Economic comparison of two strategies of oral cancer screening

Cancer is an important public health problem and new strategiesare needed for its prevention and control. Due to socioeconomicconstraints, a lack of adequate health care infrastructure andother competing health priorities in Trivandrum, there is apressing need to evaluate locally feasible and cost-effectivecancer control strategies. The Regional Cancer Centre, Thiruvananthapuram(RCCT), therefore developed and tested two innovative strategies.The first method used the mass media, the second trained unemployedyouth to carry out the initial screening process. Economic evaluationof both strategies was undertaken which showed that screeningusing young volunteers is more cost-effective, since more earlycancers and pre-cancers can be detected through this method.Screening using the mass media only, was found to be 4–9times more expensive in terms of costs per unit of outcome,than using trained volunteers. We therefore recommend the useof trained volunteers in oral cancer detection camps.     

Synthesis and biological studies of dermorphin and its analogs substituted at positions 5 and 7

Dermorphin and seven of its analogs substituted at positions 5 and/or 7, have been synthesized by the solid phase method employing mainly 9-fluorenylmethyloxycarbonylamino acid trichlorophenyl esters in presence of 1-hydroxybenzotriazole, the solid support being the Merrifield resin. Among the analogs synthesized, the most interesting is [Tyr⁷]dermorphin. It is one of the most potent dermorphin analogs reported so far. Compared to the natural peptide, it is about two times more potent in the GPI (in vitro) and nearly 1.4 times more potent in its analgesic activity in mice by the hot plate test (in vivo). Further, its antidiarrhoeal activity in mice (in vivo) is comparable to that of dermorphin. On the other hand, [Thr⁷]dermorphin is almost as potent as dermorphin.     

Crystal structure and conformation of two N-tosyl-protected dipeptides containing amino acids with polar side-chains

X-Ray diffraction studies and energy-minimization calculations were carried out on two dipeptides, N-tosyl-l -Ser-Gly-OMe monohydrate (C₁₃H₁₈N₂O₆S·H₂O, compound A) and N-tosyl-l -Thr-Gly-OMe (C₁₄H₂₀N₂O₆, compound B). Compound A crystallized in the monoclinic system, space group P2₁ with unit cell parameters a= 4.915(1), b= 15.625(4), c= 11.003(1) Å, β= 91.28(1)°, V= 844.8 ų. M_r= 348.4, d= 1.37(2) g cm^?3, Z = 2, λ(Cu Kα) = 1.5418 Å, μ= 1.99 mm^?1, T=293 K. R= 0.032 for 1451 unique reflections with I > 2σ(I). Compound B crystallized in the orthorhombic system, space group P2₁2₁2₁, with unit cell parameters a= 5.050(2), b= 16.483(3), c= 20.769(5) Å, V= 1729.3 ų, Z = 4. M_r= 344.4, d= 1.32(2) g cm^?3, μ(Cu Kα)= 1.90 mm^?1. R= 0.040 for 1060 unique reflections with I > 2σ(I). The major difference in the backbone conformation of the two compounds is in their glycine residues, with the glycine residue in compound A adopting an extended conformation with φ= - 132.6(3)° and ψ= 175.3(3)° and that in compound B having a folded conformation with φ=?56.3(6)° and ψ=?42.6(7)°. In compound A the oxygen atom of the Ser side-chain and the carbonyl oxygen atom of glycine are bridged by the water of crystallization through O—H ··· O hydrogen bonds, resulting in the relatively rare trans conformation [χ=? 175.7(2)°] for this side-chain. The Thr side-chain in compound B is in the sterically preferred (tg^?) conformation [χ^1,1=? 179.4(4)° and χ^1,2=?62.3(5)°]. The conformations were found to be in general agreement with those obtained by an energy-minimization procedure. The energy-minimized structure of N-tosyl-l -Ser-Gly-Ome (anhydrous) showed a strong hydrophobic interaction between the methyl substituents of the tosyl group and the methyl ester (C—C = 4.08 Å).     

Synthesis of peptides mediated by KOBt

Coupling of Fmoc-amino acid chlorides can be mediated by the potassium salt of 1-hydroxybenzotriazole (KOBt), the reaction being carried out in an organic medium. The use of a base like NaHC03/Na2C03 or DIEA/NMM/pyridine is not necessary. Coupling is fast and racemization free; the work-up, isolation of the product and scale-up are easy. The pentapeptide sequence of Fmoc-[Leu]enkephalin was thus synthesized in the solution phase on a 5 mmol scale without isolation of any intermediate. Acylation of C-protected N-methylamino acid esters by Fmoc-N-methylamino acid chlorides by this procedure is also feasible, as demonstrated by the synthesis of cyclosporin A fragments 4-7 and 8-11. The peptides obtained in high yields were crystalline solids, unlike earlier reports in which they were obtained mostly as oily or foamy intermediates. They showed spectral properties identical with those of the authentic compounds.