Antifungal and antiaflatoxigenic methylenedioxy-containing compounds and piperine-like synthetic compounds

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure-activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 mu g/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 mu g/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes.ope

Simultaneous determination of 13 mycotoxins in feedstuffs using QuEChERS extraction

Mycotoxins are secondary metabolites produced by various fungi and are known to have a significant negative impact on human and animal health. When feedstuffs are contaminated with mycotoxins, their toxicities may be caused a variety of diseases. In this study, the residual mycotoxins in feedstuffs were analyzed using LC-MS/MS incorporated with QuEChERS extraction. Analytical method validation was performed for LOD, LOQ, linearity, and recoveries with consideration of matrix effects prior to the residual analysis. They were all reached to the accepted range of validation level. Using 39 feedstuff samples (5 g) for mycotoxin analysis, nine samples were contaminated by four major mycotoxins such as fumonisin B1 (FB1), deoxynivalenol, fumonisin B2, and zearalenone. Among them, FB1 was detected at the highest concentration as 18.0943 mg/kg. The total sum of fumonisins in 39 samples did not exceed the maximum residual level (MRL) criterion set by Korean Food and Drug Administration. Altogether, intensive management of mycotoxins in Korean feedstuffs should be implemented with proper and routine monitoring, even their residual concentrations are not exceeded over the MRL levels because of high frequent detection found in this study

Interdigitating dendritic cell sarcoma occured alone in axilla

Interdigitating dendritic cell sarcoma (IDCS) is a very rare disease around the world and its prognosis is known to be aggressive. This reports a case diagnosed as IDCS of the axillary region treated in Soonchunhyang University Hospital. A 57-year-old female visited Soonchunhyang University Hospital with a left axillary mass. The mass was hard and fixed. Computed tomography observed a 7 cm lymph node at the left axilla, and core biopsy suspected sarcoma. In another study, there was no specific finding except the axillary lesion. Left axillary lymph node dissection (level I, II) was conducted and the pathologic report finally showed IDCS. The patient was treated with only radiotherapy and followed up without recurrence for 13 months up to now. IDCS is a very rare sarcoma that is hard to diagnose and progresses fast. Thus, treatment is very difficult. Proper treatment can be better established after more experiences

Recent Trend in the Incidence of Premalignant and Malignant Skin Lesions in Korea between 1991 and 2006

We evaluated the recent trend in the incidence of premalignant and malignant skin lesions between 1991 and 2006. Among 571,057 newly registered dermatology out-patients from our 8 affiliated university hospitals, 2,598 were diagnosed with a premalignant (899, 0.16%) or malignant skin lesions (1,699, 0.30%). Of 899 premalignant cases, 71.2% were actinic keratosis (AK), and 24.6% were Bowen's disease. Of 1,699 malignant cases, 46.2% were basal cell carcinoma, followed by squamous cell carcinoma (19.1%) and melanoma (7.1%). This 16-yr survey was divided equally into two time periods to compare the incidence of premalignant and malignant skin lesions at different time settings. Between 1991 and 1998, the incidence of cutaneous premalignancy was 0.10% which doubled during 1999-2006. For cutaneous malignancy, the incidence was 0.25% during 1991-1998 and 0.34% in 1999-2006. Incidence of AK among the new outpatients was 0.07% in 1991-1998 which staggered up to 0.15% in 1999-2006. These findings show an increase of both premalignant and malignant skin lesions, AK in particular in the dermatology outpatient-based incidence

Nomogram to Predict Insignificant Prostate Cancer at Radical Prostatectomy in Korean Men: A Multi-Center Study

PURPOSE: Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC. MATERIALS AND METHODS: The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort. RESULTS: Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827. CONCLUSION: Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are consideredope

Preoperative Nomograms for Predicting Extracapsular Extension in Korean Men with Localized Prostate Cancer: A Multi-institutional Clinicopathologic Study

We developed a nomogram to predict the probability of extracapsular extension (ECE) in localized prostate cancer and to determine when the neurovascular bundle (NVB) may be spared. Total 1,471 Korean men who underwent radical prostatectomy for prostate cancer between 1995 and 2008 were included. We drew nonrandom samples of 1,031 for nomogram development, leaving 440 samples for nomogram validation. With multivariate logistic regression analyses, we made a nomogram to predicts the ECE probability at radical prostatectomy. Receiver operating characteristic (ROC) analyses were also performed to assess the predictive value of each variable alone and in combination. The internal validation was performed from 200 bootstrap re-samples and the external validation was also performed from the another cohort. Overall, 314 patients (30.5%) had ECE. Age, Prostate specific antigen (PSA), biopsy Gleason score, positive core ratio, and maximum percentage of biopsy tumor were independent predictors of the presence of ECE (all P values <0.05). The nomogram predicted ECE with good discrimination (an area under the ROC curve of 0.777). Our nomogram allows for the preoperative identification of patients with an ECE and may prove useful in selecting patients to receive nerve sparing radical prostatectomy

Clinical Significance of a Large Difference (≥ 2 points) between Biopsy and Post-prostatectomy Pathological Gleason Scores in Patients with Prostate Cancer

We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure

Autophagy in Human Skin Fibroblasts: Impact of Age

Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 &mu;m2 cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3 (microtubule-associated protein 1 light chain 3)-II, a form associated with autophagic vacuolar membranes, was also similar between the groups from Western blot analysis. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes (BECN1, MAP1LC3B, ATG5, ATG7, ULK1, PIK3C3, mTOR) were not differentially expressed with age. Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells &ldquo;clean&rdquo;, resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging