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   2012| December  | Volume 11 | Issue 2  
    Online since July 18, 2014

 
 
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ORIGINAL ARTICLES
Safety evaluation of needle-like hydroxyapatite nanoparticles in female rats
Azza I. Hafez, Fatma Hafez, Maaly Khedr, Omayma Ibrahim, Rania Sabry, Mossad A. Abdel-Wahhab
December 2012, 11(2):67-72
DOI:10.7123/01.EPJ.0000418505.66044.c8   
Objective

The present study was designed to evaluate the safety of synthesized needle-like hydroxyapatite (HAp) nanoparticles ranging from 3 to 7 nm in diameter and from 27 to 46 nm in length when administered in female rats orally or subcutaneously at different concentrations.

Methods

Animals in different treatment groups were maintained on their respective diets as follows: group 1, untreated control; group 2, treated orally with HAp (300 mg/kg body weight) for 3 weeks; group 3, treated orally with a low dose of HAp (150 mg/kg body weight) for 3 weeks; and group 4, implanted subcutaneously with HAp (600 mg/kg body weight) once and left for 5 weeks. At the end of the experimentation period, blood samples were collected from all animals for biochemical analysis (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, uric acid, urea, and creatinine). After sacrifice, histopathological examination of the liver and kidney was carried out.

Results and conclusion

The biochemical results showed an increase in alanine aminotransferase and aspartate aminotransferase in the groups treated orally and those treated subcutaneously. There was an increase in alkaline phosphatase only in the group receiving the high oral dose; however, animals treated with the low dose or those treated subcutaneously were comparable with the control group. All the rats showed normal kidney function because of normal levels of creatinine, urea, and uric acid. The histopathological results indicated that the liver and kidney of all rats treated with HAp (oral or subcutaneously) had a normal structure. The previous results confirmed the safety of the synthesized nanoneedle HAp when administered orally or subcutaneously at the suggested dose.

  1,243 3,505 -
Comparative evaluation of in-vitro cytotoxicity, antiviral and antioxidant activities of different soyasapogenols from soybean saponin
Hala A. Amin, Hanem M. Awad, Atef G. Hanna
December 2012, 11(2):73-79
DOI:10.7123/01.EPJ.0000421669.78647.e9   
Objectives

The aim of this study was to evaluate comparative and structure–activity relationships of in-vitro cytotoxicity, antiviral and antioxidant activities of soyasapogenols A, B, D and F (SSA, SSB, SSD and SSF) together against the total soyasaponin extract (TSSE) itself.

Methods

The cytotoxicity of soyasapogenols and TSSE against human colon carcinoma cell line (HCT-116), liver carcinoma cell line (Hep-G2), human breast carcinoma cell line (MCF-7) and normal human melanocytes (HFB-4) cell lines was assessed using sulforhodamine B assay. Their antiviral activities were investigated against Rift Valley fever virus (RVFV), hepatitis C virus model (vesicular stomatitis virus, VSV), and hepatitis A virus (HAV). The antioxidant activity of soyasapogenols and TSSE was assessed using a stable DPPH free radical.

Results and conclusion

The results obtained showed that both TSSE and soyasapogenols have a potent cytotoxic effect on Hep-G2, HCT-116, MCF-7 and HBF-4 cell lines in a concentration-dependent manner. SSA and SSF showed the highest cytotoxic activities against tested cell lines. Analysis of the three-dimensional structure of the measured soyasapogenols indicated that if the β-hydroxyl group at C-21 or C-22 was aligned with the plane of the molecule, a marked increase in the cytotoxic activity of the soyasapogenol was produced. Their antiviral activities against RVFV, VSV and HAV showed significant inhibition activities compared with both TSSE and interferon. SSB showed the best activity against RVFV and HAV, whereas SSA was the best inhibitor against VSV. It was concluded that the hydroxylation at C-21 as well as the presence of a double bond in ring D might enhance anti-VSV activity, whereas they may not be essential for anti-RVFV and anti-HAV activities. On the other hand, the tested soyasapogenols and TSSE did not show good antioxidant activities.

