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Biomedical subjects

A Jayakrishnan

Publications and source records attributed to A Jayakrishnan.

At least 19 recordsLinked to original sources

Self-gelling primaquine-gum arabic conjugate: an injectable controlled delivery system for primaquine.

Primaquine, an 8-aminoquinoline, forms a cross-linked gel with periodate-oxidized gum arabic rapidly by simply mixing the drug with the oxidized polysaccharide due to Schiff's base formation between the two amino groups of primaquine and the aldehyde groups in the oxidized polysaccharide. The speed of gelation is determined by the degree of oxidation of polysaccharide, its quantity, and the drug payload. Estimation of the cross-linking density of the gels showed that the higher is the degree of oxidation of gum arabic, the higher is the cross-linking density. In vitro release of primaquine into phosphate buffered saline (PBS) at 37 degrees C demonstrated that the extent of release depended on the cross-linking density and drug payload. Repeated extraction using PBS soon after gel formation showed that not all of the primaquine was conjugated to the polysaccharide and the release seen in vitro was mostly from the unconjugated drug especially from matrices with higher cross-linking density. The gels were found to degrade in PBS, the kinetics of degradation being dependent on the cross-linking density. Cytotoxicity evaluation using MTT assay against L929 mouse fibroblasts showed that oxidized gum arabic having a degree of oxidation of 50% was only very mildly cytotoxic at a concentration of 0.025 g/mL. An injectable, biodegradable drug depot with controlled release of primaquine over several days or weeks would be advantageous for long-term delivery of this drug against malaria or leishmaniasis, and the present study shows that a primaquine-polymer conjugate that can be formed in situ could be an interesting possibility.

Animals↗

Polyurethanes with radiopaque properties.

An aliphatic, commercially available, medical grade polyurethane, Tecoflex 80A was made radiopaque by coupling a 5-iodine-containing molecule, N-(2,6- diiodocarboxyphenyl)-3,4,5-triiodo benzamide (DCPTB) onto the polymer backbone. DCPTB was synthesized by coupling 4-amino-3,5-diiodobenzoic acid and 3,4,5-triiodobenzoic acid using dicyclohexyl carbodiimide. Radiopaque polyurethane thus obtained was characterized by IR, TGA, DSC and X-radiography. By optimizing the reaction conditions, it was possible to incorporate about 8% iodine in the polymer (wt/wt) to achieve radiopacity almost equivalent to that of a 2mm thick aluminium wedge. However, the products differed from the starting polymer in thermal characteristics. The starting polymer showed two endothermic transitions, the first one due to glass transition of the soft segment and the second one due to disruption of the hard segments. After modification, the second transition shifted to a lower temperature, while the first transition remained unaltered. Also, the modified polymers showed reduced thermal stability compared to the starting polymer. These observations could be explained on the basis of the reduced extent of intermolecular hydrogen bonding among the hard segments of the end product. Radiopaque polyurethanes are expected to have significant advantage over their non-radiopaque counterparts in many medical and related applications.

Biocompatible Materials↗

Evaluation of the effect of incorporation of dibutyryl cyclic adenosine monophosphate in an in situ-forming hydrogel wound dressing based on oxidized alginate and gelatin.

Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. To explore more effective wound management, dibutyryl cyclic adenosine monophosphate (DBcAMP), a lipophilic analog of cAMP was incorporated into an in situ-forming hydrogel wound dressing based on periodate-oxidized alginate and gelatin. In vitro release of DBcAMP from the matrix into phosphate buffered saline was slow and increased with time. Only 50-60% of the compound was released into the medium over a period of 2 days suggestive of a sustained release into the wound bed over a period of few days. The wound-healing efficacy of the DBcAMP-incorporated dressing was evaluated on experimental full-thickness wounds in a rat model. It was found that dressing promoted wound healing leading to complete re-epithelialization of wounds within 10 days, whereas control wounds took 15 days for complete re-epithelialization. Data obtained in this study showed that the presence of DBcAMP accelerated healing and re-epithelialization of full-thickness wounds.

Alginates↗

Periodate oxidation of sodium alginate in water and in ethanol-water mixture: a comparative study.

Periodate oxidation of sodium alginate in aqueous solution as well as a dispersion in 1:1 ethanol-water was examined. The oxidation proceeded smoothly in both media, and the kinetics of oxidation was surprisingly similar. Polymer cleavage was observed in both media, but it was extensive in ethanol-water. The weight-average molar mass (Mw) of the oxidized product obtained from aqueous solution showed a gradual decrease with increase in the periodate concentration, whereas, except for very high periodate equivalent, the change in Mw was not reflected with increase in concentration of periodate in ethanol-water. The oxidized alginate obtained from the ethanol-water mixture was found to be more efficient in crosslinking proteins such as gelatin, leading to hydrogels. Oxidation of a dispersion has the advantage of generating large quantities of the oxidized alginate in higher yield with one reaction using less solvent.

Alginates↗

Chemical modification of poly(vinyl chloride) resin using poly(ethylene glycol) to improve blood compatibility.

Poly(vinyl chloride) (PVC) was aminated by treating the resin with a concentrated aqueous solution of ethylenediamine. The aminated PVC was then reacted with hexamethylene diisocyanate to incorporate the isocyanate group onto the polymer backbone. The isocyanated PVC was further reacted with poly(ethylene glycol) (PEG) of molecular weight 600 Da. The modified polymer was characterized using infrared and X-ray photoelectron spectroscopy (XPS) and thermal analysis. Infrared and XPS spectra showed the incorporation of PEG onto PVC. The thermal stability of the modified polymer was found to be lowered by the incorporation of PEG. Contact angle measurements on the surface of polymer films cast from a tetrahydrofuran solution of the polymer demonstrated that the modified polymer gave rise to a significantly hydrophilic surface compared to unmodified PVC. The solid/water interfacial free energy of the modified surface was 3.9 ergs/cm(2) as opposed to 18.4 ergs/cm(2) for bare PVC surface. Static platelet adhesion studies using platelet-rich plasma showed significantly reduced platelet adhesion on the surface of the modified polymer compared to control PVC. The surface hydrophilicity of the films was remarkably retained even in the presence of up to 30 wt% concentration of the plasticizer di-(2-ethylhexyl phthalate). The study showed that bulk modification of PVC with PEG using appropriate chemistry can give rise to a polymer that possesses the anti-fouling property of PEG and such bulk modifications are less cumbersome compared to surface modifications on the finished product to impart anti-fouling properties to the PVC surface.

Biocompatible Materials↗

Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds.

The injectable polymer scaffolds which are biocompatible and biodegradable are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural proteins and polysaccharides are ideal scaffolds for tissue engineering since they resemble the extracellular matrices of the tissue comprised of various amino acids and sugar-based macromolecules. Here, we report a new class of hydrogels derived from oxidized alginate and gelatin. We show that periodate-oxidized sodium alginate having appropriate molecular weight and degree of oxidation rapidly cross-links proteins such as gelatin in the presence of small concentrations of sodium tetraborate (borax) to give injectable systems for tissue engineering, drug delivery and other medical applications. The rapid gelation in the presence of borax is attributed to the slightly alkaline pH of the medium as well as the ability of borax to complex with hydroxyl groups of polysaccharides. The effect of degree of oxidation and concentration of alginate dialdehyde, gelatin and borax on the speed of gelation was examined. As a general rule, the gelling time decreased with increase in concentration of oxidized alginate, gelatin and borax and increase in the degree of oxidation of alginate. Cross-linking parameters of the gel matrix were studied by swelling measurements and trinitrobenzene sulphonic acid (TNBS) assay. In general, the degree of cross-linking was found to increase with increase in the degree of oxidation of alginate, whereas the swelling ratio and the degree of swelling decreased. The gel was found to be biocompatible and biodegradable. The potential of the system as an injectable drug delivery vehicle and as a tissue-engineering scaffold is demonstrated by using primaquine as a model drug and by encapsulation of hepatocytes inside the gel matrix, respectively.

Absorbable Implants↗

Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin.

