Retrospective Analysis of Giant Cell Tumor Lower End Radius Treated with En bloc Excision and Translocation of Ulna.

BACKGROUND: Distal end of radius is third most common site for GCT of long bones and 1% of these metastasize mostly to lungs. Reconstruction methods commonly used are fibula (vascularized and nonvascularized), centralization of ulna, translocation of ulna, and endoprosthetic replacement. We report the outcome of series of twenty cases where we did en bloc excision of tumor with translocation of ulna. MATERIALS AND METHODS: Twenty cases of giant cell tumor (GCT) of lower end of radius were included in this retrospective study. The mean age of patients was 33.15 years (range 21-55 years). We had 14 of Campanacci Grade III and 6 of Grade II. Preoperative radiographs and magnetic resonance imaging of the involved wrist and forearm were done. RESULTS: Of all twenty patients, 14 were males and 6 were females. Mean followup duration was 3.9 years (range 1.5-17 years). Mean grip strength of involved side as a percentage of normal side was 71% (range 42%-86%) and the actual mean value for operated side was 29 kg as compared to 40 kg for normal side. The average range of forearm movement was supination 80.25° (60°-90°) and pronation 77.5° (70°-90°). No patient was dissatisfied as far as cosmesis was concerned. DISCUSSION: In our opinion considering the propensity to recur with more aggressiveness after recurrence, en bloc excision with translocation of ulna has become a standard treatment option for GCT of lower end of radius, with advantages of better functional outcomes, retained vascularity, and elimination of risk of donor site morbidity.

Feed consumption, diet digestibility and mineral utilization in captive blackbuck (Antelope cervicapra) fed different levels of concentrates.

A feeding trial was conducted to know the level of concentrates in the diet of Antelope cervicapra at which diet digestibility and mineral utilization were optimum. Fifteen blackbucks (25-33 kg BW) were distributed into three groups of five each. Fresh oat (Avena sativa) and berseem (Trifolium alexandrinum) fodders were offered ad libitum to all the animals. In addition, animals in groups II and III received concentrate mixture at the rate of 0.5 and 1% of BW, whereas animals in group I received no concentrates. As the level of concentrates increased, consumption of fodder decreased resulting in decreased consumption of neutral detergent fibre (NDFom), acid detergent fibre (ADFom), hemicellulose and cellulose. However, overall total dry matter (DM) and organic matter (OM) intake was not significantly different between the groups. Digestibility of DM, OM and gross energy (GE) increased while that of NDFom and ADFom decreased with increased level of concentrates in the diet. Intake of P, Zn, Cu and Mn increased with increased level of concentrate supplementation; however, consumption of Ca and Fe followed the reverse trend. Absorption of P and Zn increased with increased level of concentrate supplementation. Serum concentration of Zn increased when concentrate was supplemented at the rate of 0.5% BW beyond which there was no further improvement. Increasing the level of concentrates in the diet was resulted in increased serum glucose and cholesterol levels. Forage-only diet was inadequate in supply of energy, P and zinc. Supplementation of concentrates at the rate of 0.5% BW was able to meet the requirement of these nutrients. Supplementation at the rate of 1% BW supplied energy and P in excess of requirement. It was concluded that the feeding of concentrates to the captive blackbuck fed forage-based diets should be restricted to 0.5% of BW.

Feed consumption, nutrient utilization and serum metabolite profile of captive blackbucks (Antelope cervicapra) fed diets varying in crude protein content.

A feeding trial was conducted to determine the optimum level of crude protein (CP) in the diet of captive blackbuck (Antelope cervicapra) in which feed consumption and nutrient utilization are maximal. Fifteen blackbucks (BW 25-34 kg) were distributed into three groups of five each in an experiment of 75-days duration including a digestion trial of 5-day collection period. All the animals were offered 200 g of concentrates and fresh maize fodder ad libitum. The overall CP content of the three respective diets was 6.9%, 10.4% and 12.7%. Blood samples were collected on the last day of the experiment. Intake and digestibility of CP increased (p < 0.01) with the increased level of CP in the diet. Feed consumption and nutrient intake were not significantly different among the groups. However, digestibilities of most of the nutrients were higher in the 10.4% CP diet than in the 6.9% CP diet. The endogenous loss of nitrogen was similar among the groups. Based on the endogenous losses, minimum N requirement was calculated to be 776 mg/kg BW(0.75) /day, and to meet this requirement, diet must contain at least 8.27% CP. Serum urea nitrogen concentration increased (p < 0.01) with increased level of dietary CP. Serum level of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase was higher (p < 0.05) in the group fed 6.9% CP diet. Animals in the group fed low protein diet also lost body mass during the experimental period. It was concluded that a diet containing 10.4% CP was optimum for maximizing nutrient utilization without any adverse effect on voluntary feed consumption and serum metabolite profile of blackbucks.

