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OBJECTIVE: Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. MATERIALS AND METHODS: 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. RESULTS: The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). CONCLUSIONS: TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Quimioterapia de Inducción , Neoplasias de la Boca , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Quimioterapia de Inducción/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Seguimiento , Adulto , Resultado del Tratamiento , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Anciano , Estadificación de Neoplasias , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Fluorouracilo/efectos adversosRESUMEN
Current drugs are inefficient for the treatment of visceral leishmaniasis an immunosuppressive ailment caused by Leishmania donovani. Regrettably, there is no plant-origin antileishmanial drug present. P2X7R is constitutively present on macrophage surfaces and can be a putative therapeutic target in intra-macrophage pathogens with function attributes towards inflammation, host cell apoptosis, altered redox, and phagolysosomal maturation by activating p38MAPK. Here we demonstrated that the initial interaction of Spergulin-A (Sp A), a triterpenoid saponin with RAW 264.7 macrophages was mediated through P2X7R involving the signaling cascade intermediates Ca++, p38MAPK, and NF-κß. Phospho (P)-p38MAPK involvement is shown to have specific and firm importance in leishmanial killing with increased NF-κßp65. Phago-lysosomal maturation by Sp A also campaigns for another contribution of P2X7R. In vivo evaluation of the anti-leishmanial activity of Sp A was monitored through expression analyses of P2X7R, P-p38MAPK, and NF-κßp65 in murine spleen and bone-marrow macrophages and supported Sp A being a natural compound of leishmanicidal functions which acted through the P2X7R-p38MAPK axis.
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Proteínas Portadoras/metabolismo , Leishmania donovani , Leishmaniasis Visceral , Animales , Leishmania donovani/metabolismo , Leishmaniasis Visceral/tratamiento farmacológico , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Receptores Purinérgicos P2X7/metabolismo , Transducción de Señal , Bazo/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Mineral lubricating oils are widely used in various industrial sectors for their applications in maintenance and functioning of machineries. However, indiscriminate dumping of these used oils have resulted in polluting the natural reservoirs which subsequently destroys ecological balance. Bacteria can emulsify or lower surface tension between phases of immiscible substrates and can acquire them as their carbon and energy sources. Such a phenomenon is mediated by production of extracellular polymers which can function as eminent surface active compounds based on their surfactant or emulsifying nature. The comparison between bacterial strains (Gram-positive Bacillus stratosphericus A15 and Gram-negative Ochrobactrum pseudintermedium C1) on utilization of pure straight chain hydrocarbons, waste mineral lubricating oils as sole carbon source and chemical characterization of the synthesized surface active compounds were studied. Characterization analysis by Ultraviolet Visible spectrophotometry, Fourier transform infrared spectroscopy, Nuclear Magnetic Resonance spectroscopy, Carbon-Hydrogen-Nitrogen analysis has given detailed structural elucidation of surface active compounds. The contrasting nature of bacterial strains in utilization of different hydrocarbons of waste mineral lubricating oils was observed in Gas Chromatography-Mass Spectroscopy analysis. The variation between both strains in utilization of hydrocarbons can be manifested in chemical structural differences and properties of the produced surface active compounds. Scanning Electron Microscopy has given detailed insight into the microstructural difference of the compounds. The utilization of lubricating oils can address waste disposal problem and offer an economical feasible approach for bacterial production of surface active compounds. Our results suggest that these surface active compounds can maneuver applications in environmental bioremediation and agriculture, pharmaceuticals and food as functional biomaterials.
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Bacillus , Ochrobactrum , Biodegradación Ambiental , Carbono , Hidrocarburos , Minerales , Aceites de Plantas , TensoactivosRESUMEN
Globally, the underlying peril of cumulative toxicity of heavy metals in water bodies contaminated by industrial effluents is a matter of great concern to the environmentalists. Heavy metals like lead, cadmium, and nickel are particularly liable for this. Such toxic water is not only hazardous to human health but also harmful to aquatic animals. Remedial measures are being taken by physico-chemical techniques, but most of them are neither eco-friendly nor cost-effective. Biological means like bioaccumulation of heavy metals by viable bacteria are often tedious. In the present study, biosorption of heavy metals is successfully expedited by surfactant exopolysaccharide (SEPS) of Ochrobactrum pseudintermedium C1 as a simple, safe, and economically sustainable option utilizing an easily available and cost-effective substrate like molasses extract. Its efficacy in bioremediation of toxic heavy metals like cadmium, nickel, and lead have been studied by UV-Vis spectrophotometry and verified by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). FTIR and zeta potential studies have also been carried out to explore this novel biosorption potential. Results are conclusive and promising. Moreover, this particular SEPS alone can remediate all these three toxic heavy metals in water. For futuristic applications, it might be a prospective and cost-effective resource for bioremediation of toxic heavy metals in aqueous environment.
