Thrombocytopenia in childhood malaria with special reference to P. vivax monoinfection: A study from Bikaner (Northwestern India)

Thrombocytopenia is commonly seen in Plasmodium vivax malaria, but its prognostic value has not been addressed in children. This prospective study included 676 admitted children of malaria [Plasmodium falciparum (Pf) monoinfection 262, Plasmodium vivax (Pv) monoinfection 380, and mixed (Pf?+?Pv) infection 34], in which thrombocytopenia (platelet count <150?×?10(3)/mm(3) on admission) was found in 442 (65.38%) children [Pf monoinfection 55.3% (145/262), Pv monoinfection 73.16% (278/380), and mixed infection 55.88% (19/34)]. The association of thrombocytopenia was statistically significant with Pv monoinfection [73.16% (278/380)] in comparison to either Pf monoinfection [55.34% (145/262); odds ratio (OR)?=?2.199 (95% confidence interval (CI) 1.577-3.068), p?相似文献   

CdTe QD-based inhibition and reactivation assay of acetylcholinesterase for the detection of organophosphorus pesticides

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides. In principle, GSH-capped CdTe QDs exhibit higher sensitivity towards H₂O₂ produced from the active enzymatic reaction of acetylcholinesterase (AChE) and choline oxidase (CHOx), which results in the fluorescence (FL) “turn-off” of the GSH-capped CdTe QDs. A “turn-on” FL of the CdTe QDs at 520 nm was recovered in the presence of organophosphate (OP). The FL changes of the GSH-capped CdTe QD/AChE/CHOx biosensor reasonably correspond to the amount of OP pesticides. The detection limit of the CdTe/AChE/CHOx biosensor towards paraoxon, dichlorvos, malathion and triazophos was 1.62 × 10⁻¹⁵ M, 75.3 × 10⁻¹⁵ M, 0.23 × 10⁻⁹ M and 10.6 × 10⁻¹² M, respectively. The GSH-capped CdTe QDs/AChE/CHOx biosensor was applied as a FL nanoprobe for assaying the enzymatic activity of AChE. The inhibited AChE was reactivated up to 94% using pyridine oximate (2-PyOx⁻), and functionalized pyridinium oximates (4-C₁₂PyOx⁻ and 4-C₁₈PyOx⁻) of varying chain lengths. It was found that the reactivation potency of the tested oximes varied with the chain length of the oximes. This biosensing system offers the promising benefit for the determination of the OP pesticides in food, water and environmental samples.

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides.     

Multistage antiplasmodial activity of hydroxyethylamine compounds,in vitro and in vivo evaluations

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species. New therapeutics acting against the pathogenic asexual and sexual stages, including liver-stage malarial infection, have now attained more attention in achieving malaria eradication efforts. In this paper, two previously identified potent antiplasmodial hydroxyethylamine (HEA) compounds were investigated for their activity against the malaria parasite''s multiple life stages. The compounds exhibited notable activity against the artemisinin-resistant strain of P. falciparum blood-stage culture with 50% inhibitory concentrations (IC₅₀) in the low micromolar range. The compounds'' cytotoxicity on HEK293, HepG2 and Huh-7 cells exhibited selective killing activity with IC₅₀ values > 170 μM. The in vivo efficacy was studied in mice infected with P. berghei NK65, which showed a significant reduction in the blood parasite load. Notably, the compounds were active against liver-stage infection, mainly compound 1 with an IC₅₀ value of 1.89 μM. Mice infected with P. berghei sporozoites treated with compound 1 at 50 mg kg⁻¹ dose had markedly reduced liver stage infection. Moreover, both compounds prevented ookinete maturation and affected the developmental progression of gametocytes. Further, systematic in silico studies suggested both the compounds have a high affinity towards plasmepsin II with favorable pharmacological properties. Overall, the findings demonstrated that HEA and piperidine possessing compounds have immense potential in treating malarial infection by acting as multistage inhibitors.

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species.     