Wound dressings that can be formed in situ offer several advantages over the use of preformed dressings such as conformability without wrinkling or fluting in the wound bed, ease of application and improved patient compliance and comfort. Here we describe such an in situ forming hydrogel wound dressing from gelatin, oxidized alginate and borax. Periodate oxidized alginate rapidly cross-links proteins such as gelatin in the presence of borax to give in situ forming hydrogels that are both non-toxic and biodegradable. The composite matrix has the haemostatic effect of gelatin, the wound healing-promoting feature of alginate and the antiseptic property of borax to make it a potential wound dressing material. The hydrogel was found to have a fluid uptake of 90% of its weight which would prevent the wound bed from accumulation of exudates. The water vapour transmission rate (WVTR) of the hydrogel was found to be 2686+/-124 g/m2/day indicating that the hydrogel can maintain a moist environment over wound bed in moderate to heavily exuding wound which would enhance epithelial cell migration during the healing process. The wound healing efficacy of hydrogel was evaluated in experimental full thickness wounds using a rat model which demonstrated that within 2 weeks, the wound covered with gel was completely filled with new epithelium without any significant adverse reactions. These in situ forming hydrogels fulfil many critical elements desirable in a wound dressing material.

Alginates↗

Properties and performance of sulfide-substituted plasticized poly(vinyl chloride) as a biomaterial.

Plasticized poly(vinyl chloride) (PVC) was surface modified by nucleophilic substitution of the chlorine atoms of PVC by sulfide ions in aqueous media in the presence of a phase-transfer catalyst (PTC) to make it migration resistant. The modified PVC was sterilized by steam autoclaving and gamma radiation and subjected to plasticizer extraction in an extraction medium such as hexane. Virtually no plasticizer migrated out of modified PVC into the medium even after prolonged incubation for 30 d. The properties of the modified surface were evaluated by contact angle measurements, scanning electron microscopy (SEM), cell-culture studies, hemolysis assay, and whole-blood clotting time measurements. The mechanical properties of modified sheets were evaluated by measurements of tensile strength and strain at break after subjecting the specimens to different modes of sterilization. The modified PVC surface showed enhanced wettability and was found to be non-hemolytic and non-cytotoxic. Whole-blood clotting profiles of unmodified and modified PVC were virtually the same. Modification imparted slight yellow color to the material. Surface modification resulted in an 8% decrease in the ultimate stress and 28% decrease in the strain at break values. The sulfide-substituted PVC was found to be blood compatible and would be useful in applications such as tubing for transfusion, dialysis etc., where migration resistance is important.

Animals↗

Surface thiocyanation of plasticized poly(vinyl chloride) and its effect on bacterial adhesion.

Thiocyanates, especially bis-alkylthiocyanates are highly effective in killing a number of bacterial strains and are reported to be potent biocides at ppm concentrations. In order to examine whether a covalently bound and immobilized thiocyanate group on a biomaterial surface is still effective as a bactericide, plasticized poly(vinyl chloride) (PVC) was thiocyanated using sodium thiocyanate in the presence of a phase transfer catalyst in aqueous media leading to the nucleophilic substitution of chlorine by thiocyanate on the PVC surface. Thiocyanation imparted hydrophilicity to the surface in comparison with bare PVC. Control and thiocyanated PVC surfaces were exposed to two strains of bacteria commonly implicated in device-associated infections, such as Staphylococcus aureus and Staphylococcus epidermidis. Bacterial adhesion and colonization was quantitated by counting the viable organisms on the adhered surface as well as by optical and scanning electron microscopy. Significantly reduced retention of S. epidermidis and S. aureus was seen on the thiocyanated PVC surface. Immobilized thiocyanate was non-cytotoxic in a preliminary cell culture assay. The study thus showed that even though an immobilized thiocyanate moiety on the polymer surface was not as effective as a bactericide unlike soluble thiocyanates, it prevented the retention and colonization of the bacteria to a considerable extent.

Anti-Bacterial Agents↗

Basal cell adenocarcinoma in minor salivary glands.

