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1.
AIDS Res Ther ; 21(1): 12, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429716

ABSTRACT

BACKGROUND: Increased incidence of lifestyle diseases as side-effects of antiretroviral therapy (ART) have been reported in people living with HIV (PLWH). Few studies have evaluated obesity and hidden obesity in Japanese PLWH and their association with ART. In order to provide more appropriate drug selection and lifestyle guidance, we investigated the relationship between the effects of HIV infection and ART on the body composition of Japanese PLWH. METHODS: PLWH who visited the outpatient clinic and had body composition measured using the body composition analyzer InBody 570 were included in this study. Medications, comorbidities, and blood test data were obtained. Body mass index (BMI), body fat percentage, and skeletal muscle mass index (SMI) were measured. RESULTS: In this study, 543 patients were included. Based on body shape, patients were classified into a thin group (13), normal weight group (14), hidden obesity group (158), apparent obesity group (14), and obesity group (218). Compared with the normal weight group, the hidden obesity group had a higher prevalence of comorbidities and a lower SMI. CONCLUSIONS: PLWH are more likely to have obesity than the general population, indicating that hidden obesity is common even among those with a normal BMI. It is important to measure body fat percentage along with body weight, as hidden obesity can be missed. Further investigation of the effects of ART on body composition is needed.


Subject(s)
HIV Infections , Humans , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Obesity/epidemiology , Obesity/complications , Body Composition , Comorbidity , Body Mass Index
2.
Int J Oral Maxillofac Surg ; 52(12): 1225-1229, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37643937

ABSTRACT

Histiocytic sarcoma is a malignant proliferation of cells that exhibit morphological and immunophenotypic features of mature histiocytes. Owing to its rarity, its clinical features and standard treatment have not yet been established. This report describes a case of histiocytic sarcoma of the palate that developed in a 76-year-old man, the first report of an intraoral histiocytic sarcoma. An extended resection was performed; however, establishing the excision line was extremely difficult because assessing the tumour boundary on imaging was challenging and the tumour underwent dynamic gross morphological changes following biopsy. Complete resection is required to obtain a favourable prognosis for high-grade tumours with indistinct borders. In this case, an intraoperative rapid examination with frozen section analysis was performed along the planned excision line to completely resect the tumours exhibiting such behaviour. At 28 months postoperatively, the patient demonstrated no recurrence or metastasis; however, he is under careful monitoring.


Subject(s)
Histiocytic Sarcoma , Male , Humans , Aged , Histiocytic Sarcoma/diagnostic imaging , Histiocytic Sarcoma/surgery , Histiocytes/pathology , Diagnostic Imaging , Biopsy , Palate
3.
J Neonatal Perinatal Med ; 16(2): 343-348, 2023.
Article in English | MEDLINE | ID: mdl-37182845

ABSTRACT

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks' gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (- 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B's urine and blood as well as in the mother's breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.


Subject(s)
Bronchopulmonary Dysplasia , Cytomegalovirus Infections , Infant , Female , Pregnancy , Infant, Newborn , Male , Humans , Milk, Human , Infant, Extremely Low Birth Weight , Infant, Premature , Prospective Studies , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus , Infectious Disease Transmission, Vertical
5.
J Dent Res ; 102(8): 938-946, 2023 07.
Article in English | MEDLINE | ID: mdl-36919893

ABSTRACT

The relationship between oral health and the development of Alzheimer's disease (AD) in the elderly is not yet well understood. In this regard, the association between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-ß(1-42) (Aß42) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Aß42 oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Aß42 oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and AppNL-G-F knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Aß42 oligomer processing in the Vmes, which exhibits high amyloid-ß (Aß) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Aß42 oligomer kinetics. Autophagosome-like membranes, which stained positive for Aß, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Aß in AppNL-G-F mice. By contrast, there was strong immunopositivity for extracellular Aß42 oligomers with the formation of Aß42 oligomer clusters in AppNL-G-F mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Aß42 oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Aß42 oligomers in AppNL-G-F mice. These results suggest that autophagy maintains homeostasis in Vmes neurons and that deterioration of autophagy due to aging or neurodegeneration leads to the diffusion of Aß42 oligomers into the extracellular space and possibly the development of AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Female , Mice , Animals , Amyloid beta-Peptides/metabolism , Mice, Transgenic , Neurons/metabolism , Autophagy , Disease Models, Animal
7.
Biochem Biophys Res Commun ; 594: 74-80, 2022 02 26.
Article in English | MEDLINE | ID: mdl-35078110