  1,280 1,538 -
The efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the treatment of physiological neonatal jaundice ( a randomized, double-blind, placebo-controlled, clinical trial)
Lamyaa M. Kassem, Mohamed E.A. Abdelrahim, Hassan F. Naguib
December 2012, 11(2):144-149
DOI:10.7123/01.EPJ.0000421667.70605.8a   
Back ground and aim of work

Unconjugated hyperbilirubinemia (UCB) is one of the most common conditions in neonates. Conventional treatments are phototherapy and exchange transfusion. Phototherapy is safe and effective, but it has several disadvantages, which indicates the need to develop alternative pharmacological treatment strategies. These alternative treatment strategies should be less invasive and at least as effective and safe as phototherapy. The present study was designed to investigate the effects of Silybum marianum (silymarin) on the duration of phototherapy, which is known to have antioxidant, anti-inflammatory, hepatic-protective, and regenerative properties, including enhancing glucuronidation activities.

Patients and methods

A randomized double-blind clinical trial was conducted on 170 full-term healthy neonates with UCB divided into two well-matched groups. Of the 170 neonates, 85 received 3.75 mg/kg of silymarin orally, twice daily, in addition to phototherapy, and 85 received placebo and phototherapy. Total serum bilirubin was measured every 24 h, and alanine aminotransferase (SGPT) and alanine transaminase (SGOT) levels were measured before and after therapy in both groups.

Results

The mean duration of phototherapy was found to be significantly reduced from 5.3±0.82 days in the control group to 4.2±0.76 days in the silymarin-treated group (P=0.001). SGPT and SGOT levels were significantly normalized (P=0.001).

Conclusion

Silymarin at a dose of 3.75 mg/kg twice daily along with phototherapy was more effective than phototherapy alone in treating full-term healthy neonates with UCB.

  1,853 178 -
Phycochemistry of some Sargassum spp. and their cytotoxic and antimicrobial activities
Azza A Matloub, Nagwa E Awad
December 2012, 11(2):99-108
DOI:10.7123/01.EPJ.0000419800.62958.79   
Purpose

A comparative study on the chemical composition as well as cytotoxic and antimicrobial activities of the brown algae Sargassum asperifolium, Sargassum dentifolium, and Sargassum linifolium (family: Sargassaceae) from the Red Sea, Hurghada, Egypt, is carried out.

Methods

The volatile constituents obtained by hydrodistillation as well as the isolated unsaponifiable matter and the fatty acids were analyzed using the gas chromatography/mass spectrometry technique. Antitumorigenic activities of the crude extracts of the three algae have been evaluated in vitro on different human cell lines. Furthermore, the antimicrobial activities of the volatile constituents, successive extractives, unsaponifiable matter, and fatty acids have been tested on 11 different microorganisms.

Results

The analysis of the volatile fraction led to the identification of sexual pheromones, terpenes, phenolic compounds, free fatty acids, and esters. The most abundant sterols of unsaponifiable matter were fucosterol and cholesterol in all algae. Palmitic acid was found in all investigated algae as a major fatty acid. Biological screening proved that the tested algae have various cytotoxic and antimicrobial activities.

Conclusion

S. asperifolium, S. dentifolium, and S. linifolium are rich in cytotoxic and antimicrobial bioactive metabolites.

  1,552 242 -
Synthesis of certain new fused pyranopyrazole and pyranoimidazole incorporated into 8-hydroxyquinoline through a sulfonyl bridge at position 5 with evaluation of their in-vitro antimicrobial and antiviral activities
Emad M. Kassem, Eslam R. El-Sawy, Howaida I. Abd-Alla, Adel H. Mandour, Dina Abdel-Mogeed, Mounir M. El-Safty
December 2012, 11(2):116-123
DOI:10.7123/01.EPJ.0000421482.33940.0b   
Background and objectives

Heterocyclic systems with a quinoline nucleus display a wide spectrum of biological activities such as antimicrobial and antiviral activities. The aim of the present study was the synthesis of new fused pyranopyrazoles, 5a-e and 6a-e, and pyranoimidazoles, 10a-e and 11a-e, incorporated to 8-hydroxyquinoline through a sulfonyl bridge at position 5 and evaluation of their antimicrobial and antiviral activities.

