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Pooja Agarwal, A R Anvikar, C R Pillai, Kumkum Srivastava
Background & objectives: : The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance. During the present study, efforts were made to establish long-term continuous in vitro culture of Indian field isolates of P. falciparum and to determine their sensitivity to standard antimalarial drugs and antibiotics. Methods: Four (MZR-I, -II, -III and -IV) P. falciparum isolates were obtained from four patients who showed artemisinin-based combination therapy (ACT) from Mizoram, a north-eastern State of India, and characterized for their in vitro susceptibility to chloroquine diphosphate (CQ), quinine hydrochloride dehydrate, mefloquine, piperaquine, artemether, arteether, dihydro-artemisinin (DHA), lumefantrine and atovaquone and antibiotics, azithromycin and doxycycline...
November 2017: Indian Journal of Medical Research
Xin Xu, Jun Wang, Kunkun Han, Shaoyan Li, Feng Xu, Yili Yang
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice...
February 17, 2018: Cancer Science
Vladimir Rancic, Bijal Rawal, Bogdan Panaitescu, Araya Ruangkittisakul, Klaus Ballanyi
The brainstem locus coeruleus (LC) controling behaviors like arousal, sleep, breathing, pain or opioid withdrawal is an established model for spontaneous action potential synchronization. Such synchronous 'spiking' might produce an extracellular field potential (FP) which is a crucial tool for neural network analyses. We found using ≥10 μm tip diameter suction electrodes in newborn rat brainstem slices that the LC generates at ∼1 Hz a robust rhythmic FP (rFP). During distinct rFP phases, LC neurons discharge with a jitter of ±33 ms single spikes that summate to a ∼200 ms-lasting population burst...
February 12, 2018: Neuroscience Letters
Sarah M Tindall, Cindy Vallières, Dev H Lakhani, Farida Islahudin, Kang-Nee Ting, Simon V Avery
Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake...
February 6, 2018: Scientific Reports
Supriya Sharma, Ram Suresh Bharti, Nitin Bhardwaj, Anupkumar R Anvikar, Neena Valecha, Neelima Mishra
BACKGROUND: Antimalarial drug resistance is a potential threat for control and elimination of malaria. To ascertain the status of antimalarial drug resistance at the study sites, correlation between in vitro drug sensitivity pattern and drug resistance molecular markers in Plasmodium falciparum malaria was undertaken. MATERIALS AND METHODS: Polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt) K76T and pfmdr1 N86Y were studied in relation to the in vitro susceptibility of P...
October 2017: Indian Journal of Medical Microbiology
Daniela F de Lima Corvino, Aditya A Chandorkar, Andres L Mora Carpio, Antonette Climaco
BACKGROUND Malaria infection during pregnancy is associated with increased perinatal and maternal morbidity and mortality. CASE REPORT A 29-year-old primigravida at 37 weeks of gestation, with no significant medical history, presented complaining of fever, chills, and generalized body aches. She had been living in Malawi for 1 year and was on atovaquone/proguanil prophylaxis until she was found to be pregnant. Prophylaxis was changed to mefloquine and discontinued upon her return to the US. Six weeks prior to presentation, she traveled to Malawi for 1 month when she was off prophylaxis...
February 5, 2018: American Journal of Case Reports
Meghna Desai, Jenny Hill, Silke Fernandes, Patrick Walker, Christopher Pell, Julie Gutman, Kassoum Kayentao, Raquel Gonzalez, Jayne Webster, Brian Greenwood, Michel Cot, Feiko O Ter Kuile
Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012...
January 30, 2018: Lancet Infectious Diseases
Xiao Zhang, Taotao Zhang, Jing Liu, Muzi Li, Yong Fu, Jianhai Xu, Qun Liu
The basic metabolic cytochrome P450 (CYP) proteins are essential for the biotransformation of sterols and xenobiotics. By contrast, the Toxoplasma gondii genome contains only one CYP gene, and the role of this enzyme in the physiology and biochemistry of apicomplexan parasites is unknown. Because it is a potential resistance gene, identifying the functionality of P450 in T. gondii is particularly important. Knocking out Tg-P450 had no significant effect on T. gondii survival, but mice infected with parasites overexpressing Tg-P450 exhibited significantly enhanced pathogenicity...
December 29, 2017: Oncotarget
Zhiyu Chen, Xiaolu Shen, La Huang, Hai Wu, Mazhong Zhang
The pathophysiology of neuropathic pain generation has not been fully investigated. Previous studies have primarily focused on changes in the properties of single neurons in the brain after nerve injury; however, little is known concerning the role of neuron-to-neuron connections in neuropathic pain pathogenesis. Synaptic transmission potentiation in anterior cingulate cortex (ACC) has been confirmed to be responsible for the formation of neuropathic pain. Thus, analysis of interneuronal connections in the ACC is an important approach for understanding the mechanism of neuropathic pain since it provides information on the potency of synaptic transmission...
January 26, 2018: Scientific Reports
Shuntaro Ikegawa, Nobuharu Fujii, Koh Tadokoro, Kota Sato, Miki Iwamoto, Masayuki Matsuda, Tomoko Inomata, Hiroyuki Sugiura, Takeru Asano, Shohei Yoshida, Hisakazu Nishimori, Ken-Ichi Matsuoka, Yoshinobu Maeda
A 52-year-old male suffered from progressive multifocal leukoencephalopathy (PML) after human leukocyte antigen (HLA)-haploidentical transplantation with post-transplantation cyclophosphamide (PTCY). Mirtazepam, mefloquine, and cytarabine failed to improve his symptoms and he finally died 4.5 months after PML onset. This is the first case report of a patient with PML after HLA-haploidentical transplantation with PTCY. Although T-cell replete HLA-haploidentical transplantation with PTCY has enabled early immune reconstitution, PML should be considered if a patient's mental condition deteriorates...
