrangement was verified for oxygen bonded Sn(IV). The synthesized complexes exhibited antimicrobial activities against various strains of bacteria and fungi by disc diffusion method and their minimal inhibitory concentrations were also found. The nature of the coordinated metal played a major role in biological actions of such complexes. While Pd(II) incorporation chiefly induces SS-DNA binding capacity and ALPs inhibition in complexes, the coordination with Sn(IV) stimulates the antibacterial and antifungal potentials. The complexes exhibited sufficiently lower hemolytic activities as compared to triton X-100 (positive control, 100% lysis) and higher than PBS (negative control, 0% lysis). [ABSTRACT FROM AUTHOR]

Multinuclear organotin(IV) dicarboxylates of the general formula (Me 3 Sn) 2 L·H 2 O ( 1 ), (Ph 3 Sn) 2 L ( 2 ) and Me 2 SnL[Sn(Cl) 2 Me 2 ] 2 ( 3 ) were synthesized by refluxing disodium iminodiacetate hydrate (Na 2 L·H 2 O) with Me 3 SnCl/Ph 3 SnCl/Me 2 SnCl 2 in methanol. The elemental analysis (C, H and N) data agreed well with the chemical compositions of the products. IR spectroscopy demonstrated a bridging coordination mode of the carboxylate group. 1 H NMR spectroscopy suggested a penta-coordinated environment around the tin(IV) center in complexes 1 and 3 . The title complex 3 represents one of the very few examples of organotin(IV) carboxylates showing simultaneously coordination with dimethyltin(IV) as well as dichlorodimethyltin(IV) moieties, by substitution and addition reactions, respectively. The 13 C NMR spectroscopy demonstrated the carboxylate-metal linkages. EIMS and ESI spectra verified the molecular skeletons of the products 1 – 3 . Thermogravimetric analysis revealed the bimetallic nature of 2 . A single crystal XRD study of 3 has shown a predominantly square pyramidal geometry with some trigonal bipyramidal characteristics around each metal center. The novel products exhibited antibacterial/antifungal potential and their minimal inhibitory concentrations (MIC) were also evaluated. In vitro hemolytic studies on human red blood cells indicated a slightly toxic nature of the synthesized complexes. [ABSTRACT FROM AUTHOR]

Fisetin is a well known flavonoid that shows several properties such as antioxidant, antiviral and anticancer activities. Its use in the pharmaceutical field is limited due to its poor aqueous solubility which results in poor bioavailability and poor permeability. The aim of our present study is to prepare fisetin loaded human serum albumin nanoparticles to improve its bioavailability. The nanoparticles were prepared by a desolvation method and characterized by spectroscopic and microscopic techniques. The particles were smooth and spherical in nature with an average size of 220 ± 8 nm. The encapsulation efficiency was found to be 84%. The in vitro release profile showed a biphasic pattern and the release rate increases with increase in ionic strength of solution. We have also confirmed the antioxidant activity of the prepared nanoparticles by a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Further its anticancer activity was evaluated using MCF-7 breast cancer cell lines. Our findings suggest that fisetin loaded HSA nanoparticles could be used to transfer fisetin to target areas under specific conditions and thus may find use as a delivery vehicle for the flavonoid. [ABSTRACT FROM AUTHOR]

Snake envenomation is a serious hazard in tropical countries. In the current study, the bioactive compound from the methanolic extract of Citrus reticulata was purified using polarity gradient chromatography and structurally characterized by UV-spectroscopy, NMR, and LC-MS. The purified metabolite, naringenin, inhibited PLA 2 (51%) and hemolytic (59.8%) activity of the Naja naja venom. Histopathological examination and edema studies carried out using mice confirmed the inhibitory effects of naringenin. This is the first report on the inhibitory potential of naringenin isolated from Citrus reticulata. The study thus unravels the possibility for the use of Citrus reticulata metabolites as a supplement during the snake bite treatment. [Display omitted] • Methanolic extract of Citrus reticulata Blanco was evaluated for the inhibition of Naja naja venom. • Activity-guided separation method was used to isolate the active fraction. • Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) Spectroscopy were utilized to identify the compound with Naja naja venom inhibitory activity. • Mice paw edema model and histopathology confirmedthe inhibition of Naja naja venom activity in vivo. [ABSTRACT FROM AUTHOR]

