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Biomedical subjects

C P Sharma

Publications and source records attributed to C P Sharma.

At least 37 records · Page 2Linked to original sources

The antithrombotic versus calcium antagonistic effects of polyethylene glycol grafted bovine pericardium.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end stage phenomenon affecting a wide variety of bioprosthesis. This study proposes a novel approach of reducing pericardial calcification and thrombosis via coupling polyethylene glycols (PEG) to glutaraldehyde treated bovine pericardium via acetal linkages. The calcification of the PEG modified tissue and the control pericardium (extracted and glutaraldehyde treated) was investigated by in vivo rat subcutaneous implantation models and by in vitro meta stable calcium phosphate solutions. Scanning electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the intrafibrillar spaces. However, the grafting of pericardium with PEG-20,000 had dramatically modified the surface and subsequently inhibited the deposits of calcium. Further, the modified tissue had also reduced the platelet surface attachment. Such a reduced calcification of PEG modified tissues can be explained by decrease of free aldehyde groups, a space filling effect and therefore improved biostability and synergistic blood compatible effects of PEG after coupling to the tissues. This simple method can be a useful anticalcification treatment for implantable tissue valves.

Animals↗

Comparative complement activation study of polypropylene hollow fibres of two different makes in static condition.

The complement activation is one of the major problems encountered in the use of extracorporeal devices. The complement-activating potential of two polypropylene hollow fibres (used in membrane oxygenator) of different make and designated as F1 and F2 was tested with time (10, 30, and 180 minutes). The fibres were brought in contact with human blood under in vitro static condition for the comparison. A direct measurement of unadsorbed concentration of the complement protein, C3, present in the liquid phase of human blood before and after the contact with polymer was made using human C3 antisera. This gave a measure of C3 adsorption on the fibres with time and probably also gave an indirect measure of C3a in the blood. IgG was also estimated using antisera of human IgG. The total protein and albumin concentration were measured to obtain an overall adsorption profile of these protein on the fibre surfaces with respect to time. The results showed that C3 adsorption was taking place mainly through the alternative pathway over and above the classical one, being more in the case of F2 than F1. SEM studies revealed poor adhesion of platelets on both fibres, though some activated platelets were also seen with slight deformation at 10 minutes and a few with prominent pseudopodia formations at a later time period on the surface of both fibres. The total protein adsorption was faster, and the surface pores of the F1 were found masked at 10 minutes observation. Later, desorption occurred making the pores visible at 180 minutes. The F2 surface examination showed a continuous deposition of protein layers with time, thereby masking the pores at 180 minutes. The present experimental finding and assessment favoured the F1 as a marginally better candidate to be considered for oxygenator development.

Adsorption↗

Activated charcoal microcapsules and their applications.

Activated charcoal, long known to the ancients as a substance of therapeutic value in a variety of maladies, has recently been "rediscovered" to be of great value in medical applications. Activated charcoal hemoperfusion is effective in blood purification for removal of various circulating toxic materials and waste metabolites, directly. However, particulate release and platelet adhesion prevent its continued clinical use. Polymeric coatings or microencapsulation of charcoal within polymers have improved their blood compatibility. Chitosan encapsulated activated charcoal (ACCB) beads have been extensively investigated in our group for the removal of various toxins such as urea, creatinine, uric acid, bilirubin, etc. This article highlights various methods of microencapsulation procedures of activated charcoal and the importance of this novel material for a variety of biomedical applications. Further, this review provides an insight to the future perspectives for using them in clinical practice.

Adsorption↗

Polyethylene glycol (PEG) modified bovine pericardium as a biomaterial: a comparative study on immunogenicity.

