Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 11234-11238 29

and neuronal drop out. Spreading infection is demonstrated among human monocytes in mouse brains when monocytes are inoculated 1 day after infection with
HIV-1. ABC was administered to SCID mice prior to the intracerebral inoculation
of HIV-1 infected monocytes. Mice were sacrificed at 1, 7 and 14 days after
inoculation.
Results: Histologic analysis showed an increase in percentage of HIV-1 infected monocytes, from < 1% to 70%, in control mice over the experimental time
period. Drug treated mice showed a 50-80% decrease in the numbers of HIV-1
infected monocytes. Vital loads performed on mouse brain tissue showed about
a 1 log decrease with ABC treatment.
Conclusion: These data suggest that ABC can reduce spreading infection in
brains of SCID mice with encephalitis. Studies with ZDV and d4T (also reported
to achieve good brain drug levels) are in progress.
S11234 Effects of glycyrrhizin on opportunistic Candida albicans
infection in MAIDS mice
Tokuichiro Utsunomlya', M. Kobayashi', R.B. Pollard', M. Ito2, F. Suzuki1.
SUniversity of Texas Medical Branch, Galveston, Texas 77555-0835, USA;
2 Yamanashi Medical University, Yamanashi, Japan
Objective: It has been reported that type 2 T cell responses (T2 responses)
play an important role in the pathogeneses of Candida albicans (C. albicans)
infection in immunocompromized hosts. A predominance of T2 responses has
been shown in MAIDS mice. As the modulatory activity of glycyrrhizin (GR) on
the differentiation of T cells into T2 cells was demonstrated, the present study
investigated the anti-fungal effects of GR on C. albicans infection in MAIDS mice.
Methods: GR was kindly supplied by Minophagen Pharmaceutical Co., Tokyo,
Japam. C57BL/6 mice were inoculated i.p. with 0.1 ml of culture fluids of SC-1
cells persistently infected with LP-BM5 MuLV. Eleven weeks after the viral infection, these mice were exposed to 1 x 105 cells/mouse of C. albicans, and treated
with GR every other day beginning 3 days before fungal infection for a total of 10
injections. For the production of cytokines, splenic mononuclear cell (SMNC) from
mice 11 weels after the viral infection were stimulated with 10 /tg/ml of anti-CD3
mAb for various hrs.
Results: The susceptibility of MAIDS mice to the fungal infection was 100 times
higher than that of normal mice. Also, normal mice treated with a mixture of type
2 cytokines (IL-4 and IL10) were susceptible to C. albicans infection at the same
levels observed in MAIDS mice. In MAIDS mice treated with GR, the susceptibility
to infection from these pathogens was recovered to levels observed in normal
mice. After stimulation with anti-CD3 mAb, SMNC from MAIDS mice produced
type 2 cytokines into their culture fluids. However, these cytokines produced were
not demonstrated in cultures of SMNC from MAIDS mice treated with GR.
Conclusions: An opportunistic infection of C. albicans in MAIDS mice was
controlled by GR. The increased susceptibility of MAIDS mice to fungal infection
was influenced by T2 responses induced by LP-BM5 MuLV, and GR regulated
the development of MAIDS-associated T2 responses. These results suggest that
GR may have an anti-fungal activity on C. albicans infection in MAIDS mice.
S11235 | Antifungal effects of lanoconazole on Cryptococcus
neoformans infection in MAIDS mice
Fujio Suzuki, K. Furukawa, H. Sasaki, R.B. Pollard. University of Texas Medical
Branch, Galveston, Texas, USA
Objective: Cryptococcus (C.) neoformans, a common opportunistic fungal
pathogen, has been shown as a serious pathogenic organism in patients with
AIDS. Even with aggressive chemotherapy, the high mortality rates of AIDS
patients infected with C. neoformans have persisted. In the present study, the
effects of a new antifungal drug, lanoconazole, on the infection of C. neoformans
in MAIDS mice were investigated.
Methods: MAIDS mice (C57BL/6 mice infected with 4.5 x 102 PFU/mouse
of LP-BM5 MuLV), 50 days after infection were exposed intratracheally to C.
neoformans, strain 613D. These mice were treated with a 10 mg/kg oral dose
of lanoconazole (Tsumura Co., Tokyo, Japan), or fluconazole (a positive control)
once daily for 30 days beginning 1 day after the fungal infection. Antifungal effects
of the two compounds were determined by the reduction in numbers of C. neoformans cells in lungs and brains of infected mice. Type 2 T cell responses were
determined as a titer of IL-4 and IL-10 in culture fluids of splenic cells derived from
infected MAIDS mice. Cytokines produced by anti-CD3 mAb stimulated splenic
cells were determined by ELISA.
Results: The growth of C. neoformans in brains was equally inhibited in normal
mice after treatment with lanoconazole or fluconazole. However, in MAIDS mice,
inhibitory efficiencies of lanoconazole on the fungal growth was greater than that
of fluconazole. The inhibitory effect of fluconazole on fungal growth was reduced
in normal mice treated with a mixture of type 2 cytokines. However, the antifungal
effect of lanoconazole showed no reduction in normal mice treated with a type 2
cytokine mixture.
Conclusions: The growth of C. neoformans was inhibited in MAIDS mice
treated with lanoconazole. The antifungal activity of fluconazole was influenced

by type 2 cytokines, whereas no inhibition was seen in lanoconazole activity. These results may suggest the potential of lanoconazole in AIDS patients
infected with C. neoformans.

