Therapeutic apheresis using a mononuclear cell program to lower the microfilaria burden of a 23‐year‐old African woman with loiasis

Apheresis has been used to lower the parasite burden of patients with Loa loa infection, but there are no reports regarding how to do this using modern, continuous flow equipment with a currently available program. A 23‐year‐old female refugee from Cameroon with known Loa loa infection presented to our Emergency Department with acute mental status changes and a picture of encephalitis. Lumbar puncture revealed Loa loa in her cerebrospinal fluid. Her midday blood microfilaria count was 15,000/mL. Because treatment with diethylcarbamazine was under consideration, we were asked to lower her parasite burden using apheresis. One single 2‐total blood volume apheresis using the mononuclear cell program (without hydroxyethyl starch) on a COBE^® Spectra Apheresis System decreased the microfilarial load from 15,000/mL to 10,666/mL, a 29% reduction. J. Clin. Apheresis 32:200–202, 2017. © 2016 Wiley Periodicals, Inc.     

Devil's Claw-a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens

Ethnopharmacological relevance

Harpagophytum procumbens subps. procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) is an important traditional medicine growing in the Kalahari region of southern Africa where it is consumed as a general health tonic and for treating diverse ailments including arthritis, pain, fever, ulcers and boils.

Aim of the review

To provide a comprehensive overview of the ethnobotany, phytochemistry and biological activity of H. procumbens and possibly make recommendations for further research.

Materials and methods

Peer-reviewed articles on H. procumbens were acquired on Scopus, ScienceDirect and SciFinder, there was no specific timeline set for the search. A focus group discussion was held with different communities in Botswana to further understand ethnobotanical uses of the plant.

Results

Harpogophytum procumbens is used for a wide variety of health conditions in the form of infusions, decoctions, tinctures, powders and extracts. In addition to the common local use for arthritis and pain, other ethnomedicinal uses include dyspepsia, fever, blood diseases, urinary tract infections, postpartum pain, sprains, sores, ulcers and boils. Scientific studies revealed that H. procumbens exhibits analgesic, anti-oxidant, anti-diabetic, anti-epileptic, antimicrobial and antimalarial activities amongst others. Iridoid glycosides and phenylpropanoid glycosides have been the focus of phytochemical investigations as the biological activity has been ascribed to the iridoid glycosides (such as harpagoside and harpagide), which are common in nature and are known to possess anti-inflammatory activity. In addition, it has been shown that the hydrolysed products of harpagoside and harpagide have more pronounced anti-inflammatory activity when compared to the unhydrolysed compounds. Harpagophytum zeyheri is a close taxonomic ally of H. procumbens but H. procumbens is the favoured species of commerce, and contains higher levels of the pharmacologically active constituents. The two are used interchangeably and H. procumbens raw material is often intentionally adulterated with H. zeyheri and this may impact on the efficacy of inadequately controlled health products. The main exporter of this highly commercialised plant is Namibia. In 2009 alone, Harpagophytum exports were worth approximately €1.06 million. The high demand for health products based on this plant has led to over-harvesting, raising concerns about sustainability. Although only the secondary tubers are utilised commercially, the whole plant is often destroyed during harvesting.

Conclusions

Harpagophytum procumbens is used to treat a wide range of ailments. Some of the ethnobotanical claims have been confirmed through in vitro studies, however, when the constituents deemed to be the biologically active compounds were isolated the efficacy was lower than that of the whole extract. This necessitates the use of a different approach where all the metabolites are considered using a robust method such as spectroscopy; the phytochemical data can then be superimposed on the biological activity. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products because the orthodox methods in current use are time-consuming and labour intensive.     

Therapeutic live vaccines as a potential anticancer strategy

The design of efficient cancer treatments is one of the major challenges of medical science. Therapeutic vaccines of cancer have been emerged as an attractive approach for their capacity of breaking the immune tolerance and invoking long-term immune response targeting cancer cells without autoimmunity. An efficient antigen delivery system is the key issue of developing an effective cancer vaccine. In this regard, live vaccination strategies including various live bacterial and viral vectors have attracted a great attention. Several bacterial strains such as Salmonella, Listeria monocytogenes and Lactococcus lactis effectively colonize solid tumors and act as antitumor therapeutics. On the other hand, the use of viruses as vaccine vectors such as Vaccinia, Adenovirus, Herpes simplex virus, Paramyxovirus and Retroviruses utilizes mechanisms that evolved in these microbes for entering cells and capturing the cellular machinery to express viral proteins. Viral/bacterial-vectored vaccines induce systemic T-cell responses including polyfunctional cytokine-secreting CD4+ and CD8+ T-cells. However, there is an urgent need for the development of new safe live vaccine vectors that are capable of enhancing antigen presentation and eliciting potent immune responses without the risk of development of disease in humans. Recently, nonpathogenic parasites including Leishmania tarentolae, Toxoplasma gondii and Trypanosoma cruzi have emerged to be a novel candidate for gene delivery and heterologous genes expression. In this review, recent researches on cancer therapy using genetically modified bacteria and virus are summarized. In addition, live parasite-based vectors will be discussed as a novel anticancer therapeutic approach.     

