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Biomedical subjects

K Narayanan

Publications and source records attributed to K Narayanan.

At least 73 records · Page 4Linked to original sources

Recombinant hirudin--initial observations in reconstructive microsurgery.

Recent advances in microvascular techniques have significantly enhanced the success rate of these procedures. Microvascular free tissue transfers at present have a 85-90% success rate. This, however, still leaves a 10-15% failure rate due primarily to thrombosis of the blood vessels at the anastomotic site. Previous work in the field has shown that anticoagulants such as heparin can reduce the rate of thrombosis. However, heparin can also cause on-site bleeding. Hirudin, a potent thrombin inhibitor of 65 amino acids, is available through recombinant technology. Our current experimental work utilized 75 male Sprague-Dawley rats for assessing the efficacy of hirudinized saline versus saline alone and heparinized saline as an irrigant in a microsurgery model of anastomosis. After exposing the right femoral artery in a standard fashion, the artery was clamped and a standard transverse division of the vessel was made. The vessel ends were irrigated with one of the three solutions then anastomosed. Vessels were observed for patency over a 3-day period. Initial results showed comparable performance of hirudinized saline and heparized saline, both of which were better than saline, for preventing thrombosis. From these initial data, and the reduced bleeding risk associated with hirudin, this agent appears to be a useful anticoagulant in microsurgery.

Anastomosis, Surgical↗

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site.

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗

The use of cryopreserved venous allografts in free tissue transfers--practical and aesthetic considerations.

A case in which multiple cryopreserved allograft saphenous veins were used as vein grafts for a difficult mandible reconstruction with a free tissue transfer is reviewed. Use of allograft veins was recently reported for lower limb vascular reconstruction but not for free tissue transfers. Such grafts may represent a viable alternative to the use of autologous vein grafts and have the potential to decrease operating time and avoid necessary scars.

Adult↗

The influence of the calcium channel blocker nimodipine on flap survival.

The calcium channel blocker nimodipine has been used successfully in neurological patients for the treatment of vasospasm after subarachnoid hemorrhage and stroke. In this study of experimental random pattern skin flaps in rats, an increase of nearly 50% in the survival rate to 94.33% (+/- 7.3% standard deviation) under nimodipine treatment versus 66.00% (+/- 16.5% standard deviation) in the controls could be demonstrated (p less than 0.001). Vital dye injections in a separate experiment indicated that the increased flap survival is mainly due to improved microcirculation. The distance traveled by the dye was 8.01 +/- 1.21 cm in the experimental versus 6.61 +/- 1.25 cm in the control group (p less than 0.05).

Animals↗

The critical relationship between free radicals and degrees of ischemia: evidence for tissue intolerance of marginal perfusion.

UNLABELLED: Skin-flap ischemia has been associated with the presence of free radicals. In this study, two enzyme systems involved in free-radical metabolism were used to compare a distal skin flap to a skin graft. Forty-two rats were divided into several test groups. A 10 X 3 cm dorsal rat flap was used, and tissue biopsies for xanthine oxidase and malonyldialdehyde (MDA) were obtained 2.5, 5.5, and 8.5 cm from the base of the flap at the hours given. In group I (control), the flap was outlined but not elevated, and biopsies were obtained. In group II, the flap was elevated, and biopsies were obtained at 6 hours. In group III, the flap was elevated, the distal 4 X 3 cm was amputated and replaced as a full-thickness skin graft, and biopsies were obtained at 6 hours. In group IV, the flap was elevated, and biopsies were obtained at 12 hours. In group V, the flap was treated as in group III, and biopsies were obtained at 12 hours. In group VI, the flap was elevated, and biopsies were obtained at 24 hours. In group VII, the flap was treated as in group III, and biopsies were obtained at 24 hours. RESULTS: Xanthine oxidase was significantly higher in all distal biopsies compared to proximal biopsies. Xanthine oxidase also increased with time. Malonyldialdehyde increased over time as well as with distance from the flap base. Distal flap biopsies at 24 hours had greatly increased levels of malonyldialdehyde compared to skin grafts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Immunomodulation of intradermal mammary carcinoma using staphage lysate in a rat model.