Blood transfusion is a common medical intervention for patients with sickle cell disease (SCD) and disease related complications. While patients with SCD are at risk for all transfusion related adverse events defined by the National Healthcare Safety Network (NHSN) Biovigilance Component Hemovigilance Module Surveillance Protocol, they are uniquely susceptible to certain adverse events. This review discusses risk factors, mitigation strategies, and management recommendations for alloimmunization, hemolytic transfusion reactions, hyperviscosity and transfusion-associated iron overload in the context of SCD. • Alloimmunization and iron overload are risks of red cell transfusion for SCD. • Prophylactic Rh and K matching of red cells is recommended for patients with SCD. • RH variation among African patients and donors contributes to Rh alloimmunization. • Immunosuppression can be tailored for severe hemolytic transfusion reactions. [ABSTRACT FROM AUTHOR]

Abstract: The host-defense peptide, esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30 CKISKQC) shows potent (MIC≤6μM) growth inhibitory activity against clinical isolates of multidrug-resistant strains of Staphylococcus aureus, Acinetobacter baumannii, and Stenotrophomonas maltophilia and differential cytotoxic activity against human erythrocytes (LC50 =150μM) and human non-small cell lung adenocarcinoma A549 cells (LC50 =10μM). Esculentin-2CHa significantly (P <0.01) stimulates the release of the anti-inflammatory cytokine IL-10 by mouse lymphoid cells and elevates its production after stimulation with concanavalin A and significantly (P <0.05) stimulates TNF-α production by peritoneal macrophages. Effects on IL-6 and IL-1β production were not significant. Removal of the hydrophobic N-terminal hexapeptide (GFSSIF) from esculentin-2CHa results in abolition of growth inhibitory activity against S. aureus and cytotoxic activity against erythrocytes and A549 cells as well as a marked (≥16-fold) reduction in potency against A. baumannii and S. maltophilia. The primary structure of esculentin-2 has been poorly conserved between frog species but evolutionary pressure has acted to maintain the hydrophobic character of this N-terminal hexapeptide sequence. Removal of the cyclic C-terminal domain (CKISKQC) and replacement of the Cys31 and Cys37 residues by serine resulted in appreciable decreases in cytotoxicity against all microorganisms and against mammalian cells. The more cationic [D20K, D27K] analog showed a modest increase in potency against all microorganisms (up to 4-fold) but a marked increase in cytotoxicity against erythrocytes (LC50 =11μM) and A549 cells (LC50 =3μM). [Copyright &y& Elsevier]

Abstract: Defined experimental regimes were used to determine the effects of nutrient limitation on the toxicity of Alexandrium peruvianum in batch culture. Subsamples for cell counts and spiroimine analysis at six day intervals were used to investigate the concentrations and composition of these compounds throughout growth. An erythrocyte lysis assay for hemolytic activity was performed on cell pellets and supernatants also collected every six days over the entire growth period from all treatments. From the data, growth rates, cellular spiroimine quotas and effective concentration-fifty (EC50s) for cellular and supernatant associated hemolytic activity were calculated. Phosphate limitation was identified as a key regulator of toxicity in this species, yielding maximum values of 54.1pgcell−1 for 13-desmethyl spirolide C, 96.4pgcell−1 for 12-methylgymnodimine and a potent hemolytic EC50 value of 7.1×103 cells. The concentrations of spiroimines detected in A. peruvianum among various treatments, in addition to a unique profile of paralytic shellfish poisoning toxins, is unique in the body of microalgal literature. Because of the multiple toxin arsenal produced by this organism, the evaluation of a single toxin clearly would have underestimated the potential virulence and significance of this clone. This study provides the first evidence that growth and toxin production of A. peruvianum are influenced by altered nutrient ratios. [Copyright &y& Elsevier]

