On Nov 18, 4:29 pm, ironjustice <teamtan...@hotmail.com> wrote:The
thread was .. IS .. chemotherapy causes .. autoimmunity.He says
chemotherapy causes autoimmunity .. not ALL .. autoimmunity. <<

"wonderfully unexpected"

http://pubs.acs.org/cen/news/85/i37/8537notw1.html

September 10, 2007 Volume 85, Number 37 p. 8
Antibiotics
All Roads Lead To Hydroxyl Radicals
Compounds with different targets trigger common killing mechanism
Celia Arnaud

Kathleen Fink/Boston University

Collins (standing left), grad students Michael Kohanski (seated left)
and Carolyn Lawrence, and postdoc Daniel Dwyer figured out that
bactericidal antibiotics have a common death mechanism.THE MAJOR
CLASSES of bacteria-killing antibiotics may not be as different as
previously thought. Antibiotics are usually classified by their
primary target--DNA replication, protein synthesis, or cell-wall
synthesis. James J. Collins, professor of biomedical engineering at
Boston University, and coworkers now report that these seemingly
different antibiotics trigger a common cell death mechanism downstream
of their initial targets, generating hydroxyl radicals that damage
DNA, proteins, and lipids (Cell 2007, 130, 797). The findings point
the way to improving existing antibiotics.

Scott F. Singleton, an associate professor of medicinal chemistry and
natural products at the University of North Carolina School of
Pharmacy, calls the results "wonderfully unexpected, but in a way that
makes one say, 'Of course, why didn't we see that before?' "

The hydroxyl radicals are the product of an oxidative damage pathway,
the authors find. The interaction between each of the antibiotics and
its target triggers the tricarboxylic acid (TCA) cycle in as-yet-
unknown ways. The TCA cycle produces the reduced form of the cofactor
nicotinamide adenine dinucleotide (NADH), which shuttles electrons
down the electron transport chain of the respiratory pathway.
Increased electron transport activity stimulates the production of
superoxide, which in turn attacks iron-sulfur clusters in proteins.
The Fe2+ that is liberated from these proteins fuels the Fenton
reaction, in which Fe2+ reacts with hydrogen peroxide to form hydroxyl
radicals. These hydroxyl radicals wreak havoc on bacterial DNA,
proteins, and lipids, ultimately killing the cell.

Some antibiotics inhibit cell growth rather than killing the bacteria
outright. These so-called bacteriostatic antibiotics don't stimulate
the hydroxyl radicals, Collins says, nor do sublethal concentrations
of bactericidal antibiotics.

This work "foreshadows the development of adjuvants for antibiotic
chemotherapy," Singleton says, referring to small molecules that could
enhance the performance of existing antibiotics. Such a prospect has
not been lost on Collins. For example, the protein RecA serves as a
gatekeeper to the so-called SOS damage response that bacteria muster
to repair their DNA. A small-molecule RecA inhibitor used in
combination with existing antibiotics could make for "super"
antibiotic duos, Collins says.

Collins doesn't think that this hydroxyl radical pathway will help
against already-resistant bugs because most resistance mechanisms
target the interaction between the drug and its primary target. "We
think that this pathway is actually a downstream consequence of the
interactions of these antibiotics with their respective targets," he
says. "If resistance has already emerged, it's likely that this
pathway is not being triggered." Exploiting this pathway, however,
might stave off the development of resistance in the first place,
Collins notes.

Many scientists have been puzzled that "nature has devised antibiotics
that interfere with only a handful of cellular targets in the
bacteria," says Shahriar Mobashery, a chemist who studies antibiotics
and antibiotic resistance at the University of Notre Dame. The paucity
of targets has been hailed as a reason we might run out of clinical
options for treating bacterial infections. "Perhaps the triggering of
this oxidative damage is at play," Mobashery says. "Perhaps that
triggering event is seen only with inhibition of a handful of cellular
targets."

Chemical & Engineering News
ISSN 0009-2347
Copyright (c) 2007 American Chemical Society

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<<

Proteinuria manifests when one goes to altitude and when one goes to
altitude one manifests  increased red blood cell production /
erythrocytosis / polycythemia / hemochromatosis / iron overload..

"Proteinuria at high altitude.Proteinuria at high altitude. A
Bradwell
and J Delamere. Full text ... Pines A. High-altitude acclimatization
and proteinuria in East Africa. ...
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1599488 -  "

Proteinuria is a marker used by .. them .. to assess disease
activity / severity.

