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Background: Colorectal cancer is a devastating disease with a dismal prognosis which is heavily hampered by delayed diagnosis. Surgical resection, radiation therapy and chemotherapy are the curative options. Due to few therapeutic treatments available i.e., mono and combination therapy and development of resistance towards drug response, novel and efficacious therapy are urgently needed. Objective: In this study, we have studied the potential of histone deacetylase inhibitors in colorectal cancer. Results: Histone deacetylase inhibitors (HDACIs) are an emerging class of therapeutic agents having potential anticancer activity with minimal toxicity for different types of malignancies in preclinical studies. HDACIs have proven less effective in monotherapy thus the combination of HDACIs with other anticancer agents are being assessed for the treatment of colorectal cancer. Conclusion: The molecular mechanism emphasizing the anticancer effect of HDACIs in colorectal cancer was illustrated and a recapitulation was carried out on the recent advances in the rationale behind combination therapies currently underway in clinical evaluations.

Cancer is a disease without limits turning out to be prime cause for raising death toll around the world. Several treatment strategies including chemotherapy, surgery and radiotherapy are being employed worldwide to combat this disease. Due to the unwanted effects of currently available therapies, scientific community is immensely interested in exploring newer alternative pathways. Fluoroquinolones have been employed as potent anti-microbial agents for last few decades and now being looked up as potential therapeutic agents in the other ailments also. Several research endeavours are carried out in different parts of the world to focus on the prospective role of fluoroquinolones in carcinogenesis and mutagenesis. This article is an earnest attempt to present recent research work carried out on fluoroquinolones in the context to cancer treatment therapies.

Histone deacetylase inhibitors (HDACi) have been enthusiastically investigated as a novel generation of chemotherapeutics for cancers usually called as epigenetic therapeutics. Histone deacetylases have been found to influence cellular function by catalyzing the removal of acetyl groups from -N-acetylated lysine residues of several protein substrates including histones, transcription factors, α-tubulin, and nuclear importers. Cyclic peptides represent the most structurally complicated and diverse class of histone deacetylase inhibitors. Each subtype of the Histone Deacetylase (HDAC) family perform a distinct role in the gene expression and cyclic peptides with their plentiful set of surface contacts, zinc binding group and macrocyclic cap, can target enzyme precisely through adequate modulation of the amino acid configurational and structural assortment. The present article summarizes current status of different peptide based macrocyclic compounds being developed as HDACi for the treatment of cancer.

Quinazolinone scaffold has been considered as a magic moiety possessing myriad spectrum of medicinal activities. Diversity of biological response profile has attracted considerable interest of several researchers across the globe to explore this skeleton for its assorted therapeutic significance. Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, CNS depressant, antiinflammatory, antihistaminic, anticancer and so on. Moreover, the nucleus constitutes an integral structural component in a number of drugs currently employed in several clinical therapies. The present paper is an earnest attempt to provide an insight view on the current medicinal aspects of quinazolinone heterocycles alongwith brief discussion of their chemistry.

Sepsis, a progressive immunological, metabolic and cardiovascular disorder, is a major cause of morbidity and mortality in Intensive care units (ICU) worldwide. Models simulating sepsis, such as endotoxemia, peritonitis, cecal ligation and puncture, provide substantial molecular and cellular evidence for structural and functional damage to cardiac myocytes during sepsis. Clinical evidence suggests abnormal left ventricular impairment and cardiac contractile dysfunction during sepsis. Norepinephrine (NE), a clinically approved positive inotrope traditionally used in ICUs for hemodynamic support, can also cause increased lactate levels and cardiomyocyte toxicity during early stages of sepsis. Our recent results demonstrated that sepsis-induced myocyte dysfunction (SIMD) is associated with decreased time of deformation and loss of contractile activity in the myocytes. The data further support the involvement of the apoptotic pathway, particularly mitochondrial-mediated intrinsic apoptosis cascade in sepsis-induced myocardial dysfunction. The recent data from our laboratory demonstrated that SIMD is a potentially life threatening event which can be exacerbated by the use of positive inotropes such as NE, which are ideally used in the management of sepsis.

Research and development for novel substances possessing anti-infective activity have attracted considerable attention due to the escalating resistance towards conventional antibiotics. Therefore, the discovery and development of effective antimicrobial drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. Triazole scaffold has been consistently rewarded as a promising versatile lead molecule with a pivotal position in modern medicinal chemistry. The literature reveals that this heterocyclic moiety has drawn attention of the chemists, pharmacologists, microbiologists and other researchers owing to its indomitable biological potential as anti-infective agents. The present communication is a cogent attempt to review the chemistry and antimicrobial activities of triazole derivatives reported in recent scientific literature. The biological profiles of these new triazole derivatives represent a fruitful matrix for further development as promising and superior anti-infective medicinal agents.

