Sperm separation in patients with urogenital infections

Summary. A total of 196 patients attending the Center of Dermatology and Andrology, Giessen, Germany, were examined for fertility problems. Polymorphonuclear elastase, reactive oxygen species (ROS) and the number of round and peroxidase-positive cells were investigated in addition to routine semen analysis. The ejaculates were also analysed before and after sperm separation by means of swim-up or glass wool filtration. In 20 cases of leukocytospermia, sperm concentration, motility, viability, production of reactive oxygen species, and the number of peroxidase-positive cells were evaluated before and after glass wool filtration. The results show that ROS production by viable spermatozoa is highly correlated with the concentration of PMN elastase and the number of both peroxidase-positive and round cells. Multiple regression analysis with motility as dependent parameter showed the number of round cells ( n = 91; r = -0.332; P = 0.0030) to be the most important parameter affecting motility, while ROS mainly affects the viability of spermatozoa ( n = 69; r = 0.250; P = 0.0107). In the case of leukocytospermia, glass wool filtration significantly reduced the number of peroxidase-positive cells and ROS production ( P = 0.0098 and P = 0.0005, respectively). Receiver operating characteristic (ROC) curve analysis for ROS production in the ejaculate using a concentration of 1.000 ng ml⁻¹ PMN elastase as decisive parameter resulted in a cut-off value of 49,489.9 counts 10⁻⁷ viable spermatozoa. The statistical parameters were: Sensitivity: 63.2%, specificity: 100%, positive predictive value: 100%, negative predictive value: 36.1%.     

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.     

The biography of Mary E. O'Sullivan: an early American headache specialist

The aim of this study was to review the life of Mary E. O'Sullivan and to summarize her important contributions to the study of migraine. Mary E. O'Sullivan underwent extensive training to become a neurologist at a time when only 5% of women in America were physicians. She published five papers on migraine. In a 1936 Journal of the American Medical Association article, she described a patient with ergotamine overuse headache and recommended that daily doses of oral ergotamine should be avoided. Three years later she described migraine as a 'complex' syndrome with multiple causes and multiple cures. Mary E. O'Sullivan, an ambitious female headache specialist of the 1930s, was an early advocate of the use of ergotamine to treat migraine, yet she was one of the first to report ergotamine overuse headache. Although her life was short, her research, knowledge and ambition at a time when women had limited opportunities in medicine have left a mark.     

Measurement of CEA, TPA, neopterin, CA125, CA153 and CA199 in sera of pregnant women, umbilical cord blood and amniotic fluid

The following tumor markers were determined in body fluids associated with pregnancy: carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), neopterin, CA125, CA153 and CA199. CEA levels (cut-off 5.0 ng/ml) were not elevated during gestation, whereas TPA was above cut-off (85 U/l) in 98 out of 107 cases (range 40-408 U/l). TPA was significantly higher during the 3rd trimester of pregnancy than during the 1st and 2nd trimesters. 38.3% of CA125 measurements were slightly above the chosen cut-off of 35 U/ml, and the mean concentration was 33.5 +/- 16.2 U/ml. During delivery, 14 out of 21 values (67%) were elevated. Only 9.4% of CA153 values were elevated. CA199 and neopterin were also hardly ever above cut-off. In general, there was a wide scattering of individual values. With the exception of CA153 (neopterin not determined), high concentrations of CEA (maximum: 207 ng/ml), TPA (maximum: 1,565 U/ml), CA125 (maximum: 2,371 U/ml) and also CA199 (maximum: 1,533 U/ml) were found in amniotic fluid. The distribution in mixed cord blood was similar but with more moderate elevations and a lower incidence of levels above cut-off. Thus, none of these antigens is tumor specific. The term 'tumor-associated antigen' instead of 'tumor marker' is more appropriate. CEA, TPA, CA125 and CA199, but not CA153, are oncofetal antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Traditional Chinese medicine (TCM): are polyphenols and saponins the key ingredients triggering biological activities?

The number of herbal formulae considered to be clinically effective and recorded in the Chinese medical literature is huge. The scientific basis for the remedial effects of these herbal formulae is not yet understood, nor has a clear need been given as to how to make use and combine traditional Chinese medicine (TCM) and Western medicine in an effective way. In this context, it is of interest to ascertain what individual constituents are responsible for the bioactive properties, and thus to extract the common characters of composition of huge formulae to provide a scientific explanation for their modes of action. We consider polyphenols and saponins as the key ingredients in TCM remedies responsible for most of the observed biological effects, reflecting the specific requirements within the TCM philosophy of treatment based on the investigation of its chemical composition.     

Emerging therapeutic targets in chronic heart failure: part I

Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.     

Patch-clamp capacitance measurements: new insights into the endocytic uptake of transferrin

Since its introduction by Neher and Sakmann in 1976 the patch-clamp technique has been extensively used to study processes such as signalling and synaptic transmission, but also for monitoring endo- and exocytosis. Since biological membranes behave like electrical capacitors high-resolution measurements of membrane capacitance allow detection of small changes in membrane surface area that accompany exocytosis and endocytosis. We here describe our recent work on patch-clamp capacitance measurements in stably transfected HeLa cells expressing HFE, the hereditary hemochromatosis gene product, under the control of a tetracycline-sensitive promotor. By means of whole-cell and cell-attached techniques we were able to reveal transferrin-induced decreases in membrane capacitance reflecting increased endocytosis at the single cell level. Moreover, cell-attached recordings revealed significant alterations in the formation of single endocytic vesicles. Time-resolved measurements of cell membrane capacitance provide a new methodological approach to study the endocytic uptake of transferrin and its regulation by HFE, the hereditary hemochromatosis protein.