Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T-cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

Recurrent Bacterial Meningitis Associated with Inflammatory Nasal Polyp

In case of no head trauma history and intact immunity, adultonset recurrent bacterial meningitis is scarce. Parameningeal infection is the crucial latent cause of recurrent bacterial meningitis in adults. Nasal polyp can cause a variety of nasal symptoms, depending on its location and size. Chronic sinusitis with nasal polyp tends to have more severe symptoms than those without nasal polyp. We report a case of adult onset third recurrent bacterial meningitis associated with inflammatory nasal polyp.

A Case of Severe Peripheral Polyneuropathy Occurring after Entecavir Treatment in a Hepatitis B Patient / 대한소화기학회지

Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.

Acute Polymyositis/systemic Lupus Erythematosus Overlap Syndrome with Severe Subcutaneous Edema and Interstitial Lung Disease

Inflammatory myopathy is characterized by symmetrical proximal muscle weakness, elevated muscle enzyme levels and favorable response to glucocorticoids therapy. Although periorbital edema is a common manifestation of inflammatory myopathy, generalized subcutaneous edema is very rare. We report here a case of a 47-year-old female patient with acute polymyositis/systemic lupus erythematosus overlap syndrome with generalized subcutaneous edema and interstitial lung disease. We aggressively treated the disease with high-dose glucocorticoids, intravenous immunoglobulin, and immunosuppressive agents.

A Case of Sclerosing Angiomatoid Nodular Transformation of the Spleen: Spoke Wheel Pattern on Computed Tomography / 대한내과학회지

Sclerosing angiomatoid nodular transformation (SANT) is a rare, benign vascular neoplasm. Most patients have no clinical symptoms, and the tumors are usually discovered incidentally on abdominal computed tomography or ultrasonography. Some studies have reported the clinical features and imaging findings of SANT, but the diagnosis is based on histopathologic examination of a tissue specimen obtained at splenectomy. We report herein an incidentally discovered case of SANT and review the related literature.

Successful Sirolimus Treatment of Kaposi's Sarcoma in Multiple Pulmonary Nodules after Kidney Transplantation / 대한이식학회지

Kaposi's sarcoma is one of the most serious complications associated with immune suppression treatment after kidney transplantation. Because it usually manifestations as skin lesions or lymphadenopathies, its clinical suspicion and tissue diagnosis is relatively easy. However, Kaposi's sarcoma presented as multiple pulmonary nodules without skin manifestations is not easily detected early and usually has a deadly prognosis. We present the case of a 36-year-old male who underwent kidney transplantation 13 months ago and has been on tacrolimus and mycophenolate mofetil (MMF)-based immune suppression presented dry cough, blood tinged sputum, and multiple pulmonary nodules without any skin lesions. Both bronchoscopic washing cytology and fine needle aspiration cytology of peripheral lung tissues were performed but failed due to low cellular yields. A video-assisted thoracoscopic biopsy subsequently revealed Kaposi's sarcoma. Following the diagnosis, we changed the immune suppression from a tacrolimus and MMF-based regimen to a sirolimus-based regimen. Respiratory symptoms gradually disappeared and we found complete remission on follow-up radiologic evaluations. Thus sirolimus may be the preferred method of treatment for patients with immune suppression after kidney transplantation.

Body Image Recognition and Dietary Behaviors of College Students According to the Body Mass Index / 대한지역사회영양학회지

This study was performed to investigate the body image perception by BMI and the dietary behaviors in 803 college students (408 males and 395 females). The degree of obesity was divided into an underweight group with BMI less than 18.5 kg/m(2), a normal group with BMI of 18.5~22.9 kg/m(2), an overweight group with BMI of 23~24.9 kg/m(2) and an obese group with BMI over 25.0 kg/m(2). The average ages of subjects were 22.9 years in males and 20.2 years in females. The average weight and height of male subjects were 175.3 cm and 69.6 kg, respectively and those of female subjects were 162.5 cm and 52.0 kg, respectively. The average BMIs of male and female subjects were 22.6 kg/m(2) and 19.7 kg/m(2), respectively. The distribution of subjects who perceived their current body image as ideal body image was 25.7% in males and 10.9% in females, showing that the body image satisfaction of male subjects was 1.5 times higher than that of female subjects. Body image perception for their own bodies was mostly shown as the average or standard shape both in males and females with 64.2% and 54.2%, respectively, but males showed a higher perception rate than females and 31.1% of females and 19.5% of males perceived their bodies as lean shape (p < 0.01). The body image satisfaction was 4.20 in males and 3.70 in females, showing more satisfaction in the male subjects (p < 0.001). The correlation between body image and physical variables in male subjects indicated that CBI and IBI showed statistically significant correlation and also BMI showed statistically significant correlation with IBI (p < 0.001) and CBI (p < 0.001). The frequency of eating out increased as the frequency of skipping meals increased (p<0.001) and the frequency of having snacks increased as the frequency of eating out increased (p < 0.01). The correlation between body image and physical variables in female subjects showed that CBI and IBI (p < 0.001) had statistically significant correlation. Body weight showed statistically significant correlation with CBI (p < 0.001), BMI (p < 0.001) and height (p < 0.001). The frequency of eating out increased as height (p < 0.01) and the frequency of skipping meals (p < 0.001) increased. When both male and female subjects wanted leaner body shapes, they preferred much leaner shapes despite their current body images belonging in the normal range. Additionally subjects preferred the body image in the normal range in cases when their current body images were lean. In particular, more female subjects had strong desires to become leaner in their body images than male subjects, which could be analyzed as a risk factor for physical harm. From the above results, it is considered that both male and female subjects need to establish proper recognition and dietary behaviors for their body images and also need nutritional education and counseling for desirable weight control methods.