CCL2-independent role of CCR2 in immune responses against Leishmania major

The chemokine CCL2 (MCP-1) and its receptor CCR2 modulate leucocyte migration and T helper differentiation. CCL2 or CCR2 knockout (KO) mice have divergent phenotypes following infection with the intracellular parasite Leishmania major (L. major). Compared to wild-type (WT) mice, intradermally infected CCR2 KO mice in the L. major-resistant C57BL/6j background become susceptible and fail to generate protective Th1 responses. In contrast, subcutaneously infected CCL2 KO mice in the L. major-susceptible BALB/c background are resistant and exhibit reduced pathogenic Th2 responses. Here we explore two variables that may account for this contrasting outcome, namely background strain and route of infection. We found that the CCR2-null state, both in the BALB/c and the C57BL/6j background, was associated with increased susceptibility to intradermal or subcutaneous L. major infection. Notably, the CCL2-null state did not change the ability of C57BL/6j mice to mount protective responses following intradermal infection. Dual genetic inactivation of CCR2 and CCL2 in the L. major-resistant C57BL/6j background resulted in a shift to a susceptible phenotype analogous to that of CCR2 KO in the C57BL/6j background. We concluded that CCL2-independent effects of CCR2 are indispensable for the control of L. major infection and the generation of protective immune responses.     

Nematicidal activity of two monoterpenoids and SER-2 tyramine receptor of Caenorhabditis elegans

In vitro cultures of two nematodes (Caenorhabditis elegans and Ascaris suum) were established to study the nematicidal activity of three monoterpenoids (thymol, carvacrol and p-cymene). Toxicity of thymol and carvacrol was found for the two nematodes tested. The study was then aimed to address whether nematode tyramine receptor (TyrR) could interact with the two compounds by using HEK293 mammalian cells transfected with a C. elegans TyrR (ser-2) sequence, in hope of developing a high-throughput cell-based platform for future screening of new antihelminthic compounds. SER-2 expression and functionality in the transfected cells was first confirmed by green fluorescent protein tagging, competitive receptor binding, intracellular cyclic AMP, and intracellular calcium [Ca²⁺]_i mobilization assays. Thymol and carvacrol were then tested and demonstrated to interact with TyrR in desensitizing SER-2 for tyramine activation in [Ca²⁺]_i mobilization assay, and in translocating SER-2 from membrane to cytoplasm in receptor internalization assay. Receptor internalization activity of thymol and carvacrol was significantly blocked in cells expressing mutant SER-2 with the S210A/S214A double mutations, thus confirming specificity of the interactions. In summary, the current study showed that the nematicidal activity of thymol and carvacrol might be mediated through TyrR as the two compounds could trigger the signaling cascade downstream from the receptor in cells expressing wild-type but not a mutant SER-2. The TyrR-expressing cell system may prove to be a good screening platform for developing new antihelmintic compounds that may overcome parasite drug resistance, especially when such chemicals are used in combination with commercial drugs.     

Cross-talk in host–parasite associations: What do past and recent proteomics approaches tell us?

A cross-talk in host–parasite associations begins when a host encounters a parasite. For many host–parasite relationships, this cross-talk has been taking place for hundreds of millions of years. The co-evolution of hosts and parasites, the familiar ‘arms race’ results in fascinating adaptations. Over the years, host–parasite interactions have been studied extensively from both the host and parasitic point of view. Proteomics studies have led to new insights into host–parasite cross-talk and suggest that the molecular strategies used by parasites attacking animals and plants share many similarities. Likewise, animals and plants use several common molecular tactics to counter parasite attacks. Based on proteomics surveys undertaken since the post-genomic era, a synthesis is presented on the molecular strategies used by intra- and extracellular parasites to invade and create the needed habitat for growth inside the host, as well as strategies used by hosts to counter these parasite attacks. Pitfalls in deciphering host–parasite cross-talk are also discussed. To conclude, helpful advice is given with regard to new directions that are needed to discover the generic and specific molecular strategies used by the host against parasite invasion as well as by the parasite to invade, survive, and grow inside their hosts, and to finally discover parasitic molecular signatures associated with their development.     

Crosstalk between Zinc Status and Giardia Infection: A New Approach

Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia.