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Background: Docosahexaenoic acid (DHA) is highly concentrated in the mammalian nervous and visual system. The fatty acid, which is required by the fetus and the newborn, is supplied by the mother from their tissue reservoirs. It has been suggested that mother's supplementation with DHA during pregnancy and even before pregnancy. Different sources of DHA are available for supplementation such as: single-cell algae triglycerides (TG), egg's yolk phospholipids (PL), DHA ethyl esther (EE), and sn-2 DHA monoacylglyceride (MG). We evaluated comparatively the effectiveness of these different DHA sources to produce tissue DHA accretion and to increase milk DHA content., Methods: Female Wistar rats fed a diet which provided no DHA, were daily supplemented by 40 days before mating (BM) and during the pregnancy with either TG, PL, EE, or MG to an amount which provided 8 mg/kg b.w. of DHA. Samples of blood plasma, erythrocytes, hepatic and adipose tissue were obtained from rats at the BM condition and after the delivery (AD), and milk samples were also obtained from the gastric content of the pups nursed by the rats at day 3, 11 and 20 of suckling. Samples were processed to assess DHA and arachidonic acid (AA) content by gas-chromatography., Results: TG, PL, EE, and MG supplementation produced a similar intestinal absorption of DHA as estimated from the plasma DHA at the BM condition. However, PL and MG supplementation produced a higher accretion of DHA into erythrocytes, hepatic, and adipose tissue than TG and EE supplementation at the BM condition. AA content was not modified by the different supplementing oils. A reduction of the DHA content of plasma, erythrocytes, hepatic and adipose tissue at the AD condition was observed, and a reduction of AA for the hepatic and adipose tissues was also observed, suggesting the importance of these tissues as DHA and AA reservoirs. Milk secretion from PL and MG supplemented rats showed a higher DHA content than secretion from TG- and EE-supplemented rats., Conclusions: We conclude that PL and MG supplementation provides higher tissue DHA accretion and higher milk DHA content than TG and EE supplementation. However, we were not able to visualize the comparative advantages derived from PL vs. MG supplementation., (Copyright (c) 2005 S. Karger AG, Basel.)

Fumonisin B(1) (FB(1)) is an amphipathic toxin produced by the pathogenic fungus Fusarium verticillioides which causes stem, root and ear rot in maize (Zea mays L.). In this work, we studied the action of FB(1) on the plasma membrane H(+)-ATPase (EC 3.6.1.34) from germinating maize embryos, and on the fluidity and lipid peroxidation of these membranes. In maize embryos the toxin at 40 microM inhibited root elongation by 50% and at 30 microM decreased medium acidification by about 80%. Irrespective of the presence and absence of FB(1), the H(+)-ATPase in plasma membrane vesicles exhibited non-hyperbolic saturation kinetics by ATPH-Mg, with Hill number of 0.67. Initial velocity studies revealed that FB(1) is a total uncompetitive inhibitor of this enzyme with an inhibition constant value of 17.5+/-1 microM. Thus FB(1) decreased V(max) and increased the apparent affinity of the enzyme for ATP-Mg to the same extent. Although FB(1) increased the fluidity at the hydrophobic region of the membrane, no correlation was found with its effect on enzyme activity, since both effects showed different FB(1)-concentration dependence. Peroxidation of membrane lipids was not affected by the toxin. Our results suggest that, under in vivo conditions, the plasma membrane H(+)-ATPase is a potentially important target of the toxin, as it is inhibited not only by FB(1) but also by its structural analogs, the sphingoid intermediates, which accumulate upon the inhibition of sphinganine N-acyltransferase by this toxin.

Cationic complexes [Mo(eta(3)-allyl)(CO)2L3]+ (L3 = either nitrogen-donor tridentate ligand or three monodentate ligands) were prepared in high yield and under mild conditions using as precursors either the triflato complex [Mo(eta(3)-allyl)(OTf)(CO)2(NCMe)2] or the combination of the chloro complex [Mo(eta(3)-allyl)Cl(CO)2(NCMe)2] and the salt NaBAr'(4)(Ar'= 3,5-bis(trifluoromethyl)phenyl). The tridentate ligands employed were 2,2':6',2'-terpyridine (terpy) and cis,cis-1,3,5-cyclohexanetriamine (CHTA), whereas the monodentate ligands imidazole (im) and 3,5-dimethylpyrazole (dmpz) were chosen. In order to stabilize the labile intermediates, an excess of acetonitrile was used in most of the syntheses. However, the pyrazole complex was prepared through a nitrile-free route to avoid reactions at the coordinated nitrile. The solid state structures of [Mo(eta(3)-methallyl)(CO)2(terpy)]OTf (2), [Mo(eta(3)-methallyl)(CO)2(CHTA)]BAr'4 (3), [Mo(eta(3)-methallyl)(CO)2(NCMe)3]BAr'4 (4), [Mo(eta(3)-allyl)(CO)2(im)3]OTf (5) and [Mo(eta(3)-allyl)(CO)2(dmpz)3]BAr'4 (6) were determined by means of single-crystal X-ray diffraction.

