MGMT gene promoter methylation and its correlation with clinicopathological parameters in glioblastomas.

BACKGROUND: MGMT (O6-methyl guanine DNA methyl transferase) promoter hypermethylation is a prognostic and predictive biomarker for glioblastomas (GBM). AIMS: To evaluate the frequency of MGMT methylation status in a single institute series of 134 GBMs and correlate it with clinical (age, sex, location, survival) and other molecular parameters [such as p53 expression, alpha thalassemia/mental retardation syndrome X-linked (ATRX) expression, isocitrate dehydrogenase (IDH) 1R132H mutation, and epidermal growth factor receptor (EGFR) gene amplification]. RESULTS: One hundred and thirty-four GBMs were evaluated by methylation-specific polymerase chain reaction (MSP) for MGMT promoter methylation status. The results were correlated with the above mentioned clinicopathological parameters. MGMT gene promoter methylation was identified in 49.2% (66/134) GBMs, and was significantly associated with IDH1R132H mutation (14/66; 21%; P - value, 0.01) and ATRX loss (15/66; 23%; P - value, 0.01). Confluent necrosis was found to be significantly associated with MGMT unmethylation status (P - value: 0.002). Multivariable logistic regression analysis showed confluent necrosis as a single independent predictor (odds ratio [OR], 2.5; confidence interval [CI], 1.0-5.8; P - value, 0.04) of MGMT unmethylation status among all the parameters studied. CONCLUSIONS: The frequency of MGMT promoter methylation in GBMs was 49.2%, which was significantly associated with IDHR132H mutation and ATRX loss. In addition, the presence of confluent necrosis was significantly associated with MGMT unmethylation and was found to be an independent predictor of the same.

Enhanced supercapacitor performance of a Cu-Fe2O3/g-C3N4 composite material: synthesis, characterization, and electrochemical analysis.

A Cu-doped Fe2O3/g-C3N4 composite, synthesized via a straightforward hydrothermal process with controlled morphologies, represents a significant advancement in supercapacitor electrode materials. This study systematically analyzes the impact of Cu doping in Fe2O3 and its synergistic combination with g-C3N4 to understand their influence on the electrochemical performance of the resulting composite, focusing on Cu doping in Fe2O3 rather than varying Fe2O3/g-C3N4 content. The comprehensive characterization of these composites involved a suite of physicochemical techniques. X-ray diffraction (XRD) confirmed the successful synthesis of the composite, while field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) were employed to investigate the morphological attributes of the synthesized materials. X-ray photoelectron spectroscopy (XPS) spectra confirmed the elemental composition of the composite with 6% Cu doped Fe2O3/g-C3N4. The composite electrode, which incorporated 6% Cu doped Fe2O3 with g-C3N4, exhibited exceptional cycling stability, retaining 94.22% of its capacity even after 2000 charge-discharge cycles at a current density of 5 mA cm-2. Furthermore, this Cu doped Fe2O3/g-C3N4 composite electrode demonstrated impressive electrochemical performance, boasting a specific capacitance of 244.0 F g-1 and an impressive maximum energy density of 5.31 W h kg-1 at a scan rate of 5 mV s-1. These findings highlight the substantial potential of the Cu doped Fe2O3/g-C3N4 electrode for supercapacitor applications.

Formulation and evaluation of a pulsatile drug delivery system using time- and pH-dependant polymers.

The aim of the present study was to develop fast-release enteric-coated tablets for pulsatile drug delivery to the colon. The novelty of this work is a combination of pH- and time-dependant enteric polymers as a single coating. Eudragit S100 was used as a pH-dependant polymer and eudragit RL100 was used as a time-dependant polymer. Theophylline was taken as a model drug. Dissolution studies of enteric-coated tablets were performed with different media having a pH of 1.2, 7.4, and 6.8. Results of the dissolution data show that drug release in the colon could be controlled by using eudragit RL100 eudragit S100. The lag time prior to the drug release was highly affected by a combination of two factors: The percentage of eudragit RL100 and coating level. The optimum formulation was found to be one containing eudragit RL100 and eudragit S100 with a ratio of 60:40 of polymer and coating level of 4.66% w/w. The present study demonstrates that the theophylline enteric-coated tablets could be successfully formulated as a pulsatile drug delivery by the design of a time- and pH-dependant modified chronopharmaceutical formulation. In conclusion, pulsatile drug release over a period of 2-12 hours, consistent with the requirements for chronopharmaceutical drug delivery, can be achieved by using time- and pH-dependant polymers.

Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers.

The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.

Development of colon targeted multiparticulate pulsatile drug delivery system for treating nocturnal asthma.

The aim of the present study was to develop theophylline fast release enteric-coated pellets as a pulsatile drug delivery to the colon. The novelty of this work is the combination of pH and time-dependant enteric polymers as a single coating for the development of multiparticulate formulation. Theophylline pellets were optimized by applying a 2-factors 3-levels full factorial design. Continuous dissolution studies were carried out in simulated gastric, intestinal, and colonic fluid with pH 1.2 (0.1 N HCl), pH 7.4 and pH 6.8 (phosphate buffer), respectively. The lag time prior to the drug release was highly affected by combination of two factors, i.e. the percentage of Eudragit RL100 in polymer mixture and coating level. The formulation containing Eudragit RL100 and Eudragit S100 with a ratio of 4:1 and coating level of 12%w/w was found to be optimum. The results of serum study in New Zealand rabbits showed that the developed formulation provided a significant lag phase of 5 h. The present study demonstrates that the theophylline enteric-coated pellets could be successfully colon targeted by the design of pH- and time-dependant modified chronopharmaceutical formulation. In conclusion, pulsatile drug release over a period of 3-12 h is consistent with the requirements for chronopharmaceutical drug delivery.