Severe Pulmonary Arterial Hypertension in Healthy Young Infants: Single Center Experience.

OBJECTIVE: We studied the clinical presentation and management of acute pulmonary arterial hypertension (PAH) in healthy young infants, and the effect of thiamine therapy. METHODS: Review of hospital records was conducted for 56 healthy infants (aged below 6 month) who developed sudden onset of pulmonary arterial hypertension as diagnosed on 2D echocardiography, and were admitted at our institution. RESULTS: All patients received supportive care and pulmonary vasodilator therapy, whereas those admitted after Sep-tember, 2019 (n=28) received thiamine in addition, as per the institute's protocol. Overall, complete recovery was seen in 80% (n=45). Infants who died had significantly lower mean pH (7.05 vs 7.27; P=0.001) and serum bicarbonate (9.1 vs 14.9; P=0.007), higher arterial lactate (72.7 vs 61.5; P=0.92), ventricular dysfunction (16 vs 10; P=0.01) and shock (7 vs 9; P=0.008) when compared to those who survived. Baseline characteristics, severity of acidosis and pulmonary hypertension, time taken to recover from PAH, presence of ventricular dysfunction were comparable among those who received thiamine and those who did not receive it. Similarly, recovery (89% vs 71%; P=0.17) and mortality (11% vs 29%) were also comparable between the two groups. CONCLUSIONS: A significant proportion of infants with PAH improve with supportive treatment and pulmonary vasodilator therapy. Thiamine supplementation may not give any additional benefit in these patients.

Engineered zinc oxide nanoparticles: an alternative to conventional zinc sulphate in neutral and alkaline soils for sustainable wheat production.

Zinc oxide nanoparticles (ZnONP) were synthesized and characterized using SEM, EDAX, DLS and UV-Vis spectra. Its use as a nanofertilizer as an alternative to conventional zinc sulphate (ZnSO4.7H2O) was evaluated in five Zn-deficient soils with a variable pH range (7.2-8.7). For this, the carbon of the soil microbial biomass (SMBC), the bacterial population, the nutrient dynamics and the biometric parameters of the wheat crop were assessed. The varying dosages (0, 100, 200 and 500 mg/L), sizes (30-100 nm), and the spherical shape of ZnONPs were evaluated in comparison to ZnSO4.7H2O levels. Results showed the maximum SMBC and bacterial population at 100 mg/L of ZnONPs but a sharp decline at higher concentrations. In addition, soil application of ZnONPs at 5 mg/kg produced a higher root elongation (4.3-8.8%), shoot elongation (3.5-4.0%), total chlorophyll (4.9-5.6%), grain yield (1.7-2.3%) and grain Zn-content (1.6-2.1%) in comparison to the conventional ZnSO4.7H2O at 10 mg/L. ZnONPs at 100 mg/L produced a higher soil microbial biomass carbon (3.9-4.6%), bacterial population (7.2-9.0%), germination (22%) and grain Zn-content (17.9-20%) as compared to the conventional ZnSO4.7H2O at 0.5%. The higher grain Zn-contents could be attributed to the small size and high surface area of ZnONPs resulting in easy entry into the plant system either through root or foliar by penetrating the pores present in the cell membranes. Conversely, the conventional ZnSO4.7H2O, due to its larger size and higher solubility as compared to ZnONPs, has low retention in plant systems, high surface run-off and low fertilizer efficiency. Thus, the authors concluded to apply spherically synthesized ZnONPs (average size-36.7 nm) at 5 mg/kg in the soil application and 100 mg/L in the foliar application for maintaining SMBC and bacterial population, improving total chlorophyll, and grain Zn-contents and overall sustaining wheat production in Zn-deficient neutral and alkaline soils. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02861-1.

Artemisinin-resistant Leishmania parasite modulates host cell defense mechanism and exhibits altered expression of unfolded protein response genes.

Artemisinin, extracted from a medicinal herb Artemisia annua, is widely used to treat malaria and has shown potent anticancer activity. Artemisinin has been found to be effective against experimental visceral and cutaneous leishmaniasis. Despite extensive research to understand the complex mechanism of resistance to artemisinin, several questions remain unanswered. The artesunate (ART)-resistant line of Leishmania donovani was selected and cellular mechanisms associated with resistance to artemisinin were investigated. ART-resistant (AS-R) parasites showed reduced susceptibility towards ART both at promastigote and amastigote stage compared with ART sensitive (WT) parasites. WT and AS-R parasites were both more susceptible to ART at the early log phase of growth compared with late log phase. AS-R parasites were more infective to the host macrophages (p < 0.05). Evaluation of parasites' tolerance towards host microbicidal mechanisms revealed that AS-R parasites were more tolerant to complement-mediated lysis and nitrosative stress. ROS levels were modulated in presence of ART in AS-R parasites infected macrophages. Interestingly, infection of macrophages by AS-R parasites led to modulated levels of host interleukins, IL-2 and IL-10, in addition to nitric oxide. Additionally, AS-R parasites showed upregulated expression of genes of unfolded protein response pathway including methyltransferase domain-containing protein (HSP40) and flagellar attachment zone protein (prefoldin), that are reported to be associated with ART resistance in Plasmodium falciparum malaria. This study presents in vitro model of artemisinin-resistant Leishmania parasite and cellular mechanisms associated with ART resistance in Leishmania.

Synthesis and biological evaluation of new [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines against Leishmania donovani.

A series of [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines were synthesized and screened for their in vitro antileishmanial activity against Leishmania donovani. Among all, 8 compounds have shown more than 90% inhibition against promastigotes and IC50 in the range of 4.01-57.78 microM against amastigotes. Compound 5, a triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative was found to be the most active and least toxic with 20- & 10-fold more selectivity (S.I.=56.61) as compared to that of standard drugs pentamidine and sodium stibogluconate (SSG), respectively.