Basal cell adenocarcinoma is a rare and relatively recently characterized malignant salivary gland tumour, the malignant counterpart of basal cell adenoma. Diagnosis depends on finding features similar to adenoma but with an infiltrative growth pattern and exclusion of adenoid cystic carcinoma, sialoblastoma and basaloid squamous carcinoma. Basal cell adenocarcinoma is very rarely reported in minor salivary glands. We report three cases of basal cell adenocarcinoma affecting the labial, buccal and palatal minor salivary glands. One recurred following complete removal but with lesional disruption and further local wide excision appeared curative. A further lesion failed to recur in 5 years' follow-up despite marginal excision and a third after 3 years' follow-up. Basal cell adenocarcinoma is considered a low-grade malignancy, and in the minor glands wide excision and radiotherapy are recommended. However, the reported lesions appear to have a more indolent behaviour than previously reported lesions in minor glands.

Adenocarcinoma↗

A floating-type oral dosage form for piroxicam based on hollow polycarbonate microspheres: in vitro and in vivo evaluation in rabbits.

A floating type dosage form (FDF) of piroxicam in hollow polycarbonate (PC) microspheres capable of floating on simulated gastric and intestinal fluids was prepared by a solvent evaporation technique. Incorporation efficiencies of over 95% were achieved for the encapsulation. In vitro release of piroxicam from PC microspheres into simulated gastric fluid at 37 degree C showed no significant burst effect. The amount released increased with time for about 8 h after which very little was found to be released up to 24 h. In intestinal fluid, the release was faster and continuous and at high drug payloads, the cumulative release reached above 90% in about 8 h. In vivo evaluation of different dosage forms of piroxicam such as free drug, drug-encapsulated microspheres and microspheres along with a loading dose of free drug in rabbits showed multiple peaking in the plasma concentration-time curve suggesting enterohepatic recirculation of the drug. Pharmacokinetic analysis showed that the bioavailability from PC microspheres alone was about 1.4 times that of the free drug and it was about 4.8 times for the dosage form consisting of the microspheres plus the loading dose. The elimination half life was increased by about three times for the microsphere preparation alone and nearly about six times for the dosage form comprising of microspheres and a loading dose in comparison to the free drug. Data obtained in this study demonstrated that FDF of piroxicam in PC microspheres was capable of sustained delivery of the drug for longer periods with increased bioavailability.

Administration, Oral↗

Bacterial adhesion onto azidated poly(vinyl chloride) surfaces.

A plasticized poly(vinyl chloride) surface was modified by azidation using sodium azide in the presence of a phase transfer catalyst in aqueous media. Subsequent to azidation, the surface was crosslinked using ultraviolet radiation. Contact angle measurements showed that the surface became hydrophilic on azidation whereas photoirradiation did not have any further effect on the hydrophilicity of the azidated surface. Control, azidated, and photocrosslinked surfaces were exposed to two strains of bacteria commonly implicated in device infection such as Staphylococcus aureus and Escherichia coli. Whereas the control and photocrosslinked surfaces showed no significant difference in bacterial adhesion, the azidated surface showed significantly reduced adhesion to both strains. Data obtained indicate that the presence of an intact azide function on the polymer surface is responsible for the reduced bacterial adherence and the surface hydrophobicity/hydrophilicity did not exert any effect in the present case. Although azides are known to be effective only against Gram-negative species, surprising was the observation that the azidated polymer surface was equally effective against a Gram-positive species such as S. aureus. Because sodium azide is routinely used as a preservative to prevent bacterial and fungal growth in many microbiology reagents and diagnostic kits, covalent binding of the azide onto a polymer surface or synthesizing azide containing polymers may be an interesting method to investigate in tackling the problem of bacterial adhesion and colonization of medical devices.

Azides↗

Synthesis, surface properties and performance of thiosulphate-substituted plasticized poly(vinyl chloride).

Plasticized poly(vinyl chloride) (PVC) was surface modified by nucleophilic substitution of the chlorine atoms of PVC by thiosulphate in aqueous media in the presence of a phase-transfer catalyst. The properties of the modified surface were evaluated by contact angle measurements, attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy. Migration of the plasticizer di-(2-ethylhexyl) phthalate from control as well as modified PVC was examined in hexane, in cottonseed oil and in poly(ethylene glycol)-400 (PEG-400). While the modified PVC was found to be highly migration resistant in hexane, cottonseed oil and PEG-400 extracted the plasticizer. The modified PVC was found to cause haemolysis and was cytotoxic. A possible explanation for the difference in performance of the modified material in different extraction media and its toxicity is presented from a mechanistic view of the substitution process.