Abstract: The leatherback turtle is an endangered sea turtle whose numbers are in decline. There is a great effort world wide on the part of many conservationists to protect these turtles and their eggs. We previously demonstrated that blood from a leatherback hatchling was infected with a hemolytic acinetobacter bacterium, Acinetobacter sp. HM 746599, implying that the developing embryo may have been infected in the egg. Only about 50% of the eggs laid on a Costa Rican beach hatch due to predation, inundation and within nest factors. This study was conducted to determine whether high bacterial infection rate of eggs incubating in the dark, moist sands of the beach contributes to the low hatching rate. Samples were taken aseptically from adult cloacal fluids and failed and opened eggs in search of potentially lethal bacteria. We identified three bacterial species in selected cloned samples that exhibited hemolytic activity. These bacteria were species of the Bacillus, Pseudomonas and Aeromonas genera. Many of these bacterial species are known pathogens to humans and may account for developmental arrest of the turtle embryo. These bacterial species may also pose a danger to human workers who come in contact with them. Knowledge of the bacteria that can infect and possibly kill leatherback embryos may lead to treatment modalities of leatherback clutches with anti-microbial agents which would allow us to improve the hatching rates of these animals under controlled conditions. [Copyright &y& Elsevier]

Abstract: Fish skin mucus has recently been recognized to be a potential source of antimicrobial peptides, which provides the first line of defense against invading pathogens. This study reports the purification and characterization of a novel linear antimicrobial peptide, pelteobagrin, from the skin mucus of yellow catfish (Pelteobagrus fulvidraco, Richardson). Pelteobagrin is 20 amino acids in length (GKLNLFLSRLEILKLFVGAL) and shows no clear homology with any known bioactive peptides. MALDI-TOF MS indicated the molecular mass of the purified peptide was 2244.4Da, which is in good agreement with pelteobagrin''s predicted molecular weight of 2244.8Da. Pelteobagrin exhibited antibacterial activity against Gram-positive and Gram-negative bacteria as well as fungi, and the activity was relatively salt-insensitive as it was not affected by NaCl concentrations of up to 137mM. Moreover, pelteobagrin displayed no hemolytic activity to rabbit red blood cells. Transmission electron microscopy suggested that pelteobagrin might kill bacteria via acting on both the cell wall and the cytoplasmic membrane of bacteria. These results suggest that pelteobagrin might be involved in the innate defense system in yellow catfish. [Copyright &y& Elsevier]

Abstract: Cyt2Aa2 produced by Bacillus thuringiensis subsp. darmstadiensis exhibits in vitro cytolytic activity against broad range of cells but shows specific in vivo toxicity against larvae of Dipteran insects. To investigate the role of amino acids in αA and αC of this toxin, 3 single-point mutants (A61C, S108C and V109A) were generated. All 3 mutant proteins were highly produced as inclusion bodies that could be solubilized and activated by proteinase K similar to that of the wild type. Hemolytic activity of A61C and S108C mutants was significantly reduced whereas the V109A mutant showed comparable hemolytic activity to the wild type. Interestingly, the A61C mutant exhibited high larvicidal activity to both Aedes aegypti and Culex quinquefasciatus. S108C and V109A mutants showed low activity against C. quinquefasciatus but relatively high toxicity to A. aegypti. These results demonstrated for the first time that amino acids in αA and αC are involved in the selectivity of the Cyt toxin to the targeted organism. [Copyright &y& Elsevier]

Abstract: An extract of the skin of the Japanese tree frog, Hyla japonica Günther, 1859 (Anura: Hylidae) did not inhibit the growth of the bacteria Escherichia coli or Staphylococcus aureus, but contained a protein that was strongly hemolytic against human erythrocytes. The protein was purified to near homogeneity by reverse-phase HPLC, and its N-terminal amino acid sequence (SGRGKGGKGL…) identified it as histone H4. The complete primary structure of the 102-amino-acid-residue histone H4 was determined by a combination of molecular cloning of genomic and complementary DNAs encoding the protein. The molecular mass of the purified histone H4 determined by electrospray mass spectrometry was 71±2 Daltons greater than that predicted from the deduced amino acid sequence of the protein. The +71 mass units is consistent with the proposal that the protein isolated from the skin was post-translationally modified by addition of one acetyl and two methyl groups. The stem-loop structure at the 3′ flanking region of the H. japonica histone H4 gene, which acts as a transcription termination signal, contained a nucleotide sequence (5′-GGCTCTCCTCAGAGCC-3′) with unusual structural features not seen in other histone genes. [Copyright &y& Elsevier]

