Early topical mitomycin-C prevents stricture formation in children with caustic ingestion.

AIM: Stricture formation is the most common remote complication of caustic ingestion. The aim of this study was evaluation of the efficacy of early topical endoscopic application of mitomycin C (MMC) in prevention of stricture formation after corrosive ingestion in children. METHODS: We enrolled 78 children with a history of caustic ingestion within 48 h in a prospective, randomised-controlled study. Only 61 children completed the study and were classified into two groups: group A and B. After initial stabilisation, patients in group A (n = 30) received topical application of MMC within the initial 48 h while patients in group B (n = 31) only received conventional management. Follow-up endoscopic dilatation was done every 2 weeks to patients in either group until no need for further dilatation. RESULTS: The barium study, which was done on the third week, revealed that all the patients (100%) on conservative management (group B) had strictures while only nine patients (30%) in group A had strictures (P < 0.001). The median number of dilatations required for patients in group B was 26 (min. = 23 and max. = 32) while in group A, it was 0 (min. = 0 and max. = 7) (P < 0.001). The success of early MMC application was complete response in 26 patients (86.7%), partial response in 3 patients (10%) and no response in 1 patient (3.3%). On the other side, conventional therapy with endoscopic dilatation achieved complete response in 11 patients (35.5%). CONCLUSION: Early topical MMC application proved its efficacy and safety in prevention of scar and stricture formation in children following caustic ingestion.

Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.

AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM. METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A ( ARSA) gene expression with their epigenetic regulators microRNA ( miR-2053) and long noncoding RNA ( lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed. RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM. CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

Synthesis, modeling and biological evaluation of hybrids from pyrazolo[1,5c]pyrimidine as antileishmanial agents.

AIM: A new series of pyrazolo[1,5-c]pyrimidines were synthesized by different hybridization strategies. METHODOLOGY: All structures were confirmed by IR, 1H, 13C, 1H-13C heteronuclear multiple-quantum correlation (HMQC) spectra and microanalysis. They were evaluated for their in vitro antileishmanial activity against miltefosine and amphotericin B deoxycholate as reference drugs. RESULTS: The most active compounds 2a and 9a demonstrated superior potencies to miltefosine by ten- and six-fold, respectively, for the promastigote form, and by 5.5-fold for the amastigote form. Their binding scenario to Leishmania major pteridine reductase was rationalized by docking experiments. In addition, all compounds were safe for the experimental animals orally up to 150 mg/kg and parenterally up to 75 mg/kg. CONCLUSION: This study provides novel chemotype class for antileishmanial activity. [Formula: see text].

Electrochemical dissolved oxygen removal from microfluidic streams for LOC sample pretreatment.

Current water quality monitoring for heavy metal contaminants largely results in analytical snapshots at a particular time and place. Therefore, we have been interested in miniaturized and inexpensive sensors suitable for long-term, real-time monitoring of the drinking water distribution grid, industrial wastewater effluents, and even rivers and lakes. Among the biggest challenges for such sensors are the issues of in-field device calibration and sample pretreatment. Previously, we have demonstrated use of coulometric stripping analysis for calibration-free determination of copper and mercury. For more negatively reduced metals, O2 reduction interferes with stripping analysis; hence, most electroanalysis techniques rely on pretreatments to remove dissolved oxygen (DO). Current strategies for portable DO removal offer limited practicality, because of their complexity, and often cause inadvertent sample alterations. Therefore, we have designed an indirect in-line electrochemical DO removal device (EDOR), utilizing a silver cathode to reduce DO in a chamber that is fluidically isolated from the sample stream by an O2-permeable membrane. The resulting concentration gradient supports passive DO diffusion from the sample stream into the deoxygenation chamber. The DO levels in the sample stream were determined by cyclic voltammetry (CV) and amperometry at a custom thin-layer cell (TLC) detector. Results show removal of 98% of the DO in a test sample at flow rates approaching 50 µL/min and power consumption as low as 165 mW h L(-1) at steady state. Besides our specific stripping application, this device is well-suited for LOC applications where miniaturized DO removal and/or regulation are desirable.

Electrochemical and microfabrication strategies for remotely operated smart chemical sensors: application of anodic stripping coulometry to calibration-free measurements of copper and mercury.

Remote unattended sensor networks are increasingly sought after to monitor the drinking water distribution grid, industrial wastewater effluents, and even rivers and lakes. One of the biggest challenges for application of such sensors is the issue of in-field device calibration. With this challenge in mind, we report here the use of anodic stripping coulometry (ASC) as the basis of a calibration-free micro-fabricated electrochemical sensor (CF-MES) for heavy metal determinations. The sensor platform consisted of a photo-lithographically patterned gold working electrode on SiO2 substrate, which was housed within a custom stopped-flow thin-layer cell, with a total volume of 2-4 µL. The behavior of this platform was characterized by fluorescent particle microscopy and electrochemical studies utilizing Fe(CN)6(3-/4-) as a model analyte. The average charge obtained for oxidation of 500 µM ferrocyanide after 60s over a 10 month period was 176 µC, corresponding to a volume of 3.65 µL (RSD = 2.4%). The response of the platform to copper concentrations ranging from 50 to 7500 ppb was evaluated, and the ASC results showed a linear dependence of charge on copper concentrations with excellent reproducibility (RSD ≤ 2.5%) and accuracy for most concentrations (≤ 5-10% error). The platform was also used to determine copper and mercury mixtures, where the total metallic content was measurable with excellent reproducibility (RSD ≤ 4%) and accuracy (≤ 6% error).

Synthesis and antibacterial activities of novel 2,5-diphenylindolo[2,3-e] pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines.

The formation of (E)-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-yl)hydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1) and isatin (or isatin derivatives) 2 at room temperature. The (E)-products could be isomerized into corresponding the (Z)-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4-7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H)-thione (11). The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.

Synthesis and antibacterial activities of novel imidazo[2,1-b]-1,3,4-thiadiazoles.

2-Amino-5-(2-aryl-2H-1,2,3-triazol-4-yl)-1,3,4-thiadiazoles 2-4 have been synthesized by the reaction of 2-aryl-2H-1,2,3-triazole-4-carboxylic acids 1 with thiosemicarbazide. Their reaction with phenacyl (p-substituted phenacyl) bromides led to formation of the respective 6-aryl-2-(2-aryl-2H-1,2,3-triazol-4-yl)imidazo[2,1-b]-1,3,4-thiadiazoles 5. Reactivity of the latter fused ring towards reaction with different electrophilic reagents afforded the corresponding 5-substituted derivatives 6-8. The structure of the above compounds was confirmed from their spectral characteristics. Some of these compounds were found to possess slight to moderate activity against the microorganisms Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and Escherichia coli.