Antithrombotic activity of an unsaturated fatty acid preparation--comments.
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Biomedical subjects
Publications and source records attributed to C P Sharma.
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The hydrolytic and enzymic degradation of poly(L-lactic acid) (PLA) and poly(gamma-benzyl L-glutamate) (PBGA) films, together with a series of surface treatments, were studied, as a function of exposure time. The degradation of these polymers was monitored by weight loss, contact angle, pH changes and tensile strength studies. Glutaraldehyde treatment retained the maximum strength of PLA in buffer, followed by carbodiimide, compared with control films. On the other hand, plasma glow reversed the effect. The ability of alpha-chymotrypsin, carboxypeptidase, ficin, esterase, bromelain and leucine aminopeptidase to modulate the degradation of PLA and PBGA was also investigated. Addition of these enzymes to the polymer-buffer system reduced the tensile strength of these polymers variably. Among the six enzymes studied, leucine aminopeptidase showed the highest enzymic effect on the degradation of the glutaraldehyde-treated and bare PLA or bare PBGA films. However, glutaraldehyde-cross-linked PLA demonstrated maximum stability in buffers or in all other enzyme systems studied compared with bare PLA. It is conceivable that surface treatments on these polymers might have altered their physical and chemical configuration and the subsequent degradation properties. Surface modifications may provide new ways of controlling the biodegradation of polymers for a variety of biomedical applications.
The adhesion of platelets, red blood cells, and lymphocytes onto various polymer substrates, hydrophobic to hydrophilic in nature, has been studied. Cell adhesion is found to be higher on hydrophilic substrates. The stability of these adhered cells has also been studied under a flow rate of 20 ml/min. Further the effect of glow discharge treatment onto various substrates is investigated. It seems the stability is more on glow discharge treated substrates due to increased surface free energy.
Since titanium is being used for various biomedical applications requiring enhanced blood compatibility, which may be partly due to its extremely stable oxide layer, an attempt is made here to understand the effect of oxide layer thickness on protein adsorption. Different thickness of oxide layers have been coated on titanium foil using anodizing method and thickness of oxide layers deposited have been measured by an ellipsometer. Studies of competitive adsorption of proteins, using I125 labelled protein from a mixture of 25 mg% albumin, 15 mg% gamma-globulin and 7.5 mg% fibrinogen indicate an increased adsorption of proteins onto the oxide layer coated surfaces compared to the bare surface.
The blood compatibility of an artificial polymeric implant largely depends on the physicochemical nature of the polymer substrate. In the present study our aim is to develop an understanding of polymer surfaces having similar surface free energy, but different chemical characteristics. We attempted to graft hydrogels onto a silastic polyurethane (Angioflex) material and optimised the surface free energy to about 35.0 ergs/cm2. We compared the protein adsorption and platelet and lymphocyte adhesion on these surfaces. It is observed that there is a relative change in behavior because of the difference in chemical nature.
Polymers like poly(methylmethacrylate) (PMMA) and poly(2-hydroxyethylmethacrylate) (PHEMA) are widely used in the development of hard and soft contact lenses. Cell adhesion and deposition of chemicals such as calcium, lipoproteins and mucin on the lens surface cause visual acuity which is the main problem in extended uses of contact ocular lenses. In order to minimise the cell adhesion and other type of depositions, a method of surface modification of lens involving the use of phosphoryl choline, a phospholipid and the glow discharge technique has been described. The power variation of the lenses after modification has been checked using Topcon lensometer. The possible power changes of the modified samples due to the exposure to the normal light in the laboratory, darkness, ultraviolet (U.V.) light or saline have been investigated by taking the visible and ultra violet spectra using Beckman spectrophotometer. Surface energy variations after modifications of the samples have been checked by sessile drop water contact angle measurements. Glow discharge treatment increases the hydrophilicity of the samples. It seems, the modifications do not affect the power of hard contact lens significantly. It is also observed that the exposure of samples to the normal light in the laboratory, darkness, U.V. light or saline make no significant change in the visible and ultraviolet spectra of the samples before and after modification.
This paper reviews our current activities of developing polyether urethane urea membranes for hemodialysis application. It is observed that the processing parameters such as precipitation medium, precipitation temperature etc. can influence the porosity of the membrane and subsequently the permeability property. Polyurethane/poly(methyl methacrylate) blended membranes have also shown high permeability. All the membranes are subjected to different sterilization processes and the pore sizes before and after sterilization are determined. The changes in the pore size due to sterilization seems to effect the permeability.
Chitosan, a polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to be nontoxic and bioabsorbable. This study highlights the use of chitosan matrix for controlled drug delivery systems. The steroid drugs, namely testosterone, progesterone and beta-oestradiol were mixed with chitosan and the films were prepared by evaporation technique. The in vitro release profile of these steroids from the film matrix was monitored, as a function of time, in phosphate buffered saline (PBS, pH 7.4) at 37 degree C using a U-V-spectrophotometer. The degradation, of these chitosan and drug loaded chitosan films, was also investigated by weight loss and tensile strength studies. The steroid release from chitosan films was compared with the release of these drugs from their microbeads. It appears, the films and the microbeads stayed intact during the dissolution study of 90 days and the possibility of using these systems in contraceptive applications and novel drug delivery systems are discussed.