Abstract: Neobatrachia is the amphibian suborder with the largest number of species and a most important source of bioactive peptides from frog skin secretions. However, 90% of the studies on this subject have been focused on the frog families Hylidae and Ranidae, while very little is known about peptides of other families, like Leptodactylidae. Our work reports for the first time the isolation and characterization of ocellatin 4 (GLLDFVTGVGKDIFAQLIKQI-NH2), a cytolytic peptide from the skin secretion of the South American frog Leptodactylus ocellatus. While most cytolytic amphibian skin peptides are selective for microorganisms and harmless for mammalian cells, the HC50 of ocellatin 4 against human erythrocytes is 14.3μM. The interaction between ocellatin 4 and zwitterionic phospholipids in mammalian plasma membranes may be favored by its neutral charge at pH 7.0. Ocellatin 4 also shows some antibacterial activity (MICs E. coli and S. aureus =64μM) and its sequence shares similarities with the only six leptodactylid peptides previously known and with four peptides from Australian hylid frogs of the genus Litoria. [Copyright &y& Elsevier]

Abstract: Background: Some patients with autoimmune hemolytic anemia (AIHA) have in their sera autohemolysins able to hemolyze RBCs in vitro by activation of complement. We describe three autohemolysins in patients with AIHA and we study clinical correlations. Study design and methods: Thirty-two patients with AIHA were explored by immuno-hematological investigations (DAT, elution and serum testing). Results: Three autohemolysins were detected in three patients. All of these autoantibodies were likely IgM and reacted in vitro only with enzyme-treated RBCs. Two warm autohemolysins were detected in patients with warm-type AIHA. The first one was active at neutral pH with low title. The second, having a wide thermal amplitude reacting at 22 °C and a title of 16, was acid. The hemolysin detected in patient 3 with cold hemagglutinin disease, was active at 4 and 22 °C, at acid pH. The thermal optimum was 4 °C and the title 64. It was also detected at 37 °C with the same title, but only at neutral pH. Conclusion: Although these autohemolysins were incomplete, hemolyzing in vitro only enzyme-treated RBCs, they were associated for the three patients with severe hemolysis. [Copyright &y& Elsevier]

Abstract: Pseudin-2, a naturally occurring 24 amino-acid-residue antimicrobial peptide first isolated from the skin of the South American paradoxical frog Pseudis paradoxa, has weak hemolytic and cytolytic activity but also relatively low potency against microorganisms. In a membrane-mimetic environment, the peptide exists in an amphipathic α-helical conformation. Analogs of the peptide with increased cationicity and α-helicity were chemically synthesized by progressively substituting neutral and acidic amino acid residues on the hydrophilic face of the α-helix by lysine. Analogs with up to three L-lysine substitutions showed increased potency against a range of gram-negative and gram-positive bacteria (up to 16-fold) whilst retaining low hemolytic activity. The analog [d-Lys3, d-Lys10, d-Lys14]pseudin-2 showed potent activity against gram-negative bacteria (minimum inhibitory concentration, MIC=5 μM against several antibiotic-resistant strains of Escherichia coli) but very low hemolytic activity (HC50>500 μM) and cytolytic activity against L929 fibroblasts (LC50=215 μM). Increasing the number of l-lysines to four and five did not enhance antimicrobial potency further but increased hemolytic activity towards human erythrocytes. Time-kill studies demonstrated that the analog [Lys3, Lys10, Lys14, Lys21]pseudin-2 at a concentration of 1×MIC was bacteriocidal against E. coli (99.9% cell death after 96 min) but was bacteriostatic against S. aureus. Increasing the hydrophobicity of pseudin-2, while maintaining the amphipathic character of the molecule, by substitution of neutral amino acids on the hydrophobic face of the α-helix by l-phenylalanine, had only minor effects on antimicrobial and hemolytic activities. [Copyright &y& Elsevier]

