A robust sebum, oil, and particulate pollution model for assessing cleansing efficacy of human skin.

With increasing concerns over the rise of atmospheric particulate pollution globally and its impact on systemic health and skin ageing, we have developed a pollution model to mimic particulate matter trapped in sebum and oils creating a robust (difficult to remove) surrogate for dirty, polluted skin. OBJECTIVE: To evaluate the cleansing efficacy/protective effect of a sonic brush vs. manual cleansing against particulate pollution (trapped in grease/oil typical of human sebum). METHODS: The pollution model (Sebollution; sebum pollution model; SPM) consists of atmospheric particulate matter/pollution combined with grease/oils typical of human sebum. Twenty subjects between the ages of 18-65 were enrolled in a single-centre, cleansing study comparisons between the sonic cleansing brush (normal speed) compared to manual cleansing. Equal amount of SPM was applied to the centre of each cheek (left and right). Method of cleansing (sonic vs. manual) was randomized to the side of the face (left or right) for each subject. Each side was cleansed for five-seconds using the sonic cleansing device with sensitive brush head or manually, using equal amounts of water and a gel cleanser. Photographs (VISIA-CR, Canfield Imaging, NJ, USA) were taken at baseline (before application of the SPM), after application of SPM (pre-cleansing), and following cleansing. Image analysis (ImageJ, NIH, Bethesda, MD, USA) was used to quantify colour intensity (amount of particulate pollutants on the skin) using a scale of 0 to 255 (0 = all black pixels; 255 = all white pixels). Differences between the baseline and post-cleansing values (pixels) are reported as the amount of SPM remaining following each method of cleansing. RESULTS: Using a robust cleansing protocol to assess removal of pollutants (SPM; atmospheric particulate matter trapped in grease/oil), the sonic brush removed significantly more SPM than manual cleansing (P < 0.001). While extreme in colour, this pollution method easily allows assessment of efficacy through image analysis.

The use of temporary vascular shunts in military extremity wounds: a preliminary outcome analysis with 2-year follow-up.

BACKGROUND: The use of temporary vascular shunts (TVS)s in the management of wartime extremity vascular injuries has received an increasing amount of attention. However, the overall impact of this adjunct remains incompletely defined. The objective of this study is to characterize outcomes of those patients who suffered wartime extremity vascular injuries managed with TVSs. METHODS: This is a retrospective review of the Navy and Marine Corps Combat Trauma Registry examining peripheral vascular injuries treated during the military conflicts in the Middle East. Patient demographics, injury severity score, mechanism of injury, and vessels injured were recorded. Operative reports were reviewed for use of TVSs, type of definitive repair, the need for amputation, and survival. RESULTS: Eighty patients were included. Forty-six (57%) had TVSs placed and 34 (43%) underwent repair at initial presentation. The mean injury severity score for the TVS group and the non-TVS groups were 15.0 +/- 5.05 and 12.9 +/- 10.18, respectively, (p = 0.229). There were a total of 13 amputations, 6 (13%) in the TVS group and 7 (21%) in the non-TVS group (p = 0.38). There was no difference in amputation rates between either group. There were no recorded mortalities in either group. Median patient follow-up was 24.5 months (range, 3-48 months). CONCLUSIONS: This study demonstrates the importance and utility of TVSs in the management of wartime extremity vascular injury. When used to restore perfusion to an injured extremity, there seems to be no adverse effects or overall increase in limb loss rates and therefore a useful adjunct in the surgery for limb salvage.

Involvement of p38 mitogen-activated protein kinase signaling in transformed growth of a cholangiocarcinoma cell line.

Although mitogen-activated protein kinase (MAPK) pathways play a key role in cell growth, their role in mediating the altered growth phenotype of transformed cells remains unclear. The p44/p42 MAPK signaling cascades are activated by mitogenic stimulation of human cholangiocytes. In contrast, the p38 MAPK pathway is activated by mitogen stimulation of malignant, but not nonmalignant cholangiocytes. Thus, our aims were to determine the role of p38 MAPK signaling in mediating the growth phenotype of transformed cholangiocytes. KMCH-1 malignant human cholangiocytes required the presence of serum for proliferation, but were able to grow in reduced serum conditions. Inhibition of p38 MAPK decreased serum-dependent proliferation of KMCH-1 cells. Furthermore, inhibition of p38 MAPK, but not of p44/p42 MAPK, reduced anchorage-independent growth of KMCH-1 cells. Although both p38 and p44/p42 MAPK are activated in response to mitogens, they have divergent effects on anchorage-independent growth. Inhibition of p38 MAPK, but not of p44/p42 MAPK signaling, decreased cell cycle progression and increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIPl). However, expression of p27(KIP1) or p16(INK4A) was not altered by either pathway. Thus, mitogen activation of p38 MAPK decreases expression of p21(WAF1/CIP1) and mediates growth independent of anchorage signals, whereas mitogen activation of p44/p42 MAPK mediates an anchorage signal-dependent growth pathway. These data provide a link between aberrant stress-activated cell signaling and the altered growth phenotype of transformed cells that may be important for the development of therapies to limit transformed cell growth.

Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line.

Biliary tract malignancies represent challenges because of the lack of effective therapy and poor prognosis, in part because of the paucity of information regarding the mechanisms regulating their growth. We have recently identified a critical role for the p44/p42 mitogen-activated protein kinase (MAPK) pathway in interleukin 6 (IL-6)-stimulated growth of human cholangiocytes. Although IL-6 is a potential mitogen for cholangiocarcinoma, the role of this cytokine and its intracellular signaling pathways in cholangiocarcinoma growth is unknown. Thus, our aims were to determine the role of IL-6-mediated signaling mechanisms, and in particular the MAPK pathways, in the growth regulation of human cholangiocarcinoma. KMCH-1 cells (malignant cholangiocyte cells) secreted IL-6 constitutively, and increased IL-6 secretion in response to inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and IL-1beta. Stimulation with IL-6 resulted in proliferation of malignant cholangiocytes. These cells also possessed the IL-6 receptor complex subunits as directly assessed by immunoblot analysis. Furthermore, proliferation was completely inhibited by preincubation with anti-IL-6 neutralizing antibodies, indicating that the proliferative response to IL-6 involved receptor-mediated signaling. Both p38 and p44/p42 MAPKs were constitutively present and active in malignant cholangiocytes, and increased activity of both was observed within 15 minutes of stimulation with IL-6. Selective inhibition of either the p44/p42 MAPK pathway, by PD098059, or of the p38 MAPK pathway, by SB203580, blocked proliferation in response to IL-6. Thus, IL-6 can contribute to the autocrine and/or paracrine growth stimulation of malignant cholangiocytes via activation of either p38 or p44/p42 MAPK signaling pathways.

Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer.

PURPOSE: The insulin-like growth factor (IGF) system appears to be important in human prostate cancer biology. Expression of specific IGF binding proteins (IGFBPs) by prostate cancer tissues may modulate IGF cellular actions, and possibly determine both IGF-dependent tumor growth and biological aggressiveness in vivo. The purpose of this study was to examine the differential expression of all six IGFBP genes in benign and malignant prostate tissue samples. MATERIALS AND METHODS: Using RNAse protection assays, we examined expression of IGFBPs 1 through 6 in 23 paired benign and neoplastic prostate tissue samples obtained from the same prostatectomy specimen. RNA expression levels on each tissue sample were determined densitometrically and groups compared using standard Student's t test. RESULTS: We found expression of IGFBPs 2 through 6, but not IGFBP-1, in both malignant and benign tissues. A statistically significant differential expression of IGFBPs 2, 3 and 5 was found between tumors with high Gleason score and those with low scores and benign tissues. Expression of IGFBPs 2 and 5 was higher (p = 0.002 and 0.04, respectively) while that of IGFBP-3 was lower (p = 0.05) in high versus low Gleason score cancer specimens. Expression of IGFBPs 4 and 6 was no different between tumors (p = 0.052 and 0.25, respectively). No significant differences in IGFBP expression were evident between benign and tumor tissues when tumor grade was not considered. CONCLUSION: Our results indicate that differential expression of certain IGFBPs in human prostate cancer correlates with tumor Gleason score. Thus, expression of certain IGFBPs in prostate cancer may be used as a surrogate marker of aggressive clinical behavior.

Acute oligoarthritis associated with Clostridium difficile pseudomembranous colitis.

The abrupt onset of a sterile inflammatory oligoarthritis developed in a patient with active Clostridium difficile pseudomembranous colitis. The arthritis affected a hip and a knee. Leukocyte counts of synovial fluid obtained from the patient's left hip and knee were elevated. He was haplotyped as HLA-B27 antigen-positive. The colitis and arthritis promptly abated after treatment with oral vancomycin hydrochloride. Three other cases of arthritis associated with antibiotic-induced colitis were reviewed. It seems as if treatment of the colitis leads to resolution of the arthritis.