Protein adsorption and subsequent cellular reactions are important biological events at the blood-polymer interface. Mediators like drugs, vitamins, and steroid hormones play a significant role in protein adsorption. An attempt is made to understand the effect of several i.v. agents on protein-platelet interaction with an artificial surface, polycarbonate. Pentothal, an anesthetic; lignocaine, a local anesthetic; pethidine, a narcotic anesthetic; Calmpose, a tranquilizer; and Novalgin, an analgesic, were drugs used for this study. Competitive adsorption of proteins is evaluated using a trace-labeled technique from a mixture of proteins (25 mg/dl of albumin, 15 mg/dl of tau-globulin, and 7.5 mg/dl of fibrinogen). Platelet and lymphocyte adhesion and plasma recalcification time are studied from calf blood. It is observed that these agents modulate the protein and cellular interaction and also the blood coagulation time. Therefore, proper selection of such including agents should not be overlooked for an implant surgery or while ministering to a patient with an implant.
To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced thrombosis needs to be better understood. It is documented that certain antihypertensive drugs can inhibit platelet adhesion to an artificial surface; on the other hand, steroid drugs increase platelet surface attachment to variable degrees. This study demonstrates the changes in protein-surface binding with certain antihypertensive and antianginal drugs--namely, digoxin, sorbitrate, thyroxine, sembrina and hydralazine--and five steroid hormones--estrone, progesterone, beta-estradiol, 7(OH) progesterone, and testosterone--using trace labelling methods. It seems that the addition of these antihypertensive drugs to the polymer-protein system has increased the level of surface-bound albumin and reduced the fibrinogen surface concentration to variable degrees. A reversed pattern of protein-surface attachment has been evident with steroid hormones. Thus, it appears that the changes in platelet attachment due to various drugs may be dependent on the availability of fibrinogen receptors at the polymer interface, along with other possible biological factors. Prolonged use of antihypertensive drugs may not have any significant side effect for patients having an implant. However, the use of steroids or steroid-containing oral contraceptive agents may not be advisable for patients having an artificial implant in contact with blood. A better understanding of the mechanism of these drugs under in vivo conditions is needed to correlate these findings.
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The changes in protein adsorption onto aluminium surfaces coated with different thicknesses of oxide layers were examined. The oxide layers on aluminium substrates were derived by the anodizing technique. Protein adsorption studies were conducted using 125I-labelled albumin and the amount of albumin adsorbed was estimated with the help of a gamma counter. An increase in albumin adsorption was observed on oxide layer coated aluminium surfaces. The effect of anti-Hageman factor on albumin and fibrinogen adsorption on to bare aluminium, oxide layer coated aluminium and bare polyether urethane urea surfaces was also investigated. It was observed that the presence of anti-Hageman factor increased the adsorption of albumin and fibrinogen on to all these substrates.
Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.
Protein adsorption and platelet adhesion are two important biological processes arising at the blood prosthetic interface. The effect of certain commonly used vaccines and hyper immune serums namely tetanus toxoid, tetanus immunoglobulin, polyvalent anti-snake venum serum and anticholera vaccine to modulate the surface induced platelet adhesion to polycarbonate substrate was investigated using washed calf platelets in presence and absence of fibrinogen. This study also demonstrated the changes in protein-surface binding with few of these vaccines, using SDS - polyacrylamide gel electrophoresis. It seems, the addition of tetanus toxoid to the polymer-protein system increased the level of surface-bound albumin and reduced the fibrinogen-surface attachment. On the other hand, tetanus immunoglobulin reversed the effect. This itself may be one of the parameters for the observed reduction in platelet-surface attachment due to tetanus toxoid. The enhanced platelet adhesion with other vaccines, may be correlated with the availability of more fibrinogen receptors for the platelets to attach. A better understanding of the mechanism of these vaccines is needed in vivo conditions for interrelating these findings.
Water soluble polyelectrolyte synthesised from natural rubber contains sulfamate and carboxylate groups similar to that of heparin. It is observed that synthetic heparinoid polyelectrolyte is capable of inhibiting blood coagulation. In the present study, we attempted to graft the same onto polystyrene and polymethylmethacrylate surfaces using glow discharge technique and 60Co-gamma-irradiation method, and the surfaces were compared with respect to water contact angle and platelet adhesion parameters. Heparinised surfaces are also evaluated for relative comparison.
Indomethacine is an analgesic and antiinflammatory drug which has antiplatelet and antithrombotic properties. In our work, we have tried to immobilize the same onto a polymer surface covalently. Surface parameters like water contact angle and platelet adhesion are studied. Similar studies are conducted on heparin immobilized surfaces, for relative comparison.
A human placental cDNA library was screened using oligonucleotide probes based on the peptide sequence of the human class III alcohol dehydrogenase. An incomplete cDNA clone covering most of the coding sequence of class III alcohol dehydrogenase was isolated from a human placental cDNA library. This was subsequently used as a probe to obtain a full-length clone from a human testicular library. The cDNA sequence codes for a protein that is identical to the enzyme purified from human liver. Southern analysis of human genomic DNA suggests that it may contain more than a single copy per haploid genome.