New receptors fac-[Re(CO)3(pz)3]BAr'4 (pz = 3,5-dimethylpyrazole or 3(5)-tert-butylpyrazole, Ar' = 3,5-(CF3)2C6H3), synthesized from [Re(OTf)(CO)5] and the pyrazoles, have been found to show a high affinity for chloride.

Introduction: Recent studies indicate that decreased energy generation by mitochondria is a feature that is common across neurodegenerative diseases., Patients and Methods: In order to obtain direct evidence that mitochondrial functioning is altered, we measured the hydrolytic activity of F0F1-ATPase and its capacity to generate a stable proton gradient in submitochondrial particles in 29 patients diagnosed with probable Alzheimer's disease (AD). Submitochondrial particles were obtained from platelets of patients with a diagnosis of probable AD and from clinically healthy controls., Results: Data revealed that the hydrolytic activity of F0F1-ATPase increases significantly in patients with probable AD (41.7+/-4.3 nmol PO4 min-1[mg protein]-1, n=29) as compared to the control subjects (29.1+/-1.9 nmol PO4 min-1 [mg protein]-1, n=29). It is important to note that, in the male population with probable AD, we found that hydrolytic activity of F0F1-ATPase increased as cerebral deterioration progressed. We also detected a lower pH gradient in the submitochondrial particles of patients with probable AD (0.28+/-0.08 pH units, n=25) as compared to the controls (0.5+/-0.1 pH units, n=20)., Conclusions: Overall, these data point to an alteration in the functioning of the enzyme.

Inhaled or ingested ultrafine nanoparticles and their effects on early pregnancy remain polemic. The objectives of the study were: (a) to determine the embryotoxic effects of nanoparticles at the 2-cell stage and (b) to localize the internalized nanoparticles in the blastocyst. Thawed mouse 2-cell embryos (no. = 128) were exposed to either mixed-size polystyrene-based nanoparticles (11 million/ml) or control G1.3 medium and assessed after 72 hours. Additionally, blastocysts (no. = 146) were exposed to nanoparticles and analyzed. The results showed that the nanoparticles did not inhibit 2-cell embryo development to the blastocyst stage (89.4 vs 96.8%; treated vs control). There were no differences in hatching (34.8 vs 43.5%), implantation (13.6 vs 24.2%) and degeneration (10.6 vs 3.2%). Delayed exposure to nanoparticles showed similar percent hatching (40.7 vs 47.3%) and implantation (17.6 vs 20.0%). Although nanoparticles were internalized, embryo development was not inhibited suggesting a lack of embryotoxicity. During hatching, the larger nanoparticles adhered to the extruding blastocyst, preferentially on trophoblasts, but interference was insignificant. Exposure to polystyrene-based nanoparticles at the concentration tested are not associated with embryonic loss.

Background/aims: Docosahexaenoic acid (C22:6, DHA) is an omega-3 fatty acid required for the normal development of the mammalian nervous and visual system. DHA is provided by the mother during pregnancy and lactating period. Mother's DHA supplementation during pregnancy, and even before pregnancy, has been suggested. DHA can be provided by marine oils, egg's yolk phospholipids, single cell algae oils, the pure fatty acid, or by the ethyl ester derivative (DHA-EE). Another way to provide DHA can be by sn-2 docosahexaenyl monoacylglyceride (DHA-MG), obtained by the treatment of fish oil with stereospecific lipases. sn-2 Fatty acid monoacylglycerides can be more easily absorbed at the intestine than other fatty acid derivatives., Methods: Female rats fed with a synthetic, which provided essentially no DHA, received a 40-day supplementation of either DHA-EE or DHA-MG. Plasma and erythrocyte fatty acid composition were assessed by gas chromatography at day 0 and 40 of supplementation., Results: DHA-EE increased plasma and erythrocyte DHA by 15 and 11.9%, respectively, with no modification of arachidonic acid (AA) content. DHA-MG supplementation increased plasma and erythrocyte DHA by 24 and 23.8%, respectively, but reduced AA by 5.5 and 3%, respectively., Conclusions: We conclude that in the rat, DHA-MG supplementation allows a higher plasma and erythrocyte DHA content than DHA-EE with minor modification of AA content., (Copyright 2005 S. Karger AG, Basel.)

Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.

