Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.     

Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

Influence of schedule and mode of administration on effectiveness of podofilox treatment of papillomas

We investigated the timing of podofilox delivery to see how it correlated with papilloma size. We looked at times ranging from once per week (morning and afternoon) to five times per week (morning and afternoon). We also looked at delivery systems that might enhance the effectiveness of the drug by increasing penetration of the overlying cutaneous horn. These included soaking prior to drug administration, the use of a grooved needle subsequent to drug administration, and the various possible combinations of these techniques. We found that the timing of treatments had relatively little effect on the size of the papillomas. For example, at the end of ten weeks, the geometric mean diameter (GMD) (mm) of the papillomas treated five times per week and induced by a 10(-1) dilution of the virus (group B) was 18. Likewise the GMD (mm) of papillomas treated once per week was 18 (group D). On the other hand, we found that soaking plus the use of a grooved needle plus podofilox resulted in the curing of all lesions induced by a 10(-2) virus dilution and of most induced by the 10(-1) dilution, whereas soak plus podofilox or podofilox alone were not as effective in curing the lesions. Podofilox plus needle approached the soak plus podofilox plus needle in effectiveness. Treatment schedule was not a critical determinant of podofilox effectiveness. Therapeutic benefits were enhanced by hydration of the overlying cutaneous horn and penetration with a grooved needle.     

Using a cost-construction model to assess the cost of educating undergraduate medical students at the University of Texas--Houston Medical School

Spontaneous resolution of deformities after excision of facial skin lesions has been known and used for a long time by plastic surgeons. The resorption mechanism of deformity is based on natural skin expansion, and seems to be directly related to the action of the muscles of facial expression and their skin relations. Natural expansion has been shown to be effective in children. Between 1990 and 1994 excision of skin lesions, including congenital nevi, leading to postoperative deformity of the cheek, labial commissure, nose, eyelid and forehead, was performed on 35 patients, aged from 3 month to 12 years. The average follow-up is 24 months. For 26 patients (74%), natural resorption was observed 4 or 6 weeks later with good aesthetic results. For 6 patients (17%), the deformity persisted 3 or 6 months later, but did not require any further surgery. For 3 patients (9%), a second operation was necessary. Using the skins natural capacity for expansion in the treatment of facial skin defects in children is a method of reconstruction which has already been used for excision in enforced position. The platysma and muscles of facial expression by their action on skin mobilisation, allow natural expansion. A better knowledge of cutaneous biomechanical properties enables plastic surgeons to find an alternative to other classical methods.     

Childhood fibrous dysplasia presenting as blindness: a skull base approach for resection and immediate reconstruction

Fibrous dysplasia is an abnormal fibroosseous process of bone of unknown cause. The incidence of skull involvement varies, painless enlargement being the most common presenting symptom. Change in vision is a rare but recognized finding. We report a 3-year-old boy with extreme fibrous dysplasia involving the skull base, who presented with blindness. He underwent exposure osteotomies of the frontal bones and orbits to provide access for skull base tumor removal. The orbital roofs were reconstructed with microplate-fixed cranial grafts. One and one half years after tumor excision followed by immediate reconstruction, the boy retains facial symmetry, and his ocular function has not deteriorated.     

trans-2-phenylcyclopropylamine is a substrate for and inactivator of horseradish peroxidase

Horseradish peroxidase (HRP) is well known for mediating the electron-transfer oxidation of electron-rich aromatic 'donors' such as phenols and anilines, but has not been described to oxidize aliphatic amines. We here confirm the inability of HRP to oxidize typical aliphatic amines, even those which would exist significantly as free bases at the operative pH. In contrast, trans-2-phenylcyclopropylamine (2-PCPA) is both a substrate (turnover product is cinnamaldehyde) and a time-dependent inactivator of HRP. These activities of 2-PCPA are consistent with either a concerted or rapid sequential one-electron-oxidation/ring-opening to give an intermediate capable of covalent binding to the enzyme. 2-PCPA is the first known example of a simple aliphatic amine which serves as a substrate for HRP under turnover conditions.     

Ratings of the performances of practicing internists by hospital-based registered nurses

PURPOSE: To examine the feasibility and reliability of ratings completed by hospital-based registered nurses of the humanistic qualities, communication skills, and selected aspects of the clinical skills of practicing internists. METHOD: In 1988-1989, registered nurses who worked in the same 175 hospitals as 232 internists with admitting privileges at these hospitals rated the internists' performances. The nurses were selected from medicine floors, specialty floors, and intensive care units and/or critical care units, using lists provided by head nurses. A total of 1,877 rating questionnaires with 13 performance categories were collected (with a mean of 8.01 nurses per internist). The ratings were analyzed to determine measurement characteristics and the relationships of the nurses' demographic characteristics to the ratings. In addition, for each of ten performance categories for 152 of the internists, the average rating each internist received from nurses was compared with the average rating each internist received from peer physicians. Statistical analysis used Pearson correlations, canonical correlations, factor analyses, Student's t-tests, analysis of variance, and stepwise multiple regression. Finally, the internists themselves, including physicians who were not actually rated by the nurses, were asked to complete a brief questionnaire that included questions about their opinions of the use of nurses' ratings. RESULTS: The nurses' ratings correlated moderately strongly with the peer physicians' ratings and had a common structure. However, the nurses' ratings were lower for several humanistic qualities, including respect, integrity, and responsibility, and their ratings were higher for medical knowledge and verbal communications. Across the 13 performance categories, approximately 10-15 ratings from nurses were needed to obtain a reliable assessment of an internist's humanistic qualities and communication skills. Many internists felt that nurses' ratings should be used equally with, or at least as a lesser contribution to, ratings by peer physicians of humanistic qualities and communication skills. CONCLUSION: Nurses' ratings appear to provide a feasible and reliable method of evaluating the internists' communication skills and humanistic qualities, when used in conjunction with ratings by peer physicians.