Mitophagy stimulation as a novel strategy for the treatment of mitochondrial diseases

Mitophagy, the selective degradation of damaged or surplus mitochondria using core autophagy machinery, plays an essential role in maintaining cellular mitochondrial function. Impaired mitophagy is closely linked to various human diseases, including neurodegenerative diseases, cardiovascular diseases, cancers and kidney disease. Defective mitophagy induces the accumulation of damaged mitochondria and thereby results in a decline in cellular survival and tissue function. Accordingly, enhancement of mitophagy has been proposed as a novel strategy for the treatment of human diseases closely linked to mitochondrial dysfunction. Recent studies showing that the stimulation of mitophagy has a therapeutic effect on several disease models highlight the possibility of disease treatment using mitophagy. The development of mitophagy inducers with toxicity and the identification of molecular mechanisms will enable the clinical application of mitophagy-based treatments.

Efficacy of Retinal Check-up Using Fundus Photography in Patients with Epiretinal Membrane

Purpose@#To investigate whether retinal check-ups using fundus photography accurately predicted the visual outcomes of patients undergoing epiretinal membrane (ERM) removal. @*Methods@#We reviewed the medical records of patients who underwent ERM removal by a single surgeon from January 2013 to June 2019. Patients were classified into two groups. The check-up group included patients who underwent fundus photography during their retinal check-ups, and were thus diagnosed with ERMs, even though they lacked any vision-related symptom. The work-up group included patients who underwent fundus photography to rule out retinal abnormalities, because they complained of vision-related symptoms such as decreased vision and metamorphopsia. The best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) findings were compared between the two groups before and 6 months after surgery. @*Results@#The check-up group included 41 eyes and the work-up group 35 eyes. The preoperative BCVA did not differ significantly between the two groups (p = 0.710). However, the proportion of photoreceptor inner segment/outer segment (IS/OS) defects evident on OCT was significantly lower in the check-up than the work-up group (34.1% vs. 68.6%, p = 0.005). Six months after surgery, the BCVA was significantly better in the check-up group (0.07 ± 0.14 logMAR) than in the work-up group (0.19 ± 0.19 logMAR, p = 0.004) and the proportion of patients with poor visual acuity was also significantly lower in the check-up group (2.4%) than the work-up group (22.9%, p = 0.010). @*Conclusions@#We found that a retinal check-up facilitates early detection of an ERM and improves the postoperative visual prognosis. This supports the necessity of fundus photography during retinal check-ups.

Efficacy of Retinal Check-up Using Fundus Photography in Patients with Epiretinal Membrane

Purpose@#To investigate whether retinal check-ups using fundus photography accurately predicted the visual outcomes of patients undergoing epiretinal membrane (ERM) removal. @*Methods@#We reviewed the medical records of patients who underwent ERM removal by a single surgeon from January 2013 to June 2019. Patients were classified into two groups. The check-up group included patients who underwent fundus photography during their retinal check-ups, and were thus diagnosed with ERMs, even though they lacked any vision-related symptom. The work-up group included patients who underwent fundus photography to rule out retinal abnormalities, because they complained of vision-related symptoms such as decreased vision and metamorphopsia. The best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) findings were compared between the two groups before and 6 months after surgery. @*Results@#The check-up group included 41 eyes and the work-up group 35 eyes. The preoperative BCVA did not differ significantly between the two groups (p = 0.710). However, the proportion of photoreceptor inner segment/outer segment (IS/OS) defects evident on OCT was significantly lower in the check-up than the work-up group (34.1% vs. 68.6%, p = 0.005). Six months after surgery, the BCVA was significantly better in the check-up group (0.07 ± 0.14 logMAR) than in the work-up group (0.19 ± 0.19 logMAR, p = 0.004) and the proportion of patients with poor visual acuity was also significantly lower in the check-up group (2.4%) than the work-up group (22.9%, p = 0.010). @*Conclusions@#We found that a retinal check-up facilitates early detection of an ERM and improves the postoperative visual prognosis. This supports the necessity of fundus photography during retinal check-ups.

