Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.
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PMID:QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. 1122 80

Thirty-three HIV-seronegative adults were recruited into a Phase I safety and immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic, monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant administered by intramuscular delivery; and a similar product encapsulated in biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids, administered by the oral route. These were administered in three sequential oral doses, followed by a parenteral boost. No serious adverse experiences were observed. Oral administration of this vaccine, alone or in combination with parenteral boosting, resulted in no significant humoral, cellular, or mucosal immune responses.
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PMID:A Phase I safety and immunogenicity trial of UBI microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects. 1131 97

Ions of structure R(2)N[N(O)NO](-) and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety of electrophilic aza- or nitroaromatic substrates to form O(2)-arylated derivatives of structure R(2)N-N(O)=N-OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R(2)N[N(O)NO](-) to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the S(N)Ar reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These O(2)-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly to eject the zinc, disrupting a structural motif critical to viral replication and suggesting possible utility in the drug discovery realm.
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PMID:The secondary amine/nitric oxide complex ion R(2)N[N(O)NO](-) as nucleophile and leaving group in S9N)Ar reactions. 1132 74

Quinolinate (pyridine-2,3-dicarboxylic acid, Quin) is a neurotoxic tryptophan metabolite produced mainly by immune-activated macrophages. It is implicated in the pathogenesis of several brain disorders including HIV-associated dementia. Previous evidence suggests that Quin may exert its neurotoxic effects not only as an agonist on the NMDA subtype of glutamate receptor, but also by a receptor-independent mechanism. In this study we address ability of ferrous quinolinate chelates to generate reactive oxygen species. Autoxidation of Quin-Fe(II) complexes, followed in Hepes buffer at pH 7.4 using ferrozine as the Fe(II) detector, was found to be markedly slower in comparison with iron unchelated or complexed to citrate or ADP. The rate of Quin-Fe(II) autoxidation depends on pH (squared hydroxide anion concentration), is catalyzed by inorganic phosphate, and in both Hepes and phosphate buffers inversely depends on Quin concentration. These observations can be explained in terms of anion catalysis of hexaaquairon(II) autoxidation, acting mainly on the unchelated or partially chelated pool of iron. In order to follow hydroxyl radical generation in the Fenton chemistry, electron paramagnetic resonance (EPR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was employed. In the mixture consisting of 100 mM DMPO, 0.1 mM Fe(II), and 8.8 mM hydrogen peroxide in phosphate buffer pH 7.4, 0.5 mM Quin approximately doubled the yield of DMPO-OH adduct, and higher Quin concentration increased the spin adduct signal even more. When DMPO-OH was pre-formed using Ti3+ /hydrogen peroxide followed by peroxide removal with catalase, only addition of Quin-Fe(II), but not Fe(II), Fe(III), or Quin-Fe(III), significantly promoted decomposition of pre-formed DMPO-OH. Furthermore, reaction of Quin-Fe(II) with hydrogen peroxide leads to initial iron oxidation followed by appearance of iron redox cycling, detected as slow accumulation of ferrous ferrozine complex. This phenomenon cannot be abolished by subsequent addition of catalase. Thus, we propose that redox cycling of iron by a Quin derivative, formed by initial attack of hydroxyl radicals on Quin, rather than effects of iron complexes on DMPO-OH stability or redox cycling by hydrogen peroxide, is responsible for enhanced DMPO-OH signal in the presence of Quin. The present observations suggest that Quin-Fe(II) complexes display significant pro-oxidant characteristics that could have implications for Quin neurotoxicity.
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PMID:Quinolinic acid-iron(ii) complexes: slow autoxidation, but enhanced hydroxyl radical production in the Fenton reaction. 1137 28

Cutaneous fungal infections in immunocompromised patients can be aggressive and difficult to treat. To determine the safety and efficacy of oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with human immunodeficiency virus (HIV) infection or diabetes, 2 prospective, randomized, open-label studies were conducted in general community and referral centers. HIV-positive (n = 6) and diabetic patients (n = 8) between the ages of 18 and 75 years diagnosed with either tinea corporis or tinea cruris, as confirmed by potassium hydroxide (KOH) wet mount microscopy, were randomized to receive either 1 or 2 weeks of the antifungal treatment. Patients received oral terbinafine 250 mg once daily for 1 or 2 weeks. Main outcome measures were mycological cure, determined at week 6 for HIV-positive and diabetic patients. Three subjects were excluded from the efficacy analyses because of negative cultures at screening (n = 2) and lack of follow-up cultures (n = 1). Efficacy results were similar between the 1- and 2-week groups in both studies. All HIV-positive subjects and 83% of diabetic subjects achieved mycological cures at week 6 based on culture results. In a safety population that included all randomized patients (N = 14), no subject experienced adverse events or significant changes in laboratory findings related to study medication. Results of these small series indicate that a short course of oral terbinafine 250 mg once daily is a safe and effective treatment for tinea corporis or tinea cruris in subjects with HIV infection or diabetes.
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PMID:Safety and efficacy of short-duration oral terbinafine for the treatment of tinea corporis or tinea cruris in subjects with HIV infection or diabetes. 1149 30

