chondroitin-sulfates and HIV-Infections

Fucosylated chondroitin sulfates (FCS) are a sulfated polysaccharide exclusively existing in the body wall of sea cucumber. FCS possesses a mammalian chondroitin sulfate like backbone, namely repeating disaccharides units composed of GlcA and GalNAc, with fucosyl branches linked to GlcA and/or GalNAc residues. It is found that FCS can prevent unhealthy dietary pattern-induced metabolic syndromes, including insulin resistance and β-cell function improvement, anti-inflammation, anti-hyperlipidemia, and anti-adipogenesis. Further studies show that those activities of FCS might be achieved through positively modulating gut microbiota composition. Besides, FCS also show therapeutic efficacy in cancer, HIV infection, and side effects of cyclophosphamide. Furthermore, bioactivities of FCS are closely affected by their molecular weights, sulfation pattern of the fucosyl branches, and chain conformations. This review summarizes the recent 20 years studies to provide references for the future studies and applications of FCS in functional foods or drugs.

Topics: Animals; Chondroitin Sulfates; Disaccharides; Gastrointestinal Microbiome; HIV Infections; Humans; Immunomodulation; Metabolic Syndrome; Mice; Molecular Weight; Neoplasms; Polysaccharides; Sea Cucumbers; Structure-Activity Relationship; Sulfates; Virus Diseases

Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the purpose of this article to emphasize the importance of this element in humans and discuss the therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant macromineral in breast milk and the third most abundant mineral based on percentage of total body weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine, homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages, mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical trails.

Topics: Amino Acids, Essential; Antioxidants; Arteriosclerosis; Chondroitin Sulfates; Diet; Dimethyl Sulfoxide; Glucosamine; Glutathione Transferase; HIV Infections; Humans; Muscle Fatigue; Sulfur; Thioctic Acid

HIV-1 infection to the central nervous system (CNS) is very common in AIDS patients. The predominant cell types infected in the brain are monocytes and macrophages, which are surrounded by several HIV-1-resistant cell types, such as astrocytes, oligodendrocytes, neurons, and microvascular cells. The effect of these HIV-1-resistant cells on HIV-1 infection is largely unknown. In this study, we examined the stability of HIV-1 cultured with several human glioblastoma cell lines, for example, NP-2, U87MG, T98G, and A172, to determine whether these HIV-1-resistant brain cells could enhance or suppress HIV-1 infection and thus modulate HIV-1 infection in the CNS. The HIV-1 titer was determined using the MAGIC-5A indicator cell line as well as naturally occurring CD4(+) T cells. We found that the stability of HIV-1 incubated with NP-2 or U87MG cells at 37°C was significantly shorter (half-life, 2.5-4 h) compared to that of HIV-1 incubated with T98G or A172 cells or in culture medium without cells (half-life, 8-18 h). The spent culture media (SCM) of NP-2 and U87MG cells had the ability to suppress both R5- and X4-HIV-1 infection by inhibiting HIV-1 attachment to target cells. This inhibitory effect was eliminated by the treatment of the SCM with chondroitinase ABC but not heparinase, suggesting that the inhibitory factor(s) secreted by NP-2 and U87MG cells was chiefly mediated by chondroitin sulfate (CS) or CS-like moiety. Thus, this study reveals that some but not all glioma cells secrete inhibitory molecules to HIV-1 infection that may contribute in lowering HIV-1 infection in the CNS in vivo.

Topics: Anti-HIV Agents; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Central Nervous System; Chondroitin ABC Lyase; Chondroitin Sulfates; Glioblastoma; Heparin Lyase; HIV Infections; HIV-1; Humans

Polyelectrolyte complexes (PECs) constituted of chitosan and chondroitin sulfate (ChonS) were formed by the one-shot addition of default amounts of polyanion to an excess of polycation. Key variables of the formulation process (e.g., degree of depolymerization, charge mixing ratio, the concentration, and pH of polyelectrolyte solutions) were optimized based on the PECs sizes and polydispersities. The PECs maintained their colloidal stability at physiological salt concentration and pH thanks to the complexation of polyelectrolytes with zinc(II) ion during the nanoPECs formation process. The PECs were capable of encapsulating an antiretroviral drug tenofovir (TF) with a minimal alteration on the colloidal stability of the dispersion. Moreover, the particle interfaces could efficiently be functionalized with anti-OVA or anti-α4β7 antibodies with conservation of the antibody biorecognition properties over 1 week of storage in PBS at 4 °C. In vitro cytotoxicity studies showed that zinc(II) stabilized chitosan-ChonS nanoPECs were noncytotoxic to human peripheral blood mononuclear cells (PBMCs), and in vitro antiviral activity test demonstrated that nanoparticles formulations led to a dose-dependent reduction of HIV-1 infection. Using nanoparticles as a drug carrier system decreases the IC50 (50% inhibitory concentration) from an aqueous TF of 4.35 μmol·L(-1) to 1.95 μmol·L(-1). Significantly, zinc ions in this system also exhibited a synergistic effect in the antiviral potency. These data suggest that chitosan-ChonS nanoPECs can be promising drug delivery system to improve the antiviral potency of drugs to the viral reservoirs for the treatment of HIV infection.

