Design and synthesis of 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity

A series of 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives was designed, synthesized, and screened for their phosphodiesterase (PDE 4B) inhibitory activity and bronchodilation ability. Compound 7e showed 41.80% PDE 4B inhibition at 10 µM. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC₅₀ values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC₅₀ = 425 µM). Molecular docking at the PDE 4B active site revealed a binding mode and docking scores comparable to those of a reference ligand, consistent with their PDE 4B inhibition activity.     

The formation of an organic coat and the release of corrosion microparticles from metallic magnesium implants

Magnesium alloys have been proposed as prospective degradable implant materials. To elucidate the complex interactions between the corroding implants and the tissue, magnesium implants were analyzed in a mouse model and the response was compared to that induced by Ti and by the resorbable polymer polyglactin, respectively. One month after implantation, distinct traces of corrosion were apparent but the magnesium implants were still intact, whereas resorbable polymeric wound suture implants were already fragmented. Analysis of magnesium implants 2 weeks after implantation by energy-dispersive X-ray spectroscopy indicated that magnesium, oxygen, calcium and phosphate were present at the implant surface. One month after implantation, the element composition of the outermost layer of the implant was indicative of tissue without detectable levels of magnesium, indicating a protective barrier function of this organic layer. In agreement with this notion, gene expression patterns in the surrounding tissue were highly similar for all implant materials investigated. However, high-resolution imaging using energy-filtered transmission electron microscopy revealed magnesium-containing microparticles in the tissue in the proximity of the implant. The release of such corrosion particles may contribute to the accumulation of calcium phosphate in the nearby tissue and to bone conductive activities of magnesium implants.     

Aspergillosis in a gyrfalcon (Falco rusticolus) in Saudi Arabia

A mixed case of chronic tracheal (syringeal) and pulmonary (lungs and air sacs) aspergillosis was diagnosed in an adult female gyrfalcon (Falco rusticolus). The bird presented with a 4-week history of severe dyspnea, exercise intolerance, depression and reduced appetite. Physical examination revealed slight emaciation. Hematological analysis showed leucocytosis, heterophilia, monocytosis, and thrombocytosis. Radiographic examination showed thickening of the air sac walls and increased radiopacity within the lung field. Caseous granulomatous lesions were observed during tracheoscopy and laparoscopy procedures. Cytological examination of specimens obtained from these lesions demonstrated Aspergillus species, which was isolated in culture and identified as Aspergillus flavus.     

Doxycycline‐Loaded β‐Tricalcium Phosphate Release Following EDTA Root Surface Etching Improved the Clinical Outcomes in Chronic Periodontitis: An In Vivo Study

Background: The main objective of the present study is to quantify doxycycline (DOX) release from β‐tricalcium phosphate (β‐TCP) after EDTA root surface treatment. Methods: Thirty systemically healthy patients with ≥1 paired contralateral interproximal intrabony defect ≥4 mm deep along with an interproximal probing depth ≥6 mm and clinical attachment level ≥4 mm were randomized into two groups. Group 1 (G1) consisted of sites treated with open flap debridement followed by placement of DOX blended with β‐TCP (DOX‐β‐TCP), whereas group 2 (G2) sites were treated with flap surgery followed by the placement of DOX blended with β‐TCP after EDTA etching of the exposed root surfaces (DOX‐β‐TCP + EDTA). Samples of gingival crevicular fluid (GCF) were obtained 1, 3, 7, 14, and 21 days after surgery. Quantitative measurements of DOX were taken with high‐performance liquid chromatography. Clinical evaluation and follow‐up for 6 months were performed. Results: At 21 days, the DOX‐β‐TCP + EDTA–treated group showed a 194.7 µg/mL value. The DOX‐β‐TCP + EDTA–treated group retained more DOX during the periods of 3, 7, 10, 14, and 21 days than the DOX‐β‐TCP–treated group. Six months after therapy, DOX‐β‐TCP + EDTA–treated sites showed more significant clinical improvements compared to DOX‐β‐TCP–treated sites (P ≤ 0.05). Conclusions: EDTA root surface etching enhances DOX availability in the GCF following its release from β‐TCP as a drug carrier.