Objective:To assess the In vivo anlioxid Fanl and hepaloproleclive activity of metlianolic exlracl of Daucus carota(D.carota) seeds in experimental animals.Methods:Methanolic extracts of D.carota seeds is used for hep...Objective:To assess the In vivo anlioxid Fanl and hepaloproleclive activity of metlianolic exlracl of Daucus carota(D.carota) seeds in experimental animals.Methods:Methanolic extracts of D.carota seeds is used for hepatoproleclion assessment.Oxidative stress were induced in rats by thioacetamide 100 nig/kg s.c.in four groups of rats(two test,standard and toxic control). Two test groups received D.carota seeds extract[DCSE) at doses of 200 mg/kg and 400 mg/kg. Standard group received silymarin(25 mg/kg) and toxic control received only thioacetamide. Control group received only vehicle.On the 8th day animals were sacrificed and liver enzyme like serum glutamic pyruvic transaminase(SGPT),serum glutamic-oxaloacetic transaminase(SCOT) and alkaline phosphatase(ALP)were estimated in blood serum and antioxidant enzyme like superoxide disnuituse(SOD),cululase(CAT),glutathione reductase(CKD),glutathione peroxidase(GPX),glutalhione-S-transferase(GST)and lipid peroxidation(LPO)were estimated in liver homogcnatc.Results:A significant decrease in SGPT,SCOT and ALP levels was observed in all drug treated groups as compared to thioacetamide group(P<0.001) and in case of antioxidant enzyme a significant(P<0.001) increase in SOD.CAT,GRD,GPX and GST was observed in all dmg treated groups as compared with thioacetamide group.But in case of LPO a significant(P <0.001) reduction was observed as compared to toxic control group.Conclusions:DCSE has contributed lo the reduction of oxidative stress and the protection of liver in experimental rals.展开更多
Colorectal cancer(CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer c...Colorectal cancer(CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog(SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a stepwise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virusdirected enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.展开更多
A rapid, sensitive, selective and validated reverse phase high-performance liquid chromatography (RP-HPLC) method for the estimation of paclitaxel in micro-sample of rat plasma and in culture of cancer cells was per...A rapid, sensitive, selective and validated reverse phase high-performance liquid chromatography (RP-HPLC) method for the estimation of paclitaxel in micro-sample of rat plasma and in culture of cancer cells was per- formed in this study. The mobile phase consisted of an (80: 20: 0.1, v/v/v). Column elution at a flow rate of 1 optimized mixture of methanol:water: trifluroacetic acid mL/minute with UV detection at 225 nm at room tern- perature was used. The RP-HPLC method was successfully applied for the determination of paclitaxel in plasma samples and in culture of cancer cells with nano-quantity of estimation. The validation studies were performed in accordance with the International Conference on Harmonization (ICH) guidelines. The intra- and inter-day pre- cision showed that the coefficients of variation ranged from 1.07% to 4.27% at different levels of concentrations. To the best of our knowledge, this study also reported for the first time the optimization of different solvents for effective extraction of paclitaxel wherein tert.-butyl methyl ether (TBME): diethyl ether (DEE) in 50:50 v/ v composition was found most efficient with extraction efficiency ranging between 77.99% and 91.74% and be- tween 76.14 and 93.66% in the plasma and cell culture, respectively. This proposed method was successfully ap- plied to study the pharmacokinetics of paclitaxel and the influence of verapamil and all-trans retinoic acid (atRA) on paclitaxel pharmacokinetics in rat models. This proposed method might emerge as a valuable aid in the labo- ratory monitoring of paclitaxel in a variety of in vitro as well as in vivo scenarios.展开更多
Colorectal cancer(CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapiesare the conventional four approaches which are currently used for t...Colorectal cancer(CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapiesare the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor(epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.展开更多
Objective:To synthesis 2-substituted-4,5-diphenyl-N- alkyl imidazole derivatives,and evaluate their antibacterial activity.Methods:A mixture of benzil(10 mmol) and ammonium acetate(0.1 mol)(immediately fused) in...Objective:To synthesis 2-substituted-4,5-diphenyl-N- alkyl imidazole derivatives,and evaluate their antibacterial activity.Methods:A mixture of benzil(10 mmol) and ammonium acetate(0.1 mol)(immediately fused) in glacial acetic acid(25 mL) was stirred at 80-100℃for 1 h under nitrogen atmosphere(to prevent incorporation of any atmospheric impurities and moisture). Substituted aldehydes(10 mmol) in glacial acetic acid(5 mL) was added drop-wise over a period of 15-20 min at the same temperature and stirred for another 4 h,the progress of the reaction was monitored by TLC test using ethyl acetate as eluent.The newly synthesized compounds were characterized by IR,<sup>1</sup>HNMR,<sup>13</sup>CNMR and by