Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte- macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all- trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.     

Custo-efetividade do Stent Farmacológico na Intervenção Coronariana Percutânea no SUS

BackgroundThe use of drug-eluting stents (DESs), compared with bare-metal stents (BMSs), in percutaneous coronary intervention (PCI) has reduced the rate of restenosis, without an impact on mortality but with an increase in costs. Medical literature lacks randomized studies that economically compare these 2 stent types within the reality of the Brazilian Unified Public Health System (SUS).ObjectiveTo estimate the incremental cost-effectiveness ratio (ICER) between DES and BMS in SUS patients with single-vessel coronary artery disease.MethodsOver a 3-year period, patients with symptomatic single-vessel coronary artery disease were randomized in a 1:2 ratio to receive a DES or BMS during PCI, with a 1-year clinical follow-up. The evaluation included in-stent restenosis (ISR), target lesion revascularization (TLR), major adverse events, and cost-effectiveness for each group. P-values <0.05 were considered significant.ResultsIn the DES group, of 74 patients (96.1%) who completed the follow-up, 1 developed ISR (1.4%), 1 had TLR (1.4%), and 1 died (1.4%), with no cases of thrombosis. In the BMS group, of 141 patients (91.5%), ISR occurred in 14 (10.1%), TLR in 10 (7.3%), death in 3 (2.1%), and thrombosis in 1 (0.74%). In the economic analysis, the cost of the procedure was R$ 5,722.21 in the DES group and R$ 4,085.21 in the BMS group. The effectiveness by ISR and TLR was 8.7% for DES and 5.9% for BMS, with an ICER of R$ 18,816.09 and R$ 27,745.76, respectively.ConclusionsIn the SUS, DESs were cost-effective in accordance with the cost-effectiveness threshold recommended by the World Health Organization (Arq Bras Cardiol. 2020; 115(1):80-89)     

Immunophenotypic Profile and Increased Risk of Hospital Admission for Infection in Infants Born to Female Kidney Transplant Recipients

Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty‐eight children born to female kidney recipients and 40 full‐term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm³, transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026–15.225; p = 0.046) higher risk of hospital admission in the first months of life—some, with severe clinical manifestations—than those born to healthy women.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Haemogregarina spp. in a wild population from Podocnemis unifilis Troschel, 1848 in the Brazilian Amazonia

The study objectives were to characterize the morphology of the parasitic forms and describe the prevalence and intensity of Haemogregarina spp. in a population of the turtle Podocnemis unifilis as well as to examine the relationships between parasitism and turtle variables such as gender, size, and weight. Samples were taken in the Tapajós and Jamanxim rivers, Itaituba, Pará state, Brazil. Blood was collected from the tail vein of 72 P. unifilis specimens, including 35 males, 36 females, and one unsexed juvenile. The prevalence of Haemogregarina spp. was 98 % (n?=?71). The mean parasite intensity of Haemogregarina spp. was 118 (1–582) parasites/2000 blood cells (6 %). There was no significant difference in the mean parasite intensity between male (137.68?±?121.8, n?=?35) and female turtles (101.42?±?123.59, n?=?35). There was no relationship between parasite intensity and carapace length. Although the relationship between parasite intensity and host body weight was significant, the relationship was weak. This is the first study on Haemogregarina parasitism with a relatively high number of turtles in Brazil.     

Long-term effects of various cleaning methods on polypropylene/ethylene copolymer retainer material

Objectives:To evaluate long-term light transmittance, surface roughness, and flexural modulus of polypropylene/ethylene copolymer retainer material after exposure to different cleaning methods.Materials and Methods:Standardized polypropylene/ethylene copolymer retainer specimens (n = 70, 50.8 mm × 12.7 mm × 1.0 mm) were subjected to seven chemical cleaning solutions: Invisalign cleaning crystals, Retainer Brite, Polident, Listerine mouthwash, 2.5% acetic acid, 0.6% NaClO, and 3% H₂O₂ for 6 months. The specimens were exposed to the different solutions twice a week for 15 minutes or according to manufacturer''s instructions, then stored in artificial saliva at 37°C. Another group of specimens (n = 10) were brushed with a standardized toothbrushing machine for 2 minutes twice a week. At baseline and 6 months, light transmittance, surface roughness, and flexural modulus of the specimens were quantified using spectrophotometry, profilometry and three-point bend testing, respectively. Qualitative analysis was performed using a scanning electron microscope (SEM). Statistical analyses were performed at a significance level of .05.Results:The results showed that light transmittance decreased significantly from baseline for all cleaning methods at 6 months. For an individual method, no significant differences were observed between specimens at baseline and 6 months in surface roughness and flexural modulus. No discernible differences in surface features were observed on SEM images.Conclusions:The results indicate that different cleaning methods affect the long-term light transmittance of the studied polypropylene/ethylene copolymer retainer material. However, for an individual cleaning method, no significant differences were shown for surface roughness or flexural modulus values at 6-months compared to baseline.