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Cerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1 × 1, 25 mg kg−1 × 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.
Cerebral malaria (CM) shows lethality rate of 15–25% despite effective antimalarial chemotherapy. The effective adjunct treatment to counteract the CM pathogenesis is urgently required. In murine CM model, most interventions studied till date are administered before the onset of CM symptoms, which belittle its translational value to human. We studied intramuscular arteether–vitamin D (ART–VD) combination treatment for CM outcome improvement after the onset of neurological symptoms. The intramuscular dose of 50 µg kg−1 VD for 3 days combined with a loading dose of 25 mg kg−1α/β arteether followed by 12·5 mg kg−1 dose for two consecutive days led to significant improvement in survival (73% in combination group vs 29 and 0% in arteether and VD monotherapy, respectively) and clinical recovery. The treatment in all the groups partially restored the blood–brain barrier integrity and reduced the level of serum proinflammatory cytokines tumour necrosis factor-α and interferon-γ. The brain transcripts of inflammatory chemokines viz. CXCL10, CXCL9, CCL4 and CCL5 and T cell migration in the brain microvasculature were significantly diminished in all the treatment groups. ART–VD treatment significantly reduced intercellular cell adhesion molecule-1 expression. Taken together, our findings show that coordinated actions of ART–VD improve the outcome of experimental CM.
Ten endophytic bacteria were isolated from different sugarcane varieties growing in the Crop Research Centre, Pantnagar on nitrogen-free medium. Plant growth-promoting potential of the isolates was reported in terms of indole acetic acid (IAA) production, phosphorus solubilization, siderophore production and antagonistic action against the pathogen Colletotrichum falcatum, which causes red rot disease in sugarcane in vitro. All the isolates were able to produce IAA (4.8–9 μg ml−1); three isolates (H3, H5 and H14) solubilized insoluble phosphorus on Pikovaskaya's agar; two isolates (H10 and H14) showed siderophore production on Chrome-azurol S (CAS) agar and antagonism against C. falcatum was exhibited by two isolates (H14 and H15) in a dual plate assay. 16 S rRNA sequencing identified isolates H3 and H12 as Pseudomonas spp., and H8, H14 and H15 as Bacillus spp. A field experiment on sugarcane was conducted with five plant growth-promoting bacterial endophytes Pseudomonas spp. (H3 and H12) and Bacillus spp. (H8, H14 and H15) along with standard strains of Gluconacetobacter and Azospirillum spp. Plant height, chlorophyll content, total nitrogen and cane length were significantly higher in almost all inoculated plants compared with the uninoculated control. An increase of 40% in cane yield over the control was obtained after inoculation with isolate H15 (Bacillus spp.). This was statistically on par with the standard endophyte Gluconacetobacter diazotrophicus, which resulted in 42% increased cane yield. Identification of new diazotrophs and their promising results towards improving plant growth in the field suggest their use as inoculants in future.
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