mass spectroscopy.Results:All the synthesized compounds were confirmed by spectroscopical techniques and evaluated for antimicrobial activity against Staphylococcus aureus(S.aurius),Bacilus subtilus(B.subtilus),and Escheria coli (E.coli).These compounds showed antibacterial activity(zone of inhibition) against S.aurius ranged from 3 mm to 9 mmin diameter,B.subtilus,4 -8 mm,and E.coli 5 -12 mm.Out of 2a-2e, only 2a and 2b showed some sort of activity but none of them had considerable activity compared with that of the standard.Conclusions:All the synthesized compounds show moderate activity against the tested bacteria S.aurius,B.subtilus,and E.coli.So,further structural modification is necessary to improve the antibacterial action of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives.展开更多
Introduction: H. pylori is a primary pathogen isolated by Warren and Marshall in 1983. They called it as Campylobacter Pylori and in 1989 Goodwin et al. renamed it as Helicobacter pylori. Helicobacter pylorus is one o...Introduction: H. pylori is a primary pathogen isolated by Warren and Marshall in 1983. They called it as Campylobacter Pylori and in 1989 Goodwin et al. renamed it as Helicobacter pylori. Helicobacter pylorus is one of the responsible factors for causing gastritis, Peptic ulcer disease and is strongly associated with gastric carcinoma and gastric Malt lymphoma. Materials and Methods: In this study 300 biopsies were collected at Deccan College of Medical Sciences and Allied Hospitals, Hyderabad, India. Of these, 101 patients had peptic ulcer, 95 patients had gastritis and 4 had gastric carcinoma. A total of four gastric biopsy specimens were collected. One was used for culturing H. pylori, one for histological lesions and the remaining two one each from the antrum & corpus was collected in phosphate buffered saline for the DNA analysis. Results: Helicobacter pylori were isolated from many of the biopsies and the identification of Helicobacter pylori was confirmed in 200 biopsies with colony characteristics, Biochemical tests, and 16S rRNA amplification. The presence of VacA marker was detected by using appropriate primers. From the data obtained in our study, in a total of 169/200 isolates s1 region was found in 84.1% and s2 was found in 36/200 i.e. 18% of the isolates. In the middle region, m1awas found in 60/200 which was 30%, m1b was found in 60/200 i.e. 60% and m2 was found in 114/200 i.e. 57.1% of the isolates. Conclusion: Thus, VacA detection might be helpful for determination of which patients are at highest risk for severe clinical outcomes such as duodenal ulcer, gastric ulcer or gastric carcinoma and eventually, to define strategies for the treatment or prevention of H. pylori infection.展开更多
Objective:Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS.There-fore, HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with dif...Objective:Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS.There-fore, HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with different physicochemical parameters.Methods:In the present work,quantitative structure activity relationship studies were performed on a series of benzodithiazines as HIV-1 integrase inhibitors using the modeling software Win CAChe version 6.1.Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated for statistical significance and predictive power by internal and external validation.Results:The best QSAR models were having good correlation coefficient (r) with low standard error of estimation(SEE) and cross validated square of correlation coefficient (q^2 ).The robustness of the models was checked by Y-randomization test and they were identified as good predictive models.The model for HIV integrase(wt) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(Z) of molecules leads to reduce 3’processing and strand transfer inhibitory activity, substitution with high electro positive groups is conducive for the 3’processing inhibitory activity,and the increase in heat of formation is favorable for 3 -processing and strand transfer inhibitory activity.Conclusion: The model for HIV integrase(C65s) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(X) of molecules leads to reduce 3’processing and strand transfer inhibitory activity,and the substitution with high hydrophobic groups is conducive for the 3’processing and strand transfer inhibitory.展开更多
Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All th...Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.展开更多
Objective: A comparative analysis on transmission of Helicobacter pylori in people who consumed food prepared in both hygienic and unhygienic conditions. Method: The study was carried out in 1000 people across India. ...Objective: A comparative analysis on transmission of Helicobacter pylori in people who consumed food prepared in both hygienic and unhygienic conditions. Method: The study was carried out in 1000 people across India. The Ratio of Male: female was 700: 300 with age group ranging from 20 - 39. Three gastric biopsies were collected for identification of Helicobacter pylori. PCR (Polymerase Chain Reaction) amplification was done by using 16srRNA primers. Result: The analysis showed the prevalence of H. pylori as 70.8% in individuals frequently consuming food prepared under less hygienic condition (street vendor’s food) whereas 60% (less prevalence) in individuals consuming food prepared under hygienic conditions. Conclusion: The results showed that most of the food that we consume daily is not involved much in the transmission of Helicobacter pylori. The study also showed that the street vendor’s food is not directly involved in the transmission of this bacterium. The unhygienic preparation of food and poor personal hygiene play a vital role in the transmission of these bacteria.展开更多