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Metales Pesados/metabolismo , Ochrobactrum/metabolismo , Polisacáridos Bacterianos/metabolismo , Tensoactivos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Biodegradación Ambiental , Cadmio/metabolismo , Análisis Costo-Beneficio , Plomo/metabolismo , Microscopía Electrónica de Rastreo , Níquel/metabolismo , Polisacáridos Bacterianos/ultraestructuraRESUMEN
Porous carbon nanospheres were synthesized from agro-waste garlic peels by a one-pot facile and easy to scale-up pyrolysis method. Surface morphology and structural features of the nanospheres have been studied by field emission scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, and Raman spectroscopy. Fourier transform infrared spectroscopy (FTIR) and N2 adsorption desorption experiments were explored to detect surface functionality, surface area, and porosity. Average particle diameter of the synthesized nanospheres was 31 ± 6.3 nm and zeta potential of - 25.2 mV ± 1.75 mV. Nanoscale carbon was mesoporous in nature with type IV isotherms, mean pore diameter of 15.2 nm, and total pore volume of 0.032 cm3/g. Minimum inhibitory concentration and minimum bactericidal concentration values of carbon nanospheres against Escherichia coli are 480 ± 0.5 µg/ml and 495 ± 0.5 µg/ml, respectively. Synthesized nanospheres exhibited gram-selective antimicrobial action against Escherichia coli probably linked to membrane deformity due to interaction of nanocarbon with the bacterial membrane. Carbon nanospheres resulting from waste to wealth transformation emerged as promising candidates for antibacterial application. Graphical abstract.
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Antiinfecciosos , Nanosferas , Antibacterianos/farmacología , Carbono , Bacterias Gramnegativas , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
The incessant need to increase crop yields has led to the development of many chemical fertilizers containing NPK (nitrogen-phosphorous-potassium) which can degrade soil health in the long term. In addition, these fertilizers are often leached into nearby water bodies causing algal bloom and eutrophication. Bacterial secondary metabolites exuded into the extracellular space, termed extracellular polymeric substances (EPS) have gained commercial significance because of their biodegradability, non-toxicity, and renewability. In many habitats, bacterial communities faced with adversity will adhere together by production of EPS which also serves to bond them to surfaces. Typically, hygroscopic, EPS retain moisture in desiccating conditions and modulate nutrient exchange. Many plant growth-promoting bacteria (PGPR) combat harsh environmental conditions like salinity, drought, and attack of pathogens by producing EPS. The adhesive nature of EPS promotes soil aggregation and restores moisture thus combating soil erosion and promoting soil fertility. In addition, these molecules play vital roles in maintaining symbiosis and nitrogen fixation thus enhancing sustainability. Thus, along with other commercial applications, EPS show promising avenues for improving agricultural productivity thus helping to address land scarcity as well as minimizing environmental pollution.
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Matriz Extracelular de Sustancias Poliméricas , Desarrollo Sostenible , Agricultura , Bacterias , Fertilizantes , SueloRESUMEN
We report here the preparation of an aminoxy amide-based pseudopeptide-derived building block using furanoid sugar molecules. Through the cyclo-oligomerization reaction, we generate a hybrid triazole/aminoxy amide macrocycle using the as-prepared building block. The novel conformation of the macrocycle has been characterized using NMR and molecular modeling studies, which show a strong resemblance of our synthesized compound to d-,l-α-aminoxy acid-based cyclic peptides that contain uniform backbone chirality. We observe that the macrocycle can efficiently and selectively bind Cl- ion and transport Cl- ion across a lipid bilayer. 1H NMR anion binding studies suggest a coherent relationship between the acidity of aminoxy amide N-H and triazole C-H proton binding strength. Using time-based fluorescence assay, we show that the macrocycle acts as a mobile transporter and follows an antiport mechanism. Our synthesized macrocycle imposes cancer cell death by disrupting ionic homeostasis through Cl- ion transport. The macrocycle induced cytochrome c leakage and changes in mitochondrial membrane potential along with activation of family of caspases, suggesting that the cellular apoptosis occurs through a caspase-dependent intrinsic pathway. The present results suggest the possibility of using the macrocycle as a biological tool of high therapeutic value.
