Reducing postsurgical exudate in breast cancer patients by using San Huang decoction to ameliorate inflammatory status: a prospective clinical trial.

Background: Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy. Methods: The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively. Results: The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 ± 93.95 mL) than in the control group (700.40 ± 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 ± 0.83 vs. 4.80 ± 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 ± 0.72 vs. 3.67 ± 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment. Conclusions: Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer.

Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.

BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.

Hair greying is associated with active hair growth.

BACKGROUND: Hair greying is an obvious sign of ageing in humans. White (nonpigmented) hair is thicker than black (pigmented) hair. The growth rate of white hair is also significantly higher than that of black hair. However, the mechanism underlying this is largely unknown. OBJECTIVES: To examine the association between hair greying and hair growth patterns by evaluating expression of the genes or proteins related to hair growth in white and black hairs. METHODS: Morphological characteristics were observed in eyebrow and scalp hairs. The differential expression of genes was analysed in black and white hairs from human scalp by a microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry for genes and proteins related to hair growth were performed in black and white hairs. RESULTS: Keratin and keratin-associated protein (KRTAP) genes in white hair were upregulated at least two-fold in comparison with black hair in a microarray analysis. Upregulation of selected keratin genes and KRTAP4 isoform genes in white hair was validated by RT-PCR. Immunoreactivity for KRT6, KRT14/16 and KRT25 was increased in the hair follicle of white hair compared with black hair. Gene expression of fibroblast growth factor 5 (FGF5) was downregulated in white hair compared with black hair. However, gene expression of FGF7 was upregulated in white hair compared with black hair. CONCLUSIONS: Expression of genes and proteins associated with active hair growth is upregulated in white (nonpigmented) hair compared with black (pigmented) hair. These results suggest that hair greying is associated with active hair growth.

Callus formation is associated with hyperproliferation and incomplete differentiation of keratinocytes, and increased expression of adhesion molecules.

BACKGROUND: A callus is a local thickening of skin, characterized by accelerated keratinization and a reduced rate of desquamation. However, the mechanism of callus formation is not fully understood. OBJECTIVES: To evaluate the expression patterns, in callused skin, of genes that are implicated in keratinization and adhesion/desquamation. METHODS: Samples of skin from the dorsum of the foot (DF), centre of the plantar arch (CP) and anterior aspect of the heel (AH) were obtained from fresh cadavers, and protein and gene expression were determined by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. RESULTS: The stratum corneum in the DF showed a splitting phenotype by conventional haematoxylin and eosin staining, while the stratum corneum was normal in the AH. Cells of the stratum corneum in the AH were nonsquamous. Expression of cornification-related molecules including involucrin, filaggrin, caspase 14 and calcium-sensing receptor was higher in the AH. Similarly, expression of adhesive proteins such as corneodesmosin, desmoglein 1 and desmocollin 1 was increased in the AH. However, protease-activated receptor 2 expression was reduced in the stratum granulosum in the AH. The number of proliferating cells in the stratum basale was significantly increased in the AH, compared with the DF and CP. CONCLUSIONS: Our data suggest that calluses form as a result of hyperproliferation and incomplete differentiation of epidermal keratinocytes, and increased expression of adhesion molecules.

Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation.

The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-κB (NF-κB) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-κB function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-κB activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis.

The causative organisms of bacterial meningitis in Korean children, 1986-1995.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.

Takayasu arteritis in Korean children: clinical report of seventy cases.

Seventy cases of Takayasu arteritis in Korean children are reported. There were 57 females and 13 males (male-to-female ratio; 1:4.4). The youngest patient was a 3-year-old female. Family history was positive in one patient. The most common chief complaints on admission were dyspnea, headache, palpitation, and edema which were due to hypertension and congestive heart failure. Hypertension was seen in 65 out of 70 patients (92.8%). The abdominal aorta, thoracic aorta, and renal arteries were the most commonly involved sites in these children. Two patients had nephrotic syndrome. The frequency of positive tuberculin reaction was much higher in children with Takayasu arteritis compared with the general population, and the intensity of the reaction was also stronger. The majority of the patients required immediate medical treatment to control congestive heart failure due to hypertension at initial presentation. When ESR was elevated, corticosteroid was administered. Surgical treatment showed good results in six out of ten cases. Percutaneous intraluminal angioplasty was effective for lowering the blood pressure in six out of nine cases. In three cases, restenosis occurred and angioplasty was repeated in two cases.