Proteinuria is a .. bad .. thing ..
Proteinuria appears in kidney disease .. in fact it is THE marker to
assess kidney function.
"Coincidentally" .. to .. **everyone** .. it seems .. increased red
blood cell production .. CAUSES .. kidney disease ..
Soooo .. the increased red blood cell production / erythrocytosis /
polycythemia / hemochromatosis / iron overload .. destroys the
kidneys ..

Pretty simple.

http://kidney.niddk.nih.gov/kudiseases/pubs/proteinuria/

<<snip>>
Serum ferritin levels are increased in patients with glomerular
diseases and proteinuria
<<snip>>

NDT Advance Access originally published online on August 17, 2004
Nephrology Dialysis Transplantation 2004 19(11):2754-2760; doi:
10.1093/
ndt/gfh454

Nephrol Dial Transplant Vol. 19 No. 11 (c) ERA-EDTA 2004; all rights
reserved

---------------------------------------------------------------------------------
Original Article

Serum ferritin levels are increased in patients with glomerular
diseases and proteinuria
Amanda J. W. Branten1, Dorine W. Swinkels2, Ina S. Klasen2 and Jack
F.
M. Wetzels1
1 Department of Medicine, Division of Nephrology and 2 Department of
Clinical Chemistry, University Medical Center, Nijmegen, The
Netherlands

Correspondence and offprint requests to: A. J. W. Branten, MD,
Department of Medicine, Division of Nephrology 545, University
Medical
Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Email: A.Bran...@nier.umcn.nl

Abstract

Background. Ferritin is a high molecular weight protein which
reflects
body iron stores, but may also rise in the case of an acute phase
response. Recently, ferritin has been identified as a predictive
factor in the development and progression of atherosclerosis. This is
the first report on serum ferritin levels in patients with
proteinuria.

Methods. We have analysed the data of 142 male patients with a
glomerular disease, and proteinuria exceeding 1 g/day. In all
patients, we measured various parameters related to proteinuria,
serum
ferritin and serum iron. Serum ß2-microglobulin and the Modification
of Diet in Renal Disease (MDRD) equation were used as measures of the
glomerular filtration rate (GFR).

Results. Mean age (±SD) was 46±15 years, MDRD-GFR 57±25 ml/min/1.73
m2
and median proteinuria 8.0 g/day [interquartile range (IQR) 3.6-13].
Serum albumin (29±9 g/l) and transferrin levels (1.7±0.5 g/l) were
low, and cholesterol levels were elevated (median 7.3, IQR 5.9-9.5
mmol/l). Median serum ferritin was 148 µg/l (IQR 89-282), and
exceeded
280 µg/l, the upper limit of normal, in 36 patients (25%). Elevated
serum ferritin levels could not be explained by an acute phase
response as determined by C-reactive protein, or haemochromatosis
(DNA
analysis). Regression analysis showed an independent relationship
between ferritin levels and serum cholesterol, GFR and serum
transferrin.

Conclusions. Serum ferritin levels are elevated in patients with
overt
proteinuria. The independent negative relationship between serum
ferritin and transferrin points to a specific process and suggests
that increased production of ferritin may compensate for the loss of
the iron-binding protein transferrin, thus reducing the amount of
free
iron. Further studies are needed to elucidate the role of ferritin in
patients with proteinuria, especially because of the suggested
association between ferritin and atherosclerosis.

Keywords: ferritin; glomerulopathy; iron; proteinuria
-------------------------

Hyperuricemia, hypertension, and proteinuria associated with high-
altitude polycythemia
Auteur(s) / Author(s)
JEFFERSON J. Ashley ; ESCUDERO Elizabeth ; HURTADO Maria-Elena ;
PANDO
KELLY Jackeline ; SWENSON Erik R. ; WENER Mark H. ; BURNIER Michel ;
MAILLARD Marc ; SCHREINER George F. ; SCHOENE Robert B. ; HURTADO
Abdias ; JOHNSON Richard J. ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
Department of Medicine and Laboratory Medicine, University of
Washington Medical Center, Seattle, WA, ETATS-UNIS
The Carlos Monge Cassinelli Nephrology Center, Hospital Loayza,
Division of Nephrology, University Cayetano Heredia, Lima, PEROU
Division of Hypertension and Vascular Medicine, Centre Hospitalier
Universitaire Vaudois, Lausanne, SUISSE
Scios Inc, Sunnyvale, CA, ETATS-UNIS
Department of Medicine, Baylor College of Medicine, Houston, TX,
ETATS-
UNIS

