Biomedical subjects

S Lakshmi

Publications and source records attributed to S Lakshmi.

At least 19 recordsLinked to original sources

PubMed2006

Role of triple bond in 1,2-diphenylacetylene crystal: A combined experimental and theoretical study.

We have performed a combined experimental and theoretical study of the molecular system of 1,2-diphenylacetylene. The occurrence of two different geometries of the molecule in the crystal structure, one being planar and the other tilted by approximately 6 degrees , has been investigated in relation to the nature of the acetylenic linker. The experimental charge density analysis shows that the acetylenic linker exhibits a noncylindrical density reminiscent of the strong conjugation present in the molecule. The pi-orbitals of the acetylenic linker derived from density functional theory (DFT) calculations are found to sustain a variety of conjugation lengths between the phenyl rings, thereby giving flexibility to the molecule to arrange itself in various packing conformations in the crystal. It is interesting that the energy involved for such distortions is only kBT, allowing several polymorphic forms of the crystal structure as reported in the literature. The distortions entertained by the molecule and the corresponding changes in the charge density distribution and energy are all relevant to molecular electronics.

Journal Article↗

PubMed2006

Coexpression of Notch1 and NF-kappaB signaling pathway components in human cervical cancer progression.

OBJECTIVES: Features of deregulated Notch1 signaling and NF-kappaB activation have independently been reported in cervical cancers. Here, we have extended these observations and examined both these pathways simultaneously in human cervical cancer tissue. Further, we have investigated the potential cross-talk between these pathways in a human cervical cancer derived cell line CaSki, which mirrors features of Notch activation as in the majority of human cervical cancers. METHODS: Cervical tissue samples were analyzed for the expression of Notch1, Jagged 1, Hes1, pAKT, NF-kappaB p50, NF-kappaB p65, IkappaB-alpha, Bcl-2, CyclinD1, Cdk9, c-Fos, and p53 by immunohistochemistry. A total of 352 samples were analyzed which included 69 normal cervical tissue, 132 preinvasive lesions and 151 squamous cell carcinomas of the uterine cervix. Dual immunofluorescent analysis was performed to evaluate the coexpression of Notch1 and NF-kappaB. Transcriptional reporter assays and xenografts were undertaken with CaSki cells. RESULTS: Features of Notch1 activation as measured by intracellular Notch1, high levels of Jagged1, Hes1 and Cdk9 were paralleled by nuclear translocation of both NF-kappaB p50 and p65 with target gene expression (IkappaB-alpha, Bcl-2, and CyclinD1) in human cervical cancer sections. Reporter assays in CaSki cells are consistent with Notch being an upstream regulator of NF-kappaB. Further, the xenografts recreate key aspects of human cancer tissue. CONCLUSIONS: Results from this study suggest that there is a co-activation of Notch1 and NF-kappaB signaling pathways at the cellular level in the majority of human cervical cancers, with Notch as an upstream regulator.

Animals↗

PubMed2006

Activation of Src/kinase/phospholipase C/mitogen-activated protein kinase and induction of neurite expression by ATP, independent of nerve growth factor.

Extracellular ATP has been reported to potentiate the neurite outgrowth induced by nerve growth factor. In the present study the neurotrophic effect of ATP and other nucleotides was examined in mouse neuroblastoma neuro2a cells which lack nerve growth factor receptor. Exposure of neuro2a cells to ATP resulted in a dramatic increase in neurite bearing cells as compared with untreated control cells. Experiments performed with purinergic receptor agonists and antagonists suggest that the ATP stimulates neurite outgrowth via P2 receptors. Neurite outgrowth was completely blocked by P2 receptor antagonist suramin whereas the P1 receptor antagonist CGS15943 was ineffective. P1 receptor agonist 5'-(N-ethylcarboxamido)adenosine failed to induce neurite outgrowth. The potency order of different P2 receptor agonists was ATP=ATPgammaS>ADP>>2Me-S-ATP. It was insensitive to UTP and antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) suggesting the involvement of P2Y11 receptor in the observed neuritogenic effect. The signaling pathway leading to ATP-induced neuritogenesis was investigated. The neuritogenic effect of ATP is independent of rise in intracellular Ca(2+) as pharmacological profile of neuritogenic P2Y receptor does not match with that of P2Y2 receptor associated with [Ca(2+)](i) signaling cascade. Exposure of cells to ATP caused activation of Src kinase, phospholipase Cgamma and extracellular signal-regulated kinases ERK1/2. Mitogen-activated protein kinase (MAPK) inhibitor U0126 drastically reduced the number of neurite bearing cells in ATP-treated cultures implying that the neurotrophic effect of ATP is mediated by MAPK. Our results demonstrate that ATP can stimulate neurite outgrowth independent of other neurotrophic factors and can be an effective trophic agent.

Adenosine↗

PubMed2006

Formation of hydroxyapatite-polyphosphazene polymer composites at physiologic temperature.