ABSTRACT

Occlusal disharmony has been reported to be affected not only by cytokine and steroid hormone secretion and sympathetic activation in peripheral organs, but also by neurotransmitter release in the central nervous system. However, little is known about whether occlusal disharmony can decrease cognitive ability. We hypothesized that hyperocclusion decreases cognition via Alzheimer's disease-associated molecule expression in the brain. The present study is aimed to elucidate the relationships among occlusal disharmony, cytokine and cognitive-regulated molecule expression in the brain, and the impairment of learning and memory cognition. We examined the effect of hyperocclusion on the relationships among cytokine expression, cognitive suppressor molecules in the hippocampus, and cognition in behavior using a hyperocclusion mouse model. Hyperocclusion dramatically increased interleukin-1ß expression in the serum and hippocampus 1 week after hyperocclusal loading in 2-month-old mice, but no effects in 12-month-old mice. The social and long-term cognitive abilities of the 2-month-old mice were transiently downregulated close to the level of the 12-month-old mice 1 week after hyperocclusion and recovered to close to basal level via the expression of cognitive suppressor clearing proteins. The expression levels of amyloid-ß and phosphorylated tau were significantly upregulated 1 week after hyperocclusal loading in the hippocampus of 2-month-old mice but were constant in 12-month-old mice. Occlusal disharmony-induced interleukin-1ß expression may contribute to accumulation of cognitive suppressor molecules such as amyloid-ß and phosphorylated tau and activate their clearance proteins, resulting in protection against transient dementia in young but not older individuals.


Subject(s)
Alzheimer Disease/metabolism , Cognition , Dementia/prevention & control , Hippocampus/metabolism , Malocclusion/genetics , Malocclusion/metabolism , Amyloid beta-Peptides/metabolism , Animals , Behavior, Animal , Disease Models, Animal , Interleukin-1beta/metabolism , Learning , Male , Mice , Mice, Inbred C57BL , Phosphorylation , tau Proteins/metabolism
8.
Acta Neurochir (Wien) ; 163(6): 1639-1663, 2021 06.
Article in English | MEDLINE | ID: mdl-33740134

ABSTRACT

BACKGROUND: The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient's counselling. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the management of PCMs.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Skull Base/surgery , Clinical Decision-Making , Counseling , Humans , Radiosurgery
9.
Aust Dent J ; 66(2): 182-187, 2021 06.
Article in English | MEDLINE | ID: mdl-33411950

ABSTRACT

BACKGROUND: The purpose of this study was to compare the displacement of tooth arrangement in dentures fabricated by additive manufacturing (AM) and heat curing. METHODS: Three-dimensional (3D) scanning was performed for edentulous jaw models. After the teeth were arranged, 3D scanning for the wax denture was performed. Heat-cured dentures were fabricated with heat-cure polymer resin. Based on data obtained by subtracting the model data from wax denture data, AM dentures were fabricated from ultraviolet-cured acrylic resin. Accuracy was verified by superimposing heat-cured and AM dentures on the tooth region data from the wax dentures and measuring displacement of the tooth arrangement. RESULTS: In the maxillary dentures, the amount of tooth displacement for the heat-cured dentures and for the AM dentures ranged from -0.08 to +0.06 mm and from -0.25 to +0.06 mm respectively. A significant difference was observed between two dentures. In the mandibular dentures, the amount of tooth displacement for the heat-cured dentures and for the AM dentures ranged from -0.09 to +0.07 mm and from -0.03 to +0.07 mm respectively. No significant difference was observed between two dentures. CONCLUSIONS: The artificial teeth of the maxillary dentures fabricated by AM showed a greater displacement compared to those by heat curing.


Subject(s)
Hot Temperature , Tooth, Artificial , Denture Bases , Dentures , Humans , Mandible , Maxilla
10.
Nutr Metab Cardiovasc Dis ; 29(5): 518-526, 2019 05.
Article in English | MEDLINE | ID: mdl-30935764