Résumé / Abstract
 Chronic exposure to high altitude is associated with the
development
of erythrocytosis, proteinuria, and, in some cases, hyperuricemia. We
examined the relationship between high-altitude polycythemia and
proteinuria and hyperuricemia in Cerro de Pasco, Peru (altitude,
4,300
m). We studied 25 adult men with hematocrits less than 65% and 27
subjects with excessive erythrocytosis (EE; hematocrit > 65%) living
in Cerro de Pasco, Peru and compared them with 28 control subjects
living in Lima, Peru (at sea level) and after 48 hours of exposure to
high altitude. Serum urate levels were significantly elevated in
patients with EE at altitude, and gout occurred in 4 of 27 of these
subjects. Urate level strongly correlated with hematocrit (r = 0.71;
P
< 0.0001). Urate production (24-hour urine urate excretion and urine
urate-creatinine ratio) was increased in this group compared with
those at sea level. Fractional urate excretion was not increased, and
fractional lithium excretion was reduced, in keeping with increased
proximal reabsorption of filtrate. Significantly higher blood
pressures and decreased renin levels in the EE group were in keeping
with increased proximal sodium reabsorption. Serum urate levels
correlated with mean blood pressure (r = 0.50; P < 0.0001).
Significant proteinuria was more prevalent in the EE group despite
normal renal function. Hyperuricemia is common in subjects living at
high altitude and associated with EE, hypertension, and proteinuria.
The increase in uric acid levels appears to be caused by increased
urate generation secondary to systemic hypoxia, although a relative
impairment in renal excretion also may contribute.
Revue / Journal Title
American journal of kidney diseases  (Am. j. kidney dis.)  ISSN
0272-6386
Source / Source
2002, vol. 39, no6, pp. 1135-1142 (36 ref.)
Langue / Language
Anglais

Editeur / Publisher
Elsevier, Orlando, FL, ETATS-UNIS (1981) (Revue)

Mots-clés anglais / English Keywords
Hemopathy ; Urinary system disease ; Cardiovascular disease ;
Metabolic diseases ; Enzyme ; Oxidoreductases ; Oxygen ; Purine ;
Human ; Hypoxia ; Uric acid ; Hematocrite ; Serum ; Quantitative
analysis ; Urate oxidase ; Chronic ; High altitude ; Polycythemia ;
Association ; Proteinuria ; Hypertension ; Hyperuricemia ;
Mots-clés français / French Keywords
Hémopathie ; Appareil urinaire pathologie ; Appareil circulatoire
pathologie ; Métabolisme pathologie ; Enzyme ; Oxidoreductases ;
Oxygène ; Purine ; Homme ; Hypoxie ; Urique acide ; Hématocrite ;
Sérum ; Analyse quantitative ; Urate oxidase ; Chronique ; Haute
altitude ; Polyglobulie ; Association ; Protéinurie ; Hypertension
artérielle ; Hyperuricémie ;
Mots-clés espagnols / Spanish Keywords
Hemopatía ; Aparato urinario patología ; Aparato circulatorio
patología ; Metabolismo patología ; Enzima ; Oxidoreductases ;
Oxígeno ; Purina ; Hombre ; Hipoxia ; Urico ácido ; Hematocrito ;
Suero ; Análisis cuantitativo ; Urate oxidase ; Crónico ; Gran
altura ; Policitemia ; Asociación ; Proteinuria ; Hipertensión
arterial ; Hiperuricemia ;
Localisation / Location
INIST-CNRS, Cote INIST : 19098, 35400010824325.0020

Copyright 2007 INIST-CNRS. All rights reserved

Toute reproduction ou diffusion même partielle, par quelque procédé
ou
sur tout support que ce soit, ne pourra être faite sans l'accord
préalable écrit de l'INIST-CNRS.
No part of these records may be reproduced of distributed, in any
form
or by any means, without the prior written permission of INIST-CNRS.

Nº notice refdoc (ud4) : 13701434

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Jesus Was A Vegetarian!
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