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

Latex products have long been recognized as a cause of latex protein allergy. The increased usage of latex gloves, with the consequent increased occurrence of latex allergies appears to have escalated with increasing awareness of the transmission of HIV-AIDS and other infections. The use of condoms as a means to prevent the transmission of STD's (sexually transmitted diseases) and HIV-AIDS has been widely promoted. Although extensive testing is done to evaluate the physical quality of condoms, no information is available regarding the biological safety of condoms. This study was undertaken to determine the effects of short-term exposure to physiological levels of condom surface material on cell viability (MTT assay) and cell growth (crystal violet assay). A direct contact cell culture testing method (FDA test method F813-83 used to evaluate the cytotoxic potential of medical materials and devices) was used. The modified test method was found to be a sensitive test system for the evaluation of the biological safety of condoms. This study reveals the importance of evaluating the biological safety of all condoms that are commercially available, because of the potential health risk that may be associated with prolonged use of certain types of condoms.
 ...
PMID:The biological safety of condom material can be determined using an in vitro cell culture system. 1190 60

Against many viral diseases caused for example by HSV, EBV, CMV, HIV, RSV, HCV for which vaccines are not available, chemiotherapeutics seem to have the principal significance. High progress in development of new antiviral compounds is observed. In addition to synthetic compounds a large number of naturally occurring substances have been shown to posses antiviral activity. One of such substance is tannic acid. In this study comparison of antiviral activity of tannic acid, acyclovir (ACV) and ganciclovir (GCV) against cytomegalovirus (CMV) is presented. The MRC5 cells infected with CMV and treated with different compounds were analyzed by flow cytometry and cythopatic effect inhibition test for inhibition of virus replication and by MTT assay for cytotoxity. It has been shown that tannic acid has antiviral activity against cytomegalovirus and that expression of virus antigens measured as median fluorescence intensity (MFI) by flow cytometry can be used for evaluation of virus replication.
 ...
PMID:Evaluation of antiviral activity of different origin compounds by flow cytometry. 1218 52

As part of our screening of anti-AIDS agents from natural sources, extracts of 15 medicinal plants widely used in the folk medicines of North America and Europe were evaluated in vitro. Most of the extracts tested were relatively nontoxic to human lymphocytic MT-2 cells, but only the extracts of Hysopp officinalis and Dittrichia viscosa exhibited anti-HIV activity in an in vitro MTT assay. The 50% hydroalcohol extract of Hysopp officinalis and the aqueous extract of Dittrichia viscosa showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 50 to 100 microg/mL and 25 to 400 microg/mL, respectively. Both extracts showed no appreciable cytotoxicity at these concentrations.
 ...
PMID:Screening of selected plant extracts for in vitro inhibitory activity on human immunodeficiency virus. 1223 13

We have previously demonstrated that tetrahedral bis(cyclopentadienyl)vanadium(IV) complexes and square pyramidal oxovanadium(IV) complexes of vanadium are rapid and selective spermicidal agents at low micromolar concentrations. This study investigated the potential utility of oxovanadium in combination with thiourea non-nucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT) for the development of an effective dual-function anti-HIV spermicide. Two rationally designed substituted phenyl-ring containing pyridyl thiourea NNIs, N-[2-(2-chlorophenethyl)]-N(')-[2-(5-bromopyridyl)-thiourea) [1] and N-[2-(2-methoxyphenethyl)]-N(')-[2-(pyridyl)-thiourea [2] that exhibited subnanomolar IC(50) values against the drug-sensitive, drug-resistant, and multidrug-resistant strains of HIV-1, were complexed with oxovanadium. The oxovanadium-thiourea [OVT] NNIs, C(29)H(27)Br(2)Cl(2)N(6)O(2)S(2)V [3], and C(31)H(35)N(6)O(4)S(2)V [4], were synthesized by reacting VOSO(4), a V(IV) compound, with the corresponding deprotonated thiourea NNI compounds as ligands. Elemental analysis showed that each OVT-NNI used two thiourea molecules as ligands. The existence of the Vz.dbnd6;O bond (968cm(-1)) was confirmed by IR spectroscopy. No d-d bands were observed in the visible spectra of OVT-NNIs and their EPR spectra were featureless, indicating that the vanadium centers were oxidized to V(V). The new OVT-NNIs as well as their thiourea NNI ligands were evaluated for (i) anti-HIV activity using the cell-free recombinant RT inhibition assays, (ii) cellular HIV replication assays, (iii) spermicidal activity against human sperm by computer-assisted sperm analysis (CASA), and (iv) cytotoxicity against normal human female genital tract epithelial cell using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye-reduction assays. Similar to thiourea NNIs 1 and 2, the OVT-NNIs 3 and 4, exhibited potent anti-HIV activity with submicromolar IC(50[p24]) values (0.08 and 0.128 microM, respectively) and submicromolar IC(50[RT]) values (2.1 and 0.87 microM, respectively). Notably, OVT-NNIs were spermicidal against human sperm at low micromolar concentrations (IC(50)=34 and 55 microM, respectively) and induced rapid sperm immobilization (T(1/2)=12 and 240s) when compared with their respective thiourea NNI ligands (EC(50)=>400 microM and T(1/2)=>180min). Moreover, OVT-NNIs displayed high selectivity indices against normal female genital tract epithelial cells (IC(50) values >250 microM) when compared to the detergent-type spermicide, nonoxynol-9, which was cytotoxic at spermicidal concentrations (IC(50) values 32-64 microM). This is the first report on the dual anti-HIV and spermicidal activities of a vanadium/oxovanadium complex. Our discovery of potent anti-HIV and rapid spermicidal activities of OVT-NNIs may be useful for the development of an effective and safe vaginal anti-HIV spermicide for women who are at high risk for acquiring HIV/AIDS by heterosexual transmission.
 ...
PMID:Potent dual anti-HIV and spermicidal activities of novel oxovanadium(V) complexes with thiourea non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1260 39