Background: Maternal omega-3 fatty acid supplementation has been suggested to provide docosahexaenoic acid (DHA) for the normal brain development during gestation. DHA can be given as such (preformed) or through the omega-3 precursor alpha-linolenic acid (LNA) which is transformed into DHA by elongation and desaturation reactions. Western diet provides low amounts of LNA and DHA; therefore, supplementation with these omega-3 fatty acids has been suggested for pregnant women. However, the bioequivalence of LNA ingestion to DHA supplementation has not been established., Methods: Recently weaning female Wistar rats were fed a diet containing a small amount of LNA and no DHA. The animals were daily supplemented 40 days before mating, during pregnancy, and until delivery with 60 mg/kg of LNA or 6 mg/kg of DHA dissolved in coconut oil. Fatty acids were given as ethyl ester derivatives. Controls received coconut oil. The fatty acid composition of blood plasma, erythrocytes, liver, visceral adipose tissue, and brain segments (frontal cortex, hippocampus, and cerebellum) was analyzed. Brain segments obtained from 16- and 19-day-old fetuses and from 2- and 21-day-old rats were also analyzed for fatty acid composition., Results: Supplementation with LNA and DHA induced a similar accretion of DHA in plasma, erythrocytes, liver, and brain segments of the mothers. The adipose tissue showed a higher DHA accretion after DHA-supplementation. The DHA accretion in frontal cortex, hippocampus, and cerebellum obtained from the fetuses and the newborn rats was similar when the mothers were supplemented with LNA and DHA. Our results show that under our experimental conditions a similar accretion of DHA in the different tissues of the mothers and in the brain segments of fetuses and newborn rats is obtained after LNA and DHA supplementation., Conclusion: LNA and DHA, at the amounts given in this study, show a similar bioequivalence for DHA accretion in different tissues of the mother and in brain segments of fetuses and newborn rats., (Copyright 2004 S. Karger AG, Basel)

The Toc complex at the outer envelope of chloroplasts initiates the import of nuclear-encoded preproteins from the cytosol into the organelle. The core of the Toc complex is composed of two receptor GTPases, Toc159 and Toc34, as well as Toc75, a beta-barrel membrane channel. Toc159 is equally distributed between a soluble cytoplasmic form and a membrane-inserted form, suggesting that assembly of the Toc complex is dynamic. In the present study, we used the Arabidopsis thaliana orthologs of Toc159 and Toc34, atToc159 and atToc33, respectively, to investigate the requirements for assembly of the trimeric Toc complex. In addition to its intrinsic GTPase activity, we demonstrate that integration of atToc159 into the Toc complex requires atToc33 GTPase activity. Additionally, we show that the interaction of the two GTPase domains stimulates association of the membrane anchor of atToc159 with the translocon. Finally, we employ reconstituted proteoliposomes to demonstrate that proper insertion of the receptor requires both Toc75 and Toc34. Collectively these data suggest that Toc34 and Toc75 act sequentially to mediate docking and insertion of Toc159 resulting in assembly of the functional translocon.

Purpose: The role of molecular monitoring of minimal residual disease (MRD) in low-grade non-Hodgkin's lymphoma is controversial. We have performed a prospective study of the molecular behavior of 35 patients with follicular non-Hodgkin's lymphoma who received cyclophosphamide-vincristine-prednisone chemotherapy in conjunction with IFN-alpha 2b., Experimental Design: Bcl-2 and clonal immunoglobulin heavy chain (IgH) gene rearrangements were assayed at diagnosis by PCR in lymph node and bone marrow (BM) and sequentially after treatment., Results: Molecular markers were detected in BM of 29 (83%) patients at diagnosis: Bcl-2 rearrangement in 20 patients (90% major breakpoint and 10% minor cluster) and clonal IgH rearrangement in 9 of 15 patients negative for Bcl-2. Molecular and clinical response was noted in 25 (86%) patients after induction treatment. Progression-free survival at 5 years was 78.1 +/- 8%. A correlation between clinical and molecular response was found in 24 patients with molecular markers in BM at diagnosis and >2 years of follow-up: 94% of patients with undetectable MRD showed continuous clinical remission, whereas 50% of patients who reverted back to positive molecular markers relapsed (P < 0.05)., Conclusions: The rate of molecular response is high in patients treated with cyclophosphamide-vincristine-prednisone and IFN and MRD sequential analysis is useful for disease surveillance.

Extracellular matrix-degrading gelatinases are mainly involved in tumor invasion and metastasis. Previous experimental data from our group and others suggested that homocysteine could have a potential modulatory role on the proteolytic balance at the extracellular matrix. Therefore, we studied the effects of homocysteine on extracellular matrix-degrading proteases using model human tumor cell lines and a combination of in vitro fluorogenic assay and zymographic techniques. Homocysteine is shown to be the thiol compound with the most potent inhibitory activity on matrix metalloproteinase 9. Zymographies reveal that matrix metalloproteinase 2 is, at least, as sensitive to inhibition by homocysteine as matrix metalloproteinase 9 is. This study opens new ways to the potential pharmacological use of thiol compounds.

Cholesterol is a molecule with a double bond in its structure and is therefore susceptible to oxidation leading to the formation of oxysterols. These oxidation products are found in many commonly-consumed foods and are formed during their manufacture and/or processing. Concern about oxysterols consumption arises from the potential cytotoxic, mutagenic, atherogenic, and possibly carcinogenic effects of some oxysterols. Eggs and egg-derived products are the main dietary sources of oxysterols. Thermally-processed milk and milk-derived products are another source of oxysterols in our diet. Foods fried in vegetable/animal oil, such as meats and French-fried potatoes, are major sources of oxysterols in the Western diet. Efforts to prevent or to reduce cholesterol oxidation are directed to the use of antioxidants of either synthetic or natural origin. Antioxidants are not only able to inhibit triglyceride oxidation, some of them can also inhibit cholesterol oxidation. Among synthetic antioxidants 2,6-ditertiarybutyl-4-methylphenol (BHT), and tertiary butylhydroquinone (TBHQ) can efficiently inhibit the thermal-induced oxidation of cholesterol. Some natural antioxidants, such as alpha- and gamma-tocopherol, rosemary oleoresin extract, and the flavonoid quercetin, show strong inhibitory action against cholesterol oxidation.

