4 research outputs found
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
- Author
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- The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
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- Publication venue
- Publication date
- 09/08/2008
- Field of study
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Association of cerebral malaria and TNF-α levels: a systematic review
- Author
- A Kantele
- A Mergani
- AN Atallah
- AR Berendt
- BD Akanmori
- BD Akinori
- BG MordmĂŒller
- CD Mulrow
- D Kwiatkowski
- D Moher
- D Prakash
- D Sullivan
- DA Hassan
- E Rovira-Vallbona
- F Esamai
- FE McKenzie
- FG Fowkes
- FM Omer
- FS Bondi
- GE Grau
- H Armah
- H Armah
- H Balshem
- H Brown
- H Hananantachai
- HC van der Heyde
- IM Medana
- J Lou
- J May
- JB de Souza
- JD Harris
- JL Baptista
- KE Lyke
- L Schofield
- LC Maia
- LH Miller
- LJMC Carvalho
- M Clarke
- ME Molyneux
- MK Pereira
- N Shaffer
- NH Hunt
- NJ White
- NJ White
- NPJ Day
- OPG Nmorsi
- P Deloron
- P Kinra
- P Nicolas
- PAHO-WHO
- PE Thuma
- R Idro
- R Manish
- R Tuteja
- R Ubalee
- R Udomsangpetch
- RW Snow
- RW Steketee
- S Cabantous
- S Chuncharunee
- T Nebl
- The Africa malaria report
- U Sahu
- V Combes
- VHM Tchinda
- W McGuire
- World report malaria
- Y Maneerat
- YC Martins
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Vision: Geniculocortical System
- Author
- A Cowey
- A Cowey
- A Cowey
- A Cowey
- A Cowey
- A Peters
- A Schwartz
- AB Wetzel
- AC Norton
- AC Norton
- AC Rosenquist
- AE Jones
- AJ Sefton
- AL Pearlman
- AM Laties
- AS Schwartz
- B Fischer
- B Fischer
- B Grafstein
- BB Boycott
- BB Boycott
- BD Thuma
- BG Cleland
- BG Cleland
- BG Cleland
- BG Cleland
- BG Cleland
- BH Bland
- BM Dow
- BV Updyke
- C Blakemore
- C Enroth-Cugell
- C Kupfer
- C Winkler
- CB Ware
- CB Ware
- CC Wood
- CL Taravella
- CM Butter
- CR Michael
- CR Michael
- D Denny-Brown
- D Lewellyn
- D Lindsley
- DA Dalby
- DA Pollen
- DA Pollen
- DE Joshua
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Hubel
- DH Kelly
- DL Stewart
- DW Watkins
- E Marg
- E Poppel
- E Poppel
- EG Keating
- EG Shkolnik-Yarros
- EG Shkolânick-Yarros
- EH Murphy
- EH Murphy
- EH Murphy
- ET Rolls
- EW Bough
- F Koerner
- F Lepore
- F Sanides
- FH Lopes da Silva
- FW Atencio
- FW Campbell
- FW Campbell
- FW Campbell
- G Baumgartner
- G Burrows
- G Holmes
- G Riddoch
- G Walls
- G Walls
- GB Arden
- GS Brindley
- H Barbas
- H Buchtel
- H HollÀnder
- H Horel
- H Ikeda
- H Ikeda
- H Ikeda
- H Ikeda
- H Ikeda
- H Ikeda
- H Killackey
- H Killackey
- H Killackey
- H KlĂŒver
- H Nöda
- H Spekreijse
- H Suzuki
- H WĂ€ssle
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HB Barlow
- HJ Freund von
- HL Teuber
- I Bodis-Wollner
- I Bodis-Wollner
- IT Diamond
- J Baden
- J Leicester
- J Packwood
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Stone
- J Szentagothai
- J TerBraak
- JA Movshon
- JC Urbaitis
- JD Pettigrew
- JE Dowling
- JE Dowling
- JG Malpeli
- JH Kaas
- JH Kaas
- JH Kaas
- JH Kaas
- JH Kaas
- JJ Braun
- JK Harting
- JL Kennedy
- JL Kennedy
- JL Kennedy
- JL OâLeary
- JP Ward
- JT Mcllwain
- JT Mcllwain
- K Albus
- K Albus
- K Albus
- K Niimi
- K Sanderson
- K Spence
- K Tansley
- KJ Sanderson
- KJ Sanderson
- KJ Sanderson
- KJ Sanderson
- KL Chow
- KL Chow
- KL Chow
- KP Hoffmann
- KP Hoffmann
- KS Lashley
- KS Lashley
- KU Smith
- KU Smith
- KU Smith
- KU Smith
- KU Smith
- KU Smith
- KU Smith
- KU Smith
- KV Anderson
- L Garey
- L Maffei
- L Maffei
- L Maffei
- L Maffei
- L Maffei
- L Weiskrantz
- L Weiskrantz
- L Weiskrantz
- L Weiskrantz
- L Weiskrantz
- L Weiskrantz
- LH Craft
- LJ Garey
- M Bekoff
- M Bender
- M Berkley
- M Bilge
- M Fillenz
- M Glickstein
- M Glickstein
- M Glickstein
- M Jacobson
- M Minkowski
- M Mishkin
- M Snyder
- M Snyder
- M Snyder
- MA Berkley
- ME Wilson
- MR Matthews
- MS Loop
- MTT Wong-Riley
- N Humphrey
- NW Daw
- NW Daw
- P Cornwell
- P Glees
- P Gouras
- P Pasik