Introduction: The importance of H. pylori as an etiological agent in gastroduodenal disease had suggested antibiotic treatment as a main target for the elimination of infection. The successful eradication of H. pylori...Introduction: The importance of H. pylori as an etiological agent in gastroduodenal disease had suggested antibiotic treatment as a main target for the elimination of infection. The successful eradication of H. pylori infection was shown to resolve the gastritis, dramatically accelerate ulcer healing, reduce ulcer recurrence and the prophylactic effect on the recurrence of ulcer bleeding. Materials and Methods: In the present study a total six antimicrobial agents such as Ciprofloxacin, Metronidazole, Norfloxacin, Tetracyclin, Amoxycillin and Clarithromycin were used against 100 clinical isolates from patients with peptic ulcer, and non-ulcer dyspepsia. H. pylori was isolated from the gastric biopsies obtained from the clinical subjects. Results: Results of our study showed 100% resistance to Metronidazole (MIC > 256 μg/ml). 97% of the isolates were observed sensitive to Ciprofloxacin (MIC 0.38 μg), whereas Tetracyclin showed 96% sensitivity (MIC 0.25 μg - 0.125 μg). Resistance to amoxycillin, Norfloxacin, and Clarithromycin were 80%, 38% and 76% respectively (MIC > 256 μg/ml). Conclusion: It is observed that 96% - 97% of the clinical isolates were sensitive to Tetracycline and ciprofloxacin, where all isolates were found to be resistant to Metronidazole. Resistance to Amoxycillin and Clarithromycin were 80% and 76% respectively. Studies attributed the high level of resistance to the frequent use of the drugs to treat various other infections and ineffective drug control policy.展开更多
Background:Tropical forests play a crucial role as source and sink in global carbon cycle.Development and other anthropogenic activities have led to degradation of forest land,and ultimately,it results in loss of biod...Background:Tropical forests play a crucial role as source and sink in global carbon cycle.Development and other anthropogenic activities have led to degradation of forest land,and ultimately,it results in loss of biodiversity and increases concentration of CO_(2) in atmospheres.Therefore,there is urgent need to estimate regional and national level carbon stock for making forest-based policies and strategies for mitigation of CO_(2).Patchy and sporadic information is available on biomass and carbon stock of Indian forests.The paper presents a systematic review and comprehensive account of studies conducted in different forest types in India.Result:There are six major forest types found in India consisting of 15 groups and other subgroups with peculiar characteristics.Methodologies used by researchers for biomass/carbon stock estimation are destructive,nondestructive,tree inventories data,species-specific biomass estimation,and remote sensing.Majority of estimates are based on nondestructive allometric equation approach.Studies showed positive correlation between tree species,diameter at breast height,and biomass/carbon stock.Small-and medium-sized growing trees,invasive species,mixed forest,Agroforestry,and Agrosilviculture also play an important role in atmospheric carbon assimilation.The results of diverse forest carbon stock studies are broadly categorized in North,Central,and Southern India.Present review will be helpful for developing conservation policies and decision to increase carbon stock and also REDD+program for particular forest ecosystem.Conclusion:The systematic literature review was carried out to gather and summarize information from different studies conducted on forest ecosystems and quantification methods used for biomass estimation and carbon stock in different forests types and states of India.In general,great variability occurs in aboveground biomass and carbon stock on account of climatic and geographic differences.To obtain good and accurate estimations,following nondestructive approach,species-specific density-based equations are required from different habitats and also in relation to degradation status of forests.As such regional volume equations would increase error of estimations.The comprehensive account of data would be helpful to formulate strategies based on carbon sequestration in Indian forests for CO_(2) mitigation.展开更多