Methods

The synthesis of the titled quinoline derivatives was achieved through cyclization of 8-hydroxyquinoline-5-sulfonyl chloride (1) with 2º-acetyl-2-cyanoacetohydrazide, 2-cyanoacetic acid hydrazide, and 3-amino-5-pyrazolone to afford 2, 3, and 4, respectively. Moreover, reaction of 1 with glycine gives 7, which on heterocyclization with ammonium thiocyanate yielded the 2-thioxoimidazolidin-2-one derivative 8. Cyclocondensation reaction of 3, 4, 8, and 9 with different arylidene malononitriles afforded fused systems, 5a-e, 6a-e, 10a-e, and 11a-e, respectively. The synthesized compounds were evaluated for their in-vitro antimicrobial activity using the disc diffusion method. In addition, they were evaluated for their in-vitro antiviral activity against avian paramyxovirus type 1 (APMV-1) and laryngotracheitis virus (LTV).

Results and conclusion

In-vitro antimicrobial activity of the newly synthesized compounds included an inhibitory effect toward the growth of Escherichia coli and Pseudomonas aeruginosa (Gram-negative bacteria). Furthermore, of the six selected compounds (2, 3, 4, 7, 8 and 9) tested for their antiviral activity, compounds 2, 3, and 4 at a concentration range of 3–4 µg/ml showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID50) and LTV of 500 TCID50 in Vero cell cultures on the basis of their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro, with inhibitory concentration fifty (IC50) ranging from 3 to 4 µg/egg against avian APMV-1 and LTV and toxic concentration fifty (CC50) ranging from 200 to 300 µg/egg.

  1,265 281 -
Synthesis of triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindolin-2-one derivatives ( part I)
Fatma A. Bassyouni, Amira S. Abdel All, Wafaa M. Haggag, Madiha Mahmoud, Mamoun M.A. Sarhan, Mohamed Abdel-Rehim
December 2012, 11(2):129-135
DOI:10.7123/01.EPJ.0000422115.68888.f2   
Objective

The aim of part I is the synthesis of different series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadiazin-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (4–13) through the reaction of 4-[1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylidineamino]benzohydrazide (3) with different reagents to be evaluated biologically.

Materials and methods

Derivatives of (1H-1,2,4-triazol-3-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one and (1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (4–6) were prepared by the reaction of 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) with benzyl, benzoyl isothiocyanate, or acetyl acetone to form 1H-1,2,4-triazole and 1H-pyrazole-5-nitroindolin-2-one derivatives. The reaction of 3 with ethyl bromoacetate, ethyl acetoacetate, or acetyl chloride afforded 1,3,4 oxadiazin-6-one, 3-methyl-5-oxo-4,5-dihydro-1H-pyrazole, or 1,3,4-oxadiazole-5-nitroindolin-2-one derivatives (7–9), respectively. Sugar hydrazone-5-nitroindolin-2-ones (10–13) were archived by the reaction of 3 with D-glucose, D-mannose, D-arabinose, and D-ribose using both conventional and green chemistry.

Results and conclusion

Conventional and microwave methods used for the synthesis of various triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindolin-2-one derivatives were applied for the synthesis of compounds 4–13. These methods were simple and gave good yields of the target compounds in short reaction times.

  1,222 268 -
Synthesis, antioxidant, and antimicrobial activities of new 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitriles, (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl)methanones, and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitriles ( QSAR and molecular docking analysis)
Fatma A. Bassyouni, Hanaa A. Tawfik, Ahmed R. Hamed, Maha M. Soltan, Mahmoud ElHefnawi, Ahmed A. ElRashedy, Maysa E. Moharam, Mohamed Abdel Rehim
December 2012, 11(2):80-92
DOI:10.7123/01.EPJ.0000422113.69898.e0   
Objectives

A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile (6a,b), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone (911), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (1416) derivatives were synthesized and evaluated for their antioxidant and antimicrobial activities; in addition, their quantitative structure–activity relationships and molecular docking were investigated.

