Effect of Milliamperage Reduction on Pre-surgical Implant Planning Using Cone Beam Computed Tomography by Surgeons of Varying Experience.

BACKGROUND: Differences in CBCT units and the lack of standardization result in exposure to radiation doses beyond what is required for diagnostic purposes, especially when planning the surgical placement of dental implants. AIM: To assess the influence of low- and high-dose milliamperage settings on CBCT images for objective and subjective implant planning among senior specialists (5 years of experience) and juniors (fresh graduates). MATERIALS AND METHODS: Two dry skulls (4 hemi-maxillary segments of the maxilla and 4 hemi-maxillary segments of the mandible) were scanned under low (2 mA) and high (6.3 mA) dosage settings using the Carestream CS 9300 machine. Cross-sectional slices of both image qualities were evaluated by the 5 seniors and the 5 juniors for subjective image utility for implant planning and for objective linear bone measurements. RESULTS: There were no significant differences in bone measurements taken on high- or low-dose images by all seniors and by the majority of juniors (p > 0.05). In qualitative image assessments, there was independence between assessment and image quality for almost all observers. For planning posterior mandibular implant placement, increased dosage improved concordance and kappa values between low- and high-dose images for senior observers (from K = 0.287 at low dose to K = 0.718 at high does) but not for juniors (K = 0.661 and K = 0.509 for low and high dose, respectively). CONCLUSION: Reduction in milliamperage did not affect diagnostic image quality for objective bone measurements and produced sufficient concordance for qualitative assessment. Judicious optimization of milliamperage settings based on individual diagnostic requirements can result in significant dose reduction without compromising diagnostic decision-making.

Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin.

Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.

[Prevalence and risk factors of peripheral arterial disease in an outpatient screening campaign]. / Évaluation de la prévalence et des facteurs de risque de l'artériopathie oblitérante des membres inférieurs dans le cadre d'une campagne de dépistage ambulatoire.

BACKGROUND: Peripheral arterial disease (PAD) is an important predictor of cardiovascular disease with major medico-economic consequences. However, systematic screening of asymptomatic patients free from history of cardiovascular disease is debated. OBJECTIVE: Determining the prevalence, risk factors for PAD in a population of outpatients at intermediate or high-risk of cardiovascular disease, free from history of cardiovascular disease to assess the potential impact of PAD screening in such groups of patients. METHODS: Multicenter 1-day screening program of PAD conducted from 2008 to 2010 in a population defined by diabetes plus age greater than 50 years, positive active smoking status, or age greater than 70 years. PAD was defined as an ankle-brachial index (ABI) less than 0.9 measured as follows: lowest systolic ankle pressure divided by highest systolic arm pressure. RESULTS: Ten thousand six hundred and fourteen patients fulfilled study inclusion criteria: 16.7% (n = 1774) exhibited an ABI less than 0.9 and 3.8% (n = 407) an ABI less than 0.7. ABI greater than 1.3 was found in 7.7% of patients (n = 818). Age greater than 70 years, male gender, active smoking status, hypertension and diabetes (treated) were independent risk factors for PAD. CONCLUSION: Primary prevention outpatient screening of a population with intermediate or high cardiovascular risk can identify numerous patients with PAD. The medical impact in terms of cardiovascular mortality and morbidity of such a screening needs to be assessed.

Semisynthesis of D-ring modified taxoids: novel thia derivatives of docetaxel.

Two novel 5(20)-thia analogues of docetaxel have been synthesized from 10-deacetylbaccatin III or taxine B and isotaxine B. The key step of these syntheses is the concomitant thietane ring formation and acetylation of the tertiary alcohol at C-4. Both compounds are less cytotoxic than docetaxel but have divergent activity on microtubule disassembly.

Effects of the hydrophobicity of taxoids on their interaction with tubulin.

Modifications of the hydrophobic character at the 7 and 10 positions of the taxoids greatly modified the effect of these drugs on the tubulin microtubule system. The presence of an alkyl chain at these positions decreased the activity while their corresponding more polar analogues restored the activity of these molecules. It appears that the recognition of taxoids by tubulin depends on the location of the most important hydrophobic area.

Structure-activity relationship of polyisoprenyl benzophenones from Garcinia pyrifera on the tubulin/microtubule system.

Microtubule disassembly inhibitory properties have been established for the known polyisoprenylated benzophenones xanthochymol (1a) and guttiferone E (1b). The compounds were isolated from the fruits of Garcinia pyrifera collected in Malaysia. A structure-activity relationship study, including natural and semisynthetic derivatives, delineated some structural features necessary for the interaction with tubulin within this compound class.

Novel allocolchicinoids with an eight membered B-ring: design, synthesis and inhibition of tubulin assembly.

Several B-ring variations of O-methyl androbiphenyline (8), newly accessible from (-)-(M,7S)-colchicine via photooxygenation and subsequent endoperoxide-transformation, were synthesized and evaluated for their inhibitory effects on tubulin assembly in vitro. The amino-allocolchicinoid (9), a key compound in this study, was transformed to the highly potent ketone 10 and by oxidation with H2O2/Na2WO4 to a mixture of syn/anti-oximes, like 11 and 12. These could easily be transformed to hitherto unknown allocolchicinoids 13 and 14 with an eight membered B-ring lactam obtained via a Beckmann rearrangement. Surprisingly both do not notably affect tubulin assembly, despite obvious structural similarities with active analogues of the thiocolchicine- and azasteganacin-series.

D-ring substituted rhazinilam analogues: semisynthesis and evaluation of antitubulin activity.

Novel (-)- and (+)-rhazinilam derivatives substituted on the D-ring (compounds 3, 4, 5 and 6) have been prepared from (+)-vincadifformine 7 and (-)-tabersonine and evaluated against the disassembly of microtubules into tubulin. Along with this study, a reproducible 'one pot' semisynthesis of (-)-rhazinilam 1 from (+)-1,2-didehydroaspidospermidine 2 was performed allowing the easy preparation of these new compounds.

Synthesis and antiproliferative activity of a cyclic analog of dolastatin 10.

A cyclic analog of the natural antiproliferative compound dolastatin 10 was synthesized by introducing an ester link between the N- and C-terminal residues which were modified accordingly. The final macrolactonization was performed by using isopropenyl chloroformate and DMAP as reagents. This analog exhibits submicromolar antiproliferative activity against the L1210 and HT29 cell lines and inhibits in vitro tubulin polymerization (IC50, 39 microM).

Incorporation of thioamide linkages into a growing peptide under SPPS conditions improved by salt effects.

Amino acid methyl dithioesters may be coupled in the presence of DMAP and salts to a growing peptide chain on a polymeric resin with high coupling yields and low racemization.