Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model

BACKGROUND@#The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarizationsensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue.METHOD: A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PSOCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. @*RESULTS@#The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue.The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. @*CONCLUSION@#Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits

BACKGROUND@#Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access.METHOD: In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2–3.4 kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. @*RESULTS@#In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. @*CONCLUSION@#We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors

BACKGROUND@#We aimed to validate a pilot study of photodiagnosis using near infrared (NIR) transillumination and assess the clinical efficacy of hypericin-mediated photodynamic therapy (HYP-PDT) in a rabbit laryngeal cancer model in order to develop a novel therapeutic modality with complete remission and preservation of the functional organ. @*METHODS@#(1) In vitro study: VX tumor cells were subcultured and subjected to HYP-PDT. (2) In vivo study: A laryngeal cancer model was developed in which 12 rabbits were inoculated with a VX tumor suspension in the submucosal area of the left vocal fold using a transoral approach. All rabbits underwent NIR transillumination using light with a wavelength of 780 nm. The survival periods of the three treatment groups (6 rabbits in Group A: HYP-PDT, 3 each in Groups B and C: laser irradiation or HYP administration only) were analyzed. @*RESULTS@#The higher the HYP concentration, the lower the VX cell viability in response to HYP-PDT using 590 nm LED. Following HYP-PDT, small tumors in Group A-1 rabbits healed completely and the animals demonstrated a long survival period, and larger tumors in Group A-2 healed partially with a survival period that extended over 3 weeks after inoculation. The survival of Groups B and C were not different over the first 3 weeks of the study, and were shorter than in Group A. @*CONCLUSION@#We found HYP-PDT could be a curative therapy for early-stage cancers that may also preserve organ function, and may inhibit tumor progression and metastasis during advanced stages of laryngeal cancer.

Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model

BACKGROUND@#The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarizationsensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue.METHOD: A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PSOCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. @*RESULTS@#The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue.The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. @*CONCLUSION@#Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits

BACKGROUND@#Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access.METHOD: In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2–3.4 kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. @*RESULTS@#In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. @*CONCLUSION@#We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Anti-oxidative Effect of Piperine from Piper nigrum L. in Caenorhabditis elegans

Piper nigrum L. (Piperaceae), which is a well-known food seasoning, has been used as a traditional medicine for the treatment of vomiting, abdominal pain, diarrhea and anorexia in Korea, China and Japan. Methanol extract from the fruit of P. nigrum was successively partitioned as n-hexane, methylene chloride, ethyl acetate, n-butanol and H₂O soluble fractions. Among those fractions the ethyl acetate soluble fraction showed the most potent DPPH radical scavenging activity, and piperine was isolated from the ethyl acetate fraction. To know the antioxidant activity of piperine, we tested the activities of superoxide dismutase (SOD) and catalase together with oxidative stress tolerance and intracellular ROS level in Caenorhabditis elegans. To investigate whether piperine-mediated increased stress tolerance was due to regulation of stress-response gene, we quantified SOD-3 expression using transgenic strain including CF1553. Consequently, piperine enhanced SOD and catalase activities of C. elegans, and reduced intracellular ROS accumulation in a dose–dependent manner. Moreover, piperine-treated CF1553 worms exhibited significantly higher SOD-3::GFP intensity.

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

Lifespan Extending and Stress Resistant Properties of Vitexin from Vigna angularis in Caenorhabditis elegans

Several theories emphasize that aging is closely related to oxidative stress and disease. The formation of excess ROS can lead to DNA damage and the acceleration of aging. Vigna angularis is one of the important medicinal plants in Korea. We isolated vitexin from V. angularis and elucidated the lifespan-extending effect of vitexin using the Caenorhabditis elegans model system. Vitexin showed potent lifespan extensive activity and it elevated the survival rates of nematodes against the stressful environments including heat and oxidative conditions. In addition, our results showed that vitexin was able to elevate antioxidant enzyme activities of worms and reduce intracellular ROS accumulation in a dose-dependent manner. These studies demonstrated that the increased stress tolerance of vitexin-mediated nematode could be attributed to increased expressions of stress resistance proteins such as superoxide dismutase (SOD-3) and heat shock protein (HSP-16.2). In this work, we also studied whether vitexin-mediated longevity activity was associated with aging-related factors such as progeny, food intake, growth and movement. The data revealed that these factors were not affected by vitexin treatment except movement. Vitexin treatment improved the body movement of aged nematode, suggesting vitexin affects healthspan as well as lifespan of nematode. These results suggest that vitexin might be a probable candidate which could extend the human lifespan.

Flail Subaortic Membrane Mimicking Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy

A subaortic membrane is an uncommon cause for left ventricular outflow tract obstruction. Hypertrophic cardiomyopathy with dynamic left ventricular outflow tract obstruction would mask the presence of the subaortic membrane on transthoracic echocardiography and cause a false diagnosis. We report a patient with subaortic stenosis due to flail subaortic membrane misdiagnosed as obstructive hypertrophic cardiomyopathy on transthoracic echocardiography, identified on transesophageal echocardiography and cardiac catheterization.

