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Biomedical subjects

A S Bourinbaiar

Publications and source records attributed to A S Bourinbaiar.

At least 19 recordsLinked to original sources
PubMed2006

Therapeutic AIDS vaccines.

Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

AIDS Vaccines↗
PubMed2004

Increased body weight and improved quality of life in AIDS patients following V-1 Immunitor administration.

OBJECTIVES: Development of affordable and safe therapy to reverse the loss of body mass is of critical importance since AIDS-related wasting is associated with increased mortality. METHOD: We have demonstrated earlier that oral therapeutic HIV vaccine, V-1 Immunitor (V1), tested in a small group of AIDS patients in Thailand not only increases T-cell counts and decreases the viral load but also results in weight gain and prolonged survival. To further expand this observation, we retrospectively analyzed 650 HIV-positive patients who were followed for an average of 23 weeks. RESULTS: The treatment with V1 resulted in a sustained and statistically significant increase in body mass across the whole population (mean+/-s.e.; 1.5+/-0.4 kg; P=6.5E-015). Among them, 384 (59%) patients gained an average of 4.2+/-0.2 kg; 107 (17%) had unchanged weight; and 159 (24%) had lost 3.8+/-0.3 kg. Thus, the prevailing majority of patients (76%) were able to gain or maintain weight. Treatment was well tolerated; in a survey of health status in a comparable but separate group of 382 patients, about 85% reported subjective improvement after V1 treatment, 6% reported no difference, and 9% of the patients reported minor adverse reactions, which did not last more than 1 week. Subjective improvement coincides with the reduction or clearance of oral thrush or mucocutaneous candidiasis in 87.5% of the patients. CONCLUSIONS: In an open label setting, V1 increases body weight, subjective assessment of quality of life, and is safe and effective for HIV patients with weight loss. These data provide the impetus of using V-1 Immunitor as an affordable and easy-to-administer means of treating AIDS-associated wasting and opportunistic infections.

AIDS Vaccines↗
PubMed2004

Effect of an oral therapeutic HIV-1 vaccine on AIDS patients with CD4 count above 250 cells/mm3.

A simple delivery route, e.g. oral, would greatly facilitate the acceptance of an AIDS vaccine by a large target population. We developed a vaccine that took advantage of inherent properties of mucosal immunity in response to oral antigen challenge, namely the V-1 Immunitor vaccine (V1), which is a polyvalent oral Human immunodeficiency virus 1 (HIV-1) vaccine. The vaccine, currently manufactured in Thailand, contains pooled, inactivated viral antigens. In order to compare this vaccine with HIV-1 therapeutic vaccines reported earlier we analyzed retrospectively 13 HIV-1-positive patients that had the baseline CD4 T-cell counts greater than 250 cells/mm3 (range 270-605 cells/mm3). The patients self-administered one 850 mg vaccine tablet at breakfast and dinnertime for an average of 32 weeks (median 26 weeks). The treatment was well tolerated without any toxic effect. Twelve of thirteen patients (92%) and 9 of 13 patients (69%) experienced an elevation in CD4 and CD8 cells. The mean increase in absolute CD4 and CD8 cell counts across this group was 98 (22%; P = 0.02) and 324 (26%; P = 0.05) cells/mm3, respectively. Viral plasma load was measured by PCR in six patients. The observed viremia reduction was within 1 log unit. Subjective parameters, i.e., appetite, energy, and sense of well-being were reported by patients as being markedly improved, reflected in a mean body weight gain of 2.75 kg (P = 0.0008). Oral administration of HIV-1 immunogens provides compelling clinical response, especially when patients are treated earlier.

AIDS Vaccines↗
PubMed1997

The effect of gramicidin, a topical contraceptive and antimicrobial agent with anti-HIV activity, against herpes simplex viruses type 1 and 2 in vitro.

