Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury

Regulated necrosis (RN) may result from cyclophilin (Cyp)D-mediated mitochondrial permeability transition (MPT) and receptor-interacting protein kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways exist. Here, we demonstrate that necroptosis in ischemia–reperfusion injury (IRI) in mice occurs as primary organ damage, independent of the immune system, and that mice deficient for RIPK3, the essential downstream partner of RIPK1 in necroptosis, are protected from IRI. Protection of RIPK3-knockout mice was significantly stronger than of CypD-deficient mice. Mechanistically, in vivo analysis of cisplatin-induced acute kidney injury and hyperacute TNF-shock models in mice suggested the distinctness of CypD-mediated MPT from RIPK1/RIPK3-mediated necroptosis. We, therefore, generated CypD-RIPK3 double-deficient mice that are viable and fertile without an overt phenotype and that survived prolonged IRI, which was lethal to each single knockout. Combined application of the RIPK1 inhibitor necrostatin-1 and the MPT inhibitor sanglifehrin A confirmed the results with mutant mice. The data demonstrate the pathophysiological coexistence and corelevance of two separate pathways of RN in IRI and suggest that combination therapy targeting distinct RN pathways can be beneficial in the treatment of ischemic injury.     

Hemorrhagic cholecystitis: ultrasound and CT imaging findings—a retrospective case review series

Emergency Radiology - Gallbladder pathology is diverse, and imaging tests are essential tools for its diagnosis. Acute cholecystitis has multiple manifestations or complications, one of which is...     

Mesenchymal stem cells from the oral cavity and their potential value in tissue engineering

Periodontal disease is one of the most common conditions affecting humans, and current treatment strategies, which focus on the removal and long‐term control of dental plaque, are generally successful in eliminating active disease and promoting tissue repair. However, regeneration of the supporting structures of the tooth remains an elusive goal and a challenge. The formation of new bone and cementum with supportive periodontal ligament is the ultimate objective, but current regeneration therapies are incapable of achieving this in a predictable way. The regeneration of periodontal tissue requires a combination of fundamental events, such as appropriate level and sequencing of regulatory signals, the presence of progenitor cells, an extracellular matrix or carrier and an adequate blood supply. Based on tissue‐engineering concepts, the regeneration process may be modulated by manipulating the signaling pathways of regulatory molecules, the extracellular matrix or scaffold, or the cellular components. The identification of mesenchymal stem cells from bone marrow started a new era in regenerative medicine. Tissue engineering using mesenchymal stem cells became a therapeutic option with several advantages, including high‐quality regeneration of damaged tissues without the formation of fibrous tissue, minimal donor‐site morbidity compared with autografts and a low risk of autoimmune rejection and disease transmission. The aim of this review was to describe the main sources of mesenchymal stem cells from tissues in the oral cavity and the potential of these cells in regenerative therapy. Special attention is paid to gingival tissue‐derived mesenchymal stem cells because they represent the most accessible source of stem cells in the human mouth.     

Clinical concepts for regenerative therapy in furcations

Furcation involvements present one of the greatest challenges in periodontal therapy because furcation‐involved molar teeth respond less favorably to conventional periodontal therapy compared with noninvolved molar or nonmolar teeth. Various regenerative procedures have been proposed and applied with the aim of eliminating the furcation defect or reducing the furcation depth. An abundance of studies and several systematic reviews have established the effectiveness of membrane therapy (guided tissue regeneration) for buccal Class II furcation involvement of mandibular and maxillary molars compared with open flap surgery. Bone grafts/substitutes may enhance the results of guided tissue regeneration. However, complete furcation closure is not a predictable outcome. Limited data and no meta‐analyses are available on the effects of enamel matrix proteins for furcation regeneration. Enamel matrix protein therapy has demonstrated clinical improvements in the treatment of buccal Class II furcation defects in mandibular molars; however, complete closure of the furcation lesion is achieved only in a minority of cases. Neither guided tissue regeneration nor enamel matrix protein therapy have demonstrated predictable results for approximal Class II and for Class III furcations. Promising preclinical data from furcation regeneration studies in experimental animals is available for growth factor‐ and differentiation factor‐based technologies, but very limited data are available from human clinical studies. Although cell‐based therapies have received considerable attention in regenerative medicine, their experimental evaluation in the treatment of periodontal furcation lesions is at a very early stage of development. In summary, the indications and the limitations for currently available treatment modalities for furcation defects are well established. New regenerative treatments are clearly needed to improve the predictability of a complete resolution of furcation defects.     

Insomnia does not affect heart rate changes when young adults watch humorous films: An exploratory study

Emotional reactivity in insomnia is affected both subjectively and on a physiological level for negative emotional material, but little is known about reactions to positive stimuli. We here investigated whether in younger adult insomnia patients, presentation of short humorous films would lead to heart rate decreases during and after film viewing, as compared to heart rate changes when falling asleep. Investigating 20 participants with DSM‐5‐diagnosed insomnia and 18 participants without insomnia, we found that heart rate decreased when falling asleep, increased when watching humorous films and returned to normal values afterwards for all participants. Film‐related heart rate increases were strongly related to humour ratings of the films. No differences were found between those with and without insomnia on subjective ratings of the films, film‐related heart rate changes or when falling asleep. We conclude that the experience of positive daily life stimuli in younger adults is not affected by insomnia in our study, despite insomnia having a known more profound effect on negative stimuli. Future studies exploring insomnia‐related autonomous nervous system responses combining different neurophysiological modalities should confirm our findings.     

Altered Peptidase Activities in Thyroid Neoplasia and Hyperplasia

Background. Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. Methods. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. Results. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. Conclusions. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.