Abeer H. A. Mohamed-Ahmed

Bio: Abeer H. A. Mohamed-Ahmed is an academic researcher from University College London. The author has contributed to research in topics: Medicine & Taste aversion. The author has an hindex of 8, co-authored 12 publications receiving 160 citations. Previous affiliations of Abeer H. A. Mohamed-Ahmed include University of London & UCL Institute of Ophthalmology.

Recent advances in development of amphotericin B formulations for the treatment of visceral leishmaniasis.

Abstract: Purpose of reviewAmphotericin B (AmpB) is considered the first-line treatment for visceral leishmaniasis in areas in which resistance to antimony is prevalent. This review describes recent advances in clinically available and novel drug delivery systems of AmpB to treat visceral leishmaniasis.Recent

Noncovalent Complexation of Amphotericin-B with Poly(α-glutamic acid)

Abstract: A noncovalent complex of amphotericin B (AmB) and poly(α-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of ∼20–50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB–PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 μg/mL respectively. This AmB–PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 ± 0.03–0.08 ± 0.01 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 o...

Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.

Abstract: Leishmaniasis is a parasitic disease that presents four main clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis/kala azar (VL), and post kala azar dermal leishmaniasis (PKDL). Causative Leishmania are protozoan parasites that are transmitted among mammalian hosts by phlebotomine sandflies. In mammalian hosts, parasite cells proliferate inside the host phagocytic cells as round amastigotes. Infection of sandflies with Leishmania occurs during insect feeding on infected mammalian hosts. After introduction into the insect gut together with the blood meal, Leishmania amastigotes transform into elongated flagellated promastigotes that propagate in the insect gut. A new round of infection is initiated after the infected sandfly takes a blood meal from a naive mammalian host and introduces Leishmania parasites into the bite wound in the host dermis (Scheme 1). More than 20 different Leishmania species have been found to cause human leishmaniasis (Table 1). Leishmaniasis is endemic in 98 countries and is closely associated with poverty. More than a million new cases are reported per year and 350 million people are at risk of contracting the infection. For the most severe form of leishmaniasis, VL, ∼300 000 new cases are estimated to occur annually resulting in ∼40 000 deaths. Approximately 90% of all VL cases occur in 3 endemic foci: 1. India, Bangladesh, and Nepal; 2. East Africa; and 3. Brazil. In spite of the high prevalence, currently available treatments for leishmaniasis are inadequate. Pentavalent antimonials, the standard treatment for leishmaniasis for many decades, are not efficacious in Bihar (∼60% of VL cases worldwide) any longer due to widespread resistance to the drug in this region. Several new VL treatments have emerged during the past 10–15 years, but each has serious shortcomings (summarized in Table 2). These include paromomycin (injectable, long treatment, region-dependent efficacy), miltefosine (cost, teratogenicity, long treatment), and liposomal amphotericin B (cost, hospitalization, region-dependent efficacy). An additional challenge is represented by patients with HIV/VL coinfections who are more difficult to cure (lower initial and final cure rates), have greater susceptibility to drug toxicity, and have higher rates of death and relapse. Due to the limitations of the existing treatments, better drugs are urgently needed. Ideally, new VL drugs would be efficacious across all endemic regions, would affect cure in ≤10 days, and would cost <$10 per course (for a complete target product profile for new VL drugs, which was formulated by DNDi, see Table 4).1 Here we describe the disease history and parasite biology followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.

Disorders affecting vitamin B6 metabolism.

Abstract: Vitamin B6 is present in our diet in many forms however only pyridoxal 5’‐phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs non‐phosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1‐carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis. Besides the role of PLP as a cofactor B6 vitamers also play other cellular roles, e.g. as antioxidants, modifying expression and action of steroid hormone receptors, affecting immune function, as chaperones and as an antagonist of ATP at P2 purinoceptors. Because of the vital role of PLP in neurotransmitter metabolism, particularly synthesis of the inhibitory transmitter GABA, it is not surprising that various inborn errors leading to PLP deficiency manifest as B6‐responsive epilepsy, usually of early onset. This includes PNPO deficiency (a disorder affecting PLP synthesis and recycling), disorders affecting PLP import into the brain (hypophosphatasia and GPI anchor synthesis defects), a disorder of an intracellular PLP‐binding protein (PLPBP, previously named PROSC) and disorders where metabolites accumulate that inactivate PLP e.g. ALDH7A1 deficiency and hyperprolinaemia type II. Patients with these disorders can show rapid control of seizures in response to either pyridoxine and/or PLP with a lifelong dependency on supraphysiological vitamin B6 supply. The clinical and biochemical features of disorders leading to B6‐responsive seizures and the treatment of these disorders are described in this review.

BitterDB: taste ligands and receptors database in 2019.

Abstract: BitterDB (http://bitterdb.agri.huji.ac.il) was introduced in 2012 as a central resource for information on bitter-tasting molecules and their receptors. The information in BitterDB is frequently used for choosing suitable ligands for experimental studies, for developing bitterness predictors, for analysis of receptors promiscuity and more. Here, we describe a major upgrade of the database, including significant increase in content as well as new features. BitterDB now holds over 1000 bitter molecules, up from the initial 550. When available, quantitative sensory data on bitterness intensity as well as toxicity information were added. For 270 molecules, at least one associated bitter taste receptor (T2R) is reported. The overall number of ligand-T2R associations is now close to 800. BitterDB was extended to several species: in addition to human, it now holds information on mouse, cat and chicken T2Rs, and the compounds that activate them. BitterDB now provides a unique platform for structure-based studies with high-quality homology models, known ligands, and for the human receptors also data from mutagenesis experiments, information on frequently occurring single nucleotide polymorphisms and links to expression levels in different tissues.