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Since the advent of biologics in human welfare various bio-molecules have been explored. Different bacterial exopolysaccharides have proved their worth in many industrial and commercial applications. In this perspective, while exploring a surfactant exopolysaccharide of Ochrobactrum pseudintermedium C1, it is strikingly observed that it possesses a potent antibacterial property which encourages its bio-medical applications. Following isolation and purification of the said exopolysaccharide, its structural configuration and functional attributes are studied by several analytical procedures involving FTIR, 13C- NMR, CHN-analysis, estimation of zeta potential, XRD-study and digital tensiometry. When treated with pathological samples in vitro, it distinctly elicits its antibacterial property by exhibiting a characteristic zone of inhibition. Combined with a standard antibiotic (like ciprofloxacin), it enhances the action of antibiotic also. Mechanism of its antibacterial action is evaluated by crystal violet entrapment assay with UV-vis spectrophotometry, bacterial cell viability assay by trypan blue staining and SEM study. Results show that its basic surfactant property, anionic character, crystalline nature and scaffolding architecture are supposed to facilitate its antibacterial property which is manifested by its capability of disrupting bacterial cell envelope causing eventual cell death. In the current global scenario, an increasing threat of antibiotic resistance is prevailing due to their indiscriminate use. If used as an adjuvant with a judicious dose of antibiotic, this bio-molecule might play a significant role in bio-medicine to combat such threat.
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Antibacterianos/biosíntesis , Antibacterianos/farmacología , Ochrobactrum , Polisacáridos Bacterianos/biosíntesis , Tensoactivos/metabolismo , Antibacterianos/metabolismo , Quimioterapia Adyuvante , Ciprofloxacina/farmacología , Escherichia coli/efectos de los fármacos , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Ochrobactrum/metabolismo , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/metabolismo , Staphylococcus aureus/efectos de los fármacosRESUMEN
The aim of this work was to develop a transdermal delivery system consisting of a glucosamine sulfate-laden xanthan hydrogel containing a nanoemulsion-loaded diacerein. The system was intended to prevent cartilage degradation typical of osteoarthritis. The nanoemulsion, made of soybean oil as the oil phase; soybean lecithin, Tween 80, and poloxamer 407 as surfactants; and propylene glycol as cosurfactant, was formed within the hydrogel. The hydrodynamic diameter of the nanoemulsion globules was 81.95 ± 0.256 nm with 0.285 ± 0.036 of PDI value and the zeta potential value of the formulation was 39.33 ± 0.812 mV. CryoSEM and TEM studies revealed the uniform morphology of the vehicle. A rheological study exposed the nanoemulsion-loaded hydrogel as a thixotropic system. Satisfactory storage stability under ICH conditions was established by the zeta potential and rheological studies. Furthermore, skin biocompatibility of the hydrogel was ascertained on the basis of skin irritation study. Additionally, the diffusion of the drugs across rat skin followed a controlled non-Fickian anomalous steady mechanism. Following in vivo administration in experimental osteoarthritis, the transdermal hydrogel showed a reduction in tumor necrosis factor-alpha, C-reactive protein, high mobility group box protein, and monocyte chemoattractant protein-1. Finally, histopathological analysis of the animals showed satisfactory chondroprotection in the in vivo study. In conclusion, the developed transdermal systems showed a potential against the progression of experimental osteoarthritis.