Animals↗

Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes of cancer patients before and after radiation treatment.

The frequency of micronucleated binucleate lymphocyte (MNBNC) was determined in the peripheral blood lymphocytes of patients suffering from various types of cancer before the onset of radiation treatment, middle (mid-) of the treatment and after completion of the treatment (post-treatment). The frequency of micronuclei increased significantly in the pretreatment sample of cancer patients when compared with the normal untreated healthy volunteers. During the middle of the radiotherapy an approximate two or > two-fold increase was observed in the micronuclei frequency in most of the patients when compared with the concurrent pretreatment samples. Immediately after the completion of treatment, the frequency of micronuclei further increased, and this increase was significantly higher than that of pretreatment and mid-treatment samples. Out of 27 patients analyzed, only nine patients did not have any history of smoking, tobacco chewing or alcohol consumption, while the remaining 18 patients had a history of either smoking, tobacco chewing or alcohol consumption or combination of two or all habits at the time of blood collection.

Adult↗

Tuberculous osteomyelitis of the mandible: a case report.

Osteomyelitis of jaws caused by infection with Mycobacterium tuberculosis is uncommon, especially in children. We present a case of tuberculous osteomyelitis in a young child. Its clinical presentation, with features similar to a dento-alveolar abscess, underline the importance of considering it in the differential diagnosis of jaw lesions. We discuss of the diagnostic techniques, management and preventive measures, and stress the importance of history taking during clinical examination.

Antitubercular Agents↗

Progesterone release from glutaraldehyde cross-linked casein microspheres: in vitro studies and in vivo response in rabbits.

Microspheres of bovine milk protein casein loaded with progesterone were fabricated by glutaraldehyde cross-linking of an aqueous alkaline solution of the protein dispersed in a hexane and dichloromethane non-aqueous dispersion medium with an aliphatic polyurethane as the stabilizer. Microspheres were characterized for their surface morphology and internal structure using scanning electron microscopy. In vitro release studies in phosphate buffer at 37 degrees C demonstrated that the rate of release of the steroid from the microsphere matrix was a function of cross-linking density, particle size, and drug payload. Microsphere formulations released 50% to 60% of the incorporated steroid in about 30 days and, thereafter, attained a steady state. In the presence of a protein-digesting enzyme such as protease, complete release of the steroid was observed in about 4 days in vitro into phosphate buffer. Intramuscular injection of progesterone-loaded microspheres into rabbits showed a plasma concentration of 1 to 2 ng/mL up to 5 months without any significant burst effect, whereas the powdered steroid administered in saline demonstrated a large burst effect peaking over 20 ng/mL, and the plasma concentration was not sustained beyond 4 days. Data obtained suggest that casein microspheres would be promising as a biodegradable drug carrier for sustained delivery of steroids.

Animals↗

Oral myiasis: a case report.

Oral myiasis is a rare condition caused by the invasion of tissues by larvae of flies. A case of gingival myiasis is presented in a 12-year-old boy with learning disability. The patient was unaware of the lesion, although it produced a swelling partially covering the teeth. The lesion was treated with ether, which forced the larvae out, and irrigated with warm saline solution. Follow-up examination revealed complete subsidence and healing of the lesion.

Animals↗

Peripheral giant cell granuloma--a case report.

Peripheral giant cell granuloma is a lesion arising mainly from the connective tissue of gingiva or periosteum of alveolar ridge. A case of peripheral giant cell granuloma involving a deciduous molar and the succedaneous tooth is reported. The lesion was large and interfered with occlusion. Surgical excision of the lesion along with the deciduous first molar was done. The underlying permanent first premolar was also involved, and had to be removed. The importance of an adequate salivary flow and maintenance of oral hygiene in the prevention of such lesions is stressed.

Bicuspid↗