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Biomedical subjects

T Chandy

Publications and source records attributed to T Chandy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Influence of steroid hormones on protein-platelet interaction at the blood-polymer interface.

To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced thrombosis needs to be better understood. Steroidal hormones have a profound role in thrombosis and haemostasis, although adequate studies are not available to demonstrate their part in the thromboembolic phenomena that occur at the blood-foreign material interface. We studied the interfacial phenomena of five steroid hormonal drugs, Sustanon, Menstrogen, Mixogen, Durabolin and Ovral and their interaction with proteins and platelets toward an artificial surface using contact angle, polyacrylamide gel electrophoresis, trace labelling methods, etc. This study demonstrates the effect of these hormones to modulate platelet-surface attachment in the presence of platelet inducers. The addition of steroid hormones to the polymer-protein system can inhibit the level of surface-bound albumin where the fibrinogen binding to an artificial surface has been enhanced or unaltered. Steroids also increase platelet-surface attachment to variable degrees. Prolonged use of steroids or the oestrogen-containing oral contraceptive agents may not be advisable for patients having an artificial implant in contact with blood.

Adsorption↗
PubMed1989

The effect of antihypertensive drugs on protein adsorption, platelet adhesion, and blood coagulation toward an artificial surface.

Protein adsorption and platelet adhesion are two important biological processes arising at the blood-prosthetic interface. The ability of certain antihypertensive and anticholesterol drugs, namely, clonidine, hydralazine, sembrina, frusemide, clofibrate, sorbitrate, thyroxine, etc., to modulate the surface-induced platelet adhesion to polycarbonate substrate was investigated using washed calf platelets in the presence and absence of fibrinogen. This study also demonstrated the changes in protein-surface binding with these drugs using electrophoretic techniques. It seems that the addition of these drugs to the polymer-protein system increased the level of surface-bound albumin variably. These drugs also reduced the fibrinogen surface concentration and inhibited the surface-induced platelet adhesion to variable degrees. Therefore, it may be possible that the enhanced albumin-surface concentration, or reduced fibrinogen-surface binding, in the presence of these drugs may be one of the parameters for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. A better understanding of the mechanism of these drugs under in vivo conditions is needed to correlate these findings.

Adsorption↗
PubMed1989

The preparation of a urokinase-AT-III-PGE1-methyldopa complex, and its effects on platelet adhesion, coagulation times, protein adsorption, and fibrinolysis.

Modifications of urokinase by substances possessing useful therapeutic activity permit combined action preparations to be obtained. Here an attempt was made to develop a complex having combined action for therapeutic activity. The possibility of repeatedly modified urokinase with antithrombin-III-methyldopa-prostaglandin E1 had been experimentally demonstrated. The complex was immobilized on albuminated substrate, which showed fibrinolytic, anticoagulant, and antiplatelet effects simultaneously, in addition to the normal antihypertensive action of methyldopa. The complex immobilized substrate also demonstrated an increase in albumin-surface attachment and a reduction in fibrinogen binding. This may be one of the parameters for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. The approaches suggested indicate the possible new ways of creating nonthrombogenic surfaces with wider applications. A better understanding of the mechanism of these complexes are needed in in vivo conditions to correlate these findings.

Animals↗
PubMed1988

Changes in albumin/platelet interaction with an artificial surface--due to a antibiotics, pyridoxal phosphate, and lymphocytes.

Protein adsorption and platelet adhesion are two important biological processes arising at the blood prosthetic interface. The effect of certain antibiotics, namely, neomycin, gentamicin, ampicillin, penicillin-G, and streptomycin to modulate the albumin polycarbonate surface interaction was investigated using 125I albumin from a protein mixture in the presence and absence of isolated calf lymphocytes. This study also demonstrated the changes in platelet-surface adhesion with these antibiotics. The effect of pyridoxal phosphate to modulate the red blood cell-mediated platelet-surface attachment was also attempted. It appears from pyridoxal phosphate studies that pyridoxal 5'-phosphate (PLP) could modify the surface-platelet attachment. It also inhibited the fibrinogen-induced platelet adhesion. It seems, the addition of antibiotics to the polymerprotein system increased the level of surface-bound albumin variably whereas lymphocytes incubated in the medium did not affect the surface-albumin concentration with time course. These antibiotics also inhibited the surface-induced platelet adhesion to variable degrees. Our earlier studies have indicated that certain antibiotics or antiplatelet drugs can inhibit the fibrinogen binding to an artificial surface. Therefore, it may be possible that the enhanced albumin-surface concentration or reduced fibrinogen-surface binding, in the presence of these antibiotics, may itself be one of the parameter for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. A better understanding of the mechanism of antibiotics is needed in in vivo conditions to correlate these findings.

