Vestibular dysfunction in lateral semicircular canal dysplasia

IntroductionLateral semicircular canal (LSCC) dysplasia is the most common inner ear malformation. The severity of dysplasia can appear in various spectrums, from a short and broad LSCC with normal or small-sized central bony island (CBI) to a single fluid-filled cavity confluent with the vestibule without CBI. However, reports on the association between LSCC dysplasia and the loss of vestibular function are still lacking. In this study, the results of vestibular function tests [caloric test and video-head impulse test (vHIT)] in patients with LSCC dysplasia were analyzed and compared between groups with and without CBI.MethodsThis study retrospectively enrolled 17 patients (23 ears) who had LSCC dysplasia following computed tomography or magnetic resonance imaging and underwent vestibular function tests.ResultsLSCC dysplasia was observed unilaterally in 11 patients and bilaterally in six patients. Nine of 23 ears had CBIs, and 14 ears had no CBI. Three of 17 patients experienced dizziness. Abnormal caloric tests were detected in 11 of the 16 patients who underwent the caloric tests (69%); in contrast, 11 of 12 patients who underwent the vHIT (92%) had normal LSCC vestibulo-ocular reflex (VOR) gain on vHIT. A significant correlation was found between the maximum slow-phase velocity of the caloric test and LSCC VOR gain of the vHIT (correlation coefficient 0.792, p = 0.004). The CBI-absent group showed significantly lower SPV and LSCC VOR gains than the CBI-present group (p = 0.001 and 0.004, respectively).DiscussionLSCC dysplasia impairs VOR function, especially in the absence of CBI

Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

BACKGROUND: Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. METHODS: Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. RESULTS: Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. CONCLUSION: Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients

Early Detection of Cerebral Infarction With Middle Cerebral Artery Occlusion With Functional Near-Infrared Spectroscopy: A Pilot Study

Background: NIRSIT, a functional near-infrared spectroscopy (fNIRS) device with 204 channels, can measure oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) in non-pulsatile blood flow non-invasively using the absorption difference between HbO2 and HbR at a wavelength of 700–1,000 nm and can display the perfusion status in real time.Objective: We applied NIRSIT to patients with stroke to evaluate the usefulness of NIRSIT as an fNIRS device for the early detection of stroke.Methods: We performed a prospective pilot study in an emergency department (ED). Adult patients who had suspected symptoms and signs of stroke within 12 h of the first abnormal time and who underwent intravenous thrombolysis (IVT) or intra-arterial thrombectomy with acute middle cerebral artery (MCA) or internal carotid artery (ICA) infarction were enrolled. NIRSIT was applied to the patients before the imaging study, and the perfusion status of the brain was displayed in real time at the bedside. We compared the NIRSIT results with the mean transit time (MTT) map from perfusion computed tomography (PCT) and the time-to-peak (TTP) map from perfusion-weighted magnetic resonance imaging (PWI).Results: Six male and three female patients were enrolled, and the median age was 74 years. The most common symptom was unilateral extremity weakness (77.8%), followed by dysarthria (33.3%) and aphasia (11.1%). The median National Institutes of Health Stroke Scale (NIHSS) score was 17. All cases of MCA infarction showed different cerebral oxygen saturation values between bilateral lobes of the brain in fNIRS imaging, and these values matched the PCT and PWI results.Conclusions: The brain hemisphere with low oxygen saturation on fNIRS showed hypoperfusion on PCT or PWI. The fNIRS device could be useful in assessing the perfusion status of the brain and detecting MCA or ICA infarction in real time at the bedside

Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts

Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1(-/-) mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs

Does Tumor Size Influence the Diagnostic Accuracy of Ultrasound-Guided Fine-Needle Aspiration Cytology for Thyroid Nodules?