- P Pasik
- P Schilder
- P Schilder
- P Schilder
- PC Dodwell
- PD Spear
- PD Spear
- PD Spear
- PD Wilson
- PM Daniel
- PM Meyer
- PM Meyer
- PO Bishop
- PO Bishop
- PO Bishop
- PO Bishop
- R Galambos
- R Jung
- R Kanagasuntheram
- R Malmo
- R Otsuka
- R Rodieck
- R Thompson
- R Tusa
- RF Fox
- RF Sarmiento
- RH Steinberg
- RH Wurtz
- RL deValois
- RR Mize
- RT Marrocco
- RW Doty
- RW Doty
- RW Guillery
- RW Guillery
- RW Guillery
- RW Guillery
- RW Rodieck
- RW Rodieck
- S LeVay
- S LeVay
- S Polyak
- S Polyak
- SA Winans
- SJ Ramon
- SM Sherman
- SS Winans
- SW Alder
- SW Kufifler
- T Pasik
- TJ Tucker
- TN Wiesel
- TN Wiesel
- TT Norton
- UC DrÀger
- UC DrÀger
- VA Casagrande
- W Marshall
- W Pitts
- W Richards
- W Singer
- W Singer
- WA Beresford
- WC Hall
- WC LeGros
- WEC LeGros
- WEC LeGros
- WJ Kinston
- WR Hayhow
- WR Levick
- WR Levick
- Y Fukuda
- Y Fukuda
- Y Fukuda
- Y Fukuda
- Z Wiesenfeld
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1978
- Field of study
Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial
- Author
- Abach J
- Abdallah J
- Abdallah S
- Abdallah S
- Aberle-Grasse J
- Abimiku A
- Abishev A
- Abongomera G
- Aboud M
- Aboud M
- Abramovitz D
- Abrams E
- Abrams E
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- Abravaya K
- Abreu L
- Achra A
- Adera F
- Adetokunboh O
- Adeyemi O
- Adeyemi O
- Adipo T
- Affolabi D
- Agegnehu D
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- Agolory S
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- Agot K
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- Aguiar P
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- Agutu C
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- Ahmed S
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- Ahmed S
- Aizire J
- Ajibola G
- Ajok S
- Albert-Hope C
- Alejos B
- Alexander G
- Alicea C
- Allen H
- Allen M
- Allen S
- Allen S
- Allen S
- Alloui C
- Altice F
- Altice F
- Amara R
- Ambani A
- Ambrose K
- Amico R
- Amin J
- Amin T
- Amole C
- Amoros I
- Anahtar M
- Ananworanich J
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- Ancuta P
- Andama A
- Anderegg N
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- Anderson E
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- Andrade A
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- Angelidou K
- Anglaret X
- Anoma C
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- Ardiet D
- Arellano G
- Arenas-Pinto A
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- Publication venue
- 'International AIDS Society'
- Publication date
- 01/01/2016
- Field of study
Meeting abstract FRAB0101LB from 21st International AIDS Conference 18â22 July 2016, Durban, South Africa.
Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIVâinfected adults and children with advanced disease in subâSaharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown.
Methods:
The REALITY 2Ă2Ă2 factorial openâlabel trial (ISRCTN43622374) randomized ARTânaĂŻve HIVâinfected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (antiâtuberculosis) and fluconazole (antiâcryptococcal/candida), 5 days azithromycin (antiâbacterial/protozoal) and singleâdose albendazole (antiâhelminth)), versus standardâofâcare cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixedâdose combination. Two other randomizations investigated 12âweek adjunctive raltegravir or supplementary food. The primary endpoint was 24âweek mortality.
Results:
1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% lossâtoâfollowâup). Median baseline CD4 was 36 cells/mm3 (IQR: 16â62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54â0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58â0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2).
Conclusions:
Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIVâinfected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this lowâcost broad infection prevention package which could save 3.3 lives for every 100 individuals treated