Nitrooxyethylation Reverses the Healing-Suppressant Effect of Ibuprofen

Nonsteroidal antiinflammatory drugs like ibuprofen impede tissue repair by virtue of retarding inflammation. The present study was undertaken to explore if linking of nitrooxyethyl ester to ibuprofen reverses its healing-depressant propensity. Nitrooxyethyl ester of ibuprofen (NOE-Ibu) was synthesized in our laboratory through a well-established synthetic pathway. NOE-Ibu was screened for its influence on collagenation, wound contraction and epithelialization phases of healing, and scar size of healed wound in three wound models, namely, incision, dead space, and excision wounds. Besides, its influence on the oxidative stress (levels of GSH and TBARS) was also determined in 10-day-old granulation tissue. NOE-Ibu was further screened for its antiinflammatory activity in rat paw edema model. NOE-Ibu promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction and epithelialization phases of healing. NOE-Ibu also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to ibuprofen. Results vindicate that the esterification of ibuprofen with nitrooxyethyl group reverses the healing-suppressant effect of ibuprofen. The compound also showed equipotent antiinflammatory activity as ibuprofen

Performance Analysis of Nano Transistor Based Binary and Ternary Logic Gates

As technology scales down to the nanoscale regime, several short channel effects emerge, which have a greater impact on device performance. Researchers are exploring for innovative materials that can fit into nanometer-sized spaces to improve the performance of digital circuits. This paper provides Nano transistor-based digital circuits for improving digital circuit performance over traditional MOSFET-based circuits. Carbon nanotubes (CNTs) and graphene nano ribbons (GNR) have been investigated as possible candidates because to their high carrier mobility. The influence of CNTFET and GNRFET parametric variation with threshold voltage on performance metrics such as delay, and power has been investigated. A comparison of MOSFET, CNTFET, and GNRFET-based logic circuits is performed. A primer on ternary logic is also provided. Because of the dependence of the threshold voltage on the shape of carbon nanotubes and graphene nano ribbons, it is possible to use it for ternary logic design. Following that, ternary logic circuits are constructed with CNTFETs and GNRFETs. It has been determined that CNTFET and GNRFET-based circuits are more energy efficient than standard MOSFET circuits. It is also established that innovative ternary logic offers a relatively fast and low power digital circuit design option. All digital circuits were simulated using the HSPICE tool for the 32nm technology node

SODIUM ALGINATE/GELATIN MICROBEADS-INTERCALATED WITH KAOLIN NANOCLAY FOR EMERGING DRUG DELIVERY IN WILSON’S DISEASE

Objective: The aim of the present study was to fabricate and evaluate the drug release studies using Sodium Alginate (SA) and Gelatin (GE) microbeads intercalated with Kaolin (KA) nanoclay for sustained release of D-Penicillamine (D-PA). Methods: Sodium alginate/gelatin/Kaolin blend microbeads were prepared by an extrusion method by using glutaraldehyde (GA) as a crosslinker. The obtained microbeads were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X–ray diffraction (XRD). Drug release kinetics of the microbeads was investigated in simulated intestinal fluid (pH 7.4) at 37 °C. Results: Microbeads formation was confirmed by FTIR spectroscopy. X-RD reveals that the KA should be intercalated with the drug and also it confirms the molecular level dispersion of D-Penicillamine into microbeads. Scanning Electron Microscopy (SEM) studies reveal that the beads were in spherical shape with some wrinkled depressions on the surface. The in vitro release study indicates the D-Penicillamine released in a controlled manner. The in vitro release kinetics was assessed by Korsmeyer-Peppas equation and the ‘n’ value lies in between 0.557-0.693 indicates Non-Fickian diffusion process. Conclusion: The results suggest that the developed KA intercalated microbeads are good potential drug carrier for the controlled release of D-PA

A rat model against chemotherapy plus radiation-induced oral mucositis

AbstractObjectivesPresent study was aimed at developing an experimental model of oral mucositis in rats using a combination of chemotherapeutic agent and radiation.Study designFemale Wistar rats (150–200g) were divided into 3 groups (n=6). Rats in group 1 (normal control) and group 2 (mucositis control) were treated with vehicle. Rats in group 3 were treated with l-glutamine (1g/kg, p.o.; 15days) before and after mucositis induction. Oral mucositis was induced by busulfan (6mg/kg, p.o.; 4days) and the tongue exposed to infrared (IR) radiation of intensity 40mV/cm2 for 5 s on the 1st, 4th and 10th days of challenge using a tail flick apparatus. Parameters monitored were body weight, food intake, blood count and survival. Oral mucositis score (OMS) was recorded daily. Histological changes of the irradiated tongue were assessed by hematoxylin and eosin staining.ResultsBusulfan and IR radiation significantly reduced body weight and food intake of the mucositis control group as compared to normal control. Clear ulceration of the tongue reflected in the OMS. Histopathology of the tongue revealed intense lymphocytic infiltration, decreased thickness of squamous epithelial cell layer, decrease in number of blood vessels, and necrosis of cells along with pseudo-membrane formation in the mucositis control group. These findings suggested that oral mucositis was successfully induced and treatment with l-glutamine partially reversed these conditions.ConclusionOral mucositis was established successfully in rats by the combination of chemotherapeutic agent and IR radiation. This may be a useful model for screening drugs in the treatment of oral mucositis

In vitro and in vivo anticancer studies of 2'-hydroxy chalcone derivatives exhibit apoptosis in colon cancer cells by HDAC inhibition and cell cycle arrest

