Comparative in silico and in vitro Study of N-(1- Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent

Doxorubicin, also known as Adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemia, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, antiinflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl) benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2 μM.

Selection of Saccharomyces cerevisiae Strains Tolerant to Lead and Cadmium Toxicity

The aim of this study was to select the best strains of Saccharomyces cerevisiae able to resist lead and cadmium. Ten strains were screened on the basis of their resistance at different concentrations of 0, 2, 4, 8, 12, 16, 20 and 24 ppm for Pb and 0, 0.5, 1, 2, 4, 6, 8 and 10 ppm for Cd. The properties of baker's yeast quality were decreased by the increase of Pb or Cd in growth medium. The slope values of yield, total viable cells and gassing power of produced baker's yeast were investigated as an indicator of metal resistant. In addition, concentrations of Pb and Cd in produced baker's yeast were determined. The strain of S. cerevisiae FH-620 had the highest resistance against Pb and Cd and had the minimum levels of both two investigated metals in produced baker's yeast.

Hepatotoxicity Induced by Arsenic Trioxide in Adult Mice and Their Progeny

In this investigation, we have evaluated the effects of arsenic trioxide on hepatic function in pregnant and lactating Swiss albino mice and their suckling pups. Experiments were carried out on female mice given 175 ppm As2O3 in their drinking water from the 14th day of pregnancy until day 14 after delivery. Our results showed a significant decrease in plasma levels of total protein and albumin, cholesterol and triglyceride in As2O3 treated mice and their pups. The hyperbilirubinemia and the increased plasma total alkaline phosphatase activity suggested the presence of cholestasis. Transaminase activities as well as lactate deshydrogenase activity in plasma, known as biomarkers of hepatocellular injury, were elevated indicating hepatic cells’ damage after treatment with As2O3. Exposure to arsenic led to an increase of liver thiobarbituric acid reactive substances level along with a concomitant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase and in glutathione.

In vitro Cytotoxic and Genotoxic Effects of Arsenic Trioxide on Human Keratinocytes

Although, arsenic trioxide has been the subject of toxicological research, in vitro cytotoxicity and genotoxicity studies using relevant cell models and uniform methodology are not well elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by arsenic trioxide in human keratinocytes (HaCaT) using the MTT [3-(4, 5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet) assays, respectively. Human keratinocytes were treated with different doses of arsenic trioxide for 4 h prior to cytogenetic assessment. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HaCaT cells in a dose-dependent manner, showing an IC50 value of 34.18 ± 0.6 μM. Data generated from the comet assay also indicated a significant dose-dependent increase in DNA damage in HaCaT cells associated with arsenic trioxide exposure. We observed a significant increase in comet tail length and tail moment, showing an evidence of arsenic trioxide -induced genotoxic damage in HaCaT cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by arsenic.

Mathematical Modeling for Continuous Reactive Extrusion of Poly Lactic Acid formation by Ring Opening Polymerization Considering Metal/Organic Catalyst and Alternative Energies

PLA emerged as a promising polymer because of its property as a compostable, biodegradable thermoplastic made from renewable sources. PLA can be polymerized from monomers (Lactide or Lactic acid) obtained by fermentation processes from renewable sources such as corn starch or sugarcane. For PLA synthesis, ring opening polymerization (ROP) of Lactide monomer is one of the preferred methods. In the literature, the technique mainly developed for ROP of PLA is based on metal/bimetallic catalyst (Sn, Zn and Al) or other organic catalysts in suitable solvent. However, the PLA synthesized using such catalysts may contain trace elements of the catalyst which may cause toxicity. This work estimated the usefulness and drawbacks of using different catalysts as well as effect of alternative energies and future aspects for PLA production.

Characterization and Detection of Cadmium Ion Using Modification Calixarene with Multiwalled Carbon Nanotubes

Water contamination by toxic compound is one of the serious environmental problems today. These toxic compounds mostly originated from industrial effluents, agriculture, natural sources and human waste. These studies focus on modification of multiwalled carbon nanotube (MWCNTs) with nanoparticle of calixarene and explore the possibility of using this modification for the remediation of cadmium in water. The nanocomposites were prepared by dissolving calixarene in chloroform solution as solvent, followed by additional multiwalled carbon nanotube (MWCNTs) then sonication process for 3 hour and fabricated the nanocomposites on substrate by spin coating method. Finally, the nanocomposites were tested on cadmium ion (10 mg/ml). The morphology of nanocomposites was investigated by FESEM showing the formation of calixarene on the outer walls of carbon nanotube and cadmium ion also clearly seen from the micrograph. This formation was supported by using energy dispersive x-ray (EDX). The presence of cadmium ions in the films, leads to some changes in the surface potential and Fourier Transform Infrared spectroscopy (FTIR).The nanocomposites MWCNTs-calixarene have potential for development of sensor for pollutant monitoring and nanoelectronics devices applications.

