Doses Of GA Research Articles

Assessing the stoichiometric efficacy of mammalian expressed paraoxonase-1 variant I-F11 to afford protection against G-type nerve agents

We evaluated the ability of evolved paraoxonase-1 (PON1) to afford broad spectrum protection against G-type nerve agents when produced in mammalian cells via an adenovirus expression system. The PON1 variants G3C9, VII-D11, I-F11, VII-D2 and II-G1 were screened in vitro for their ability to hydrolyze G-agents, as well as for their preference towards hydrolysis of the more toxic P(−) isomer. I-F11, with catalytic efficiencies of (1.1 ± 0.1) × 106 M−1 min−1, (2.5 ± 0.1) × 106 M−1 min−1, (2.3 ± 0.5) × 107 M−1 min−1and (9.2 ± 0.1) × 106 M−1 min−1 against tabun (GA), sarin (GB), soman (GD) and cyclosarin (GF), respectively, was found to be a leading candidate for further evaluation. To demonstrate the broad spectrum efficacy of I-F11 against G-agents, a sequential 5 × LD50 dose of GD, GF, GB and GA was administered to ten mice expressing I-F11 on days 3, 4, 5 and 6 following virus injection, respectively. At the conclusion of the experiment, 80% of the animals survived exposure to all four G-agents. Using the concept of stoichiometric efficacy, we determined that I-F11 affords protection from lethality against an administered dose of 10, 15, 90 and 80 molar equivalents of GA, GB, GD and GF, respectively, relative to the molar equivalents of I-F11 in circulation. It also appears that I-F11 can associate with high density lipoprotein in circulation, suggesting that I-F11 retained this function of native PON1. This combination of attractive attributes demonstrates that I-F11 is an attractive candidate for development as a broad-therapeutic against G-type nerve agent exposure.

Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. 8 healthy neonatal calves. Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

Silicon-based nanostructures formed by plasma etching through a mask formed by a focused beam of Ga+ ions

A method of formation of three-dimensional silicon-based nanostructures by a mask formation with the use of focused ion beam, for following plasma etching, is presented. A surface relief pattern, with depths of less than 80 nm, dependent on a dose of interstitial ions, was formed by plasma etching of an undoped area. A range of values of a dose of Ga+ ion beam for silicon doping was determined. Three-dimensional silicon-based structures with linear dimensions of about 100 nanometers were obtained.

The teratogenicity and the action mechanism of gallic acid relating with brain and cervical muscles.

Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. A CEM was used to administer GA at 2, 6, 10, and 14 μM. GA at 2 μM did not exhibit cytotoxicity. At 6, 10, and 14 μM, GA caused severe decreases in body and liver weights, causing -5.6%, -21.3%, and -27.5% body weights and 4.0, 3.8, and 3.2-g, liver weights, respectively, in day-1 chicks. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. The mechanism of action of GA is multidisciplinary: The liposis can be ascribed to downregulation of PPAR-α; the erythrocyte hemolysis can be attributed to its unique autooxidative and prooxidant behavior and the inhibition of carbonic anhydrase; and the proliferation and differentiation deficits can be attributed to the upregulation of the Ras/Raf/JAK/STAT pathway.

Gallic acid exhibits risks of inducing muscular hemorrhagic liposis and cerebral hemorrhage--its action mechanism and preventive strategy.

Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6-14 μM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N-acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif-1α and downregulated ratio vegf-r2/vegf-a, leading to dys-vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H2O2, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N-acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds.

The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.

A novel phase I trial design featuring a two-dimensional dose-finding algorithm optimizing the dose of gemcitabine and doxorubicin with bortezomib in metastatic urothelial carcinoma (UC).