Aspects of the formation of bone analog composites at 37 degrees C are described. The composites are composed of hydroxyapatite (HAp) and the calcium salt of a biocompatible polymer and are capable of forming under in vivo conditions. Composite formation involves the formation of monolithic HAp from particulate calcium phosphate precursors while Ca ions liberated to the aqueous medium in which this reaction is occurring form crosslinks with the acidic polymer. The reactants are poly[bis(carboxylatophenoxy)phosphazene] (acid-PCPP), tetracalcium phosphate [Ca4(PO4)2O, TetCP], and anhydrous dicalcium phosphate (CaHPO4, DCPA). The effects of the proportion of polymer (5, 10, or 15 wt %) on the kinetics of HAp formation were studied. Compositional evolution of the solid calcium phosphates present was followed by X-ray diffraction and infrared spectroscopy analyses. HAp formation through a dissolution-precipitation process provided a mildly alkaline medium suitable for deprotonation of the acid-PCPP and for the formation of the calcium crosslinks, as monitored by infrared spectroscopy. Concurrence of crosslinking of the polymer and HAp formation was established, indicating true composite formation can be realized at physiologic temperature.

Biocompatible Materials↗

PubMed2006

Biochemistry of homocysteine in health and diseases.

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.

Animals↗

PubMed2005

Composite formation from hydroxyapatite with sodium and potassium salts of polyphosphazene.

The low temperature synthesis of composites potentially suitable as bone substitutes which form in vivo, was investigated. The composites were comprised of stoichiometric hydroxyapatite (SHAp) and water-soluble poly phosphazenes. These constituents were selected because of their biocompatibility, and were mixed as powders with a phosphate buffer solution (PBS) to form the composites. The effects of poly[bis(sodium carboxylatophenoxy)phosphazene] (Na-PCPP) or poly[bis(potassium carboxylatophenoxy) phosphazene] (K-PCPP) on stoichiometric hydroxyapatite (SHAp) formation from tetracalcium phosphate and anhydrous dicalcium phosphate were assessed. The kinetics and reaction chemistries of composite formation were followed by isothermal calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. In the presence of 1% by weight of polyphosphazenes, composites comprised of SHAp and calcium cross-linked polymer salts were formed. Thus a mechanism for binding between polymer chains was established. Elevated proportions (5 and 10% by weight) of polyphosphazene, however, resulted in the inhibition of SHAp formation. This is attributed to the formation of viscous polymer solution coatings on the calcium phosphate precursors, retarding their reaction, and consequently inhibiting SHAp formation.

Biocompatible Materials↗

PubMed2005

Low temperature formation of hydroxyapatite-poly(alkyl oxybenzoate)phosphazene composites for biomedical applications.

The formation of biodegradable composites which may be suitable as bone analogs is described. Polyphosphazene-hydroxyapatite (HAp) composites were produced via an acid-base reaction of tetracalcium phosphate and anhydrous dicalcium phosphate in the presence of polyphosphazenes bearing alkyl ester containing side-groups. The polyphosphazenes used were poly(ethyl oxybenzoate)phosphazene (PN-EOB) and poly(propyl oxybenzoate) phosphazene (PN-POB). The effects of temperature and the proportions of polymers, PN-EOB and PN-POB on the kinetics, reaction chemistry and phase evolution during the formation of stoichiometric HAp were studied. Kinetics, phase evolution and microstructural development were evaluated using isothermal calorimetry, X-ray diffraction and scanning electron microscopy, respectively. Analysis of solution chemistry revealed that the increases in the pH during the formation of SHAp, resulted in partial hydrolysis of the polymer surfaces, which led in turn to the formation of a calcium cross-linked polymer surface. The calcium cross-linked polymer surface appeared to facilitate the nucleation and growth of apatite deposits on the polymer. The current study illustrates the in situ formation of HAp in the presence of polyphosphazenes, where HAp is chemically bonded to the polymer.

Absorbable Implants↗

PubMed2005

Schwannoma of the palatine tonsil.

Schwannoma is a solitary, benign tumour arising from the neural sheath Schwann cells of the peripheral, cranial or autonomic nerves. In the head and neck region, it occurs most commonly in association with the acoustic nerve within the skull and is rarely found in oral structures. When it is found in oral structures, the tongue is reported to be the favoured site. Schwannoma of the tonsil is extremely rare, with only two cases reported in the literature. We report what is, to our knowledge, the third case of schwannoma of the tonsil, diagnosed by histopathology.

Adult↗

PubMed2004

Effect of electron-phonon coupling on the conductance of a one-dimensional molecular wire.