Bioprosthetic heart valves made from glutaraldehyde (GA)-fixed porcine aortic valves or bovine pericardium (BP) are having some advantages over mechanical valves. However, their durability is low due to the calcification and immunological rejection. Study on immunogenicity is an important part in understanding the biocompatibility of materials. Polyethylene glycol (PEG) on pericardium can control biodegradation and calcification. Also, PEG exhibits low immunogenicity. We have studied the complement activation potential and the contribution of complement factors (biologic factors) on the calcification of PEG grafted pericardium samples and compared with standard (control) glutaraldehyde-treated pericardium samples. PEG-grafted BP activated using GA and carbodiimide (EDC) could be selected for further studies since complement activation and calcification observed on these samples has been relatively low.

Animals↗

Use of chitosan as a biomaterial: studies on its safety and hemostatic potential.

Chitosan, a mucopolysaccharide of marine origin, was studied for its safety and hemostatic potential. Its surface was treated with glutaraldehyde, carbodiimide, and plasma glow discharge to elicit effects of enzyme degradation. Of the seven enzymes used, leucine amino peptidase caused maximum degradation. Autoclaving appeared to be an ideal sterilizing method as it caused least decrease in tensile strength and effected a negligible rate of hemolysis. Sterilizing with glutaraldehyde with a physiologic pH retained the maximum tensile strength of chitosan. In vivo toxicity tests indicated that it is nontoxic, and the sterilized films were free of pyrogen. Coagulation and hemagglutination tests showed that the hemostatic mechanism of chitosan seems to be independent of the classical coagulation cascade and appears to be an interaction between the cell membrane of erythrocytes and chitosan.

Animals↗

Development of chitosan/polyethylene vinyl acetate co-matrix: controlled release of aspirin-heparin for preventing cardiovascular thrombosis.

Aspirin and heparin were embedded in chitosan/polyethylene vinyl acetate co-matrix to develop a prolonged release form. The in vitro release profiles of these drugs from the co-matrix system were monitored in Tris HCl buffer pH 7.4, using a UV spectrophotometer. The amount of drug release was initially much higher. followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with styrenebutadiene coatings. From scanning electron microscopy studies it appears that the drugs diffuse out slowly to the dissolution medium through the micropores of the co-matrix. The released aspirin-heparin from the co-matrix system had shown their antiplatelet and anticoagulant functions. The results propose the possibility of delivering drug combinations, having synergestic effects for therapeutic applications.

Animals↗

Integrin-ligand interactions: scratching the surface.

Integrins provide cells with critical means of communication with their microenvironments. By linking events at the cell surface to a dynamic cytoskeleton-signaling complex, integrins enable cells to rapidly modify their mechanical and genetic machinery in response to environmental cues. This review highlights major advances made in understanding the structural basis of integrin-ligand interactions and their regulation.

Animals↗

Glutaraldehyde treated bovine pericardium: changes in calcification due to vitamins and platelet inhibitors.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.

Animals↗

Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: effect of drug release on blood compatibility and permeability.

Membranes developed from poly(vinyl alcohol) (PVA) have superior permeability because of the highly hydrophilic character of PVA. However, its blood compatibility needs to be further improved. For this we have developed acetylsalicylic acid (ASA, aspirin) loaded PVA membranes. It seems that the slow release of aspirin from the membrane provides a surface concentration of aspirin sufficient for partially inhibiting platelet adhesion. PVA membrane with 531 micrograms cm-2 of ASA loaded, may be selected for hemodialysis applications. This may help to reduce the amount of heparin infused during hemodialysis, thereby reducing the side-effects associated with the systemic administration of heparin.

Anticoagulants↗

Influence of polyethylene glycol graftings on the in vitro degradation and calcification of bovine pericardium.