Depth and combined infection is important predictor of lower extremity amputations in hospitalized diabetic foot ulcer patients

BACKGROUND/AIMS: As the prevalence of diabetes mellitus and its complications increase rapidly, diabetic foot ulcers (DFUs), which are a major diabetic complication, are expected to increase. For prevention and effective treatment, it is important to understand the clinical course of DFUs. The aim of this study was to investigate the natural course and predictors of amputation in patients with DFUs who required hospitalization. METHODS: A total of 209 patients with type 2 diabetes, aged 30 to 85 years, who visited emergency department or needed hospitalization due to DFUs were consecutively enrolled from May 2012 to January 2016, by retrospective medical record review. The main outcome was lower extremity amputation (LEA). RESULTS: Among 192 patients who completed follow-up, 113 patients (58.9%) required LEAs. Compared to patients without amputation, baseline levels of white blood cell counts and C-reactive protein were higher in patients with amputation. In addition, bone and joint involvement was more frequently observed in patients with amputation. Multivariable regression analysis revealed that combined infection (odds ratio [OR], 11.39; 95% confidence interval [CI], 2.55 to 50.93; p = 0.001) and bone or joint involvement (OR, 3.74; 95% CI, 1.10 to 12.70; p = 0.035) were significantly associated with an increased risk of LEA. CONCLUSIONS: The depth of the wound and combined infection of DFU, rather than the extent of the wound, were significant prognostic factors of LEAs in patients with type 2 diabetes.

Clinical characteristics and treatment propensity in elderly patients aged over 80 years with colorectal cancer

BACKGROUND/AIMS: Elderly patients (≥ 80 years) with colorectal cancer (CRC) tend to avoid active treatment at the time of diagnosis despite of recent advances in treatment. The aim of this study was to determine treatment propensity of elderly patients aged ≥ 80 years with CRC in clinical practice and the impact of anticancer treatment on overall survival (OS). METHODS: Medical charts of 152 elderly patients (aged ≥ 80 years) diagnosed with CRC between 1998 and 2012 were retrospectively reviewed. Patients’ clinical characteristics, treatment modalities received, and clinical outcome were analyzed. RESULTS: Their median age was 82 years (range, 80 to 98). Of 152 patients, 148 were assessable for the extent of the disease. Eighty-two of 98 patients with localized disease and 28 of 50 patients with metastatic disease had received surgery or chemotherapy or both. Surgery was performed in 79 of 98 patients with localized disease and 15 of 50 patients with metastatic disease. Chemotherapy was administered in only 24 of 50 patients with metastatic disease. Patients who received anticancer treatment according to disease extent showed significantly longer OS compared to untreated patients (localized disease, 76.2 months vs. 15.4 months, p = 0.000; metastatic disease, 9.9 months vs. 2.6 months, p = 0.001). Along with anticancer treatment, favorable performance status (PS) was associated with longer OS in multivariate analysis of clinical outcome. CONCLUSIONS: Elderly patients aged ≥ 80 years with CRC tended to receive less treatment for metastatic disease. Nevertheless, anticancer treatment in patients with favorable PS was effective in prolonging OS regardless of disease extent.

Baseline-Corrected QT (QTc) Interval Is Associated with Prolongation of QTc during Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged. RESULTS: The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders. CONCLUSION: A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.

Study on Energy and Nutrient Intake and Food Preference of the Elderly in Care Facilities / 대한지역사회영양학회지

OBJECTIVES: The purpose of this study was to assess energy and nutritional intake and investigate the preference for food and cooking methods of the residents in elderly care facilities. METHODS: Data were collected from 72 residents (10 males and 62 females) aged ≥ 70 years in elderly care facilities using questionnaires, food photographs for estimating dietary intake and records for daily physical activity. RESULTS: Average age of the study participants was 85.0 years and 41, 36 and 8 had dementia, hypertension and diabetes mellitus, respectively. 15%, 65% and 19% of subjects were physically mobile, enervated, and immobile, respectively. Daily energy intake was 1360.2 kcal in men and 1378.0 kcal in women, which were 68.0% and 86.1% of the estimated energy requirement (EER) of dietary reference intake for Koreans (KDRI) for ≥ 75 year old individuals, respectively. Estimated energy expenditure (EEE) of subjects calculated using formula from KDRI was 1361.9 kcal and EER calculated using estimated daily physical activity (EDPA) was 1232.9 kcal. Energy intake and EEE from KDRI were higher than EER from EDPA. Dietary intake of dietary fiber, calcium, potassium, zinc, vitamin B2, niacin, vitamin C were lower, and protein, phosphorous, iron, sodium, vitamin A, vitamin B1, vitamin B6, vitamin E were higher than the corresponding ones of KDRI. Subjects liked meats, fishes and shellfish, and fruits, while subjects disliked milk, seaweeds and salted fish and salted vegetables. Cooked rice, soybean paste soup, beef, cooked sliced radish strip, and yogurt were favorite foods, with steam being a favorite cooking method. Subjects considered nutrition as the most important factor for improving food service quality. CONCLUSIONS: Results of this study could be utilized for improving food-service for the residents in elderly care facilities, and provide a basis for setting reference intake of energy and nutrients of the elderly having very low activity levels.

