Interdisciplinary Perspectives on Infectious Diseases, 2015
Objective. To determine the level of knowledge, opinions, and preventive practices followed by de... more Objective. To determine the level of knowledge, opinions, and preventive practices followed by dental students against Hepatitis B. The study also explored if any correlation existed between knowledge, opinion, and preventive practices score. Materials and Methods. A cross-sectional study was conducted in a dental teaching institution. The subjects comprised 216 dental students. The study was conducted using a pretested, self-administered questionnaire. The questionnaire was prepared to assess knowledge, opinion, and preventive practices against Hepatitis B. Kruskal-Wallis and Kendall Tau test were performed. Results. The study found that only 44.4% of the students were vaccinated with Hepatitis B vaccine. 59.3% of the students reported washing their hands after contact with patient's body fluids. 63.9% used personal protective measures like facemask, aprons, head cap, eye shields, and so forth, while treating patients. Median knowledge, opinion, and practice scores were found to be 5.00, 3.00, and 3.00, respectively. Significant correlation was obtained between knowledge and preventive practices score (r = 0.385, p value <0.0001). Conclusion. Effective measures need to be taken to improve preventive practices of the students to prevent them from risk of Hepatitis transmission. Mandatory vaccination against Hepatitis B needs to be implemented.
The paper highlights the possibility of using Polypyrrole (PPy) for planar microstrip patch anten... more The paper highlights the possibility of using Polypyrrole (PPy) for planar microstrip patch antenna (MPA).The MPA has been designed using a conducting polymer PPy and Plexiglas TM laminate with a thickness of 1.8mm. The bulk conductivity of polypyrrole is 1200 and thickness is taken as 90mm.An analogous structure is designed using copper patch validating the design and comparing the performance. The antenna was designed for operations at 5.8 GHz. The PPy structure shows a gain of 4.6dB in contrast to 4.8dB gain of Cu structure. A comparative analysis is done between performance characteristics of Cu and PPy material fabricated on Plexiglas substrate results with good performance of PPy material. The result obtained confirms the advantage of using polymer materials in microwave applications as compare to the copper generally used.
Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydra... more Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydrates, protein and lipid metabolism; leading to elevated blood glucose levels. The present study was conducted to evaluate the correlation between blood glucose and salivary glucose levels in known diabetic patients and control group and also to evaluate salivary glucose level as a diagnostic tool in diabetic patients. A total number of 250 patients were studied, out of which 212 formed the study group and 38 formed the control group. Among 250 patients, correlation was evaluated between blood glucose and salivary glucose values which on analysis revealed Pearson correlation of 0.073. The p-value was 0.247, which was statistically non significant. Salivary glucose values cannot be considered as a diagnostic tool for diabetic individuals.
Members of the superfamily of major intrinsic proteins (MIPs) facilitate water and solute permeab... more Members of the superfamily of major intrinsic proteins (MIPs) facilitate water and solute permeability across cell membranes and are found in sources ranging from bacteria to humans. Aquaporin and aquaglyceroporin channels are the prominent members of the MIP superfamily. Experimental studies show that MIPs are involved in important physiological processes in mammals and plants. They are implicated in several human diseases and are considered to be attractive drug targets for a wide range of diseases such as cancer, brain edema, epilepsy, glaucoma, and congestive heart failure. Three-dimensional structures of MIP channels from diverse sources reveal that MIPs adopt a unique conserved hourglass helical fold consisting of six transmembrane helices (TM1-TM6) and two half-helices (LB and LE). Conserved NPA motifs near the center and the aromatic/arginine selectivity filter (Ar/R SF) toward the extracellular side constitute two narrow constriction regions within the channel. Structural knowledge combined with simulation studies have helped to investigate the role of these two constriction regions in the transport and selectivity of the solutes. With the availability of many genome sequences from diverse species, a large number of MIP genes have been identified. Homology models of 1500 MIP channels have been used to derive structure-based sequence alignment of TM1-TM6 helices and the two half-helices LB and LE. Thirteen residues are highly conserved in different transmembrane helices and half-helices. High group conservation of small and weakly polar residues is observed in 27 positions at the interface of two interacting helices. Thus, although the MIP sequences are diverse, the hourglass helical fold is maintained during evolution with the conservation of these 40 positions within the transmembrane region. We have proposed a generic structure-based numbering scheme for the MIP channels that will facilitate easier comparison of the MIP sequences. Analysis of Ar/R SF in all 1500 MIPs indicates the extent of diversity in the four residues that form this narrow region. Certain residues are completely avoided in the SF, even if they have the same chemical nature as that of the most frequently observed residues. For example, arginine is the most preferred residue in a specific position of Ar/R SF, whereas lysine is almost always avoided in any of the four positions. MIP channels with highly hydrophobic or hydrophilic Ar/R SF have been identified. Similarly, there are examples of MIP channels in which all four residues of Ar/R SF are bulky, thus almost occluding the pore. Many plant MIPs possess small residues at all SF positions, resulting in a larger pore diameter. A majority of MIP channels are yet to be functionally characterized, and their in vivo substrates are not yet identified. A complete understanding of the relationship between the nature of Ar/R SF and the solutes that are transported is required to exploit MIP channels as potential drug targets.