By modifying the degree of hydrogenation of dietary fat, it is possible to modify the fatty acid composition and the biochemical activity of cellular tissues. The age can be another variable influencing these modifications. The effect of isocaloric diets containing oils with different degrees of hydrogenation: fish oil (FO, 0.3% TRANS), partially hydrogenated fish oil (PHFO, 29% TRANS), or highly hydrogenated fish oil (HHFO, 2.3% TRANS), in the fatty acid composition (CIS and TRANS isomers) of hepatic microsomes from young (70-day-old) and aged (18-month-old) rats, in the microsomal cytochrome P-450 (C-450) content, and in the aminopyrine N-demethylase (AND), aniline hydroxylase (AH), NADPH cytochrome P-450 reductase (NCR), UDP-glucuronyl transferase (UGT), and GSH-S transferase (GST) enzymatic activities were studied. Fatty acid composition and n-6/n-3 ratio of microsomal membranes was modified to a higher extent in young rats. C-450 content and AND activity were reduced when the degree of hydrogenation of dietary fat was increased in the young and the aged rats. AH activity was higher after the PHFO diet in the young rats only. NCR activity was reduced in the young animals when the hydrogenation of the fat was increased. However, in aged rats the enzyme exhibited a higher activity after the PHFO and HHFO diet. UGT and GST activities where not affected by the level of hydrogenation of the dietary fat in both the young and the aged rats. However, UGT activity was higher in the young rats, while GST activity was higher in the aged animals. We conclude that hydrogenation of dietary fat can modify the fatty acid composition of hepatic microsomes, young animals being more sensitive to these changes than aged animals. These effects were also reflected in the amount and/or the activity of some molecular components of the hepatic microsomal mixed-function oxidase enzyme system. Microsomal TRANS fatty acid composition is not affecting the activity of the enzymes, the age of the animals being the most important factor., (Copyright 2003 S. Karger AG, Basel)

We report a patient with progressive multifocal leukoencephalopathy (PML) after autologous stem cell transplantation (SCT) for non-Hodgkin's lymphoma (NHL). This is an unusual association, and to date only seven cases have been reported. This is the first case of PML after SCT treated with cidofovir, and the fifth case treated with this drug in a patient without human immunodeficiency virus (HIV) infection. In the previous four patients treated with cidofovir the outcome was discouraging, as was the case in this patient.

Objectives: To assess the usefulness of a technique for inserting hookwires guided by computed tomography to locate and resect pulmonary nodules by video-assisted thoracoscopy. To describe the procedure and its complications., Patients and Methods: Nine pulmonary nodules were located in nine patients. All were

High levels of homocysteine induce a sustained injury on arterial endothelial cells which accelerates the development of thrombosis and atherosclerosis. Some of the described effects of homocysteine on endothelial cells are features shared with an anti-angiogenic response. Therefore, we studied the effects of homocysteine on key steps of angiogenesis using bovine aorta endothelial cells as a model. Homocysteine decreased proliferation and induced differentiation. Furthermore, 5 mM homocysteine produced strong inhibitions of matrix metalloproteinase-2 and urokinase, two proteolytic activities that play a key role in extracellular matrix re-modeling, and decreased migration and invasion, other two key steps of angiogenesis. This study demonstrates that homocysteine can inhibit several steps of the angiogenic process.

The authors describe a new technique for reconstruction of mandibular body defects. The feasibility of distraction osteogenesis with submerged (internal) devices for reconstruction of segmental mandibular defects is investigated in an experiment with five adult dogs. A segmental mandibulectomy was performed on the horizontal ramus. The bony defect was regenerated using distraction osteogenesis (bone transport) at a rate of 1 mm daily. The animals were killed after the consolidation period. Complete bone regeneration of the surgically created gap was successful in three of five dogs. Two animals failed to create new bone. In these two cases, the screws did not offer proper stability to the bony fragments, and this caused a lack of ossification. This experimental study demonstrates the possibility to use internal distraction devices to reconstruct segmental mandibular defects in a canine model. Internal devices show enormous advantages in comparison with the external ones. This method with no donor-site morbidity may become a very useful option in human mandibular reconstruction.

(+)-aeroplysinin-1, an antibacterial brominated compound produced by certain sponges, was selected during a blind high-throughput screening for new potential antiangiogenic compounds obtained from marine organisms. In a variety of experimental systems, representing the sequential events of the angiogenic process, aeroplysinin-1 treatment of endothelial cells resulted in strong inhibitory effects. Aeroplysinin-1 inhibited the growth of endothelial cells in culture and induced endothelial cell apoptosis. Capillary tube formation on Matrigel was completely abrogated by addition of aeroplysinin-1 at the low micromolar range. Aeroplysinin-1 also exhibited a clear inhibitory effect on the migration capabilities of endothelial cells. Zymographic assays showed that aeroplysinin-1 treatment produced a decrease in the concentration of matrix metalloproteinase-2 and urokinase in conditioned medium from endothelial cells. Finally, aeroplysinin-1 exhibited a dose-dependent inhibitory effect on the in vivo chorioallantoic membrane assay, showing potent apoptosis-inducing activity in the developing endothelium. The in vivo inhibition of angiogenesis by aeroplysinin-1 was confirmed by the Matrigel plug assay. Together, our data indicate that aeroplysinin-1 is a compound that interferes with key events in angiogenesis, making it a promising drug for further evaluation in the treatment of angiogenesis-related pathologies.