Intensive Individualized Reinforcement Education Is Important for the Prevention of Hypoglycemia in Patients with Type 2 Diabetes

BACKGROUND: We investigated whether an intensive individualized reinforcement education program could influence the prevention of hypoglycemic events in patients with type 2 diabetes. METHODS: From March 2013 to September 2013, patients aged 35 to 75 years with type 2 diabetes who had not previously participated in diabetes education, and treated with insulin or a sulfonylurea-containing regimen were included in the study. After structured group education, the patients assigned to the intensive individualized education group (IT) were requested to visit for reinforcement. All subjects in the IT were encouraged to self-manage dose adjustments. Participants in both groups (control group [CG, group education only; n=22] and IT [n=24]) attended follow-up visits at 2, 8, 12, and 24 weeks. At each visit, all patients were asked whether they had experienced hypoglycemia. RESULTS: The total study population consisted of 20 men (43.5%; mean age and diabetic duration of 55.9+/-11.0 and 5.1+/-7.3 years, respectively). At 24 weeks, there were no significant differences in hemoglobin A1c values between the CG and IT. The total number of hypoglycemic events per patient was 5.26+/-6.5 in the CG and 2.58+/-2.3 times in the IT (P=0.004). Adherence to lifestyle modification including frequency of exercise, self-monitoring of blood glucose, or dietary habit was not significantly different between the groups. However, adherence to hypoglycemia management, especially the dose adjustment of medication, was significantly higher in the IT compared with the CG. CONCLUSION: Compared with the structured group education, additional IT resulted in additional benefits in terms of avoidance of hypoglycemia and treating hypoglycemia in patients with type 2 diabetes.

Two Pediatric Osteosarcoma Cases with Delayed Methotrexate Excretion: Its Clinical Course and Management / Journal of the Korean Cancer Association, 대한암학회지

High-dose methotrexate (MTX) chemotherapy extends the duration of hospitalization and introduces the risks of serious complications related to delayed MTX excretion. The treatment of delayed MTX excretion is largely dependent on invasive measures such as hemodialysis because the clinical data regarding the efficacy or safety of carboxypetidase G2 is limited. We report here on the cases of two pediatric osteosarcoma patients with delayed MTX excretion and who were successfully managed using supportive measures. Potential life-threatening complications were prevented by administering high doses of leucovorin.

Pulmonary tuberculosis misdiagnosed as lung Metastasis in childhood cancer patients / 소아과

PURPOSE: The differential diagnosis for a pulmonary nodule is intriguing in cancer patients. Metastasis might be a preferential diagnosis, and yet possibilities of other medical conditions still exist. Pulmonary tuberculosis should be enlisted in the differential diagnosis for a pulmonary nodule in cancer patients in Korea. This study was aimed at analyzing the incidence and clinical features of pulmonary tuberculosis that were misdiagnosed as pulmonary metastasis during radiologic follow-up in pediatric cancer patients. METHODS: We retrospectively studied 422 cancer patients less than 18 years old in the Korea Cancer Center Hospital from January 2001 to June 2007. We collected episodes of lung metastasis of primary tumor and tuberculosis during treatment or follow-up, and analyzed medical records. RESULTS: There were 5 cases of tuberculosis confirmed after surgery which were initially regarded as cancer. Two patients had respiratory symptoms such as cough and sputum but the other 3 patients did not. One patient had a family history of tuberculosis. Acid-fast M. tuberculosis was found in one case upon tissue specimen analysis. Two cases were Mantoux positive and the sputum examination was negative in all cases. The polymerase chain reaction for tuberculosis on a pathologic specimen was used to differentiate M. tuberculosis from non-tuberculosis mycobacterium (NTM). It was positive in one case. Lung lesions in one case showed a concurrence of tuberculosis along with lung metastasis. One of these patients died after cancer recurrence. CONCLUSION: It is necessary to consider the possibility of tuberculosis when a lung mass is newly detected during treatment or follow-up in patients with childhood cancer.