A homodimeric trypsin inhibitor with a molecular mass of 54 kDa was isolated from the seeds of Clausena lansium (Lour) Skeels with a very simple procedure comprising extraction with an aqueous buffer and ion exchange chromatography on CM-cellulose. It inhibited trypsin with an IC50 of 2.2 nM but was without any inhibitory effect on chymotrypsin and proteinase K. The uptake of MTT by human leukemia HL60 and hepatoma Hep G2 cells was inhibited with an IC50 of 100 microM. Translation in the cell-free rabbit reticulocyte lysate system was inhibited with an IC50 of 3.6 microM. The activity of HIV-1 reverse transcriptase was reduced in the presence of the trypsin inhibitor. The trypsin inhibitor exerted antifungal activity toward Physalospora piricola but not Mycosphaerella arachidicola, Botrytis cinerea, Fusarium oxysporum or Coprinus comatus.
 ...
PMID:A homodimeric sporamin-type trypsin inhibitor with antiproliferative, HIV reverse transcriptase-inhibitory and antifungal activities from wampee (Clausena lansium) seeds. 1267 22

The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, beta-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, beta-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier.
 ...
PMID:3'-azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta. 1455 Jul 50

The use of condoms to prevent sexually transmitted diseases, especially HIV, is widely encouraged. Condoms contain latex, nonspermicidal lubricants (such as dimethylsiliconium) and other nonspecified compounds, such as colorants and flavorings. Latex causes allergy reaction in susceptible individuals but little is known regarding the cytotoxic effects of other additives. The objective of this study was to develop a sensitive in vitro system to determine the toxic effects of condom material. The modified L929 FDA method and a more specific cell type, such as the cervical epithelial tumor cell line HeLa, was used. Lubricated (LC), lubricated and flavored (LFC), and lubricated, flavored and colored condoms (LFCC) were evaluated. Washings containing condom surface material were prepared by washing condom fragments in medium for different time intervals. Changes in cell number, viability and lysosome integrity in the L929 and HeLa cell lines was determined using the Crystal Violet, MTT and Neutral Red assays, respectively. The condom type affected cell viability and lysosome integrity, with LC inducing an increase in cell viability and LFC a decrease in lysosome integrity. The HeLa cell line in combination with the MTT and NR assay was themost sensitive in vitro system to determine the toxic effects of condom material.
 ...
PMID:An in vitro study of biological safety of condoms and their additives. 1499 28

Limited information is available on the activity of antiretroviral drugs against human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) strains to guide their use in treatment or prophylaxis. We evaluated the antiviral activity of 16 approved drugs and one experimental drug, AMD3100, against two wild-type HIV-2 (ROD and EHO) isolates, two strains of SIV (mac251 and B670), and two strains of simian-human immunodeficiency virus (SHIV) that contain the reverse transcriptase (RTSHIV) or envelope glycoprotein (SHIV89.6) of human immunodeficiency virus type 1 (HIV-1) in a SIV(mac239) background. Drug susceptibility was measured conventionally by the MT-4/MTT assay, and results were analysed as fold changes in 50% effective concentration (EC50) relative to the EC50 for HIV-1 (IIIB). The nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, lamivudine, stavudine, didanosine, zalcitabine and abacavir as well as the nucleotide reverse transcriptase inhibitor tenofovir retained full activity against all six viruses except for SIV and SHIV89.6 that showed low-level resistance to didanosine. The protease inhibitors (PIs) ritonavir, indinavir, saquinavir and nelfinavir were found to be active against some HIV-2 or SIV strains. However, a significant reduction in susceptibility was seen with indinavir against SHIV89.6 (3.3-fold), and with amprenavir against HIV-2(ROD) (8.8-fold). All viruses except for RTSHIV showed a >200-fold decrease in susceptibility for the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, delavirdine and efavirenz, indicating high-level resistance. AMD3100, a CXCR4 antagonist, was active against HIV-2 and SHIV89.6, a finding consistent with the use of the CXCR4 co-receptor by these isolates, but was inactive against SIV strains. In contrast, enfuvirtide (T-20) was active against SHIV89.6 but had reduced inhibitory activity against both HIV-2 and SIV strains predicting little therapeutic value against these viruses. These findings support the use of NRTIs, tenofovir, but not NNRTIs, for treating HIV-2-infected persons or for prophylaxis against HIV-2 and SIV. The clinical significance of the low-level resistance of HIV-2 and SIV to some PIs is unclear. Co-receptor antagonists such as AMD3100 show promising anti-HIV-2 therapeutic modalities. Both AMD3100 and enfuvirtide could be used for prophylaxis against SHIV89.6.
 ...
PMID:Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. 1504 May 30