ABSTRACT

BACKGROUND AND AIMS: Gastric bypass is known to have larger effects on weight and metabolism than gastric banding. However, scarce data exist as to whether the differences are translated into differential risks of cardiovascular disease (CVD)-related morbidities. The objective was to examine whether adults with obesity and CVD who underwent gastric bypass have a lower rate of acute care use (emergency department [ED] visit or unplanned hospitalization) for CVD than those with gastric banding. METHODS AND RESULTS: We performed a comparative effectiveness study of gastric bypass versus banding among adults with obesity and CVD who underwent either surgery, using population-based [ED] and inpatient samples in California, Florida, and Nebraska from 2005 through 2011. The primary outcome was acute care use for CVD during a two-year postoperative period. We constructed negative binomial regression models to compare the event rate during sequential 6-month periods, using gastric banding group as the reference. We identified 11,229 adults with obesity and CVD who underwent gastric bypass and 3896 adults who had gastric banding. Patients with gastric bypass had significantly lower rate of the outcome compared to those with banding in the 7-12 months postoperative period (adjusted rate ratio [aRR] 0.77; 95% confidence interval [CI], 0.61-0.98; P = 0.03). The significant reduction in the rate persisted during 13-18 months (aRR 0.71; 95% CI, 0.57-0.90; P = 0.005) and 19-24 months (aRR 0.66; 95% CI, 0.52-0.82; P < 0.001) after bariatric surgery. CONCLUSION: In this population-based comparative effectiveness study of adults with obesity and CVD, the rate of acute care use for CVD was lower after gastric bypass compared to gastric banding.


Subject(s)
Cardiovascular Diseases/therapy , Gastric Bypass , Gastroplasty , Obesity/surgery , Adult , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Comparative Effectiveness Research , Female , Gastric Bypass/adverse effects , Gastroplasty/adverse effects , Humans , Male , Middle Aged , Obesity/diagnosis , Obesity/epidemiology , Risk Factors , Time Factors , Treatment Outcome , United States/epidemiology
12.
Oral Dis ; 25(1): 34-43, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29250913

ABSTRACT

Numerous neuroimaging studies have attempted to identify how the brain responds to stimuli mimicking dental treatment in normal non-phobic individuals. However, results were sometimes inconsistent due to small sample sizes and methodological variations. This meta-analysis employs standardized procedures to summarize data from previous studies to identify brain regions that were consistently activated across studies, elicited by stimuli such as pictures, sounds, or audiovisual footage mimicking those encountered during dental treatments. A systematic literature search was carried out using PubMed and Scopus. The meta-analysis analyzed data from 120 healthy subjects from seven neuroimaging studies. We assessed the risk of bias among the included studies with the Risk of Bias Assessment Tool for Nonrandomized Studies. One study appeared to have a high risk of selection bias, whereas the others were considered to have a low risk of bias. Results revealed three clusters of activation with cluster sizes ranging from 768 mm3 to 1,424 mm3 . Stimuli mimicking dental treatment consistently activated the bilateral anterior insula; right dorsal anterior cingulate, putamen, and medial prefrontal cortex; and left claustrum. This study confirmed that audio and/or visual stimuli mimicking dental treatment consistently activated the fear-related brain regions among healthy subjects, mostly consistent with activations from general anxiety but without the involvement of the amygdala.


Subject(s)
Brain/physiology , Dentistry , Neuroimaging , Anxiety , Fear , Humans
13.
Radiat Prot Dosimetry ; 182(4): 508-517, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30032259

ABSTRACT

The aim of this study is to estimate tube current modulation (TCM) profiles in paediatric computed tomography (CT) examinations with a TCM scheme (Volume-EC) and evaluate the estimation accuracy of TCM profiles. Another aim is to validate organ doses calculated using Monte Carlo-based CT dosimetry software and estimated TCM profiles by comparing them with those measured using 5-year-old and 10-year-old anthropomorphic phantoms and radio-photoluminescence glass dosemeters. Dose calculations were performed by inputting detailed descriptions of a CT scanner, scan parameters and CT images of the phantoms into the software. Organ doses were evaluated from the calculated dose distribution images. Average relative differences (RDs) between the estimated and actual TCM profiles ranged from -3.6 to 5.6%. RDs between the calculated and measured organ doses ranged from -4.2 to 13.0% and -18.1 to 4.9% for 5-year-old and 10-year-old phantoms, respectively. These results validate dose calculations for paediatric CT scans using TCM.


Subject(s)
Radiation Dosage , Radiometry/methods , Tomography, X-Ray Computed , Child , Child, Preschool , Humans , Monte Carlo Method , Phantoms, Imaging , Software , Thermoluminescent Dosimetry
14.
Lipids Health Dis ; 17(1): 132, 2018 Jun 02.
Article in English | MEDLINE | ID: mdl-29859535

