Current aspects of hemolytic uremic syndrome in children

The authors are approaching the problem of hemolytic uremic syndrome, a common cause of acute renal failure in children. This review present an update about the pathophysiology of typical hemolytic uremic syndrome, useful for understanding the clinical picture and the base for some modern therapeutical models. Concerning the evolution, the authors underline the importance of identifying the risk factors for acute phase, the extrarenal manifestations being considered of vital risk. The atypical hemolytic uremic syndrome still has some uncertainties; the article try to make a synthesis of ethiopathogeneity, clinical manifestations, evolution and therapeutical modern approaches.     

Polymorphisms in the human monomethylarsonic acid (MMA V) reductase/hGSTO1 gene and changes in urinary arsenic profiles

Large interindividual variability in urinary arsenic profiles, following chronic inorganic arsenic exposure, is well-known in humans. To understand this variability, we studied the relationship between polymorphisms in the gene for human monomethylarsonic acid (MMA(V)) reductase/hGSTO1 and the urinary arsenic profiles of individuals chronically exposed to arsenic in their drinking water. To ensure that we did not overlook rare polymorphisms, not included in the public databases, we amplified and sequenced all six exons of the gene and their flanking regions, using DNA isolated from peripheral blood samples of 75 subjects, living in the vicinity of Torreon, Mexico. Four groups, based on the levels of arsenic (9-100 microg/L) in their drinking water, were studied. We identified six novel polymorphisms and two reported previously. The novel polymorphisms were a three base pair deletion (delGGC) in the first intron; a G > C transversion, leading to a serine-to-cysteine substitution at amino acid 86; a G > T transversion and a A > T transversion in intron 5; a G > A transition resulting in glutamate-to-lysine substitution in amino acid 208; and a C > T transition producing an alanine-to-valine substitution in amino acid 236. Two subjects displayed significant differences in patterns of urinary arsenic; they had increased levels of urinary inorganic arsenic and reduced levels of methylated urinary arsenic species as compared to the rest of the study population. These two subjects had the same unique polymorphisms in hGSTO1 in that they were heterozygous for E155del and Glu208Lys. The identified SNPs may be one of the reasons for the large interindividual variability in the response of humans to chronic inorganic arsenic exposure. The findings suggest the need for further studies to identify unambiguously specific polymorphisms that may account for interindividual variability in the human response to chronic inorganic arsenic exposure.     

Pathology of posterior capsule,a literature review

The posterior capsule opacification (PCO) is a frequent complication in the modern cataract surgery, uncomfortable for the patient and expensive for the health care system. According to prof. Apple, the main health care expenditure in U.S. is represented by cataract surgery, laser capsulotomy for PCO ranking next. Under these circumstances, it is not surprising that the lens bag pathology and the prevention of aftercataract hold the attention of many research groups all over the world. This paper is a literature review of the last 15 years, presenting the data we have considered to be the most significant.     

DOTA-NOC,a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals

Earlier studies have shown that modification of the octapeptide octreotide in positions 3 and 8 may result in compounds with increased somatostatin receptor affinity that, if radiolabelled, display improved uptake in somatostatin receptor-positive tumours. The aim of a recent research study in our laboratory was to employ the parallel peptide synthesis approach by further exchanging the amino acid in position 3 of octreotide and coupling the macrocyclic chelator DOTA(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to these peptides for labelling with radiometals like gallium-67 or -68, indium-111, yttrium-90 and lutetium-177. The purpose was to find radiopeptides with an improved somatostatin receptor binding profile in order to extend the spectrum of targeted tumours. A first peptide, [¹¹¹In,⁹⁰Y-DOTA]-1-Nal³-octreotide (¹¹¹In,⁹⁰Y-DOTA-NOC), was isolated which showed an improved profile. In^III-DOTA-NOC exhibited the following IC₅₀ values (nM) when studied in competition with [¹²⁵I][Leu⁸, d-Trp²², Tyr²⁵]somatostatin-28 (values for Y^III-DOTA-NOC are shown in parentheses): sstr2, 2.9±0.1 (3.3±0.2); sstr3, 8±2 (26±1.9); sstr5, 11.2±3.5 (10.4±1.6). Affinity towards sstr1 and 4 was very low or absent. In^III-DOTA-NOC is superior to all somatostatin-based radiopeptides having this particular type of binding profile, including DOTA-lanreotide, and has three to four times higher binding affinity to sstr2 than In^III,Y^III-DOTA-Tyr³-octreotide (In^III,Y^III-DOTA-TOC). In addition, [¹¹¹In]DOTA-NOC showed a specific and high rate of internalization into AR4-2J rat pancreatic tumour cells which, after 4 h, was about two times higher than that of [¹¹¹In]DOTA-TOC and three times higher than that of [¹¹¹In]DOTA-octreotide ([¹¹¹In]DOTA-OC). The internalized radiopeptides were externalized intact upon 2 h of internalization followed by an acid wash. After 2–3 h of externalization a plateau is reached, indicating a steady-state situation explained by reactivation of the receptors followed by re-endocytosis. Biodistribution studies in CA 20948 tumour-bearing rats showed rapid clearance from all sstr-negative tissues except the kidneys. At 4 h the uptake of [¹¹¹In]DOTA-NOC in the tumour and sstr-positive tissues, such as adrenals, stomach and pancreas, was three to four times higher than that of [¹¹¹In]DOTA-TOC. Differential blocking studies indicate that this is at least partially due to the uptake mediated by sstr3 and sstr5. These very promising preclinical data justify the use of this new radiopeptide for imaging and potentially internal radiotherapy studies in patients.Abbreviations of the common amino acids are in accordance with the recommendations of IUPAC-IUB [IUPAC-IUB Commission of Biochemical Nomenclature (CBN), Symbols for amino-acid derivatives and peptides, recommendations 1971. Eur J Biochem 1972; 27:201–207].     

