We have investigated the reactions of silver nitrate and 3-(aryl)-2-sulfanylpropenoic acids [H(2)xspa, x: p = 3-phenyl-, f = 3-(2-furyl)-, t = 3-(2-thienyl)-, py = 3-(2-pyridyl)-] and 2-cyclopentylidene-2-sulfanylacetic acid (H(2)L) in 1 : 1 and 2 : 1 molar ratios. The 1 : 1 molar ratio gave compounds of type [Ag(HL)]; reaction of these compounds with diisopropylamine and NaOH gave [HQ][Ag(L)] (HQ = diisopropylammonium) and Na[Ag(L)] x H(2)O, respectively. These compounds, as well as those of type [Ag(2)(L)] obtained with the 1 : 2 molar ratio, were isolated and characterized by IR and NMR ((1)H and (13)C) spectroscopy. (109)Ag NMR spectroscopy and ESI-MS spectrometry were also used in some cases. The crystal structures of [HQ][Ag(pspa)] (11), in which the presence of structural isomers was detected, and [HQ][Ag(cpa)] (15) were determined by X-ray diffractometry. The antimicrobial activity of the complexes against E. coli, S. aureus, B. subtilis, P. aeruginosa/Resistant P. aeruginosa, and C. albicans was tested.

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Three new triphenyltin(IV) sulfanylcarboxylates with the general formula [Q][SnPh 3 (L)] (Q = diisopropylammonium cation; L = tspa, pspa or pyspa, where t = 3-(2-thienyl)-, p = 3-(2-phenyl)-, py = 3-(2-pyridinyl)-and spa = 2-sulfanylpropenoato) have been prepared by reaction of triphenyltin(IV) hydroxide with the corresponding acid in the presence of di-isopropylamine in ethanol. The compounds have been characterized by elemental analysis and mass spectrometry and by IR, Mössbauer and NMR ( 1 H, 13 C, 119 Sn) spectroscopy. X-ray studies of the crystal structures of [Q][SnPh 3 (pspa)] and [Q][SnPh 3 (pyspa)] show that in both compoundsthe tin atom is coordinated to three phenyl C atoms and to S and one O atom of the ligand L. All three complexes are active against strains of the Gram-positive bacterium Staphylococcus aureus, but are inactive or only slightly active against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa.

ImportanceThere is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF).ObjectiveTo assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF.Design, Setting, and ParticipantsThe 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2.InterventionsPatients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks.Main Outcomes and MeasuresThe primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life).ResultsAt the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL (95% CI, −178.0 to −71.2 mL) with 600 mg of ziritaxestat vs –147.3 mL (95% CI, −199.8 to −94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, −52.3 to 97.6 mL]), and –173.9 mL (95% CI, −225.7 to −122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, −26.7 mL [95% CI, −100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was –173.8 mL (95% CI, −209.2 to −138.4 mL) with 600 mg of ziritaxestat vs –176.6 mL (95% CI, −211.4 to −141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, −46.9 to 52.4 mL]) and –174.9 mL (95% CI, −209.5 to −140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, −47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo.Conclusions and RelevanceZiritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment.Trial RegistrationClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444

Treatment with antibiotics within the periodontal pocket against bacterial infections represents a useful and adjunctive tool to conventional therapy for healing and teeth preservation. With this function in view, an implantable, tetracycline delivery device for the treatment of periodontal disease was developed. The aim of this study was to develop biodegradable, tetracycline-loaded microparticles made of two polymers: PLGA and zein which were compressed into monolithic devices. In this polymer delivery system, the encapsulation efficiency, release characteristics, drug-polymer interaction, and antibacterial activity of loaded drug were investigated. The interaction of tetracycline with the corn protein zein was studied by nuclear magnetic resonance (NMR), Fourier transform infrared, and X-ray diffraction. The hydrophobic interaction of tetracycline with zein in the formulations was deduced from the NMR studies, whereas X-ray diffraction studies showed a new crystalline state of the drug in the presence of the protein. Zein was not denatured by preparation of inserts. Sustained release of tetracycline was obtained, and the proportion of zein in the inserts had a great impact on the drug release. Finally, an effective tetracycline release from inserts against Staphylococcus aureus was achieved over 30 days. In conclusion, the PLGA:zein delivery system described in this study was found to be effective in controlled delivery of tetracycline, and hence may be suitable for intra-pocket delivery of antimicrobial agents in the treatment of periodontitis.