Topics: Anti-HIV Agents; Chitosan; Chondroitin Sulfates; Colloids; HIV Infections; Humans; Leukocytes, Mononuclear; Polymers; Zinc

HIV infection increases the risk of malaria infection in pregnant women. Antibodies to variant surface antigens (VSA) on infected erythrocytes might protect against malaria in pregnancy. We postulated that HIV-induced impairment of humoral immunity to VSA mediates the increased susceptibility to malaria.. We compared serum concentrations of antibodies to VSA by flow cytometry or agglutination, and to merozoite proteins AMA-1 and MSP119 by ELISA, in 298 pregnant Malawian women, and related the findings to malaria and HIV infection, CD4-positive T-cell count, and HIV-1 viral load.. Concentrations of IgG to placental type VSA were lower in HIV-infected women than in HIV-uninfected women (median 8 units [IQR 4-23] vs 20 [12-30]; p<0.0001), among women with malaria (p=0.009) and those without malaria (p=0.0062). The impairment was greatest in first pregnancy. Agglutinating antibodies to placental VSA were present in a lower proportion of HIV-infected than HIV-uninfected women (58 [35.1%] of 165 vs 50 [53.8%] of 93, p<0.001). The degree of antibody binding by flow cytometry was correlated with CD4-positive T-cell count (r=0.16, p=0.019) and inversely with HIV-1 viral load (r=-0.16, p=0.030). Concentrations of antibodies to AMA-1 were lower in HIV infection (p<0.0001) but were not correlated with CD4-positive T-cell count or viral load. Responses to MSP119 were little affected by HIV infection. In multivariate analyses, HIV was negatively associated with amount of antibody to both VSA and AMA-1 (p<0.001 for each) but not MSP119.. HIV infection impairs antimalarial immunity, especially responses to placental type VSA. The impairment is greatest in the most immunosuppressed women and could explain the increased susceptibility to malaria seen in pregnant women with HIV infection.

Topics: Adult; Animals; Antibodies, Protozoan; Antigens, Protozoan; Antigens, Surface; CD4 Lymphocyte Count; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Erythrocyte Membrane; Erythrocytes; Female; Gravidity; HIV Infections; HIV-1; Humans; Immunoglobulin G; Malaria, Falciparum; Membrane Proteins; Merozoite Surface Protein 1; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Protein Subunits; Protozoan Proteins

We investigated whether culture conditions could affect the RANTES antiviral effect on human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages. Monocyte-derived macrophages (MDM) were obtained either as (1) the adherent cells of 5-day cultures of blood mononuclear cells (PBMC), followed by 2 days without nonadherent PBMC or added cytokines (MDM-5d), or (2) as the adherent cells recovered from 1-h incubation of PBMC, which were cultured for 7 days with macrophage colony-stimulating factor (M-CSF; MDM-MCSF). Infection of MDM-5d from different donors with HIV-1 R5 strains was reproducibly inhibited by RANTES (IC50 < or = 10 nM), but infection of MDM-MCSF was not inhibited by > or = 100 nM RANTES, even when added at initiation of cultures, although it was still inhibited by a CD4 antibody. RANTES had no antiviral effect when MDM-5d were treated with physiological concentrations of M-CSF or GM-CSF before infection. CCR5 and CXCR4 expression as well as that of other cell surface molecules, including adhesion molecules, was not affected by the cytokines. MDM-MCSF from delta 32CCR5 homozygous individuals did not render them permissive to HIV-1, suggesting that it is unlikely that the virus uses another coreceptor. RANTES binding to MDM was chondroitin sulfate, but not heparan sulfate, dependent, and RANTES bound more efficiently to MDM-5d than to MDM-MCSF. Chondroitin sulfate removal partially offset the RANTES antiviral effect for MDM-5d. Thus RANTES anti-HIV-1 activity for primary macrophages depends on culture conditions and their consequent activation status, which may lead to differences in proteoglycan surface expression. These data may be relevant for the development of chemokine-based therapy for HIV-1 infection.

Topics: Cell Adhesion; Cells, Cultured; Chemokine CCL5; Chondroitin Sulfates; Granulocyte-Macrophage Colony-Stimulating Factor; Heparitin Sulfate; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Macrophage Activation; Macrophage Colony-Stimulating Factor; Macrophages

Elderberry, chondroitin, and glucosamine sulfate have been found to block HIV replication at three distinct points in the replication cycle. For quadruple therapy, a reverse transcriptase inhibitor such as olive leaf extract or Epivir (3TC) could be added. In one case, a female, taking no HIV drugs, used an elderberry extract, called Sambucol, with olive leaf extract and experienced a viral load drop from 17,000 to 4,000. Instructions are given for making both alcohol-free and alcohol-based elderberry extracts. In 1993, researchers at Jerusalem?s Hebrew University Medical School found in a placebo-controlled double-blind study that Sambucol led to a rapid recovery from influenza and inhibited replication of nine other strains of the flu virus. A theory is that elderberry renders viruses nonfunctional by staining and coating them. Another promising treatment is soil based organisms, which improved Natural Killer cell function in a person with CFIDS.