Assessing Chemo-Radiotherapy Induced Toxicity and Quality of Life of Cancer Patients

Chemotherapy and radiotherapy are one of the major treatment modalities that play important role in the management of a number of different cancers. This study for the first time evaluates the toxicity of these treatment modalities and its impact on quality of life of cancer patients in Pakistan. The study also for the first time determines what cancer patients of different ages and cancer stages believe would be an effective intervention to manage their psychosocial needs and treatment induced toxicity. The article also provides evidence based approach for the use of variety of interventions to mange cancer treatment induced morbidity and toxicity. In light of the present study and reviewed research data, evidence based recommendations are also made for selection of appropriate interventions to manage Pain, Nausea and Vomiting, Anxiety and Depression, Fatigue and Overall QOL of cancer survivors.

Formulation and ex vivo Evaluation of Solid Lipid Nanoparticles (SLNS) Based Hydrogel for Intranasal Drug Delivery

Risperidone (RISP) is an antipsychotic agent and has low water solubility and nontargeted delivery results in numerous side effects. Hence, an attempt was made to develop SLNs hydrogel for intranasal delivery of RISP to achieve maximum bioavailability and reduction of side effects. RISP loaded SLNs composed of 1.65% (w/v) lipid mass were produced by high shear homogenization (HSH) coupled ultrasound (US) method using glycerylmonostearate (GMS) or Imwitor 900K (solid lipid). The particles were loaded with 0.2% (w/v) of the RISP & surface-tailored with a 2.02% (w/v) non-ionic surfactant Tween® 80. Optimization was done using 32 factorial design using Design Expert® software. The prepared SLNs dispersion incorporated into Polycarbophil AA1 hydrogel (0.5% w/v). The final gel formulation was evaluated for entrapment efficiency, particle size, rheological properties, X ray diffraction, in vitro diffusion, ex vivo permeation using sheep nasal mucosa and histopathological studies for nasocilliary toxicity. The entrapment efficiency of optimized SLNs was found to be 76 ± 2%, polydispersity index

Anthocyanin Complex: Characterization and Cytotoxicity Studies

Complexation of anthocyanins to mimic natural copigmentation process was investigated. Cyanidin-rich extracts from Zea mays L. ceritina Kulesh. and delphinidin-rich extracts from Clitoria ternatea L. were used to form 4 anthocyanin complexes, AC1, AC2, AC3 and AC4, in the presence of several polyphenols and a trace metal. Characterizations of the ACs were conducted by UV, FTIR, DSC/TGA and morphological observations. Bathochromic shifts of the UV spectra of 4 formulas of ACs were observed at peak wavelengths of about 510-620 nm by 10 nm suggesting complex formation. FTIR spectra of the ACs indicate shifts of peaks from 1,733 cm-1 to 1,696 cm-1 indicating interactions and a decrease in the peak areas within the wavenumber of 3,400-3,500 cm-1 indicating changes in hydrogen bonding. Thermal analysis of all of the ACs suggests increases in melting temperature after complexation. AC with the highest melting temperature was morphologically observed by SEM and TEM to be crystal-like particles within a range of 50 to 200 nm. Particle size analysis of the AC by laser diffraction gave a range of 50-600 nm, indicating aggregation. This AC was shown to have no cytotoxic effect on cultured HGEPp0.5 and HGF (all p> 0.05) by MTT. Therefore, complexation of anthocyanins was simple and self-assembly process, potentially resulting in nanosized particles of anthocyanin complex.

Anti-Inflammatory Activity of Topical Anthocyanins by Complexation and Niosomal Encapsulation

Anthocyanins are natural pigments with effective UV protection but their topical use could be limited due to their physicochemical characteristics. An attempt to overcome such limitations by complexation of 2 major anthocyanin-rich sources, C. ternatea and Z. mays, has potentiated its use as topical antiinflammatory. Cell studies indicate no cytotoxicity of the anthocyanin complex (AC) up to 1 mg/ml tested in HaCaT and human fore head fibroblasts by MTT. Croton oil-induced ear edema in Wistar rats suggests an effective dose of 5 mg/cm2 of AC as a topical anti-inflammatory in comparison to 0.5 mg/cm2 of fluocinolone acetonide. Niosomal encapsulation of the AC significantly prolonged the anti-inflammatory activity particularly at 8 h after topical application (p = 0.0001). The AC was not cytotoxic and its anti-inflammatory and activity was dose-dependent and prolonged by niosomal encapsulation. It has also shown to promote collagen type 1 production in cell culture. Thus, AC could be a potential candidate for topical anti-inflammatory agent from natural resources.

