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Biochemistry. 2002 Sep 24;41(38):11466-71.
Identification of oxidized derivatives of neuroketals.

Bernoud-Hubac N, Roberts LJ 2nd.

Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6602, USA.

Oxidative stress and protein aggregation have been implicated in the pathogenesis of neurodegenerative diseases. The formation of neuroprostanes, isoprostane-like compounds formed from oxidation of docosahexaenoic acid, which is uniquely enriched in the brain, is increased in Alzheimer's disease. We recently identified the formation of a new class of highly reactive gamma-keto aldehydes, neuroketals, in vivo as products of the neuroprostane pathway. Neuroketals adduct to lysine residues of proteins with remarkable rapidity and induce cross-linking. Because neuroketals have either a 1,4-pentadiene or 1,4,7-octatriene side chain structure, we hypothesized that they could undergo further oxidation to form neuroketals with an additional hydroxyl group. Oxidation of docosahexaenoic acid in vitro yielded a series of compounds that were confirmed to be oxidized neuroketals by mass spectrometric analyses. Analysis of oxidized neuroketal adducts during oxidation of docosahexaenoic acid in the presence of lysine revealed the formation of oxidized Schiff base and hydroxylactam adducts. Oxidized hydroxylactam neuroketal-lysyl protein adducts, analyzed after digestion of proteins to individual amino acids, were not detected in nonoxidized rat brain synaptosomes but were readily detected following oxidation of synaptosomes. These studies indicate that neuroketals can undergo further oxidation, which in turn suggests that measurement of only unoxidized neuroketal adducts likely underestimates the amount of neuroketal adducts present in the brain in disorders of oxidant stress.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234189&dopt=Abstract

Kidney Int. 2002 Oct;62(4):1187-95.
High-protein induced renal enlargement is growth hormone independent.

van Neck JW, Cingel V, van Vliet AK, Drop SL, Flyvbjerg A.

Laboratory of Pediatrics, Subdivision of Molecular Endocrinology, Erasmus University/Sophia Children's Hospital Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. vanneclch.fgg.eur.nl

BACKGROUND: Growth hormone (GH) and insulin-like growth factors (IGFs) have been postulated as pathogenic factors in several forms of renal growth, including that induced by high-protein (HP) diets. Compensatory renal growth (CRG) following renal uninephrectomy is strictly GH dependent, while the exact role of GH as a regulating factor in HP induced renal growth has not been fully clarified. METHODS: To elucidate a possible direct role for GH in HP-induced renal growth, we examined the effect of a newly developed specific GH-receptor (GHR) antagonist (B2036-PEG) on renal growth and renal GH/IGF-system expression in HP-fed mice. RESULTS: Mice fed a HP diet (45% protein) for one week demonstrated renal hypertrophy and increased renal IGF-I. GH receptor antagonist (GHRA) treatment neither modified renal IGF-I nor abolished the renal hypertrophy. In contrast, however, GHRA administration did modify renal mRNA expression of many members of the GH and IGF systems. CONCLUSIONS: The major new finding is that HP-induced renal growth in adult mice is GH independent.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234289&dopt=Abstract

Kidney Int. 2002 Oct;62(4):1196-207.
Reduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients with advanced secondary hyperparathyroidism.

Tokumoto M, Tsuruya K, Fukuda K, Kanai H, Kuroki S, Hirakata H.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Tokumotntmed2.med.kyushu-u.ac.jp

