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1.
Nutrients ; 16(3)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38337668

ABSTRACT

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Lipopolysaccharides , Humans , Lipopolysaccharides/pharmacology , Ascorbic Acid/pharmacology , Receptors, Purinergic P2X7 , Autophagy , Adenosine Triphosphate/pharmacology
2.
Clinics (Sao Paulo) ; 77: 100021, 2022.
Article in English | MEDLINE | ID: mdl-35303586

ABSTRACT

OBJECTIVE: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. METHODS: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1ß, IL-6, CXCL-1, TNF-α, TGF-ß, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. RESULTS: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. CONCLUSIONS: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.


Subject(s)
Lipopolysaccharides , Pneumonia , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Cytokines , Disease Models, Animal , Lung , Mice , Mice, Inbred C57BL , NF-kappa B
3.
Clinics ; Clinics;77: 100021, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1375194

ABSTRACT

ABSTRACT Objective: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. Methods: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1β, IL-6, CXCL-1, TNF-α, TGF-β, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. Results: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. Conclusions: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.

4.
Cell Biol Int ; 45(7): 1459-1467, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33675269

ABSTRACT

Although the existence of the renin-angiotensin system (RAS) in the bone marrow is clear, the exact role of this system in hematopoiesis has not yet been fully characterized. Here the direct role of angiotensin II (AngII) in hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), granulocyte/monocyte progenitors (GMPs), and megakaryocytes/erythroid progenitors (MEPs), using a system of coculture with stromal S17 cells. Flow cytometry analysis showed that AngII increases the percentage of HSC and GMP, while reducing CMP with no effect on MEP. According to these data, AngII increased the total number of mature Gr-1+ /Mac-1+ cells without changes in Terr119+ cells. AngII does not induce cell death in the population of LSK cells. In these populations, treatment with AngII decreases the expression of Ki67+ protein with no changes in the Notch1 expression, suggesting a role for AngII on the quiescence of immature cells. In addition, exposure to AngII from murine bone marrow cells increased the number of CFU-GM and BFU-E in a clonogenic assay. In conclusion, our data showed that AngII is involved in the regulation of hematopoiesis with a special role in HSC, suggesting that AngII should be evaluated in coculture systems, especially in cases that require the expansion of these cells in vitro, still a significant challenge for therapeutic applications in humans.


Subject(s)
Angiotensin II/pharmacology , Hematopoietic Stem Cells/drug effects , Stromal Cells/drug effects , Animals , Cell Differentiation , Cell Line , Coculture Techniques , Hematopoiesis , Hematopoietic Stem Cells/cytology , Mice , Stromal Cells/metabolism
5.
J Pediatr ; 230: 23-31.e10, 2021 03.
Article in English | MEDLINE | ID: mdl-33197493

ABSTRACT

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.


Subject(s)
COVID-19/epidemiology , Hospitalization , Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , Biomarkers/analysis , C-Reactive Protein/analysis , COVID-19/blood , Child , Child, Preschool , Connecticut/epidemiology , Female , Humans , Hypoxia/epidemiology , Infant , Intensive Care Units , Lymphocyte Count , Male , Multivariate Analysis , New Jersey/epidemiology , New York/epidemiology , Pediatric Obesity/epidemiology , Procalcitonin/blood , Prospective Studies , Retrospective Studies , Systemic Inflammatory Response Syndrome/blood , Troponin/blood , Young Adult
6.
J Esthet Restor Dent ; 32(1): 5-11, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31758748

ABSTRACT

OBJECTIVE: This clinical case report addresses the step-by-step of the application of a core-and-post system that uses a single resin composite material to fiber post cementation and core build-up in a maxillary left central incisor. CLINICAL CONSIDERATIONS: The literature reports several materials and methods for the restoration of endodontically treated teeth with coronal destruction that require an intra-radicular fiber post for the core build-up. The present case report describes a core-and-post or "monoblock" technique. A dual resin composite (Core-X Flow; Dentsply DeTrey) highly filled material and cement was used for luting the fiber post (Blue X-Post) and build-up the core structure in an easy application. CONCLUSIONS: The "core-and-post" technique that uses a single material system protocol minimizes the material interfaces, steps of procedures, and chair-time in comparison to conventional techniques. CLINICAL SIGNIFICANCE: The use of different materials for post cementation and core build-up requires more steps, which increases the chair-time and number of interfaces among the materials. Since the "monoblock" technique uses only one material, it can streamline the clinical procedures, thus, saving time and materials. Moreover, techniques based on core-and-post systems are easily applied, versatile, and esthetics, and can be applicable to posterior and anterior teeth.


