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Biomedical subjects

Gundu H R Rao

Publications and source records attributed to Gundu H R Rao.

5 recordsLinked to original sources

Effect of low doses of ethanol on platelet function in long-life abstainers and moderate-wine drinkers.

In vitro, high concentrations of ethanol (EtOH) reduce platelet aggregation. Less is known about the effect of low EtOH doses on platelet function in a selected human population of long-life abstainers and low moderate-wine drinkers to avoid rebound effect of EtOH on platelet aggregation. Results of our experiments suggest that moderate-wine drinkers have higher levels of high density lipoprotein (HDL) than long-life abstainers while fibrinogen levels are unchanged. Furthermore, platelets obtained from these individuals do not differ in their response when stimulated by agonists such as AA and collagen. The effect of in vitro exposure of low doses of EtOH has been studied in PRP and in washed platelets. EtOH (0.1-10 mM) inhibits platelet aggregation induced by collagen at its ED50 while is ineffective when aggregation was triggered by U-46619 and by 1 microM adenosine diphosphate (ADP). 5-10 mM EtOH partially reduces the second wave of aggregation induced by 3 microM ADP. 0.1-10 mM EtOH dose-dependently lowers the aggregation induced by AA at its ED50 but it is less effective at ED75 of AA. The antiaggregating effect of EtOH on aggregation induced by AA is unchanged by inhibitor of nitric oxide synthase. In addition, 10 mM EtOH reduces thromboxane (Tx) formation. In washed platelets, 1-10 mM EtOH partially inhibits platelet aggregation induced by thrombin. In washed resting platelets, 10 mM EtOH does not change the resting [Ca++]i while significantly reduces the increase in [Ca++]i triggered by AA. The results of ex vivo experiments have demonstrated that wine increases the HDL. However, this observation may or may not influence the response of platelets to agonists. Results of our studies demonstrate that low doses of alcohol reduces platelet function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

The development of porous alginate/elastin/PEG composite matrix for cardiovascular engineering.

The development of suitable three-dimensional matrices for the maintenance of cellular viability and differentiation is critical for applications in tissue engineering and cell biology. To this end, gel matrices of different proportions of alginate/elastin/polyethylene glycol (Alg/Ela/PEG) were prepared and examined. The composite matrix membranes were evaluated for their porous scaffold using SEM, enzymatic degradation and water content. An equal blend of Alg/Ela with a ratio of Alg/Ela: PEG (7:3) was selected for fabricating Alg/Ela/PEG scaffolds for this study. The Alg/Ela/PEG membranes fabricated at 20 degrees C and - 20 degrees C had a mean surface pore size of 35-45 microm. However, their ultrastructures had shown bigger pore structures (60-75 microm) compared to their surface. It is interesting to note that the membranes of Alg/Ela/PEG prepared at 20 degrees C had larger ultrastructural pores than that of membranes prepared at -20 degrees C. Further, the SEM studies revealed that in the absence of PEG the composite membranes of Alg/Ela formed with less porous structures. The water content of membranes prepared at 20 degrees C was higher with Alg/Ela/PEG (61.6 +/- 4.8%), compared to Alg/Ela (49.9 +/- 0.3%). The enzymatic degradation and water content studies also revealed that the membranes fabricated at - 20 degrees C had high water uptake and low enzymatic degradation, as that of the membranes prepared at 20 degreees C. In other words the larger pore structured membranes had less water content and high degradation profile. This study proposes that this novel composite matrix produces a hierarchical structure that is useful for generating tissue scaffolds for repairing the failing cardiac muscles. However, more detailed investigations with cytocompatibility studies are needed to find applications.

Alginates↗

A new platelet preservative.

A new platelet preservative, ViaCyte trade mark (balanced salt solution, physiological buffer, D-ribose, bovine serum albumin, D-glucose, sterile water) was tested against the presently used storage solution (citrate-phosphate-dextrose; CPD) and results revealed that ViaCyte demonstrated added protection for platelets during storage-induced activation. Following five days of storage at room temperature, only 12.2% of platelets stored in ViaCyte exhibited P-selectin expression at rest and, upon thrombin challenge, 64.2% were activated, an increase of 42%. In control platelets (platelets stored in CDP), 44.4% were activated due to storage-induced lesions, and thrombin stimulation resulted in 47.9% P-selectin expression, an increase of only 2.5%. ViaCyte storage maintained the resting state and preserved platelet function, making more platelets available for activation upon agonist challenge. This preliminary study demonstrated that the presently used standard preservative does not offer protection from storage-induced lesions. Partially dysfunctional platelets do not contribute significantly to hemostasis in vivo and play little role, if any, in clot retraction and wound healing processes.

Blood Platelets↗

Changes in cisplatin delivery due to surface-coated poly (lactic acid)-poly(epsilon-caprolactone) microspheres.

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 sustained drug delivery to the arterial wall is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, cisplatin, in a series of surface coated biodegradable microspheres composed of poly(lactic acid)poly(caprolactone) blends, with a mean diameter of 2-10 pm. The microspheres were surface coated with poly ethylene glycol (PEG), chitosan (Chit), or alginate (Alg). A solution of cisplatin and a 50:50 blend of polylactic acid (PLA)-polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol or Chit or Alg) with stirring using a high speed homogenizer, for the formation of microspheres. Cisplatin recovery in microspheres ranged from 25-45% depending on the emulsification system used for the preparations. Scanning electron microscopy revealed that the PLA-PCL microspheres were spherical in shape and had a smooth surface texture. The amount of drug release was much higher initially (20-30%), this was followed by a constant slow-release profile for a 30-day period of study. It has been found that drug release depends on the amount of entrapped drug, on the presence of extra cisplatin in the dispensing phase, and on the polymer coatings. This PEG or Alg-coated PLA/PCL microsphere formulation may have potential for the targeted delivery of antiproliferative agents to treat restenosis.

Cisplatin↗

Delivery of LMW heparin via surface coated chitosan/peg-alginate microspheres prevents thrombosis.

Heparin remains the gold-standard inhibitor of the process involved in the vascular response to injury. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin (LMW Hep) or with an orally active anticoagulant such as warfarin. An oral heparin would avoid the inconvenience of subcutaneous injections and adverse events associated with warfarin. A mild chitosan/PEG/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as heparin and LMW Hep was investigated. Heparin and LMW Hep entrapped alginate beads were further surface/enteric coated with chitosan and cellulose acetate phthalate (CAP) via carbodiimide (EDC) functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 hours and no significant release of LMW Hep was observed from enteric coated microspheres (12%) during treatment with 0.1 M HCl, pH 1.0 for 4 hours. But acid treated capsules had released almost all the entrapped LMW Hep into Tris-HCl, pH 7.4 media within 6 hours. From scanning electron microscopic and swelling studies, it appeared that the surface coatings (via chitosan and CAP) had modified the alginate microspheres and subsequently the drug release. The released heparin and LMW Hep had shown their anticoagulant functions. These results established the feasibility of modifying the formulation in order to obtain the desired controlled release of bioactive agent (LMW Hep), for a convenient pH dependent delivery system.

Alginates↗