Vanilloid receptor TRPV1-positive sensory afferents in the mouse ankle and knee joints

TRPV1, a cation channel on sensory nerves sensitive to heat and capsaicin, plays an important role in the transduction of noxious stimuli to the spinal cord. It is expressed by neurons in dorsal root ganglia (DRG) that may also express neuropeptides, which are important for the development of inflammation. Mice with genetic deletion of TRPV1 have been used to study the involvement of this receptor in the mediation of pain and inflammation in animal models of arthritis. However, the expression of TRPV1 in the mouse articular afferents has not been studied. We here provide numerical data on expression of TRPV1 in an identified population of sensory afferents to the mouse L3–L5 DRG that innervate joints, in comparison with that from bladder and skin. A combination of tracing and immunocytochemistry revealed that TRPV1-positive fibers innervate the mouse knee and ankle. At the level of DRG, ~40% of articular afferents from these joints express TRPV1 and the majority of them are peptidergic, as revealed by simultaneous immunostaining for the neuropeptide calcitonin gene-related peptide. These findings are consistent with the idea that activation of TRPV1 in peripheral axons of joint afferents may mediate the synovial release of neuropeptides in arthritis

Meibomian Epithelioma of the Lower Eyelid in a Thoroughbred Horse

A 9-year old, castrated male, thoroughbred horse presented for a left lower eyelid mass with ocular signs of mucopurulent discharge, conjunctival hyperemia and ocular discomfort. On physical examination, there was no other abnormality. Surgically, the mass arising from the inner surface of left lower eyelid was excised and examined histopathologically. Microscopically, the eyelid mass exhibited neoplastic basaloid cells forming irregular cell masses of variable size separated by thin fibrous tissues. The basaloid cells showed mildly pleomorphic and undifferentiated appearances with prominent oval nuclei and scant cytoplasm. Poorly differentiated meibocytes were observed occasionally in the periphery regions of the cell masses suggesting the mass of lower eyelid originated from meibomian glands. Based on histopathological observation, the present case was diagnosed as an equine meibomian epithelioma in the lower eyelid. To the author’s knowledge, the present case is the first report of equine meibomian epithelioma in veterinary literatures

PKCε-mediated ERK1/2 activation involved in radiation-induced cell death in NIH3T3 cells

AbstractProtein kinase C (PKC) isoforms play distinct roles in cellular functions. We have previously shown that ionizing radiation activates PKC isoforms (α, δ, ε, and ζ), however, isoform-specific sensitivities to radiation and its exact mechanisms in radiation mediated signal transduction are not fully understood. In this study, we showed that overexpression of PKC isoforms (α, δ, ε, and ζ) increased radiation-induced cell death in NIH3T3 cells and PKCε overexpression was predominantly responsible. In addition, PKCε overexpression increased ERK1/2 activation without altering other MAP-kinases such as p38 MAPK or JNK. Co-transfection of dominant negative PKCε (PKCε-KR) blocked both PKCε-mediated ERK1/2 activation and radiation-induced cell death, while catalytically active PKCε construction augmented these phenomena. When the PKCε overexpressed cells were pretreated with PD98059, MEK inhibitor, radiation-induced cell death was inhibited. Co-transfection of the cells with a mutant of ERK1 or -2 (ERK1-KR or ERK2-KR) also blocked these phenomena, and co-transfection with dominant negative Ras or Raf cDNA revealed that PKCε-mediated ERK1/2 activation was Ras–Raf-dependent. In conclusion, PKCε-mediated ERK1/2 activation was responsible for the radiation-induced cell death

Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea

Background/AimsThe prevalence of nonalcoholic fatty liver disease (NAFLD) in Korea has increased recently. The aim of the present study was to determine the regional differences in the prevalence and characteristics of NAFLD.MethodsFrom January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents receiving a health examination at our institution were enrolled in this cross-sectional study. After applying exclusion criteria, the data of 141,610 subjects (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was established by ultrasound examination.ResultsThe overall prevalence of NAFLD was 27.3% (38.3% in men, 12.6% in women). When standardized according to age, area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001). The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi-do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001).ConclusionsThe regional prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are needed to establish the etiology of this difference

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803)

Changes of Alpha1-Antitrypsin Levels in Allergen-induced Nasal Inflammation

ObjectivesAlpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation.MethodsForty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II.ResultsAt baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II.ConclusionThe increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation

Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma

Background/Aims Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. Methods In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. Results During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. Conclusions Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence

Chromosomal end fusion resulting from telomere erosion increases susceptibility to radiation via multinucleation: Effect of p53

and telomerase activation are frequently found in human cancers. p53 inactivation, however, eliminates or attenuates the biological responses to telomerase inhibition and the eventual telomere erosion. We show that telomere erosion can increase the susceptibility to radiation, irrespective of p53 status. Both telomerase inhibition and critically shortened telomere with significant change of chromosomal end-to-end fusion were essential for the enhancement of radiosensitivity. The enhancement was correlated with greater formation of multinucleated cells. p53 inactivation did not eliminate the observed generation of chromosomal fusion and multinucleation, and the resulting increased susceptibility to radiation, as opposed to the previously proved role of p53 in mediating cellular responses to telomere dysfunction. The present findings suggest the importance of chromosomal end fusion in modulating radiosensitivity rather than p53 DNA damage signaling. Thus, the suggested anticancer radiotherapeutic strategy combined with telomerase inhibition could clinically be applicable to cancers, irrespective of p53 status.We thank Professor Woon Ki Paik for critical reading of the manuscript and Eun-Ju Lee for assistance in the preparation of the manuscript. This work was supported by a grant from National Nuclear R&D program and Human Genome Project (FG-1-1), Korean Ministry of Science and Technology