The effect of an anti-HIV compound, gramicidin, previously used as a topical antibiotic and vaginal contraceptive, on the replication of herpes simplex viruses (HSV) type 1 and 2 has been examined. Human WI-38 fibroblasts were inoculated with either HSV type in the presence of serial dilutions of gramicidin and reduction in viral yield was measured by ELISA. The 50% inhibitory dose (IC50) of gramicidin against 3 HSV-1 and 4 HSV-2 isolates was equal to 0.3 microgram/ml and was comparable to the efficacy of the anti-HSV agent acyclovir (ACV). The IC50 of gramicidin required to protect WI-38 from cytolytic effect of HSV was 10 micrograms/ml at day 5 postinfection, indicating that at this time point the activity of gramicidin was inferior than that of ACV. Nevertheless, gramicidin suppressed the replication of ACV-resistant thymidine kinase and DNA polymerase HSV mutants at doses effective against ACV-sensitive strains. The results suggest that the antimicrobial and spermostatic agent, gramicidin, has potential against sexually transmitted diseases (STDs) and for prophylaxis of sex-borne HIV and HSV infections.

Anti-HIV Agents↗
PubMed1997

The role of carboxy-terminal portion of beta subunit of human chorionic gonadotropin in human immunodeficiency virus infection.

Human chorionic gonadotropin (hCG) and the beta subunit of this dimer glycoprotein hormone (beta hCG) have been reported by us to inhibit HIV replication. In order to identify the active site responsible for the antiviral activity, twelve overlapping peptides spanning across beta hCG were examined for their effect against HIV-caused cell death. Although the NH2-terminus of beta hCG appeared to contribute to activity, the core region was biologically inert. The most potent activity was observed with the fragment representing the carboxy-terminus of beta hCG. The dose response curve to serial dilutions of the peptide, containing amino acid residues 106-145, had a bell-shaped appearance - characteristic of hCG and beta hCG. The peak of activity corresponded to 100 ng/ml - the dose at which two thirds of virus-exposed MT-4 T lymphocytes survived. None of the tested peptides were toxic to MT-4. While the mechanism of action remains unclear, the results suggest that the COOH-terminal portion, unique to beta hCG, confers anti-HIV activity.

Anti-HIV Agents↗
PubMed1996

The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus in vitro.

We examined the effect on anti-HIV proteins MAP30 and GAP31, from Momordica charantia and Gelonium multiflorum, on the infection and replication of Herpes Simplex Viruses (HSV). Human lung WI-38 fibroblasts cultured in the presence of tenfold dilutions of MAP30 or GAP31 were exposed to HSV and viral yield was measured at 24-48 hours by ELISA. The effective concentrations for 50% inhibitions (EC50) were 0.1-0.2 microM for HSV-2, and 0.3-0.5 microM for HSV-1 for MAP30 and GAP31, respectively. In comparison, the EC(50) for acyclovir (ACV), a commonly used anti-HSV drug, was 0.2 and 1.7 microM for HSV-2 and HSV-1, respectively. The cytotoxicity of all three antivirals was negligible and comparable. However, the antiherpetic activity of the plant proteins against acyclovir-resistant strains was two to three logs more potent than ACV. These results suggest that MAP30 and GAP31, previously shown to be active against HIV, may be useful for the therapy of herpesvirus infections.

Antiviral Agents↗
PubMed1996

Simple procedure for estimating the efficiency of PCR.

The extension efficiency of PCR-driven DNA amplification was examined by step-controlled limiting dilution method using as internal controls 8E5 lymphocytes carrying a single copy of HIV genome. The results reveal that under standard conditions recommended by the PCR kit manufacturer the exponential growth of DNA template is approximately one third of the theoretical doubling rate.

DNA↗
PubMed1996

Synergistic effect of gramicidin and EDTA in inhibiting sperm motility and cervical mucus penetration in vitro.