ABSTRACT

BACKGROUND: Lectin-like oxidized low-density-lipoprotein receptor 1 (Lox-1) is the receptor for oxidized low-density lipoprotein (oxLDL), a mediator in dyslipidemia. Toll-like receptor (TLR)-2 and - 4 are receptors of lipopolysaccharide (LPS) from Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Although some reports have demonstrated that periodontitis has an adverse effect on dyslipidemia, little is clear that the mechanism is explained the effects of dyslipidemia on osteoclastogenesis. We have hypothesized that osteoclast oxLDL has directly effect on osteoclasts (OCs), and therefore alveolar bone loss on periodontitis may be increased by dyslipidemia. The present study aimed to elucidate the effect of Lox-1 on osteoclastogenesis associated with TLRs in vitro. METHODS: Mouse bone marrow cells (BMCs) were stimulated with macrophage colony-stimulating factor into bone marrow macrophages (BMMs). The cells were also stimulated with synthetic ligands for TLR2 (Pam3CSK4) or TLR4 (Lipid A), with or without receptor activator of nuclear factor kappa-B ligand (RANKL), and assessed for osteoclastogenesis by tartrate-resistant acid phosphatase (TRAP) staining, immunostaining, western blotting, flow activated cell sorting (FACS) analysis, real-time polymerase chain reaction (PCR), and reverse transcription PCR. RESULTS: Lox-1 expression was significantly upregulated by Pam3CSK4 and Lipid A in BMCs (p < 0.05), but not in BMMs. FACS analysis identified that Pam3CSK4 upregulated RANK and Lox-1 expression in BMCs. TRAP-positive cells were not increased by stimulation with Pam3CSK4 alone, but were increased by stimulation with combination combined Pam3CSK and oxLDL. Expression of both Lox-1 and myeloid differentiation factor 88 (MyD88), an essential adaptor protein in the TLR signaling pathway, were suppressed by inhibitors of TLR2, TLR4 and mitogen-activated protein kinase (MAPK). CONCLUSIONS: This study supports that osteoclastogenesis is promoted under the coexistence of oxLDL by TLR2-induced upregulation of Lox-1 in BMCs. This indicates that periodontitis could worsen with progression of dyslipidemia.


Subject(s)
Bone Marrow Cells/metabolism , Osteogenesis , Scavenger Receptors, Class E/physiology , Signal Transduction , Toll-Like Receptor 2/metabolism , Animals , Bone Marrow Cells/physiology , Cell Differentiation , Lipoproteins, LDL , Macrophages , Male , Mice , Periodontitis , Scavenger Receptors, Class E/metabolism
15.
J Neonatal Perinatal Med ; 11(2): 191-194, 2018.
Article in English | MEDLINE | ID: mdl-29843264

ABSTRACT

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test <5%, prolonged PT and APTT, and a marked elevation of protein induced by vitamin K absence or antagonist-II. This case highlighted a potential risk of intracranial bleeding due to maternal vitamin K deficiency and difficulty in its prediction before delivery. Vitamin K supplementation to high risk mothers might be indispensable for preventing severe fetal vitamin K deficiency. Even when coagulation studies in mothers is normal, it is imperative to provide vitamin K supplementation for total protection.


Subject(s)
Feeding and Eating Disorders/complications , Intracranial Hemorrhages/etiology , Mothers , Pregnancy Complications, Hematologic/blood , Prenatal Exposure Delayed Effects/blood , Vitamin K Deficiency/complications , Vitamin K/therapeutic use , Adult , Feeding and Eating Disorders/blood , Feeding and Eating Disorders/physiopathology , Female , Humans , Infant, Newborn , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/diagnostic imaging , Maternal Nutritional Physiological Phenomena , Pregnancy , Pregnancy Complications, Hematologic/physiopathology , Prenatal Exposure Delayed Effects/physiopathology , Treatment Outcome , Vitamin K Deficiency/blood , Vomiting/complications
16.
Orthop Traumatol Surg Res ; 104(6): 823-827, 2018 10.
Article in English | MEDLINE | ID: mdl-29567320

ABSTRACT

Long-term follow-up of patients with adhesive capsulitis (AC) reveals that approximately half of them suffer from a limited range of shoulder motion, particularly external and/or internal rotation. We report the surgical technique and short-term clinical outcomes of ultrasound-guided release of the thickened coracohumeral (CH) ligament in 8 patients (9 shoulders) with AC. Passive external rotation with the arm by the side significantly increased from an average of 18° preoperatively to 47° immediately after CH ligament release. VAS and ASES scores were improved at 3months follow-up in all 9 shoulders, and maintained at 6months follow-up in 6 shoulders. No procedure-related adverse events developed over the 6-month follow-up period. Ultrasound-guided release for thickened CH ligament is a reliable and effective minimally invasive surgery for persistent limited external rotation due to AC of the shoulder.


