Hyperoxia reduces salivary secretion by inducing oxidative stress in mice

OBJECTIVE: The aim of this study was to determine the effects of prolonged hyperoxia on salivary glands and salivary secretion in mice. DESIGN: Male C57BL/6 J mice were kept in a 75% oxygen chamber (hyperoxia group) or a 21% oxygen chamber for 5 days. We measured the secretion volume, protein concentration, and amylase activity of saliva after the injection of pilocarpine. In addition, we evaluated the histological changes induced in the submandibular glands using hematoxylin and eosin and Alcian blue staining and assessed apoptotic changes using the TdT-mediated dUTP nick end labeling (TUNEL) assay. We also compared the submandibular gland expression levels of heme oxygenase-1 (HO-1), superoxide dismutase (SOD)-1, and SOD-2 using the real-time polymerase chain reaction. RESULTS: In the hyperoxia group, salivary secretion was significantly inhibited at 5 and 10 min after the injection of pilocarpine, and the total salivary secretion volume was significantly decreased. The salivary protein concentration and amylase activity were also significantly higher in the hyperoxia group. In the histological examinations, enlargement of the mucous acini and the accumulation of mucins were observed in the submandibular region in the hyperoxia group, and the number of TUNEL-positive cells was also significantly increased in the hyperoxia group. Moreover, the expression levels of HO-1, SOD-1, and SOD-2 were significantly higher in the hyperoxia group. CONCLUSION: Our results suggest that hyperoxia reduces salivary secretion, and oxidative stress reactions might be involved in this

Heme oxygenase-1 induction in the brain during lipopolysaccharide-induced acute inflammation

Delirium occurs in 23% of sepsis patients, in which pro-inflammatory cytokines and nitric oxide are suggested to be involved. However, in animal experiments, even a subseptic dose of lipopolysaccharide (LPS) injection induces both pro-inflammatory cytokines and inducible nitric oxide synthase in the brain, suggesting that the brain oxidative reaction can be induced in the subseptic condition. Then, we evaluated the changes of heme oxygenase-1 (HO-1), a sensitive oxidative marker, as well as interleukin (IL)-1β, IL-6, and inductible nitric oxide synthase (iNOS) mRNA in the hypothalamus and hippocampus of rats using real-time PCR after peripheral injection of LPS (2.0 mg/kg). As a result, these four kinds of mRNAs were induced significantly in both areas after LPS injection. These results suggest that peripheral inflammation induces an oxidative reaction in the brain, even if the inflammation is not lethal. It is also considered that several pathways are involved in brain HO-1 induction

Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder

Background: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. Methods: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. Results: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. Conclusion: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson’s disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding

Multi-drug therapy for epilepsy influenced bispectral index after a bolus propofol administration without affecting propofol's pharmacokinetics: a prospective cohort study

Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol

DH Training in Spanish: Digital Humanities as an e-learning platform to teach between Spain and Latin America

#dariahTeach is developing open source, community-driven, source, high quality, multilingual teaching materials for the digital arts and humanities. Begun in January 2015 and running through June 2017, #dariahTeach is funded through an Erasmus + Strategic Partnership Grant. The #dariahTeach consortium has eight partners, coordinated by Maynooth University, Ireland. LINHD UNED is part of this initiative and is collaborating through the experience of Elena González Blanco and Gimena del Rio as experts in online distant teaching on Digital Humanities.Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET

Exosome-Based Molecular Transfer Activity of Macrophage-Like Cells Involves Viability of Oral Carcinoma Cells: Size Exclusion Chromatography and Concentration Filter Method