Subject(s)
Post and Core Technique , Tooth, Nonvital , Cementation , Composite Resins , Dental Materials , Humans , Resin Cements
7.
Biomed Pharmacother ; 92: 1045-1054, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28618649

ABSTRACT

To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Coffea/chemistry , Diterpenes/pharmacology , Leukemia/drug therapy , Animals , Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , CD11b Antigen/metabolism , Caspase 3/metabolism , Cell Cycle Checkpoints/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytarabine/pharmacology , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Fucosyltransferases/metabolism , HL-60 Cells , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/pathology , Humans , K562 Cells , Leukemia/metabolism , Leukemia/pathology , Lewis X Antigen/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Phosphatidylserines/metabolism , Phytotherapy , Plants, Medicinal , Reactive Oxygen Species/metabolism
8.
Front Physiol ; 8: 248, 2017.
Article in English | MEDLINE | ID: mdl-28491040

ABSTRACT

Background: Atherosclerotic carotid intima-media thickness (IMT) may be associated with alterations in the sensitivity of carotid baroreceptors. The aim of this study was to investigate the association between carotid IMT and the autonomic modulation of heart rate variability (HRV). Methods: A total of 101 subjects were enrolled in this prospective observational study. The carotid IMT was determined by duplex ultrasonography. The cardiac autonomic function was determined through HRV measures during the Deep Breathing Test. Linear regression models, adjusted for demographics, comorbidities, body mass index, waist-hip-ratio, and left ventricular ejection fraction were used to evaluate the association between HRV parameters and carotid IMT. Results: Participants had a mean age of 60.4 ± 13.4 years and an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk score (using the Pooled Cohort Equations) of 16.4 ± 17. The mean carotid media thickness was highest (0.90 ± 0.19 mm) in the first quartile of the standard deviation of all RR intervals (SDNN) (19.7 ± 5.1 ms) and progressively declined in each subsequent quartile to 0.82 ± 0.21 mm, 0.81 ± 0.16 mm, and 0.68 ± 0.19 in quartiles 2 (36.5 ± 5.9 ms), 3 (57.7 ± 6.2 ms) and 4 (100.9 ± 22.2 ms), respectively. In multivariable adjusted models, there was a statistical significant association between SDNN and carotid IMT (OR -0.002; 95%CI -0.003 to -0.001, p = 0.005). The same significant association was found between carotid IMT and other measures of HRV, including coefficient of variation of RR intervals (CV) and dispersion of points along the line of identity (SD2). Conclusions: In a cohort of individuals at increased cardiovascular risk, carotid IMT as a marker of subclinical atherosclerosis was associated with alterations of HRV indicating an impaired cardiac autonomic control, independently of other cardiovascular risk factors.