Background. Fine-needle aspiration cytology (FNAC) is diagnostic standard for thyroid nodules. However, the influence of size on FNAC accuracy remains unclear especially in too small or too large thyroid nodules. The objective of this retrospective cohort study was to investigate the effect of nodule size on FNAC accuracy. Methods. All consecutive patients who underwent thyroidectomy for nodules in 2010 were enrolled. FNAC results (according to the Bethesda system) were compared to pathological diagnosis. The nodules were categorized into groups A–E on the basis of maximal diameter on ultrasound (≤0.5, >0.5–1, >1-2, >2–4, and >4 cm, resp.). Results. There were 502 cases with 690 nodules. Overall FNAC sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.4%, 98.2%, 99.4%, 86.4%, and 96.0%, respectively. False-negative rates (FNRs) of groups A–E were 3.2%, 5.1%, 1.3%, 13.3%, and 50%, respectively. Accuracy rates of groups A–E were 96.8%, 94.8%, 99%, 94.7%, and 87.5%, respectively. Conclusion. Although accuracy rates of FNAC in thyroid nodules smaller than 0.5 cm are comparable to the other group, thyroid nodules larger than 4 cm with benign cytology carry a higher risk of malignancy, which suggest that those should be considered for intensive follow-up or repeated biopsy

JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin

<p>Abstract</p> <p>Background</p> <p>Bee venom therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. We previously found that bee venom and melittin (a major component of bee venom) have anti-inflammatory effect by reacting with the sulfhydryl group of p50 of nuclear factor-kappa B (NF-κB) and IκB kinases (IKKs). Since mitogen activated protein (MAP) kinase family is implicated in the NF-κB activation and inflammatory reaction, we further investigated whether activation of MAP kinase may be also involved in the anti-inflammatory effect of melittin and bee venom.</p> <p>Methods</p> <p>The anti-inflammatory effects of melittin and bee venom were investigated in cultured Raw 264.7 cells, THP-1 human monocytic cells and Synoviocytes. The activation of NF-κB was investigated by electrophoretic mobility shift assay. Nitric oxide (NO) and prostaglandin E₂(PGE₂) were determined either by Enzyme Linked Immuno Sorbent Assay or by biochemical assay. Expression of IκB, p50, p65, inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) as well as phosphorylation of MAP kinase family was determined by Western blot.</p> <p>Results</p> <p>Melittin (0.5–5 μg/ml) and bee venom (5 and 10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml) and sodium nitroprusside (SNP, 200 μM)-induced activation of c-Jun NH2-terminal kinase (JNK) in RAW 264.7 cells in a dose dependent manner. However, JNK inhibitor, anthra [1,9-cd]pyrazole-6 (2H)-one (SP600215, 10–50 μM) dose dependently suppressed the inhibitory effects of melittin and bee venom on NF-κB dependent luciferase and DNA binding activity via suppression of the inhibitory effect of melittin and bee venom on the LPS and SNP-induced translocation of p65 and p50 into nucleus as well as cytosolic release of IκB. Moreover, JNK inhibitor suppressed the inhibitory effects of melittin and bee venom on iNOS and COX-2 expression, and on NO and PGE₂generation.</p> <p>Conclusion</p> <p>These data show that melittin and bee venom prevent LPS and SNP-induced NO and PGE₂production via JNK pathway dependent inactivation of NF-κB, and suggest that inactivation of JNK pathways may also contribute to the anti-inflammatory and anti-arthritis effects of melittin and bee venom.</p

Polymer Micelle Formulation for the Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy and Pharmacokinetic Studies in Mice

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic acid (CFZ-PM) and assessed its in vivo anticancer efficacy and pharmacokinetic profiles. Despite in vitro metabolic protection of CFZ, CFZ-PM did not display in vivo anticancer efficacy in mice bearing human lung cancer xenograft (H460) superior to that of the clinically used cyclodextrin-based CFZ (CFZ-CD) formulation. The plasma pharmacokinetic profiles of CFZ-PM were also comparable to those of CFZ-CD and the residual tumors that persisted in xenograft mice receiving CFZ-PM displayed an incomplete proteasome inhibition. In summary, our results showed that despite its favorable in vitroperformances, the current CFZ-PM formulation did not improve in vivo anticancer efficacy and accessibility of active CFZ to solid cancer tissues over CFZ-CD. Careful consideration of the current results and potential confounding factors may provide valuable insights into the future efforts to validate the potential of CFZ-based therapy for solid cancer and to develop effective CFZ delivery strategies that can be used to treat solid cancers

Inflammatory bowel disease–associated intestinal fibrosis

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end