Dilinoleoylphosphatidylcholine protects human low density lipoproteins against oxidation

LDL oxidation may promote atherosclerosis. We found that polyenyphosphatidylcholine (PPC), a mixture of polyunsaturated phospholipids extracted from soybeans, has antioxidant effects in in vivo models of oxidative stress. To assess whether components of PPC affect the in vitro oxidizability of LDL, plasma from 15 healthy volunteers was incubated with 10 microM of either dilinoleoyl-, palmitoyl-linoleoyl-, linoleoyl-palmitoyl- or distearoyl-phosphatidylcholine as well as 10 microM and 1 mM alpha-tocopherol. LDL oxidation was initiated with 5 microM Cu(2+) sulfate and monitored by conjugated diene production, or with 2, 2'-azobis (2-amidinopropane) dihydrochloride, a free radical generator, and monitored by O(2) consumption. After addition of Cu(2+), the lag phase (indicative of resistance of LDL to oxidation) was longer (140% of controls; P<0.001) for LDL incubated with dilinoleoyl-, but not with the other phosphatidylcholine species. This effect was similar to that of 1 mM alpha-tocopherol (135%). After addition of 2,2'-azobis (2-amidinopropane) dihydrochloride, the inhibition time (also reflecting the antioxidant content of LDL) was prolonged (P<0.001) for alpha-tocopherol (206%) and dilinoleoyl-(188%), but not for distearoyl-phosphatidyl-choline. Thus, dilinoleoyl-phosphatidylcholine (the main component of PPC) protects against LDL oxidation, a possible mechanism for its reported anti-atherosclerosis effects.     

Flow cytometric analysis of deoxyribonucleic acid ploidy in benign and malignant aldosterone-producing neoplasms of the adrenal gland

Studies of nuclear deoxyribonucleic acid (DNA) ploidy were performed to determine if ploidy was a marker of a malignant disease or a predictor of prognosis. Paraffin-embedded specimens from 20 benign and six malignant aldosterone-producing neoplasms were examined by flow cytometry. For 17 of the benign aldosteronomas, the DNA histograms were similar to those for samples of normal adrenal cortical parenchyma of adult humans. The three DNA histograms from benign (histologically and clinically) aldosteronomas and all six malignant aldosterone-producing neoplasms were abnormal. Tissue from the adrenal gland from three of the patients with malignant aldosterone-producing tumors exhibited a DNA tetraploid and polyploid pattern; adrenal tissue from three other patients with malignant tumors were classified as having DNA aneuploid histogram patterns. Only patients with DNA aneuploid histogram patterns subsequently died of the disease. Flow cytometry may have an important role prognostically, rather than diagnostically, in the evaluation of aldosterone-producing malignant neoplasms, because the DNA histograms from three benign adenomas were abnormal.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

Genetic Engineering and Medical Ethics

In the introduction I express the need of introducing the point of view of Ethics when we are dealing with problems of science, technology, and especially medicine. In the first part of my presentation I deal with the problem of the value of human life, coming to the conclusion that human life might not be completely absolute, but is extremely important and “ceteris paribus” should be respected, and the problem of when it starts. Some of the main arguments are discussed. In this connection the question of abortion is briefly discussed. In the second part I deal with some problems related to human reproduction. Most people will be willing to support programmes for treating individuals with genetic disease; but at the same time the dangers of increasing depersonalization of the reproductive process are pointed out. In the third part I take up the problem of In Vitro Fertilisation. IVF has certainly brought benefits to some couples suffering from infertility, but at the same time it has raised quite a few human and moral problems. Is it permissible to fertilise an egg with a donor sperm, replacing the embryo in the womb? What about fertilising a donor egg with the husband's sperm? Is it acceptable to store or freeze embryos for future use? Is it moral to implant such an embryo in a woman who has no genetic relationship with the embryo? Is it moral to use surrogate mothers? Is it moral for ‘spare’ embryos to be killed or used as tissue for research? At the end I stress the need of dialogue between life sciences and ethics.     

Dilinoleoylphosphatidylcholine reproduces the antiapoptotic actions of polyenylphosphatidylcholine against ethanol-induced hepatocyte apoptosis

