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.

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.

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.

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.

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.

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.

Intraosseous neurilemmoma of L2 vertebra--a case report.

Intraosseous neurilemmoma (schwannoma) is a rare bone tumor with incidence less than 0.2% of all primary bone tumors. It is a benign neoplasm arising from the schwann cells of the nerve sheath. When they occur, they are usually found in the mandible. This paper reports an unusual occurrence of intraosseous neurilemmoma in L2 vertebral body. This patient presented with complaints of backache and progressively increasing weakness in both lower limbs. Roetengenograms showed an osteolytic lesion of L2 vertebra localized in the left half of the body and pedicle. Computed tomograph revealed a large soft tissue component of the tumor mass with thecal sac compression. A computed tomograph assisted needle biopsy revealed the tumor to be neurilemmoma. Subsequently, during decompression, it was possible to shell out tumor from surrounding tissues. Remaining tumor was curettedfrom bone and the cavity packed with autograft. The recovery was uneventful with incorporation of graft. The aim of this article is to highlight intraosseous neurilemmoma as a possible differential diagnosis in bony tumors. Intraosseous neurilemmoma of lumbar vertebrae is an extremely rare occurrence and till date only four cases are reported in English literature.

Design and development of integrase inhibitors as anti-HIV agents.

A review is presented on different categories of compounds that have been studied for the inhibition of the HIV-1 integrase to develop anti-HIV agents. These compounds are: oligonucleotides (double-stranded, triplex, and G-quartet), curcumin analogues, polyhydroxylated aromatic compounds, diketo acids, caffeoyl- and galloyl - based compounds, hydrazides and amides, tetracyclines, and depsides and depsidones. For all these compounds, the important structural features essential for the inhibition of the integrase are pointed out.

Quantitative structure-activity relationships of antiarrhythmic drugs.

A Comprehensive review of quantitative structure-activity relationship (QSAR) studies on antiarrhythmic agents is presented. From the discussion point of view, the antiarrhythmic agents have been put into two broad classes: specific and nonspecific. While the main members of the former class can be beta-adrenergic blocking agents (beta-blockers), any chemical that can act directly on the myocardial cell membrane, producing a cardiodepressant effect via changes in basic electrophysiological properties of the membrane, such as automaticity, excitability, conductivity, and refractoriness, has been put in the latter class. QSARs exhibit that the biological actions of a variety of drugs belonging to any class depend primarily on the lipophilic haracter of the molecule or substituents. Thus, the hydrophobic interaction is found to play a dominant role in the action of antiarrhythmic agents. In certain cases, the QSARs also exhibit the role of electronic parameters, suggesting that certain receptors may have electronic site also, permitting the drugs to involve in some electronic interactions, too.

Quantitative structure-activity relationships of antianginal drugs.

Quantitative structure-activity relationships (QSARs) of various classes of antianginal drugs, e.g. nitrates, beta-adrenergic blocking agents (beta-blockers), and calcium channel blockers (calcium antagonists), have been reviewed. This review gives an overall picture of the mode of action of each class of drugs and points out the specific physicochemical and structural properties that govern their activity. It is observed that in almost all kinds of antianginal drugs the lipophilic factor plays an important role and the next important factor seems to be the steric ones. The electronic factors are found to be occasionally important. In the case of beta-blockers, the most common factor that appeared to govern the activity remained the lipophilicity. In nitrates, too, the activity is observed to primarily depend upon the lipophilicity. In calcium channel blockers, however, the dominant effect is seen to be of steric factors. The steric roles may be essential in drug-receptor interactions, which seem to involve both hydrophobic, and to a lesser extent, electronic interactions.

Quantitative structure-activity relationships of cardiotonic agents.

Quantitative structure-activity relationships (QSARs) of different cardiotonic agents are presented. A critical analysis of all QSARs provides a very vivid picture of the mechanisms of varying cardiotonic agents. The cardiotonics can be broadly put into 2 categories: cardiac glycosides and nonglycoside cardiotonics, which include phosphodiesterase of type III (PDE III) inhibitors, sympathomimetic (adrenergic) stimulants, A1-selective adenosine antagonists, Ca2+ channel activators and vasopressin antagonists. For cardiac glycosides, QSARs reveal that the position of carbonyl oxygen in their lactone moiety and shifting of the lactone ring from its original position or its replacement by another group would be crucial for their activity. The carbonyl group or its isostere like CN is indicated to be the sole binding entity and the hydrogen bonding through this group is considered to be the most likely binding force. For nonglycoside cardiotonics that include PDE III inhibitors and A1-selective antagonists, a five-point model has been established for their activity, the salient features of which are: (1) the presence of a strong dipole, (2) an adjacent acidic proton, (3) a methyl-sized lipophilic space, (4) a relatively flat overall topography and (5) a basic or hydrogen-bond acceptor site opposite to the dipole. For Ca2+ channel activators, the importance of steric, electrostatic, lipophilic and hydrogen-bonding properties of molecules is indicated, while for vasopressin antagonists the lipophilic and electronic properties are suggested to be the most important.

Quantitative structure-activity relationships of antihypertensive agents.

Quantitative structure-activity relationships of various classes of antihypertensive agents, e.g., sympatholytic agents, diuretics, direct or peripheral vasodilators, potassium channel activators, angiotensin-converting enzyme inhibitors, renin inhibitors and miscellaneous agents (platelet aggregation inhibitors) are reviewed. This review gives an overall picture of the mode of action of each class of drugs and points out their specific physicochemical and structural properties governing their action. For example, in the case of centrally acting drugs (sympatholytic agents) it has surfaced that the prime factors governing their activity are lipophilic and steric properties of the molecules, and at the receptor level a charge-transfer complex is formed between the molecule and the receptor. It is, however, observed that for peripherally acting sympatholytic agents the prime role is played by only lipophilicity. In the case of diuretics, the electronic characters of molecules are found to be more dominant than their lipophilic property, but for direct vasodilators and ACE inhibitors both electronic and lipophilic properties seem to be equally important. In renin or platelet aggregation inhibitors, the structural properties appear to be more important. However, the fundamental property that is overwhelmingly involved in the majority of antihypertensive agents appears to be the lipophilicity, suggesting that in most of the cases the hydrophobic interaction would play the major role in drug action.