Objective:To investigate the effects of Chlorophytum borivilianum(CB) on sexual dysfunction, loss of body weight,and lack of libido in hyperglycemic rats induced with streptozotocin or alloxan.Methods: Wistar strain m...Objective:To investigate the effects of Chlorophytum borivilianum(CB) on sexual dysfunction, loss of body weight,and lack of libido in hyperglycemic rats induced with streptozotocin or alloxan.Methods: Wistar strain male albino rats were divided into five groups of six animals each:the control group(2% polyvinylpyrollidone solution),the streptozotocin control group(50 mg/kg),the alloxan control group(100 mg/kg), the streptozotocin + CB treated group(200 mg/kg),and the alloxan + CB treated group(200 mg/kg).O...展开更多
Solid polymer electrolyte films containing poly(vinyl alcohol) (PVA) and magnesium nitrate (Mg(NO3)2) were prepared by solution casting technique and characterized by using XRD, FTIR, DSC and AC impedance spec...Solid polymer electrolyte films containing poly(vinyl alcohol) (PVA) and magnesium nitrate (Mg(NO3)2) were prepared by solution casting technique and characterized by using XRD, FTIR, DSC and AC impedance spectroscopic analysis. The amorphous nature of the polymer electrolyte films has been confirmed by XRD. The complex formation between PVA and Mg salt has been confirmed by FTIR. The glass transition temperature decreases with increasing the Mg salt concentration. The AC impedance studies are performed to evaluate the ionic conductivity of the polymer electrolyte films in the range of 303-383 K, and the temperature dependence seems to obey the Arrhenius behavior. Transport number measurements show that the charge transport is mainly due to ions. Electrochemical cell of configuration Mg/(PVA + Mg(NO3)2) (70:30)/(12 + C + electrolyte) has been fabricated. The discharge characteristics of the cell were studied for a constant load of 100 kΩ.展开更多
This paper presents an inventory model with a constant rate of deterioration of the product,and shortages are allowed at the end of the cycle.The stock-dependent and price-sensitive demand have been considered with a ...This paper presents an inventory model with a constant rate of deterioration of the product,and shortages are allowed at the end of the cycle.The stock-dependent and price-sensitive demand have been considered with a policy of providing price discount to uplift the market demand.Preservation technology is applied to preserve the items from deterioration.The objective of this model is to maximize the total profit function by finding the optimal replenishment time,the optimal preservation technology investment and the optimal quantity.Next,we have shown that the total profit is a concave function of the replenishment time and preservation technology cost.Discount in pricing may be offered at a time of festival,season breaks down,lockdown and clearance of stock,before introducing a new product with up-gradations,etc.Numerical examples and graphical analysis are provided to explain the model.The discount policy could help any business organizations for smooth running of the business and obtain respective optimal profit.展开更多
Phyllanthus amarus plant is used in the traditional system of medicine as a hepatoprotective drug for which the majorlignans phyllanthin and hypophyllanthin are responsible.So far,no significant work has been done on ...Phyllanthus amarus plant is used in the traditional system of medicine as a hepatoprotective drug for which the majorlignans phyllanthin and hypophyllanthin are responsible.So far,no significant work has been done on the culture of this plant.Realizingthe hepatoprotective potential,the present investigation was undertaken.A cost effective process was developed for enhancingphyllanthin and hypophyllanthin utilizing the immobilization technique.HPTLC was used to compare the phyllanthin and hypophyllanthincontents in calcium alginate immobilized cells obtained from fresh grown plants and MS medium was supplemented withdifferent abiotic elicitors,under aseptic conditions for the treatment with chitosan,copper sulphate,phenylalanine and silver nitratesolution to make the whole process commercially viable.It was revealed that silver nitrate and phenylalanine at low concentrationenhances phyllanthin and hypophyllanthin yield as compared to control immobilized cell culture.The study revealed that an increase inthe content of phyllanthin and hypophyllanthin was elicitor concentration dependent and silver nitrate treatment gave a maximum yieldof hepatoprotective bioactives as compared to the other abiotic elicitors used.展开更多
In a declining market for goods,we optimize the net profit in business when inventory management allows change in the selling prices n times over time horizon.We are computing optimal number of changes in prices,respe...In a declining market for goods,we optimize the net profit in business when inventory management allows change in the selling prices n times over time horizon.We are computing optimal number of changes in prices,respective optimal prices,and optimal profit in each of the cycle for a deteriorating product.This paper theoretically proves that for any business setup there exists an optimal number of price settings for obtaining maximum profit.Theoretical results are supported by numerical examples for different setups(data set)and it is found that for every setup the dynamic pricing policy out-performs the static pricing policy.In our model,the deterioration factor has been taken into consideration.The deteriorated units are determined by the recurrence method.Also we studied the effect of different parameters on optimal policy with simulation.For managerial purposes,we have provided some“suggested intervals”for choosing parameters depending upon initial demand,which help to predict the best prices and arrival of customers(demand).展开更多