The critical pathways determining the resistance of tumor cells to ionizing radiation are poorly ... more The critical pathways determining the resistance of tumor cells to ionizing radiation are poorly defined. Because the ras oncogene, a gene activated in many human cancers treated with radiotherapy, can induce increased radioresistance, we have asked which Ras effector pathways are significant in conferring a survival advantage to tumor cells. The phosphoinositide-3-kinase (PI3K) inhibitor LY294002 radiosensitized cells bearing mutant ras oncogenes, but the survival of cells with wild-type ras was not affected. Inhibition of the PI3K downstream target p70S6K by rapamycin, the Raf-MEK-MAPK pathway with PD98059, or the Ras-MEK kinase-p38 pathway with SB203580 had no effect on radiation survival in cells with oncogenic ras. Expression of active PI3K in cells with wild-type ras resulted in increased radiation resistance that could be inhibited by LY294002. These experiments have indicated the importance of PI3K in mediating enhanced radioresistance and have implicated PI3K as a potential...
Transformation with ras oncogenes results in increased radiation sur vival in many but not all ce... more Transformation with ras oncogenes results in increased radiation sur vival in many but not all cells. In addition, prenyltransferase inhibitors which inhibit ras proteins by blocking posttranslational modification radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrinsic radiation resistance. However, because introduction of ras oncogenes does not increase radiation survival in all cells and because prenyltransferase inhibitors target molecules other than ras, these studies left the conclusion that ras increases the intrinsic radi ation resistance of tumor cells in doubt. Here we show that genetic inactivation of K- or N-ras oncogenes in human tumor cells (DLD-1 and HT1080, respectively) leads to increased radiosensitivity. Reintroduction of the activated N-ras gene into the HT1080 line, having lost its mutant allele, resulted in increased radiation resistance. This study lends further support to the hypothesis that expression of act...
Our aim was to examine a possible correlation between drinking water nitrate concentration, recur... more Our aim was to examine a possible correlation between drinking water nitrate concentration, recurrent stomatitis, and cytochrome b5 reductase activity. Dietary nitrate can form nitrite in vivo. This can cause methemoglobinemia in the red blood cells. Cytochrome b5 reductase is an enzyme in the red blood cells that reduces methemoglobin back to hemoglobin. Five areas were selected in the State of Rajasthan, India, having drinking water nitrate concentration (as nitrate) of 26, 45, 95, 222, and 459 mg of NO3/L. House schedules were prepared in these areas in accordance with a statistically designed protocol. We selected 193 age- and weight-matched persons, representing 10% of the total population in each of these areas. Detailed history was taken for recurrent stomatitis, medical examination was conducted, and blood samples were taken to ascertain cytochrome b5 reductase activity in the selected population. Collected data were statistically analyzed to ascertain a relationship between...
We have investigated the effect of glucose deprivation treatment on the activation of mitogen act... more We have investigated the effect of glucose deprivation treatment on the activation of mitogen activated protein kinases (MAPKs) in the drug-sensitive human breast carcinoma cells (MCF-7) and its drug resistant variant (MCF-7/ADR) cells. Western blots and in-gel kinase assays showed that glucose free medium was a strong stimulus for the activation of MAPK in MCF-7/ADR cells. No activation was seen in MCF-7 cells. MAPK was activated within 3 min of being in glucose free medium and it remained activated for over 1 h in MCF-7/ADR cells. After being returned to complete medium, 1 h was required for the MAPK to become deactivated. To investigate whether alternative sources of ATP could inhibit glucose deprivation induced MAPK activation, we added glutamine and glutamate to glucose deprived medium. The addition of glutamine did not reverse glucose deprivation induced MAPK activation in MCF-7/ADR cells. The addition of glutamate, however, decreased the MAPK activation and the length of time...
Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (s... more Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (surgery, chemotherapy, and radiation). Glioblastomas fre- quently display loss of PTEN and/or epidermal growth factor receptor activation, both of which activate the PI3Kpathway.Thispathwaycanincreasevascularendo- thelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1A expression. We examined the effects of two human immunodeficiency virus protease inhibi- tors, nelfinavir and amprenavir,
The removal of fluoride from drinking water by the method of adsorption on activated alumina is f... more The removal of fluoride from drinking water by the method of adsorption on activated alumina is found superior than other defluoridation techniques mostly due to the strong affinity between aluminium and fluoride. Dissolution of aluminium from the alumina surfaces into its free and hydroxide ions in the aqueous medium is reported to be very low, but the presence of high fluoride concentrations may increase its solubility due to the formation of monomeric aluminium fluoride and aluminium hydroxyl fluoride complexes. An Activated Alumina Defluoridation Model Simulator (AAD) has been developed to represent fluoride adsorption on the basis of the surface complexation theory incorporating aspects of aluminium solubility in presence of high fluoride concentrations and pH variations. Model validations were carried out for residual aluminium concentrations in alumina treated water, by conducting a series of batch fluoride adsorption experiments using activated alumina (grade FB101) treating...
A heterotopic pregnancy is the coexistence of one or more ectopic and a single or multiple eutopi... more A heterotopic pregnancy is the coexistence of one or more ectopic and a single or multiple eutopic pregnancy. Heterotopic pregnancy currently occurs in approximately 1 of 7000 spon-taneous pregnancies. However, artificial reproductive techniques increase the incidence to 1%. ...
In this paper, the build up of mathematical model for prediction of pollutant transport in the su... more In this paper, the build up of mathematical model for prediction of pollutant transport in the subsurface flow of Sanganer area has been detailed. The model was calibrated for its performance with the actual observed concentrations at select locations. The results showed that mass transport modelling simulation can effectively be used for studying the pollutant migration in underground strata. The
To evaluate the impact of facial nerve sacrifice and postoperative radiotherapy on the outcome of... more To evaluate the impact of facial nerve sacrifice and postoperative radiotherapy on the outcome of adenoid cystic carcinoma of the parotid gland. Inception cohort. Retrospective review of Department of Pathology, SNOMED database, and Tumor Registry including health-related quality of life data for the subset enrolled in the longitudinal Outcomes Assessment Project. Fisher exact, chi, and Wilcoxon tests were used to determine significant differences. Fifty-two cases (follow-up mean: 9.1 years, range: 0.5-40.8 years) demonstrated local control rates of 84.6% (5 years), 76.9% (10 years), and 50% (20 years). Compared with facial nerve preservation, facial nerve sacrifice had better control at 5 years (100 vs. 78.9% P = .259) while having detrimental effects on eating, speech, and esthetics. Local control at 5 years was significantly better (P = .048) with postoperative radiotherapy (100%) than without (84.6%). Overall survival was 79.4% (5 years), 50% (10 years), and 32.3% (20 years). At...
This article presents an overview of preclinical studies and clinical trials of a number of indep... more This article presents an overview of preclinical studies and clinical trials of a number of independently derived farnesyltransferase inhibitors (FTIs). Potential targets and biological modes of action of FTIs are discussed, and the results of clinical trials are summarized. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in clinical Phase II-III trials. These results reveal a substantial gap in the understanding of the complex activity of FTIs and their interactions with cytotoxic agents. We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs.
A series of novel ammonium derivatives were synthesized and examined for their antimicrobial effi... more A series of novel ammonium derivatives were synthesized and examined for their antimicrobial efficacy. Comparison of antimicrobial spectrum revealed that compounds 9, 11, 16 and 23 had strong potential against pathogens in vitro. Cytotoxicity results showed compound 9 to be least toxic, it is non-toxic to A549 and U87 cells in MTT assay and exhibits marginal toxicity (15-20%) to human erythrocytes at a concentration of 1000 μg/ml as compared to 100% lysis of cells by 31.25 μg/ml of the standard drug amphotericin B. This compound has MIC values in the range of 1.95-31.25 μg/disc in DDA against different pathogens and may considered to be an important lead antimicrobial molecule for further exploration.