Long-Term Safety and Efficacy of Sirolimus- and Paclitaxel-Eluting Stents in Patients With Acute Myocardial Infarction: Four-Year Observational Study

BACKGROUND AND OBJECTIVES: The comparison of long-term clinical effects between Sirolimus-eluting stent (SES) and Paclitaxel-eluting stents (PES) for treatment of acute myocardial infarction (AMI) remains unclear. Seeking to clarify this issue, we performed a retrospective analysis to evaluate four-year clinical outcomes of SES compared to PES treated AMI patients. SUBJECTS AND METHODS: From January 2004 to August 2006, all patients with acute ST-segment elevation myocardial infarction and acute non-ST segment elevation myocardial infarction who underwent percutaneous coronary intervention (PCI) by implantation of either SES or PES were enrolled. The occurrences of cardiac and non-cardiac deaths, recurrent infarction, target vessel revascularization (TVR) and stent thrombosis were analyzed. The composite end points of these major adverse cardiac events (MACE) were also analyzed. RESULTS: During the study period, a total of 668 AMI patients had visited, of which 522 patients (299 with SES and 223 with PES) were enrolled. During the four-year clinical follow-up, both groups showed similar occurrences of non-cardiac death (14.6+/-2.2% vs. 18.3+/-3.0%, p=0.26); cardiac death (6.8+/-1.52% vs. 11.2+/-2.6%, p=0.39); re-infarction (3.3+/-1.1% vs. 6.4+/-1.8%, p=0.31); and stent thrombosis (3.2+/-1.1% vs. 5.4+/-1.7%, p=0.53). However, occurrences of TVR {4.0+/-1.2% vs. 10.0+/-3.0%, hazard ratio (HR)=0.498, 95% confidence interval (CI)=0.257-0.967, p=0.039} and MACE (19.4+/-2.5% vs. 29.4+/-3.5%, HR=0.645, 95% CI=0.443-0.940, p=0.021) were significantly lower in the SES population. CONCLUSION: In AMI patients treated with either SES or PES implantation, the former had a significantly lower risk of TVR and MACE during four-year clinical follow-up. Rates of death, cardiac death or recurrent infarction, and stent thrombosis were similar.

Effects of Selenium on Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in Mouse Model with High-Iron Diet / 한국실험동물학회지

Selenium (Se) is known to prevent several cancers while the relationship between high iron and the risk of colorectal cancer is controversial. To investigate the effects of Se in colon carcinogenesis, we subjected three different levels of Se and high-iron diet to a mouse model of colon cancer in which animals were treated with three azoxymethane (AOM) injections followed by dextran sodium sulfate (DSS) administration. There were five experimental groups including vehicle group [normal-Fe (NFe, 45 ppm)+medium-Se (MSe, 0.1 ppm)], positive control group (AOM/DSS+NFe+MSe), AOM/DSS+high-Fe (HFe, 450 ppm)+low-Se (LSe, 0.02 ppm), AOM/DSS+HFe+MSe, and AOM/DSS+HFe+high-Se (HSe, 0.5 ppm). The animals were fed on the three different Se diets for 24 weeks. The incidence of colon tumor in the high-Se diet group (AOM/DSS+HFe+HSe) showed 19.4% lower than positive control group, 5.9% lower than AOM/DSS+HFe+MSe diet group, and 11.1% lower than AOM/DSS+HFe+LSe group. The tumor multiplicity was significantly higher in the low-Se diet group (AOM/DSS+HFe+LSe) compare to all other AOM/DSS treated groups. In the high-Se diet group, the activity of hepatic GPx was comparable to that of positive control group, and significantly higher than those of low-Se or medium-Se diet groups. Expression level of hepatic GPx-1 showed similar results. Hepatic malondialdehyde (MDA) level (indicator of oxidative stress) in the low-Se diet group showed the highest compared to the other groups, and it was significantly higher than positive control group. In the high-Se diet group the level of MDA in the liver was significantly lower than all other AOM/DSS treated groups. High-Se diet group showed significantly lower proliferative index than low-Se and medium-Se groups. The apoptotic indices in low-Se group and medium-Se group were significantly lower than positive control group. However, apoptotic index of high-Se diet group was significantly higher than all other AOM/DSS treated groups. These findings suggest that dietary Se supplement may have protective effect against colon cancer by decreasing proliferation, increasing apoptosis of tumor cells, and reducing oxidative stress in mice with high iron diet.