Breast conserving surgery --7 years of experience

The breast cancer treatment is based nowadays on a new surgical option: breast-conserving surgery, which is reliable at least for the first and second stage of cancer, with radical intention, obviously. We have started to practice the breast-conserving surgery in our surgical clinic (at CFR Hospital, from Craiova) for 7 years; until now we have performed 159 breast-conserving operation and, as results, we have recorded 3 local recurrences (2.12%) and 1 death due to cancer evolution. Our protocol includes removal of the primary tumor with enough surrounding tissue to ensure negative margins of resectable specimen, associated with total axillary lymph-node dissection and postoperative breast irradiation. Our oncologist on different postoperative conditions indicated the chemotherapy: tumor size, axillary lymph node involvement, patient age, etc. The purpose of this paper is to emphasize our unassuming experience but especially to draw attention on important results, obtained by long-term monitoring the patient who underwent breast-conserving surgery, in a two prospective protocols, which demonstrate the importance and applicability of breast-conserving therapy. The conclusion of this study is that breast-conserving surgery followed by breast irradiation is reliable, as the results are similar with the radical mastectomies; the main objective is to obtain a good cosmetic result, which depends on tumor size/size of the breast ratio.     

Malignant peripheral nerve sheath tumor cell invasion is facilitated by Src and aberrant CD44 expression

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies that arise within peripheral nerves. These tumors occur with increased incidence in patients with neurofibromatosis type 1 (NF1), exhibiting increased Ras activity due to loss of the NF1 gene product, neurofibromin, and abnormal expression of the epidermal growth factor receptor (EGFR). We previously found that MPNSTs express increased levels of the CD44 family of transmembrane glycoproteins that have been implicated in tumor cell invasion and metastasis. In two MPNST cell lines, we have found that elevated CD44 expression and cell invasion are dependent on Src kinase activity but are independent of mitogen-activated protein kinases (MAPK) kinase (MEK) activity. In contrast, inhibition of Src kinase activity has no influence on MPNST cell proliferation. Reduction of CD44 levels, using antisense oligonucleotides, results in reduced MPNST cell invasion in vitro, suggesting that Src contributes in part to MPNST cell invasion by increasing CD44 levels. At least some of this increased CD44 expression results from elevated EGFR levels through a Src-dependent mechanism, consistent with the notion that EGFR promotes constitutive Src activation in MPNSTs. These data indicate that Src and CD44 are putative targets for the treatment of MPNST invasion and metastasis.     

Influence des acides gras polyinsaturés n-3 et des antioxydants alimentaires sur les acides gras de la viande et la lipoperoxydation chez le bovin en finition

This study aimed at analysing the impact, on beef lipids and fatty acids and on beef colour, of dietary lipid supplements provided by extruded linseeds (rich in n-3 polyunsaturated fatty acids, n-3 PUFA) alone or with extruded rapeseed (rich in n-6 and n-3 PUFA and in 18:1n-9) in association or not with dietary antioxidants in cull dairy cows in finition. Dietary linseeds increased significantly proportions of 18:3n-3 (+56% and +36% respectively), of total trans 18:1 (+66% and +105%); and of 9cis,11trans 18:2 (CLA) (+50% and +41%) in Longissimus thoracis and Semitendinosus muscles, 18:3n-3 and CLA being known to be beneficial for the human health. Antioxidant supplements (association of vitamin E with plant extracts rich in polyphenols, PERP) reinforced the stimulating effect of lipid supplements on proportions of 18:3 n-3, 18:1trans, and 9cis,11trans 18:2 in lipids of the two muscles. Dietary n-3 PUFA reduced the capacity of plasma to resist against lipoperoxidation (−11%) favouring the formation of peroxides such as conjugated dienes (× 1.75) and malonedialdehyde (MDA, ×2). Intensity of lipoperoxidation tended to increase in beef packaged under modified atmosphere rich in oxygen (O₂/CO₂: 70/30) of the linseed group (2.96 μg/g fresh tissue) when compared to that in the control group (2.19 μg/g, p = 0.1). Combined supply of vitamin E and PERP efficiently protected beef against lipoperoxidation, even in beef packaged under modified atmosphere rich in oxygen. Beef samples packaged under air from cows of the linseed group exhibited a more intense red colour than that of cows of the control group. In cows of the linseed group submitted to an emotional stress 2 hours before slaughtering, beef samples packaged under the air or the O₂-rich atmosphere had a red colour with a lower intensity that beef samples from cows of the linseed plus antioxidants group. In conclusion, feeding strategy for finishing cull cows combining lipid (from linseed rich in n-3 PUFA) and antioxidant (vitamin E + PERP) supplements improve the health value of beef fatty acids avoiding the major risks of beef lipoperoxidation and of alteration of beef colour whatever (i) the conditions of beef ageing and packaging (especially with O₂), (ii) the level of emotional stress of animals just before slaughtering.