Auditory Functional MRI Findings in Patients with Unilateral Hearing Loss / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Auditory pathway is a unique sensory system in that its ascending pathway has both contralateral and ipsilateral projection to auditory cortex. It has been known that monaural auditory stimulation with auditory functional MRI (fMRI) in normal hearing subject produces bilateral auditory cortical activation, slightly lateralized to opposite side. Our goal was to assess the pattern of auditory cortical activation in patients with unilateral sensory neural hearing loss. SUBJECTS AND METHOD: Auditory fMRI studies using a single-shot gradient-recalled echo-planar imaging (EPI) sequence were performed in eight normal volunteers, thirteen patients with unilateral hearing loss of acute onset (AO, 3 months). A box-car design of 1, 000-Hz sine tone stimuli was given to right or left ear of normal volunteer and to healthy ears of patients. The data were analyzed by BOLD Analysis package. The lateralization index (LI) between contralateral and ipsilateral hemispheric activation were obtained by calculating and comparing the number of activated pixels in each auditory hemisphere. RESULTS: In normal volunteers, the LI was 2.9-5.2 for monaural stimuli suggesting contralateralization of auditory cortex to monaural stimuli. The LI was increased for the AO (8.1-19.2) and decreased for the LD (0.8-1.2). CONCLUSION: The auditory cortical activation in patients with unilateral sensory neural hearing loss showed different pattern according to the duration of hearing loss. The present results might suggest the time course of neuronal plasticity of auditory cortex after deterioration of input function of auditory ascending pathway.

Homonymous Hemianopia after Embolization of an Aneurysm-associated AVM Supplied by the Anterior Choroidal Artery

The primary objective for the treatment of arteriovenous malformations (AVM) of the brain is to reduce the risk of hemorrhage. The risk of hemorrhage is known to increase with the presence of an aneurysm associated with AVM. The purpose of this report is to describe the development of visual complications after the embolization of a hemorrhagic anterior choroidal artery feeding AVM with an associated aneurysm and to describe the possible causes.

Homonymous Hemianopia after Embolization of an Aneurysm-associated AVM Supplied by the Anterior Choroidal Artery

The primary objective for the treatment of arteriovenous malformations (AVM) of the brain is to reduce the risk of hemorrhage. The risk of hemorrhage is known to increase with the presence of an aneurysm associated with AVM. The purpose of this report is to describe the development of visual complications after the embolization of a hemorrhagic anterior choroidal artery feeding AVM with an associated aneurysm and to describe the possible causes.

Usefulness of MR Cholangiography in the Evaluation of Neonatal Cholestasis: Comparison with 99mTc DISIDA Scan

PURPOSE: To evaluate the diagnostic validity of MR cholangiography as a second-line imaging tool following sonography in the evaluation of neonatal cholestasis, we compared MR cholangiography with 99mTc DISIDA scan. MATERIALS AND METHODS: We retrospectively evaluated sonography, 99mTc DISIDA scan and MR cholangiography in twenty-two neonates and infants (age range, 23-103 days; mean age, 57 days) presenting with conjugated hyperbilirubinemia. Of the 22 patients, 15 were diagnosed as biliary atresia by operative cholangiography and liver biopsy and six as neonatal hepatitis by imaging finding and clinical data. Remaining one patient was diagnosed as neonatal hepatitis by operative cholangiography and liver biopsy. Two independent observers for each study were assigned to review the images of 99mTc DISIDA scan and MR cholangiography without giving the final diagnosis or other clinical data. Diagnostic accuracy and interobserver variability for each study were evaluated. RESULTS: On 99mTc DISIDA scan, biliary atresia was mistaken for neonatal hepatitis in eight patients and vice versa in four patients. On MR cholangiography, it was mistaken biliary atresia as neonatal hepatitis and vice versa in each two patients. Sensitivity, specificity, accuracy, positive and negative predictive values of 99mTc DISIDA scan were 48%, 47%, 48%, 66% and 30%, respectively, and those of MR cholangiography were 90%, 71%, 84%, 87% and 81%, respectively. Interobserver variabilities for 99mTc DISIDA scan and MR cholangiography were 0.62 and 0.85, respectively. CONCLUSION: In the evaluation of patients with neonatal cholestasis, it would be advisable to use MR cholangiography, having superior diagnostic accuracy to 99mTc DISIDA scan, as a second-line imaging tool following sonography.