Polymer(polar/nonpolar)/metal composites(PMC)were prepared under different process conditions.In polar PMC,dipolar relaxation plays a predominant role below percolation threshold(f_(c))and anomalous low frequency disp...Polymer(polar/nonpolar)/metal composites(PMC)were prepared under different process conditions.In polar PMC,dipolar relaxation plays a predominant role below percolation threshold(f_(c))and anomalous low frequency dispersion(ALFD)becomes dominant above f_(c)while ALFD is the only likely possibility for nonpolar PMC above f_(c).The magnitude of relaxation exponents"m","p"and"n",evaluated from the experimental results using Jonscher's universal dielectric response(JUDR)laws,falls within the universal limit[0,1]with additional feature of strong dependence on volume fraction of conductor(f_(c)on).The decrease in the relaxation exponent"m"with an increase of f_(c)on is directly linked with decrease in the number of dipoles of the polymer in the composite and is accompanied by a distribution of relaxation time due to increased heterogeneity of the system.The magnitude of the relaxation exponent"n"decreases at f_(c),due to the prevalence of Maxwell–Wagner–Sillar polarization contributed by uncorrelated electrons.展开更多
文摘Objective:To assess the In vivo anlioxid Fanl and hepaloproleclive activity of metlianolic exlracl of Daucus carota(D.carota) seeds in experimental animals.Methods:Methanolic extracts of D.carota seeds is used for hepatoproleclion assessment.Oxidative stress were induced in rats by thioacetamide 100 nig/kg s.c.in four groups of rats(two test,standard and toxic control). Two test groups received D.carota seeds extract[DCSE) at doses of 200 mg/kg and 400 mg/kg. Standard group received silymarin(25 mg/kg) and toxic control received only thioacetamide. Control group received only vehicle.On the 8th day animals were sacrificed and liver enzyme like serum glutamic pyruvic transaminase(SGPT),serum glutamic-oxaloacetic transaminase(SCOT) and alkaline phosphatase(ALP)were estimated in blood serum and antioxidant enzyme like superoxide disnuituse(SOD),cululase(CAT),glutathione reductase(CKD),glutathione peroxidase(GPX),glutalhione-S-transferase(GST)and lipid peroxidation(LPO)were estimated in liver homogcnatc.Results:A significant decrease in SGPT,SCOT and ALP levels was observed in all drug treated groups as compared to thioacetamide group(P<0.001) and in case of antioxidant enzyme a significant(P<0.001) increase in SOD.CAT,GRD,GPX and GST was observed in all dmg treated groups as compared with thioacetamide group.But in case of LPO a significant(P <0.001) reduction was observed as compared to toxic control group.Conclusions:DCSE has contributed lo the reduction of oxidative stress and the protection of liver in experimental rals.
文摘Colorectal cancer(CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog(SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a stepwise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virusdirected enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.
基金supported by Senior Research Fellowship and Commonwealth Split Site Fellowship awards from the Council for Scientific Industrial Research(CSIR)New Delhi(India) and the Association of Commonwealth Universities+1 种基金UKrespectively
文摘A rapid, sensitive, selective and validated reverse phase high-performance liquid chromatography (RP-HPLC) method for the estimation of paclitaxel in micro-sample of rat plasma and in culture of cancer cells was per- formed in this study. The mobile phase consisted of an (80: 20: 0.1, v/v/v). Column elution at a flow rate of 1 optimized mixture of methanol:water: trifluroacetic acid mL/minute with UV detection at 225 nm at room tern- perature was used. The RP-HPLC method was successfully applied for the determination of paclitaxel in plasma samples and in culture of cancer cells with nano-quantity of estimation. The validation studies were performed in accordance with the International Conference on Harmonization (ICH) guidelines. The intra- and inter-day pre- cision showed that the coefficients of variation ranged from 1.07% to 4.27% at different levels of concentrations. To the best of our knowledge, this study also reported for the first time the optimization of different solvents for effective extraction of paclitaxel wherein tert.-butyl methyl ether (TBME): diethyl ether (DEE) in 50:50 v/ v composition was found most efficient with extraction efficiency ranging between 77.99% and 91.74% and be- tween 76.14 and 93.66% in the plasma and cell culture, respectively. This proposed method was successfully ap- plied to study the pharmacokinetics of paclitaxel and the influence of verapamil and all-trans retinoic acid (atRA) on paclitaxel pharmacokinetics in rat models. This proposed method might emerge as a valuable aid in the labo- ratory monitoring of paclitaxel in a variety of in vitro as well as in vivo scenarios.