We have re-evaluated the selectivity of fumagillin against endothelial cell proliferation and compared it to the reported selectivity of its potent analog TNP-470. We showed that fumagillin does not inhibit endothelial cell proliferation in a specific manner, but on the contrary it inhibits the proliferation of other cell types at the same range of concentrations. Furthermore, the IC50 values of fumagillin for endothelial cells are two orders of magnitude higher than those values reported for TNP-470 on endothelial cells; on the contrary, the IC50 value of fumagillin for human breast cancer MDA-MB231 cells is four orders of magnitude lower than the value reported for TNP-470 on the same cell line.

We report four children with acute megakaryoblastic leukemia (AML-M7) and t(1;22)(p13;q13), two of them with Down syndrome; their ages were 7 months, and 6, 7, and 10 years. These findings differ from those reported in children with M7 and t(1;22) at the age of presentation (exclusively under 1-year-old) and in the two cases associated with Down syndrome (t[1;22],+21c) that may be due to the high heterogeneity of the chromosomal changes in children with AML. We cannot disregard ethnic difference distribution of chromosomal changes and age of presentation in Mexican children with AML.

Detection of human papillomaviruses DNA (HPV) in tumour samples is often determined by a PCR based approach with standard universal consensus oligonucleotides. It is shown that these primers under the same amplification conditions can amplify a human genomic sequence of 1361 nucleotides in oral carcinomas and normal DNA samples. This sequence is detected more easily as the copy number of HPV DNA decreases. Therefore, in tumour samples that have a low copy number of HPV or that are contaminated by normal tissue there is a potential risk of misidentification of the presence of HPV if this observation is not taken into account.

Background: Ehrlich ascites tumor is an experimental tumor model very suitable for performing comparative studies relating its growth in vitro and in vivo. We used this tumor model to study the potential modulatory effects of genistein and 2-methoxyestradiol, two anti-angiogenic compounds, on the proteolytic balance MMP/TIMP. Ehrlich cells grown in vitro secreted MMP-9, MMP-2 and two TIMPs; the treatment with either of the anti-angiogenic compounds here tested stimulated all these activities, but the increase in TIMPs activities of genistein-treated cells were higher than those of MMPs, thus inducing a decrease in the proteolytic balance. On the other hand, Ehrlich cells growing in vivo did not produce any detectable TIMP activity, but accumulated MMP-9 and MMP-2 during tumor growth. Both compounds induced significant decrease of MMPs activity when tumor cells were actively proliferating. It was concluded that both genistein and 2-methoxyestradiol could shift the proteolytic balance MMP/TIMP towards antiproteolysis in media or ascitic fluid conditioned by actively growing Ehrlich cells.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.

We report a woman with acute arsenic poisoning, who developed an erythroderma with vesicles and pustules after the ingestion of 8-16 g of sodium arsenite. Simultaneously, she presented a herpes simplex virus infection. Skin biopsies showed unique features which included multiple small pigment granules inside and outside the histiocytes. In our opinion, these findings are consistent with acute arsenic poisoning, and constitute the first histological description of this entity in skin.

We report two cases of myofibroblastoma with unusual pathological features, in a 66-year-old woman and a 49-year-old man. Both tumours were unilateral, grossly nodular and well circumscribed, but not encapsulated. The lesions were made up of bipolar spindle cells arranged in fascicular clusters separated by bands of hialinized collagen; one included several islands of mature cartilage next to fat cells. The other contained atypical mononucleated and multinucleated giant cells. No mitotic figures were observed. Immunohistochemically, both tumours showed strong and diffuse cytoplasmic staining for vimentin and CD 34 and focal positivity for alpha-smooth muscle actin, and both were negative for cytokeratins, CD 68, Ham 5, 6, Mac 387, and S-100 protein. Desmin was positive in one case. Ultrastructural study revealed populations composed of fibroblastic cells without signs of myofibroblastic differentiation in one case; the second featured abundant undifferentiated mesenchymal cells with myofibroblastic differentiation. Both patients remain disease-free 38 and 36 months after lumpectomy.