Animals↗
PubMed1987

Influence of L-ascorbic acid, blood cells and components on protein adsorption/desorption on polycarbonate.

In a previous study we have shown that vitamin C has some effect on the polymer surface by adsorption to it, which would probably affect the protein adsorption and platelet adhesion. The present work has been extended to demonstrate the influence of vitamin C on the kinetics of protein-polymer interaction, using labeled proteins, in the presence and absence of red blood cells, platelets and white blood cells. It appears that vitamin C causes an increase in albumin surface concentration compared to bare substrate which seems to decrease slightly in the presence of blood cells. On the other hand, the infusion of vitamin C to the fibrinogen blood cells system dramatically inhibits the fibrinogen surface binding. The role of L-ascorbic acid to reduce the protein adsorption in the presence of blood cells is discussed by taking into account the interaction of vitamin C with the polymer surface, the interaction of vitamin C with the proteins and cellular membrane, and the interaction of proteins and cells with the polymer itself. The effect of various blood components also seems to be important, and slight differences in the adsorption pattern of proteins are observed in the presence of urea, creatinine, bilirubin, Fe ion and zinc at normal blood levels.

Adsorption↗
PubMed1987

Inhibition of platelet adhesion to glow discharge modified surfaces.

Plasma glow technique has created much interest in the field of surface modification of polymers due to its versatility of generating active polar groups on the surface without affecting the bulk properties. Here an attempt is made to inter-relate the surface properties and platelet adhesion on various polymeric substrates due to plasma treatments. Initially, a critical review of the process and development of thrombosis upon contact of an artificial surface with blood, has been provided, which has been extended with the need for surface modifications to improve their blood compatibility and the versatility of plasma treatments for such modifications have been emphasized. Phospholipids like phosphoryl choline, phosphatidyl choline and phosphoryl ethanolamine were attached to Angioflex surface by plasma glow. The role of such modified substrates to interact with platelets were investigated using Tyrode washed calf platelets. It seems, glow discharge modified phosphoryl choline bilayers dramatically inhibited the platelet-surface binding, which may be due to their biochemical resemblance with thromboresistant surfaces of human blood cells. Further, the behaviour of all phospholipids towards bloodpolymer interaction is not similar and may change depending on the nature of their functional groups, net charge of the phospholipid adsorbed surface and their interaction with platelets and its activation. It is possible to chemically immobilize lipid bilayers on standard polymers, using plasma glow, to improve their biological performance; by suitably selecting the phospholipid combinations.

Adhesiveness↗
PubMed1986

Protein/platelet interaction with an artificial surface: effect of vitamins and platelet inhibitors.

Protein adsorption and platelet adhesion are two important biological processes arising at the blood-prosthetic interface. The effect of Vitamins and antiplatelet drugs to modulate the surface induced platelet adhesion to polycarbonate was investigated using washed calf platelets in presence and absence of fibrinogen. This study also demonstrated the effects of Vitamins and antiplatelet drugs towards protein adsorption to an artificial surface. It seems Vitamin B6, Vitamin E, combinations of Aspirin-Persantine, Aspirin-Vitamin C, a synthetic Polyelectrolyte and Galactosamine reduced the fibrinogen (fg) surface concentration from a mixture of proteins. These antiplatelet agents also enhanced the albumin surface concentration. This itself may be one of the parameters to reduce the platelet adhesion towards an artificial surface. A combination of Aspirin-Vitamin C-Vitamin B6-Vitamin E inhibited the fibrinogen surface binding, which might be beneficial to improve the blood compatibility of an artificial surface.

Adsorption↗
PubMed1985

Changes in protein adsorption on polycarbonate due to L-ascorbic acid.