Understanding the underutilization of cervical brachytherapy for locally advanced cervical cancer

PurposeTo understand the reasons behind current low utilization of brachytherapy for locally advanced cervical cancer in the United States.Methods and MaterialsA 17-item survey was e-mailed to the American Brachytherapy Society (ABS) listserv of active members in 2018. Responses of attending physicians in the United States were included in the analysis.ResultsAmong a total of 135 respondents, 81 completed the survey. Eighty-four percent agree/strongly agree that cervical brachytherapy is underutilized, and 46.9% disagree/strongly disagree that residents are receiving adequate training for brachytherapy; 75.3% agree/strongly agree that inadequate maintenance of brachytherapy skills is a major obstacle to brachytherapy use; and 71.6% agree/strongly agree that increased time requirement constitutes a major obstacle. Over 97% will recommend brachytherapy for most patients with cervical cancer if given access/time; 72.8% always perform their own brachytherapy, whereas 29.6% reported some type of barrier exists in performing brachytherapy themselves, with time required to perform brachytherapy (9.9%) being a leading factor. A quarter (24.7%) routinely refer to other radiation oncologists for brachytherapy. Even among ABS members, 37.0% reported that they would perform an intensity-modulated radiation therapy or stereotactic body radiation therapy boost in specific scenarios in potentially curable patients. The most common scenario is inability to place a uterine tandem (56.7%).ConclusionsThe underutilization of brachytherapy in cervical cancer is widely recognized by ABS members with inadequate training during residency and inadequate maintenance of skills being possible major contributing factors. Even among ABS members, there are identifiable barriers. Continued advocacy and future initiatives in enhancing access to brachytherapy training and efficiency are needed.     

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Isolation of Aspergillus nidulans from a case of fungal rhinosinusitis: a case report

A rare species i.e. A. nidulans is reported as a causative agent of allergic fungal rhinosinusitis in this study. It is an increasingly recognized type of chronic recurring hypertrophic sinus disease. There are more than 185 species of aspergillus and over 95% of all infections are caused by A. fumigatus, A. flavus and A. niger. A. fumigatus alone accounts for the large majority of cases of both invasive and non invasive aspergillosis. A young immunocompetent lady presented with bilateral nasal obstruction due to multiple polypoid mass at Sheth Vadilal Sarabhai General Hospital, Ahmedabad. Provisional diagnosis of sinonasal polyposis possibly due to fungal cause with infiltration in to nasal cavity was made. Bilateral functional endoscopic sinus surgery with polypectomy was done. The specimen was examined by standard methods and the fungus was identified as A. nidulans by slide culture.     

Arginine-α, β-dehydrophenylalanine Dipeptide Nanoparticles for pH-Responsive Drug Delivery

Purpose

Nanoparticles (NPs) exhibiting responsiveness towards pH variations in organs, tissue microenvironments and cellular compartments can significantly add on to the drug delivery potential. Here, we have developed NPs from an amphipathic dipeptide, Arginine-α, β-dehydrophenylalanine (RΔF), and tried to explore their pH responsive drug delivery potential in various cancer cells.

Methods

RΔF-NPs were architectured by harnessing the process of molecular self-assembly followed by the assessment of effect of pH on NPs morphology using zetasizer, SEM and CD. FTIR and PXRD analysis of the dipeptide and doxorubicin (Dox) were carried out for compatibility assessment followed by encapsulation of Dox in RΔF-NPs. RΔF-Dox-NPs were evaluated for pH dependent release as well as for in-vitro cellular internalization and efficacy in cancer cells.

Results

RΔF self-assembled to form monodispersed particles at pH 7. SEM analysis revealed a loss of overall particle morphology along with particle aggregation at highly acidic and basic pH respectively. The NPs demonstrated a slow and sustained release behaviour at pH 7 (97.64?±?4.71% after 36 h) in comparison to pH 2 (90.27?±?1.45% after 8 h) and pH 10 (96.39?±?3.87% after 12 h). In-vitro efficacy studies carried-out in various cancer cells revealed that RΔF-Dox-NPs exhibited higher efficacy with 1.65, 1.95 and 13.34 fold lower IC₅₀ values in comparison to Dox in C6, HCT-116 and AGS cell lines.

Conclusions

RΔF-Dox-NPs with higher drug release at acidic pH, enhanced internalization in cancer cells along with higher cytotoxic potential can act as effective pH responsive drug delivery systems.