We are presenting 20 patients with hepatitis C, who developed anemia on interferon alpha-2b/ribavirin treatment and were treated with recombinant human c alpha. Median age was 43 years (range 25–72). Four patients received previous treatment. Interferon-alpha-2b was given at six million units three times a week to 10 patients and at three million units three times a week to five patients. PEG-interferon-alpha-2b (80–120 μg/week) was given to five patients. The dose of ribavirin was 800–1200 mg/day (19 patients) and 200 mg/day (one patient with renal failure). Duration of an interferon/ribavirin treatment was 6–12 months. Baseline median hemoglobin was 13.3 g/dl (range 12.2–15.8); median hemoglobin nadir: 9.8 g/dl (range 8.4–11.2). On erythropoietin, the hemoglobin increased to median 11.7 g/dl (range 9.6–12.8). The ribavirin dose had been decreased to 800 mg in four patients, to 600 mg in four patients, to 400 mg in one patient. Thirteen patients responded to interferon/ribavirin treatment, six patients (all genotype 1) did not. Of the 13 initial responders 11 had sustained response, one still under treatment and two patients relapsed. In conclusion, in our patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, erythropoietin was beneficial in the treatment of ribavirin-induced anemia. [Copyright &y& Elsevier]

A total of 87 market fish samples representing five types of fish were evaluated for the presence of Aeromonas spp. Of the samples examined, 69%, 55%, 11.5% and 2.3% harbored Aeromonas spp., A. veronii biovar sobria, A. hydrophila and A. caviae, respectively. The 60 isolated Aeromonas spp. strains were further examined for hemolytic activity, resistance to antimicrobial agents and presence of plasmids. Hemolytic activity varied widely among the isolated strains. Though all the isolates demonstrated resistance to three or more of the antibiotics tested, all were susceptible to ceptazidime. Thirty-four (56.7%) of the sixty isolates harbored plasmids, with sizes ranging from 2.3 to 15.7 kb. These results indicate that hemolytic, multiple antibiotic resistant and genetically diverse aeromonads are easily recovered from fish in this region. [Copyright &y& Elsevier]

Some biologically active polypeptides, three high and two low molecular weight cytolysins and four trypsin inhibitors were isolated from the sea anemone Radianthus macrodactylus and characterized. The purification steps involved acetone precipitation, gel filtration, ion-exchange, and affinity chromatography, and ion-exchange and reverse-phase HPLC. The relative molecular weight of high molecular weight Radianthus cytolysins named according to their N-terminal amino acids RTX-A (Ala), RTX-S (Ser) and RTX-G (Gly) was about 20,000. The isoelectric points were 9.8 for RTX-A and RTX-S, and 10.5 for RTX-G. The hemolytic activities of RTX-A, RTX-S and RTX-G were 3.5×104, 5.0×104, and 1.0×104 HU/mg, respectively, and were inhibited by sphingomyelin. The N-terminal amino acid sequence of RTX-A was determined as ALAGAIIAGAGLGLKILIEVLGEG–VKVKI–. Molecular weight of low molecular weight Radianthus cytolysins RmI, RmII, and of one trypsin inhibitor InI were 5100, 6100 and 7100, respectively. Isoelectric points for RmI and RmII were 9.2 and 9.3. Their hemolytic activity worked out 25 and 20 HU/mg, and was not inhibited by sphingomyelin. Toxicity of RmI and RmII was assessed by their histaminolytic activity. Amino acid composition of RmI and RmII was similar to that of tealiatoxin, histaminolytic cytolysin from the sea anemone Tealia felina. [Copyright &y& Elsevier]