In the present paper, the simulation of the mechanical responses of individual carbon nanotubes treated as thin shells has been done using finite element method. The resonant frequencies of the fixed free single wall carbon nanotube have been investigated. This analysis explores the resonant frequency shift of Single Walled Carbon Nanotubes caused by the changes in the size of Carbon Nanotube in terms of length as well as the attached masses. The results showed the sensitivity of the single walled carbon nanotubes to different masses (attached to the tip and at the centre of Single Walled Carbon Nanotube) and different lengths. It has also observed that the mass sensitivity of carbon nanotube can reach upto 10-21 g of attached mass and the mass sensitivity increases when smaller size nanotubes resonators are used in mass sensors. In order to explore the suitability of the Single walled carbon nanotube as a mass detector device, the simulation results of the resonant frequency of fixed free Single Walled Carbon Nanotube are compared to the published experimental data. It is shown that the FEM simulation results are in good agreement with the experimental data and hence the current modelling approach is suitable as a coupled-field design tool for the development of Single Walled Carbon Nanotube -based NEMS applications.

ABSTRACTThere is much interest in using renewable energy sources such as wind, wave, and sun to generate electrical energy. The local power companies, Trinidad & Tobago Electricity Commission (TTEC) and Powergen (Power Generation Company of Trinidad & Tobago), have expressed an interest in wind power generation and integration to supplement its conventional fossil fuel, i.e., natural gas, approach. The Caribbean island. Of Tobago was chosen for investigation of its wind power potential mainly due to its better alignment to the prevailing winds, i.e., the North East Trades, than Trinidad.This article focuses on an optimal selection method of matching a Wind Energy Conversion System (WECS) to wind patterns, such as Tobago. It incorporates various techniques and economical decisions which are to be considered and used when sizing available commercial WECSs to potential wind patterns.

BACKGROUND: Endoscopic sphincterotomy has been shown to inhibit stone formation in the gall bladder of experimental animals. AIMS: To investigate the alterations in bile composition and gall bladder motility after endoscopic sphincterotomy. PATIENTS: A study was performed of gall bladder bile composition and gall bladder motility in patients with gallstone disease ((n = 20; age 40-60 years, median age 55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had received endoscopic sphincterotomy for common bile duct stones. Age and sex matched disease controls comprised 20 patients with gallstone disease but without stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and diseased gall bladder without gall bladder calculi (n = 10)). METHODS: Gall bladder motility was assessed by ultrasound. Duodenal bile collected by nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid infusion was analysed for cholesterol, phospholipid, and bile acid concentrations, cholesterol saturation index, and nucleation time. RESULTS: There was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4 (2.5) ml; p < 0.001) and mean (SEM) residual volume (4.34 (0.9) ml v 14.7 (0.98) ml; p < 0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6 (5.52)%; p < 0.001) and mean (SEM) rate constant of gall bladder emptying (-0.031/min v -0.020/min; p < 0.01) in patients who had been subjected to endoscopic sphincterotomy. Median nucleation time was significantly longer (17 days v 6 days; p < 0.006) in treated patients. There was a reduction in total mean (SEM) lipid concentrations (6.73 (0.32) g/dl v 7.72 (0.84) g/dl; p < 0.05), cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p < 0.001) and CSI (0.72 (0.15) v 1.32 (0.31); p < 0.001). There was no significant change in mean (SEM) phospholipid (25.6 (3.5) mmol/l v 23.4 (6.28) mmol/l) and bile acid (93.7 (7.31) mmol/l v 105.07 (16.6) mmol/l) concentrations. CONCLUSIONS: After endoscopic sphincterotomy there was enhanced contractility of the gall bladder, accompanied by a prolongation of nucleation time and reduction in cholesterol saturation index.

Juvenile nasopharyngeal angiofibroma is a benign disease affecting young males with a propensity to invade intracranially and into the orbit along preformed pathways. Complete surgical excision is the mainstay of management. Patients with multiple recurrences along with tumour extension into skull base and orbit can be considered for external beam radiation as either adjuvant or definitive treatment. Possibility of radiation-induced malignancy has been speculated by many authors, proof of which exists in only two studies so far. This report focuses on radiation-induced leiomyosarcoma in a patient with recurrent juvenile nasopharyngeal angiofibroma.

