Cartilage tissue engineering for craniofacial reconstruction

Severe cartilage defects and congenital anomalies affect millions of people and involve considerable medical expenses. Tissue engineering offers many advantages over conventional treatments, as therapy can be tailored to specific defects using abundant bioengineered resources. This article introduces the basic concepts of cartilage tissue engineering and reviews recent progress in the field, with a focus on craniofacial reconstruction and facial aesthetics. The basic concepts of tissue engineering consist of cells, scaffolds, and stimuli. Generally, the cartilage tissue engineering process includes the following steps: harvesting autologous chondrogenic cells, cell expansion, redifferentiation, in vitro incubation with a scaffold, and transfer to patients. Despite the promising prospects of cartilage tissue engineering, problems and challenges still exist due to certain limitations. The limited proliferation of chondrocytes and their tendency to dedifferentiate necessitate further developments in stem cell technology and chondrocyte molecular biology. Progress should be made in designing fully biocompatible scaffolds with a minimal immune response to regenerate tissue effectively.

Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

BACKGROUND/OBJECTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

Inhibitory effect of Erythronium japonicum on the human breast cancer cell metastasis

BACKGROUND/OBJECTIVES: In this study, the inhibitory effect of Erythronium japonicum extracts on the metastasis of MDA-MB-231 human breast cancer cell line was determined. MATERIALS/METHODS: Cells were cultured with DMSO or with 50, 75, 100 or 250 microg/ml of Erythronium japonicum methanol or ethanol extract. RESULTS: Both methanol and ethanol extracts significantly inhibited the growth and induced apoptosis of MDA-MB-231 cells in a dose-dependent manner. Erythronium japonicum extracts inhibited the adhesion of MDA-MB-231 cells. The invasion of breast cancer cells was suppressed by Erythronium japonicum extracts in a dose-dependent manner. The motility and MMP-2 and MMP-9 activities were also inhibited by both methanol and ethanol extracts. CONCLUSIONS: Our results collectively indicate that Erythronium japonicum extracts inhibit the growth, adhesion, migration and invasion as well as induce the apoptosis of human breast cancer cells. Clinical application of Erythronium japonicum as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.

Pear pomace water extract inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes

Obesity occurs when a person's calorie intake exceeds the amount of energy burns, which may lead to pathologic growth of adipocytes and the accumulation of fat in the tissues. In this study, the effect and mechanism of pear pomace extracts on 3T3-L1 adipocyte differentiation and apoptosis of mature adipocytes were investigated. The effects of pear pomace extract on cell viability and the anti-adipogenic and proapoptotic effects were investigated via MTT assay, Oil red O staining, western blot analysis and apoptosis assay. 3T3-L1 preadipocytes were stimulated with DMEM containing 10% FBS, 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), 5 microg/ml insulin and 1 microM dexamethasone for differentiation to adipocytes. 3T3-L1 cells were cultured with PBS or water extract of pear pomace. Water extract of pear pomace effectively inhibited lipid accumulations and expressions of PPAR-gamma and C/EBPalpha in 3T3-L1 cells. It also increased expression of p-AMPK and decreased the expression of SREBP-1c and FAS in 3T3-L1 cells. The induction of apoptosis was observed in 3T3-L1 cells treated with pear pomace. These results indicate that pear pomace water extract inhibits adipogenesis and induces apoptosis of adipocytes and thus can be used as a potential therapeutic substance as part of prevention or treatment strategy for obesity.

Evaluation of the Performance of LABGEO PT Hepatic Test 9

BACKGROUND: The Samsung LABGEO PT Hepatic Test 9 (Samsung electronics, Korea) was developed as a point-of-care (POC) testing device. The levels of 9 analytes, namely, albumin, AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, glucose, total bilirubin, direct bilirubin, and total protein, could be evaluated simultaneously by using 70 microL of whole blood, plasma, or serum samples. In this study, we assessed the performance of the Samsung LABGEO PT Hepatic Test 9. METHODS: The precision and linearity of the test were evaluated according to the CLSI EP5-A2 and CLSI EP6-A guidelines, respectively. Correlational analyses between Samsung LABGEO PT Hepatic Test 9 and Cobas 8000 modular analyzer (Roche, Switzerland) were carried out as per the CLSI EP9-A2 guidelines. Additionally, the results between 3 different specimen types, whole blood, plasma, and serum samples obtained from the same individual were compared to evaluate the matrix effect. RESULTS: The total imprecision at both low and high levels of the 9 analytes was within 10% and in the clinically important concentration range for all test items, all obtained results were linear. We compared the above results with those obtained using Cobas 8000 and a good correlation was observed with a correlation coefficient of more than 0.975 for all 9 analytes. Simple linear regression analyses between the 3 different specimen types indicated that there was no statistically significant difference (P<0.001). CONCLUSIONS: The Samsung LABGEO PT Hepatic Test 9 showed good precision and linearity when compared to established assays for 9 clinical test items and could be useful in cases where the POC testing is required.

Factors Associated with Activities of Daily Living (ADL) in Elderly with Mild Cognitive Impairment (MCI) and Early Dementia

OBJECTIVES: To identify the factors that are most significantly associated with the decline of Activities of Daily Living (ADL) status in subjects with Mild Cognitive Impairment (MCI) and early dementia of primary degenerative cause. METHODS: Medical records, results of neuropsychological tests, and Activities of Daily Living scale were retrospectively analyzed in 134 subjects meeting the diagnostic criteria of MCI or early dementia, respectively. Demographic factors, memory functions, depressive symptoms and executive functions of the participants were also analyzed. RESULTS: Correlations revealed that measures of executive functions were significantly associated with ADL status in participants with MCI, while both memory and executive functions were significantly associated in early demented elderly. Stroop test which measures the ability of inhibition showed the closest relation to executive function. Depressive symptoms did not have a significant influence on ADL status. CONCLUSION: Among participants with MCI, the early functional difficulties are associated mainly with executive function, which enables inhibition in particular. In participants with early dementia, on the contrary, the ADL status was associated with both executive function and memory. Further studies on the symptom pattern and related neuropathology in process of dementia progression are needed for Quality of Life (QoL) in elderly population.

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (I) : Initial Treatment Strategy / 신경정신의학

OBJECTIVES: This study investigated the consensus about treatment strategies for the initial treatment of generalized anxiety disorder (GAD). This issue represents one of the subjects addressed by the Korean Medication Algorithm Project for GAD in Korea. METHODS: The executive committee of the Korean Medication Algorithm Project for GAD, supported by The Korean Association of Anxiety Disorders, developed questionnaires about treatment strategies for patients with GAD, based on guidelines or algorithms and clinical trial studies previously published in foreign countries, especially by the International Psychopharmacology Algorithm Project, the National Institute for Clinical Excellence, and the Canadian Psychiatric Association. Fifty-five (64%) of 86 experts on a committee reviewing GAD in Korea responded to the questionnaires. We classified the consensus of expert opinions into three categories (first-line, second-line, and third-line treatment strategies) and identified the treatment of choice according using a Chi-square test and a 95% confidence interval. RESULTS: For the initial treatment of GAD, antidepressant monotherapy and the combination of antidepressants and benzodiazepines as anxiolytics were recommended as the first line strategies. Escitalopram, paroxetine CR and venlafaxine XR were selected as first-line antidepressant treatments, and alprazolam, clonazepam and lorazepam were the preferred benzodiazepines. The mean starting doses and mean maximum doses of the drugs were 7.55+/-3.09 mg and 24.91+/-8.14 mg for escitalopram, 12.57+/-2.83 mg and 44.76+/-15.00 mg for paroxetine CR, and 46.81+/-16.74 mg and 223.32+/-60.64 mg for venlafaxine XR. CONCLUSION: These results, which reflect recent studies and clinical experiences, may provide guidelines for the initial.

