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)

Pregnant women in developing countries are vulnerable to multiple micronutrient deficiencies. Studies assessing serum levels of the micronutrients and magnitude of their deficiencies are very scarce in African subjects. This study was aimed at determining serum levels of micronutrients in 375 pregnant (42 HIV seropositive) and 76 non-pregnant women (20 HIV seropositive) who visited the University of Gondar Hospital, Gondar, Ethiopia. Serum concentrations of zinc,\ copper, selenium, calcium, and magnesium were determined using an inductively coupled plasma mass spectrometer. Irrespective of HIV serostatus, pregnant women had significantly higher serum concentrations of copper and copper/zinc ratio and significantly lower magnesium compared to those in non-pregnant women (P < 0.05). Except for selenium, which was significantly lower in HIV-seropositive pregnant women (P < 0.05), the mean serum concentrations of zinc, copper, calcium, and magnesium were not significantly different between pregnant women by HIV serostatus. The prevalence of deficiency in zinc, magnesium, selenium, and calcium in the pregnant women, irrespective of their HIV serostatus, was 66.7%, 25.6%, 21.9%, and 9.3%, respectively. The magnitude of deficiency in zinc, magnesium, and selenium was significantly higher in HIV seropositive pregnant women (76.2%, 52.4%, and 45.2%) than that in HIV-seronegative pregnant women (65.5%, 22.2%, and 18.9%) and in HIV-seronegative non-pregnant women (42.9%, 8.1%, and 30.4%; P < 0.05). Deficiency in one, two, three, or four mineral elements was observed in 44.8%, 14.4%, 9.9%, and 5.1% of the pregnant women, respectively. Only 25.9% of the pregnant women and 44.7% of the non-pregnant women were not deficient in any of the micronutrients. The high prevalence of micronutrient deficiencies in pregnant and non-pregnant women in Gondar, Ethiopia warrants the need for strategies on prevention and control of the deficiencies.
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PMID:Serum zinc, copper, selenium, calcium, and magnesium levels in pregnant and non-pregnant women in Gondar, Northwest Ethiopia. 1820 35

We have carried out the study of the photochemical properties of a series of synthetic meso-tetraphenylsulfonated porphyrins (TPPMS4) bonded to several metal ions such as: Cu(II), Zn(II), Pd(II), Mn(II), Fe(III), Ni(II) and Co(II) for the optimization of their clinical applications as antiviral agents against the human immunodeficiency virus (HIV-1) as well as the study of the in vitro antiviral photoinactivation mechanisms with future application in blood sterilization. A selective inhibition has been determined in the viral growth (HIV-1) when this is irradiated in the presence of the complex TPPFeS4 and TPPMnS4 (photosensitizer-mediated Type I reaction) as well as in the 1O2-mediated (Type II reaction) in the presence of TPPPdS4 and TPPZnS4, remaining cellular viability unaltered in each case.
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PMID:Comparative antiviral (HIV) photoactivity of metalized meso- tetraphenylsulfonated porphyrins. 1833 33

Copper deficiency myelopathy (CDM) is an increasingly recognised mimic of subacute combined degeneration (SCD) of the cord due to cobalamin (vitamin B(12)) deficiency. It has been suggested that copper deficiency induces myelopathy through dysfunction of cytochrome oxidase, which is known to be copper-dependent. However, cytochrome oxidase is not cobalamin-dependent, so this hypothesis fails to explain the phenotypic similarity between CDM and SCD. We propose that the first step in a final common pathway of CDM and SCD is dysfunction of the methylation cycle. This cycle includes both copper and cobalamin-dependent enzymes and catalyses the net transfer of a methyl group from methyltetrahydrofolate to a variety of macromolecules, including myelin proteins. Dysfunction of the cycle might therefore cause failure of myelin maintenance and ultimately myelopathy. One step of the methylation cycle is catalysed by methionine synthase, which is known to be cobalamin-dependent. Nitrous oxide specifically inhibits this enzyme by inactivating methylcobalamin, causing SCD in animals and humans. Both animal and human data suggest that methionine synthase also requires copper, implying that the enzyme may be involved in the pathogenesis of CDM. Another enzyme involved in the methylation cycle, S-adenosylhomocysteine hydrolase, may be regulated by copper. Although this enzyme is not cobalamin-dependent, its potential impairment in copper deficiency may contribute to the overall dysfunction of the methylation cycle. In cases of congenital deficiencies of methylation cycle enzymes, spinal and cerebral demyelination was observed, providing further support for a critical role of the methylation cycle in myelination. Biochemical dysfunction of the methylation cycle has been reported in HIV myelopathy, which has pathological parallels with SCD. This raises the possibility that other demyelinating myelopathies might involve an impairment of the methylation cycle. Our hypothesis could be tested by measuring CSF concentrations of methylation cycle intermediates in cases of CDM, as these reflect spinal cord tissue levels. If it were confirmed, the hypothesis would not only provide a plausible explanation for the phenotypic similarity between CDM and SCD, but might also open up further therapeutic options such as methionine and betaine supplementation.
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PMID:Copper deficiency myelopathy and subacute combined degeneration of the cord - why is the phenotype so similar? 1847 29

In this work, we identified a high affinity and potency metallocene-containing triazole peptide conjugate that suppresses the interactions of HIV-1 envelope gp120 at both its CD4 and co-receptor binding sites. The ferrocene-peptide conjugate, HNG-156, was formed by an on-resin copper-catalysed [2+3] cycloaddition reaction. Surface plasmon resonance interaction analysis revealed that, compared to a previously reported phenyl-containing triazole conjugate HNG-105 (105), peptide 156 had a higher direct binding affinity for several subtypes of HIV-1 gp120 due mainly to the decreased dissociation rate of the conjugate-gp120 complex. The ferrocene triazole conjugate bound to gp120 of both clade A (92UG037-08) and clade B (YU-2 and SF162) virus subtypes with nanomolar KD in direct binding and inhibited the binding of gp120 to soluble CD4 and to antibodies that bind to HIV-1YU-2 gp120 at both the CD4 binding site and CD4-induced binding sites. HNG-156 showed a close-to nanomolar IC50 for inhibiting cell infection by HIV-1BaL whole virus. The dual receptor site antagonist activity and potency of HNG-156 make it a promising viral envelope inhibitor lead for developing anti-HIV-1 treatments.
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PMID:Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120. 1849 83

Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X protease mutant arising from in vitro selection with compound 1, a C 2-symmetric diol protease inhibitor, has been previously described. We now show that compound 2, a copper(I)-catalyzed 1,2,3-triazole derived compound previously shown to be potently effective against wild-type protease (IC 50 = 6.0 nM), has low nM activity (IC 50 = 15.7 nM) against the multidrug-resistant 6X protease mutant. Compound 2 displays similar efficacy against wild-type and 6X HIV-1 in viral replication assays. While structural studies of compound 1 bound to wild type and mutant proteases revealed a progressive change in binding mode in the mutants, the 1.3 A resolution 6X protease-compound 2 crystal structure reveals nearly identical interactions for 2 as in the wild-type protease complex with very little change in compound 2 or protease conformation.
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PMID:A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant. 1882 10

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations.
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PMID:How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food. 1883 33

Copper metabolism Murr1 domain 1 (COMMD1) is a 21-kDa protein involved in copper export from the liver, NF-kappaB signaling, HIV infection, and sodium transport. The precise function of COMMD and the mechanism through which COMMD1 performs its multiple roles are not understood. Recombinant COMMD1 is a soluble protein, yet in cells COMMD1 is largely seen as targeted to cellular membranes. Using co-localization with organelle markers and cell fractionation, we determined that COMMD1 is located in the vesicles of the endocytic pathway, whereas little COMMD1 is detected in either the trans-Golgi network or lysosomes. The mechanism of COMMD1 recruitment to cell membranes was investigated using lipid-spotted arrays and liposomes. COMMD1 specifically binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in the absence of other proteins and does not bind structural lipids; the phosphorylation of PtdIns at position 4 is essential for COMMD1 binding. Proteolytic sensitivity and molecular modeling experiments identified two distinct domains in the structure of COMMD1. The C-terminal domain appears sufficient for lipid binding, because both the full-length and C-terminal domain proteins bind to PtdIns(4,5)P2. In native conditions, endogenous COMMD1 forms large oligomeric complexes both in the cytosol and at the membrane; interaction with PtdIns(4,5)P2 increases the stability of oligomers. Altogether, our results suggest that COMMD1 is a scaffold protein in a distinct sub-compartment of endocytic pathway and offer first clues to its role as a regulator of structurally unrelated membrane transporters.
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PMID:COMMD1 forms oligomeric complexes targeted to the endocytic membranes via specific interactions with phosphatidylinositol 4,5-bisphosphate. 1894 Jul 94