文摘Colorectal cancer(CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapiesare the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor(epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.
文摘Objective:To synthesis 2-substituted-4,5-diphenyl-N- alkyl imidazole derivatives,and evaluate their antibacterial activity.Methods:A mixture of benzil(10 mmol) and ammonium acetate(0.1 mol)(immediately fused) in glacial acetic acid(25 mL) was stirred at 80-100℃for 1 h under nitrogen atmosphere(to prevent incorporation of any atmospheric impurities and moisture). Substituted aldehydes(10 mmol) in glacial acetic acid(5 mL) was added drop-wise over a period of 15-20 min at the same temperature and stirred for another 4 h,the progress of the reaction was monitored by TLC test using ethyl acetate as eluent.The newly synthesized compounds were characterized by IR,<sup>1</sup>HNMR,<sup>13</sup>CNMR and by mass spectroscopy.Results:All the synthesized compounds were confirmed by spectroscopical techniques and evaluated for antimicrobial activity against Staphylococcus aureus(S.aurius),Bacilus subtilus(B.subtilus),and Escheria coli (E.coli).These compounds showed antibacterial activity(zone of inhibition) against S.aurius ranged from 3 mm to 9 mmin diameter,B.subtilus,4 -8 mm,and E.coli 5 -12 mm.Out of 2a-2e, only 2a and 2b showed some sort of activity but none of them had considerable activity compared with that of the standard.Conclusions:All the synthesized compounds show moderate activity against the tested bacteria S.aurius,B.subtilus,and E.coli.So,further structural modification is necessary to improve the antibacterial action of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives.
文摘Introduction: H. pylori is a primary pathogen isolated by Warren and Marshall in 1983. They called it as Campylobacter Pylori and in 1989 Goodwin et al. renamed it as Helicobacter pylori. Helicobacter pylorus is one of the responsible factors for causing gastritis, Peptic ulcer disease and is strongly associated with gastric carcinoma and gastric Malt lymphoma. Materials and Methods: In this study 300 biopsies were collected at Deccan College of Medical Sciences and Allied Hospitals, Hyderabad, India. Of these, 101 patients had peptic ulcer, 95 patients had gastritis and 4 had gastric carcinoma. A total of four gastric biopsy specimens were collected. One was used for culturing H. pylori, one for histological lesions and the remaining two one each from the antrum & corpus was collected in phosphate buffered saline for the DNA analysis. Results: Helicobacter pylori were isolated from many of the biopsies and the identification of Helicobacter pylori was confirmed in 200 biopsies with colony characteristics, Biochemical tests, and 16S rRNA amplification. The presence of VacA marker was detected by using appropriate primers. From the data obtained in our study, in a total of 169/200 isolates s1 region was found in 84.1% and s2 was found in 36/200 i.e. 18% of the isolates. In the middle region, m1awas found in 60/200 which was 30%, m1b was found in 60/200 i.e. 60% and m2 was found in 114/200 i.e. 57.1% of the isolates. Conclusion: Thus, VacA detection might be helpful for determination of which patients are at highest risk for severe clinical outcomes such as duodenal ulcer, gastric ulcer or gastric carcinoma and eventually, to define strategies for the treatment or prevention of H. pylori infection.
文摘Objective:Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS.There-fore, HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with different physicochemical parameters.Methods:In the present work,quantitative structure activity relationship studies were performed on a series of benzodithiazines as HIV-1 integrase inhibitors using the modeling software Win CAChe version 6.1.Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated for statistical significance and predictive power by internal and external validation.Results:The best QSAR models were having good correlation coefficient (r) with low standard error of estimation(SEE) and cross validated square of correlation coefficient (q^2 ).The robustness of the models was checked by Y-randomization test and they were identified as good predictive models.The model for HIV integrase(wt) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(Z) of molecules leads to reduce 3’processing and strand transfer inhibitory activity, substitution with high electro positive groups is conducive for the 3’processing inhibitory activity,and the increase in heat of formation is favorable for 3 -processing and strand transfer inhibitory activity.Conclusion: The model for HIV integrase(C65s) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(X) of molecules leads to reduce 3’processing and strand transfer inhibitory activity,and the substitution with high hydrophobic groups is conducive for the 3’processing and strand transfer inhibitory.
文摘Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.
