Drug Resistance in Toxoplasma gondii

Toxoplasma gondii (T. gondii) is a global protozoan parasite infecting up to one-third of the world population. Pyrimethamine (PYR) and sulfadiazine (SDZ) are the most widely used drugs for treatment of toxoplasmosis; however, several failure cases have been recorded as well; suggesting the existence of drug resistant strains. This review aims to give a systematic and comprehensive understanding of drug resistance in T. gondii including mechanisms of resistance and sites of drug action in parasite. Analogous amino acid substitutions in the Toxoplasma enzyme were identified to confer PYR resistance. Moreover, resistance to clindamycin, spiramycin, and azithromycin is encoded in the rRNA genes of T. gondii. However, T. gondii SDZ resistance mechanism has not been proved yet. Recently there has been a slight increase in SDZ resistance. That is why the majority of studies were carried out using SDZ. Six strains resistant to SDZ were found in clinical cases between 2013 and 2017 which among Brazilian T. gondii isolates, TgCTBr11, Ck3, and Pg1 were identified in human toxoplasmosis, as well as in livestock intended for human consumption. In conclusion, recent experimental studies in clinical cases have clearly shown that drug resistance in Toxoplasma is ongoing. Thus, establishing a more effective therapeutic scheme in the treatment of toxoplasmosis is critically needed. The emergence of T. gondii strains resistant to current drugs, reviewed here, represents a concern not only for treatment failure but also for increased clinical severity in immunocompromised patients. To improve the therapeutic outcome in patients, a greater understanding of the exact mechanisms of drug resistance in T. gondii should be developed. Thus, monitoring the presence of resistant parasites, in food products, would seem a prudent public health program

Pharmacological treatments of COVID-19

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies. © 2020, Maj Institute of Pharmacology Polish Academy of Sciences

Facile green synthesis of silver nanoparticles using Crocus Haussknechtii Bois bulb extract: Catalytic activity and antibacterial properties

Green synthesis of silver nanoparticles (AgNPs) is of particular interest due to their catalytic and antibacterial properties. In this study, the extract of Crocus Haussknechtii Bois was used to synthesize small-sized AgNPs and the effective parameters were investigated. The experimental optimization of temperature and pH reveals that spherical nanoparticles with a size of about 10-25 nm could be obtained using 0.5 mL of AgNO3 (20 mM) and 0.5 mL of the plant extract with total volume of 20 mL at pH= 7 and temperature of 75 degrees C within 120 min. The catalytic activity of synthesized nanoparticles was evaluated in the degradation of a Congo Red dye in the presence of sodium borohydride. The results indicate that 16.67 mu M Congo Red dye could be degraded in only 220 s (first-order kinetic model constant of Kapp= 0.011 s(-1) for only 5.39 mu g of synthesized AgNPs). The rate of degradation is one of the highest values reported for catalytic reduction of Congo Red dye. In addition, the synthesized AgNPs showed a significant inhibitory effect against both gram-positive and gram-negative bacteria, where the minimum inhibitory concentration (MIC) values of 26.9 and 20.2 mu g/mL were obtained for synthesized AgNPs against S. aureus and P. aeruginosa, respectively

Modelling of dye adsorption from aqueous solution on polyaniline/carboxymethyl cellulose/TiO2 nanocomposites

In the present study, a polyaniline/carboxymethyl cellulose/TiO2 nanocomposite (PAn/CMC/TiO2) was synthesized by a polymerization method, and was used for adsorption of Congo Red from aqueous solution. The effects of operational parameters of the adsorption process including pH, initial dye concentration, temperature, adsorbent dosage, and adsorption time on adsorption efficiency were investigated, and response surface methodology was used for their optimization. Optimal adsorption conditions were determined at pH of 2.6, initial concentration of , temperature of 56 °C, adsorption time of 24 min, and adsorbent dose of 0.14 g. In addition, the system was also simulated using artificial neural network (ANN) and genetic programming (GP). It was found that the behavior of the system could be well predicted by ANN using 5, 1 and 8 neurons for input, middle and output layers, respectively. Kinetic and isothermal analyses showed that the maximum adsorption capacities were obtained at 94.28, 97.53 and 119.9 by Langmuir model at temperatures of 25, 40 and 50 °C, respectively and that adsorption kinetics followed the pseudo-second-order model. The nano-adsorbent was also found to be reusable without a significant change in adsorption capacity for at least five adsorption-desorption cycles. Finally, the mechanism of dye adsorption on the nano-adsorbent was investigated and proposed

What is the appropriate aganglionic bowel length on contrast enema for attempting single stage transanal endorectal pull-through in Hirschsprung disease?

Purpose: To identify influence of different values of age and abnormal bowel length in HD patients selected for single stage TERPT which affects the technique of surgery. Methods: This observational study was carried out for over 2.5 years. All children younger than 14 years old with clinical suspicion for HD, typical transitional zone (TZ) on contrast enema (CE) distal to splenic flexure, preoperative diagnosis approved by full thickness biopsy, no previous surgical history and no urgency were included. The distance between the anus and TZ was considered as aganglionic length on CE. Biopsy was taken from distal to proximal of resected bowel to reach circumferentially normal innervated bowel. Paired sample Student's t-test, Pearson correlation test, receiver operating characteristic (ROC) analysis were performed. Results: Forty-eight patients were enrolled in this study. Measured mean for aganglionic bowel length on CE and pathology were 33.5 ± 17.1 cm and 56.8 ± 33.5 cm, respectively (p < 0.01). Correlation coefficient (R) and coefficient of determination (R2) were 0.632 and 40, respectively (p < 0.01). The difference between radiologic and pathologic measurements in females was higher than males (mean: 29.3 vs 21.9 cm) but was not statistically significant (p = 0.75). There was statistically significant difference between CE and pathologic results in the infants younger than 10 months (p =.004). Abnormal bowel length equal to 52 cm predicted requirement of laparoscopy assistance/laparotomy with 75 sensitivity and 85 specificity. Conclusion: Our investigation showed it is safe to attempt for single stage TERPT when aganglionic length on CE is less than 52 cm and the child with HD is older than 10 months. Chance of requiring additional laparotomy or laparoscopy assistance is low in these patients. Type of study: Study of diagnostic test. Level of evidence: Level II. © 2020 Elsevier Inc