A dinoflagellate bloom was found associated with a fish kill event in a South Carolina brackish water retention pond. A multi-analytical approach was used to confirm the identity of the bloom dinoflagellate and evaluate its potential toxicity. Karlodinium micrum was confirmed through light microscopy, pigment profile comparisons, species-specific PCR, and gene sequence data. Necropsy findings on several fish were suggestive of an acute kill event. Toxicity of filtrate from bloom samples was tested by a hemolytic assay using rainbow trout (Oncorhynchus mykis) erythrocytes and an ichthyotoxicity assay using larval zebrafish (Danio rerio). Hemolytic activity was measurably high (>80% hemolysis) in both whole filtrate and fractionated filtrate (from the 80% MeOH C18 column elution). This fraction also demonstrated high ichthyotoxic activity as exposed fish experienced rapid death. These results implicate toxic K. micrum as a causative factor in fish death in a non-aquaculture brackish pond associated with a housing development, and extend recent findings linking this species to fish kills in aquaculture ponds. [Copyright &y& Elsevier]

Summary A case of cytomegalovirus (CMV) colitis mimicking travelers’ diarrhea following short-term travel is reported. The patient was a Croatian man visiting Korea for work. He presented with fever and severe bloody diarrhea. He was diagnosed with a primary CMV infection complicated with CMV colitis and hemolytic anemia and recovered with antiviral therapy and concomitant steroid therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Magnesium incorporated hydroxyapatite was synthesized by using microwave-assisted wet chemical method. • The spectrophotometer method was used to perform the hemolytic activity of the samples. • The chemical bonding of the samples was confirmed by the FTIR spectrum. • The HR-TEM confirms the spherical morphology of the synthesized samples. • The in vitro antibacterial activity of the samples was studied. • The in vitro anti-inflammatory activity against standard drug diclofenac sodium for the samples were studied. • The samples were non-hemolytic according to the ASTM F756-00 (American Society for Testing and Materials Designation). In this work, we have investigated the antibacterial and hemolytic efficacy of hydroxyapatite (HA) and Magnesium (Mg) incorporated hydroxyapatite (MHA), where the composite was synthesized by a rapid and cost-effective microwave-assisted wet chemical method. The synthesized MHA composite was characterized by using X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), High-resolution transmission electron microscopy (HRTEM), in vitro antibacterial and anti-inflammatory activities. Also, the hemolytic activity of the sample was studied using the spectrophotometer technique. From the analysis, the XRD diffractogram confirms the presence of HA and MHA by the JCPDS card no: 09-0432. The chemical bonding confirmed the presence of Mg and HA in the nanocomposite and the HRTEM confirmed the spherical shape morphology of synthesized samples. The in vitro antibacterial activity of the nanocomposite was studied against the gram-positive bacteria Staphylococcus aureus and gram-negative bacteria Escherichia coli. Also, the in vitro anti-inflammatory activity of the sample was studied against the standard drug Diclofenac sodium and found to be compatible with the standard values. Further, the samples are investigated to be non-hemolytic according to the ASTM F756-00 (American Society for Testing and Materials Designation). Based on the studies, the prepared Mg-HA nanocomposite can be potential for the biomedical applications of dental, orthopaedic, and stem cell research. [ABSTRACT FROM AUTHOR]

• Cyclotides are ultrastable miniproteins with cyclic cystine knot topology. • Literature survey revealed134 bioactive cyclotides from four angiosperm families. • Native bioactive cyclotides have applications in agriculture and pharmaceutics. • Mode of action of cyclotides is via binding to target membrane and its disruption. • More than 350 cyclotides remain to be investigated for bioactivities. Cyclotides are plant-derived mini-proteins of 28 - 37 amino acids. They have a characteristic head-to-tail cyclic backbone and three disulfide cross-linkages formed by six highly conserved cysteine residues, creating a unique knotted ring structure, known as a cyclic cystine knot (CCK) motif. The CCK topology confers immense stability to cyclotides with resistance to thermal and enzymatic degradation. Native cyclotides are of interest due to their multiple biological activities with several potential applications in agricultural (e.g. biopesticides, antifungal) and pharmaceutical (e.g. anti-HIV, cytotoxic to tumor cells) sectors. The most recent application of insecticidal activity of cyclotides is the commercially available biopesticidal spray known as 'Sero X' for cotton crops. Cyclotides have a general mode of action and their potency of bioactivity is determined through their binding ability, pore formation and disruption of the target biological membranes. Keeping in view the important potential applications of biological activities of cyclotides and the lack of an extensive and analytical compilation of bioactive cyclotides, the present review systematically describes eight major biological activities of the native cyclotides from four angiosperm families viz. Fabaceae, Poaceae, Rubiaceae, Violaceae. The bioactivities of 94 cytotoxic, 57 antibacterial, 44 hemolytic, 25 antifungal, 21 anti-HIV, 20 nematocidal, 10 insecticidal and 5 molluscicidal cyclotides have been comprehensively elaborated. Further, their distribution in angiosperm families, mode of action and future prospects have also been discussed. [ABSTRACT FROM AUTHOR]