Calcification is a frequent cause of the clinical failure of bio-prosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). This article reports on various chemical techniques for grafting polyethylene glycol (PEG) on bovine pericardium, their biostability, and calcification. The process of calcification profile was studied by in vitro experiments via the incubation of pericardial samples in a metastable solution of calcium phosphate. The calcification profile of PEG-modified bovine pericardium through glutaraldehyde linkages was significantly reduced compared to other methods of grafting. The mechanical property of these PEG-modified tissues after enzyme (collagenase) digestion and calcification were also investigated. PEG grafting of BP via glutaraldehyde or hexamethylene diisocyanate had shown better mechanical stability compared to other grafting methods used. In conclusion, it seems that the surface modification of bovine pericardium through high molecular weight PEGs via glutaraldehyde linkages may provide new ways of controlling tissue biodegradation and calcification.

Animals↗

Modified polyacrylamide microspheres as immunosorbent.

Extracorporeal immunoadsorption system has been used for the specific removal of immunologically active substances from the blood. In this study, an attempt is made to utilise polyacrylamide microspheres as a matrix for immunoadsorption. Phenyl alanine is coupled onto the polymer beads using glutaraldehyde. These modified beads exhibit a high binding affinity for gamma-globulin compared to bare beads. The surface modified ones showed selective adsorption of immunoglobulins of IgG class. The C3 adsorption pattern is not altered significantly upon modification. Modified beads are found to be less hemolytic after modification. However, more studies are to be conducted for the development of a hemoperfusion column based on this modified matrix.

Acrylic Resins↗

Effect of liposome-albumin coatings on ferric ion retention and release from chitosan beads.

Ferric chloride was embedded in a chitosan matrix to develop a prolonged-release form. The in vitro release profiles of ferric ions from chitosan beads were monitored in 0.1 M Tris-HCl buffer, pH 7.4, using a UV spectrophotometer. The amount of drug release was much higher initially, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with liposome and albumin coatings. From scanning electron microscope studies, it appears that the ferric ions diffuse out slowly to the dissolution medium through the micropores of the chitosan matrix. Further, the liposome forms a phospholipid membrane layer in the pores of chitosan beads and encapsulates the ferric ions within their vesicles and controls the release profile. The chitosan beads loaded with ferric ions substantially inhibited the polyurethane-associated calcification, in an in vitro model system. The released ferric ions, appeared to alter the protein-surface binding and improved the biocompatibility of the matrix. The results propose the possibility of modifying the polymer matrix to obtain a desired controlled release of the drug for a prolonged period.

Albumins↗

Structural studies on bovine bioprosthetic tissues and their in vivo calcification: prevention via drug delivery.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end-stage phenomenon affecting a wide variety of bioprostheses. To study the process of calcification in tissue prosthetics, glutaraldehyde-treated bovine pericardium, dura mater and fascialata were implanted subcutaneously in rats and retrieved 21 days later and thereby morphological findings were correlated with biochemically determined levels of calcium. Transmission electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The deposition of calcium was higher with dura and fascia prostheses compared to pericardium. However, the release of Fe3+ ions from chitosan matrix had substantially inhibited the deposits of calcium in all implanted tissues. It seems that the structural and anatomical features of the tissue is one of the important factors for tissue-associated calcification. It is also confirmed that glutaraldehyde-preserved pericardium is the most suitable material for the development of cardiac prosthesis, with an appropriate drug combination therapy for prevention of pathological calcification.

Animals↗

Changes in polyurethane calcification due to antibiotics.

To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced calcification must be better understood. Calcification was examined on porous polyurethane incubated in metastable solutions of calcium phosphate, and the role of certain antibiotics in the medium was evaluated. It seems that certain aminoglycoside antibiotics can modify polyurethane surfaces and, subsequently, their mineralization process. In addition, these antibiotics may alter the calcium transport through polyurethanes. Therefore, it is conceivable that certain antibiotics can, in addition to producing their antibacterial effect, modulate surface calcium binding by changing the calcium mobilization and crystallization. Additional studies are needed to develop applications.

Aminoglycosides↗

Development of silastic polyurethane (Angioflex) materials with antibacterial agent.