Topics: Chondroitin Sulfates; Complementary Therapies; Cooking; Drug Therapy, Combination; Glucosamine; HIV Infections; Humans; Plant Extracts; Virus Replication; Wine

Drug combinations have saved thousands of lives, but no one knows how long this will continue. A low-cost combination that can reduce viral loads to low or undetectable levels without side effects is desperately needed. Ideally, a treatment would be available for $50 a month rather than the current average of $1,500 a month. Treatment with elderberry combined with glucosamine and chondroitin sulfate is being considered; it costs about $50 a month. Other treatments involving herbs induce a low grade fever, which may help to destroy the virus. Protease inhibitors and why the editorial staff has dropped double protease inhibitors from its list are also discussed.

Topics: Chondroitin Sulfates; Complementary Therapies; Coronary Disease; Drug Therapy, Combination; Glucosamine; HIV Infections; HIV Protease Inhibitors; Humans; Hyperthermia, Induced; Lipid Metabolism; Plant Extracts

Chondroitin sulfate, a fusion inhibitor found in human milk, appears to work by blocking the ability of a virus, such as HIV, to infect a cell. There are questions about whether cow or goat milk can offer the same fusion-inhibiting benefits. One sulfated monosaccharide, glucosamine 6-sulfate, appears to have significant anti-HIV activity. Carrageenan, a seaweed derivative, shows promise as a vaginal microbicide, and should be tested further to determine its effectiveness against HIV transmission.

Topics: Agar; Carrageenan; CD4 Antigens; Chondroitin Sulfates; Complementary Therapies; Drug Therapy, Combination; Excipients; Glucosamine; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Milk, Human; Polysaccharides; Seaweed; Silicon Dioxide; Sulfates; T-Lymphocytes

Several HIV patients offer anecdotal reports in which they attribute significant viral load reductions to taking elderberry extract. Thy-Mate was also used. Case studies from six patients are presented. In an interview, Steven Rahn describes his self-imposed treatment and its effect on his viral load. Another case discusses reports of dicalcium phosphate, a binding agent found in some dietary supplements such as glucosamine, inhibiting absorption of the supplements. Other cases are described, and contact information is included.

Topics: AIDS-Related Opportunistic Infections; Calcium Phosphates; Chondroitin Sulfates; Complementary Therapies; Drug Synergism; Drug Therapy, Combination; Glucosamine; HIV Infections; HIV Protease Inhibitors; Humans; Plant Extracts; Pneumonia, Pneumocystis; Viral Load

Considerable evidence suggests that sexual transmission of human immunodeficiency virus (HIV) is mediated via mononuclear cells that can infect epithelia of the genital tract. We describe here an in vitro model that can be used to examine the mechanism of cell-to-cell transmission of this virus. We have employed the system to identify agents that may be effective in a vaginal formulation to prevent HIV transmission via sexual contact. We have previously shown that chronically HIV-infected mononucleocytes can infect CD4-negative epithelial monolayers in the following manner: adhesion, via multiple microvilli, of HIV-infected mononucleocyte-derived cells to epithelial monolayers activates rapid virion secretion. Virions are then shed from the attached surface of the infected lymphocyte into a partially enclosed, microvilli-laden space between the cells. The shedding results in uptake of the virus and epithelial cell infection as demonstrated by ultrastructural examination and in vitro virological techniques. In this report, we present evidence from time-lapse films that HIV-infected lymphocytes adhere to the epithelium for a few minutes and then shift position to another site on the epithelium. As a result, one infected lymphocyte appears to be able to sequentially infected several cells of the epithelial monolayer. Using a fluorescence-based cell-cell adhesion assay to examine the effect of seminal fluid and a variety of chemical compounds on lymphocyte-to-epithelial adherence, we found that seminal fluid significantly increases the number of lymphocytes adhering to epithelia. This suggests that semen can serve as an effective medium for cell-cell transmission of HIV. On the other hand, sulfated polysaccharides and glutathione effectively inhibit cell-cell adhesion. Since the cell-cell adhesion step is critical to epithelial cell infection by HIV, these results suggest that anti-cell adhesion compounds may be effective in a vaginal formulation to reduce the probability of HIV infection.

Topics: Cell Adhesion; Cell Line; Chondroitin Sulfates; Dextran Sulfate; Epithelium; Female; HIV Infections; Humans; Lymphocytes; Male; Microscopy, Electron, Scanning; Semen; Sexual Behavior; Vagina