Dietary Selenium Supplement Prevents Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in ICR Mice / 한국실험동물학회지

The role of selenium (Se) in modulating colon carcinogenesis induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) was investigated in mice. Five-week old ICR mice were fed on diets containing different concentrations (0.02, 0.1 or 0.5 ppm) of Se for 24 weeks. Animals received three (0-2nd weeks) intraperitoneal injections of AOM (10 mg/kg body weight), followed by 2% DSS with drinking water for additional 1 week. There were 4 experimental groups including vehicle control group, positive control group given AOM/DSS with AIN-93G normal diet containing 0.1% Se (NSe), a low (0.02 ppm)-Se diet group (LSe) and a high (0.5 ppm)-Se diet group (HSe). Hematology was analyzed with a blood cell differential counter. Liver Se was analyzed by inductively coupled plasma-mass spectroscopy. Cell proliferation and apoptosis were determined by using proliferating cell nuclear antigen (PCNA) for proliferative activity and apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. HSe group showed a low incidence of colonic tumor (64.7%), compared with the NSe positive control (75%) and LSe (77.8%) groups. In contrast, HSe group exhibited lower rate of PCNA-positive cells (39.3+/-6.9%) than positive control (64.3+/-0.3%) and LSe (57.3+/-2.9%) groups. In addition, apoptotic index of HSe group was higher than those of positive control and LSe groups. These results indicate that Se is a chemopreventive agent for colon carcinogenesis induced by AOM+DSS in male ICR mice.

Dietary Selenium Supplement Prevents Colon Carcinogenesis Induced by Azoxymethane and Dextran Sodium Sulfate in ICR Mice / 한국실험동물학회지

The role of selenium (Se) in modulating colon carcinogenesis induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) was investigated in mice. Five-week old ICR mice were fed on diets containing different concentrations (0.02, 0.1 or 0.5 ppm) of Se for 24 weeks. Animals received three (0-2nd weeks) intraperitoneal injections of AOM (10 mg/kg body weight), followed by 2% DSS with drinking water for additional 1 week. There were 4 experimental groups including vehicle control group, positive control group given AOM/DSS with AIN-93G normal diet containing 0.1% Se (NSe), a low (0.02 ppm)-Se diet group (LSe) and a high (0.5 ppm)-Se diet group (HSe). Hematology was analyzed with a blood cell differential counter. Liver Se was analyzed by inductively coupled plasma-mass spectroscopy. Cell proliferation and apoptosis were determined by using proliferating cell nuclear antigen (PCNA) for proliferative activity and apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively. HSe group showed a low incidence of colonic tumor (64.7%), compared with the NSe positive control (75%) and LSe (77.8%) groups. In contrast, HSe group exhibited lower rate of PCNA-positive cells (39.3+/-6.9%) than positive control (64.3+/-0.3%) and LSe (57.3+/-2.9%) groups. In addition, apoptotic index of HSe group was higher than those of positive control and LSe groups. These results indicate that Se is a chemopreventive agent for colon carcinogenesis induced by AOM+DSS in male ICR mice.

Effect of Sodium Silicate on Hair Growth in C57BL/6 Mice / 한국실험동물학회지

A promoting effect of Na2SiO3 on hair regrowth was investigated using an animal model of C57BL/6 mice. There were four experimental groups including distilled water (DW, a negative control), 5% minoxidil (MXD, a positive control), 50% Na2SiO3, and 100% Na2SiO3 solution. The animals were shaved with an electric clipper and then test solutions applied daily with a volume of 0.2 ml per to the dorsal skin of mice for 3 weeks. Body weight and food and water consumption were measured weekly. Photographs of hair regrowth were taken at experimental day 0, 4, 7, 10, 14, 17, and 21. Activities of alkaline phosphatase and gamma-glutamyl transpeptidase as well as expressions of growth factors were also determined in the dorsal skin of mice. The animal body weight were not significantly changed among the experimental groups. The MXD and Na2SiO3 accelerated hair regrowth compared with DW. The elongation of hair follicles were evidently observed in MXD and 50 or 100% Na2SiO3 groups. MXD significantly increased gamma-glutamyl transpeptidase at day 14, compared with DW (P<0.05). But the activities of alkaline phosphatase and gamma-glutamyl transpeptidase were not significantly increased in Na2SiO3 groups, compared with DW. The expression of epidermal growth factor was significantly increased in MXD and Na2SiO3 groups, compared with DW (P<0.05). The expression of vascular endothelial growth factor was not significantly changed by MXD or Na2SiO3 treatments. The expression of transforming growth factor (TGF)-beta1 was clearly decreased in MXD and Na2SiO3 groups, compared with DW. These results indicate that Na2SiO3 may have a hair growth-promoting activity and it can be used for treatment of alopecia or boldness in humans.

A Case of Isolated Neurofibroma Arising from the Epiglottis / 대한이비인후과학회지

Neurofibroma in the larynx is unusual and associated with von Recklinghausen's disease. A case of solitary endolaryngeal neurofibroma was first reported by Suchanek in 1925. Following the first report, there have been sporadic reports of solitary endolaryngeal neurofibroma. The aryepiglottic folds are the usual sites of occurrence for laryngeal neurofibroma, because the branch of the superior laryngeal nerve is involved. Rarely, a vocal cord is also concerned. We present here a case of neurofibroma in a 35 year-old male who complained of snoring, throat discomfort and hoarseness, all of which persisted for 5 months. This neurofibroma arose from the lingual surface of the epiglottis, thus making intubation difficult. We removed this tumor completely by transoral approach under the retrograde wire-guided endotracheal intubation. No evidence of recurrence was found for about two years. The solitary neurofibroma arising from the epiglottis has not been reported yet. So we present the first case of solitary neurofibroma of the epiglottis.