9.
Rev. bras. ciênc. mov ; 25(3): 158-169, mar.-abr.2017.
Article in Portuguese | LILACS | ID: biblio-880964

ABSTRACT

A relação entre a alcalose metabólica e o desempenho esportivo tem sido investigada através de anipulações do pH sanguíneo. Entre as formas de manipulação do pH, o bicarbonato de sódio (NaHCO3) é o componente químico mais utilizado quando se pretende induzir um estado de alcalose sanguínea previamente ao exercício. Embora os benefícios do NaHCO3 no desempenho tenham sido amplamente demonstrados em exercícios intermitentes de alta intensidade, não há um consenso na literatura e pouco ainda é conhecido quanto aos efeitos do NaHCO3 em exercícios contínuos de ciclismo de alta intensidade. Nesse sentido, foram abordados na presente revisão os principais aspectos envolvidos na ingestão aguda e crônica de NaHCO3, enfatizando os mecanismos de ação dessa substância, especificações acerca da dose utilizada e seus efeitos sobre o desempenho em ciclismo de alta intensidade. Os resultados dos estudos apresentados na presente revisão revelam que a ingestão aguda de 0,3 g∙kg-1 de massa corporal (MC) de NaHCO3 é eficaz em melhorar o desempenho em eventos de alta intensidade se consumido em torno de 90 minutos antes do exercício. Para a ingestão crônica, uma dose de 0,5 g∙kg-1 ∙dia1 de MC durante 5-6 dias seria benéfica para o exercício de alta intensidade. Esses seriam os limites em ambos os protocolos para induzir um estado de alcalose metabólica e posteriormente melhorar o desempenho sem promover ou atenuando qualquer sintoma relacionado à sensações de desconforto gastrointestinal. Dessa forma, ambas as formas de ingestão de NaHCO3, aguda e/ou crônica, parecem melhorar o desempenho durante o ciclismo de alta intensidade realizados de modo contínuo, enfatizando a importância da suplementação de NaHCO3 como um recurso ergogênico. Porém, pesquisas adicionais utilizando protocolos de ingestão crônica e testando seus efeitos sobre o desempenho em provas mais prolongadas são requeridas devido ao reduzido número de investigações e o potencial efeito ergogênico dessa substância...(AU)


The relationship between metabolic alkalosis and exercise performance has been investigated through manipulation of the blood and muscle pH. Among the forms of pH manipulation, the sodium bicarbonate (NaHCO3) is the most used chemical component when is intentioned to induce a blood alkalosis state prior to exercise. While the benefits of NaHCO3 in performance have been widely demonstrated in high-intensity intermittent exercise, there is no consensus in the literature and little is known about the effects of NaHCO3 in continuous high-intensity cycling exercise. Thus, it was addressed in this present review the main aspects involved in acute and chronic NaHCO3 ingestion, giving a focus to the action mechanisms of this substance, specifications about the used dose and their effects on highintensity cycling performance. The results of the present review show that acute ingestion of 0.3 g∙kg-1 of body mass (BM) of NaHCO3 is effective in improving performance in high-intensity events if this substance is consumed in about 90 minutes prior to exercise. For chronic ingestion, a dose of 0.5 g∙kg1 ∙day-1 BM during 5-6 days should be beneficial for the high-intensity exercise. For both protocols these would be the limits to induce a metabolic alkalosis state and further improve the performance without promoting or attenuating any symptoms related to the gastrointestinal discomfort sensations. Thus, both acute and/or chronic NaHCO3 ingestion seem to improve performance during high-intensity cycling performed in a continuous mode, emphasizing the importance of NaHCO3 supplementation as an ergogenic aid. However, further research using chronic ingestion of protocols and testing their effects on performance in more prolonged tests are required due to the small number of studies and the potential ergogenic effect of this substance...(AU)


Subject(s)
Humans , Male , Female , Alkalosis , Athletic Performance , Bicycling , Sodium Bicarbonate
10.
BMC Infect Dis ; 16: 125, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26975185

ABSTRACT

BACKGROUND: Our understanding of the epidemiology of influenza is limited in tropical regions, which in turn has hampered identifying optimal region-specific policy to diminish disease burden. Influenza-like illness (ILI) is a clinical diagnosis that can be used as a surrogate for influenza. This study aimed to define the incidence and seasonality of ILI and to assess its association with climatic variables and school calendar in an urban community in the tropical region of Salvador, Brazil. METHODS: Between 2009 and 2013, we conducted enhanced community-based surveillance for acute febrile illnesses (AFI) among patients ≥ 5 years of age in a slum community emergency unit in Salvador, Brazil. ILI was defined as a measured temperature of ≥ 37.8 °C or reported fever in a patient with cough or sore throat for ≤ 7 days, and negative test results for dengue and leptospirosis. Seasonality was analyzed with a harmonic regression model. Negative binomial regression models were used to correlate ILI incidence with rainfall, temperature, relative humidity and the number of days per month that schools were in session while controlling for seasonality. RESULTS: There were 2,651 (45.6% of 5,817 AFI patients) ILI cases with a mean annual incidence of 60 cases/1,000 population (95% CI 58-62). Risk of ILI was highest among 5-9 year olds with an annual incidence of 105 cases/1,000 population in 2009. ILI had a clear seasonal pattern with peaks between the 35-40th week of the year. ILI peaks were higher and earlier in 5-9 year olds compared with > 19 year olds. No association was seen between ILI and precipitation, relative humidity or temperature. There was a significant association between the incidence of ILI in children 5-9 years of age and number of scheduled school days per month. CONCLUSIONS: We identified a significant burden of ILI with distinct seasonality in the Brazilian tropics and highest rates among young school-age children. Seasonal peaks of ILI in children 5-9 years of age were positively associated with the number of school days, indicating that children may play a role in the timing of seasonal influenza transmission.