文摘Objective: A comparative analysis on transmission of Helicobacter pylori in people who consumed food prepared in both hygienic and unhygienic conditions. Method: The study was carried out in 1000 people across India. The Ratio of Male: female was 700: 300 with age group ranging from 20 - 39. Three gastric biopsies were collected for identification of Helicobacter pylori. PCR (Polymerase Chain Reaction) amplification was done by using 16srRNA primers. Result: The analysis showed the prevalence of H. pylori as 70.8% in individuals frequently consuming food prepared under less hygienic condition (street vendor’s food) whereas 60% (less prevalence) in individuals consuming food prepared under hygienic conditions. Conclusion: The results showed that most of the food that we consume daily is not involved much in the transmission of Helicobacter pylori. The study also showed that the street vendor’s food is not directly involved in the transmission of this bacterium. The unhygienic preparation of food and poor personal hygiene play a vital role in the transmission of these bacteria.
文摘Introduction: The importance of H. pylori as an etiological agent in gastroduodenal disease had suggested antibiotic treatment as a main target for the elimination of infection. The successful eradication of H. pylori infection was shown to resolve the gastritis, dramatically accelerate ulcer healing, reduce ulcer recurrence and the prophylactic effect on the recurrence of ulcer bleeding. Materials and Methods: In the present study a total six antimicrobial agents such as Ciprofloxacin, Metronidazole, Norfloxacin, Tetracyclin, Amoxycillin and Clarithromycin were used against 100 clinical isolates from patients with peptic ulcer, and non-ulcer dyspepsia. H. pylori was isolated from the gastric biopsies obtained from the clinical subjects. Results: Results of our study showed 100% resistance to Metronidazole (MIC > 256 μg/ml). 97% of the isolates were observed sensitive to Ciprofloxacin (MIC 0.38 μg), whereas Tetracyclin showed 96% sensitivity (MIC 0.25 μg - 0.125 μg). Resistance to amoxycillin, Norfloxacin, and Clarithromycin were 80%, 38% and 76% respectively (MIC > 256 μg/ml). Conclusion: It is observed that 96% - 97% of the clinical isolates were sensitive to Tetracycline and ciprofloxacin, where all isolates were found to be resistant to Metronidazole. Resistance to Amoxycillin and Clarithromycin were 80% and 76% respectively. Studies attributed the high level of resistance to the frequent use of the drugs to treat various other infections and ineffective drug control policy.
文摘Background:Tropical forests play a crucial role as source and sink in global carbon cycle.Development and other anthropogenic activities have led to degradation of forest land,and ultimately,it results in loss of biodiversity and increases concentration of CO_(2) in atmospheres.Therefore,there is urgent need to estimate regional and national level carbon stock for making forest-based policies and strategies for mitigation of CO_(2).Patchy and sporadic information is available on biomass and carbon stock of Indian forests.The paper presents a systematic review and comprehensive account of studies conducted in different forest types in India.Result:There are six major forest types found in India consisting of 15 groups and other subgroups with peculiar characteristics.Methodologies used by researchers for biomass/carbon stock estimation are destructive,nondestructive,tree inventories data,species-specific biomass estimation,and remote sensing.Majority of estimates are based on nondestructive allometric equation approach.Studies showed positive correlation between tree species,diameter at breast height,and biomass/carbon stock.Small-and medium-sized growing trees,invasive species,mixed forest,Agroforestry,and Agrosilviculture also play an important role in atmospheric carbon assimilation.The results of diverse forest carbon stock studies are broadly categorized in North,Central,and Southern India.Present review will be helpful for developing conservation policies and decision to increase carbon stock and also REDD+program for particular forest ecosystem.Conclusion:The systematic literature review was carried out to gather and summarize information from different studies conducted on forest ecosystems and quantification methods used for biomass estimation and carbon stock in different forests types and states of India.In general,great variability occurs in aboveground biomass and carbon stock on account of climatic and geographic differences.To obtain good and accurate estimations,following nondestructive approach,species-specific density-based equations are required from different habitats and also in relation to degradation status of forests.As such regional volume equations would increase error of estimations.The comprehensive account of data would be helpful to formulate strategies based on carbon sequestration in Indian forests for CO_(2) mitigation.
文摘Objective:To investigate the effects of Chlorophytum borivilianum(CB) on sexual dysfunction, loss of body weight,and lack of libido in hyperglycemic rats induced with streptozotocin or alloxan.Methods: Wistar strain male albino rats were divided into five groups of six animals each:the control group(2% polyvinylpyrollidone solution),the streptozotocin control group(50 mg/kg),the alloxan control group(100 mg/kg), the streptozotocin + CB treated group(200 mg/kg),and the alloxan + CB treated group(200 mg/kg).O...