1112361

A prospective, controlled study to evaluate the effect of
an essential sterol and sterolin formulation as a putative
immune modulator in FIV (feline immunodeficiency virus)
infected laboratory cats

Johan Lamprecht, P. Bouic', M. Freestone2, M. Austin1. Dept. of Pharmacology,
Faculty of Medicine; 'University of Stellenbosch, PO Box 19063, Tygerberg,
Cape Town; 2Essential Sterolin Product, Cape Town, South Africa
Background: The results of a small pilot study treating FIV infected domestic
cats with capsules containing a combination of BSS (Betasitosterol) and BSSG
(Betasitosterol glucoside) in the naturally occurring ratio supported the anecdotal
success of an African folk remedy and the results of vitro studies with HIV. A
controlled prospective study in FIV infected laboratory cats was planned.
Methods: Two small groups (13 and 12) of purpose bred, random source
domestic cats, housed in an access controlled facility were used in the study. The
groups were similar in genetic origin, sex, age, weight and randomly selected.
Both groups were infected with the Petaluma strain of FIV. One group was treated
once daily with a capsule containing the active ingredients while the other served
as a control. Blood sampling and clinical examination was done weekly for 6
weeks and thereafter once every 6 weeks for a total of 63 weeks. Repeated
measured analysis was done on various parameters and tested for statistical
significance. These included sero conversion, Full Blood Count, Lymphocyte
subsets, Blood Chemistry, Lymphadenopathy scoring, Weight and Temperature.
The female cats were also allowed to breed with uninfected males and the kitten
survival was monitored. Surviving kittens were tested for FIV antibodies 3 months
after birth.
Results: Significant differences in CD4 counts, Total lymphocyte counts, Weight
and kitten survival were noted between the two groups. The untreated group also
exhibited a dramatic deterioration in general condition and behaviour. All surviving kittens tested FIV negative at three months of age. No clinical or laboratory
evidence of toxicity was found in the treated group.
Conclusions: The preliminary analysis of the results supports the hypothesis
that this formulation is an immune modulator in FIV infected domestic cats and
that treated queens have greater breeding success than untreated queens. These
results suggest that a larger study should be undertaken, investigating the reason
for better kitten survival and that that this formulation should be studied in humans
with HIV infection.
i 11237 Evaluation of the corneal endothelium in rabbits treated
with subconjunctival ganciclovir (DHPG)
Maria De Lourdes Veronese Rodrigues, M. Saad Avila Morales, L. Ventura,
S.J. Faria Esousa, J. Coutinh O Neto, N.V. Souza, J.F. Castro Figueiredo.
Tamoios 262-ap 101, 14020-700 Ribeirao, Fac. Medicina Ribeirao Preto
(FMRP-USP), Laboratorio Fisica Oftalmica FMRP-USP Ribeirao Preto, SP
Brasil
Objectives: To detect possible changes in the corneal endothelium at different
times after subconjunctival DHPG injection.
Design: A prospective, masked, experimental study.
Methods: The study was conducted on 24 eyes of 12 rabbits who received 8
mg of DHPG diluted in 0.16 ml distilled water in one eye and the same volume of
distilled water in the other eye (control). The rabbits were picked at random for
sacrifice at different times (24, 48 and 72 hours after injection). The eyes were
enucleated under aseptic conditions, placed in sterilized flasks containing physiological saline with the cornea looking up and examined by specular microscopy.
The specular microscopy was performed by a investigator that did not know the
kind of treatment administered to each eye.
Results: All the eyes of the rabbits sacrificed 24 hours after the experiment
presented excellent or good endothelial cell density, regardless of whether they
had received DHPG or distilled water. In the rabbits sacrificed 48 hours after
the experiment, the corneal endothelium was in excellent condition in three eyes
injected with DHPG and in all the controls, whereas the remaining one presented
endothelial edema in the lower part, with good conditions in the remainder of the
cornea. In the group sacrificed 72 hours after the injection, the endothelium of
two eyes that had received DHPG and in two control eyes we noted infiltration
and alterations in the corneal endothelial layer.
Conclusions: Subconjunctival injection of 8 mg DHPG seems not to be toxic
to corneal endothelium of rabbits after 24 and 48 hours of injection. The lesion
observed in one eye after 48 hours was focal, with preserved endothelial cellular
density in other regions. Furthermore, the alterations observed in the corneal
endothelium after 72 hours were similar in controls and treated eyes.
546*/11238 Attenuated SIV vaccines: Safety and efficacy
following heterologous challenge
Mark G. Lewis', F. Novembre2, R. Desrosiers3, Y. Lu4, E. Rud5, V. Hirsch6,
D. Birx7. 1 Henry M. Jackson Foundation, 1600 E. Gude Dr., Rockville MD
20850; 2Yerkes Primate Center, Atlanta GA; 3New England Primate Center,
Southborough MA; 4 Virus Research Institute, Cambridge MA; 6National
Institutes of Health NIAID-LID, Rockville MD; 7WRAIR-Retrovirology, Rockville
MD, USA; 5Health Canada, Ottawa OT, Canada
Objectives: To determine the degree of protection stimulated by attenuated SIV
vaccines.

Design: Two nef deleted SIV were evaluated: SIVmac239Anef and SIVsmPBj6.6Anef
Each isolate was constructed with a large nef gene deleted and a frame shift