Methods

The target compounds 6a,b were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide (2) with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases 3a,b, which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles 4a,b; N-methylation of 4a,b afforded 5a,b, which reacted with 4-aminoantipyrine to give 6a,b. In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide (8) or 8-cyano-6-isocyano-5-oxo-7-phenyl-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-2-carbohydrazide (13) reacted with different carboxylic acids such as crotonic acid, 3,4-diaminobenzoic acid, and 6-hydroxy-4-methoxybenzofuran-5-carboxylic acid to form compounds 911 and 1416, respectively. The synthesized compounds were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and the diffusion plate method for antimicrobial activity.

Results and conclusion

Among other tested compounds, compounds 15, 11, and 10 possessed the highest antioxidant activity, whereas compounds 4a, 5b, 6b, 10, and 11 displayed high activity against Staphylococcus aureus, Salmonella typhimurium, and Candida albicans. The quantitative structure–activity relationships of the studied compounds 4a, 4b, 5b, 6b, 10, 11, 14, 15, and 16 indicated a high correlation (r 2=0.82) between the predicted and actual activities as obtained from molecular descriptors and the inhibitory activity of this set of tested molecules measured as antioxidant activity. Moreover, the three-dimensional (3D) pharmacophore was generated, and docking of the most active antibacterial compound 4a against the dihydropteroate synthase enzyme gave comparable scores for hydrogen bond interaction (−13.5 kcal/mol) and binding mode to the reference antibiotic sulfamethoxazole (−13.00 kcal/mol).

  1,251 205 -
Characterization and purification of the crude Trematosphaeria mangrovei laccase enzyme
Atalla M. Mabrouk, Zeinab H. Kheiralla, Eman R. Hamed, Amani A. Youssry, Abeer A. Abd El Aty
December 2012, 11(2):93-98
DOI:10.7123/01.EPJ.0000419801.40087.2a   
Objectives

The aim of this work was to study the purification and characterization of the crude extracellular laccase produced by the marine-derived fungus Trematosphaeria mangrovei.

Methods

The general properties of the crude laccase enzyme produced by T. mangrovei were investigated. These include the effect of temperature, pH, thermal and pH stabilities, and enzyme and substrate concentrations on the laccase activity. Partial purification of the T. mangrovei laccase enzyme was carried out by fractional precipitation with ammonium sulphate, ethanol and acetone. Further purification was carried out on a Sephadex G-100 column.

Results and conclusion

The results obtained showed that the crude enzyme reached its maximal activity at 35πC, pH 4.5, at an enzyme concentration of 5.429 mg protein/reaction mixture and at a substrate concentration of 40 mmol/l 2,2-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid). The enzyme was stable for 60 min at 35πC and retained about 80–90% of its activity after treatment for 60 min from 40 to 50πC. The enzyme showed maximum stability (100%) at pH 4.5 and 91.6% at pH 4.0 after 60 min. Fractional precipitation of the fungal extracellular T. mangrovei laccase enzyme with different methods showed that the enzyme fraction precipitated at 60% acetone was the most favourable enzyme fraction; it showed 4.84 purification fold. Laccase obtained from the 50–60% acetone fraction was purified by Sephadex G-100. The final preparation thus obtained reached 31.47-fold that of the culture filtrate (1466.49 U/mg protein) and showed a single band on native polyacrylamide gel electrophoresis.

  1,049 152 -
In-vitro bioassays on the metabolites of the fungus Emericella nidulans isolated from the Egyptian Red Sea algae
Usama W. Hawas, Lamia T.A. El-Kassem, Eman F. Ahmed, Mahmoud Emam
December 2012, 11(2):124-128
DOI:10.7123/01.EPJ.0000421517.80892.ed   
Aim

There are a number of theories on which organisms provide the most interesting bioactive metabolites. In this study, we discuss the biochemical activities of the marine-derived endophyte Emericella nidulans, isolated from the Egyptian Red Sea algae.

Methods

The fungus E. nidulans was isolated as an endophyte from the Egyptian Red Sea brown alga Turbinaria elatensis. The fungus was identified by a morphological method and 18S rDNA sequence comparison. Chemical constituents were isolated using chromatographic techniques.

