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N V Prabhu

Publications and source records attributed to N V Prabhu.

11 recordsLinked to original sources
PubMed2001

Structural basis for the activity of pp60(c-src) protein tyrosine kinase inhibitors.

Conformational searches on three closely related pp60(c-src) protein tyrosine kinase inhibitors of varying potencies were performed to determine a structural basis for their activity. The first was a linear peptide (PDNEYAFFQf), the second its 10-membered cyclic analogue, and the third a cyclic analogue with a para carboxyphenylalanine in place of one the F residues. A common backbone conformation with an antiparallel beta-sheet-like geometry capped by similar beta-turns was found for all three peptides, which may be a binding conformation and gives a candidate pharmacophore for further testing. The interaction between some polar side chains and between some of the aromatic rings may be important for maintaining the correct conformation. The differences in potencies of these inhibitors may be attributed to certain thermodynamic and chemical reasons.

Amino Acid Sequence↗
PubMed1999

Comparison of the potentials of mean force for alanine tetrapeptide between integral equation theory and simulation.

The dielectrically consistent reference interaction site model (DRISM) integral equation theory is applied to determine the potential of mean force (PMF) for an alanine tetramer. A stochastic dynamics simulation of the alanine tetramer using this PMF is then compared with an explicit water molecular dynamics simulation. In addition, comparison is also done with simulations using other solvent models like the extended reference interaction site model (XRISM) theory, constant dielectric and linear distance-dependent dielectric models. The results show that the DRISM method offers a fairly accurate and computationally inexpensive alternative to explicit water simulations for studies on small peptides.

Algorithms↗
PubMed1999

Structure and dynamics of alpha-MSH using DRISM integral equation theory and stochastic dynamics.

The structural and dynamical features of the hormone alpha-MSH in solution have been examined over a 100 ns time scale by using free energy molecular mechanics models at room temperature. The free energy surface has been modeled using methods from integral equation theory and the dynamics by the Langevin equation. A modification of the accessible surface area friction drag model was used to calculate the atomic friction coefficients. The molecule shows a stable beta-turn conformation in the message region and a close interaction between the side chains of His6, Phe7, and Trp9. A salt bridge between Glu5 and Arg8 was found not to be a preferred interaction, whereas a Glu5 and Lys11 salt bridge was not sampled, presumably due to relatively high free energy barriers. The message region was more conformationally rigid than the N-terminal region. Several structural features observed here agree well with experimental results. The conformational features suggest a receptor-hormone interaction model where the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the MC1 receptor. Also, the positively charged side chain of Arg8 and the imidazole side chain of His6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops.

Algorithms↗
PubMed1999

Modeling of alpha-MSH conformations with implicit solvent.

A conformational search for the most probable structures of the hormone alpha-MSH in aqueous solution was performed in order to help determine the structural features necessary for biological activity. The free-energy surface was modeled using methods from integral equation theory, and high-temperature molecular dynamics was used to enhance conformational sampling. Families of low free-energy structures have been found. The minimum energy structure shows a stable beta-turn conformation in the putative message region that is stabilized by a salt bridge between Glu5 and Lys11. The orientation of the side chains reflects the amphiphilic nature of the peptide, and a close interaction between the side chains of the His6, Phe7 and Trp9 was observed. Several structural features observed in the minimum energy structure agree well with experimental results. The conformational features led to a hypothesis of a receptor-hormone interaction model in which the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the human melanocortin (MC1) receptor. Also, the positively charged side chain of Arg8 and the imidazole side chain of His6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops.

Computer Simulation↗
PubMed1995

Rationalizing venepuncture pain: comparison of lignocaine injection, Butterfly (21 gauge and 23 gauge) and Venflon (20 gauge).

Two hundred and seventy-eight patients scheduled for all types of surgery and premedicated with diazepam and metoclopramide were randomly allocated to one of four groups to compare the relative pain of an injection of 0.25 ml of lignocaine 1% via a 25 gauge needle with the pain of the siting of a 21 gauge Butterfly (Abbott), 23 gauge Butterfly or a 20 gauge Venflon (Vigo Spectramed). The injection of lignocaine and insertion of the 23 gauge Butterfly were associated with the least complaints of pain and least observed responses to pain. The 21 gauge Butterfly and 20 gauge Venflon were associated with complaints of greater pain and more pain responses. We conclude that a pre-cannulation injection of lignocaine causes minimal discomfort and is the most appropriate means of reducing the discomfort of venous cannulation when not using skin penetrating analgesic creams.

Adolescent↗
PubMed1995

Comparison of total intravenous, balanced inhalational and combined intravenous-inhalational anaesthesia for tympanoplasty, septorhinoplasty and adenotonsillectomy.

Two hundred and thirty-five consecutive Saudi patients aged between two and fifty-three years undergoing elective tympanoplasty (n = 32), septorhinoplasty (n = 68) or adenotonsillectomy (n = 135) were studied. They were randomized to receive either a total intravenous anaesthetic (10 ears, 23 noses, 44 throats) consisting of propofol for induction of anaesthesia followed by a propofol infusion, a combined intravenous-inhalational anaesthetic (11 ears, 22 noses, 46 throats) consisting of the above with isoflurane in oxygen-enriched air, or a balanced inhalational anaesthetic (11 ears, 23 noses, 45 throats) consisting of thiopentone for induction of anaesthesia and oxygen in nitrous oxide with isoflurane for maintenance. During tympanoplasty, all three anaesthetic techniques produced stable heart rates and arterial pressures. During septorhinoplasty, blood pressure rose in patients who received total intravenous anaesthesia, while combined and balanced techniques produced haemodynamic stability. During adenotonsillectomy, total intravenous anaesthesia produced a rise in both heart rate and blood pressure, the combined technique produced a rise in heart rate alone while balanced anaesthesia produced haemodynamic stability. Postoperatively, vomiting, pain scores and analgesic requirements were similar following all three types of anaesthetic within each surgical site subgroup. Our findings support the choice of balanced inhalational anaesthesia for all three types of ENT surgery and, where cost and facilities permit, total intravenous anaesthesia for tympanoplasty and combined intravenous-inhalational anaesthesia for septorhinoplasty.

Adenoidectomy↗
PubMed1995

Spontaneous respiration versus controlled ventilation anaesthesia with halothane for intra-ocular surgery.

One hundred and thirty-seven patients were randomly allocated to receive halothane anaesthesia for intra-ocular surgery either by IPPV (n = 71) or breathing spontaneously (n = 66). Both techniques provided satisfactory operating conditions in 87% and 80% of procedures, respectively. Intra-ocular pressure was reduced in a similar majority of patients, rose in a similar percentage (spontaneous = 11%, controlled = 21%) and remained unchanged in a few. Surgeons' reports of good operative conditions correlated very well with intra-ocular pressure changes whether they rose or fell intra-operatively. The duration of anaesthesia and the time taken to achieve full recovery following the two techniques were similar. Post-operative vomiting, headache, sore throat and confusion occurred with similar frequency, and analgesic and antiemetic requirements were not influenced by the technique. Resumption of ambulation, oral intake and micturation occurred similarly. In both groups, patients with a low normal pre-operative intra-ocular pressure tended to show a rise in intra-ocular pressure during anaesthesia, and those with a high normal pre-operative intra-ocular pressure tended to show a fall.

Anesthesia, Inhalation↗
PubMed1994

Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia.

1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery.

Adolescent↗