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (II) : Medication Algorithm & Long-Term Medication Treatment Strategy / 신경정신의학

OBJECTIVES: This study was performed to investigate the consensus about medication algorithms, including long-term medication treatment strategies, in the treatment of generalized anxiety disorder (GAD). METHODS: The executive committee of the Korean Medication Algorithm Project for GAD developed questionnaires about the psychopharmacologic treatment strategies for patients with GAD. Fifty-five (65%) of 84 experts of a reviewing committee answered the questionnaires. The consensus of expert opinion was classified into three categories, and the treatments of choice were selected by use of 95% confidence intervals and chi-square-tests. RESULTS: The consensus on the first-line treatment strategy for GAD was as follows. Step 1 is the use of the one of a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenaline reuptake inhibitor (SNRI) and buspirone for at least four to six weeks. Step 2 is to switch from a SSRI to a SNRI or buspirone or vice versa. Step 3 is to augment medication with an atypical antipsychotic or add a benzodiazepine or antihistamine. Step 4 is to switch to another combination, which includes a SSRI, a SNRI, mirtazapine or a tricyclic antidepressant Step 6 is to review the diagnosis, and 'benzodiazepines including clonazepam and alprazolam can be combined with another drug even from the initial period'. In terms of long-term medication treatment, the consensus first-line tr-eatment strategy involved the use of venlafaxine XR, escitalopram, fluoxetine, paroxetine CR, sertraline and buspirone. CONCLUSION: This study provided information about the consensus among Korean experts regarding medication algorithms, including long-term medication treatment strategies, in the treatment of GAD.

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (III) : Treatment Strategy for Comorbid Conditions / 신경정신의학

OBJECTIVES: This study investigated the consensus about treatment strategies for comorbid conditions in generalized anxiety disorder (GAD). METHODS: The executive committee of the Korean Medication Algorithm Project for GAD developed questionnaires about treatment strategies for patients with panic disorder based on guidelines or algorithms and clinical trial studies previously published in foreign countries. This study analyzed the treatment strategies for comorbid conditions in GAD. Fifty-five (65%) of 84 experts on a committee reviewing GADs responded to the questionnaires. We classified the consensus of expert opinions into three categories (first-line, second-line, and third-line treatment strategies) and identified the treatment of choice according using a chi2 test and 95% confidence interval. RESULTS: The consensus about treatment strategies in the case of GAD with comorbid depression recommended a selective serotonin reuptake inhibitor (SSRI) and a serotonin norepinephrine reuptake inhibitor (SNRI) as the first-line drug treatment. An SSRI, an SNRI and a benzodiazepine (e.g. alprazolam, clonazepam) are recommended in GAD patients with other comorbid anxiety disorders. CONCLUSION: This study provided information about the consensus among Korean experts with regard to treatment strategies for comorbid conditions of GAD.

Korean Medication Algorithm for Panic Disorder 2008: Initial Treatment Strategies / 대한정신약물학회지

OBJECTIVE: The Korean Association of Anxiety Disorders developed a Korean treatment algorithm for panic disorder to help clinicians make treatment decisions. This study investigated a consensus about initial treatment strategies as part of developing a medication algorithm for panic disorders in Korea. METHODS: Based on current treatment algorithms published by the American Psychiatric Association, the National Institute for Clinical Excellence, and the Canadian Psychiatric Association, we developed questionnaires about initial treatment strategies for patients with panic disorder. Fifty-four experts in panic disorder answered the questionnaires. We classified expert opinions into three categories (first-, second-, and third-line treatment strategies) by chi-square tests. RESULTS: Antidepressants and anxiolytics were recommended as first-line strategies for the initial treatment of panic disorder. A combination of medical treatment and cognitive-behavioral therapy was also recommended for more severe cases. Paroxetine, escitalopram, alprazolam, and clonazepam were preferred from among many anti-panic drugs. The mean starting dose of anti-panic drugs in the initial treatment for panic disorder was relatively lower than that for such other psychiatric illnesses as major depressive disorder. CONCLUSION: These results, reflecting recent studies and clinical experiences, may provide guidelines about initial treatment strategies for panic disorder.

