Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Is gender crucial for cardiovascular adjustments induced by exercise training in female spontaneously hypertensive rats?

Evidence of mild hypertension in women and female rats and our preliminary observation showing that training is not effective to reduce pressure in female as it does in male spontaneously hypertensive rats (SHR) prompt us to investigate the effects of gender on hemodynamic pattern and microcirculatory changes induced by exercise training. Female SHR and normotensive controls (Wistar-Kyoto rats) were submitted to training (55% VO(2) peak; 3 months) or kept sedentary and instrumented for pressure and hindlimb flow measurements at rest and during exercise. Heart, kidney, and skeletal muscles (locomotor/nonlocomotor) were processed for morphometric analysis of arterioles, capillaries, and venules. High pressure in female SHR was accompanied by an increased arteriolar wall:lumen ratio in the kidney (+30%; P<0.01) but an unchanged ratio in the skeletal muscles and myocardium. Female SHR submitted to training did not exhibit further changes on the arteriolar wall:lumen ratio and pressure, showing additionally increased hindlimb resistance at rest (+29%; P<0.05). On the other hand, female SHR submitted to training exhibited increased capillary and venular densities in locomotor muscles (+50% and 2.3-fold versus sedentary SHR, respectively) and normalized hindlimb flow during exercise hyperemia. Left ventricle pressure and weight were higher in SHR versus WKY rats, but heart performance (positive dP/dt(max) and negative dP/dt(max)) was not changed by hypertension or training, suggesting a compensated heart function in female SHR. In conclusion, the absence of training-induced structural changes on skeletal muscle and myocardium arterioles differed from changes observed previously in male SHR, suggesting a gender effect. This effect might contribute to the lack of pressure fall in trained female SHRs.     

Aumento de Óbitos Domiciliares devido a Parada Cardiorrespiratória em Tempos de Pandemia de COVID-19

BackgroundCardiovascular diseases constitute an important group of causes of death in the country. Ischemic heart diseases that are the main causes of cardiopulmonary arrest, leading to an impact on the mortality of the cardiovascular diseases in the health system.ObjectiveAssess the number of home deaths by cardiopulmonary arrest notified by the Mobile Emergency Medical Service (SAMU) in March 2018, 2019 and 2020.MethodsObservational study carried out from the analysis of cardiopulmonary arrest mortality data of citizens assisted by SAMU in Belo Horizonte, Minas Gerais, Brazil. Social and clinical characteristics and occurrence information of the patients were analyzed. The mortality rate due to cardiopulmonary arrest in relation to the total number of attendances was assessed. A significance level of 95% was considered.ResultsThere was increase of home deaths due to cardiopulmonary arrest in March 2020 compared to March 2018 (p<0.001) and March 2019 (p=0.050). Of the deaths reported in 2020, 63.8% of the patients were aged 60 years or older, 63.7% of the occurrences were performed in the afternoon and approximately 87% of the cardiopulmonary arrest notified had associated clinical comorbidities, with systemic arterial hypertension and heart failure represented by 22.87% and 13.03% of the reported cases, respectively. The majority of the evaluated sample of this study did not have any medical care follow-up (88.7%).ConclusionConsidering the increase in the number of the deaths, we suggest reflections and readjustments regarding the monitoring of chronic non-transmissible diseases during a pandemic, as well as improvements in death surveillance. (Arq Bras Cardiol. 2021; 116(2):266-271)     

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia

Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."     

Low Quality of Life,Falls, and Pre-Frailty are Associated with Depressive Symptoms in Virologically Suppressed PLWHIV in Salvador,Brazil

AIDS and Behavior - Depression is the leading cause of years lived with disability worldwide and PLWHIV present a higher risk of developing depressive symptoms. We aimed to evaluate depressive...     

Myocardial bridging of coronary arteries associated with an impending acute myocardial infarction

A 57-year-old woman developed severe substernal chest pain radiating to the left arm accompanied by pallor and marked diaphoresis. These symptoms appeared at rest, lasted 45 minutes, and terminated spontaneously. The patient had been treated for mild hypertension during the last 6 months. An ECG tracing obtained at the beginning of treatment was unremarkable. However, an ECG tracing recorded shortly after the end of the symptoms showed T-wave inversion in all anterior leads. Coronary arteriography was then performed and showed no fixed obstructive coronary artery disease. Nonetheless, a lengthened and constricted myocardial bridging of both the left anterior descending coronary artery and its major diagonal branch was detected. Also, the left anterior descending coronary artery was observed to be very short, terminating before the cardiac apex. The left ventricle was hypertrophied. The patient was treated with a beta-blocking agent which eliminated all symptoms. An ECG tracing obtained about three months after the onset of the clinical picture was normal. Our findings suggest that marked myocardial ischemia at rest does occur in patients having myocardial bridges under special circumstances, such as lengthened and constricted myocardial bridging of a short coronary artery which supplies a hypertrophied ventricle. This anomaly should be taken into account as a possible cause of a threatened myocardial infarction, which may be successfully treated with a beta-blocking agent.     

von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers

When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.