Bis-benzimidazolium salts and their silver(I)- N -Heterocyclic Carbene (Ag-NHC) complexes are efficient antibacterial tool and can be employed for pre-clinical trials as they are safe to erythrocytes. • Ag(I)-NHC complexes are easy to synthesize. • NHC ligands and their silver complexes are potential antibacterial agents. • Presence of benzene ring in ligand and complexes affects their biological potential. • Ag(I)-NHC complexes are safe to mouse blood. • The compounds can be used as active thrombolytic agents for pre-clinical trials. A new series of N -Heterocyclic carbene based ligands and their silver(I) complexes was obtained and tested in vitro on three bacterial strains (Bacillus subtillis , Bacillus cereus and Macrococcus brunensis) to assess their antibacterial potential. Hemolytic and thrombolytic activities of ligands and complexes on normal mouse erythrocytes were also assessed. In vitro antibacterial study of ligands and complexes revealed that the complexes are relatively more antibiotically active than the ligands. Zones of inhibition and MIC values revealed that B. subtillis is more sensitive to complexes than B. cereus and M. brunensis while reverse is the case for NHC salts. Hemolytic and thrombolytic assays revealed that the compounds are safe to mouse blood for pre-clinical trials. [ABSTRACT FROM AUTHOR]

A series of CuII, CoII, ZnII and NiII, complexes of 34,74-dimethyl-12,15,52,55-tetrahydro-2,4,6,8-tetraaza-1,5(2,5)-difurana-3,7(1,2)-dibenzenacyclooctaphane based ligand have been synthesized by template methodology. Characterization of the synthesized complexes has been carried out with the help of various physicochemical and spectroscopic techniques like Infra-Red, ESI-MS, ESR, UV–visible, CHN (elemental analyses), molar conductance, magnetic moment and NMR. Antimicrobial efficacy of the newly designed macrocyclic complexes has performed by the assistance of agar well diffusion method. In-vitro hemolytic and DNA binding studies were also performed in order to analyze or interpret the mode and binding efficiencies as well as the % hemolysis exhibited by the complexes. DFT/TD-DFT studies were carried out in order to elucidate the better insight into the structural parameters. Energy minimization and quantum chemical parameters were calculated using Gaussian09W program. Unlabelled Image • Ten new furan based macrocyclic complexes were prepared and spectroscopically characterized. • Antimicrobial, DNA binding and hemolytic activities were evaluated for bio-potency. • DFT studies were carried out for calculations of quantum chemical parameters. [ABSTRACT FROM AUTHOR]

Diosgenyl 2-amino-2-deoxy-β- d -glucopyranoside is a semisynthetic saponin with antimicrobial and antitumor activities. To search for more effective analogues, N -aminoacyl and N -hydroxyacyl derivatives of this saponin were synthesized conventionally and with microwave assistance, and tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. None of the tested compounds exhibit activity against Gram-negative bacteria. Almost all of the synthesized N -aminoacyl saponins exhibit antifungal activity and act effectively against Gram-positive bacteria, some better than the parent compound. The best acting saponins are the same size and possess sarcosine or l - or d -alanine attached to the parent glucosaminoside. Shorter and longer aminoacyl residues are less advantageous. d -Alanine derivative is the most effective against Gram positive bacteria. Structure-activity relationship (SAR) analysis indicates that the free α-amino group in aminoacyl residue is necessary for antimicrobial activities of the tested saponins. (N -Acetyl)aminoacyl and N -hydroxyacyl analogs are inactive. Measurements of the hemolytic activities demonstrate that the best acting saponins are not toxic towards human red blood cells. [ABSTRACT FROM AUTHOR]