4548 Background: Preclinical studies suggested that bortezomib (B) enhanced the activity of gemcitabine and doxorubicin (GA) in UC; thus we sought to define possible combinations of bortezomib with this doublet. We employed a novel phase I trial design systematically exploring doses in 2 dimensions. The method estimates an isotoxic curve allowing not only a combination with approximately equal (with respect to single component MTD) contributions of the two components to be found, but also combinations emphasizing one component or the other. Methods: Since 11/06, 74 patients with previously treated metastatic cancer were enrolled (70 UC, 3 prostate, 1 renal). GA was treated as a single component and given in a fixed ratio to a maximum of 900 and 50 mg/m2, and B to a maximal dose of 1.6 mg/m2 IV, with dosing every 14 days. After determining the MTD along the diagonal, we then decreased the dose of B, increasing GA, and vice versa, exploring doses along an isotoxic curve aiming for ≤ 30% dose limiting toxicity (DLT) in cycle 1. The objective response rate (ORR) includes PR or CR, and excludes SD. Results: The MTD along the diagonal for GAB was 756, 42, and 1.4 mg/m2, respectively. Doses maximizing the GA (900, 50) required reduction of B to 1.2 mg/m2. Likewise, doses maximizing B (1.6) required reduction of GA to 559 and 33 mg/m2. The most common DLT were thrombocytopenia 14%, neutropenic fever 5%, and mucositis 1%. There was minimal activity at the on-diagonal MTD with an ORR 1/10. Of the tolerable doses along the isotoxic curve, the greatest activity was seen when maximizing B (1.5-1.6 mg/m2, ORR 7/12 (58%)). The ORR when maximizing GA was 4/10. The most frequent ≥ G3 toxicities include: thrombocytopenia (26%), neutropenia (26%), anemia (24%), fatigue (8%), and neutropenic fever or infection (12%). Treatment was tolerable in poor renal function; 36 patients (49%) had a GFR < 50 ml/min. Conclusions: The combination of GAB has promising activity at doses maximizing proteosome inhibition, despite relatively low doses of GA. Traditional phase 1 design dosing to the MTD "along the diagonal" would have lead to the incorrect conclusion that there was minimal activity. Clinical trial information: NCT00479128.

A novel phase I trial design featuring a two-dimensional dose-finding algorithm optimizing the dose of gemcitabine and doxorubicin with bortezomib in metastatic urothelial carcinoma (UC).

263 Background: Preclinical studies suggested that bortezomib (B) enhanced the activity of gemcitabine and doxorubicin (GA) in UC; thus we sought to define possible combinations of bortezomib with this doublet. We employed a novel phase I trial design systematically exploring doses in 2 dimensions. The method estimates an isotoxic curve allowing not only a combination with approximately equal (with respect to single component MTD) contributions of the two components to be found, but also combinations emphasizing one component or the other. Methods: Since 11/06, 74 patients with previously treated metastatic cancer were enrolled (70 UC, 3 prostate, 1 renal). GA was treated as a single component and given in a fixed ratio to a maximum of 900 and 50 mg/m2, and B to a maximal dose of 1.6 mg/m2 IV, with dosing every 14 days. After determining the MTD along the diagonal, we then decreased the dose of B, increasing GA, and vice versa, exploring doses along an isotoxic curve aiming for ≤ 30% dose limiting toxicity (DLT) in cycle 1. The objective response rate (ORR) includes PR or CR, and excludes SD. Results: The MTD along the diagonal for GAB was 756, 42, and 1.4 mg/m2, respectively. Doses maximizing the GA (900, 50) required reduction of B to 1.2 mg/m2. Likewise, doses maximizing B (1.6) required reduction of GA to 559 and 33 mg/m2. The most common DLT were thrombocytopenia 14%, neutropenic fever 5%, and mucositis 1%. There was minimal activity at the on-diagonal MTD with an ORR 1/10. Of the tolerable doses along the isotoxic curve, the greatest activity was seen when maximizing B (1.5-1.6 mg/m2, ORR 7/12 (58%)). The ORR when maximizing GA was 4/10. The most frequent ≥ G3 toxicities include: thrombocytopenia (26%), neutropenia (26%), anemia (24%), fatigue (8%), and neutropenic fever or infection (12%). Treatment was tolerable in poor renal function; 36 patients (49%) had a GFR < 50 ml/min. Conclusions: The combination of GAB has promising activity at doses maximizing proteosome inhibition, despite relatively low doses of GA. Traditional phase I design dosing to the MTD "along the diagonal" would have lead to the incorrect conclusion that there was minimal activity. Clinical trial information: NCT00479128.