The development of new therapies to treat hypertension and cardiovascular diseases. A series of 2,4,5-trisubstituted triazolinones aryl and nonaryl derivatives were subjected to Group-based QSAR, k-nearest neighbour molecular field analysis, and pharmacophore mapping. Multiple linear regression (MLR) methodology coupled with feature selection method namely simulated annealing, was applied to derive Group based QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The best physicochemical descriptors, namely, R1chiV1, R2T_N_O_3, R2chlorines count, R2T_C_N_4, and R2SssNHE index, contribute significantly to the biological activity. The statistically significant best Group-based QSAR model has r2=0.8357 and q2=0.7266 with pred_r2=0.8138. The 3D-QSAR studies were performed using the simulated annealing selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2=0.7461 and predicate activity pred_r2=0.7790 were obtained. Contour maps using this approach showed that steric, electrostatic, and hydrophobic effects dominantly determine binding affinities. Pharmacophore hypotheses were generated by the mol sign module and found to contain common features like hydrogen bond donor acceptor, donor, positive, negative ionizable, and hydrophobic features. This model can be used for preliminary screening of large number of substituted 3H-1,-2,-4 triazolinone aryl and nonaryl derivatives. The information rendered by 3D-QSAR models may lead to a better understanding of structural requirements of triazolinone aryl and nonaryl derivatives and also aid in designing novel potent antihypertensive molecules.

Little data is available on microsatellite dynamics in the duplicated regions of the rice genome, even though efforts have been made in the past to align genome sequences of its two sub-species. Based on the coordinates of duplicated sequences in the indica genome as available in the public domain, we identified microsatellites in these regions. CCG and GAAAA repeats occurred most frequently. In all, 259 microsatellites could be identified in the duplicated sequences using the criteria of minimum 90% alignability spread over a minimum of 1 Kb sequence. More than 25% of the repeats in duplicated regions occurred in the genic sequences. Only 45 (17%) of these 259 microsatellites were found conserved in the duplicated paralogues. Among these repeats, 40% maintained both sequence and length conservation. The effect of mutability of nearby regions could also be clearly seen in microsatellite regions. The overall purpose of this study was to investigate, whether microsatellites follow an independent course of evolutionary dynamics subsequent to events like genome reshuffling that simply drives these elements to different locations in the genome. To the best of our knowledge, this is the first comprehensive analysis of microsatellite conservation in the duplicated regions of any genome.

The daily dietary intakes and total contents of Cs and I in skeletal muscle and thyroid, respectively, for an average Indian adult were estimated by determining their concentrations in the total cooked diet and tissue samples using instrumental neutron activation analysis. These data were then used to predict the biological half-lives of Cs and I and their radioactive counterparts for the Reference Indian Man. The predicted biological half-lives of Cs and I for Reference Indian Man were found to be comparable with the reported values for the ICRP Reference Man.

The potential internal occupational exposure encountered as a consequence of the 232Th-233U fuel cycle are likely to arise predominantly from the inhalation of 232Th, 233U and (232Th + 233U) compounds of absorption Types M and S. In the past, although direct and indirect methods for assessments of internal exposure to 232Th and its daughters were developed, standardised and employed, no such attempts have been made with regard to 233U and 233U+232Th. Therefore, feasibility studies for assessing internal exposures to 233U have been conducted using three methods: urine bioassay, in vivo counting and measurement of thoron gas in the exhaled breath of a worker. This paper describes details of these studies and discusses the results obtained.

A computational study of the urinary excretion rates for 239Pu has been carried out using a methodology which involved the solution of a complete compartmental model describing the biokinetic behaviour of inhaled plutonium aerosols in the human body. The methodology, after proper validation, was applied to investigate the dependence of urinary excretion rates for 239Pu on the transfer rates given in the complete compartmental model. For this purpose, the default values of the transfer/absorption rates were modified by factors of 2 and 4 and urinary excretion rates were computed on 1, 10, 100, 1000 and 10,000 d post-intake. The percentage variations in the urinary excretion rates as a result of the modified transfer rates were computed for exposures to Type M and S aerosols of 239Pu. These results facilitated the identification of parameters significantly affecting the short-term and long-term urinary excretion rates. In addition, time variations of the predicted ratios of 239Pu activity in daily urine to that in blood (excretion ratios) were studied for the three biokinetic models of plutonium: the ICRP 67 model, the modified ICRP 67 model with the compartment ST1 to urinary bladder removed and Luciani & Polig's model. All the computational results are presented and discussed in this paper.