BACKGROUND: In uremic patients with secondary hyperparathyroidism (2HPT), nodular hyperplasia of parathyroid gland shows a monoclonal pattern of cell proliferation, in which a decreased density of vitamin D receptor (VDR) also is demonstrated. The present study aimed at elucidating the mechanism of parathyroid cell proliferation in relation to cell cycle determinants in patients with advanced 2HPT. METHODS: The expression of cyclin-dependent kinase inhibitors, p21 and p27, and VDR were examined and compared among four groups of nodular (Nd; N = 23) or diffuse (Df; N = 6) hyperplastic parathyroid glands resected due to 2HPT, primary adenomas (Ad; N = 15), and histologically-normal parathyroid glands (C; N = 20) removed during thyroidectomy. Immunohistochemical analyses for VDR, p21, p27 and Ki67 antigen were performed in formalin-fixed paraffin-embedded tissues by using specific polyclonal antibody. The distribution and the intensity of immunoreactivity was quantified by using NIH imaging, and was expressed as the labeling index (LI) of positive nuclear staining in a random set of 1000 cells. RESULTS: p21 LI was significantly diminished in both Nd (85 +/- 110; mean +/- SD) and Ad (136 +/- 122) as compared to that in Df (360 +/- 191) or C (359 +/- 228; P < 0.01). p27 LI was also significantly diminished in both Nd (97 +/- 156) and Ad (187 +/- 196) as compared to that in Df (532 +/- 146) or C (631 +/- 170; P < 0.01). VDR LI in Nd (162 +/- 194) was also significantly lower than that in Df (495 +/- 337), Ad (383 +/- 262), or C (659 +/- 234), respectively (P < 0.01). Parathyroid sections with high nuclear VDR expression elicited high p21 and p27 expression. Both p21 and p27 LI in Nd correlated significantly with nuclear VDR LI (r = 0.92; P < 0.01, r = 0.76; P < 0.01), but not with p53 LI, and inversely correlated with the glandular weight (r = 0.44; P < 0.05, r = 0.41; P < 0.05). CONCLUSIONS: The reduced expression of p21 and p27, in a VDR-dependent manner, is a major pathogenic factor for a nodular parathyroid gland growth.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234290&dopt=Abstract

Kidney Int. 2002 Oct;62(4):1338-48.
Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome.

Dran GI, Fernandez GC, Rubel CJ, Bermejo E, Gomez S, Meiss R, Isturiz MA, Palermo MS.

Division Medicina Experimental, Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Capital Federal, Buenos Aires, Republica Argentina. colodraotmail.com

BACKGROUND: Nitric oxide (NO) is an endogenous vasodilator and platelet inhibitor. An enhanced NO production has been detected in patients with hemolytic uremic syndrome (HUS), although its implication in HUS pathogenesis has not been clarified. METHODS: A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to study the role of NO in the development of the disease. Modulation of l-arginine-NO pathway was achieved by oral administration of NO synthase (NOS) substrate or inhibitors, and renal damage, mortality and platelet activity were evaluated. The involvement of platelets was studied by means of a specific anti-platelet antibody. RESULTS: Inhibition of NO generation by the NOS inhibitor L-NAME enhanced Stx2-mediated renal damage and lethality; this effect was prevented by the addition of l-arginine. The worsening effect of L-NAME involved enhanced Stx2-mediated platelet activation, and it was completely prevented by platelet depletion. CONCLUSIONS: NO exerts a protective role in the early pathogenesis of HUS, and its inhibition potentiates renal damage and mortality through a mechanism involving enhanced platelet activation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234304&dopt=Abstract

J Appl Microbiol. 2002;93(4):566-76.
Antifungal activities of two Lactobacillus plantarum strains against Fusarium moulds in vitro and in malting of barley.

Laitila A, Alakomi HL, Raaska L, Mattila-Sandholm T, Haikara A.

VTT Biotechnology, Espoo, Finland. arja.laitiltt.fi

AIMS: The Lactobacillus plantarum strains VTT E-78076 (E76) and VTT E-79098 (E98) were studied for their antifungal potential against Fusarium species. METHODS AND RESULTS: In vitro screening with automated turbidometry as well as direct and indirect impedimetric methods clearly showed Lact. plantarum cell-free extracts to be effective against Fusarium species including Fusarium avenaceum, F. culmorum, F. graminearum and F.oxysporum. However, great variation in growth inhibition was observed between different Fusarium species and even between strains. The antifungal potential of Lact. plantarum E76 culture, including cells and spent medium, was also examined in laboratory-scale malting with naturally contaminated two-rowed barley from the crops of 1990-96. The growth of the indigenous Fusarium flora was restricted by the addition of Lact. plantarum E76 to the steeping water. However, the antifungal effect was greatly dependent on the contamination level and the fungal species/strains present on barley in different years. CONCLUSIONS: Lactobacillus plantarum strains E76 and E98 had a fungistatic effect against different plant pathogenic, toxigenic and gushing-active Fusarium fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicates that Lact. plantarum strains with known and selected characteristics could be used as a natural, food-grade biocontrol agent for management of problems caused by Fusarium fungi during germination of cereals.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234339&dopt=Abstract

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