Pharmacological activity of Mexican basidiomycetes species cultivated in vitro

A great variety of Basidiomycetes grow in Mexico, but most of their properties, includying pharmacological ones, have been scarcely investigated. In this study, the hypoglycemic, immunomodulating and antioxidant activity of aqueous extracts prepared from cultured mycelia of Lentinus lepideus (Ll), Calvatia cyatiformis (Cc) and Ganoderma applanatum (Ga) collected in Nuevo León, Mexico are presented. Hypoglycemic activity was evaluated in alloxan-induced diabetic rats which received a single dose (100mg/kg po) of Ll, Cc or Ga, and the serum glucose was measured at 0, 3, and 6h after administration, immunomodulating activity was evaluated in Balb/c mice according to the the Cunningham hemolytic plate assay. The antioxidant (DCFDA test) and cytotoxic (MTT test) effect were evaluated in Chang liver cells. None of the species tested had cytotoxic activity, Ll, Cc, and Ga lowered the serum glucose levels at 3h and 6h after administration Ll and Cc showed significant immunostimulation, Ll, Cc and Ga demonstrated relevant antioxidant activity (49%-75%); Ll was the species with major hypoglycemic, immunostimulating and antioxidant activity. A fractionation of Ll was carried out and four fractions were obtained (FI-FIV) and evaluated. Fractions II and III were the most active. Conclusion: Mexican Basidiomycetes are a potential source of compounds with hypoglycemic, immunomodulating and antioxidant activity.

Effects of Gibberellic Acid on Hemocytes ofGalleria mellonellaL. (Lepidoptera: Pyralidae)

The impacts of different doses of the plant growth regulator gibberellic acid (GA(3)) in diet on the number of total and differential hemocytes, frequency of apoptotic, and necrotic hemocytes, mitotic indices, encapsulation, and melanization responses were investigated using the greater wax moth Galleria mellonella L. (Lepidoptera: Pyralidae) larvae. Total hemocyte counts increased in G. mellonella larvae at all treatment doses whereas GA(3) application had no effect on the number of different hemocyte types. The occurrence of apoptosis, necrosis and mitotic indices in GA(3) treated and untreated last instars were detected by acridine orange or ethidium bromide double staining by fluorescence microscopy. While the ratio of necrotic hemocytes increased at all GA(3) treatments, that of late apoptotic cells was only higher at doses >200 ppm when compared with untreated larvae. The percentage of mitotic index also increased at 5,000 ppm. Positively charged DEAE Sephadex A-25 beads were used for analysis of the levels of encapsulation and melanization in GA(3) treated G. mellonella larvae. At four and 24 h posttreatments with Sephadex A-25 bead injection, insects were dissected under a stereomicroscope. Encapsulation rates of larval hemocytes were dependent on the extent of encapsulation and time but not treatment groups. While the extent of melanization of hemocytes showed differences related to time, in general, a decrease was observed at all doses of GA(3) treated larvae at 24 h. We suggest that GA(3) treatment negatively affects hemocyte physiology and cell immune responses inducing cells to die by necrosis and apoptosis in G. mellonella larvae.

Effect of gibberellic acid on the quality of chrysanthemum (Dendranthema grandiflora L.) cv. Faroe

The aim of the present work was to evaluate the quality of chrysanthemum cultivar Faroe, subjected to different gibberellic acid (GA 3 ) concentrations applied to the field. The treatments were composed of four doses of GA 3 (0, 15, 30 and 45 mg L -1 ) applied at the beginning of the formation of buttom floral (28 days after transplanting of seedlings). According to the results, a single low concentration of GA 3 application did not interfere with the phenotypic characteristics of the chrysanthemum cultivar Faroe. Key words : Dendranthema grandiflora, height, diameter, flowering.

