Growth and development: hereditary and mechanical modulations

Growth and development is the net result of environmental modulation of genetic inheritance. Mesenchymal cells differentiate into chondrogenic, osteogenic, and fibrogenic cells: the first 2 are chiefly responsible for endochondral ossification, and the last 2 for sutural growth. Cells are influenced by genes and environmental cues to migrate, proliferate, differentiate, and synthesize extracellular matrix in specific directions and magnitudes, ultimately resulting in macroscopic shapes such as the nose and the chin. Mechanical forces, the most studied environmental cues, readily modulate bone and cartilage growth. Recent experimental evidence demonstrates that cyclic forces evoke greater anabolic responses of not only craniofacial sutures, but also cranial base cartilage. Mechanical forces are transmitted as tissue-borne and cell-borne mechanical strain that in turn regulates gene expression, cell proliferation, differentiation, maturation, and matrix synthesis, the totality of which is growth and development. Thus, hereditary and mechanical modulations of growth and development share a common pathway via genes. Combined approaches using genetics, bioengineering, and quantitative biology are expected to bring new insight into growth and development, and might lead to innovative therapies for craniofacial skeletal dysplasia including malocclusion, dentofacial deformities, and craniofacial anomalies such as cleft palate and craniosynostosis, as well as disorders associated with the temporomandibular joint.     

Intracanal reinforcement fiber in pediatric dentistry: a case report.

A technique for the restoration of carious primary maxillary incisors using indirect resin composite crowns and intracanal reinforcement fiber is described. Endodontic treatment was previously performed on each tooth. The advantages of using an intracanal reinforcement fiber include resin composite crown reinforcement, translucency, and relative manipulation facility. In addition, the use of indirect resin composite crowns provides good shape and esthetics, as well as reduced chair time for the child. The technique is illustrated in a case report in which indirect resin composite crowns and an intracanal reinforcement fiber are placed in a 3-year-old girl.     

Vulvar carcinoma in young patients and its relationship with genital warts.

We report the occurrence of aggressive vulvar carcinoma associated with condyloma acuminata in three patients under 33 years old. Discussion of the role of the human papilloma virus (HPV) in the development of vulvar cancer is also presented. Three patients with condyloma associated with aggressive vulvar squamous cell carcinoma, in situ (1 case) and invasive (2 cases), documented by biopsy and/or vulvectomy are presented. In situ hybridization (ISH) was used to characterize the subtypes of HPV. One patient with erythematous systemic lupus developed in situ carcinoma after 5 years. The other two cases also developed aggressive multicentric, invasive squamous cell carcinoma after 10 years of diagnosis of condyloma. In all cases HPV cytological abnormalities were seen throughout the pathological examination. HPV 16 and 18 were present in cells of invasive squamous cell carcinoma in cases 2 and 3. HPV 6 and 11 were detected only in the condyloma area in case 2. HPV 30 was seen only in the condyloma area in case 3. This report emphasizes the need for biopsies of all unusually persistent or treatment-resistant condylomas, particularly in young and/or immunosuppressed patients.     

Long-term Outcomes of Direct Endoscopic Necrosectomy for Complicated or Symptomatic Walled-Off Necrosis: A Korean Multicenter Study

Background/AimsThe endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis.MethodsThe data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected.ResultsSixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites).ConclusionsConsidering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.     

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.     

Effects of quercetin on α9α10 nicotinic acetylcholine receptor-mediated ion currents

Quercetin, one of the flavonoids, is a low molecular weight substance found in fruits and vegetables. Quercetin, like other flavonoids, has a wide range of neuropharmacological actions and antioxidant effects. The α9α10 nicotinic acetylcholine receptor is one of the numerous nicotinic acetylcholine receptors that exist as a heteropentameric form between efferent olivocochlear fibers and hair cells of the cochlea. In this study, we report the effects of quercetin on rat α9α10 nicotinic acetylcholine receptor-mediated ion currents using the two-electrode voltage-clamp technique. Treatment with acetylcholine evoked inward currents (I_ACh) in oocytes heterologously expressing the α9α10 nicotinic acetylcholine receptor. Quercetin blocked I_ACh in concentration-dependent and reversible manners, and the blocking effect on I_ACh was stronger with pre-application than co-application of quercetin. The half maximal inhibitory concentration (IC₅₀) of quercetin was 45.4 ± 10.1 μM. Quercetin-mediated I_ACh inhibition was not affected by acetylcholine concentration and was independent of membrane-holding potential. Although the inhibitory effect of quercetin was significantly attenuated in the absence of extracellular Ca²⁺, the action of quercetin was independent of extracellular Ca²⁺ concentration, indicating that the presence of extracellular Ca²⁺ might be needed for quercetin-related effects and might play an important role in quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor. These results indicate that quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor could provide a molecular basis for quercetin actions at the cellular level.     

Effect of dextromethorphan on human K(v)1.3 channel activity: involvement of C-type inactivation

Dextromethorphan exhibits neuroprotective effects against inflammation-mediated neurodegeneration. However, relatively little is known regarding the molecular mechanism for this inflammation-mediated neuroprotection. Human K(v)1.3 channels, one of the voltage-gated potassium channels, are widely expressed in the immune and nervous systems. Activation of human K(v)1.3 channels causes neuroglia-mediated neurodegeneration. Agents that inhibit human K(v)1.3 channel activity have been developed as novel drugs for immunosuppression. In the present study, we investigated the effects of dextromethorphan on human K(v)1.3 or K(v)1.2 channel activity heterologously expressed in Xenopus laevis oocytes. The channel currents were measured with the two-electrode voltage clamp technique. Activation of both channels induced outward peak and steady-state currents. Dextromethorphan treatment induced a slight inhibition of peak currents in human K(v)1.2 and K(v)1.3 channels, whereas dextromethorphan profoundly inhibited the steady-state currents of human K(v)1.3 channels compared to K(v)1.2 channel currents. Dextromethorphan's action on steady-state currents of human K(v)1.3 channels was in a concentration-dependent manner. The half-maximal inhibitory concentration (IC(50)) on steady-state currents of human K(v)1.3 channels was 12.8±1.6μM. Dextromethorphan also accelerated the C-type inactivation rate, increased the current decay rate, and inhibited currents in a use-dependent manner. These results indicate that dextromethorphan accelerates C-type inactivation of human K(v)1.3 channels and acts as an open-channel blocker. These results further suggest the possibility that dextromethorphan-mediated acceleration of C-type inactivation of human K(v)1.3 channels might be one of the cellular bases of dextromethorphan-mediated protection against inflammation-mediated neurodegeneration.