Headache Attributed to Temporomandibular Disorder and Primary Cough Headache.

Orofacial pain is a frequent chief complaint of many systemic disorders. A primary cough headache may mimic the clinical symptoms of a temporomandibular disorder (TMD) or may be associated with TMDs. Case report: A 52-year-old man presented with a 1-year history of TMD symptoms with clicking. He presented with the chief complaint of a sudden and severe headache when coughing, sneezing, or crouching. Comprehensive intra- and extra-oral examinations were performed, which revealed myofascial pain involving the right masseter and temporalis muscles, disc displacement with reduction in the right temporomandibular joint, and headache attributed to TMD, but no severe headaches appeared in the cough-induced test at the first visit. Initially, we advised the patient to minimize activities that require jaw function (e.g., chewing), avoid jaw parafunction (e.g., bruxism), and to perform at-home jaw exercises to stretch the jaw muscles. The patient's symptoms reduced by more than half after the TMD home care and physiotherapy. He was then treated with 75 mg of indomethacin per day, which eliminated his headache. The patient was then referred to a headache specialist, who diagnosed primary cough headache.

Synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles, and in vivo pharmacokinetics depending on the structural characteristics.

For designing nanoparticles as drug carriers, a covalently crosslinked structure is necessary for the structural stability in vivo. In this study, we prepared core crosslinked nanoparticles through the formation of nanoemulsions stabilized by poly(ethylene glycol) (PEG)-bearing surfactants. The structural characteristics of these particles were carefully evaluated using small-angle scattering techniques including dynamic, static, X-ray, and neutron scattering. The particles demonstrated high stability even in vivo, with the suppression of premature drug release owing to the crosslinked structure. Interestingly, the ability to retain encapsulated molecules was dependent on the molecular weight of PEG in vivo, presumably due to the difference in the crowding density of PEG chains at the outermost surface. This suggests that conferring structural stability via a core crosslinked structure is surely important, but we also need to consider controlling the crowding density of the hydrophilic polymer chains in the particle shell when designing drug carriers.

Creation of simulated papillae for endoscopic sphincterotomy and papillectomy training by using in vivo and ex vivo pig model (with videos).

BACKGROUND: There are few in vivo and ex vivo models for training in endoscopic sphincterotomy (ES) and endoscopic papillectomy (EP). OBJECTIVE: We describe in vivo and ex vivo training pig models that use a simulated papilla for hands-on teaching of ES and EP. DESIGN: Animal experiment. SETTING: A referral center. MATERIALS AND INTERVENTIONS: Hyaluronate solution (0.4%) was injected submucosally using a 25-gauge sclerotherapy needle to create a submucosal bleb by using porcine in vivo stomach, ex vivo stomach, and ex vivo rectum. ES and EP were then performed by using a pull-type sphincterotome and snare, respectively. MAIN OUTCOME MEASUREMENT: The feasibility of creating a simulated papilla for ES and EP procedures was tested by experienced and nonexperienced ERCP endoscopists. RESULTS: Creation of a hemispheroidal bulge was successful in 13 of 17 (76%) areas within an in vivo stomach, 13 of 16 (81%) areas of an ex vivo stomach, and 16 of 16 (100%) areas in an ex vivo rectum. In the in vivo stomach model, ES was successfully and realistically performed on the anterior wall of the stomach rather than in other walls. In the ex vivo stomach model, endoscopists experienced in ERCP and trainees performed ES without difficulty, whereas it was difficult or impossible for nonexperienced trainees to perform ES. In the ex vivo rectum model, all 3 endoscopists were able to complete not only ES but also EP. LIMITATIONS: Pilot study. CONCLUSIONS: Although further studies are necessary to evaluate the reproducibility and cost-effectiveness, this novel pig model appears useful for ES and EP training.

Endoscopic ultrasound-guided double stenting for biliary and duodenal obstruction.

Endoscopic biliary stenting for malignant biliary obstruction is currently the gold standard for biliary drainage. Biliary cancer treatment is crucial. Cases of gastric outlet obstruction that includes the duodenum because of cancer invasion and biliary obstruction are seldom observed. The required treatment for such cases is simple biliary stenting and a different treatment for duodenal obstruction. Hence, double stenting for bile duct and duodenal obstruction has drawn attention. In the present review, we state different treatment strategies for malignant duodenal obstruction and then describe double stenting in biliary obstruction that also includes non-biliary cancer malignant lesions and duodenal obstruction.

Large balloon dilatation following endoscopic sphincterotomy using a balloon enteroscope for the bile duct stone extractions in patients with Roux-en-Y anastomosis.