Severe combined immunodeficient (SCID) mice have been evaluated for applicability as hosts for a human immunodeficiency virus (HIV) animal model, compatible with the pathogenesis of HIV disease and/or for testing compounds for antiviral efficacy. McCune et al. [Science 241 (1988) 1632] described the SCID/hu model and Namikawa et al. [J. Exp. Med. 172 (1990) 1055] and Rabin et al. [Antimicrob. Agents Chemother. 40 (1996) 755] described the SCID/hu (Thy/Liv) model which was developed for the evaluation of HIV pathogenic mechanisms and for the prioritization of antiviral compounds that were efficacious in vitro. Hollingshead et al. [Antiviral Res. 28 (1995) 265] and Xu et al. [Bioorg. Med Chem. Lett. 9 (1999) 133] described the HIV hollow fiber SCID mouse model. This model was developed to be a low cost, high throughput, time efficient, simple in vivo screening system for preliminary anti-HIV efficacy evaluation for the prioritization of antiviral compounds that demonstrated in vitro efficacy. The hollow fiber model is used as a pharmacologic tool to help separate active and inactive agents and direct the best lead compounds into additional animal model testing (e.g. SCID/hu). Compounds that are known to have an antiviral effect in man (e.g. 3'-azo-3'-deoxythymidine (AZT), dideoxyinosine (ddI) and dideoxycytidine (ddC)) were evaluated in both models. The endpoints (e.g. PCR, flow cytometry, MTT, p24, RT) evaluated in both models indicate that HIV-1 virus replicates in both models and infection is suppressed in the SCID/hu and hollow fiber SCID mouse models when treated with approved clinical antiviral agents. While both models are useful for the evaluation of antiviral therapies, there are distinct advantages (e.g. cost, time, material, equipment, expediency) with the hollow fiber assay over the SCID/hu model (Thy/Liv) for antiviral drug evaluations particularly in terms of cost effectiveness.
 ...
PMID:HIV hollow fiber SCID model for antiviral therapy comparison with SCID/hu model. 1519 14

The conjugation of the protein transduction domain (PTD) from the HIV-1 Tat protein to shell cross-linked (SCK) nanoparticles is a method to facilitate cell surface binding and transduction. In the previous report, the preparation, derivatization, and characterization of peptide-functionalized SCK nanoparticles were reported in detail. Following assembly, the constructs were evaluated in vitro and in vivo to obtain a preliminary biocompatibility assessment. The effects of SCK exposure on cell viability were evaluated using a metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and a fluorescent apoptosis assay. Furthermore, stages of apoptosis were quantified by flow cytometry. Although higher levels of peptide functionalization resulted in decreased metabolic function as measured by MTT assay, significant apoptosis was not observed below 500 mg/L for all the samples. To evaluate the potential immunogenic response of the peptide-derivatized constructs, a real-time polymerase chain reaction (RT-PCR) system that allows for the in vitro analysis and quantification of the cellular inflammatory responses tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL1-beta) was utilized. The inflammatory response to the peptide-functionalized SCK nanoparticles as measured by RT-PCR show statistically significant increases in the levels of both TNF-alpha and IL1-beta relative to tissue culture polystyrene (TCPS). However, the measured cytokine levels did not preclude the further testing of SCKs in an in vivo mouse immunization protocol. In this limited assay, measured increases in immunoglobulin G (IgG) concentration in the sera were minimal with no specific interactions being isolated, and more importantly, none of the mice (>50) subjected to the three 100 microg immunization protocol have died. Additionally, no gross morphological changes were observed in postmortem organ histology examinations.
 ...
PMID:Peptide-derivatized shell-cross-linked nanoparticles. 2. Biocompatibility evaluation. 1526 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>