Enzymatic Process for Corn Dry‐Grind High‐Solids Fermentation

ABSTRACTA modified dry‐grind process that combined the use of conventional amylases (glucoamylase [GA]), phytase, and granular starch hydrolyzing enzymes (GSHE) to achieve low liquefaction viscosities and low glucose concentrations during simultaneous saccharification and fermentation (SSF) with a high slurry solids content (>33% w/w) was developed. Doses of GSHE and GA were optimized for the modified process. At 35% solids content, the modified process had 80% lower slurry viscosity, 24% lower peak glucose concentration, 7.5% higher final ethanol concentration, and 51% higher fermentation rate compared with the conventional dry‐grind process. At 40% solids content, the modified process had lower viscosities, lower peak and residual glucose concentrations, and higher ethanol concentrations than the conventional process; however, the results were in contrast to those for 35% solids content. At 40% solids content, SSF did not run to completion for conventional or modified processes, and more than 2.5% w/v of residual glucose was left in the fermentation broth. Final ethanol concentration achieved with the modified process at 40% solids content was 19.5% v/v, similar to the ethanol concentration achieved with the modified process at 35% solids content. At 35% slurry solids content, a GSHE level of 1.25 μL/g db of corn and a GA level of 0.25 μL/g db of corn were selected as optimum enzyme doses for the modified process.

The various facets of the protein‐folding activity of the ribosome

In addition to its involvement in protein synthesis, the ribosome is implicated in protein folding. Some co-translational events, such as the rhythm of protein synthesis, the passage through the exit tunnel of the ribosome, or the interaction with ribosome-associated chaperones may help protein folding. Ribosomes from prokaryotes, eukaryotes, and mitochondria have also been shown to assist the folding of denatured proteins in vitro in a translation-independent way. This intriguing protein-folding activity of the ribosome (PFAR, also termed RPFA) has been mapped to the domain V of the large rRNA of the large subunit of the ribosome. Unfolded, newly synthesized proteins catalyze the dissociation of the two ribosomal subunits in vitro, thereby promoting ribosome recycling and facilitating accessibility of domain V to these proteins, which in turn may help their folding by PFAR. The recent identification of 6AP and GA - the two first drugs that specifically inhibit PFAR without affecting protein translation - will help decipher the biological significance of PFAR in vivo. Of note, 6AP and GA were initially isolated on the basis of their activity against prion-based diseases. Recently, 6AP and GA were also shown to be active in vivo in a drosophila model for oculopharyngeal muscular dystrophy, which is another amyloid-based disease. This effect is mimicked by large deletions in the ribosomal DNA (rDNA) locus. In addition, small deletions in the rDNA locus show a synergistic effect with low doses of 6AP and GA. Hence, PFAR may be involved in various amyloid-based diseases.

A Combination of Low Doses of Curcumin and Gramicidin Selectively kills Cancer Cells that Express Multidrug Resistance‐linked ABCG2 Transporter

