Dimensional alterations and solubility of new endodontic sealers

This study evaluated the dimensional alterations and the solubility of two experimental endodontic sealers based on Copaifera multijuga oil-resin (Biosealer) and castor oil bean cement (Poliquil), maintained in different storage solutions. Twenty specimens (3 mm diameter and 2 mm height) of each sealer were assigned to 2 groups (n=10) according to the storage solution: simulated tissue fluid (STF) or distilled water (DW). The specimens were stored in these solutions during 90 days, being removed every 30 days for weighting. The solutions were renewed every 15 days. The results were subjected to statistical analysis by Dunn's and Mann-Whitney tests (a=0.05). The solubility of Poliquil was higher in STF (38.4 ± 36.0) than in DW (28.4 ± 15.0), while Biosealer showed higher solubility in DW (34.61 ± 6.0) than in STF (18.59 ± 8.0). The storage solution influenced the behavior of sealers in relation to the weight variation (p=0.0001). Poliquil presented higher variation of weight independent of the solution (p=0.239). Biosealer also presented higher variation of weight regardless of the solution (p=0.0001). The solubility of Biosealer was different from that of Poliquil, but both sealers showed low solubility in STF. Under the tested conditions, neither of the materials were according to the ADA'S specification.     

Deciphering the immuno-pathological role of FLT,and evaluation of a novel dual inhibitor of topoisomerases and mutant-FLT3 for treating leukemia

Acute myeloid leukemia (AML) is a type of leukemia with an aggressive phenotype, that commonly occurs in adults and with disappointing treatment outcomes. Genetic alterations were implicated in the etiology of cancers and form the basis for defining patient prognoses and guiding targeted therapies. In the present study, we leveraged bulk and single-cell RNA sequencing datasets from AML patients to determine the clinical significance of Fms-related receptor tyrosine kinase 3 (FLT3) alterations on the T-cell phenotype and immune response of AML patients. Subsequently, we evaluated the therapeutic potential of Lwk-n019, a novel small-molecule derivative of thiochromeno[2,3-c]quinolin-12-one. Our results suggested that FLT3 plays an important role in the progression, aggressive phenotype, and worse immune response of patients. An FLT3 mutation was associated with dysfunctional T-cell phenotypes, and high risk and shorter survival of AML patients. Our findings further suggested that the aggressiveness of AML and the prognostic role of FLT3 are associated with the co-occurrence of NPM1 and DNMT3A mutations. Lwk-n019 demonstrated dose-dependent anticancer activities against various leukemia cancer cell lines. Lwk-n019 demonstrated highly selective kinase inhibitory activities against the wild-type FLT3 (D835V) and mutant FLT3 (internal tandem duplication (ITD), D835V) with >95% and 99% inhibitory levels, respectively. Moreover, the compound demonstrated the best binding constant (Kd value) of 0.77 µM against FLT3 (ITD, 835V). In addition, Lwk-n019 significantly inhibited the activities of both the topoisomerase I (TOPI) and TOPII enzymes, with higher TOPI inhibitory activity than camptothecin, a clinical inhibitor. While the jejunum, duodenum, cecum, and colon were prime sites of absorption, Lwk-n019 achieved maximum concentration (Cmax), Vd, blood/plasma ratio, time to maximum concentration (Tmax), area under the receiver operating concentration curve (AUC)_(0-24), and AUC_(0-∞) values of 0.665 µg/mL, 5.21 Vc, L/kg, 1.5 h, 6634.7, and 6909.2, respectively. In conclusion, Lwk-n019 demonstrated anticancer activities via multi-target inhibition of TOPs and kinases with high inhibition preference for mutant ITD-FLT3. The present pioneer study provides a basis for advanced optimization of drug potency, selectivity, specificity, and other properties desired of anticancer drug leads. Studies are ongoing to determine the full therapeutic properties of Lwk-n019 and the detailed mechanisms of FLT3 in TOP inhibition.     

Wasserstoffionconcentration und Fermentgehalt im Duodenalsaft.

Durch eine fractionierte Aufheberung des Duodenalsafts wurde folgendes festgestellt. Die PH-werte der einzelnen Proben schwanken innerhalb weiten Grenzen von PH 8.5 bis > 1.0, kleinere Schwankungen sind häufiger. Die grössten Schwankungen werden durch das Einströmen des sauren Magensafts ins Duodenum, die die neutrale oder leicht alkalische Reaktion in eine stark saure ändert, hervorgerufen. In Fällen von Achylia gastrica sind die Schwankungen der PH-Werte viel kleiner um etw. 1.5 PH. In einem Falle starker Hyperazidität wurde in allen Proben konstant sehr niedrige PH-Werte gefunden. Die Lipasemenge der einzelnen Proben ist eine sehr variierende, und schwankt im grossen und ganzen mit den PH-Werten parallel. Bei PH-Werten bis 4.5-5.0 findet man konstant eine sehr geringe Lipasewirkung, bei Werten von PH 6.5–8.5 ist die lipolytische Kraft des Duodenalsafts am stärksten, aber in den einzelnen Proben eine sehr schwankende, auch bei ungefähr derselben Reaktion. Die Diastase und das Trypsin folgen im allgemeinen die für die Lipase aufgestellten Regeln, doch findet man auch bei relativ stark saurer Reaktion eine wenn auch nicht grosse Trypsinwirkung. Es scheint als ob die Salzsäure die Lipase direkt zerstört. In einem Falle pancreatogener Fettdiarrhoe wurde in allen den aufgeheberten Proben innerhalb c. 2 1/2 Stunden konstant eine sehr geringe Lipasemenge bei einem hohen und stetig steigenden PH-Wert gefunden, was als pathologisch angesehen werden muss.     

Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals

Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.     

Some considerations on middle ear cholesteatoma in ‘foreign workers’*

The treatment of cholesteatoma in patients without a permanent residence or in medically underdeveloped countries presents a serious problem in middle ear surgery. Methods which erradicate disease safely and reduce the risk of recurrence to a minimum are necessary. We differentiate 3 clinical types of cholesteatoma: 1 Retraction of Shrapnell's membrane or in the postero-superior quadrant with very little cholesteatoma lateral to the ossicles. A transcanal technique is used to evert the cholesteatomatous pocket into the meatus intact, followed by reconstruction of the outer attic wall. 2 Circumscribed cholestatoma lateral and often also medial to the ossicles. Combined approach tympanoplasty is used in such cases. 3 Marginal perforations with large cholesteatomas, situated medial to the ossicular chain. For these ears, classical radical mastoidectomy is the method of choice. (Radical mastoidectomy also has to be performed in all cases of type II, where luxation of the matrix in toto has failed.) Results: No recurrence has been detected in cases where follow-up was possible.