Staphage lysate (SPL), a preparation of Staphylococcus aureus obtained by bacteriophage lysis, is an interferon-inducer and stimulator of T and B lymphocytes. Does SPL, as an immunopotentiator, have an effect on the growth and metastases of an intradermal mammary carcinoma? To answer this question, a study using SPL in female Fischer rats injected with 7 x 10(6) viable 13762 mammary tumor cells on the midback were used. Four groups were created with 10 animals in each group. Group I was the control group. They received no treatment. Group II received 0.3 ml of medium in which SPL was carried on alternate days. Group III received 0.3 ml SPL on alternate days. Group IV were sensitized with dead staphylococcal organisms prior to SPL treatment as in Group III. Tumor diameters were recorded on days 10, 13, 17, and 21, and autopsies were performed to determine the extent of metastases. Histologic examination and serum antibody measurements were performed. The mean tumor diameters on day 21 were: Group I: 4.1 +/- 0.2 cm; Group II: 3.80 +/- 0.19 cm; Group III: 3.04 +/- 0.13 cm; and Group IV: 2.97 +/- 0.14 cm. Rats receiving SPL treatment in Groups III and IV had significantly smaller tumors (P less than .001). The incidence of axillary lymph node involvement was: Group I: 100%; Group II: 87.5%; Group III: 62.5%; and Group IV: 40%. Lung metastases were seen in all groups. Groups I and II had 100% incidence of grossly visible nodules, whereas Groups III and IV had 75% and 70% involvement. Gross findings were confirmed by microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A simple microretractor.

The use of bulky retractors in experimental microsurgical procedures creates interference with the limited operative field. The current article describes a small but effective retractor made from ordinary staples, which are inexpensive and easily accessible.

Animals↗

Augmentation of skin flap survival with allopurinol.

Although allopurinol is primarily known as an effective medication for gout, it has been shown to enhance tissue survival in a wide range of ischemic conditions. The study reported here investigated the effects of allopurinol on flap survival in a dorsal rat model. In a preliminary study, animals were given varying doses of allopurinol (0 to 400 mg per kilogram). A clinically efficacious dose was established upon conclusion of the test period by laboratory determinations and necropsy data. Other animals were divided into 3 groups: 1 (saline control), N = 11; 2 (50 mg per kilogram of allopurinol daily), N = 10; 3 (100 mg per kilogram of allopurinol qd), N = 11. Flaps were raised and necrosis assessed at 8 days. Flaps treated with allopurinol 100 mg per kilogram had significantly better survival than the controls (p less than 0.001) and 50 mg per kilogram (p less than 0.01). Allopurinol 50 mg per kilogram had no effect on flap survival.

Allopurinol↗

Deferoxamine increases skin flap survival: additional evidence of free radical involvement in ischaemic flap surgery.

This study presents further evidence of free radical involvement in skin flap necrosis in a dorsal rat flap model. Rats receiving deferoxamine, a free radical scavenger and iron chelator had significantly less necrosis (p less than 0.001) than saline treated rats. In a separate experiment, tissue determinations for malonyldialdehyde (MDA) were consistent with the survival results in showing a significant decrease in MDA in all biopsy sites (p less than 0.05 or less), indicative of reduced lipoperoxidation in the deferoxamine treated rats.

Animals↗

Studies on the nature of the flap/bed interaction in rodents--Part I: Flap survival under varying conditions.

A flap needs close contact with its bed for optimal flap survival. Using a rat dorsal flap model, flap/bed contact times were varied by use of a sterile polyethylene film. In addition, the flap was modified either by removing the panniculus carnosus or by converting the distal flap into a skin graft. Finally, the effect of using a dressing was assessed. Several observations were made: (1) The initial 6 to 12 hours of a flap's interaction with its bed is critical for optimal survival; (2) fluorescein accurately predicted flap survival upon polyethylene removal; (3) removing the panniculus carnosus increased flap and skin graft survival; (4) dressing allowed flaps and skin grafts to better withstand bed deprivation; and (5) distal flaps and skin grafts under various conditions responded differently to bed deprivation.

Animals↗