BACKGROUND: Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines extracted from soybeans, attenuates hepatocyte apoptosis induced by ethanol feeding of rats. Our aims were to evaluate whether dilinoleoylphosphatidylcholine (DLPC), the main component of PPC, reproduces the antiapoptotic actions of PPC against alcohol-induced apoptosis and to identify the apoptotic proteins that are affected by PPC and DLPC. METHODS: Rats were fed Lieber-DeCarli liquid diets containing ethanol (35% of energy) or an isocaloric amount of carbohydrate for 4 weeks. Another group of rats were given the ethanol diet supplemented with PPC (3 g/liter) or DLPC (1.5 and 3 g/liter). Hepatocyte apoptosis was assessed by terminal transferase-mediated dUTP nick end labeling staining and by caspase 3 enzyme activity. Activity of caspases 3 and 9 was assayed by using fluorogenic peptide substrates. Cytochrome c was quantified by enzyme-linked immunosorbent assay. The protein contents of cytochrome c, procaspase 3, caspase 3, Bcl-x(L), and Bax were analyzed by Western blot and quantified by densitometry. Lobular localization of active caspase 3 was examined by immunoperoxidase staining. RESULTS: PPC and DLPC decreased ethanol-induced increases in hepatocyte apoptosis, cytosolic cytochrome c, and caspase 3 content and its activity. Caspase 3 activity correlated with the number of apoptotic hepatocytes. Active caspase 3 was present predominantly in perivenular hepatocytes, and ethanol feeding extended it to lobular hepatocytes; this ethanol effect was reduced by PPC and DLPC. Ethanol significantly decreased Bcl-x(L) in homogenate, mitochondria, and cytosol, and there was a trend for increased Bcl-x(L) in these fractions after PPC and DLPC supplementation. Microsomal Bcl-x(L) did not differ between treatment groups. Bax was detected in homogenate and cytosol, and its level was not affected by ethanol. CONCLUSIONS: DLPC, at a dose contained in PPC, reproduces the antiapoptotic actions of PPC through a reduction in cytosolic cytochrome c concentration and caspase 3 activity, possibly in association with up-regulation of Bcl-x(L) expression. Because DLPC is a pure and well defined compound, it may be more suitable than PPC for intervention against alcohol-induced apoptosis.     

Spastic muscle cells are shorter and stiffer than normal cells

The mechanical properties of isolated single muscle fiber segments were measured in muscle cells obtained from patients undergoing surgery for correction of flexion contractures secondary to static perinatal encephalopathy (cerebral palsy). "Normal" muscle cells from patients with intact neuromuscular function were also mechanically tested. Fiber segments taken from subjects with spasticity developed passive tension at significantly shorter sarcomere lengths (1.84 +/- 0.05 microm, n = 15) than fibers taken from normal subjects (2.20 +/- 0.04 microm, n = 35). Elastic modulus of the stress-strain relationship in fibers from patients with spasticity (55.00 +/- 6.61 kPa) was almost double that measured in normal fibers (28.25 +/- 3.31 kPa). The fact that these muscle cells from patients with spasticity have a shorter resting sarcomere length and increased modulus compared with normal muscle cells suggests dramatic remodeling of intracellular or extracellular muscle structural components such as titin and collagen. Such changes in muscles of patients with spasticity may have implications for therapy.     

Prevalence of prostatitis-like symptoms in a community based cohort of older men

PURPOSE: We describe a community based study to estimate the prevalence of prostatitis-like symptoms using questions similar to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). MATERIALS AND METHODS: Study subjects were a randomly selected sample of Olmsted County, Minnesota white men 40 to 79 years old in January 1990 who participated in a longitudinal study of lower urinary tract symptoms. Subjects were evaluated biennially using self-administered questionnaires. In 2000 questions similar to the NIH-CPSI were incorporated into the questionnaire and questionnaire responses were used to categorize men as having prostatitis-like symptoms. RESULTS: Of 1,541 men 182 (12%) had at least 1 urogenital pain symptom. Pubic (76 men, 4.9%) and testicular (73, 4.7%) pain were the most frequent pain symptoms. A total of 34 men with prostatitis-like symptoms (2.2%) had higher mean pain (6.7 versus 0.5), urinary symptom (3.5 versus 2.1) and quality of life impact (3.7 versus 1.9) scores compared to men who did not (all p <0.001). Pain frequency (OR 39.2, 95% CI 18.8, 81.9) and pain intensity (OR 21.5, 95% CI 8.7, 52.9) were more strongly associated with prostatitis-like symptoms than urinary symptom score (OR 2.8, 95% CI 1.4, 5.6) or quality of life impact score (OR 4.5, 95% CI 1.9, 10.7). CONCLUSIONS: Although urogenital pain is common among community dwelling men, prostatitis-like symptoms based on the modified questions from the NIH-CPSI are less common. While pain measures may be useful in distinguishing between men with and without prostatitis-like symptoms, the urinary symptom and quality of life impact scores could partly reflect benign prostatic hyperplasia.     

S-Adenosylmethionine: molecular,biological, and clinical aspects--an introduction

In clinical research, a novel approach has emerged: some of the essential nutrients are being used to treat pathologic conditions. Many of these nutrients, including methionine, must first be activated in the liver or in other tissues before they can exert their key functions. However, this activating process is impaired in disease states and, as a consequence, nutritional requirements change. For instance, for methionine to act as the main cellular methyl donor, it must first be activated to S-adenosylmethionine (SAMe; also known as ademethionine). SAMe is required and is of fundamental importance for the metabolism of nucleic acids and polyamines, the structure and function of membranes, and as a precursor of glutathione. These processes are often seriously altered in various pathologic states addressed in this symposium, but they cannot be restored by simply administering methionine. For instance, in liver disease associated with impairment of the enzyme that activates methionine to SAMe, supplementation with methionine is useless and may even become toxic as it accumulates because it is not used. Accordingly, one must correct the lack of SAMe by bypassing the deficiency in enzyme activation; this is done by providing the product of the defective reaction, namely SAMe. Under these pathologic conditions, SAMe becomes crucial for the functioning of the cell. Thus SAMe, which is found in all living organisms, becomes the essential nutrient instead of methionine. This symposium reviewed the biological and corresponding molecular aspects of SAMe metabolism and the clinical consequences of its deficiency or supplementation in various tissues.