Dietary fatty acids are actively incorporated into membrane lipids, and fat intake can modify the composition and the biochemical activity of cellular membranes and the pattern of plasma lipoproteins. Industrial hydrogenation of polyunsaturated oils leads to the formation of isomeric trans fatty acids which are incorporated into cellular membranes when they are present in the diet. The trans fatty acid amount present in hydrogenated oils depends on the degree of hydrogenation, being high for partially hydrogenated oils and low for highly hydrogenated oils. Hydrogenated fish oil is widely used in some countries for the production of margarine and industrial fats. This study compares the fatty acid composition of plasma, erythrocytes, subcutaneous adipose tissue, and hepatic microsomal membranes and the plasma lipoprotein profile after feeding rats with a synthetic diet containing either fish oil, partially hydrogenated fish oil, or highly hydrogenated fish oil. It is observed that the tissue content of monounsaturated fatty acids increases and that the content of polyunsaturated fatty acids decreases after an increase of the degree of hydrogenation of the dietary fat. Tissues from animals fed partially hydrogenated fish oil show significant amounts of trans fatty acids only. The plasma triacylglyceride composition and the lipoprotein profile are also altered by the degree of hydrogenation of the dietary fat. Triacylglycerides decrease after highly hydrogenated fat feeding only. Total cholesterol and low-density lipoprotein cholesterol are significantly increased after partially hydrogenated fat feeding. Although no direct evidence is presented, this effect may be attributable to the high content of trans isomers of this dietary fat which nutritionally may behave as saturated fatty acids.

ATP hydrolysis from H+-ATPase of plasma membrane was measured in vesicles from maize embryos imbibed at times between 0 and 5 h. The activity had a maximum at 2 h of imbibition. In order to detect whether the enzyme had the same characteristics through the first 5 h of imbibition, vanadate and lysophophatydilcholine sensitivities, as well as trypsin, pH and temperature effects on the activity of the H+-ATPase from plasma membrane vesicles isolated from embryos imbibed at 0 or 5 h were studied. The results indicate that the activity expressed at 0 h is very different from the activity at 5 h. The activity from embryos imbibed for 5 h was less sensitive to vanadate, trypsin and lysophosphatidylcholine, more sensitive to denaturing temperatures and with a broader pH dependence, as compared to the activity from embryos that were not imbibed. When vanadate-sensitive ATPase activity was purified by anion exchange chromatography, the peaks obtained from the 0 and 5 h imbibed embryos were different and non-overlapping. These data could be interpreted in terms of different enzyme structures from dry and imbibed embryos due to either different primary structures or covalent modifications, or differences in membrane vicinities.

The degree of fat hydrogenation and the trans fatty acid content of the diet affect the fatty acid composition of membranes, and the amount and the activity of some membrane enzymes. We describe the effects of four isocaloric diets containing either sunflower oil (SO, 0% trans), fish oil (FO, 0.5% trans), partially hydrogenated fish oil (PHFO, 30% trans), or highly hydrogenated fish oil (HHFO, 3.6% trans) as fat sources on the lipid composition and the trans fatty acid content of rat hepatic microsomes. We also describe the effect of these diets on the cytochrome P-450 content and on the aminopyrine N-demethylase, aniline hydroxylase, and UDP-glucuronyl transferase microsomal activities. Cytochrome P-450 content was dependent on the degree of unsaturation of the diet, being higher for the FO-containing diet and lower for the HHFO diet. Aminopyrine N-demethylase activity also correlated with the degree of unsaturation of the diet as did the cytochrome P-450 content did (FO > SO > PHFO > HHFO). Aniline hydroxylase activity appeared to be independent of the degree of unsaturation of the dietary fat, but correlated with the trans fatty acid content of the diet, which was also reflected in the trans content of the microsomal membranes. UDP-glucuronyl transferase activity was higher for the FO-containing diet than for the SO diet, showing intermediate values after the PHFO and HHFO diets.

A total of 438 sera were collected from dairy goats on 10 farms located around Aregue Village, Lara State, Venezuela and evaluated for Toxoplasma gondii antibodies using the indirect hemagglutination assay. Antibodies to T. gondii were found in 26 of 386 > or =4-yr-old does from 8 of 10 farms; antibody titers were 1:64 (10 does), 1: 256 (3 does), 1:512 (5 does), 1:1,024 (1 doe), and 1:4,096 (7 does). Antibodies were not found in 52 <12-mo-old goats.

Metaplastic synovial cyst is a recently reorganized entity characterized by a cystic space lined by polygonal cells and villous structures resembling synovium pointing toward the lumen. It usually develops following trauma. We report a 15-year-old girl with Ehlers-Danlos syndrome who developed a nodular lesion of her elbow without previous trauma. Histopathological and immunohistochemical studies yielded results similar to those reported in cases of cutaneous metaplastic synovial cyst. This case appears to be the first one reported of cutaneous metaplastic synovial cyst associated with an Ehlers-Danlos syndrome. Cutaneous fragility and anomalous scarring typical of Ehlers-Danlos syndrome may be related to the development of this pseudocyst. If so, other connective-tissue diseases with increased skin fragility could be susceptible to development of such lesions.

