Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells

Background/Aims@#Patients with liver cirrhosis (LC) have low levels of branchedchain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). @*Methods@#LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real- time quantitative polymerase chain reaction and Western blotting. @*Results@#The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively. @*Conclusions@#BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Efficacy and safety of metronomic chemotherapy for patients with advanced primary hepatocellular carcinoma with major portal vein tumor thrombosis / 대한간학회지

BACKGROUND/AIMS: Low-dose metronomic chemotherapy involves the frequent administration of comparatively low doses of cytotoxic agents with no extended breaks, and it may be as efficient as and less toxic than the conventional maximum tolerated dose therapy. This study evaluated the feasibility and therapeutic efficacy of metronomic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) with major portal vein thrombosis (PVT). METHODS: Thirty consecutive HCC patients with major PVT with or without extrahepatic metastasis were prospectively allocated to metronomic chemotherapy consisting of epirubicin being infused through the correct hepatic artery at a dose of 30 mg/body surface area (BSA) every 4 weeks, and cisplatin (15 mg/BSA) and 5-fluorouracil (50 mg/BSA) every week for 3 weeks, with intervening 1 week breaks. The treatment response was assessed using response evaluation criteria in solid tumors (RECIST). RESULTS: In total, 116 cycles of metronomic chemotherapy were administered to the 30 patients, with a median of 3 cycles given to individual patients (range, 1-15 cycles). Six patients (20.0%) achieved a partial response and six patients (20.0%) had stable disease. The median time to disease progression and overall survival were 63 days (range, 26-631 days) and 162 days (95% confidence interval; range, 62-262 days), respectively. Overall survival was significantly associated with baseline alpha-fetoprotein level (P=0.001) and tumor response (P=0.005). The baseline alpha-fetoprotein level was significantly associated with the disease control rate (P=0.007). Adverse events were tolerable and managed successfully with conservative treatment. CONCLUSIONS: Metronomic chemotherapy may be a safe and useful palliative treatment in HCC patients with major PVT.

Clinicopathological Study of 12 Cases of Erythromelanosis Follicularis Faciei et Colli / 대한피부과학회지

BACKGROUND: Erythromelanosis follicularis faciei et colli(EFFC) is an infrequently diagnosed disorder. This condition consists of the clincal triad of well-demarcated erythema, hyperpigmentation, and follicular plugging on the face and neck. The etiology of EFFC remains obscure, and therapy for EFFC is only moderately successful. OBJECTIVE: The aim of this study is to examine the clinical and histopathologic findings of erythromelanosis follicularis faciei et colli and suggest the new treatment method of erythema by 585nm flashlamp-pumped dye laser. METHODS: We evaluated 12 patients of erythromelanosis follicularis faciei et colli. Among them, we made a trial of 585nm flashlamp-pumped dye laser in erythema of EFFC on 11 cases. RESULTS: The results were as follows; 1. The mean age of onset and that of the first visits made by patients was 12.1 and 18.9 years, respectively, and there was a male predominance. 2. Histologic features revealed hyperpigmentation in basal layer, perivascular and periadnexal lymphocytic infiltration, and vessel dilatation in upper dermis in all specimens. Follicular plugging(62.5%), hyperkeratosis without parakeratosis(55.6%), enlarged hair follicle containing lamellar body(25.0%), and sebaceous gland hypertrophy(22.2%) were also observed. 3. Electron microscopic studies showed abnormal melanosomes, such as a stippled appearance of the periphery of a melanosome and a large number in the cytoplasm of basal cells. 4. 585nm flashlamp-pumped dye laser treatment with fluences that ranged from 6.5-7.5J/cm2 was given on 1 time. In 2 cases, results were achieved in fair improvement of erythema. Hyperpigmentation occurred in 2 cases(2/11) . CONCLUSION: Characteristically, EFFC affects adolescent males predominantly. The histologic features, although nondiagnostic, correlate with the clinical features. We suggest the new treatment modality, 585nm flashlamp-pumped dye laser, for the treatment of erythema in EFFC. EFFC, which can cause significant cosmetic problems to patients, maybe much more common than recognized. However, it is not well known, may be because the small number of cases have been reported in the literature. It can be helpful to understand the pathogenesis and improve treatment modalities when it will be recognized by more physicians and patients.

