No abstract

Background: Monocytes are major effector cells during Leishmania infection and any perturbance in their functions may potentially influence prospective immune responses. However functional phenotype acquired by blood monocytes in Visceral Leishmaniasis (VL) patients is poorly understood. They can acquire inflammatory or anti-inflammatory phenotypes depending upon activation signals, where later phenotype is associated with suppression of cell mediated immunity and can result in susceptibility to intracellular parasites. We speculated that VL induces a distinct monocyte phenotype which possess anti-parasitic activity and with present perspective we began to characterize activation status of blood monocytes as the basis of better parasite survival in human VL.Methods & Materials: Peripheral blood monocytes from VL and healthy controls from endemic area of Muzaffarpur, Bihar, India were compared both ex-vivo and after culture with parasite or soluble leishmanial antigen to establish activation status by assessing various pro-inflammatory and anti-inflammatory markers at phenotypic, genotypic and functional levels employing flow cytometry and RT-qPCR based assays.Results: Here we report that circulating monocytes in VL patients display anti-inflammatory phenotype composed of upregulated genes such as TGM2, C type lectin receptors, VDR, PKM, SOCS1 accompanied by downregulation in expression of inflammatory markers notably NOS2 and FCER2 at the mRNA level. These cells are non-inflammatory as they demonstrate decreased frequencies of IL6 and IL1␤ producing monocytes. We showed these are poor effector cells according to decrease in phagocytosis capacity, expression of NADPH sub-units p47 and p67 phox and ROS production. Subjects with VL had high circulating monocyte counts but they express more anti-inflammatory markers and show reduced effector functions than after treatment or healthy controls.Conclusion: These findings suggest that encounters between Leishmania and monocytes in VL promote a phenotype which is non inflammatory and is skewed towards an anti-inflammatory phenotype, that might sustain chronic infection. Strategies to manipulate the polarization of these cells may provide therapeutic advantage with appropriate pharmacological interventions.

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model. A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 ​mg/kg), SLN-CRYP (5 ​mg/kg), ABZ (50 ​mg/kg) DXM (0.5 ​mg/kg), and PHE (30 ​mg/kg). were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains. All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p ​< ​0.0001); as were frequency (p ​< ​0.0001) and duration (p ​< ​0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p ​= ​0.0016) and IFN-γ (p ​< ​0.0001). Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 18 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laninamivir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.

Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 19 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laminavir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.