Extracellular vesicles (EV) heterogeneity is a crucial issue in biology and medicine. In addition, tumor-associated macrophages are key components in cancer microenvironment and immunology. We developed a combination method of size exclusion chromatography and concentration filters (SEC-CF) and aimed to characterize different EV types by their size, cargo types, and functions. A human monocytic leukemia cell line THP-1 was differentiated to CD14-positive macrophage-like cells by stimulation with PMA (phorbol 12-myristate 13-acetate) but not M1 or M2 types. Using the SEC-CF method, the following five EV types were fractionated from the culture supernatant of macrophage-like cells: (i) rare large EVs (500-3000 nm) reminiscent of apoptosomes, (ii) EVs (100-500 nm) reminiscent of microvesicles (or microparticles), (iii) EVs (80-300 nm) containing CD9-positive large exosomes (EXO-L), (iv) EVs (20-200 nm) containing unidentified vesicles/particles, and (v) EVs (10-70 nm) containing CD63/HSP90-positive small exosomes (EXO-S) and particles. For a molecular transfer assay, we developed a THP-1-based stable cell line producing a GFP-fused palmitoylation signal (palmGFP) associated with the membrane. The THP1/palmGFP cells were differentiated into macrophages producing palmGFP-contained EVs. The macrophage/palmGFP-secreted EXO-S and EXO-L efficiently transferred the palmGFP to receiver human oral carcinoma cells (HSC-3/palmTomato), as compared to other EV types. In addition, the macrophage-secreted EXO-S and EXO-L significantly reduced the cell viability (ATP content) in oral carcinoma cells. Taken together, the SEC-CF method is useful for the purification of large and small exosomes with higher molecular transfer activities, enabling efficient molecular delivery to target cells

Chronic Orofacial Pain in Dental Patients: Retrospective Investigation over 12 years

Orofacial pain is often difficult to diagnose and treat. However, there have been few reports on the clinical observation of dental patients with orofacial pain. We retrospectively investigated the characteristics of 221 dental patients who had suffered from persistent orofacial pain. Data were collected from the outpatient medical records in our clinic over the past 12 years. More than half of the patients (53.8%) had suffered with pain for more than 6 months from pain onset until the first visit to our clinic. The main diagnoses were neuropathic pain (30.3%), myofascial pain (23.5%), psychogenic pain (20.4%), odontogenic toothache (17.2%), and others (7.7%) such as temporomandibular disorders and glossitis. The treatments included pharmacotherapy, splint therapy, and others such as nerve block, dental treatment, physiotherapy, and/or psychotherapy. Excluding the patients (52 of 221 initially enrolled patients) with unknown responses to treatment, 65.7% showed remission or a significant improvement in pain in response to treatment. Although only a small group of patients had odontogenic toothache, the rate of improvement was highest for this disorder. In conclusion, early consultation with a dentist is useful to prevent chronicity of odontogenic pain and to make a differential diagnosis in patients with orofacial pain

Gravity sensing in plant and animal cells

Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space

A Multidisciplinary Approach to the Management of Chronic Pain through a Self-managed Behavioral Exercise Program : A Pilot Study in Japan

We conducted this study to determine the short-term treatment outcomes of multidisciplinary approaches to chronic pain management for outpatients in Japan. We evaluated pain reduction and improvement in quality of life (QOL) after treatment. We analyzed 32 patients who had experienced intractable chronic pain for > 3 months. The patients received multidisciplinary therapeutic self-managed exercise instructions and then underwent evaluations 1 and 3 months after the treatment. We used the Pain Disability Short Form-36 (SF-36), Pain Catastrophizing Scale (PCS), and Pain Disability Assessment Scale (PDAS) to evaluate QOL. Although the pain levels were the same before and after the physical exercise program, the patients showed significant improvements in physical function on the SF-36 (48.5 vs. 54.5, 3 months vs. 1 month; p=0.0124), the magnification subscale on the PCS (6.8 vs. 5.9, 1 month vs. before; p=0.0164) and the PDAS (29.2 vs. 23.4, 3 months vs. before; p=0.0055). Chronic pain should be treated with a biopsychosocial approach, but time constraints and costs have limited the implementation of multidisciplinary and behavioral approaches to chronic pain management. Our findings demonstrate that clinical improvements are possible for patients with chronic pain, using multidisciplinary team resources widely available in Japanese clinical practice