Colorectal cancer has been studied from the point of view of the relationships between several variables, including proliferative activity and p53 protein expression. However, stereologic evaluation of nuclear size has not been thoroughly described. In the present study, measurements of the volume-weighted mean nuclear volume (nuclear Vv), have been performed in well, moderately and poorly differentiated colorectal adenocarcinomas and correlated with the Dukes' stage and other factors such as proliferative activity and p53 protein immunoreactivity. Although the mean values of nuclear Vv were higher in poorly differentiated cancers or Dukes' C&D stage than in well and moderately differentiated tumors or Dukes' A&B stage, these differences were not significant. However, the variability of nuclear size in colorectal cancers was more relevant than the mean values of nuclear Vv with respect to their invasive classification. The carcinomas which extended beyond the serosa (Dukes' stage C&D) had higher biologic variation than those grouped as Dukes' stage A&B. The results of the present study also indicate that nuclear size in colorectal cancers has a positive correlation with both proliferative activity and p53 protein expression. The relationship between nuclear Vv and proliferative activity emphasizes the possible prognostic relevance of this stereologic estimate of nuclear size in colorectal adenocarcinoma.

Intravenous leiomyomatosis is a very rare uterine neoplasm, characterized by histological benignity. In some cases, it could extend through the ovaric or iliac veins up to the vena cava and the right chambers of the heart. We report a patient with symptoms of right heart failure, who was diagnosed by transesophagic echocardiography of intravenous leiomyomatosis with extension to the right ventricle. Complete excision was achieved employing simultaneous sternotomy and laparotomy with echocardiographic intraoperative monitorization.

Alcohol ingestion may promote lipid peroxidation, and the presence of polyunsaturated fatty acids in liver lipids may be essential for the generation of liver damage through this mechanism. The aim of this study is to examine fatty acid composition of liver lipids in chronic alcoholics with and without histological liver damage. A percutaneous liver biopsy was performed to 28 patients hospitalized for treatment of their alcoholism. Liver total lipids were extracted from a portion of the tissue sample and fatty acid composition was measured by gas chromatography. Another piece of the sample was sent for histological study. Six patients had histological cirrhosis or alcoholic hepatitis in their biopsies, the rest of the patients had minimal changes. Patients with liver damage had higher levels of oleic acid and total monoenoic fatty acids, a higher 18:1/18:0 ratio, lower levels of polyunsaturated fatty acids, a lower 20:4/18:2 ratio, and a lower peroxidability index in liver total lipids, than patients without liver damage. Alcoholic patients with asymptomatic liver damage have less unsaturated fatty acids in liver total lipids than their counterparts with normal livers.

The objective was to know the principal risk factors that influence in the development of surgical would infection, and the economical saving achieved with the control of a single variable, that is, right prophylaxis. A prospective study was carried out at the Traumatology Department of La Paz Hospital. A total of 5260 patients operated during 1990-1993 are included. Active epidemiological surveillance was used to check patients; logistic regression was used in the multivariant analysis. The principal risk factors found were: immunodeficiency (OR = 8.67), incorrect healing (OR = 14.42), reoperated patient (patients who needed more than one surgical procedure while they are admitted; reoperations) (OR = 3.57), type of surgery (OR = 4.71) and wrong prophylaxis (OR = 6.36). Making constant all the variables except for prophylaxis, we calculated the percentage of infections prevented by a right prophylaxis, and the cost was calculated starting from the number of extra days of infection. The number of infections prevented during the four years was 310, saving a total of 194 million pesetas (1.5 million dollars), due to right prophylaxis. Cost-benefice ratio = 1/17. We consider of special importance to control this manipulable risk factor, in order to avoid the development of infections.

We report a case of synchronous squamous cell carcinoma and signet ring cell carcinoma in an augmented bladder 22 years after ileocystoplasty. The clinical features, predisposing factors and pertinent literature are reviewed.

Purpose: To compare a procedure of blood processing via a quadruple bag for the preparation of white-cell-poor blood components with the results obtained with triple-bag-system, in order to adopt it as routine in our blood centre., Material and Methods: Blood was collected in 289 quadruple-bag-system containing 63 mL of CPD as anticoagulant and 100 mL of SAG M solution as additive for the red cells. We used 237 standard quadruple-bags supplied by Fenwal (195) and NPBI (42), and 52 of the top-and-bottom system supplied by Fenwal. Blood separation was made automatically by CompomatR (NPBI) and platelet concentrates were prepared from the buffy-coat fraction. Standard bags were processing as follows: After the first centrifugation of the whole blood (28,800 g), the plasma was transferred into the 300-mL bag until the interface of red cells and plasma was detected; then approximately 80 mL of plasma and buffy-coat (BC) were collected into the 100-mL satellite bag. Top-and-bottom bags were centrifuged at 43,500 g., the red-cells were transferred into the bottom-bag containing SAGM, and plasma was transferred into the top-bag. The buffy-coat fraction remains in the original bag. In both procedures, platelet concentrates were prepared from buffy-coat fraction. After the centrifugation of this fraction (1,400 g and 1,600 g), the supernatant (concentrated platelets in plasma) was transferred into a 300-mL bag and the bag with the residual buffy-coat was then discarded. 287 triple-bags were separated in the traditional way, using platelet-rich plasma (PRP) as a source for the preparation of platelet concentrate (PC). Volumes were measured by weigh and specificity gravity. Platelet, leukocytes and red-cells were counted in the Coulter-Counter (STKR.Izasa). T-Student test and Chi2 test were used for statistical analysis and p < 0.05 was taken as a significant difference between samples., Results: The three kinds of quadruple-bags showed results very homogeneous with little differences. For all brand of bags packed-red-cells showed a volume of 300 +/- 2.9 mL, EVF of 51.9 +/- 0.7%. The recovery of red cells into the packed red cells and of platelets into the platelet concentrate was 90 +/- 0.4 percent and 69 +/- 2 percent respectively, of the original value. White cells in the packed red cells were 9.7 +/- 03 x 10(9) with recovery of 30.1 +/- 1.4 percent of the original value; statistical difference was found in comparison with triple bags PRC (p < 0.001). The PC volumes averaged 71 +/- 1 mL and the overall mean platelet concentration was 77 +/- 2 x 10(9). Eighty three percent of PC contained more than 55 x 10(9). White cells contamination of platelet concentrates was 0.283 +/- 0.039 x 10(9), with a recovery of 9.5 +/- 1.5 percent of the leukocytes present in the whole blood. This value is below the threshold that prevents febrile reactions and microaggregate formation. The plasma yield in the quadruple-bag system was much greater than that in the triple-bag system (p < 0.001). With this process we removed about 77 +/- 0.5 percent of the plasma present in the original unit in comparison with 56 +/- 1 percent removed in that of the triple-bag system., Conclusion: With this procedure leukocyte-poor blood components are obtained in which more of 90 percent original white cells have been removed, with a red-cell recovery of 90 percent. Moreover, the plasma yield is also excellent.