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Antraquinonas/administración & dosificación , Glucosamina/administración & dosificación , Osteoartritis , Absorción Cutánea , Administración Cutánea , Animales , Emulsiones , Osteoartritis/tratamiento farmacológico , Ratas , Piel/metabolismoRESUMEN
The development of drug carriers based on nanomaterials that can selectively carry chemotherapeutic agents to cancer cells has become a major focus in biomedical research. A novel pH-sensitive multifunctional envelope-type mesoporous silica nanoparticle (SBA-15) was fabricated for targeted drug delivery to human colorectal carcinoma cells (HCT-116). SBA-15 was functionalized with folic acid (FA), and the material was loaded with the water-insoluble flavonoid, quercetin (QN). Additionally, acid-labile magnetite Fe3O4 nanoparticles were embedded over the FA-functionalized QN-loaded monodisperse SBA-15 to prepare the highly orchestrated material FA-FE-SBA15QN. The in vitro and in vivo anti-carcinogenic efficacy of FA-FE-SBA15QN was carried out to explore the pH-sensitive QN release with putative mechanistic aspects. FA-FE-SBA15QN caused a marked tumor suppression, and triggered mitochondrial-dependent apoptosis through a redox-regulated cellular signaling system. Furthermore, FA-IO-SBA-15-QN initiated the c-Jun N-terminal Kinase (JNK)-guided H2AX phosphorylation, which relayed the downstream apoptotic signal to the phosphorylate tumor suppressor protein, p53. On the other hand, the selective inhibition of heat shock protein-27 (HSP-27) by FA-FE-SBA15QN augmented the apoptotic fate through JNK/H2AX/p53 axis. The in vitro and in vivo magnetic resonance imaging (MRI) studies have indicated the theranostic perspective of the composite. Thus, the result suggested that the newly synthesized FA-FE-SBA15QN could be used as a promising chemo theranostic material for the management of carcinoma.
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BACKGROUND: Many of present chemotherapeutics are inadequate and also resistant against visceral leishmaniasis (VL), an immunosuppressive ailment caused by Leishmania donovani. Despite the interest in plant-based drug development, no antileishmanial drugs from plant source are currently available. Glinus oppositifolius had been reported in favor of being immune modulators along with other traditional uses. Novel anti-VL therapies can rely on host immune-modulation with associated leishmanicidal action. OBJECTIVE: Discovery of novel plant-based antileishmanial compound from G. oppositifolius having permissible side effects. METHODS: With this rationale, an n-BuOH fraction of the methanolic extract of the plant and obtained triterpenoid saponin Spergulin-A were evaluated against acellular and intracellular L. donovani. Immunostimulatory activity of them was confirmed by elevated TNF-α and extracellular NO production from treated MФs and was found nontoxic to the host cells. Identification and structure confirmation for isolated Spergulin-A was performed by ESI-MS,13C, and 1H NMR. RESULTS: Spergulin-A was found ineffective against the acellular forms while, against the intracellular parasites at 30 µg/mL, the reduction was 92.6% after 72 hrs. Spergulin-A enhanced ROS and nitric oxide (NO) release and changes in Gp91-phox, i-NOS, and pro and anti-inflammatory cytokines elaborated its intracellular anti-leishmanial activity. CONCLUSION: The results supported that G. oppositifolius and Spergulin-A can potentiate new lead molecules for the development of alternative drugs against VL.
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During production and characterization of exopolysaccharides (EPS) of Ochrobactrum pseudintermedium C1, it was observed that an experimental change in the basic hydrocarbon type of substrate for bacterial utilization led to elicitation of different surface-active properties in the EPS produced. In the sugar substrate, it elicited surfactant property, while in oil substrates it elicited emulsifying property, which indicated that the EPS might be different. Consequently, attention was focused on a detailed analysis of this substrate-specific EPS. Utilizing waste sugar, edible, and mineral oil substrates, EPS produced in each situation was characterized. Besides estimating surface activity and thermostability, each substrate-specific EPS was analyzed by Fourier-transform infrared spectroscopy, gas chromatography-mass spectroscopy, 1 H-nuclear magnetic resonance, and matrix-assisted laser desorption/ionization-time of flight mass spectroscopy to find any structural difference. The results were significantly contrasting although the similarity in molecular mass suggested a basic similarity in polysaccharide structure. Morphological differences were also evident both macroscopically and microscopically with scanning electron microscopy. As the surface-active property of EPS was dependent on the substrate utilized, their structural differences might account for it. These diverse surface activities of EPS produced by a single bacterial strain simply by changing the nature of substrate would also augment their bioapplications. Moreover, utilization of waste and easily available substrates should make such applications convenient, ecofriendly, and cost-worthy.
