HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the Treatment of Leishmaniasis

Barat, Corinne; Chang, Zhao; Ouellette, Marc; Tremblay, Michel J.

doi:10.1086/510398

Cited by 19 publications

(20 citation statements)

References 37 publications

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“…Although data from Africa and India are lacking, the high frequency of vomiting and mortality among antimonial-treated HIV-positive patients in Ethiopia suggests that similar toxicity occurs (215,216). In addition, it has been demonstrated in vitro that sodium stibogluconate stimulates HIV-1 replication (22).…”

Section: Vl-hiv Coinfectionmentioning

confidence: 99%

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The Relationship between Leishmaniasis and AIDS: the Second 10 Years

et al. 2008

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SUMMARY To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.

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Section: Vl-hiv Coinfectionmentioning

confidence: 99%

“…An additional disadvantage of antimonials is that they were shown to stimulate HIV-1 replication in vitro, a finding that merits further investigation (22).…”

Section: Treatment Of Leishmaniasis In Hiv-positive Patientsmentioning

confidence: 99%

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

et al. 2008

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Section: Europe Pmc Funders Author Manuscripts Europe Pmc Funders Autmentioning

confidence: 99%

“…However, these have the disadvantage of high toxicity. [1][2][3][4] Since the available treatment for leishmaniasis poses many problems, researchers are looking at novel biochemical targets in order to develop new drugs.Leishmania produce characteristic glycoconjugates: LPGs, secreted phosphoglycans, and secreted and membrane-bound proteophosphoglycans. Several studies have emphasized the importance of LPG, the most abundant molecules on the parasite cell surface.…”

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confidence: 99%

“…Several studies have emphasized the importance of LPG, the most abundant molecules on the parasite cell surface. [7][8][9][10][11][12] The basic LPG structure in all Leishmania consists of a 1-O-alkyl-2-lyso-phosphatidylinositol lipid anchor and heptasaccharide core, to which is joined a long phosphoglycan polymer composed of 15-30 repeating units with the backbone structure of [−6)Gal(β1-4)Man(α1-OPO 3 H−]. LPG is terminated at the non-reducing end with a capping oligosaccharide.…”

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Probing Elongating and Branching β-d-Galactosyltransferase Activities in Leishmania Parasites by Making Use of Synthetic Phosphoglycans

et al. 2011

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Protozoan parasites of the genus Leishmania synthesize lipophosphoglycans (LPGs), phosphoglycans and proteophosphoglycans that contain phosphosaccharide repeat units of [−6)Gal(β1-4)Man(α1-OPO 3 H−]. The repeat structures are assembled by sequential addition of Manα1-OPO 3 H and β-Gal. In this study, an UDP-Gal-dependent activity was detected in L. donovani and L. major membranes using synthetic phospho-oligosaccharide fragments of lipophosphoglycan as acceptor substrates. Incubation of a microsomal preparation from L. donovani or L. major parasites with synthetic substrates and UDP-[6-3 H]Gal resulted in incorporation of radiolabel into these exogenous acceptors. The [ 3 H]galactose-labeled products were characterized by degradation into radioactive, low molecular mass fragments upon hydrolysis with mild acid and treatment with β-galactosidases. We showed that the activity detected with L. donovani membranes is the elongating β-D-galactosyltransferase associated with LPG phosphosaccharide backbone biosynthesis (eGalT). The eGalT activity showed a requirement for the presence of at least one phosphodiester group in the substrate and it was enhanced dramatically when two or three phosphodiester groups were present. Using the same substrates we detected two types of galactosyltransferase activity in L. major membranes: the elongating β-Dgalactosyltransferase and a branching β-D-galactosyltransferase (bGalT). Both L. major enzymes required a minimum of one phosphodiester group present in the substrate, but acceptors with two or three phosphodiester groups were found to be superior. Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsThe trypanosomatid protozoan parasite Leishmania infects over 12 million people worldwide, causing a variety of diseases that range from mild cutaneous lesions to fatal visceral infections. General aspects of leishmaniasis and overall control strategies have been reviewed. 1,2 The parasite exists in two forms: the flagellated promastigote in the female sand fly vector and the amastigote in the mammalian host. Amastigotes are obligate intracellular parasites of macrophages, where they survive and multiply. A key step of the infectious cycle is the ability of the parasite to be transmitted to new hosts by the insect vector. In the recent years, visceral leishmaniasis is reported to be rapidly emerging as an opportunistic infection in HIV patients, 3,4 in pregnant females, and in organ transplant patients. 5 Globalization and consequent travel of people across the world has increased the chances of spreading the infection. 6 Pentavalent antimonials were brought into use against leishmaniasis more than 50 years ago. Along with Pentostam and Glucantime, non-antimonial polyene antibiotic Amphotericin B, as well as Paromomicin and Miltefosine have also proved to be successful for the treatment of L. donovani induced visceral leishmaniasis. However, these have the disadvantage of high toxicity. [1][2][3][4] Since the available treatment for leishmaniasis poses ma...

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Metals in Medicine: Therapeutic Agents

Mukherjee¹,

Sadler²

2009

Wiley Encyclopedia of Chemical Biology

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Within the emerging field of medicinal inorganic chemistry, the realization that metal complexes can be designed as both therapeutic and diagnostic agents with novel mechanisms of action is increasing. Some recent advances are highlighted in this review, beginning with the success of platinum anticancer complexes and attempts to extend such activity to other transition metals, even to arsenic. Lithium is widely used for bipolar affective disorders, and gold is used for the treatment of rheumatoid arthritis. Metal ions also play crucial roles in contrast agents for magnetic resonance imaging and in radiopharmaceuticals used for imaging and therapy. Metal complexes offer flexible design platforms as enzyme inhibitors, and metals in enzyme active sites can be key drug targets. The antimicrobial and antiviral activities of certain metal complexes may prove useful in the fight against antibiotic resistance. Metals play key roles, too, in the control of small signaling molecules such as nitric oxide and carbon monoxide. Control of the uptake and distribution of the essential metals also presents a challenge, which is aided by modern genomic knowledge.

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HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the Treatment of Leishmaniasis

Cited by 19 publications

References 37 publications

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

The Relationship between Leishmaniasis and AIDS: the Second 10 Years

Probing Elongating and Branching β-d-Galactosyltransferase Activities in Leishmania Parasites by Making Use of Synthetic Phosphoglycans

Metals in Medicine: Therapeutic Agents

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