Interdisciplinary Perspectives on Infectious Diseases, 2015
Objective. To determine the level of knowledge, opinions, and preventive practices followed by de... more Objective. To determine the level of knowledge, opinions, and preventive practices followed by dental students against Hepatitis B. The study also explored if any correlation existed between knowledge, opinion, and preventive practices score. Materials and Methods. A cross-sectional study was conducted in a dental teaching institution. The subjects comprised 216 dental students. The study was conducted using a pretested, self-administered questionnaire. The questionnaire was prepared to assess knowledge, opinion, and preventive practices against Hepatitis B. Kruskal-Wallis and Kendall Tau test were performed. Results. The study found that only 44.4% of the students were vaccinated with Hepatitis B vaccine. 59.3% of the students reported washing their hands after contact with patient's body fluids. 63.9% used personal protective measures like facemask, aprons, head cap, eye shields, and so forth, while treating patients. Median knowledge, opinion, and practice scores were found to be 5.00, 3.00, and 3.00, respectively. Significant correlation was obtained between knowledge and preventive practices score (r = 0.385, p value <0.0001). Conclusion. Effective measures need to be taken to improve preventive practices of the students to prevent them from risk of Hepatitis transmission. Mandatory vaccination against Hepatitis B needs to be implemented.
The paper highlights the possibility of using Polypyrrole (PPy) for planar microstrip patch anten... more The paper highlights the possibility of using Polypyrrole (PPy) for planar microstrip patch antenna (MPA).The MPA has been designed using a conducting polymer PPy and Plexiglas TM laminate with a thickness of 1.8mm. The bulk conductivity of polypyrrole is 1200 and thickness is taken as 90mm.An analogous structure is designed using copper patch validating the design and comparing the performance. The antenna was designed for operations at 5.8 GHz. The PPy structure shows a gain of 4.6dB in contrast to 4.8dB gain of Cu structure. A comparative analysis is done between performance characteristics of Cu and PPy material fabricated on Plexiglas substrate results with good performance of PPy material. The result obtained confirms the advantage of using polymer materials in microwave applications as compare to the copper generally used.
Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydra... more Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydrates, protein and lipid metabolism; leading to elevated blood glucose levels. The present study was conducted to evaluate the correlation between blood glucose and salivary glucose levels in known diabetic patients and control group and also to evaluate salivary glucose level as a diagnostic tool in diabetic patients. A total number of 250 patients were studied, out of which 212 formed the study group and 38 formed the control group. Among 250 patients, correlation was evaluated between blood glucose and salivary glucose values which on analysis revealed Pearson correlation of 0.073. The p-value was 0.247, which was statistically non significant. Salivary glucose values cannot be considered as a diagnostic tool for diabetic individuals.
Members of the superfamily of major intrinsic proteins (MIPs) facilitate water and solute permeab... more Members of the superfamily of major intrinsic proteins (MIPs) facilitate water and solute permeability across cell membranes and are found in sources ranging from bacteria to humans. Aquaporin and aquaglyceroporin channels are the prominent members of the MIP superfamily. Experimental studies show that MIPs are involved in important physiological processes in mammals and plants. They are implicated in several human diseases and are considered to be attractive drug targets for a wide range of diseases such as cancer, brain edema, epilepsy, glaucoma, and congestive heart failure. Three-dimensional structures of MIP channels from diverse sources reveal that MIPs adopt a unique conserved hourglass helical fold consisting of six transmembrane helices (TM1-TM6) and two half-helices (LB and LE). Conserved NPA motifs near the center and the aromatic/arginine selectivity filter (Ar/R SF) toward the extracellular side constitute two narrow constriction regions within the channel. Structural knowledge combined with simulation studies have helped to investigate the role of these two constriction regions in the transport and selectivity of the solutes. With the availability of many genome sequences from diverse species, a large number of MIP genes have been identified. Homology models of 1500 MIP channels have been used to derive structure-based sequence alignment of TM1-TM6 helices and the two half-helices LB and LE. Thirteen residues are highly conserved in different transmembrane helices and half-helices. High group conservation of small and weakly polar residues is observed in 27 positions at the interface of two interacting helices. Thus, although the MIP sequences are diverse, the hourglass helical fold is maintained during evolution with the conservation of these 40 positions within the transmembrane region. We have proposed a generic structure-based numbering scheme for the MIP channels that will facilitate easier comparison of the MIP sequences. Analysis of Ar/R SF in all 1500 MIPs indicates the extent of diversity in the four residues that form this narrow region. Certain residues are completely avoided in the SF, even if they have the same chemical nature as that of the most frequently observed residues. For example, arginine is the most preferred residue in a specific position of Ar/R SF, whereas lysine is almost always avoided in any of the four positions. MIP channels with highly hydrophobic or hydrophilic Ar/R SF have been identified. Similarly, there are examples of MIP channels in which all four residues of Ar/R SF are bulky, thus almost occluding the pore. Many plant MIPs possess small residues at all SF positions, resulting in a larger pore diameter. A majority of MIP channels are yet to be functionally characterized, and their in vivo substrates are not yet identified. A complete understanding of the relationship between the nature of Ar/R SF and the solutes that are transported is required to exploit MIP channels as potential drug targets.