Korean Medication Algorithm for Panic Disorder 2008: Consensus Regarding Treatment Strategies in Cases of Non-Responsive and Comorbid Conditions / 대한정신약물학회지

OBJECTIVE: This study investigated the consensus about treatment strategies for non-responsive and comorbid conditions in panic disorder, which represents one subject addressed by the Korean medication algorithm project for panic disorders 2008. METHODS: The executive committee developed questionnaires about treatment strategies for patients with panic disorder based on guidelines or algorithms and clinical trial studies previously published in foreign countries. This study analyzed the treatment strategies in cases of non-responsive panic disorder and comorbid conditions accompanying panic disorder. Fifty-four (68%) of 80 experts on a committee reviewing panic disorders responded to the questionnaires. We classified the consensus of expert opinions into three categories (first-line, second-line, and third-line treatment strategies) and identified the treatment of choice according using a chi-square test and 95% confidence interval. RESULTS: The consensus about first-line treatment strategies in cases of non-responsive panic disorder included "switch from a selective serotonin reuptake inhibitor to venlafaxine XR or vice versa" and "clonazepam or alprazolam can be combined with another drug even from the initial period". Second-line strategies included tricyclic antidepressants (clomipramine, imipramine) and high dosages of high potency benzodiazepines (alprazolam, clonazepam). The consensus about treatment strategy in cases of comorbid disorders (e.g., depression or other anxiety disorders) recommended antidepressants combined with anxiolytics and cognitive-behavioral therapy as the treatments of choice. Antidepressants combined with anxiolytics were recommended as the first-line strategy, and antidepressant monotherapy and antidepressants combined with cognitive-behavioral therapy emerged as second-line strategies. In cases of comorbid conditions accompanying panic disorder, paroxetine was selected as the treatment of choice. Escitalopram, venlafaxine XR, sertraline, citalopram, alprazolam, and clonazepam were selected as first-line treatments and fluoxetine, mirtazapine, and imipramine were selected as second-line treatments. CONCLUSION: This study provided information about the consensus among Korean experts in regard to treatment strategies for non-responsive panic disorder and comorbid conditions accompanying panic disorder.

Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line

We examined the inhibitory effects of loquat methanol extract on the adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of MDA-MB-231 human breast cancer cell line. Cells were cultured with DMSO or with 10, 25, or 50 microg/ml of loquat methanol extract. Both leaf and seed extracts significantly inhibited growth of MDA-MB-231 cells in a dose-dependent manner, although leaf extract was more effective. Adhesion and migration were significantly inhibited by loquat extracts in a dose-dependent manner. Loquat extract also inhibited the invasion of breast cancer cells in a dose-dependent manner and leaf extract was more effective than seed extract. MMP-2 and MMP-9 activities were also inhibited by loquat extract. Our results indicate that methanol extracts of loquat inhibit the adhesion, migration and invasion of human breast cancer cells partially through the inhibition of MMP activity and leaf extract has more anti-metastatic effects in cell based assay than seed extract. Clinical application of loquat extract as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.

Clinical Characteristics and Heart Rate Variability in Patients with Comorbid Panic Disorder and Major Depressive Disorder / 수면정신생리

