Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Project Outreach: Organizations Unified to Reach Youth

Youths of today are forced to deal with the external pressures of alcohol and drug abuse on all levels-from the older youngsters across the street pressuring them to be "cool," to the "cute dog" enticing them with the glamour of being the original "party animal." Through today's mass communications, young people are exposed to negative, self-destructive attitudes. It is important, therefore, to expose them to a more positive influence and try to reach them through parental guidance, personal contact, and peer pressure. To achieve this, the University of Missouri's Kansas City Chapter of the American Pharmaceutical Association's Academy of Students of Pharmacy, in conjunction with the Metropolitan Kansas City Area Task Force on Alcohol and Other Drug Abuse, proposed the development of an annual drug abuse prevention program that specifically targets fifth graders in the greater Kansas City metropolitan area. A primary goal of Project Outreach (Organizations Unified to Reach Youth) is to unite drug abuse prevention programs in the greater Kansas City metropolitan area in their outreach efforts to give positive support to Kansas City's youth against alcohol and other drugs. Phase I of Project Outreach consisted of a series of programs for the parents in the community. Phase II entailed college students who spoke to fifth graders in their classrooms. These students also participated in poster and poem contents centered around drug abuse prevention. In Phase III, which featured an outstanding, motivated speaker, the sample group of 600 fifth graders in the area participated in a major event to give positive peer pressure to say no to drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

Pyridinyl imidazoles inhibit IL-1 and TNF production at the protein level

The mechanism by which SK&F 86002 and other pyridinyl imidazoles inhibit the production of IL-1 and TNF from LPS-stimulated human monocytes was examined. Inhibition of IL-1 and TNF production was found to depend on the time of addition of SK&F 86002, with diminishing effect when added more than 2 h after LPS stimulation. Analysis of Western blots confirmed that both intracellular IL-1β and extracellular TNF were significantly reduced in response to SK&F 86002, but these reductions were not paralleled by changes in IL-1 and TNF mRNA.³⁵S methionine pulse and pulse-chase studies on IL-1 biosynthesis suggest that significant inhibition by SK&F 86002 and related compounds occurs at the translational level.

     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

Protective effect of flavonoids against red blood cell hemolysis by free radicals

BACKGROUND:

Flavonoids are polyphenolic substances with antioxidant properties, and they are found in different vegetables and fruits. Epidemiological studies have shown that the consumption of flavonoids reduces the prevalence of cardiovascular diseases. The use of synthetic antioxidants, however, has been limited because of their toxicity. Therefore, medical researchers have intensified their quest to find natural antioxidants.

OBJECTIVES:

To investigate the effect of several pure flavonoids, such as kaempferol, quercetin, morin and rutin, on red blood cell hemolysis and evaluate their -SH capacity as an indicator of membrane protection.

METHODS:

The rate of hemolysis and cell membrane -SH capacity were determined by spectrophotometry. Red blood cell peroxidation was induced using 2,2′-azo-bis-(2-amidinopropane) dihydrochloride. The effect of each flavonoid on hemolysis was examined at three concentrations (0.5 μg/mL, 5 μg/mL and 10 μg/mL), however, only the greatest concentration (10 μg/mL) of each flavonoid was used to study the effect on -SH groups.

RESULTS:

In all cases, the antioxidant activity was dose-dependent. Rutin showed the highest inhibitory effect on hemolysis among flavonoids (42.5%). The protective effect of kaempferol, rutin and morin against -SH group oxidation measured 7.7%, 23.3% and 26.4%, respectively.

CONCLUSIONS:

Results showed that flavonoids and flavonoid-containing plants can be used as natural antioxidants for the treatment and prevention of disease conditions, the pathogenesis of which is mediated by lipid peroxidation.     

Effect of vitamin E on tamoxifen-treated breast cancer cells

BACKGROUND: Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (alpha-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. METHODS: Cells were treated in vitro with 20-muM TAM alone and in combination with 10-muM alpha-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. RESULTS: Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10muM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. CONCLUSIONS: These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.     

Team training for surgical trainees

Healthcare professionals work in teams but are rarely trained together. Realizing the adverse impact of poor teamwork on patient care, the Accreditation Council for Graduate Medical Education requires surgical trainees to demonstrate a mastery of teamwork-related competencies. A number of team training curricula are available in the USA, the best known of which is TeamSTEPPS – developed by the U.S. Department of Defense Patient Safety Program in collaboration with the Agency for Healthcare Research and Quality.     

Outcome of major cardiac injuries at a Canadian trauma center

Background  

Canadian trauma units have relatively little experience with major cardiac trauma (disruption of a cardiac chamber) so injury outcome may not be comparable to that reported from other countries. We compared our outcomes to those of other centers.