When a synthetic material is introduced into blood, plasma proteins are rapidly adsorbed on to its surface, followed by the attachment of formed elements of blood, leading to thrombus formation. Previous research reported that vitamin C (L-ascorbic acid) prolongs the clotting time due to the formation of vitamin C-calcium complexes, which reduce the availability of Ca2+ ions for the clotting mechanism in in vitro conditions. Contact angle and platelet adhesion studies have indicated that vitamin C modifies the surface-protein interaction and surface-platelet binding at the interface. In this paper an increased thickness of protein layer deposited on the polycarbonate substrate has been observed in the presence of vitamin C (approximately 50 A) using ellipsometric measurements. Further polyacrylamide gel electrophoresis (PAG) and infrared attenuated total reflection spectroscopy (IR-ATR) techniques have provided a better understanding of the interfacial phenomena. It seems, that the adsorption of albumin is increased, relatively, in the presence of vitamin C, when compared with that of fibrinogen and gamma-globulin from an equal amount of protein mixture.

Adsorption↗
PubMed1984

Structural relevance of adsorbed aminosugars on polycarbonate - antithrombogenicity.

The effects of glucosamine, galactosamine, and mannosamine on platelet adhesion and coagulation induced by an artificial surface were investigated. Glucosamine and galactosamine showed both antiplatelet and anticoagulant effects, but in case of mannosamine none of the above effects was found significant. The three analogs studied were having the same molecular weight and common molecular structure, however from our preliminary observations it could be suggested, that the spatial arrangement of functional groups in the glucopyranose ring at C2, C4 positions were important for it's activity.

Animals↗
PubMed1975

[Medical interruption of pregnancy in India (author's transl)].

The law on medical interruption of pregnancy was introduced in India in 1971. According to this, a pregnancy may be interrupted (only by a specialist) if the life or mental health of the mother is threatened or if there is a danger of severe bodily or mental abnormality in the child. The methods of interruption used are: 1. simple suction, 2. dilatation and curettage (one or two sessions), 3. vacuum aspiration, 4. hysterotomy (abdominal, vaginal), 5. intrauterine injections (hypertonic saline or glucose solution, urea, prostaglandins), 6. intrauterine bougie. After the operation the doctor must advice the patient on methods of contraception.

Abortion, Legal↗
PubMedDate not supplied

The antithrombotic effect of prostaglandin E1 immobilized on albuminated polymer matrix.

For intravascular implantation, a biofunctional surface seems to retard surface thrombosis upon synthetic materials. Prostaglandins, like PGI2, PGE1, and PGD2, etc., are believed to stimulate membrane-bound adenyl cyclase and thereby raise intracellular levels of c-AMP within platelets, which inhibit platelet adhesion and aggregation. A new procedure is suggested for the immobilization of prostaglandin E1 on an albuminated polymer matrix, through glutaraldehyde coupling. Materials thus prepared show dramatic antiplatelet effects, with regard to platelet adhesion, when compared with albumin-immobilized surfaces. The affinity of various modified surfaces toward platelet adhesion is studied, using washed platelets suspended in Tyrode's solution. Octane contact angle studies are used to develop an understanding of the varied nature of bound substrates at equilibrium on polymer surfaces. These are studied at the solid/liquid interface, which is closest to in vivo conditions. The plasma recalcification time demonstrates the anticoagulant properties of various surfaces. A possible role of PGE1 in reducing platelet activity in the presence and absence of vitamin C is discussed. This technique may be used in the development of non-thrombogenic surfaces on existing biomedical polymers. Simultaneous pharmaceutical modification of the blood with vitamin C may enhance the blood compatibility of the surface.

Albumins↗
PubMedDate not supplied

5-Fluorouracil-loaded chitosan coated polylactic acid microspheres as biodegradable drug carriers for cerebral tumours.