Oral health is an integral component of general health and well being and a basic human right. Dental public health is probably the most challenging specialty of dentistry. Because of the lack of adequate resources among other factors, many people are likely to suffer from dental diseases. Despite great improvements in the oral health status of populations across the world, the burden and impact of dental diseases are still high. This is particularly true among underprivileged groups in both developed and developing communities. Oral diseases and conditions, including oral cancer, oral manifestations of HIV/AIDS, dental trauma, craniofacial anomalies, and noma, all have broad impacts on health and well-being. Oral cancer, the sixth most common cancer worldwide continues to be most prevalent cancer related to the consumption of tobacco, alcohol and other carcinogenic products. Nevertheless, significant reduction in mortality can be achieved by advances in early diagnosis and implementation of multidisciplinary treatment programs leading to improvement of survivorship and better quality of life. The present study was designed to evaluate the immunologic and biochemical markers in oral carcinogenesis using circulating immune complexes (CIC), copper, iron, and selenium concentrations as assessment endpoints. Study results indicated an increase in CIC and copper levels, and a decrease in iron and selenium concentrations in oral cancer patients compared to controls. The implications of these findings for public health are discussed.
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PMID:Immunological and biochemical markers in oral carcinogenesis: the public health perspective. 1915 37

A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties to the receptor protein in comparison to the drug AMD3100 (Plerixafor, Mozobil). The interaction of the metallodrug has been optimized by using ultrarigid chelator units that offer an equatorial site for coordination to the amino acid side chains of the protein. Binding competition assays with anti-CXCR4 antibodies show that the new compound stays bound longer and it has improved anti-HIV potency in vitro (EC(50) = 4.3 nM). X-ray structural studies using acetate as a model for carboxylate amino acid side chains indicate the nature of the coordination interaction.
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PMID:Binding optimization through coordination chemistry: CXCR4 chemokine receptor antagonists from ultrarigid metal complexes. 1923 46

Sandwich-cultured hepatocytes (SCH) from rats (SCRH), dogs (SCDH), and humans (SCHH) were used as an in vitro model to assess the hepatobiliary disposition of copper (Cu). The expression of Cu transporters, ceruloplasmin synthesis, Cu uptake, and biliary excretion and species differences in drug-induced alterations in Cu disposition were determined in SCH from all species. Western blot analysis verified basolateral Cu uptake transporter 1 (CTR1) and canalicular Cu efflux transporter (ATP7B) expression: enzyme-linked immunosorbent assay verified synthesis/secretion of ceruloplasmin (major Cu binding protein found in blood). Endogenous Cu in SCRH, SCDH, and SCHH were 17.2 +/- 7.00, 490 +/- 44.8, and 43.5 +/- 15.8 ng/well, respectively. The hepatobiliary disposition of Cu as measured by uptake (increase in intracellular Cu in comparison to endogenous levels) and biliary excretion (increase in Cu in wash solutions obtained from hepatocytes exposed to calcium-free versus standard buffer) was determined as a function of Cu concentration and incubation time. In general, an increase in Cu concentration or incubation time resulted in an increase in Cu uptake and/or biliary excretion; however, the extent to which they affected Cu disposition was species dependent. 5-(1,1-Dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (L-000870810) (an anti-HIV compound, the development of which was halted due to an observed Cu-specific toxicity in the liver and kidneys of dogs after long-term exposure) showed no effect on Cu disposition in SCRH; however, it increased the biliary excretion of Cu in SCDH and SCHH. This is the first report to demonstrate the utility of SCH as a model to assess hepatobiliary disposition of Cu in an in vitro system.
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PMID:Characterization of sandwich-cultured hepatocytes as an in vitro model to assess the hepatobiliary disposition of copper. 1923 14


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