Considering the therapeutic values of bioflavonoids in colon cancer treatment, six 2′-hydroxy chalcones (C1-C6) were synthesized, characterized and screened for in vitro cytotoxicity on human colon carcinoma (HCT116) and African green monkey kidney epithelial cells (Vero). Only C5 showed selective cytotoxicity against HCT116 cells. Other potent cytotoxic compounds were C1, C2 and C3. Further screening included enzyme inhibition studies on histone deacetylase (HDAC) enzyme where C1 showed lowest IC50 value (105.03 µM). Based on cytotoxicity data C1, C2 and C3 were selected for further in vitro mechanistic studies, namely apoptotic studies (Acridine or- ange/Ethidium bromide (AO/EB) and Annexin V), cell cycle analysis using propidium iodide (PI) stain and in vivo anticancer efficacy in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in Wistar rats. The com- pounds induced apoptosis in more than 30 % cells in AO/EB and Annexin V staining. They also showed cell cycle arrest in G2/M phase with PI staining. They showed a significant reduction in aberrant crypt foci formation and adenocarcinoma count along with a significant (p<0.05) reduction in TNF-α levels as compared to DMH control at 100 mg/kg dose. Thus, it can be concluded that the synthesized 2′-hydroxychalcones were effective against colon adenocarcinoma in in vitro and in vivo studies

Evaluation of in vitro and in vivo anticancer potential of two 5-acetamido chalcones against breast cancer

Two 5’acetamido chalcones, C1 and C2 were synthesized by Claisen-Schmidt condensation method and characterized by IR, LC-MS, 1H NMR and 13C NMR. These compounds were evaluated for anticancer activity in vitro in breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT assay, anti-metastatic assay, apoptotic screening by AO/EB staining and in vivo in N-Methyl-N-nitrosourea (MNU) induced breast carcinoma model. Sprague-Dawley rats with developed tumors (50 mg/kg MNU i.p.) were grouped in four, namely MNU control (0.25 % of CMC p.o.), standard group (doxorubicin 2 mg/kg once in 4 days, i.p.), C1 and C2 groups (50 mg/kg p.o. each). After 21 days of treatments, tumor volume and weight were assessed. Excised tumors were subjected to DNA fragmentation study. MTT assay showed IC50 values of 62.56 and 37.8 µM by for C1 and C2. Both compounds increased apoptotic bodies more than 3 fold compared to normal control in AO/EB staining. Antimeta- static (scratch wound) assay showed a significant (p<0.05) reduction in cell migration after 24 h and 48 h treat- ments compared to normal control. In in vivo studies, tumor weight and tumor volume were significantly (p<0.05) reduced in the doxorubicin group as well as in test groups compared to MNU control. DNA fragmentation assay showed an increase in the number of bands formed in C1 and C2 compared to normal control. Results obtained from in vitro and in vivo studies demonstrated the significant anticancer potentials of C1 and C2

Selected novel 5'-amino-2'-hydroxy-1,3-diaryl-2-propen-1-ones arrest cell cycle of HCT-116 in G0/G1 phase

A series of 5’-amino-2’-hydroxy-1,3-diaryl-2-propen-1-ones (AC1-AC15) were synthesized by Claisen-Schmidt condensation of 5'-acetamido-2’-hydroxy acetophenone with various substituted aromatic aldehydes. The synthesized compounds were characterized by FTIR, 1H NMR and mass spectrometry and evaluated for their selective cytotoxicity using MTT assay on two cancer cell lines namely breast cancer cell line (MCF-7), colon cancer cell line (HCT-116) and one normal kidney epithelial cell line (Vero). Among the tested compounds, AC-10 showed maximum cytotoxic effect on MCF-7 cell line with IC50 value 74.7 ± 3.5 μM. On HCT-116 cells, AC-13 exhibited maximum cytotoxicity with IC50 value 42.1 ± 4.0 μM followed by AC-14 and AC-10 with IC50 values 62 ± 2.3 μM and 95.4 ± 1.7 μM respectively. All tested compounds were found to be safe on Vero cell line with IC50 value more than 200 μM. Based on their highest efficacy on HCT-116, AC-10, AC-13 and AC-14 were selected for mechanistic study on this cell line by evaluating changes nucleomorphological characteristics using acridine orange-ethidium bromide (AOEB) dual stain and by analyzing cell cycle with flow cytometry using propidium iodide stain. In AOEB staining, all three tested compounds showed significant (p < 0.05) increase in percentage apoptotic nuclei compared to control cells, with highest increase in apoptotic nuclei by AC-13 treatment (31 %). Flow cytometric studies showed cell cycle arrest by AC-10 and AC-14 treatment in G0/G1 phase and by AC-13 in G0/G1 and G2/M phase. The study reflected the potential of AC-10, AC-13 and AC-14 to be the lead molecules for further optimization

Introgression of disease resistance genes from Arachis kempff-mercadoi into cultivated groundnut

Arachis kempff-mercadoi is a wild species from the section Arachis. All kempff-mercadoi accessions originate from the Santa Cruz province of Bolivia and they represent Arachis species with the A genome. From molecular analysis it was found that although cultivated A. hypogaea is made up of A and B genomes, A. kempff-mercadoi may not be as closely related to it as are some of the other A genome species. Arachis kempff-mercadoi is of interest because it has multiple disease resistance. It was crossed with a Spanish A. hypogaea cultivar which is susceptible to foliar diseases and to the insect pest Spodoptera litura. The success rate of the cross A. hypogaea (2n=40) × A. kempff-mercadoi (2n=20) was very low, but it could be increased by culturing immature seeds in vitro. Although the hybrids were triploids, a few fertile pollen grains were obtained due to the formation of restitution nuclei in the F1 plants. Interspecific derivatives at the BC2F2 generation were scored for early leaf spot, late leaf spot and to Spodoptera damage. Screening results showed that 29% of the derivatives had both early and late leaf spot resistance and that less than 5% of the derivatives had resistance to both the foliar diseases and to Spodopter