Bioimplants incorporated with antimicrobial agents are needed to control Foreign Body Associated Infection (FBAI) in clinical settings. Attempts are made here to develop five different types of polyurethane (Angioflex), viz., (1) bare polymer, (2) bare polymer glow discharged, (3) bare polymer coated with chlorhexidine, (4) chlorhexidine coated polymer glow discharged, and (5) material (4) recoated with another layer of chlorhexidine digluconate. These materials are tested for their in vitro antibacterial effects using disc diffusion technique against five different standard clinical staphylococcus strains, viz., Wood 46 (Staph. aureus), A 182 (Staph. epidermidis), A 313 (Staph. epidermidis), A 61 (Staph. epidermidis), and A 72 (Staph. epidermidis). Maximum antibacterial effects (zone of inhibition) are observed with polyurethanes incorporated with chlorhexidine digluconate (3) and chlorhexidine incorporated and glow discharged (4). Findings of this study indicate that glow discharge does not seem to produce either additive 8r synergistic antibacterial effects with chlorhexidine digluconate coated Angioflex material.

Anti-Bacterial Agents↗

Characterization and cell distribution of polycystin, the product of autosomal dominant polycystic kidney disease gene 1.

BACKGROUND: In a majority of cases, autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations within a putative open reading frame of the PKD1 gene. The encoded protein, polycystin, is predicted to span the plasma membrane several times and contains extracellular domains, suggestive of a role in cell adhesion. The cellular distribution and function of polycystin is not known. MATERIALS AND METHODS: We selected as immunogens two conserved 15 amino acid peptides: P1, located in a predicted extracellular region of polycystin, and P2, located in the C-terminal putative cytoplasmic tail. The anti-peptide antibodies from immunized rabbits were affinity purified on peptide-coupled resins and their specificity confirmed by their selective binding to recombinant polycystin fusion proteins. Western blotting and immunohistochemistry were used to characterize the size, tissue, and cell distribution of polycystin. RESULTS: A high-molecular mass protein (about 642 kD) was detected by Western blotting in rat brain tissue. A few additional bands, in the 100- to 400-kD range, probably representing tissue-specific variants and/or proteolytic fragments, were recognized in human and rat tissues. Polycystin was abundantly expressed in fetal kidney epithelia, where it displayed basolateral and apical membrane distribution in epithelial cells of the ureteric buds, collecting ducts, and glomeruli. In normal human adult kidney, polycystin was detected at moderate levels and in a cell surface-associated distribution in cortical collecting ducts and glomerular visceral epithelium. Expression of polycystin was significantly increased in cyst-lining epithelium in ADPKD kidneys, but was primarily intracellular. CONCLUSIONS: Polycystin appears to be a developmentally regulated and membrane-associated glycoprotein. Its intracellular localization in the cyst-lining epithelium of ADPKD kidneys suggests an abnormality in protein sorting in this disease.

Animals↗

Copper effect on photosynthesis and transpiration in safflower.

The young leaves of safflower plants subjected to deficient supply of copper (0.00063 mg Cu L-1) developed visible symptoms of Cu deficiency and showed a decrease in chlorophyll concentration, Hill activity, net photosynthesis and transpiration. On giving normal supply of Cu (0.063 mg Cu L-1), these changes were partially reversed.

Copper↗

Chromium uptake and toxicity effects on growth and metabolic activities in wheat, Triticum aestivum L. cv. UP 2003.

Chromium (Cr) at graded levels when added in sand culture of wheat (T. aestivum L. cv. UP2003) under glasshouse conditions resulted in reduction in biomass, chlorophyll and activities of catalase and peroxidase while enhanced acid phosphatase and ribonuclease activities. Elevated levels of Cr supply significantly reduced the concentration of inorganic phosphorus. With an increase in Cr supply the uptake of chromium also increased significantly in different plant parts especially in roots. Above metabolic lesions due to Cr in wheat provided evidence that the element in nutrient medium if present in excess may be inhibitory to plant growth and development.

Biomass↗