OBJECTIVES: This study was designed to evaluate the differences in clinical characteristics and severity of symptoms between panic patients with and without comorbid major depressive disorder, and to ascertain the differences in the function of the autonomic nerve system measured by heart rate variability (HRV). METHODS: The subjects were 60 patients who have panic disorder without major depressive disorder and 19 patients who met DSM-IV criteria for both panic disorder and major depressive disorder. First, they drew up symptom checklists and self-rating scales, and were measured by Anxiety Disorder Inventory Schedule-Panic Attack & Agoraphobia (ADIS-P& A), Clinical Global Impression (CGI), Hamilton Rating Scale for Depression (HAM-D), Panic Disorder Severity Scale (PDSS) and Heart Rate Variability (HRV). For statistical analysis, we performed t-test to compare the scores of self reported scales and clinician's rating scales in panic patients with comorbid major depressive disorder and those without major depressive disorder. ANCOVA was used to compare the variables of HRV, considering age as a covariate. RESULTS: The subjective severities of depression and anxiety that comorbid patients complained of were higher than those of patients with only panic disorder. Futhermore, comorbid patients were more sensitive to anxiety and physical sensations, and they tend to be more negative in their thinking. The scores of clinician-rating scales such as CGI and PDSS were also higher in the comorbid patients. However, there were no significant differences in HRV variables between both groups, despite a tendency to low heart rate variability in the comorbid group. CONCLUSION: This study suggests that patients with panic disorder and comorbid major depressive disorder tend to complain of more symptoms and to be more sensitive to various symptoms than those with panic disorder without comorbid depression. However, in this study comorbid major depressive disorder did not have a significant impact on the HRV variables of patients with panic disorder.

Sleep Patterns and Morning Heart Rate Variability Among Daytime Workers in Korea / 대한산업의학회지

OBJECTIVES: This study was performed to evaluate the sleep patterns in a population of Korean labor workers and to assess the activity of the autonomic nervous system in relation to sleep habits. METHODS: A sampler of 1238 daytime workers (male 911, female 327) completed questionnaires on sleep habits and their short term heart rate variability(HRV) was also examined. We used the SA-2000 (medi-core) instrument for 5 minutes for each participant in the morning and performed basic physical examinations including height, weight, and blood pressure. RESULTS: Bed time and wake up time were negatively correlated with age, while the frequencies of waking up through the night and in the early morning showed positive correlation with age. We found that bed time and wake up time during weekdays, sleep latency during weekdays, frequency of waking up through the night, and the degree of sleepiness all varied significantly according to the average nightly amount of sleep within the last week. There was a positive correlation between wake up time at weekdays with mean heart rate. However, the other variables of sleep habits and pattern did not show significant correlation with HRV. CONCLUSION: Among Korean daytime workers, sleep phases become advanced with aging. In spite of the aging processes, general sleep health seems to be maintained among the healthy worker group. However, short-term HRV was not useful parameter to measure the alternation of autonomic nervous system resulting from the difference of sleep habits and pattern.

Comparison of Protein Expression in Normal Myometrium and Uterine Leiomyoma Using Two-Dimensional Gel Electrophoresis in Korean Women / 대한산부인과학회잡지

OBJECTIVE: Comparison of protein expression by two-dimensional gel electrophoresis (2-DE) in normal myometrium and uterine leiomyoma in Korean women. METHODS: Normal myometrium and uterine leiomyoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH4-8 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS- PAGE) and sliver stain. Scanned image analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrums identification were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: In this study, we found 17 up-regulated proteins (phosphate carrier protein, 60 kDa heat shock protein, acidic calcium-independent, glutathione transferase omega, chloride intracellular channel 4, Ras-related protein Rab-11B, phosphatidylinositol transfer protein alpha isoform, type II keratin subunit protein, Cofilin 2 isoform 1, transgelin, ATP carrier protein, alpha-catenin homolog, parkinson disease 2, apo-cellular retinoic acid binding protein II, osteoglycin preproprotein, proteasome activator subunit 1 isoform, Unnamed protein) and 7 down-regulated proteins (Serum amyloid P component, annexin IV, alpha 1 actin precursor, hypoxanthine-guanine phosphoribosyltransferase, tumor necrosis factor receptor superfamily member EDAR precursor, peroxiredoxin 2, translation elongation factor EF-Tu precursor) between myometrium and leiomyoma. CONCLUSION: 2-DE offer total protein expression between normal myometrium and uterine leiomyoma, and searching of differently expressed protein for the diagnostic markers of leiomyoma.