The important physiological properties described for marine oils rich in n-3 polyunsaturated fatty acids have give rise to increasing efforts to develop procedures for obtaining, preserve and concentrate these oils aiming its nutritional and pharmacological use. The fish meal industry provides high quantities of fish oil, however this oil being not suitable for human consumption must be subjected to different refining procedures to allow its use for feeding purposes. This review describes the current research about the employment of different procedures to incorporate n-3 polyunsaturated fatty acid to our feeding. The feasibility for the application of chemical methods and stereospecific enzyme-transesterification procedures for obtaining oil concentrates, and the use of natural substances for stabilizing the oil against oxidation are discussed. The possibility that some birds such as the chicken, feeding a diet rich in n-3 polyunsaturated fatty acids, as a healthy, safe and suitable vehicle to provide these fatty acid for human nutrition is also discussed.

Renal angiomyolipoma is a relatively uncommon entity which can occur either as a solitary angiomyolipoma or associated to a systemic condition such as Bourneville's disease or tuberous sclerosis. Presentation of one case of a large, fast growing renal angiomyolipoma associated to pregnancy, which required surgery during the third month of pregnancy.

A sensitive method for the determination of boldine in blood plasma is described. The procedure involves a direct pH-buffered chloroform extraction of boldine from blood plasma, followed by its assay under isocratic conditions by HPLC with UV detection. The extraction recovery is excellent, and sensitivity and precision of the method are very high, when applied to plasma samples containing pharmacologically relevant concentrations of boldine.

We studied 11 patients with severe mitral regurgitation (MR). With 2-D echocardiogram we could obtain the septal and posterior wall thickness, left ventricular internal dimensions and ventricular function. With parasternal short axis view we calculate the h/r ratio (left ventricular thickness/radius). The results were compared with normal values: we found important left atrial and ventricle dilatation with significative difference from the normal values (P < 0.001), the diastolic and systolic h/r ratio was significative lower than the normal values (P < 0.005): the systolic wall stress was significative higher in relation to normal values (P < 0.001). We conclude that patients with severe (MR) initially have an important ventricular dilatation but no hypertrophy despite volume overload. The possible explanation is that in early stages of the disease, the afterload of the left ventricle is low and does not trigger the development of hypertrophy. The hypertrophy appears only when the systolic stress is high secondary to myocardial failure. The excessive dilatation of the left ventricle probably damages the myocardial fibers by excessive stretch. This mechanism probably explains the poor late surgical evolution of patients with mitral prosthesis. This we propose that the optimal surgical timing for such patients is when the systolic wall stress elevates over the normal limits, because this is an early sign of myocardial failure.

We describe a modified colorimetric method that quantitates inorganic phosphate linearly up to 60 nmol, with high stability of the developed color and with a low interference by ATP concentration (up to 30 mM). This method is very suitable for use in ATPase enzymatic assays, especially with enzymes that have low specific activities and (or) high Km values for ATP.

The effect of an allelopathic compound, diacetyl-piquerol on the H(+) -ATPase activity of the microsomal fraction from the radicles of a common weedIpomoea purpurea was studied. The diacetyl-piquerol inhibited the germination and radicle growth fromI. purpurea; the radicle growth was increasingly inhibited (10% to 100%) as piquerol concentrations were raised (10 μM to 1000 μM). The H(+)-ATPase activity was inhibited (48%) by 500 μM diacetyl-piquerol, and this inhibition was higher in plasma membrane ATPase (67.2%) than in tonoplast membrane ATPase (31.4%). Additional studies of the precise physiological mechanisms of interference caused by allelopathic compounds are needed.