In vivo monitoring techniques are needed to estimate the amount of an actinide in the skeleton in addition to that in the lungs and liver. Skull counting with external detectors has been a standard procedure for this purpose. Realistic skull phantoms are normally used to calibrate the counting systems. However, the fabrication of realistic phantoms is extremely difficult and expensive. Therefore, a theoretical approach based on Monte Carlo methods in conjunction with a Cristy mathematical phantom has been examined for assessing skull burdens of actinides. A computer program that generates surface sources of actinides on the skull and simulates low-energy photon transport in the heterogeneous media of the head region of the Cristy phantom was developed for this purpose. The program determines the observable pulse height spectrum of the detector and the corresponding calibration factors for different counting geometries. The computer program was used to generate the pulse height spectra and the corresponding calibration factors of 20 cm and 15 cm diameter phoswich detectors, each positioned on the left and right sides and on the top of the head region of the Cristy phantom, whose skull surfaces were assumed to have a uniform distribution of 241Am. The computed calibration factor for a counting geometry consisting of three phoswich detectors (15 cm diameter each) surrounding the phantom's skull was found to be in excellent agreement with the experimental results obtained for the same geometry using a realistic phantom skull phantom. This provided a validation of the realistic design of the skull in the Cristy phantom, implying that the results reported in this paper could be used for in vivo measurements of skull burdens of 241Am for the stated counting geometry.

A standard shielded chair whole-body monitor has been developed as a computer controlled, unattended, walk-in-type of whole-body monitor for internal dosimetry of radiation workers. A radiation worker enters his personal computer code through the attached computer terminal and follows a few instructions on the screen. The chair door then opens automatically and after the worker has positioned himself into the counting geometry in the chair, the door closes. At the end of the whole-body monitoring for a pre-set time, the chair door opens again and the worker moves out. The monitoring data acquired on a 4K-MCA is saved in the computer memory automatically and the chair door closes again making it available for the monitoring of the next worker. The system also gives audio instructions to the worker to occupy the chair and to move out after the counting is over. A system supervisor can come at any convenient time and get a print out of the monitoring report in the standardised format or carry out any detailed analysis if required. The system has the software for calculating intakes and the committed effective doses using the latest ICRP methodologies, from the measured retained activities of the various important fission and activation products like 137Cs, 131I, 60Co, 125Sb etc. This type of system with trained staff is also expected to be of value in case of emergencies as a quick monitoring system.

After Endoscopic sphincterotopy (ES) gallbladder motility increases leading to expulsion of crystals and stones. But this is not a universal phenomenon. We evaluated cholangiographic findings in patients emptying their gallbladder after ES for common bile duct (CBD) stones. Cholangiographic features of twenty patients expelling gallbladder calculi after ES were studied. Controls included 20 age and sex matched patients with gallstones and CBD stones, who did not expel gallstones after ES. Of 20 cases in study group, 9 recovered more than 20 stones each in the stool within 7 days of ES. Repeat ERCP showed empty gallbladder in all, whereas CBD was full of stones in 11 of the 20 cases. In the study group, low insertion of the cystic duct was more common (10 vs 0, p<0.04), the cystic duct made a narrow angle (20±5° vs 50±10°, p<0.04) with CBD before insertion and cystic duct diameter was higher (5 mm vs 2.5 mm, p<0.04) as compared to controls. We conclude that in patients undergoing ES with intact gallbladder and small gallbladder calculi, spontaneous emptying of gallbladder calculi occurs, if cystic duct is wider, has low insertion and makes narrow angle with CBD before insertion.

Bleeding from antral and duodenal varices is an uncommon feature in patients with portal hypertension. We report a patient with cirrhosis and portal vein thrombosis, who had a massive bleed from antral and duodenal varices. Bleeding was controlled with endoscopic injection of varices using histoacryl. Endoscopic treatment and the relatively uncommon occurrence of antral and duodenal varices are highlighted.

Extrahepatic portal vein obstruction has been reported to be associated with tumors of liver, bile ducts and pancreas. We report two cases, one with gastric leiomyosarcoma and another with Non Hodgkin’s lymphoma, complicated by portal vein block and presenting with gastric variceal bleeding. Portal vein block in both cases was due to direct vascular infiltration. Development of portal hypertension posed difficulties in management.

Isolated bile duct injuries after blunt abdominal trauma are rare. Surgery is the usual mode of treatment. We report a patient with a right hepatic duct injury following blunt abdominal trauma who was managed successfully by endoscopic papillotomy.

The stability of the plane interface separating two viscous superposed conducting fluids through porous medium is studied when the whole system is immersed in a uniform horizontal magnetic field. The stability analysis is carried out for two highly viscous fluids of equal kinematic viscosities, for mathematical simplicity. It is found that the stability criterion is independent of the effects of viscosity and porosity of the medium and is dependent on the orientation and magnitude of the magnetic field. The magnetic field is found to stabilize a certain wave number range of the unstable configuration. The behaviour of growth rates with respect to viscosity, porosity and medium permeability are examined analytically.