Electronic structure--activity relationships of antibacterial acridines.

The antibacterial activity of a series of amino- and fluorinated acridines was studied in the framework of their electronic structures. To calculate the electronic structure, a simple Hückel molecular orbital theory was used. A statistical regression analysis revealed linear correlations between the activity and the electronic indexes, particularly the electron density at the ring nitrogen.

A quantitative structure-activity relationship study on a novel class of calcium-entry blockers: 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines.

A quantitative structure-activity relationship (QSAR) study has been made on two different series of 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines acting as calcium entry blockers, using some physicochemical and structural parameters. Two different assays were reported for both the series: (IC(50))(A), referring to the molar concentration of the compound required to reduce [3H] nitrendipine binding by 50%, and (IC(50))(B), referring to that required to block Ca(2+) induced concentration of K(+) depolarised rat aorta by 50%. For series 1, where the 2-position substituents of indolizine ring were varied along with the aminoalkoxy moieties of the phenyl ring, the QSAR analysis shows that the 2-position substituents can equally affect both the activities through their hydrophobic and electronic properties and the aminoalkoxy moiety through some steric effects. For series 2, where the indolizine ring has been replaced by varying heterocyclic rings, along with the changes in aminoalkoxy moiety of the phenyl ring, the QSAR exhibits that these different heterocyclic rings affect both the activities through some steric roles, altering the conformations of the receptors from system A to system B. Among the different heterocyclic rings, the N-substituted indole ring is shown to be more conducive to both the activities than any other ring. However, a 5-membered ring is indicated to be less effective than a 9- or 10-membered ring for activity B. Additionally, the amino moieties having phenyl ring with methoxy groups at 3,4,and 5-positions are shown to favour both A and B activities.

Left ventricular filling pressures after rapid blood transfusion in cases of chronic severe anemia.

Left ventricular filling pressure as reflected by pulmonary artery wedge pressure was measured in 15 adult cases of chronic severe anemia before and after rapid and large blood transfusion, using Swan-Ganz monitoring catheters. Pre-transfusion PAWP was normal in 80% of the cases but increased significantly after blood transfusion (P less than 0.001), reaching more than 18.0 mm Hg in 3 cases. No correlation was found between right atrial pressure and PAWP. In is concluded that administration of 2 units of blood at a rapid speed (8.92 +/ 1.73 ml/minute) in cases of CSA is not always quite safe so far as pulmonary hemodynamics are concerned and should therefore be avoided.

Haemodynamic changes following blood transfusion in cases of chronic severe anemia: increased safety with simultaneous furosemide administration.

Left ventricular filling pressures as reflected by pulmonary capillary wedge pressure (PCWP) were measured in 20 adult subjects of chronic severe anemia before and after transfusing one unit of blood. The cases were divided into two groups of ten each. In both groups blood was transfused at a speed of 5 ml/mt; group II cases received, in addition, 40 mg furosemide intravenously just before the start of the transfusion. Pretransfusion PCWP was normal in all the cases. Following transfusion, 'wedge' pressure increased significantly (P less than 0.001) in group I but not in group II patients, in whom it actually decreased (P less than 0.001). It is concluded that prior administration of furosemide completely prevents any increase in LVFP following transfusion of one unit of blood at a moderately rapid speed, and makes such a transfusion quite safe, at any rate, so far as pulmonary haemodynamics are concerned.

A comparative study of conventional vs rapid speed of blood transfusion in cases of chronic severe anemia.

Pulmonary capillary 'wedge' pressure (PCWP) was studied in 20 cases of chronic severe anemia before and after transfusing one unit of blood. They were divided into 2 groups of 10 age and sex matched cases. Blood was transfused at a speed of 2 ml/min in group A and 5 ml/min in group B. Pretransfusion PCWP was normal in all the cases. Following blood transfusion (BT) 'wedge' pressure increased significantly (p less than 0.001) in both the groups being 17.2% and 29.2% in group A and B respectively. The difference in the rise of PCWP between the two groups was not statistically significant (p greater than 0.05). All the cases tolerated BT very well. It is therefore, concluded that transfusion of one unit of blood at a speed of 5 ml/min is nearly as safe as when it is transfused at a rate of 2 ml/min (conventional speed) so far as the cardiopulmonary haemodynamics are concerned.

Development of matrix-membrane transdermal drug delivery system for atenolol.

A polymer matrix system for transdermal delivery of Atenolol was developed for its prolonged and controlled release systemic availability. To achieve the desired and controlled release rate, different combinations of Eudragit RL with polyvinyl pyrrolidone and polyethylene glycol 4000 were used in the preparations of polymeric matrix system. These preparations were evaluated for in vitro release and permeation of the drug across pig skin. The desired systems exhibited linear relationship between drug release (Q) versus ne0.8(hr0.8). The product exhibiting required skin permeation 64 mcg/h/cm2 to achieve an effective plasma concentration was selected for the in vivo performance evaluation. The drug plasma profile was compared with the plasma profile obtained following the administration of a conventional oral dose of Atenolol. The study revealed that the designed polymeric matrix transdermal drug delivery system of Atenolol could be successful with improved performance.