Unruptured Aneurysms with Cranial Nerve Symptoms: Efficacy of Endosaccular Guglielmi Detachable Coil Treatment

OBJECTIVE: To evaluate the efficacy of endosaccular Guglielmi detachable coil (GDC) treatment of unruptured aneurysms causing cranial nerve (CN) symptoms. MATERIALS AND METHODS: Among a database of 218 patients whose aneurysms were treated using GDC, seven patients met the criteria for unruptured aneurysms presenting with symptoms and signs of CN palsy. Changes in CN symptoms before and after GDC treatment were reviewed. RESULTS: Aneurysms were located in the internal carotid-posterior communicating artery (n=3), the basilar bifurcation (n=1) and the cavernous internal carotid artery (n=3). CN symptoms included ptosis (n=6), mydriasis (n=2), and extraocular muscle (EOM) disorder (CN III: n=4; CN VI: n=3). Overall, improvement or resolution of CN symptoms after treatment was noted in five patients. CN symptoms in cases involving small (< or =10 mm) and intradural aneurysms tended to respond better to GDC treatment. Ptosis was the initial symptom to show improvement, while EOM dysfunction responded least favourably. CONCLUSION: GDC coil packing appears to be an appropriate treatment method for the relief of CN symptoms associated with intracranial aneurysms.

Measurement of Fractional Anisotropy in Normal Cerebral White Matter and Brain Tumors with Diffusion Tensor Imaging

PURPOSE: The purpose of this study was to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of normal adult brain tissue and tumors, and to compare the differences. MATERIALS AND METHODS: Eight normal adults and ten patients in whom intracranial tumors had been diagnosed were included. Imaging was performed using a 1.5 T MR unit and a single-shot spin-echo EPI pulse sequence (TR/TE=4024/94 msec, 128 acquisition/256 reconstruction, 23 cm FOV, 5 mm thickness, 2 mm interslice gap, 4 NSA), six different direction gradients (x, y, z, xy, yz, xz), and 2 b-values (0, 1000). Isotropic ADC (D) was obtained from seven images per slice, and fractional anisotropy (FA) was calculated from the isotropic ADC and eigenvalues of three directions. A region of interest was drawn at frontal gray and white matter, periventricular white matter, the corpus callosum, internal capsule, caudate nucleus and center of the tumor mass, and for each region, fractional anisotropy readings were obtained. RESULTS: In normal adults, the findings were as follows: frontal gray matter: D=0.81+/-0.06, FA=0.32+/-0.03; frontal white matter: D=0.79+/-0.04, FA=0.56+/-0.09, periventricular white matter: D=0.77+/-0.02, FA=0.51 +/-0.04; corpus callosum: D=0.79+/-0.07, FA=0.82+/-0.07; internal capsule: D=0.73+/-0.04, FA=0.77+/-0.05; caudate nucleus: D=0.76+/-0.05, FA=0.35+/-0.05. High anisotropy was demonstrated in white matter, especially in the corpus callosum and internal capsule, and the degree of anisotropy was similar in gray and deep gray matter. For most brain tumors, isotropic ADC was similar to that of white matter, but fractional anisotropy was lower. A low-grade astrocytoma showed higher isotropic ADC and lower fractional anisotropy than normal white matter, and at the center of a meningioma, fractional anisotropy was high. CONCLUSION: For the classification of brain tumors and determination of the extent of disease, comparison between the apparent diffusion coefficient and fractional anisotropy is useful.

MR Imaging of Trigeminal Neuropathy

Research Institute of Radiological Science, Yonsei University The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it.

The effect of sodium nitroprusside on muscle tension in guinea-pig ileum

Nitric oxide (NO) has been known as a mediator of nonadrenergic, noncholinergic inhibitory neurotransmitter in intestinal smooth muscles. It has been suggested that NO donor such as sodium nitroprusside (SNP) produces relaxation of smooth muscle via activation of guanylate cyclase and elevation of cGMP levels. We have therefore investigated the effects of NO, using SNP, on muscle tension in the longitudinal smooth muscle of guinea-pig ileum. The possible role of cGMP was also investigated as well as the involvement of K+ channel on SNP-induced inhibitory effect. The results are summarized as follows; high KCl-or CCh-activated contractions were inhibited by SNP in a concentration-dependent manner. 8-Br-cGMP also showed a similar effect in that of SNP. TEA (1 mM) significantly reduced the SNP-induced inhibitory effect. SNP-induced effect was further reduced by the presence of 10 mM TEA. On the other hand, 4-AP (0.1 mM), glibenclamide (10 muM) and apamin (0.1 muM) showed little effects on SNP-induced relaxation. Zaprinast significantly potentiated the SNP-induced inhibitory effect in all ranges. ODQ also significantly decreased the SNP-induced inhibitory effect. Pretreatment with CPA (10 muM) slightly reduced the SNP-induced inhibitory effect. From the above results, both effect mediated by NO and cGMP might be responsible for the activation of Ca2+/-activated K+ channel by SNP in guinea-pig ileum. And this K+ channel activation by SNP also contributes to the SNP-induced membrane hyperpolarization and relaxation.