Gramicidin, a linear polypeptide with antiviral and antimicrobial properties, was compared in vitro with a commonly used spermicidal detergent-nonoxynol-9 (N9). The inhibition of sperm functions was evaluated by computer-assisted semen analysis (CASA) for sperm motility, in cervical mucus penetration assay, and by colorimetric tetrazolium salt and lactate dehydrogenase release assays routinely employed for testing the toxicity of drugs. The effective 100% inhibitory concentration (IC100) of gramicidin in a 2-min sperm immobilization assay by CASA was equal to 4 micrograms/ml, whereas IC100 of N9 was equal to 200 micrograms/ml. The presence of 0.1% of chelating agent, EDTA, reduced IC100 of gramicidin to 10 ng/ml, while less than a twofold enhancement in N9 activity was observed upon combination with EDTA. Likewise, the gramicidin/EDTA combination was 100,000 times more potent than N9/EDTA in the sperm penetration assay. Quantitative toxicity tests confirmed that gramicidin is a potent spermostatic rather than spermicidal agent. Further development of a gramicidin/EDTA formulation is warranted as a nontoxic topical contraceptive with activity against viral and microbial sexually transmitted diseases (STDs).

Cervix Mucus↗
PubMed1996

The effect of histamine type 2 receptor antagonists on human immunodeficiency virus (HIV) replication: identification of a new class of antiviral agents.

The suppression of human immunodeficiency virus (HIV) replication by histamine type 2 (H2) receptor antagonists, cimetidine, ranitidine, and famotidine was examined in vitro. The 50% reduction (IC50) in p24 antigen expression caused by the anti-ulcer agent, cimetidine, was observed at 26.8 nM with IC100 at 10 microM. Unlike azidothymidine-a reverse transcriptase inhibitor-cimetidine blocked HIV infection without affecting cell growth, as no cytotoxicity was observed even at the highest 1 mM dose. Ranitidine and famotidine were less potent than cimetidine. H1 antagonists, cyproheptadine and diphenhydramine, had no effect on HIV replication. Although the activity of cimetidine was observed at concentrations attainable by oral administration, the mechanism of anti-HIV action is unknown. This is the first report on antiretroviral action of H2 blockers. Further studies are warranted to establish the potential of a new class of anti-HIV agents with immunomodulating properties.

Anti-HIV Agents↗
PubMed1995

Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31.

MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium anti-HIV protein of 31 kDa) are anti-HIV plant proteins that we have identified, purified, and cloned from the medicinal plants Momordica charantia and Gelonium multiflorum. These antiviral agents are capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells. They are not toxic to normal uninfected cells because they are unable to enter healthy cells. MAP30 and GAP31 also possess an N-glycosidase activity on 28S ribosomal RNA and a topological activity on plasmid and viral DNAs including HIV-1 long terminal repeats (LTRs). LTRs are essential sites for integration of viral DNA into the host genome by viral integrase. We therefore investigated the effect of MAP30 and GAP31 on HIV-1 integrase. We report that both of these antiviral agents exhibit dose-dependent inhibition of HIV-1 integrase. Inhibition was observed in all of the three specific reactions catalyzed by the integrase, namely, 3' processing (specific cleavage of the dinucleotide GT from the viral substrate), strand transfer (integration), and "disintegration" (the reversal of strand transfer). Inhibition was studied by using oligonucleotide substrates with sequences corresponding to the U3 and U5 regions of HIV LTR. In the presence of 20 ng of viral substrate, 50 ng of target substrate, and 4 microM integrase, total inhibition was achieved at equimolar concentrations of the integrase and the antiviral proteins, with EC50 values of about 1 microM. Integration of viral DNA into the host chromosome is a vital step in the replicative cycle of retroviruses, including the AIDS virus. The inhibition of HIV-1 integrase by MAP30 and GAP31 suggests that impediment of viral DNA integration may play a key role in the anti-HIV activity of these plant proteins.

Antiviral Agents↗
PubMed1995

Potentiation of anti-HIV activity of anti-inflammatory drugs, dexamethasone and indomethacin, by MAP30, the antiviral agent from bitter melon.