January 23, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W Wright
BACKGROUND: Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues...
December 28, 2017: Malaria Journal
Aida Paivandy, Martin Sandelin, Helena Igelström, Per Landelius, Christer Janson, Fabio R Melo, Gunnar Pejler
Mast cells are implicated as detrimental players in inflammatory lung diseases, particularly asthma. Mast cells respond to activating stimuli by releasing a wide panel of pro-inflammatory compounds that can contribute profoundly to the pathology, and there is currently an unmet need for strategies that efficiently ameliorate harmful effects of mast cells under such conditions. Here, we sought to evaluate a novel concept for targeting human lung mast cells, by assessing the possibility of selectively depleting the lung mast cells by induction of apoptosis...
2017: Frontiers in Immunology
Meltzer Eyal, Galia Rahav, Schwartz Eli
Background: Atovaquone-Proguanil is considered causal prophylaxis (inhibition of liver-stage schizonts) for Plasmodium falciparum, however, its causal prophylactic efficacy for P. vivax is not known. Travelers returning to non-endemic areas, provide a unique opportunity to study P. vivax prophylaxis. Methods: A retrospective observational study. For 11 years Israeli rafters who had traveled to the Omo River in Ethiopia, a highly malaria endemic area, were followed for at least one year after their return...
December 7, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ming Ni, Jin-Gang He, Hai-Yun Zhou, Xiao-Jia Lu, Yuan-Lang Hu, Li Mao, Fang Wang, Jian-Guo Chen, Zhuang-Li Hu
Mefloquine (MFQ) is widely used for the treatment of malaria clinically. Apart from antimalarial effect, psychiatric side effects such as depression and anxiety of MFQ have been reported. Interestingly, MFQ is also known as a broad-spectrum pannexin-1 (Panx1) inhibitor. Panx1 is a new gap junction channel expressed in the brain which mediates efflux of adenosine triphosphate (ATP). Although exogenous ATP has been known to produce a potential antidepressant-like effect, little is known about the role of Panx1 in pathophysiology of depression, especially the depression induced by administration of MFQ...
December 5, 2017: Neuropharmacology
Nele Seemann, Andrea Welling, Ingo Rustenbeck
The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a KATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca2+ channel activity, cytosolic Ca2+ concentration ([Ca2+ ]i ) and insulin secretion...
December 5, 2017: Molecular and Cellular Endocrinology
Stefan H F Hagmann
No abstract text is available yet for this article.
November 20, 2017: Travel Medicine and Infectious Disease
Benjamin E Zucker, Sybil R L Stacpoole
A 69-year-old woman presented with a cortical hand syndrome progressing over several weeks. MRI brain showed characteristic appearances of progressive multifocal leukoencephalopathy (PML), confirmed by detection of the JC virus in CSF, despite the absence of any evidence of immunosuppression. Treatment with mirtazapine, mefloquine and cidofovir did not affect the progression of the disease, which was fatal within 7 months of presentation. This report adds to the small case literature that suggests that PML can occur in immunocompetent people, albeit extremely rarely...
November 14, 2017: Journal of Neurovirology
Papichaya Phompradit, Wanna Chaijaroenkul, Kesara Na-Bangchang
The recent reports of high failure rates and decline in in vitro sensitivity of Plasmodium falciparum to artemisinin-based combination therapies (ACTs) suggest the possibility of clinical artemisinin resistance along the Thai-Cambodian and Thai-Myanmar borders. The study investigated cellular mechanisms of action and resistance of P. falciparum to artesunate (stage specific activity, interaction with hemozoin, and anti-oxidant levels) in the two paired P. falciparum isolates (MSF046 and MSF060) collected before treatment with a 3-day artesunate-mefloquine and at the time of recrudescence...
December 2017: Parasitology Research
Do Hung Son, Nguyen Thuy-Nhien, Lorenz von Seidlein, Truong Le Phuc-Nhi, Ngo Thi Phu, Nguyen Thi Kim Tuyen, Nguyen Huyen Tran, Nguyen Van Dung, Bui Van Quan, Nicholas P J Day, Arjen M Dondorp, Nicholas J White, Guy E Thwaites, Tran Tinh Hien
BACKGROUND: Prophylaxis for high-risk populations, such as forest workers, could be one component for malaria elimination in the Greater Mekong Sub-region. A study was conducted to assess the malaria incidence in forest rangers and the feasibility of malaria prophylaxis for rangers sleeping in forest camps. METHODS: Forest rangers deployed in the Bu Gia Map National Park, Vietnam were invited to participate in the study. Plasmodium infections were cleared using presumptive treatment, irrespective of malaria status, with a 3-day course dihydroartemisinin/piperaquine (DP) and a 14-day course of primaquine...
November 6, 2017: Malaria Journal
Maya Tickell-Painter, Rachel Saunders, Nicola Maayan, Vittoria Lutje, Alberto Mateo-Urdiales, Paul Garner
BACKGROUND: Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. METHODS: We carried out a systematic review to identify and critically appraise any death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports...
October 25, 2017: Travel Medicine and Infectious Disease
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