BACKGROUND: Extraction of bile duct stones in patients who have undergone Roux-en-Y anastomosis can be challenging. Recently, large balloon dilation following endoscopic sphincterotomy has been shown to be useful for the removal of bile duct stones. AIM: We retrospectively evaluated the feasibility and safety of endoscopic sphincterotomy large balloon dilation for the removal of bile duct stones in patients with Roux-en-Y anastomosis. METHODS: Large balloon papillary dilation following EST for the removal of bile duct stones was performed on the intact papilla in 15 patients with Roux-en-Y anastomosis at our institution. When we could not use the long-type accessories, a conventional forward-viewing upper endoscope passed through the over tube of the single-balloon or double-balloon enteroscope for the use of short-type accessories. Following endoscopic sphincterotomy, a large balloon catheter was positioned across the main duodenal papilla. The size of large balloon used ranged from 15mm to 20mm. RESULTS: Complete clearance of bile duct stones was achieved in all cases in the initial session without any adverse events. A mechanical lithotriptor for crushing stones was used in one patient (6.7%). CONCLUSION: Large balloon papillary dilation following EST appears to be an effective and safe treatment for difficult-to-remove bile duct stones in patients with Roux-en-Y anastomosis .

Connective tissue growth factor is a substrate of ADAM28.

ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala(181)-Tyr(182) and Asp(191)-Pro(192) bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor(165) (VEGF(165)), releasing biologically active VEGF(165) from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF(165)-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF(165) complex.

Puma is a novel target of soy isoflavone genistein but is dispensable for genistein-induced cell fate determination.

Here, we attempted to identify novel target genes of genistein in human A549 cells. Using analysis of proteins related to cell cycle and apoptotic pathways, we confirmed an elevated level of p53 accompanying p21 Waf1/Cip1 protein in genistein-treated or genistin-treated A549 and WI-38 cells, but not in HeLa cells. In addition, a p53-upregulated modulator of apoptosis (Puma) protein accumulated significantly in genistein-treated A549 and WI-38 cells, but not in genistin-treated or beta-estradiol-treated cells, though the growth of any ingredient-treated cells was severely inhibited. Intriguingly, the caspase-3 activity of genistein-treated A549 cells, in which Puma or p53 expression was knocked-down by RNA interference (RNAi), remained unaltered compared to that in cells transfected with irrelevant RNAi. These results raise a concern that molecular targets identified by powerful omic approaches may not necessarily represent key molecules responsible for given cellular phenotypes and thus must be verified by conclusive assays.

Transcriptional regulation of human chromatin assembly factor ASF1.

Antisilencing function 1 (ASF1) is a conserved histone chaperone implicated in nucleosome assembly, transcriptional silencing, and the cellular response to DNA damage. Here, we report the identification of human ASF1B, but not ASF1A, as a direct transcriptional target of transcription factor E2F1. We demonstrated that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated ASF1B mRNA expression in HeLa cells. Analysis of human ASF1B promoter constructs showed that an E2F-responsive sequence was necessary for E2F1-induced activation of the ASF1B gene transcription. Oligonucleotides including an E2F consensus sequence were specifically bound by E2F1 protein in vitro. Chromatin immunoprecipitation analysis demonstrated that E2F1 bound to an E2F-responsive sequence of the human ASF1B gene. Among the members of the E2F family, E2F1 to E2F5, but not E2F6, activated the ASF1B reporter construct. Sp1 and NFYA failed to induce the activity of the ASF1A and ASF1B promoter. ASF1A and ASF1B mRNA were upregulated by serum stimulation. Taken together, our results suggest that the expression of human ASF1A and ASF1B are upregulated followed by cell proliferation signal, but that of ASF1B is uniquely regulated by transcription factors E2F during cell cycle progression.

Systems biology-based identification of crosstalk between E2F transcription factors and the Fanconi anemia pathway.

Fanconi anemia (FA) is an autosomal recessive disorder characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. At least eleven members of the FA gene family have been identified using complementation experiments. Ubiquitin-proteasome has been shown to be a key regulator of FA proteins and their involvement in the repair of DNA damage. Here, we identified a novel functional link between the FA/BRCA pathway and E2F-mediated cell cycle regulome. In silico mining of a transcriptome database and promoter analyses revealed that a significant number of FA gene members were regulated by E2F transcription factors, known to be pivotal regulators of cell cycle progression - as previously described for BRCA1. Our findings suggest that E2Fs partly determine cell fate through the FA/BRCA pathway.