MAP30 is an antiviral protein from bitter melon (Momordica charantia). The enhancement of weak HIV antagonists, dexamethasone and indomethacin, by MAP30 has been examined by measuring the reduction in p24 expression in acutely infected MT-4 lymphocytes. In the presence of 1.5 nM MAP30 the IC50 dose of dexamethasone and indomethacin has been lowered, without concurrent cytotoxicity, at least a thousand-fold to 10(-7) M and 10(-8) M, respectively. This observation indicates that MAP30, a multifunctional antiviral plant protein capable of topological inactivation of viral DNA and specific cleavage of 28 S ribosomal RNA, may regulate HIV replication in concert with steroid and non-steroidal inhibitors of prostaglandin synthesis. The results suggest that use of MAP30 in combination with low pharmacological doses of dexamethasone and indomethacin may improve the efficacy of anti-HIV therapy.

Antiviral Agents↗
PubMed1995

The non-steroidal anti-inflammatory drug, indomethacin, as an inhibitor of HIV replication.

Indomethacin, a common non-steroidal anti-inflammatory drug (NSAID), has been used to treat rheumatoid arthritis. Although indomethacin has also been used as an immunopotentiator and symptomatic NSAID in AIDS, its effect on HIV replication is unknown. MT-4 lymphocytes were inoculated with HIV in the presence of indomethacin and tested for p24 expression by ELISA. The 50% inhibition (IC50) was 10 microM, corresponding to plasma levels after administration of 50 mg oral indomethacin. The antiviral effect appears to be specific since no toxicity has been observed at the IC50 dose, and unrelated NSAIDs have not shown the activity at clinical doses. Indomethacin may, thus, represent a new class of anti-HIV drug.

Antiviral Agents↗
PubMed1995

Acrosin inhibitor, 4'-acetamidophenyl 4-guanidinobenzoate, an experimental vaginal contraceptive with anti-HIV activity.

Serine proteases are involved in a wide variety of seemingly unrelated physiological functions including capacitation of the spermatozoa and potentiation of human immunodeficiency virus (HIV) infection. The experimental vaginal contraceptives derived from 4-guanidinobenzoic acid act through inhibition of acrosin--a serine protease from the sperm. The serial ten-fold dilutions of 4'-acetamidophenyl 4-guanidinobenzoate (AGB) were tested in vitro for the effect against HIV infection by assaying the suppression of de novo p24 synthesis in virus-inoculated MT-4 T lymphocytes. The results reveal that complete inhibition of HIV occurred at 100 micrograms/ml--a dose corresponding to previously reported concentrations responsible for preventing fertilization in rabbits. These findings suggest that serine protease inhibitors and in particular the guanidinobenzoates, reported to be up to 100-fold more potent and less irritating than nonoxynol-9, can be potentially operative against sexual transmission of HIV.

Acrosin↗
PubMed1995

Anti-HIV effect of beta subunit of human chorionic gonadotropin (beta hCG) in vitro.

Human chorionic gonadotropin (hCG)--a pregnancy-associated immunomodulating hormone--has been recently shown in vitro to suppress reverse transcriptase activity in chronically HIV-infected lymphocytes and monocytes and to block viral transmission resulting from cell-cell contact between virus-carrying lymphocytes and placental trophoblasts. In further pursuit of the query into the mechanism of action, purified alpha and beta subunits of hCG were tested for the inhibition of p24 gag protein synthesis in virus-producing ACH-2 lymphocytes and U1 monocytes. Unlike the alpha subunit, beta-hCG displayed a distinct U-shaped dose response, characteristic of the effect of dimer hCG. Maximum inhibition of viral expression has been achieved at 10-100 ng/ml, the concentration corresponding to blood levels of beta-hCG in pregnant women. The doses that were several logs higher of normal levels seemed to increase viral production in monocytes. The data presented supports our original observations regarding the effect of intact hCG on HIV replication. While the mechanism of action remains to be established, the results suggest that the virus-interfering activity of hCG is determined by hormone-specific beta chain but not by the alpha subunit--shared with the family of glycoprotein hormones from the pituitary--follicle-stimulating hormone, luteinizing hormone and thyrotropin.

Cell Division↗