The critical pathways determining the resistance of tumor cells to ionizing radiation are poorly ... more The critical pathways determining the resistance of tumor cells to ionizing radiation are poorly defined. Because the ras oncogene, a gene activated in many human cancers treated with radiotherapy, can induce increased radioresistance, we have asked which Ras effector pathways are significant in conferring a survival advantage to tumor cells. The phosphoinositide-3-kinase (PI3K) inhibitor LY294002 radiosensitized cells bearing mutant ras oncogenes, but the survival of cells with wild-type ras was not affected. Inhibition of the PI3K downstream target p70S6K by rapamycin, the Raf-MEK-MAPK pathway with PD98059, or the Ras-MEK kinase-p38 pathway with SB203580 had no effect on radiation survival in cells with oncogenic ras. Expression of active PI3K in cells with wild-type ras resulted in increased radiation resistance that could be inhibited by LY294002. These experiments have indicated the importance of PI3K in mediating enhanced radioresistance and have implicated PI3K as a potential...
Transformation with ras oncogenes results in increased radiation sur vival in many but not all ce... more Transformation with ras oncogenes results in increased radiation sur vival in many but not all cells. In addition, prenyltransferase inhibitors which inhibit ras proteins by blocking posttranslational modification radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrinsic radiation resistance. However, because introduction of ras oncogenes does not increase radiation survival in all cells and because prenyltransferase inhibitors target molecules other than ras, these studies left the conclusion that ras increases the intrinsic radi ation resistance of tumor cells in doubt. Here we show that genetic inactivation of K- or N-ras oncogenes in human tumor cells (DLD-1 and HT1080, respectively) leads to increased radiosensitivity. Reintroduction of the activated N-ras gene into the HT1080 line, having lost its mutant allele, resulted in increased radiation resistance. This study lends further support to the hypothesis that expression of act...
Our aim was to examine a possible correlation between drinking water nitrate concentration, recur... more Our aim was to examine a possible correlation between drinking water nitrate concentration, recurrent stomatitis, and cytochrome b5 reductase activity. Dietary nitrate can form nitrite in vivo. This can cause methemoglobinemia in the red blood cells. Cytochrome b5 reductase is an enzyme in the red blood cells that reduces methemoglobin back to hemoglobin. Five areas were selected in the State of Rajasthan, India, having drinking water nitrate concentration (as nitrate) of 26, 45, 95, 222, and 459 mg of NO3/L. House schedules were prepared in these areas in accordance with a statistically designed protocol. We selected 193 age- and weight-matched persons, representing 10% of the total population in each of these areas. Detailed history was taken for recurrent stomatitis, medical examination was conducted, and blood samples were taken to ascertain cytochrome b5 reductase activity in the selected population. Collected data were statistically analyzed to ascertain a relationship between...
We have investigated the effect of glucose deprivation treatment on the activation of mitogen act... more We have investigated the effect of glucose deprivation treatment on the activation of mitogen activated protein kinases (MAPKs) in the drug-sensitive human breast carcinoma cells (MCF-7) and its drug resistant variant (MCF-7/ADR) cells. Western blots and in-gel kinase assays showed that glucose free medium was a strong stimulus for the activation of MAPK in MCF-7/ADR cells. No activation was seen in MCF-7 cells. MAPK was activated within 3 min of being in glucose free medium and it remained activated for over 1 h in MCF-7/ADR cells. After being returned to complete medium, 1 h was required for the MAPK to become deactivated. To investigate whether alternative sources of ATP could inhibit glucose deprivation induced MAPK activation, we added glutamine and glutamate to glucose deprived medium. The addition of glutamine did not reverse glucose deprivation induced MAPK activation in MCF-7/ADR cells. The addition of glutamate, however, decreased the MAPK activation and the length of time...
Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (s... more Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (surgery, chemotherapy, and radiation). Glioblastomas fre- quently display loss of PTEN and/or epidermal growth factor receptor activation, both of which activate the PI3Kpathway.Thispathwaycanincreasevascularendo- thelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1A expression. We examined the effects of two human immunodeficiency virus protease inhibi- tors, nelfinavir and amprenavir,
The removal of fluoride from drinking water by the method of adsorption on activated alumina is f... more The removal of fluoride from drinking water by the method of adsorption on activated alumina is found superior than other defluoridation techniques mostly due to the strong affinity between aluminium and fluoride. Dissolution of aluminium from the alumina surfaces into its free and hydroxide ions in the aqueous medium is reported to be very low, but the presence of high fluoride concentrations may increase its solubility due to the formation of monomeric aluminium fluoride and aluminium hydroxyl fluoride complexes. An Activated Alumina Defluoridation Model Simulator (AAD) has been developed to represent fluoride adsorption on the basis of the surface complexation theory incorporating aspects of aluminium solubility in presence of high fluoride concentrations and pH variations. Model validations were carried out for residual aluminium concentrations in alumina treated water, by conducting a series of batch fluoride adsorption experiments using activated alumina (grade FB101) treating...
A heterotopic pregnancy is the coexistence of one or more ectopic and a single or multiple eutopi... more A heterotopic pregnancy is the coexistence of one or more ectopic and a single or multiple eutopic pregnancy. Heterotopic pregnancy currently occurs in approximately 1 of 7000 spon-taneous pregnancies. However, artificial reproductive techniques increase the incidence to 1%. ...
In this paper, the build up of mathematical model for prediction of pollutant transport in the su... more In this paper, the build up of mathematical model for prediction of pollutant transport in the subsurface flow of Sanganer area has been detailed. The model was calibrated for its performance with the actual observed concentrations at select locations. The results showed that mass transport modelling simulation can effectively be used for studying the pollutant migration in underground strata. The
To evaluate the impact of facial nerve sacrifice and postoperative radiotherapy on the outcome of... more To evaluate the impact of facial nerve sacrifice and postoperative radiotherapy on the outcome of adenoid cystic carcinoma of the parotid gland. Inception cohort. Retrospective review of Department of Pathology, SNOMED database, and Tumor Registry including health-related quality of life data for the subset enrolled in the longitudinal Outcomes Assessment Project. Fisher exact, chi, and Wilcoxon tests were used to determine significant differences. Fifty-two cases (follow-up mean: 9.1 years, range: 0.5-40.8 years) demonstrated local control rates of 84.6% (5 years), 76.9% (10 years), and 50% (20 years). Compared with facial nerve preservation, facial nerve sacrifice had better control at 5 years (100 vs. 78.9% P = .259) while having detrimental effects on eating, speech, and esthetics. Local control at 5 years was significantly better (P = .048) with postoperative radiotherapy (100%) than without (84.6%). Overall survival was 79.4% (5 years), 50% (10 years), and 32.3% (20 years). At...
This article presents an overview of preclinical studies and clinical trials of a number of indep... more This article presents an overview of preclinical studies and clinical trials of a number of independently derived farnesyltransferase inhibitors (FTIs). Potential targets and biological modes of action of FTIs are discussed, and the results of clinical trials are summarized. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in clinical Phase II-III trials. These results reveal a substantial gap in the understanding of the complex activity of FTIs and their interactions with cytotoxic agents. We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs.
A series of novel ammonium derivatives were synthesized and examined for their antimicrobial effi... more A series of novel ammonium derivatives were synthesized and examined for their antimicrobial efficacy. Comparison of antimicrobial spectrum revealed that compounds 9, 11, 16 and 23 had strong potential against pathogens in vitro. Cytotoxicity results showed compound 9 to be least toxic, it is non-toxic to A549 and U87 cells in MTT assay and exhibits marginal toxicity (15-20%) to human erythrocytes at a concentration of 1000 μg/ml as compared to 100% lysis of cells by 31.25 μg/ml of the standard drug amphotericin B. This compound has MIC values in the range of 1.95-31.25 μg/disc in DDA against different pathogens and may considered to be an important lead antimicrobial molecule for further exploration.
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