Results and conclusion

Cultivation of this fungus in Czapek’s peptone media led to the isolation of five known metabolites: sterigmatocystin (1), emericellin (2), cordycepin (3), ergosterol peroxide (4), and myristic acid (5) from the ethyl acetate extract of the culture broth. The structures were elucidated on the basis of NMR spectroscopic analysis and mass spectrometry. The ethyl acetate extract and the isolated compounds were tested for antimicrobial properties, activity against cancer cell lines, and inhibition of the hepatitis C virus protease.

  981 160 -
Regioselective addition of alkyl phosphites on 6-(aryliminomethyl)-furobenzopyran-5-one derivatives
Nabila M. Ibrahim, Asmaa A. Magd-El-Din, Amira S. Abd El-All, Eman F. Al-Amrousi, Hisham Abdallah A. Yosef
December 2012, 11(2):109-115
DOI:10.7123/01.EPJ.0000421666.94096.f5   
Aim

Trialkyl phosphites 2a,b attack 6-(aryliminomethyl)furobenzopyran-5-ones 1a–e regiospecifically at the carbon–carbon double bond of the γ-pyrone ring to yield new 1,2-addition phosphonate products for which structures 3a–e have been respectively assigned.

Methods

The alkyl phosphites 2a,b attacked the monoanils 1a–e at the azomethine carbon of the C=N bond to yield corresponding phosphonate adducts 5a–e when reactions were carried out in the presence of a controlled amount of acetic acid. Phosphonates 5a–e could also be obtained by the reaction of dialkyl phosphites 4a,b with anils 1a–e. Structures of the new phosphonates 3a–e were elucidated by elemental analyses as well as spectroscopic methods. The 1H and 13C nuclear magnetic resonance and infrared measurements were helpful tools in confirming the structures of the new products.

Results and conclusion

The insecticidal activities of phosphonates 3a–e and their respective regioisomers 5a–e against adult Aphis gossypii (Glover), which infest cotton crops, were determined. The structure–activity relationship has been discussed.

  980 134 -
Antimicrobial, anti-inflammatory, and antinociceptive activities of triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindoline-2-one derivatives and a study of their computational chemistry ( part II)
Fatma A. Bassyouni, Amira S. Abdel All, Wafaa M. Haggag, Madiha Mahmoud, Mamoun M.A. Sarhan, Mohamed Abdel-Rehim
December 2012, 11(2):136-143
DOI:10.7123/01.EPJ.0000422114.91245.38   
Objective

The aim of this study (part II) is to evaluate the antibacterial, anti-inflammatory, and antinociceptive activities of a series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadizine-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (1–13) and, in addition, to investigate their computational chemistry.

Methods

The synthesized compounds in (part I) 1–9 were evaluated for their antibacterial and antifungal activities using different strains of Gram-positive bacteria (Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa), yeast (Candida albicans), and four mold fungi (Fusarium solani, Aspergillus niger, Colletotrichum gloeosporioides, and Phomopsis obscurans). The anti-inflammatory and antinociceptive activities of compounds 1–13 were evaluated using a hot-plate test, acetic acid-induced writhing in mice, formalin-induced nociception, a tail immersion test, and carrageenan-induced hind paw edema. For computational chemistry, a semiempirical MNDO method (Modified Neglect of Differential Overlap is a semi-empirical method for the quantum calculation of molecular electronic structure in computational chemistry) associated with HyperChem professional 7.5 programs was adapted.

Results and conclusion

Compounds 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) and 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (9) showed the highest antibacterial and antifungal activities compared with clotrimazole and sulfamethoxazole as reference drugs. In contrast, compounds ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), 3-(4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl) phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (8), D-glucose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (10), and D-arabinose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (12) showed significantly high anti-inflammatory and antinociceptive activities when compared with indomethacin and morphine as reference drugs. From the computational chemistry compounds, ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), ethyl 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzoate (2), and 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) yielded the lowest values of total energy and heat of formation, and had higher stability than other molecules.

  899 171 -
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