Antibodies Against Glycolipids Enhance Antifungal Activity of Macrophages and Reduce Fungal Burden After Infection with Paracoccidioides brasiliensis

Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs) from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-gamma and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P brasiliensis adding to other well-studied mediators of the immune response to this fungus.CapesFAPESPUniv Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo, BrazilUniv Sao Paulo, Lab Med Mycol IMTSP LIM53, Sao Paulo, BrazilAlbert Einstein Coll Med, Dept Med, New York, NY USAAlbert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USAUniv Fed Fluminense, Niteroi, RJ, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilFAPESP: 2011/17267-4FAPESP: 2013/18655-3Web of Scienc

Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer's type

Aims The aim of this study was to analyze if the pre-administration of anthocyanin on memory and anxiety prevented the effects caused by intracerebroventricular streptozotocin (icv-STZ) administration-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Moreover, we evaluated whether the levels of nitrite/nitrate (NOx), Na+,K+-ATPase, Ca2 +-ATPase and acethylcholinesterase (AChE) activities in the cerebral cortex (CC) and hippocampus (HC) are altered in this experimental SDAT. Main methods Male Wistar rats were divided in 4 different groups: control (CTRL), anthocyanin (ANT), streptozotocin (STZ) and streptozotocin + anthocyanin (STZ + ANT). After seven days of treatment with ANT (200 mg/kg; oral), the rats were icv-STZ injected (3 mg/kg), and four days later the behavior parameters were performed and the animals submitted to euthanasia. Key findings A memory deficit was found in the STZ group, but ANT treatment showed that it prevents this impairment of memory (P < 0.05). Our results showed a higher anxiety in the icv-STZ group, but treatment with ANT showed a per se effect and prevented the anxiogenic behavior induced by STZ. Our results reveal that the ANT treatment (100 μM) tested displaces the specific binding of [3H] flunitrazepam to the benzodiazepinic site of GABAA receptors. AChE, Ca+-ATPase activities and NOx levels were found to be increased in HC and CC in the STZ group, which was attenuated by ANT (P < 0.05). STZ decreased Na+,K+-ATPase activity and ANT was able to prevent these effects (P < 0.05). Significance In conclusion, these findings demonstrated that ANT is able to regulate ion pump activity and cholinergic neurotransmission, as well as being able to enhance memory and act as an anxiolytic compound in animals with SDAT

Proportional Assist Ventilation Improves Leg Muscle Reoxygenation After Exercise in Heart Failure With Reduced Ejection Fraction

BackgroundRespiratory muscle unloading through proportional assist ventilation (PAV) may enhance leg oxygen delivery, thereby speeding off-exercise oxygen uptake (V.⁢O2) kinetics in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).MethodsTen male patients (HFrEF = 26 ± 9%, age 50 ± 13 years, and body mass index 25 ± 3 kg m2) underwent two constant work rate tests at 80% peak of maximal cardiopulmonary exercise test to tolerance under PAV and sham ventilation. Post-exercise kinetics of V.⁢O2, vastus lateralis deoxyhemoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy, and cardiac output (QT) by impedance cardiography were assessed.ResultsPAV prolonged exercise tolerance compared with sham (587 ± 390 s vs. 444 ± 296 s, respectively; p = 0.01). PAV significantly accelerated V.⁢O2 recovery (τ = 56 ± 22 s vs. 77 ± 42 s; p &lt; 0.05), being associated with a faster decline in Δ[deoxy-Hb + Mb] and QT compared with sham (τ = 31 ± 19 s vs. 42 ± 22 s and 39 ± 22 s vs. 78 ± 46 s, p &lt; 0.05). Faster off-exercise decrease in QT with PAV was related to longer exercise duration (r = −0.76; p &lt; 0.05).ConclusionPAV accelerates the recovery of central hemodynamics and muscle oxygenation in HFrEF. These beneficial effects might prove useful to improve the tolerance to repeated exercise during cardiac rehabilitation

The Barretos Cancer Hospital Animal Facility: implementation and results of a dedicated platform for preclinical oncology models

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.This study was funded by the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) and by Pio XII Foundation, Barretos Cancer Hospital internal funds, Grant Number: 13/2021

Genomic history of coastal societies from eastern South America

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr bp) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr bp from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr bp, corroborating evidence of cultural change

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

<p>Abstract</p> <p>Background</p> <p>HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort.</p> <p>Methods</p> <p>A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression.</p> <p>Results</p> <p>A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (<it>p </it>= 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (<it>p </it>= 0. 038).</p> <p>Conclusion</p> <p>Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.</p