The development of injectable microspheres for anticancer drug delivery into the brain is a major challenge. The possibility of entrapping 5-fluorouracil (5-FU) in chitosan coated monodisperse biodegradable microspheres with a mean diameter of 10-25 um was demonstrated. An emulsion of 5-FU (in water) and polylactic acid (PLA) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of chitosan (or poly-vinyl alcohol) with stirring using a high-speed homogenizer, for the formation of microspheres. 5-FU recovery in microspheres ranged from 44-66% depending on the polymer and emulsification systems used for the preparation. Scanning electron microscopy revealed that the chitosan coated microspheres had less surface micropores compared to PVA based preparations. The drug release behaviour from microspheres suspended in phosphate buffered saline exhibited a biphasic pattern. The amount of drug release was much higher initially (approximately 25%), followed by a constant slow release profile for a 30 days period of study. This chitosan coated PLA/PLGA microsphere formulation may have potential for the targeted delivery of 5-FU to treat cerebral tumours.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Colchicine encapsulation within poly(ethylene glycol)-coated poly(lactic acid)/poly(epsilon-caprolactone) microspheres-controlled release studies.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses have the potential to prevent restenosis. However, the development of injectable microspheres for maintaining high tissue levels of drugs at the site of vascular injury is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, colchicine, in polyethylene glycol (PEG)-coated biodegradable microspheres composed of poly(lactic acid)/poly(epsilon-caprolactone) blends, with a mean diameter of 3-6 microm. A solution of colchicine and blends of polylactic acid (PLA)/polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol) with stirring by a high-speed homogenizer to form microspheres. Colchicine recovery in microspheres ranged from 30-50% depending on the emulsification system and the ratio of polymer blends used for the preparations. Scanning electron microscopy revealed that the PLA/PCL microspheres were spherical in shape and had a smooth surface texture. Results of in vitro release studies showed that it is possible to control the colchicine release by choosing the appropriate particle size, loading, and PLA/PCL composition. Water permeability through the PLA membrane was greater, when compared with PCL blends. The amount of drug release also was much higher (58.3%) in PLA compared with PCL (39.3%) microspheres, for 30 days. Therefore, we concluded that the drug release from the microspheres followed a diffusion mechanism where bulk erosion and surface deposition were negligible. These PEG-coated PLA/PCL microspheres may have potential for targeting antiproliferative agents for prolonged periods to treat restenosis.

Caproates↗
PubMedDate not supplied

Development of poly(Lactic acid)/chitosan co-matrix microspheres: controlled release of taxol-heparin for preventing restenosis.

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Controlled release of appropriate drugs alone and in combinations is one approach for treating coronary obstructions, balloon angioplasty, restenosis associated with thrombosis, and calcification. We demonstrated the possibility of encapsulating taxol-loaded polylactic acid (PLA) microspheres within heparin-chitosan spheres to develop a prolonged release co-matrix form. The in vitro release profile of taxol and heparin from this co-matrix system was monitored in phosphate buffered saline pH 7.4, using an ultraviolet spectrophotometer. The amount of taxol/heparin release was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release of taxol (15.8%) and heparin (32.7%) from the co-matrix was modified with polyethylene glycol coatings (13.5% and 25.4%, respectively, for 24 hr). From scanning electron microscopy studies, it appears that these drugs diffuse out slowly to the dissolution medium through the micropores of the co-matrix. However, the surface micropores were modified with polyethylene glycol (PEG) coatings for a constant slow release profile. This PEG-coated PLA/chitosan co-matrix may target drug combinations having synergestic effects for prolonged periods to treat restenosis.

Anticoagulants↗
PubMedDate not supplied

Preparation and performance of chitosan encapsulated activated charcoal (ACCB) adsorbents for small molecules.

A technique is described to encapsulate activated charcoal for haemoperfusion to be used in an artificial liver support. Activated charcoal was encapsulated within chitosan matrix (ACCB) in different concentrations, and was used as the supports for perfusion of a mixture of solutes, having molecular weight ranges from 60 to 69,000; under a flow rate of 8 ml/min. It seems the ACCB may be a good adsorbent system for the removal of toxic uric acid, creatinine, bilirubin, etc., from solutions; while larger molecules such as albumin are adsorbed less. The encapsulated charcoal did not leach out from the matrix during perfusion, and the system may be useful for detoxification of blood. The haemolytic potential of ACCB has been compatible with polystyrene control tubes. However, further studies are needed to determine their behaviour under clinical conditions.

Adsorption↗
PubMedDate not supplied

Chitosan/calcium alginate microcapsules for intestinal delivery of nitrofurantoin.

A new sustained-release dosage form of nitrofurantoin (NF) as microcapsules has been prepared by a mild chitosan/calcium alginate microencapsulation process. These microcapsules have been prepared by adding, dropwise, a solution of sodium alginate containing NF into a chitosan-CaCl(2) system. About 70-80% of the drug is released into phosphate buffer, pH = 7.4 within 6 h. Drug release into the gastric medium is found to be relatively slow compared to that into the intestinal medium. From scanning electron microscopic studies, it appears that the chitosan modifies the NF-alginate microspheres. These findings suggest the possibility of modifying the formulation to obtain the controlled release of NF in an oral sustained-delivery system.

Administration, Oral↗