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Hidrocarburos/metabolismo , Ochrobactrum/química , Polisacáridos Bacterianos/química , Medios de Cultivo/metabolismo , Microscopía Electrónica de Rastreo , Peso Molecular , Ochrobactrum/crecimiento & desarrollo , Ochrobactrum/metabolismo , Polisacáridos Bacterianos/biosíntesis , Polisacáridos Bacterianos/ultraestructura , Solubilidad , Propiedades de Superficie , TemperaturaRESUMEN
Bacterial extracellular polymeric substances, which are basically bacterial metabolites, have currently become a subject of great concern of modern day microbiologists and biotechnologists. Among these metabolites, bacterial exopolysaccharides or EPS, in particular, have gained a significant importance. EPS are formed by the bacteria in their late exponential or stationary phase of growth under special situations for specific purposes. They take part in the formation of bacterial biofilms. There is a great diversity in the types of EPS. Strikingly enough, a same species of bacterium can produce different types of EPS under different situations. The importance of EPS is largely because of their different applications in various industries. Now that the bacterial EPS has got the potentiality to become an upcoming tool in various futuristic applications of human benefit, the focus currently develops towards how better they can be produced in the laboratory by promoting the favorable factors for their production. While studying with different EPS forming bacteria, both the intrinsic factors like genetic configuration of the bacteria and the extrinsic factors like culture conditions under the influence of different physico-chemical parameters in order to maximize the EPS production have been taken into consideration. Both the factors have proved their worth. Hence, towards a better outcome for EPS production, it is indicated that a genetic manipulation of the bacteria should be synchronized with a proper selection of its culture condition by controlling different physico-chemical parameters.
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Bacterias/metabolismo , Microbiología Industrial/métodos , Ingeniería Metabólica/métodos , Polisacáridos Bacterianos/metabolismo , Bacterias/genética , Bacterias/crecimiento & desarrollo , Reactores Biológicos/microbiología , Fenómenos Químicos , Medios de Cultivo/química , Polisacáridos Bacterianos/genética , TemperaturaRESUMEN
Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future.
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Escherichia coli/efectos de los fármacos , Glucolípidos/farmacología , Lipopéptidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Tensoactivos/farmacología , Antibacterianos/farmacología , Bacillus/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Sinergismo Farmacológico , Escherichia coli/crecimiento & desarrollo , Escherichia coli/ultraestructura , Cinética , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Microscopía Electrónica de Rastreo , Pseudomonas aeruginosa/química , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/ultraestructuraRESUMEN
ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.
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Estudio Comparativo , Métodos de Análisis de Laboratorio y de Campo , Diclofenaco/análisis , Análisis Espectral/métodos , Cromatografía Líquida de Alta Presión/instrumentación , Estudio de Validación , Formas de Dosificación/normasRESUMEN
Osteoarthritis is a chronic degenerative joint disease causing pain and disability. Glucosamine sulphate is a well known oral supplement for its treatment. The present pioneering study provides an overview of the accentuated transdermal delivery of glucosamine sulphate through the optimized gel formulation with guar gum and sodium carboxymethyl cellulose (Na-CMC). Response surface methodology based on the three-level three-factor central composite design provided the optimum concentration of guar gum, Na-CMC and glycerol for a maximum flux. The transdermal characterization, ex vivo permeation study and in vivo study were performed with optimized gel formulation. The factorial design predicted the optimum values of guar gum, Na-CMC and glycerol which were 418.53 mg, 444.97 mg and 2322.4 mg respectively for 25 g of the gel. This optimized gel demonstrated the maximum flux, i.e., 1047.46 µg cm-2 h-1. The optimized gel showed satisfactory results with respect to drug uniformity, pH, stability, rheological properties, zeta potential, drug-excipient compatibility and skin irritation. The release of the drug from the optimized transdermal gel followed the controlled first order Fickian (non-steady) release pattern. The in vivo study was carried out in a rat model of osteoarthritis induced by monosodium iodoacetate damaging the tibial plateau. In this study the optimized formulation effectively reduced the symptoms like reduction in swelling of the knee joint, gross changes in digitized radio images and morphological and histopathological alterations. Additionally the changes in the release pattern of the proinflammatory cytokine tumor necrosis factor-α illustrated the efficacy of the transdermal gel for the treatment of experimental osteoarthritis. Thus the optimized gel was found to be a unique potential vehicle for transdermal application of glucosamine sulphate which effectively attenuates the experimental osteoarthritis.