Analysis of Dermatologic Counseling by PC Communication / 대한피부과학회지

BACKGROUND: Telemedicine(tele+medicine=medicine at a distance) is a health care delivery system to deliver health care to patients at distant sites. In Korea, medical counseling by PC communication is nearly the only available field in the telemedicine at present. However, the concerns of telemedicine is growing as an issue, and dermatologists in Korea should be prepared for "the era of teledermatology". OBJECTIVE: We analyzed the queries of PC communication and the internet. Based on the results of the analysis, we tried to establish a more effective medical counseling system by PC communication and make them basic data to prepare the utilization of telemedicine system. METHODS: We analyzed questions and answers in ten sites in a computer mediated communication system from Jan 1 to Dec 31, 1997. RESULTS: The proportion of questions in dermatologic area among all medical fields was relatively high(8.7-13.4%). The frequency was acne, urticaria, alopecia, and so on, in an order of high frequency, which was different from previous results in a statistical study of outpatients in dermatology. Reasons for questions were to know the treatment method(42.2%), to get the diagnosis (23.7%), and so on. Contents of answers were explanation(46.5%), advice to visit doctors(40.4%), and so on. CONCLUSION: The proportion of dermatologic questions in telemedicine was high, and there are possibilities of dermatology's being important in the future of telemedicine. Therefore, dermatologists should be prepared for the future telemedicine era. However, teledermatology should be evaluated thoroughly and improved because we could see some problems in that.

A Case of Tuberculosis Verrucosa Cutis / 대한피부과학회지

We report a case of tuberculosis verrucosa cutis in a 64-year-old male patient, who had multiple verrucous plaques on his right hand for twenty years. His past history revealed a previous history of injury on his lesion site. Histologic features consisted of hyperkeratosis, acanthosis in the epidermis with inflammatory infiltrate and tuberculoid granuloma in the dermis. It was suspected that the patient had tuberculosis verrucosa cutis, but no bacilli was found in the lesion in the AFB stain. Then we performed PCR, which showed a positive result. We started antituberculosis medication, and the lesions cleared up after 6 months of treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol. The lesions were later confirmed to be tuberculosis by the AFB culture. We suggest that early diagnosis of tuberculosis verrucosa cutis can be made by using PCR.

Telomerase Activity in Various Benign, Premalignant and Malignant Skin Tumors / 대한피부과학회지

BACKGROUND: Telomerase is a ribonucleoprotein complex with RNA-dependent DNA polymerase which is necessary in maintenance of the length of chromosome, and therefore, in preventing genomic instability. Its activity is regarded as an indicator of cell immortalization. So far, there is no comprehensive answer on which step the telomerase activity is required; in some studies, telomerase activity has been found in benign, premalignant, and malignant conditions equally, which means it affects early stage of carcinogenesis, but in other studies, it has been found in malignant conditions at a higher rate. OBJECTIVE: This study was performed to examine telomerase activity in normal and skin cancer tissues and to assess the role of telomerase in the development of malignant transformation of skin cancer by examining benign, premalignant, and malignant conditions together. METHODS: Telomerase activities in four benign skin tumors, five precancerous lesions, and 17 skin cancer tissues of the skin were measured by a method telomeric repeat amplification protocol(TRAP). TRAP assay was also performed on normal control tissue of the same patients and eight skin tissues of the healthy volunteers. RESULTS: Telomerase activity was detected in 50% of benign tumors, 100% of precancerous, and 82% of malignant tissues. Among them, three out of four BCC tissues were shown to contain telomerase activity, whereas normal tissue of the same patients were not. No telomerase activity was detected in all of the eight skin samples of the healthy volunteers. CONCLUSION: Telomerase activities may be required at early stage of tumorigenesis as these activities are required for further steps down of the oncogenesis.

Congenital Triangular Alopecia / 대한피부과학회지

Congenital triangular alopecia is a rarely reported idiopathic congenital circumscribed alopecia. It presents with isolated patches of permanent alopecia involving the frontotemporal suture area of the scalp. It is necessary to differentiate it from other conditions such as alopecia areata in order to avoid prolonged treatment which may cause adverse side effects. We report a case of 7-year-old boy with congenital triangular alopecia.

Two Cases of Linear and Whorled Nevoid Hypermelanosis / 대한피부과학회지

No Abstract Available.