Breakthroughs in Medicinal Chemistry: New targets and mechanisms, new drugs, new hopes

The Editorial Board of the Medicinal Chemistry section of the journal Molecules publishes here its first Editorial, which has been prepared by highlighting, in sub-editorials of about one hundred words, some selected recently published articles that may have a profound impact on drug discovery and therapy. In particular, this editorial highlights new drug targets and mechanisms of action and new classes of drugs, as well as new therapeutic uses for known drugs or the involvement of known biological targets in new diseases. We also discuss some structural biology studies and new computational tools that may pave the way for the rational design or identification of more efficacious and safer drugs. Overall, the findings reported in these highlighted papers raise our hopes for the management of difficult-to-treat diseases that are posing a growing health threat, with new or repurposed drugs that overcome the limitations of currently applied therapies

Sinus Floor Elevation with Modified Crestal Approach and Single Loaded Short Implants: A Case Report with 4 Years of Follow-Up

Tooth extraction is usually followed by bone reduction. In the maxillary posterior region, this remodelling combined with sinus pneumatisation and periodontal defects may lead to a reduced basal bone height available for implant placement. Sinus floor elevation can be performed with different surgical techniques. Crestal approach has demonstrated to be effective, less invasive, and associated with a reduced morbidity. This article reports a modified sinus floor elevation by means of rotary, noncutting instruments, addition of xenograft, and 2 short-threaded implant placements. The aim of the study was to evaluate the implant’s success and intrasinus radiographical bone gain after 4 years of functional loading. The premolar implant site presented a starting basal bone height of 6 mm, while the molar site was of 2 mm. In the first surgical step, sinus floor elevation was performed mesially and the implant was inserted, and distally only sinus floor elevation was performed. After 6 months, the mesial implant was uncovered and the second implant was inserted; 4 months later, the second fixture was uncovered, and both fixtures were loaded with single provisional screw-retained crowns and later with single screw-retained porcelain fused to metal crowns. Implants integrated successfully, and crestal bone remodelling did not exceed the smooth collar. Bone gain was 3 mm for the mesial implant and more than 5 mm for the distal one

Sinus Floor Elevation with Modified Crestal Approach and Single Loaded Short Implants: A Case Report with 4 Years of Follow-Up

Tooth extraction is usually followed by bone reduction. In the maxillary posterior region, this remodelling combined with sinus pneumatisation and periodontal defects may lead to a reduced basal bone height available for implant placement. Sinus floor elevation can be performed with different surgical techniques. Crestal approach has demonstrated to be effective, less invasive, and associated with a reduced morbidity. This article reports a modified sinus floor elevation by means of rotary, noncutting instruments, addition of xenograft, and 2 short-threaded implant placements. The aim of the study was to evaluate the implant’s success and intrasinus radiographical bone gain after 4 years of functional loading. The premolar implant site presented a starting basal bone height of 6 mm, while the molar site was of 2 mm. In the first surgical step, sinus floor elevation was performed mesially and the implant was inserted, and distally only sinus floor elevation was performed. After 6 months, the mesial implant was uncovered and the second implant was inserted; 4 months later, the second fixture was uncovered, and both fixtures were loaded with single provisional screw-retained crowns and later with single screw-retained porcelain fused to metal crowns. Implants integrated successfully, and crestal bone remodelling did not exceed the smooth collar. Bone gain was 3 mm for the mesial implant and more than 5 mm for the distal one

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–4

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules. In these Editorials, we highlight in brief reports (of about one hundred words) a number of recently published articles that describe crucial findings, such as the discovery of novel drug targets and mechanisms of action, or novel classes of drugs, which may inspire future medicinal chemistry endeavours devoted to addressing prime unmet medical needs

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC. © 2013 Worm et al.; licensee BioMed Central Ltd

EXAFS Study of Ti, Fe and Ga Substituted Silicalites

The local environment of isomprphous substituted Ti, Fe and Ga metal atoms in silicalite (hereafter indicated as TS-1, Fe-S and Ga-S respectively) has been studied by means of EXAFS spectroscopy. Measurements have been carried out on the samples in presence of template and after template removal at increasing temperatures in order to follow the evolution of the local environment of the metal heteroatoms. Ti(IV) atoms in (TS-1) show a great stability, while Ga(III) and particularly Fe(III) atoms have propensity to migrate from framework into extraframework positions, forming small oxide particles trapped inside the MFI channels upon increasing the template burning temperature. The established stability scale is Ti(IV) &gt; Ga(III) &gt; Fe(III). These conclusions are qualitatively supported by UV-Vis, IR and Raman data. </jats:p