The effect of inelastic scattering, particularly that of the electron-phonon interactions, on the current-voltage characteristics of a one-dimensional tight-binding molecular wire has been investigated. The wire has been modeled using the Su-Schreiffer-Heeger Hamiltonian and we compute the current using the Landauer's scattering formalism. Our calculations show that the presence of strong electron-lattice coupling in the wire can induce regions of negative differential resistance (NDR) in the I-V curves. The reasons for this can be traced back to the quasidegeneracy in few of the low-energy molecular levels in the presence of electron-phonon coupling and an external applied bias. The molecular levels become highly delocalized at the critical bias at which the NDR is seen, corresponding to the vanishing of the electron-phonon coupling with equal bond lengths.

Journal Article↗

PubMed2003

Biodegradable polyphosphazenes for drug delivery applications.

Biodegradable polymers such as poly(alpha-hydroxy acids), poly(anhydrides), poly(ortho esters), poly(amino acids) and polyphosphazenes have raised considerable interest as short-term medical implants due to their transient nature. Among these, polyphosphazenes are a relatively new class of polymers, quite distinct from all the biodegradable polymers synthesized so far, due to their synthetic flexibility and versatile adaptability for applications. These are high molecular weight, essentially linear polymers with an inorganic backbone of alternating phosphorous and nitrogen atoms bearing two side groups attached to each phosphorous atom. Controlled tuning of physico-chemical properties, including biodegradability, can be achieved in this class of polymers via macromolecular substitutions. Biodegradable polyphosphazenes, due to their hydrolytic instability, nontoxic degradation products, ease of fabrication and matrix permeability, are an excellent platform for controlled drug delivery applications. This review discusses the mode of degradation and drug delivery applications of biodegradable polyphosphazenes.

Animals↗

PubMed2003

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↗

PubMed2002

Toxicity, biodegradation and elimination of polyanhydrides.

Although originally developed for the textile industry, polyanhydrides have found extensive use in biomedical applications due to their biodegradability and excellent biocompatibility. Polyanhydrides are most commonly synthesized from diacid monomers by polycondensation. Efficient control over various physicochemical properties, such as biodegradability and biocompatibility, can be achieved for this class of polymers, due to the availability of a wide variety of diacid monomers as well as by copolymerization of these monomers. Biodegradation of these polymers takes place by the hydrolysis of the anhydride bonds and the polymer undergoes predominantly surface erosion, a desired property to attain near zero-order drug release profile. This review examines the mode of degradation and elimination of these polyanhydrides in vivo as well as the biocompatibility and toxicological aspects of various polyanhydrides.

Anhydrides↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2001

Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting.

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin-mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 microg x kg(-1) x min(-1) (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24-h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml x min(-1) (p < 0.01) and from 107 (36) to 79 (26) ml x min(-1) (p < 0.01) for the 0-4 h and 4-8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.

Acute Kidney Injury↗

PubMed2001

The effects of fenoldopam on coronary conduit blood flow after coronary artery bypass graft surgery.

OBJECTIVE: To quantify the effects of fenoldopam, 0.1 microg/kg/min, on left internal mammary artery (LIMA) and saphenous vein blood flow after coronary anastomosis. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: University teaching hospital, single institution. PARTICIPANTS: Thirty-one American Society of Anesthesiologists III patients undergoing elective coronary revascularization. INTERVENTIONS: A perivascular ultrasonic flow probe (Linton Instrumentation, Norfolk, UK) was placed around the LIMA and saphenous vein graft after coronary anastomosis. MEASUREMENTS AND MAIN RESULTS: Immediately before and at 5-minute intervals for 15 minutes after starting the infusion, blood flow was measured in the LIMA and one saphenous vein graft using a transit time ultrasonic flow probe. Heart rate, blood pressure, and central venous pressure were documented at these time points. Administration of fenoldopam, 0.1 microg/kg/min, did not alter heart rate or blood pressure. A small, nonsignificant increase in LIMA blood flow occurred during the 15-minute study period (30 +/- 12 to 35 +/- 10 mL/min) in patients who received fenoldopam. No significant changes occurred in the placebo group. CONCLUSIONS: The findings indicate that fenoldopam, 0.1 microg/kg/min, did not influence coronary conduit blood flow to a clinically significant extent. The small increase in LIMA blood flow may be of greater importance in high-risk patients or in the prevention of coronary arterial spasm.

Aged↗

PubMed2001

Evaluation of psychopharmacological effects of Clerodendrum phlomidis Linn. extract.

The methanolic extract of Clerodendrum phlomidis Linn. (MECP) leaves was evaluated for its psychopharmacological activities in several experimental models using Swiss albino mice and Wistar albino rats. The MECP was found to cause significant reduction in spontaneous activity, and decreases in exploratory behavioral profiles by the Y-maze and head dip test. It also showed reduction in muscle relaxant activity by rotarod, 30 degrees inclined screen and traction tests, as well as significantly potentiated the phenobarbitone sodium-induced sleeping time in the doses examined (200, 400 and 600 mg/kg body wt.). All the results were compared with respective controls for the evaluation of significance.

Acacia↗