The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myeloproliferative disorder, sAML-MPD). Leukaemic colony forming units (L-CFU) were assayed by plating peripheral blood (PB) blast cells in methyl-cellulose and using LCM-PHA as stimulant. In each case parallel cultures were made with and without stimulating factors. Plating efficiency (PE) was defined as the number of clusters plus colonies/10(5) cells plated. Autonomous growth (AG) was the number of colonies plus clusters growing without stimulant. The autonomous proliferative index (API) was calculated as the number of clusters + colonies without stimulating factor divided by the number of clusters + colonies with stimulating factor. No significant differences in the PE between de novo and secondary AML were found. Autonomous growth was significantly higher in sAML-MPD. The FAB subtype M3 leukaemias displayed a significantly greater PE and a significantly lower API when compared with the other FAB subgroups (P=0.0002). Upon analysing the relationship with the immunophenotype, only CD33 expression showed a significant relationship with the in vitro growth pattern; CD33+ cases displayed a higher PE (P=0.0002) and AG (P=0.0003) than CD33- cases. When patients were grouped according to the level of rh123 efflux (MDR1) it was observed that cases with >30% elimination showed a higher AG and API than those with <30% (P=0.03). Finally we found that patients with higher API (>0.05) displayed a significantly shorter overall survival as compared with patients with API<0.05 (P=0.04). The in vitro study properties of clonogenic cells produces relevant clinical information of leukaemic cell biology in AML patients.

Combinatorial phage display technology offers a new possibility for making human antibodies which could be used in immune therapy. We explored the use of this technology to make human scFvs specific for crotoxin, the main toxic component of the venom of the South-American rattlesnake Crotalus durissus terrificus. Crotoxin, a phospholipase A2 neurotoxin constituted by the association of two subunits, exerts its lethal action by blocking neuromuscular transmission. This is the first report of human anticrotoxin scFvs (scFv 1, scFv 6 and scFv 8) isolated from a naive library of more than 1010 scFv clones with in vivo neutralizing activity. Nevertheless, differences are observed at the level of biological and immunological effects. Only scFv 8 is able to reduce the myotoxicity induced by crotoxin and scFv 1 is capable of altering the in vitro enzymatic activity of this toxin. All three scFvs recognize a region of one subunit located at the junction with the other one. Moreover these scFvs share strong amino acid homologies at the level of either the heavy or the light chain. Taken together, our results suggest that the use of human anticrotoxin scFvs may lead to a new and less aggressive passive immune therapy against poisoning by the venom of Crotalus durissus terrificus.

According to the World Health Organisation, on March 27, 2020, the number of confirmed cases of COVID-19 has already exceeded 509.000 with about of 23.000 deaths worldwide. Given this, the impact of COVID-19 on humanity cannot be overlooked, and basic research are urgently needed. This research aims to find antagonists already approved for another diseases, that may inhibit activity of the main protease <i>(Mpro)</i> of the SARS-CoV-2 virus, as well as modulate the <i>ACE2</i> receptors, largely found in lung cells and reduce viral replication by inhibiting <i>NSP12 RNA Polymerase</i>. Docking molecular simulations were realized among a total of <i>28 ligands</i> published in the literature against COVID-19. Docking studies were made with algorithm of <i>AutoDock Vina 1.1.2</i> software. A structure-based virtual screening was performed with <i>MTiOpenScreen</i>. Subsequently, the physical-chemical and pharmacokinetic parameters were analyzed with <i>SwissADME</i> in order to select only the most promising ones. Finally, simulations of molecular dynamics with elapsed time of <i>4 nanoseconds</i> (ns) were analysed in order to better understand the action of drugs to the detriment of the limitations of molecular docking. This work has shown that, in comparative terms, <i>Simeprevir</i>, <i>Paritaprevir</i>, <i>Remdesivir</i> and <i>Baricitinib</i> are currently among the most promising in remission of symptoms from the disease. <i>Hydroxy-chloroquine</i>, <i>Chloroquine</i> and <i>Azithromicin</i> were not showed effective, as monotherapies, against COVID-19 or <i>lung cell</i> receptors.

A pilot, open, comparative study was performed on patients with locally advanced cervical cancer to investigate the efficacy and safety of amifostine. Twenty patients with a histologic diagnosis of squamous cervical cancer were treated with radiotherapy and randomized in two groups. Group A received cisplatin at 20 mg/m2 for five days in two cycles during intracavitary radiotherapy and 100 mg/m2 x 2 cycles during external radiotherapy, and amifostine 825 mg/m2 15 min before the cisplatin infusion. Patients in group B received cisplatin in the same doses without amifostine. All patients had complete responses during a median follow-up of 20 months. Grade three neutropenia was present in two patients in group A and in four of the control group, P = 0.31; grade 2 neurologic toxicity was seen in four patients in group B and in one of the patients in group A, P = 0.15. One patient needed temporary interruption of amifostine due to hypotension. Eight of 10 patients in group A developed hypocalcemia during the treatment with amifostine. Our findings indicate that amifostine was well tolerated. In this series a mild neurologic and hematologic protection was found in patients that received amifostine, although this was not statistically significant. No differences in disease-free survival response and overall survival was seen between the two groups.

Problem statement: The IEEE802.11 standard states that all stations have the same probability of accessing the network, but does not consider important parameters such as transmission rates and signal-to-noise ratios. However, these networks present an anomaly that allows a station with a low transmission rate to use the communication channel for a long time. Approach: In this context, this study presents a Quality of Service (QoS) policy, based on the implementation of the IEEE802.11e standard, that aims to keep or find the most fair scenario for IEEE802.11 networks. Hence, an algorithm for determining a fairness index is proposed based on physical parameters such as connection rates, service types and necessary conditions for the communication service. Results: The results obtained using the NS2 simulation software show that the proposed QoS policy was able to improve the network throughput or, at least, to keep a condition similar to the original one, when the proposed policy was not applied. Conclusion: All simulated scenarios presented a network performance gain or, at least, a similar result when compared to the results obtained when the IEEE802.11 standard was applied.