文摘Solid polymer electrolyte films containing poly(vinyl alcohol) (PVA) and magnesium nitrate (Mg(NO3)2) were prepared by solution casting technique and characterized by using XRD, FTIR, DSC and AC impedance spectroscopic analysis. The amorphous nature of the polymer electrolyte films has been confirmed by XRD. The complex formation between PVA and Mg salt has been confirmed by FTIR. The glass transition temperature decreases with increasing the Mg salt concentration. The AC impedance studies are performed to evaluate the ionic conductivity of the polymer electrolyte films in the range of 303-383 K, and the temperature dependence seems to obey the Arrhenius behavior. Transport number measurements show that the charge transport is mainly due to ions. Electrochemical cell of configuration Mg/(PVA + Mg(NO3)2) (70:30)/(12 + C + electrolyte) has been fabricated. The discharge characteristics of the cell were studied for a constant load of 100 kΩ.
文摘This paper presents an inventory model with a constant rate of deterioration of the product,and shortages are allowed at the end of the cycle.The stock-dependent and price-sensitive demand have been considered with a policy of providing price discount to uplift the market demand.Preservation technology is applied to preserve the items from deterioration.The objective of this model is to maximize the total profit function by finding the optimal replenishment time,the optimal preservation technology investment and the optimal quantity.Next,we have shown that the total profit is a concave function of the replenishment time and preservation technology cost.Discount in pricing may be offered at a time of festival,season breaks down,lockdown and clearance of stock,before introducing a new product with up-gradations,etc.Numerical examples and graphical analysis are provided to explain the model.The discount policy could help any business organizations for smooth running of the business and obtain respective optimal profit.
文摘Phyllanthus amarus plant is used in the traditional system of medicine as a hepatoprotective drug for which the majorlignans phyllanthin and hypophyllanthin are responsible.So far,no significant work has been done on the culture of this plant.Realizingthe hepatoprotective potential,the present investigation was undertaken.A cost effective process was developed for enhancingphyllanthin and hypophyllanthin utilizing the immobilization technique.HPTLC was used to compare the phyllanthin and hypophyllanthincontents in calcium alginate immobilized cells obtained from fresh grown plants and MS medium was supplemented withdifferent abiotic elicitors,under aseptic conditions for the treatment with chitosan,copper sulphate,phenylalanine and silver nitratesolution to make the whole process commercially viable.It was revealed that silver nitrate and phenylalanine at low concentrationenhances phyllanthin and hypophyllanthin yield as compared to control immobilized cell culture.The study revealed that an increase inthe content of phyllanthin and hypophyllanthin was elicitor concentration dependent and silver nitrate treatment gave a maximum yieldof hepatoprotective bioactives as compared to the other abiotic elicitors used.
文摘In a declining market for goods,we optimize the net profit in business when inventory management allows change in the selling prices n times over time horizon.We are computing optimal number of changes in prices,respective optimal prices,and optimal profit in each of the cycle for a deteriorating product.This paper theoretically proves that for any business setup there exists an optimal number of price settings for obtaining maximum profit.Theoretical results are supported by numerical examples for different setups(data set)and it is found that for every setup the dynamic pricing policy out-performs the static pricing policy.In our model,the deterioration factor has been taken into consideration.The deteriorated units are determined by the recurrence method.Also we studied the effect of different parameters on optimal policy with simulation.For managerial purposes,we have provided some“suggested intervals”for choosing parameters depending upon initial demand,which help to predict the best prices and arrival of customers(demand).
文摘Polymer(polar/nonpolar)/metal composites(PMC)were prepared under different process conditions.In polar PMC,dipolar relaxation plays a predominant role below percolation threshold(f_(c))and anomalous low frequency dispersion(ALFD)becomes dominant above f_(c)while ALFD is the only likely possibility for nonpolar PMC above f_(c).The magnitude of relaxation exponents"m","p"and"n",evaluated from the experimental results using Jonscher's universal dielectric response(JUDR)laws,falls within the universal limit[0,1]with additional feature of strong dependence on volume fraction of conductor(f_(c)on).The decrease in the relaxation exponent"m"with an increase of f_(c)on is directly linked with decrease in the number of dipoles of the polymer in the composite and is accompanied by a distribution of relaxation time due to increased heterogeneity of the system.The magnitude of the relaxation exponent"n"decreases at f_(c),due to the prevalence of Maxwell–Wagner–Sillar polarization contributed by uncorrelated electrons.