Current perspective of HCV NS5B inhibitors: a review.

Hepatitis C virus (HCV) infection has emerged as one of the most significant disease to affect humans. Despite its large medical and economical impact, there are no vaccines or efficient therapies without major side effects. The HCV non-structural protein 5B (NS5B) is the RNA-dependent RNA polymerase responsible for the complete copy of the RNA viral genome and is a target of choice for the development of anti-HCV drugs. Although many small molecules have been identified as allosteric inhibitors of NS5B, very few are active in clinical applications. Developments in the field have prompted us to review the research work on HCV NS5B polymerase inhibitors, especially their structure activity relationships and molecular modeling studies. This review will focus on the journey of drug discovery of HCV NS5B inhibitors covering both nucleoside and non-nucleosides.

A QSAR study on a series of simplified digitalis-like compounds acting on Na+,K(+)-ATPase.

Among the cardiotonics (agents against congestive heart failure), the most important group is of the digitalis cardiac glycosides, but since these compounds suffer from a low therapeutic index, attention has been paid to investigating safer cardiotonic agents through the inhibition of Na+,K(+)-ATPase, the mechanism by which the digitalis cardiac glycosides elicit their action. Recently, a series of perhydroindenes were studied for their Na+,K(+)-ATPase inhibition activity. We report here a QSAR study on them to investigate the physicochemical and structural properties of the molecules that govern their activity in order to rationalize the structural modification to have more potent drugs. A multiple regression analysis reveals a significant correlation between the Na+,K(+)-ATPase inhibition activity of the compounds and Kier's first order valence molecular connectivity index of their R5-substituents and some indicator parameters, suggesting that the R5-substituents of the compounds containing atoms with low valence and high saturation and the R1-substituents having =N-O- moiety will be conducive to the activity.

Recent advances in studies on hydroxamates as matrix metalloproteinase inhibitors: a review.

Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc- containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. The inappropriate expression of these MMPs constitutes part of the pathogenic mechanism in several diseases, therefore they are subject to inhibition. They can be inhibited by endogenous proteinase inhibitors such as 2-macroglobulin or by the family of tissue inhibitors of metalloproteinases (TIMPs), which are glycoproteins of molecular weight 21-30 kDa, consisting of 184-194 amino acid residues. Recently, many different classes of synthetic inhibitors have been developed in which the hydroxamic acidbased class of compounds (hydroxamates) have been most widely studied, as their hydroxamic acid group (CONHOH) enables them to act as a bidentate ligand with the zinc ion present in MMPs, leading to much stronger interaction with the receptor as compared to any other class of inhibitors. The present review describes in detail the recent development on this class of MMP inihibitors. Compounds like 12,17e, f, g and h, 45j, 45k, 50f, 62a, 63a, and 63b have been reported to be highly promising for further development.

Sjogren-Larsson syndrome: A case report of a rare disease.

We report a case of Sjogren-Larsson syndrome with clinical profile (spastic diplegia, icthyosis, mental retardation) and imaging findings on magnetic resonance imaging.

Design and development of anti-hepatitis B virus agents.

Hepatitis B virus (HBV) infected hepatitis is the common infectious disease. In the World Conservative Estimate Plan, the number of persons chronically infected with HBV is more than 300 million. Current regimen of treatment is far from satisfactory, as it is associated with certain side effects and viral resistance capacity. Therefore, a serious attention has recently been paid to the design and development of new potent anti-HBV agents. A variety of drugs have been synthesized and screened for their anti-HBV effects. These include nucleosides, natural compounds, quinolines, benzodiazepines, indoles, etc. Many of them are in wide trend in current treatment regimen. In this review, we have presented the recent development on the design and development of all categories HBV inhibitors studied.

A 3D-QSAR study on a series of benzimidazole derivatives acting as hepatitis C virus inhibitors: application of kNN-molecular field analysis.

A k nearest neighbor-molecular field analysis (kNN-MFA) of benzimidazole derivatives, a series of hepatitis C virus (HCV) inhibitors, has been performed to determine the factors contributing the corresponding activities. The energy minimized conformations were obtained by molecular mechanics using VLife QSAR 1.0 package. The developed model was verified by performing leave-one out (LOO) cross-validation, which showed q2 value of 0.900 and pred_r2 value of 0.783. The model indicates the dominance of the steric field and also points out the regions around the benzamidazole ring where the bulky or less bulky groups can be substituted to increase the activity of the compounds.

3D-QSAR studies on quinazoline antifolate thymidylate synthase inhibitors by CoMFA and CoMSIA models.

