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)

Human immunodeficiency virus 1 (HIV-1) encephalopathy is thought to result in part from the toxicity of HIV-1 envelope glycoprotein gp120 for neurons. Experimental systems for studying the effects of gp120 and other HIV proteins on the brain have been limited to the acute effects of recombinant proteins in vitro or in vivo in simian immunodeficiency virus-infected monkeys. We describe an experimental rodent model of ongoing gp120-induced neurotoxicity in which HIV-1 envelope is expressed in the brain using an SV40-derived gene delivery vector, SV(gp120). When it is inoculated stereotaxically into the rat caudate putamen, SV(gp120) caused a partly hemorrhagic lesion in which neuron and other cell apoptosis continues for at least 12 weeks. Human immunodeficiency virus gp120 is expressed throughout this time, and some apoptotic cells are gp120 positive. Malondialdehyde and 4-hydroxynonenal assays indicated that there was lipid peroxidation in these lesions. Prior administration of recombinant SV40 vectors carrying antioxidant enzymes, copper/ zinc superoxide dismutase or glutathione peroxidase, was protective against SV(gp120)-induced oxidative injury and apoptosis. Thus, in vivo inoculation of SV(gp120) into the rat caudate putamen causes ongoing oxidative stress and apoptosis in neurons and may therefore represent a useful animal model for studying the pathogenesis and treatment of HIV-1 envelope-related brain damage.
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PMID:A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors. 1952 94

(1) Intrauterine devices (IUDs) are placed in the uterine cavity with the objective of providing long-term contraception, mainly by preventing fertilisation. The best-known IUDs contain copper, but there is also an IUD delivering levonorgestrel, a progestin; (2) How effective are these devices, and what are their adverse effects? To answer these questions, we analysed the literature using the standard Prescrire methodology; (3) T-shaped copper IUDs, with a copper surface area of 380 mm2 on 3 arms, and the levonorgestrel-releasing device, have similar contraceptive efficacy as combined oral contraceptives that are used correctly. In contrast, IUDs are more effective than oral contraception used incorrectly; (4) Among IUD users, there are on average about 6 pregnancies per 1000 woman-years. There is less experience with the levonorgestrel IUD which seems to be at least as effective as copper IUDs; (5) The rare intrauterine pregnancies that occur in women using an IUD generally end in miscarriage. About 25% of these pregnancies end in a live birth if the device is left in place, compared to about 90% if the device is removed; (6) Ectopic pregnancies are rarer in IUD users than in women who do not use contraception. However, about one in 20 pregnancies that occur in women using an IUD is ectopic; (7) The IUD is expelled in about 5% to 10% of cases within 5 years, and expulsion recurs in about 30% of these women; (8) Problems such as difficult insertion, pain, bleeding and syncope are reported in less than 1.5% of cases overall; (9) Uterine perforation during insertion is rare, occurring in 0.6 to 16 cases per 1000 insertions, regardless of the type of IUD. The risk of perforation is higher when the IUD is inserted less than 4 to 6 weeks after delivery or elective abortion; (10) During the first 3 months after insertion, the risk of pelvic infection is slightly higher than in the general population, especially in women with pre-existing asymptomatic Chlamydia trachomatis infection. There are about 6 pelvic infections per 1000 woman-years of IUD use. Routine antibiotic prophylaxis is unnecessary. The interview and physical examination may lead to diagnosis of C. trachomatis infection or other sexually transmitted infections. In these cases, treatment may be needed before IUD insertion. Women must be warned that IUDs do not protect them from sexually transmitted diseases; (11) Menstrual bleeding is often heavier in women with cooper IUDs than in women who do not use IUDs, and may be associated with menstrual pain; (12) The levonorgestrel IUD is associated with a marked reduction in menstrual blood loss and irregular bleeding; amenorrhoea occurs in 35% of women after 2 years of use. The levonorgestrel IUD also has hormonal adverse effects such as headache, acne, breast tension and functional ovarian cysts; (13) IUDs can safely be used in breastfeeding women, immediately after a pregnancy, in cases of diabetes or HIV infection, during nonsteroidal antiinflammatory drug therapy, and after an ectopic pregnancy. The only problems occurring in women who have never had children are pain during insertion and more frequent expulsions; (14) A copper IUD is a first-line contraceptive method for women with a history of deep venous thrombosis, pulmonary embolism, or coronary events; (15) It is better to postpone IUD insertion when the woman has a genital tract infection or unexplained vaginal bleeding; (16) IUD insertion is an effective alternative to "morning-after" hormonal contraception.
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PMID:Intrauterine devices: an effective alternative to oral hormonal contraception. 1963 36

This chapter describes the development of new intrauterine drug delivery products, which are designed to provide improved methods for the prevention and treatment of gynaecological conditions, improvements to birth control methods, and higher levels of safety, user acceptability, compliance, and quality of life for women. The development of frameless intrauterine systems is such an attempt to improve on the performance and acceptability of established intrauterine contraception, potentially solving major problems encountered with conventional IUDs (e.g., expulsion, abnormal or excessive bleeding, and pain). However, the performance of frameless devices depends on proper anchoring of the device, which requires specific technical skills not required for the insertion of conventional IUDs. Moreover, current research paves the way for new developments. The frameless copper and LNG-releasing IUDs/IUSs and framed LNG-IUS are the beginning of a series of innovative developments in this field. New compounds, such as progesterone antagonists and selective progesterone receptor modulators (SPRMs), could be incorporated into polymeric drug delivery platforms for use in the uterus, cervix, or vagina, or subdermally. It is likely that current and new hormone-releasing intrauterine systems could also be useful for bleed-free contraception in HIV-positive (HIV+ women). It is hoped that this work will contribute to the increase in worldwide use of intrauterine contraception and to non-surgical treatment of frequently occurring women's health problems.
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PMID:Intrauterine drug delivery for contraception and gynaecological treatment: novel approaches. 2021 34

Since the 1959 revival of the IUD, non-hormonal devices have become the most widely used of all reversible contraceptives. Pregnancy rates of copper-releasing IUDs in current use range from approximately 0.5 to 1.5 per hundred continuing users in the first year, with somewhat lower annual pregnancy rates thereafter. Evidence-based research has been systematically conducted and translated into guidelines for eligibility criteria and problem management. Recent device research, beyond the T, Multiload and frameless devices has centred on improved designs such as U ,Y and Slimline shapes, or enhanced copper release, the latter through electrochemical effects or nanotechnology applications. Other IUD research foci concern devices that decrease bleeding and pain by releasing non-steroidal anti-inflammatory drugs. Yet other research lines indicate noncontraceptive benefits of copper intrauterine devices in protecting against endometrial cancer, and favourable risk-benefit analyses of IUD use by women at risk of or post HIV infection. IUD mechanisms of action and the relation of IUDs to pelvic infection and ectopic pregnancy are briefly reviewed. For our literature search we used Medline, Popline and Cochrane Library data bases, Google search, our personal files, and the references contained in articles in our files.
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PMID:State-of-the-art of non-hormonal methods of contraception: III. Intrauterine devices. 2023 Mar 37

The duration of pneumonia and of diarrhea is reported to be longer in HIV-infected than in uninfected children. We assessed the effect of a multi-micronutrient supplement on the duration of hospitalization in HIV-infected children. In a double-blind, randomized trial, HIV-infected children (4-24 mo) who were hospitalized with diarrhea or pneumonia were enrolled (n = 118) and given a daily dose of a multi-micronutrient supplement (containing vitamins A, B complex, C, D, E, and folic acid, as well as copper, iron, and zinc at levels based on recommended daily allowances) or a placebo until discharge from the hospital. Children's weights and heights were measured after enrollment and micronutrient concentrations were measured before discharge. On recovery from diarrhea or pneumonia, the children were discharged and the duration of hospitalization was noted. Anthropometric indices and micronutrient concentrations did not differ between children who received supplements and those who received placebos. Overall, the duration of hospitalization was shorter (P < 0.05) among children who were receiving supplements (7.3 +/- 3.9 d) (mean +/- SD) than in children who were receiving placebos (9.0 +/- 4.9); this was independent of admission diagnosis. In children admitted with diarrhea, the duration of hospitalization was 1.6 d (19%) shorter among children receiving supplements than in those receiving placebos, and hospitalization for pneumonia was 1.9 d (20%) shorter among children receiving supplements. Short-term multi-micronutrient supplementation significantly reduced the duration of pneumonia or diarrhea in HIV-infected children who were not yet receiving antiretroviral therapy and who remained alive during hospitalization.
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PMID:Short-term micronutrient supplementation reduces the duration of pneumonia and diarrheal episodes in HIV-infected children. 2033 32

To date only a ribonuclease and a protein with anti-HIV-1 reverse transcriptase activity have been isolated from mushrooms of the genus Russula. In this study a novel lectin, with a molecular weight of 32 kDa, and a unique N-terminal sequence different from other lectins, was isolated from the mushroom Russula lepida. It represents the first lectin isolated from Russula mushrooms. The purification scheme involved (NH4)2SO4 precipitation, ion exchange chromatography on diethylaminoethyl DEAE-cellulose and SP-Sepharose, and fast protein liquid chromatography-gel filtration on Superdex 75. The hemagglutinating activity of the lectin (RLL) was inhibited by inulin and O-nitrophenyl-beta-D-galacto-pyranoside. The lectin was stable at temperatures up to 70 degrees C (half of the activity was preserved at 80 degrees C), and in the presence of NaOH or HCl solutions up to a concentration of 12.5 mM. Its hemagglutinating activity was reduced in the presence of Mn2+, Co2+, and Hg2+ ions, and enhanced by Cu2+ ions. It exhibited antiproliferative activity toward hepatoma Hep G2 cells and human breast cancer MCF-7 cells with an IC(50) of 1.6 microM and 0.9 microM, respectively. Daily intraperitoneal injections of RLL (5.0 mg/kg body weight/day for 20 days) brought about 67.6% reduction in the weight of S-180 tumor. RLL was devoid of antifungal, ribonuclease, and HIV-1 reverse transcriptase inhibitory activities.
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PMID:First isolation and characterization of a novel lectin with potent antitumor activity from a Russula mushroom. 2037 19

Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for approximately 1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a polysaccharide capsule necessary for virulence. Capsule production inhibits phagocytosis by macrophages. Here we describe results that link copper homeostasis to capsule production and the inhibition of phagocytosis. Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified an insertion in the promoter region of the putative copper transporter-encoding gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper starvation and defects in polysaccharide capsule production and melanization. These defects were all reversed by genetic correction of the promoter insertion by homologous targeting. Several melanization-defective mutants identified previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity to copper starvation, reduced capsule production and increased phagocytosis. Together these results indicate a previously undescribed link between copper homeostasis to polysaccharide capsule production and phagocytosis inhibition in Cryptococcus neoformans.
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PMID:Ctr2 links copper homeostasis to polysaccharide capsule formation and phagocytosis inhibition in the human fungal pathogen Cryptococcus neoformans. 2082 73

Noncovalent interactions between complex carbohydrates and proteins drive many fundamental processes within biological systems, including human immunity. In this report we aimed to investigate the potential of mannose-containing glycopolymers to interact with human DC-SIGN and the ability of these glycopolymers to inhibit the interactions between DC-SIGN and the HIV envelope glycoprotein gp120. We used a library of glycopolymers that are prepared via combination of copper-mediated living radical polymerization and azide-alkyne [3+2] Huisgen cycloaddition reaction. We demonstrate that a relatively simple glycopolymer can effectively prevent the interactions between a human dendritic cell associated lectin (DC-SIGN) and the viral envelope glycoprotein gp120. This approach may give rise to novel insights into the mechanisms of HIV infection and provide potential new therapeutics.
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PMID:High-affinity glycopolymer binding to human DC-SIGN and disruption of DC-SIGN interactions with HIV envelope glycoprotein. 2093 25

Thiosemicarbazones display a wide antimicrobial activity by targeting bacteria, fungi, and viruses. Here, we report our studies on the antiviral activity of two thiosemicarbazone metal complexes, [bis(citronellalthiosemicarbazonato)nickel(II)] and [aqua(pyridoxalthiosemicarbazonato)copper(II)] chloride monohydrate, against the retroviruses HIV-1 and HTLV-1/-2. Both compounds exhibit antiviral properties against HIV but not against HTLVs . In particular, the copper complex shows the most potent anti-HIV activity by acting at the post-entry steps of the viral cycle.
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PMID:Antiretroviral activity of thiosemicarbazone metal complexes. 2112 32

The chemokine receptor CXCR4 is a member of the seven transmembrane GPCR family, which is implicated in multiple diseases, including HIV infection, cancers, and rheumatoid arthritis. Low-molecular-weight nonpeptidic compounds, including AMD3100 and various pyridyl macrocyclic zinc(II) complexes, have been identified as selective antagonists of CXCR4. In the present study, structure-activity relationship studies were performed by combining the common structural features of alkylamino and pyridiyl macrocyclic antagonists. Several new zinc(II) or copper(II) complexes demonstrated potent anti-HIV activity, strong CXCR4-binding activity, and significant inhibitory activity against Ca(2+) mobilization induced by CXCL12 stimulation. These results may prove useful in the design of novel CXCR4 antagonists, and the compounds described could potentially be developed as therapeutics against CXCR4-relevant diseases or chemical probes to study the biological activity of CXCR4.
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PMID:Azamacrocyclic metal complexes as CXCR4 antagonists. 2131 34


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