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Notes: The skin is colonized by an array of microorganisms which form its natural microflora. Disruption to the normal barrier function of the skin (due to trauma or disease) may result in invasion of the dermis by opportunistic bacteria. To date, these organisms, which may contribute to the chronicity of skin wounds, have been analyzed solely by culture methods. It is increasingly realized that standard culture methods of analysis do not accurately reflect the full diversity of complex microflora. This review discusses the limitations of traditional culture approaches and reviews recent advances in molecular microbiological techniques which facilitate a more comprehensive characterization of the microflora within clinical samples. The currently available technologies and techniques are described, as is their use in clinical practice and their potential for diagnostic screening. Chronic venous ulceration of the lower limbs is an important skin disorder in which the microflora invading the dermal tissues contribute to the observed delayed healing. Using chronic leg ulcers as a working example, we show how strict culture and molecular microbiological techniques may be employed, for the first time in combination, to definitively characterize the invading microbial community of the dermis.

Notes: Increasing evidence implicates excessive reactive oxygen species (ROS) generation and ROS-derived degradation products in the pathogenesis of many skin diseases. While numerous attempts have been made to identify prognostic biomarkers of wound healing in skin, these have met with limited success. This study examined the profiles of various oxidative stress biomarkers, namely total protein carbonyl content (from protein oxidation), malondialdehyde content (from lipid peroxidation), and the total antioxidant capacities, in acute wound fluid (n= 10) and chronic wound fluid (n= 12), using a rapid, noninvasive collection technique. Protein carbonyl content was quantified spectrophotometrically and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blotting, following 2,4-dinitrophenylhydrazine derivitization. Malondialdehyde levels were similarly quantified, following N-methyl-2-phenylindole derivitization. Total antioxidant capacity was determined via wound fluid inhibition of cytochrome C reduction by a superoxide radical flux. Acute wound fluid contained higher protein carbonyl content than chronic wound fluid, particularly evident following sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis under nonreducing and reducing conditions (p 〈 0.001 and p 〈 0.02, respectively), related to significantly higher protein levels (p = 0.0005) in acute wound fluid. Human serum albumin (∼66 kDa) was identified as the most prominent protein oxidized in both acute and chronic wound fluid, which may contribute to the reduced albumin and total protein levels in chronic wound fluid. No significant difference (p 〉 0.1) in malondialdehyde levels or total antioxidant capacities were determined between acute and chronic wound fluids, although chronic wound fluid exhibited significantly higher total antioxidant capacities (p 〈 0.005), accounting for variations in wound fluid protein content. These findings suggest an adaptation in the antioxidant profiles of chronic wound fluid to counteract the loss of consumed antioxidants in the chronic wound environment. This study highlights the roles of ROS/antioxidants in skin wound healing, their possible involvement in chronic wounds and the potential value of ROS-induced biomarkers in wound healing prognosis.

Notes: Abstract:  Breast cancer is commonly diagnosed at late stages in countries with limited resources. Efforts aimed at early detection can reduce the stage at diagnosis, potentially improving the odds of survival and cure, and enabling simpler and more cost-effective treatment. Early detection of breast cancer entails both early diagnosis in symptomatic women and screening in asymptomatic women. Key prerequisites for early detection are ensuring that women are supported in seeking care and that they have access to appropriate, affordable diagnostic tests and treatment. We therefore propose the following sequential action plan: 1) promote the empowerment of women to obtain health care, 2) develop infrastructure for the diagnosis and treatment of breast cancer, 3) begin early detection efforts through breast cancer education and awareness, and 4) when resources permit, expand early detection efforts to include mammographic screening. Public education and awareness can promote earlier diagnosis, and these goals can be achieved in simple and cost-effective ways, such as dissemination of messages through mass media. All women have the right to education about breast cancer, but it must be culturally appropriate and targeted and tailored to the specific population. When resources become available for screening, they should be invested in screening mammography, as it is the only modality that has thus far been shown to reduce breast cancer mortality. Clinical breast examination (CBE) and breast self-examination (BSE) are important components of routine breast care in countries with access to mammography and are important for general breast health education in all countries. However, the evidence does not support the use of CBE and BSE as lifesaving screening methods at this time, recognizing that data from countries with very limited resource are lacking. When widespread screening is not possible, screening can begin in an institution, city, or region, or by targeting screening to women at highest risk. A pilot program can be an ideal way to define the best approach to screening. To succeed, early detection efforts must include the health care providers with whom women have contact; these providers may be physicians, nurses, midwives, traditional healers, or others. There are tremendous differences among and within countries, and a program to promote early detection must be tailored to each country's unique situation. 

Notes: Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic growth factor produced principally by cells of mesenchymal origin. HGF/SF is an important mitogen, morphogen, and motogen and plays an important role in wound healing, tumorigenesis and particularly fetal development. Oral mucosal fibroblasts exhibit a fetal phenotype, including an increased extracellular matrix reorganizational ability, cellular migration and experimental wound repopulation in comparison to skin fibroblasts. In this study the expression, production, and bioactivity of HGF/SF by oral mucosal and skin fibroblasts was investigated. Although both oral mucosal and skin fibroblasts expressed HGF/SF, the oral mucosal fibroblasts produced significantly increased amounts of total HGF/SF (p 〈 0.01) as measured by enzyme-linked immunosorbent assay and bioactive HGF/SF as measured by cell scatter and cell-dissociation techniques (p 〈 0.01). The possible effect of increased HGF/SF in production mediating the previously described preferential responses of oral mucosal fibroblasts was studied in vitro. Reverse transcriptase-polymerase chain reaction–Western blotting and immunocytochemistry methods all showed that both oral mucosal and skin fibroblasts expressed and produced the c-Met receptor. Recombinant HGF (20–40 ng/mL) however, failed to affect fibroblast repopulation of monolayer wounds or cellular proliferation. In contrast, recombinant HGF significantly increased ECV304 wound repopulation. These studies provide direct evidence of another mechanism by which site-specific variations in fibroblast phenotype may contribute in a paracrine fashion to the rapid reepithelialization and revascularization of oral wounds.

Notes: Although more than 80% of infected and 70% of noninfected leg ulcers have been shown to harbor anaerobic organisms, their role in mediating impaired wound healing in the skin is frequently overlooked. There is now increasing evidence that the gram-positive anaerobic cocci play a role (both directly and indirectly) in mediating impaired wound healing in vivo. This article discusses the mechanisms by which these microorganisms may interfere with the inflammation, repair, and remodeling phases of the wound healing process. (WOUND REP REG 2002;10:–353)