Thymidylate synthase (TS) is a crucial enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. Herein, we report some 3D-QSAR analyses using CoMFA and CoMSIA on quinozoline antifolates in order to have a better understanding of the mechanism of action and structure-activity relationship of these compounds. By applying leave-one-out (LOO) cross-validation study, we obtained cross-validated q(2) value of 0.573 for CoMFA and 0.445 for CoMSIA, while the non-cross-validated r(2) values for them were found to be 0.935 and 0.893, respectively. The models were graphically interpreted using CoMFA and CoMSIA contour plots. The results obtained from this study could be used for rational design of potent inhibitors against thymidylate synthase.

A QSAR study on some series of sodium and potassium channel blockers.

A quantitative-structure activity relationship (QSAR) study has been made on two different series of sodium channel blockers--namely, a series of 3-(4-phenoxyphenyl)pyrazoles and a series of 2-alkyl-4-arylimidazoles--and a series of potassium channel blockers that comprises of khellinone derivatives, which act on voltage-gated K(+) channels Kv1.3. In both the cases--the inhibition of Na+ channels or the inhibition of K+ channels--the significant correlations were obtained between the inhibition potencies and the hydrophobic properties of the compounds. This led to suggest that the hydrophobic property of the compounds is a major determining factor of the Na+/K+ channel blocking activity and that the compounds might elicit their effects through the hydrophobic interactions with the receptors.

A practical approach to designing operating instructions for medical products in late or post-design phases.

User instructions, and especially operating instructions, are an essential part of the FDA's "medical device labeling" requirements and are intended to help ensure that the device is used safely and effectively. Their design should go hand-in-hand with the design of the product that they are going to accompany. However, for one reason or another, they are usually treated as something that can be tacked on at the end of the device development process. At this stage, it is often realized that, had the device been designed differently, it would have been easier to instruct the potential users. However, it is generally too late and the instructions have to be formulated around the fixed design of the product. Also, in the clinical engineering environment of healthcare organizations, sometimes there is a requirement to produce tailored operating instructions for certain groups of users (especially patients and carers) in certain circumstances, e.g. when the manufacturer's instructions are inadequate or a device has been configured for a particular type of user group. This paper attempts to demonstrate a practical approach to producing effective operating instructions for a product that is already at the far end of its development process or even marketed.

A quantitative structure-activity relationship study on some series of potassium channel blockers.

There has been an increasing interest in compounds that modulate potassium ion channels (K(+)-channels) since they can be developed as important therapeutic agents against ischemic heart diseases. Of the diverse family of K(+)-channels, the voltage-gated potassium channel Kv1.3 constitutes an attractive target for the selective suppression of effector memory T cells in autoimmune diseases. For the development of antiarrythmic drugs, the blockade of the rapidly activating delayed rectifier (I(Kr)) and slowly activating delayed rectifier (I(Ks)) potassium currents has been specifically studied. Since the discovery of I(Ks)-channel, its blockers have been particularly more studied. In this communication, we present QSAR studies on a few series of Kv1.3-channel blockers and a series of I(Ks)-channel blockers in order to provide some guidelines to the drug development.

A quantitative structure-activity relationship study on some novel series of hydroxamic acid analogs acting as matrix metalloproteinase inhibitors.

A quantitative structure-activity relationship study has been made on some pyranyl hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The inhibition potencies of two different series of compounds against two MMP enzymes (MMP-1 and MMP-13) have been analyzed and found to be well correlated with hydrophobic and some indicator parameters of the substituents. In both the cases, hydrophobic parameter of substituents has been found to be a dominant factor. The results of this study led to discuss the selectivity of the compounds for MMP-13 over MMP-1.

A quantitative structure-activity relationship study on matrix metalloproteinase inhibitors: piperidine sulfonamide aryl hydroxamic acid analogs.

A quantitative structure-activity relationship (QSAR) study has been made on a series of piperidine sulfonamide aryl hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The inhibitory potencies of the compounds against two MMPs, MMP-2 and MMP-13, are found to be significantly correlated with the hydrophobic properties of the molecules, suggesting that in both enzymes the hydrophobic interaction is playing a dominant role.

Transdermal atenolol releasing system: an approach towards its development.

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.

Quantitative structure-activity relationship studies on matrix metalloproteinase inhibitors: hydroxamic acid analogs.

A quantitative structure-activity relationship study has been conducted on two different series of acyclic hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The results suggest that in a few cases, the hydrophobic property of the molecules is the major governing factor. However, in some cases, the polarizability of the molecules is shown to be dominant. The two enzymes, MMP-9 and MMP-13, are shown to behave in a similar fashion with any group of inhibitors.