BACKGROUND: The abnormal barrier function in atopic dermatitis(AD) is caused by a reduction in the amounts of ceramides in the intercellular lipids in the stratum corneum(SC). Replenishing the SC via the topical application of ceramides and pseudoceramides leads to effective recovery of the barrier function of skin. OBJECTIVES: An open clinical crossover evaluation was conducted to investigate the effects in AD of a multi-lamellar emulsion(MLE) that contained pseudoceramide(PC-9s). METHODS: The study group included 30 AD patiendaverage age: 4.4 yr, range: 1-8 yr), who applied MLE or a commercial moisturizing cream(CMC, 5% urea) alternately for four weeks each. We divided the subjects into two subgroups and started with different treatments in each subgroup. Treatment efficacy was evaluated using the average subjective satisfaction scores for each symptom and the global clinical response. In addition, the SCORAD(Scoring AD) index was adopted to evaluate the severity of AD as objectively as possible. The patients were evaluated using this index every other week. RESULTS: Although the SCORAD improved in both subgroups, the patients had better results (p<0.05) when applying MLE(31-35% decrease) than CMC(13% increase to 14% decrease). The subjective satisfaction scores of the symptoms and signs of patients, including itching, erythema, and dry skin, were higher in the MLE group than in the CMC group, and the global response to treatment was also better in the MLE group. During the follow-up period, AD improved in all patients. MLE was more effective than CMC in our patients. CONCLUSIONS: The topical application of a multi-lamellar emulsion containing pseudoceramide is an effective regimen for improving symptoms of AD.
Ceramides ; Cross-Over Studies* ; Dermatitis, Atopic* ; Erythema ; Follow-Up Studies ; Humans ; Pruritus ; Skin ; Treatment Outcome

Estimation of the minimum post-mortem interval (PMI-min) by means of forensic entomology is mainly based on the results of the growth rate studies on necrophagous flies. However, results of these studies are difficult to use because these studies have only been undertaken for a select few necrophagous flies, and experimental methods and results processing have not been standardized. In this review, we have summarized the current state of growth rate studies on necrophagous fly species that are frequently found in human cadavers. Criteria have been suggested in order to select reliable data, and the accumulated degree hours and base temperatures to be used in the calculation of PMI-min for each species have been tabulated.

We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca2+ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [Ca2+] bigger in mitochondria as well as in cytosol. As L-type Ca2+ channel has key influence on the amplitude of Ca2+-induced Ca2+ release, the relation between stimulus frequency and the amplitude of Ca2+ transients was examined under the low density (1/10 of control) of L-type Ca2+ channel in model simulation, where the relation was reversed. In experiment, block of Ca2+ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca2+ transients, while it failed to affect the cytosolic Ca2+ transients. In computer simulation, the amplitude of cytosolic Ca2+ transients was not affected by removal of Ca2+ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca2+] in cytosol and eventually abolished the Ca2+ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca2+ channel to total transsarcolemmal Ca2+ flux could determine whether the cytosolic Ca2+ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca2+ affects mitochondrial Ca2+ in a beat-to-beat manner, however, removal of Ca2+ influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca2+ transients.
Animals ; Computer Simulation ; Cytosol ; Hydrazones ; Ion Transport ; Membranes ; Mitochondria ; Mitochondrial Membranes ; Muscle Cells ; Nitriles ; Rats

Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca²⁺. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs.
Adenosine Triphosphate ; Animals ; Cell Lineage ; Embryonic Stem Cells ; Membrane Potentials ; Mice* ; Mitochondria ; Mouse Embryonic Stem Cells* ; Myocytes, Cardiac* ; Oxidoreductases ; Pyruvate Dehydrogenase (Lipoamide)-Phosphatase* ; Pyruvic Acid* ; RNA, Messenger

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+ levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.
Acetylcysteine/pharmacology ; Apoptosis/*drug effects ; Boronic Acids/*pharmacology ; Calcium/metabolism ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Synergism ; Estradiol/*analogs & derivatives/pharmacology ; Humans ; Mitochondria/drug effects/metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Pyrazines/*pharmacology ; Reactive Oxygen Species/metabolism

OBJECTIVE: ICSI with testicular sperm could achieve optimal fertilization and pregnancy. This study was performed to observe the influence on fertilization and pregnancy of motility of fresh testicular sperm and sperm extracted from frozen-thawed seminiferous tubules in obstructive azoospermia. MATERIALS ANDMETHODS: We analysed clinical outcome of ICSI using fresh testicular sperm and sperm extracted from thawed seminiferous tubules. The presence of motility were compared to determine the factor for optimal fertilization and pregnancy rates. RESULTS: In 316 cases of TESE-ICSI in obstructive azoospermia, ICSI with fresh testicular sperm (fresh sperm group) were 163 cases and ICSI with sperm testicular sperm extracted from frozen-thawed seminiferous tubule (thawed sperm group) were 153 cases. The fertilization rates were 71.3% and pregnancy rates were 32.5% in fresh sperm group, in thawed sperm group, 65.1% and 33.3% respectively. The fertilization and pregnancy rates of motile and non-motile testicular sperm were 72.9% and 33.6%, 50.0% and 18.2%, respectively (p<0.05). The fertilization and pregnancy rates of motile and non-motile sperm extracted from the thawed seminiferous tubule were 67.8% and 34.7%, 55.1% and 28.1%, respectively (p<0.05). The comparative of the results of ICSI using motile fresh testicular sperm and motile sperm extracted from thawed seminiferous tubule, fertilization and pregnancy rates were not significantly different (72.9% and 33.6%, 67.8% and 34.7%, respectively). CONCLUSION: These results suggest that successful pregnancy in TESE-ICSI treatment is influenced by the motility of fresh testicular sperm and sperm extracted from thawed seminiferous tubule in obstructive azoospermic patients.
Azoospermia ; Fertilization ; Humans ; Pregnancy Rate* ; Pregnancy* ; Seminiferous Tubules ; Sperm Injections, Intracytoplasmic ; Spermatozoa*

BACKGROUND AND OBJECTIVES: It is necessary to establish the most efficient diagnostic and therapeutic method for benign paroxysmal positional vertigo (BPPV), which is appropriate for Korean healthcare system. We aimed to evaluate current state of Korean clinician's diagnostic and therapeutic approaches for BPPV. MATERIALS AND METHODS: A 16-item survey was emailed to the members of dizziness department of Otology Research Interest Group in the Korean Otologic Society (n=68). 43 were returned and analyzed. RESULTS: All respondents (100%) used Dix-Hallpike test as a diagnostic tool for vertical canal-BPPV. Supine roll test was used for diagnosing lateral canal BPPV in nearly all the respondents (97.7%). Epley maneuver was chosen as otolith repositioning maneuver (ORM) for posterior canal BPPV in all respondents and barbecue rotation (BBQ) was used for treating lateral canal BPPV with geotropic nystagmus in 95.3% of respondents. Extreme variation was noted for therapeutic approach of lateral canal BPPV with ageotropic nystagmus BBQ, with 4 kinds of ORM and adjunctive measures to liberate otolith from cupula, while BBQ was again the most commonly used ORM (76.7%). CONCLUSION: The development of practical and efficient ORM for lateral canal BPPV with ageotropic nystagmus is necessary.
Surveys and Questionnaires ; Delivery of Health Care ; Dizziness ; Electronic Mail ; Korea ; Otolaryngology ; Otolithic Membrane ; Public Opinion ; Vertigo