Subject(s)
Bursitis/physiopathology , Bursitis/surgery , Ligaments, Articular/diagnostic imaging , Ligaments, Articular/surgery , Shoulder Joint/physiopathology , Adult , Aged , Bursitis/complications , Coracoid Process , Female , Humans , Humerus , Male , Middle Aged , Range of Motion, Articular , Rotation , Shoulder Joint/surgery , Shoulder Pain/etiology , Surgery, Computer-Assisted , Ultrasonography
17.
Aliment Pharmacol Ther ; 47(7): 1012-1022, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29424449

ABSTRACT

BACKGROUND: Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS: A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS: Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION: Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Liver/pathology , Sustained Virologic Response , Aged , Cohort Studies , Elasticity , Elasticity Imaging Techniques , Female , Follow-Up Studies , Hepacivirus/genetics , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Humans , Liver/diagnostic imaging , Liver/virology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , Remission Induction , Viral Load/drug effects
18.
Allergy ; 73(2): 369-378, 2018 02.
Article in English | MEDLINE | ID: mdl-28857178

ABSTRACT

BACKGROUND: Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs. METHODS: Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies. RESULTS: Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4. CONCLUSION: These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arachidonic Acids/pharmacology , Asthma/prevention & control , Eosinophilia/prevention & control , Inflammation/physiopathology , Lung/physiopathology , Animals , Asthma/immunology , Asthma/physiopathology , Disease Models, Animal , Eosinophilia/immunology , Eosinophilia/physiopathology , Inflammation/immunology , Lung/immunology , Male , Mice , Mice, Inbred C57BL
19.
Anaesthesia ; 72(10): 1251-1264, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28737223

ABSTRACT

We conducted both conventional pairwise and Bayesian network meta-analyses to compare the clinical properties of supraglottic airway devices in children. We searched six databases for randomised clinical trials. Our primary end-points were oropharyngeal leak pressure, risk of insertion failure at first attempt, and blood staining risk. The risk of device failure, defined as the abandonment of the supraglottic airway device and replacement with a tracheal tube or another device, was also analysed. Sixty-five randomised clinical trials with 5823 participants were identified, involving 16 types of supraglottic airway device. Network meta-analysis showed that the i-gel™, Cobra perilaryngeal airway™ and Proseal laryngeal mask airway (LMA® -Proseal) showed statistically significant differences in oropharyngeal leak pressure compared with the LMA® -Classic, with mean differences (95% credible interval, CrI) of 3.6 (1.9-5.8), 4.6 (1.7-7.6) and 3.4 (2.0-4.8) cmH2 O, respectively. The i-gel was the only device that significantly reduced the risk of blood staining of the device compared with the LMA-Classic, with an odds ratio (95%CrI) of 0.46 (0.22-0.90). The risk (95%CI) of device failure with the LMA-Classic, LMA® -Unique and LMA-Proseal was 0.36% (0.14-0.92%), 0.49% (0.13-1.8%) and 0.50% (0.23-1.1%), respectively, whereas the risk (95%CI) of the i-gel and PRO-Breathe was higher, at 3.4% (2.5-4.7%) and 6.0% (2.8-12.5%), respectively. The risk, expressed as odds ratio (95%CrI), of insertion failure at first attempt, was higher in patients weighing < 10 kg at 5.1 (1.6-20.1). We conclude that the LMA-Proseal may be the best supraglottic airway device for children as it has a high oropharyngeal leak pressure and a low risk of insertion. Although the i-gel has a high oropharyngeal leak pressure and low risk of blood staining of the device, the risk of device failure should be evaluated before its routine use can be recommended.


Subject(s)
Laryngeal Masks , Air Pressure , Anesthesia, General/instrumentation , Bayes Theorem , Child , Equipment Design , Equipment Failure , Humans , Laryngeal Masks/adverse effects , Oropharynx , Randomized Controlled Trials as Topic/methods
20.
J Neuroendocrinol ; 29(6)2017 06.
Article in English | MEDLINE | ID: mdl-28475285

ABSTRACT

Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18ß-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling enhances synchronised activities among neighbouring KNDy neurones, and that both neurone-neurone and neurone-glia communications via gap junctions possibly contribute to synchronised activities among KNDy neurones.


Subject(s)
Gap Junctions/physiology , Neuroglia/physiology , Neurons/physiology , Peptide Fragments/pharmacology , Substance P/analogs & derivatives , Animals , Cells, Cultured , Connexins/metabolism , Dynorphins/physiology , Gap Junctions/drug effects , Gap Junctions/metabolism , Glycyrrhetinic Acid/analogs & derivatives , Glycyrrhetinic Acid/pharmacology , Kisspeptins/genetics , Medulla Oblongata/metabolism , Mefloquine/pharmacology , Mice, Transgenic , Neuroglia/metabolism , Neurokinin B/physiology , Neurons/drug effects , Neurons/metabolism , Peptide Fragments/antagonists & inhibitors , Substance P/antagonists & inhibitors , Substance P/pharmacology
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