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Our results from the cross-sectional study of patients
treated
with HAART receiving subcutaneous IL-2 supported the
findings
of the longitudinal study of patients receiving nucleoside
analogues
with intravenous IL-2 In the HAART-treated cohort! a lower
"#$
T-cell proliferation was observed in patients treated with
IL-2
compared to controls in a wide %& log' range of viral
loadInterestingly! this difference seemed to depend on the higher
"#$
T-cell counts of the IL-2 recipients! and thus correlated with
the
desired biologic effect of intermittent IL-2 immunotherapy
Although an alternative interpretation
could be that different infection times in the 2 groups led to
these findings! the IL-2 group had a
significantly longer time since diagnosis This is presumably
a
close surrogate for time of infection Additionally! the
longitudinal
randomi(ed study confirmed these findings in a group of
patients
with suboptimal virologic control! where the added effect of
viral
load on T-cell proliferation could also be studied In a
randomi(ed
study testing the use of corticosteroids to improve the
tolerance of
IL-2 cycles! in patients receiving HAART! it was also found that
the blunted "#$ T-cell e)pansions in the patients treated
with
steroids and IL-2 were associated with smaller *i+, decreases in
the
"#$ T cell pool compared to the group that received IL-2
alone
The fact that IL-2 leads to rises of specific subsets of "#$
T cells! naive and recall memory! without affecting the effector
pool
is most relevant for its potential clinical applications given
the
recently described dichotomy of functional characteristics
of
memory T cells&!&+ Our results suggest that
although no bene ficial
effect toward active infections should be anticipated! one
may
e)pect improvement of host defenses against recall or
neoantigens
and that the timing of IL-2 with respect to immuni(ations should
be
carefully designed "onsidering the fact that immunologic
chal-
lenges with remote recall or neoantigens are infre.uent in
adults!
the clinical efficacy of this approach will ta/e time to
establish
0hase & clinical trials addressing this .uestion&,
are ongoing with results anticipated in $ to year
in summary! intermittent IL-2 administration to HI1-infected
patients decreased activation and proliferation of "#$T
cellsThese decreases were observed in
the naive! recall memory! and"#2"#$ T-cell subsets! were
independent of viral load
changes! and correlated strongly with the degree of "#$ T-cell
e)pansions These data suggestthat intermittent IL-2 treatment in
HI1 infection could be viewed predominantly as
immunotherapy targeting and reversing increased T-cell
proliferation and immune
activation
il2 menstimulasi cd$
il2 proliferasi cd$
virus masu/ cd$ turun!il2 tinggi
cd$ tetep ga nae/
factor e)hausted turun /e IL-2
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Metabolit aktif DMBA ini dapat membentuk DNA Adduct
danmenginduksi reactie oxygen spesies (ROS) (eimer et al!"
#$$$)!Reacti%e oxygen species(ROS) yang terangkut aliran
dara&keseluru& tubu& akan menyebabkan inflamasi
sistemik padauterus
!Reacti%e oxygen species yang mengalami peningkatan
sangatberba&aya karena memiliki sifat reaktifitas
tinggi!'eberadaan ROSyang berlebi&an akan menyebabkan teradinya
stres oksidatif!
Stres oksidatif teradi karena adanya ketidak seimbangan
antararadikal bebas dan antioksidan dalam tubu& yang
dapatmenyebabkankerusakan sel yang ditandai dengan penurunankadar
antioksidan tubu& (i*riyana" #$+$)Sel yang mengalami kerusakan
akan mengakti%asi pelepasan darimediator inflamasi! Adanya mediator
inflamasi akan mendorongakti%asi dari platelet se&ingga
menyebabkan peningkatanpermeabilitas dan dilatasi dari pembulu&
dara&! 'eadaanini akan memicu monosit ke bagian aringan yang
mengalami luka
dan berdiferensiasi menadi makrofag (Boyer et al!"
#$$$)! Akti%asimakrofag meng&asilkan radikal bebas dan
sitokinproinflamasi ,-.#!(Abbas et al!" +//+)! ,nterleukin.#
akanmenstimulasi teradinya inflamasi sistemik pada
uterus!,nterleukin# merupakan &asil sekresi dari sel 0&+
yang terakti%asiole& akti%itas makrofag akan merangsang sel
tersebutuntuk memperbanyak diri dan meng&asilkan sitokin yang
lebi& aktiflagi (1ampbell" #$$2)! 3ernyataan tersebut
menyebabkan ekspresi
,-.# pada aringan uterus meningkat! Sitokin ,-.# berfungsi
sebagaifaktor pertumbu&an autokrin dan memicu pertumbu&an
dandiferensiasi sel 0 1D4 menadi sel 0 sitotoksik (Abbas et al!"
+//+)
Abbas" A!'!" A!5! -ic&tman and 6!S! 3ober! +//+!
1ellular andmolecular immunology! B Saunders
1ompany73&iladelp&iaBoyer" B!" A!M! 8alles and N! 9dme!
#$$$! ,nduction and regulationof epit&elial.mesnc&ymal
transitions! Bioc&em 3&armacol! :$7+$/+.+$//i*riyana" M!A!"
#$+$! 3engaru& pemberian ekstrak 9uc&ema
spinom ter&adap kadar glukosa dalam dara& dan
akti%itassuperoksida dismutase (SOD) pada tikusterpapar multiple
lo;
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NOVEL METHODOLOGY FOR THESYNTHESIS OF XANTHONES
Jeremy Morgan Naidoo
A dissertation submitted to the Faculty of Science,
University of the Witwatersrand, Johannesburg,
in fulfilment of the requirements for the
Degree of Master of Science
March !!" The xanthone nucleus comprises of an
important class of the oxygenatedheterocycles9. The growing
interest in this class of compounds has beenassociated
with its diverse pharmacological properties.
Pharmacologicalinvestigations of xanthones date back to 1968
when !hattacharya reported the diureticand cardiotonicactions of
the natural glycoside mangeferin "10#1$.Figure 3: The
structure of mangeferin "10#.%iscussed below are a few xanthones
that exhibit activity against cancer&'()*'%+and malaria
,ore recently natural xanthones have shown activity against the
humanimmunode-ciency virus "&'(#. *part from their activity
against the virusdirectlymany xanthones have secondary therapeutic
properties against fungalinfections inimmune)compromised patients
due to acuired
immunode-ciencysyndrome"*'%+#/9.SERTIFRAN!HESIDE+wertifrancheside
""## a complex xanthone containing compound was-rst isolated
by 0ordell and co)workers in 199 from Swertia
franchetiana$.+wertifrancheside""## is a 2avone xanthone glycoside
and is a moderately potent inhibitorof &'(reverse
transcriptase.3ver the past 45 years substantial progress has been
made in de-ningstrategies forthe treatment of &'( infection the
cause of *'%+1. +ince reversetranscriptase isreuired early in
proviral synthesis4 inhibition of reverse
transcriptase)catalyed