The ATP‐binding cassette (ABC) G2 (also called breast cancer resistance protein, BCRP) is a transporter that provides malignant cells with a mechanism to evade chemotherapy by developing multidrug resistance (MDR). This phenomenon has led to wide spread interest in developing strategies to circumvent ABC transporter‐mediated MDR in cancer cells. This study reports a strategy to selectively kill cancer cells that overexpress the ABCG2 transporter. The control vector‐transfected HEK 293 and HEK 293‐ABCG2 cells were treated with curcumin, the bioactive compound in turmeric, and gramicidin A (gA), a pore‐forming peptide from Bacillus brevis. The treatment of cells with sub‐toxic doses of curcumin, or gA had no effect on the viability of HEK‐control cells or HEK‐ABCG2 cells. However, the simultaneous administration of sub‐toxic doses of curcumin (2 μM) and gA (35 nM) selectively killed HEK‐ABCG2 cells and inhibited the transport function of ABCG2 as measured by flow cytometry, while HEK 293‐control cells remained unaffected. Consistent with previously published data, curcumin stimulated ATP hydrolysis by ABCG2, while gA did not have an effect on basal and curcumin‐stimulated ATPase activity of this transporter. These results suggest that gA enhances the cytotoxic effect of curcumin without interacting directly with the ABCG2 transporter. Taken together, these findings provide a potential strategy to target, in particular, those malignant cancer cells that develop MDR due to overexpression of ABCG2 transporter.

Coupled effects of ion beam chemistry and morphology on directed self-assembly ofepitaxial semiconductor nanostructures

We study the coupled effects of ion beam chemistry and morphology on the assembly of templatedepitaxial nanostructures. Using a focused ion beam (FIB) system equipped with a mass-selectingfilter, we pattern Si substrates with local ion doses of Si, Ge and Ga to control subsequentGexSi1 − x epitaxial nanostructure assembly. This capability to employ different templating speciesallows us to study how different incorporated ion species in the near surface region affectthe ability to localize nucleation during subsequent epitaxial growth. Our results indicatethat FIB-directed self-assembly is a complex process, dependent on dose-inducedmorphology in addition to ion-specific chemical effects.

Effects of combined administration of low‐dose gossypol with steroid hormones on the mitotic phase of spermatogenesis of rat

Our previous studies suggested that combined low-dose gossypol with steroid hormones possesses a reversible antifertility role on adult male rat. Spermatocyte apoptosis during the meiosis of spermatogenesis is the main reason for the antifertility. This study evaluates the effects of the regimen on the mitosis of spermatogenesis. Thirty-two adult male rats were divided into four groups randomly, Group GH: rats were fed orally with gossypol acetic acid (GA, 12.5 mg/kg d) and desogestrel (DSG, 0.125 mg/kg d)/ethinylestradiol (EE, 0.025 mg/kg d)/testosterone undecanoate (TU, 100 mg/kg d); Group G: a single dose of GA (12.5 mg/kg d); Group H: the same dosage of DSG/EE/TU as in Group GH; Group C: rats were treated with vehicle (1% methyl cellulose) as control. Testes were removed at the 8th week after treatment to assess the weight, volumes, diameter, and degenerated rate of seminiferous tubule, spermatogonia is quantitated by stereological assay. TUNEL assay and proliferating cell nuclear antigen immunohistochemistry were used to determine the germ cell apoptosis and proliferation. The changes of gene expression of glial cell line-derived neurotrophic factor (GDNF) and Ets variant gene 5 (Etv5) were analyzed. The results manifested that the spermatogenesis was suppressed, the type A and intermediate spermatogonia reduced, and spermatocyte and spermatid apoptosis increased both in Group GH and Group H. The expressions of GDNF protein in these two groups were downregulated, but no change was observed in Etv5 expression. However, the numbers of spermatogonia, germ cell apoptosis and proliferation, and the expressions of GDNF and Etv5 were unchanged in Group G compared with Group C. Above all, we concluded that the mitotic phase of spermatogenesis is suppressed by the combination regimen, it might be the steroid hormones in the regimen that caused the reduction of spermatogonia through the downregulation of GDNF.