Stabilization of γ-Sterilized Food-Packaging Materials by Synergistic Mixtures of Food-Contact Approval Stabilizers

Food is widely packaged with plastic materials to prevent microbial contamination and spoilage. Ionizing radiation is widely used to sterilize the food-packaging materials. Sterilization by γ-radiation causes degradation such as embrittlement, stiffening, softening, discoloration, odour generation, and decrease in molecular weight. Many antioxidants can prevent γ-degradation but most of them are toxic. The migration of antioxidants to its environment gives rise to major concerns in case of food packaging plastics. In this attempt, we have aimed to utilize synergistic mixtures of stabilizers which are approved for food-contact applications. Ethylene-propylene-diene terpolymer has been melt-mixed with hindered amine stabilizers (HAS), phenolic antioxidants and organophosphites (hydroperoxide decomposer). Results were discussed by comparing the stabilizing efficiency of mixtures with and without phenol system. Among phenol containing systems where we mostly observed discoloration due to the oxidation of hindered phenol, the combination of secondary HAS, tertiary HAS, organo-phosphite and hindered phenol exhibited improved stabilization efficiency than single or binary additive systems. The mixture of secondary HAS and tertiary HAS, has shown antagonistic effect of stabilization. However, the combination of organo-phosphite with secondary HAS, tertiary HAS and phenol antioxidants have been found to give synergistic even at higher doses of Gamma-irradiation. The effects have been explained through the interaction between the stabilizers. After γ-irradiation, the consumption of oligomeric stabilizer significantly depends on the components of stabilization mixture. The effect of the organo-phosphite antioxidant on the overall stability has been discussed.

Protective Effect of Saponin Extract from the Root of Garcinia kola (Bitter kola) against Paracetamol- Induced Hepatotoxicity in Albino Rats

Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity and high mortality, its medical management is currently inadequate. This study was designed to evaluate the hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced wistar albino rats. Twenty five (25) male adult wistar albino rats were divided into five (5) groups. Group I was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV and V were pre-treated with 100, 200 and 400mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty four (24) h after administration, the rats were sacrificed and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and conjugated bilirubin, glucose and protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained in Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Nanoparticles-Protein Hybrid Based Magnetic Liposome

Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III) / Iron (II) chloride with the leaf extract of Datura inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

The Impact of the Number of Neurons in the Hidden Layer on the Performance of MLP Neural Network: Application to the Fast Identification of Toxic Gases

In this work, neural networks methods MLP type were applied to a database from an array of six sensors for the detection of three toxic gases. The choice of the number of hidden layers and the weight values are influential on the convergence of the learning algorithm. We proposed, in this article, a mathematical formula to determine the optimal number of hidden layers and good weight values based on the method of back propagation of errors. The results of this modeling have improved discrimination of these gases and optimized the computation time. The model presented here has proven to be an effective application for the fast identification of toxic gases.

Oncological Management of Medulloblastoma and New Viral Therapeutic Targets

Medulloblastoma (MB) is one of the most prevalent brain tumours among paediatrics. Although its management has evolved over time still there is need to find new therapeutic targets for MB that can result in less normal tissue toxicity while improving survival and reducing recurrence. This literature review is aimed at finding new potential therapeutic targets for MB focusing on viruses that can be used as potential targets for MB. The review also gives an over-view of management of paediatric Medulloblastoma focusing on Radiotherapy management.

Semiconductor Supported Gold Nanoparticles for Photodegradation of Rhodamine B

Rhodamine B (RB) is a toxic dye used extensively in textile industry, which must be remediated before its drainage to environment. In the present study, supported gold nanoparticles on commercially available titania and zincite were successfully prepared and then their activity on the photodegradation of RB under UV A light irradiation were evaluated. The synthesized photocatalysts were characterized by ICP, BET, XRD, and TEM. Kinetic results showed that Au/TiO2 was an inferior photocatalyst to Au/ZnO. This observation could be attributed to the strong reflection of UV irradiation by gold nanoparticles over TiO2 support.