Anti-idiotypic antibodies (Ab2) mimicking antigens (Ags)-defined by antibodies (Ab1) directed to tumors or pathogens have elicited Ag-specific humoral, cellular and/or protective immunity in experimental animals and in humans. In immunizations of rodents with Ab1, factors such as animal species, form of Ab1 and choice of adjuvant are crucial for the successful induction of Ab2 as candidate vaccines against tumors and pathogens. Here we survey the outcome of 362 fusion events (each event representing one animal), using nine immunization schedules in mice and seven schedules in rats and including 10 different Ab1 directed against human tumor- and immunodeficiency virus (HIV-1)-associated Ags. Ab1 IgG or F(ab')2 were administered uncoupled or coupled to keyhole limpet hemocyanin (KLH). As adjuvants, complete and incomplete Freund's adjuvant (CFA/IFA), lipid A, aluminum hydroxide, TiterMax or vaccinia virus were used. In syngeneic immunizations with murine Ab1 in mice, F(ab')2 coupled to KLH and emulsified in CFA/IFA preferentially induced Ab2 mimicking tumor or HIV-1 associated epitopes. In xenogeneic immunizations with mouse Ab1 in rats, various forms of Ab1 and adjuvants successfully induced Ab2 mimicking tumor Ags.
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PMID:Immunization procedures for anti-idiotypic antibody induction in mice and rats. 1219 16

A preformulation study was performed for the evaluation of a vaccine candidate against HIV-1. Aluminium hydroxide was used in the preformulation. However, this adjuvant is not a good adsorbent for basic proteins since it is positively charged at a physiological pH. In the present study, we determined the adsorption of TAB9 (basic protein, pI: 11.3) by treating Alhydrogel with different ions. The immunogenicity of the vaccine candidate against HIV was also evaluated using three batches, 9801-A, 9802-A and 9803-A, and a placebo P-001. The evaluation was performed twice (0 and 9 months). Each batch was tested using groups of 10 mice that had a single inoculation. The results showed that the protein was totally adsorbed to the aluminium gel. Seroconvertion was attained in all analysed batches, indicating the potentiality of TAB9 as a vaccine candidate.
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PMID:Preformulation study of the vaccine candidate TAB9 against HIV-1. 1224 57

Stretches of guanines can associate in vitro through Hoogsteen hydrogen bonding to form four-stranded structures. In the HIV-1 central DNA flap, generated by reverse transcriptase at the end of retrotranscription, both the two 99 nt-long overlapping (+) strands contain two adjacent tracts of guanines. This study demonstrates that oligonucleotides containing these G-clusters form highly stable G-quadruplexes of various structures in vitro, whose formation was controlled by an easy and reversible protocol using sodium hydroxide. Among these sequences, a G'2 hairpin dimer was the most stable structure adopted by the 5'-tail of the (+) downstream strand. Since the two (+) strands of the HIV-1 central DNA flap hold these G-clusters, and based on the properties of reverse branch migration in DNA flaps, constructions using HIV-1 sequences were assembled to mimic small DNA flaps where the G-clusters are neighbors. G-quartets were successfully probed in such flaps. They were induced by potassium and by a dibenzophenanthroline derivative already known to stabilize them. Such results suggest some function(s) for G-quartets associated with a DNA flap in the HIV-1 pre-integration steps, and argue for their transient formation during the processing of G-rich DNA flaps at the time of replication and/or repair.
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PMID:G-quartets assembly within a G-rich DNA flap. A possible event at the center of the HIV-1 genome. 1246 53

An increased prevalence of candidal carriage and oral candidiasis is common in cases of human immunodeficiency virus (HIV) infection, and the reasons for this may include the enhanced ability of colonizing yeasts to produce biofilms on mucosal surfaces. The aim of the present study was therefore to examine the differences, if any, in the biofilm-forming abilities of 26 Candida albicans yeast isolates from HIV-infected individuals and 20 isolates from HIV-free individuals, as this attribute of yeast isolates from patients with HIV disease has not been examined before. Biofilm formation in microtiter plate wells was quantitatively determined by both the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) reduction method and the crystal violet method. Although candidal biofilm formation could be quantitatively evaluated by either technique, the better reproducibility (P < 0.05) of the XTT reduction assay compared with that of the crystal violet method led us to conclude that the former is more reliable. There were no significant quantitative differences in biofilm formation between C. albicans isolates from HIV-infected patients and isolates from HIV-free individuals during in vitro incubation in a multiwell culture system over a period of 66 h. Three of eight host factors in the HIV-infected group were found to be associated with candidal biofilm formation. Thus, yeasts isolated from older individuals and those with higher CD4-cell counts exhibited decreased biofilm formation, while the findings for yeasts from individuals receiving zidovudine showed the reverse (P < 0.05 for all comparison). Our data indicate that attributes other than biofilm formation may contribute to the increased oral yeast carriage rates in cases of HIV infection.
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PMID:Biofilm-forming ability of Candida albicans is unlikely to contribute to high levels of oral yeast carriage in cases of human immunodeficiency virus infection. 1284 27

3beta-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane-type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti-HIV-1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti-HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti-HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post-binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV-1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma-derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer.
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PMID:Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. 1459 73


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