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The growth kinetics and biodegradation of two waste lubricating oil samples including waste engine oil (WEO) and waste transformer oil (WTO) were studied using pure isolates and mixed culture of Ochrobactrum sp. C1 and Bacillus sp. K1. The mixed culture significantly influenced degradation efficiency of the pure isolates through bioaugmentation process. In particular, the mixed culture was capable of growing on various n-alkanes and polycyclic aromatic hydrocarbons and was able to tolerate unusually high concentrations of waste lubricants (WEO-86.0 g/L and WTO-81.5 g/L). The initial concentration of waste lubricating oils has been varied in the range of 1-10 % (v/v). Under this experimental range, the bacterial growth has been observed to follow Haldane-type kinetics characterizing the presence of substrate inhibition. Haldane model was used to fit the exponential growth data and the following kinetic parameters were obtained: µ max = 0.078 h(-1), K S = 23.101 g/L, K i = 43.844 g/L for WEO; and µ max = 0.044 h(-1), K S = 10.662 g/L, K i = 58.310 g/L for WTO. The values of intrinsic kinetic parameters, like specific growth rate µ max, half saturation constant, K S, inhibition constant, K i and the maximum substrate concentration, S max and growth yield coefficient Y x/s , have been determined using each model hydrocarbon and their mixture as limiting substrate. Relative changes in the values of the kinetic parameters have been correlated to the number of carbon atoms present in n-alkanes. The metabolites from degradation of model hydrocarbon compounds have been identified by GC-MS to elucidate the possible pathway of waste lubricating oil degradation process.
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Bacillus/crecimiento & desarrollo , Reactores Biológicos , Consorcios Microbianos , Aceite Mineral/metabolismo , Modelos Biológicos , Ochrobactrum/crecimiento & desarrollo , Biodegradación AmbientalRESUMEN
The aim of our present work was to optimize the ratio of a very novel polymer, starch-polyvinyl alcohol (PVA), for controlled delivery of Ornidazole. Polymer-coated drug microparticles were prepared by emulsion method. Microscopic study, scanning electron microscopic study, and atomic force microscopic study revealed that the microparticles were within 10 micrometers of size with smooth spherical shape. The Fourier transform infrared spectroscopy showed absence of drug polymer interaction. A statistical 3(2) full factorial design was used to study the effect of different concentration of starch and PVA on the drug release profile. The three-dimensional plots gave us an idea about the contribution of each factor on the release kinetics. Hence this novel polymer of starch and polyvinyl alcohol can be utilized for control release of the drug from a targeted delivery device.
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A potential degrader of paraffinic and aromatic hydrocarbons was isolated from oil-contaminated soil from steel plant effluent area in Burnpur, India. The strain was investigated for degradation of waste lubricants (waste engine oil and waste transformer oil) that often contain EPA (Environmental Protection Agency, USA) classified priority pollutants and was identified as Ochrobactrum sp. C1 by 16S rRNA gene sequencing. The strain C1 was found to tolerate unusually high waste lubricant concentration along with emulsification capability of the culture broth, and its degradation efficiency was 48.5 ± 0.5 % for waste engine oil and 30.47 ± 0.25 % for waste transformer oil during 7 days incubation period. In order to get optimal degradation efficiency, a three level Box-Behnken design was employed to optimize the physical parameters namely pH, temperature and waste oil concentration. The results indicate that at temperature 36.4 °C, pH 7.3 and with 4.6 % (v/v) oil concentration, the percentage degradation of waste engine oil will be 57 % within 7 days. At this optimized condition, the experimental values (56.7 ± 0.25 %) are in a good agreement with the predicted values with a calculated R 2 to be 0.998 and significant correlation between biodegradation and emulsification activity (E 24 = 69.42 ± 0.32 %) of the culture broth toward engine oil was found with a correlation coefficient of 0.972. This is the first study showing that an Ochrobactrum sp. strain is capable of degrading waste lubricants, which might contribute to the bioremediation of waste lubricating oil-contaminated soil.
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UNLABELLED: Abstract Context: Ursodeoxycholic acid (UDCA) exerts dose-dependent chemoprevention in colonic inflammation. Polycationic UDCA nanoparticles (UNPs) are envisaged for solubility enhancement and site directed drug delivery. OBJECTIVE: The objective was to study the ameliorative efficacy of UNPs through localized delivery of the drug. METHODS: UNPs were prepared through nanoprecipitation technique. Particle size, morphology, in vitro drug release and in vivo protective efficacy in inflammatory bowel disease (IBD) of these nanoparticles were studied. RESULTS AND DISCUSSION: The average particle size was around 100 nm, and the average drug encapsulation was about 99%. In vitro drug release study shows optimal drug release in simulated colonic fluid. The lowering of tissue nitric oxide, malondialdehyde, myeloperoxidase and histology of the colon tissue supported the protective efficacy of the nanoparticles. CONCLUSION: This study presents the improved efficacy of UNPs in animal model of IBD due to complete release of drug at the desired site of action.