Use of Hair as an Indicator of Environmental Lead Pollution: Characteristics and Seasonal Variation of Lead Pollution in Egypt

Lead being a toxic heavy metal that mankind is exposed to the highest levels of this metal from environmental pollutants. A total of 180 Male scalp hair samples were collected from different environments in Greater Cairo (GC), i.e. industrial, heavy traffic and rural areas (60 samples from each) having different activities during the period of, 1/5/2010 to 1/11/2012. Hair samples were collected during five stages. Data proved that the concentration of lead in male industrial areas of Cairo ranged between 6.2847 to 19.0432 μg/g, with mean value of 12.3288 μg/g. On the other hand, lead content of hair samples of residential-traffic areas ranged between 2.8634 to 16.3311 μg/g with mean value of 9.7552 μg/g. While lead concentration on the hair of the male residents living in rural area ranged between 1.0499-9.0402μg/g with mean value of 4.7327 μg/g. The Pb concentration in scalp hair of Cairo residents of residential-traffic and rural traffic areas was observed to follow the same pattern. The pattern was that of decrease concentration of summer and its increase in winter. Then, there was a marked increase in Pb concentration of summer 2012, and this increase was significant. These were obviously seen for the residential-traffic and rural areas residents. Pb pollution in residents of industrial areas showed the same seasonal pattern, but there was marked to decrease in Pb concentration of summer 2012, and this decrease was significant. Lead pollution in residents of GC was serious. It is worth noting that the atmosphere is still contaminated by lead despite a decade of using unleaded gasoline. Strong seasonal variation in higher Pb concentration on winter than in summer was found. Major contributions to the pollution with Pb could include industry emissions, motor vehicle emissions and long transported dust from outside Cairo. More attention should be paid to the reduction of Pb content of the urban aerosol and to the Pb pollution health.

Treatment of Simulated Textile Wastewater Containing Reactive Azo Dyes Using Laboratory Scale Trickling Filter

The present study was conducted to evaluate the potential applicability of biological trickling filter system for the treatment of simulated textile wastewater containing reactive azo dyes with bacterial consortium under non-sterile conditions. The percentage decolorization for the treatment of wastewater containing structurally different dyes was found to be higher than 95% in all trials. The stable bacterial count of the biofilm on stone media of the trickling filter during the treatment confirmed the presence, proliferation, dominance and involvement of the added microbial consortium in the treatment of textile wastewater. Results of physicochemical parameters revealed the reduction in chemical oxygen demand (58.5-75.1%), sulphates (18.9-36.5%), and phosphates (63.6-73.0%). UV-Visible and FTIR spectroscopy confirmed decolorization of dye containing wastewater was ultimate consequence of biodegradation. Toxicological studies revealed the nontoxic nature of degradative metabolites.

Efficiency of Wood Vinegar Mixed with Some Plants Extract against the Housefly (Musca domestica L.)

The efficiency of wood vinegar mixed with each individual of three plants extract such as: citronella grass (Cymbopogon nardus), neem seed (Azadirachta indica A. Juss), and yam bean seed (Pachyrhizus erosus Urb.) were tested against the second instar larvae of housefly (Musca domestica L.). Steam distillation was used for extraction of the citronella grass while neem and yam bean were simple extracted by fermentation with ethyl alcohol. Toxicity test was evaluated in laboratory based on two methods of larvicidal bioassay: topical application method (contact poison) and feeding method (stomach poison). Larval mortality was observed daily and larval survivability was recorded until the survived larvae developed to pupae and adults. The study resulted that treatment of wood vinegar mixed with citronella grass showed the highest larval mortality by topical application method (50.0%) and by feeding method (80.0%). However, treatment of mixed wood vinegar and neem seed showed the longest pupal duration to 25 day and 32 days for topical application method and feeding method respectively. Additional, larval duration on treated M. domestica larvae was extended to 13 days for topical application method and 11 days for feeding method. Thus, the feeding method gave higher efficiency compared with the topical application method.

Determination of Acute Toxicity of Atrazine Herbicide in Caspian Kutum, Rutilus frisii kutum, Larvae

Pesticides and drugs used in agriculture and veterinary medicine may end up in aquatic environments and bioaccumulate in the food chain, thus causing serious problems for fauna and human health. For determination of the toxic effects of atrazine herbicide on Caspian kutum, Rutilus frisii kutum larvae, the 96-h LC50 of atrazine was measured for newly hatched larvae as 18.53 ppm. Toxicity of atrazine herbicide on Caspian kutum larvae was investigated using concentrations: 9.25ppm, 4.62 ppm and 2.31 ppm for 7 days. Comparison of the length, weight and condition factor showed that no significant differences between atrazine exposed and control groups. The concentration of Na+, K+, Ca2+, Mg2+ and Cl- in whole body of larvae in control and atrazine exposure groups were measured and the results showed that concentrations of all these ions is higher in atrazine exposure group than control group. It is obvious from this study that atrazine negatively affects osmoregulation process and changes ion compositions of the body even at sublethal concentration and acute exposure but have no effects on growth parameters of the body.