Conjunctivitis, keratoconjunctivitis, and corneal ulcers are common eye disorders frequently diagnosed in both humans and animals, and are currently treated by topical administration of eye drops containing anti-inflammatory and antibacterial agents. The current molecules often lack efficacy because infections in hypoxic tissue contain methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa; thus, new products for the treatment of ocular pain and inflammation are needed. The use of ozone, a molecule stabilized for topical use as an ozonide, could be providential due to its anti-inflammatory and bactericidal activity in certain anterior segment pathologies, in addition to promoting tissue repair properties. Ozonated oils have the same properties as gaseous ozone and are well tolerated by tissues. In the present study the repair and regeneration effect of ozonated oil in liposomes plus hypromellose (Ozodrop®, FB Vision, Ascoli Piceno, Italy) instilled 3–4 times a day in external ocular spontaneous pathologies both in animals and humans are reported.
Clostridioides difficile infection (CDI) causes nosocomial/antibiotic-associated gastrointestinal diseases with dramatically increasing global incidence and mortality rates. The main C. difficile virulence factors, toxins A and B (TcdA/TcdB), cause cytopathic/cytotoxic effects and inflammation. We demonstrated that TcdB induces caspase-dependent, mitochondria-independent enteric glial cell (EGC) apoptosis that is enhanced by the pro-inflammatory cytokines TNF-α and IFN-γ (CKs) by increasing caspase-3/7/9 and PARP activation. Because this cytotoxic synergism is important for CDI pathogenesis, we investigated the apoptotic pathways involved in TcdB- and TcdB + CK-induced apoptosis indepth. EGCs were pre-treated with the inhibitors BAF or Q-VD-OPh (pan-caspase), Z-DEVD-fmk (caspase-3/7), Z-IETD-fmk (caspase-8), PD150606 (calpains), and CA-074Me (cathepsin B) 1 h before TcdB exposure, while CKs were given 1.5 h after TcdB exposure, and assays were performed at 24 h. TcdB and TcdB + CKs induced apoptosis through three signalling pathways activated by calpains, caspases and cathepsins, which all are involved both in induction and execution apoptotic signalling under both conditions but to different degrees in TcdB and TcdB + CKs especially as regards to signal transduction mediated by these proteases towards downstream effects (apoptosis). Calpain activation by Ca2+ influx is the first pro-apoptotic event in TcdB- and TcdB + CK-induced EGC apoptosis and causes caspase-3, caspase-7 and PARP activation. PARP is also directly activated by calpains which are responsible of about 75% of apoptosis in TcdB and 62% in TcdB + CK which is both effector caspase-dependent and -independent. Initiator caspase-8 activation mediated by TcdB contributes to caspase-3/caspase-7 and PARP activation and is responsible of about 28% of apoptosis in both conditions. Caspase-3/caspase-7 activation is weakly responsible of apoptosis, indeed we found that it mediates 27% of apoptosis only in TcdB. Cathepsin B contributes to triggering pro-apoptotic signal and is responsible in both conditions of about 35% of apoptosis by a caspase-independent manner, and seems to regulate the caspase-3 and caspase-7 cleaved fragment levels, highlighting the complex interaction between these cysteine protease families activated during TcdB-induced apoptosis. Further a relevant difference between TcdB- and TcdB + CK-induced apoptosis is that TcdB-induced apoptosis increased slowly reaching at 72 h the value of 18.7%, while TcdB + CK-induced apoptosis increased strongly reaching at 72 h the value of 60.6%. Apoptotic signalling activation by TcdB + CKs is enriched by TNF-α-induced NF-κB signalling, inhibition of JNK activation and activation of AKT. In conclusion, the ability of C. difficile to activate three apoptotic pathways represents an important strategy to overcome resistance against its cytotoxic activity.
Nutritional supplements, also known as complementary feeds, are products administered with the aim of furnishing health benefits, regardless of nutritional needs. They have been used since ancient times in veterinary dermatology, and a number of studies have focused on investigating the health benefits of some ingredients found in commercially available complementary feed for dogs. The aim of this paper is to review the literature available on the use of nutritional supplementation for the management of canine skin diseases, critically appraising the clinical efficacy of such interventions and summarizing the current state of knowledge. This review highlights how these feeds can be considered useful in the management of dermatological disorders and outlines their beneficial effects in the prevention of dietary deficiencies and treatment of diseases, alone, or in addition to conventional pharmacological therapy. In recent years, nutritional supplements have found increasing potential application in veterinary medicine, and the scientific proofs of their beneficial effects are described in this review.