Bilateral retinoblastoma: Long-term follow-up results from a single institution / 소아과

PURPOSE: The authors aimed to analyze the long-term effects of treatments, especially external beam radiotherapy (EBRT), in bilateral retinoblastoma patients. METHODS: This retrospective study analyzed the medical records of 22 bilateral retinoblastoma patients who were registered between October, 1987 and October, 1998 and followed-up for more than 10 years. They were treated by enucleation, EBRT, and systemic chemotherapy. Age at diagnosis, sex, delay prior to treatment, Reese-Ellsworth (RE) classification, and the local treatment modalities were analyzed in relation to recurrence-free survival (RFS) and complications. RESULTS: Median age at diagnosis was 7.0 months (range 1.7-31.6 months). Leukocoria was the most common presenting feature. Two patients had a familial history. The RE classifications of the 44 eyes were group II in 4, III in 14, IV in 4, and V in 22. At the end of a median follow-up period of 141 months (range 55-218 months), 20 patients were alive. The 10-year ocular survival rate of the 44 eyes was 56.8+/-7.5%. The 10-year RFS and ocular survival rate of the 29 eyes treated by combined EBRT and chemotherapy were 75.9% and 86.2%, respectively. Treatment delay (>3 months) was found to be related to higher risk of recurrence. Complications after EBRT were cataract, retinal detachment, phthisis bulbi, and facial asymmetry. No patient developed a second malignancy during the follow-up period. CONCLUSION: Early detection and prompt treatment can increase ocular survival rates. In addition, careful attention should be paid to possible long-term sequelae in these patients.

Sex Differences in Body Composition in Prepubertal Korean Children by Dual-energy X-ray Absorptiometry / 대한소아내분비학회지

PURPOSE: To find sexual dimorphism of total body composition (BC) and to establish regression equations for each BC by anthropometric data in prepubertal children. METHODS: Cross-sectional study of 118 healthy children (58 boys, 60 girls, age; 5.1-9.9y) was done. We examined total BC (bone mineral contents, BMC; lean tissue mass, LTM; and fat mass, FM) and regional BC by dual-energy x-ray absorptiometry (DXA). We evaluated the differences in BC between both sexes by independent T-test and performed regression analysis for each BC using SPSS ver 15.0. RESULTS: In total BC, boys had more LTM than girls (P<0.01), while girls had more FM (P=0.05). The percent body fat (PBF) of girls was higher than that of boys (15.0+/-5.4 vs. 11.6+/-5.2, P<0.01). In regional BC, boys had more LTM than girls except arms region. Girls had greater leg and gynoid FM than boys. As a result, girls showed more PBF in all regions. When we did multiple regression analysis including age and anthropometric values, height (Ht) and weight (Wt) were related to BMC and LTM. The regression equations were as follows. For boys: BMC (g)=12.2xHt (cm)+16.1xWt (kg)- 1,025, LTM (kg)= 0.21xHt+0.35xWt-14.3. For girls: BMC (g)=8.0xHt+21.1xWt-881, LTM (kg)=0.18xHt+0.31xWt-10.7. CONCLUSION: We identified sex differences in total BC and regional fat distribution and made regression equations for each BC in prepubertal Korean children.

Binder Syndrome Infant Born from Mother with Cholelithiasis / 대한소아내분비학회지

Binder syndrome is a maxillonasal dysostosis characterized by midface and nasal hypoplasia. It is sometimes associated with short terminal phalanges of fingers and toes and transient radiological features of chondrodysplasia punctata. It is associated with vitamin K deficiency during pregnancy. We describe here a baby with Binder syndrome who was born from mother with cholelithiasis during pregnancy.

The optimal conditions to improve retrovirus-mediated transduction efficiency to NIH 3T3 cells / 소아과

PURPOSE: We tried to assess the optimal conditions to improve low transduction efficiency and their effect on target cells. METHODS: Cultured NIH 3T3 cells were incubated with retroviral vectors bearing an enhanced green fluorescent protein (eGFP) gene. We varied the ratio of viral vectors to target cells (1:1-1:8) and the number of transfections (x1, x2), and compared transduction efficiencies. Also, the effects of polybrene on transduction efficiency and viability of target cells were assessed. Transduction of the eGFP gene was evaluated by observing NIH 3T3 cells under a fluorescence microscope and efficiencies were measured by the percentage of eGFP positive cells using FACscan. RESULTS: As the ratio of retroviral vectors to target cells increased, transduction efficiency was greatly improved, from 7% (1:1) to 38% (1:4). However, transduction efficiency did not increase any more when the ratio increased from 1:4 to 1:8. Cells transfected twice showed higher transduction efficiencies than cells transfected once, at a ratio of 1:8. The eGFP gene transduced to NIH 3T3 cells sustained its expression during repeated passages. However, after the third passage (day 9), the percentage of eGFP positive cells began to decline. The degree of this decline in eGFP expression was lower in cells transfected twice than in cells transfected once (P<0.05). The addition of polybrene did not have any toxic effect on NIH 3T3 cells and greatly increased transduction efficiency (P=0.007). In addition to vector component, transduction efficiency was very sensitive to culture confluence. Cells cultured and transfected in 24-well plate showed higher transduction efficiency, although cells cultured in 6- well plate proliferated more (P=0.024). CONCLUSION: Our data could be used as a basis for retrovirus-based gene therapy. Further study will follow using human cells as target cells.

Cytoplasmic Domain of Intercellular Adhesion Molecule-1(ICAM-1)is Important for the ICAM-1 Mediated Membrane Projection of Endothelial Cells / 대한해부학회지

Intercellular adhesion molecule-1 (ICAM-1)has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 alpha-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM-1_GFP mutant without alpha-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1alpha. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without alpha-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.

Bacterial Lipopolysaccharide - Induced Generation of Nitric Oxide is Mediated by ERK1 and JNK1 / SAPK in Primary Rat Neonatal Astrocytes / 대한면역학회지

No abstract available.

A Study of Voiding Pattern and Symptom-Related Quality of Life in a Healthy Female Population / 대한비뇨기과학회지

No abstract available.

Comparison of Nephron-Sparing and Radical Surgery in Patients with Unilateral Stage T1 Renal Cell Carcinoma / 대한비뇨기과학회지

No abstract available.

Clinical Experience of Nephron Sparing Surgery for Renal Tumor with a Normal Opposite Kidney / 영남의대학술지

The aims of this retrospective study were to determine whether a nephron sparing surgery might be feasible in patients with a small solid renal tumor. Materials and methods: Between 1988 and 1999, 21 patients with radiologically detectable small solid renal tumor underwent enucleoresection, wedge resection and polar segmental nephrectomy. The mean age of the 11 men and 10 women in this study was 43 years (range 14 to 68). According to the preoperative radiological diagnosis, 15 among the 21 patients were considered to have renal cell carcinoma, 4 were considered to have angiomyolipoma, and the remaining 2 patients were difficult to differentiate as renal tumors radiologically. Among 15 patients considered to have renal cell carcinoma, 14 were found to have renal cell carcinoma and the remaining one patient was diagnosed as having oncocytoma on pathologic examination. Radiological determination of angiomyolipoma in four patients was confirmed to be correct on pathological examination. The 2 patients whose radiological diagnose wasdificult were founf to have cavernous hemangioma and angiomyolipoma. One patient with renal cell carcinoma developed arteriocaliceal fistula, the only immediate complication in this series, and underwent nephrectomy on postoperative 10th day. The mean follow-up duration for the 14 patients with renal cell carcinoma was 18.6 months(range:1-103). There were no other tumor involvement in the resection margins following the nephron sparing surgery. These results suggest that nephron sparing surgery provides an effective treatment for patients with a single, small, unilateral, localized renal tumor. Longer follow-up is suggested for more definite verification of the role of nephron sparing surgery.

A Case of Retroperitoneal Neuroenteric Cyst / 대한비뇨기과학회지

Neuroenteric cyst derives from endodermal tissue displaced dorsally into the spinal canal ventral to the neural plaque through the interposed mesodermal layer that forms the vertebral bodies, embryologically. It is located along the alimentary canal, or ventral to the spinal cord in the cervical, thoracic area, or at the cervicothoracic junction within the boundaries of C3 above and T7 below and lies in an intramedullary or intradural extramedullary location in most patients. To date, retroperitoneal neuroenteric cyst has been described in only few cases. We report a case of asymptomatic retroperitoneal neuroenteric cyst in a 28-year-old man with a brief review of literatures, which found incidentally on health care center.