Gallium Disrupts Iron Uptake by Intracellular and ExtracellularFrancisellaStrains and Exhibits Therapeutic Efficacy in a Murine Pulmonary Infection Model

Francisella tularensis requires iron (Fe) for growth, but the biologic sources of Fe for this organism are largely unknown. We found that Francisella sp. growing in broth culture or within human macrophages can acquire Fe from the two major host Fe-binding proteins, lactoferrin (Lf) and transferrin (Tf). Fe acquisition is a potential target for novel therapies. Gallium (Ga) is a transition metal that interferes with cellular Fe metabolism by competing with Fe for uptake/utilization. Growth of either F. tularensis live vaccine strain (LVS) or Francisella novicida was inhibited by >or=2 microM Ga chelated to Tf or Lf, with GaLf being somewhat more potent. Francisella spp. express two Fe-containing antioxidant enzymes, catalase (KatG) and Fe cofactored superoxide dismutase (FeSOD). Growth of LVS with 10 muM GaTf or GaLf led to a dramatic decrease in bacterial catalase activity and in FeSOD activity that was associated with an increased susceptibility to H(2)O(2). Ga also protected mice from intranasal challenge with F. novicida. Whereas 100% of the F. novicida-infected mice died by day 9, 75% of the mice receiving Ga continued to survive to at least day 15. Thus, a single intranasal dose of Ga followed by daily intraperitoneal Ga at a dose tolerated by the animals resulted in prolonged survival. These data support the potential utility of Ga as a therapy for F. tularensis infection of the lung.

Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA- 198AuNP nanoconstruct in prostate tumor–bearing mice

Biocompatibility studies and cancer therapeutic applications of nanoparticulate β-emitting gold-198 ( 198Au; β max = 0.96 MeV; half-life of 2.7 days) are described. Gum arabic glycoprotein (GA)–functionalized gold nanoparticles (AuNPs) possess optimum sizes (12–18 nm core diameter and 85 nm hydrodynamic diameter) to target individual tumor cells and penetrate through tumor vasculature and pores. We report the results of detailed in vivo therapeutic investigations demonstrating the high tumor affinity of GA- 198AuNPs in severely compromised immunodeficient (SCID) mice bearing human prostate tumor xenografts. Intratumoral administration of a single dose of β-emitting GA- 198AuNPs (70 Gy) resulted in clinically significant tumor regression and effective control in the growth of prostate tumors over 30 days. Three weeks after administration of GA- 198AuNPs, tumor volumes for the treated animals were 82% smaller as compared with tumor volume of control group. The treatment group showed only transitory weight loss in sharp contrast to the tumor-bearing control group, which underwent substantial weight loss. Pharmacokinetic studies have provided unequivocal evidence for the optimum retention of therapeutic payload of GA- 198AuNPs within the tumor site throughout the treatment regimen with minimal or no leakage of radioactivity to various nontarget organs. The measurements of white and red blood cells, platelets, and lymphocytes within the treatment group resembled those of the normal SCID mice, thus providing further evidence on the therapeutic efficacy and concomitant in vivo tolerance and nontoxic features of GA- 198AuNPs. From the Clinical Editor In this study, the biocompatibility and cancer therapeutic applications of glycoprotein (GA) functionalized gold nanoparticles containing b-emitting Au-198 are described in SCID mice bearing human prostate tumor xenografts. The findings of significant therapeutic efficacy, good in vivo tolerance and non-toxic features make these particles ideal candidates for future human applications.

Experimental observation of FIB induced lateral damage on silicon samples

Scanning spreading resistance microscopy (SSRM) and scanning capacitance microscopy (SCM) were used to analyze focused ion beam (FIB) induced lateral damage around milled structures on silicon. For this purpose, circular shaped structures were realized, and the influence of the implanted Ga dose (ranging from 10 15 to 10 17 cm −2) and of the patterned area dimension (diameters ranging from 1 to 4 μm) on the damage were examined. It is shown that the extension of the lateral damage around FIB milled structures is much larger than the area of the purposely irradiated regions (up to a factor of 5) and increases with both, Ga dose and pattern diameter. Besides, the unique capability of SCM and SSRM techniques for the detection of FIB induced damage is demonstrated. In particular, it is shown that their high sensitivity to low densities of defects allows detecting larger damaged areas compared to Atomic Force Microscopy (AFM) topography maps.

In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans

Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC).