Francisco Santaolalla

Increased APN/CD13 and acid aminopeptidase activities in head and neck squamous cell carcinoma.

Involvement of peptidases in carcinogenic processes of several tumor types has been investigated in recent years. Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and accounts for more than 90% of all head and neck cancers. Increased understanding of its pathophysiology has led to implication of several proteinases, specially matrix metalloproteinases, in its genesis, growth, and dissemination. However, very little is known about involvement of peptidases in this neoplasm.

Increased prolyl endopeptidase activity in human neoplasia.

Prolyl endopeptidase (EC 3.4.21.26) (PEP) is a serine peptidase that converts several biologically active peptides. This enzyme has been linked to several neurological, digestive, cardiovascular and infectous disorders. However, little is known about its involvement in neoplastic processes. This study analyzes fluorimetrically cytosolic and membrane-bound PEP activity in a large series (n=122) of normal and neoplastic tissues from the kidney, colon, oral cavity, larynx, thyroid gland and testis. Cytosolic PEP activity significantly increased in clear cell renal cell carcinoma, urothelial carcinoma of the renal pelvis and head and neck squamous cell carcinoma. Both cytosolic and membrane-bound PEP activity were also increased in colorectal adenomatous polyps. These data suggest the involvement of PEP in some mechanisms that underlie neoplastic processes.

Inflammatory myofibroblastic tumour of the larynx

A case of inflammatory myofibroblastic tumour of the larynx in a 74-year old man is reported. The lesion presented as a polypoid tumour arising in the left true vocal fold. The patient died of non-tumour-related causes and the autopsy showed persistence of the laryngeal tumour. Multicentricity and distant metastases were not detected. The literature about this entity and its differential diagnosis is reviewed and briefly commented upon.

Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches

Hypoxic–ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia–ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia–ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic–ischemic brain injury, in the light of the most recent advances.

Efficacy of selective percutaneous embolization for the treatment of intractable posterior epistaxis and juvenile nasopharyngeal angiofibroma (JNA)

Conclusion. Percutaneous embolization reduces the reappearance of epistaxis and the mean length of hospital stay for patients with intractable epistaxis or juvenile nasopharyngeal angiofibroma (JNA). Objectives. To assess whether percutaneous embolization is effective for the treatment of intractable epistaxis and JNA. Patients and methods. Twenty-eight patients with intractable posterior epistaxis treated by embolization (25 males; m = 59.78 years; SD = 14.3) and 28 unembolized patients (24 males; m = 59.21 years; SD = 15.13) were studied retrospectively. Eight patients with JNA (all males; mean = 16.5 years; SD = 2.35; four embolized before surgery and four unembolized) were also analyzed. Results. Embolization was bilateral in 71.4% of subjects, blood transfusion was required in 28.57%, incidence of complications was 53.57%, and seven of the embolized patients with intractable epistaxis suffered from recurrence of the epistaxis. There were no statistically significant differences between the embolized and unembolized groups. The mean hospital stay was longer in unembolized patients (4.46 days; SD = 2.42) than for the embolized patients (3.78 days; SD = 3.9), p=0.394. The most serious complications occurred in patients embolized with idiopathic epistaxis and the mean post-embolization hospital stay was longer in this subgroup (4.14 days; SD = 4.39) than in patients with Rendu-Osler-Weber syndrome (2.40 days; SD = 1.140), p=0.395. Unembolized patients with JNA presented greater hemorrhage (m = 2025 ml; SD = 325) and a longer mean hospital stay (m = 18 days; SD = 3) than the group of embolized patients (m = 360 ml; SD = 185 and m = 9 days; SD = 1, respectively).

DLK1 regulates branching morphogenesis and parasympathetic innervation of salivary glands through inhibition of NOTCH signalling

Delta‐like proteins 1 and 2 (DLK1, 2) are NOTCH receptor ligands containing epidermal growth factor‐like repeats, which regulate NOTCH signalling. We investigated the role of DLK and the NOTCH pathway in the morphogenesis of the submandibular salivary glands (SMGs), using in vitro organotypic cultures.

Inner ear hair cell regeneration: A look from the past to the future

Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neurosensory hearing loss. This suggests that cochlear hair cell regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cell regeneration.

Usefulness of the BAST-24 smell and taste test in the study of diabetic patients: a new approach to the determination of renal function

Abstract Conclusion: A reduction in the percentage of correct responses in the olfactory test indirectly indicated increased albuminuria and worse glomerular filtration rate (GFR) in diabetic patients. The olfactory function test is an indirect indicator of early microvascular complications in diabetic patients. Objectives: Diabetes mellitus is a highly prevalent disease that causes numerous complications. The aim of this study was to determine whether olfactory and taste sensations are related to renal failure in diabetic patients. Methods: We studied 61 patients diagnosed with diabetes mellitus, mean age = 65.9 years (SD = 16.8), 54.1% male. We evaluated olfactory and taste sensations by determining the capacity of detection, identification and percentage of correct responses of the 29 components of the Barcelona Smell-taste Test-24 (BAST-24). We determined the relationship between these results and glycosylated haemoglobin (HbA1c), creatinine, albumin/creatinine, albuminuria and GFR (normal = GFR ≥ 60 ml/min/1.73 m2; impaired renal function = GFR < 60 ml/min/1.73 m2). Results: There was no significant relationship between HbA1c and olfactory and taste sensations. There was a significant relationship between the percentage of correct responses and albuminuria (p = 0.03) and between identification of odours through the olfactory nerve and GFR (p = 0.029), and the percentage of correct responses and GFR (p = 0.03). There was no significant relationship between taste and renal failure.

Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing

Human ageing is associated with a gradual decline in the physiological functions of the body at multiple levels and it is a key risk factor for many diseases, including cancer. Ageing process is intimately related to widespread cellular senescence, characterised by an irreversible loss of proliferative capacity and altered functioning associated with telomere attrition, accumulation of DNA damage and compromised mitochondrial and metabolic function. Tumour and senescent cells may be generated in response to the same stimuli, where either cellular senescence or transformation would constitute two opposite outcomes of the same degenerative process. This paper aims to review the state of knowledge on the biomolecular relationship between cellular senescence, ageing and cancer. Importantly, many of the cell signalling pathways that are found to be altered during both cellular senescence and tumourigenesis are regulated through shared epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs are emerging as pivotal players linking ageing and cancer. These small RNA molecules have generated great interest from the point of view of future clinical therapy for cancer because successful experimental results have been obtained in animal models. Micro-RNA therapies for cancer are already being tested in clinical phase trials. These findings have potential importance in cancer treatment in aged people although further research-based knowledge is needed to convert them into an effective molecular therapies for cancer linked to ageing.

Recent advances in cochlear hair cell regeneration—A promising opportunity for the treatment of age-related hearing loss

The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing. More research will be needed in order to translate them into an effective treatment for deafness linked to cochlear senescence in humans.