Subject(s)
Influenza, Human/epidemiology , Adolescent , Adult , Brazil/epidemiology , Child , Child Health , Child, Preschool , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Seasons , Urban Population , Young Adult
11.
J Pediatr ; 165(1): 134-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24726712

ABSTRACT

OBJECTIVES: To describe the results of brain magnetic resonance imaging (MRI) of infants with bacterial meningitis and how the findings affected clinical management. STUDY DESIGN: This retrospective study included all infants <12 months of age who were hospitalized at Children's Medical Center, Dallas and had culture-confirmed bacterial meningitis and a brain MRI from January 1, 2001 to December 1, 2011. Infants were identified by review of all positive bacterial cultures of cerebrospinal fluid (CSF) from the Children's Medical Center Microbiology Laboratory. Demographic, clinical, laboratory, and neuroimaging data were reviewed. Infants with ventriculoperitoneal shunt or whose CSF culture yielded skin commensals were excluded. A neuroradiologist blinded to clinical information reviewed all MRI studies. RESULTS: Of the 440 infants who had a positive CSF culture result, 111 (25%) had a pathogen isolated from CSF and were enrolled in the study. Of these, 68% (75/111) had a brain MRI performed during the hospitalization; abnormalities included leptomeningeal enhancement (57%), cerebral infarct (43%), subdural empyema (52%), cerebritis (26%), hydrocephalus (20%), and abscess (11%). By multiple logistic regression analysis, infants with late seizures and an abnormal neurologic examination were more likely to have an abnormal MRI (P < .05). MRI results led to neurosurgical intervention in 23% of infants; a positive bacterial culture of CSF obtained >48 hours after initiation of antibiotic therapy was associated with neurosurgical intervention (P = .01). Fourteen (19%) infants with bacterial meningitis had a normal brain MRI. CONCLUSIONS: Brain MRIs were performed frequently and often were abnormal in infants with bacterial meningitis, leading to changes in clinical management.


Subject(s)
Brain/pathology , Magnetic Resonance Imaging/methods , Meningitis, Bacterial/diagnosis , Neuroimaging/methods , Cerebrospinal Fluid/microbiology , Child , Child, Preschool , Female , Humans , Infant , Logistic Models , Male , Meningitis, Bacterial/cerebrospinal fluid , Retrospective Studies , Texas
12.
Chem Biol Interact ; 184(3): 388-95, 2010 Mar 30.
Article in English | MEDLINE | ID: mdl-20096676

ABSTRACT

Angiotensin I-converting enzyme (ACE), a common element of renin-angiotensin system (RAS) and kallikrein-kinin system (KKS), is involved in myelopoiesis modulation, mainly by cleaving the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Based on this finding and in our results showing B1 and B2 kinin receptors expression in murine bone marrow (BM) cells, we evaluated the ACE influence on myelopoiesis of kinin B1 receptor knockout mice (B1KO) using long-term bone marrow cultures (LTBMCs). Captopril and AcSDKP were used as controls. Enhanced ACE activity, expressed by non-hematopoietic cells (Ter-199(-) and CD45(-)), was observed in B1KO LTBMCs when compared to wild-type (WT) cells. ACE hyperfunction in B1KO cells was maintained when LTBMCs from B1KO mice were treated with captopril (1.0microM) or AcSDKP (1.0nM). Although no alterations were observed in ACE mRNA and protein levels under these culture conditions, 3.0nM of AcSDKP increased ACE mRNA levels in WT LTBMCs. No alteration in the number of GM-CFC was seen in B1KO mice compared to WT animals, even when the former were treated with AcSDKP (10microg/kg) or captopril (100mg/kg) for 4 consecutive days. Hematological data also revealed no differences between WT and B1KO mice under basal conditions. When the animals received 4 doses of lipopolysaccharide (LPS), a decreased number of blood cells was detected in B1KO mice in relation to WT. We also found a decreased percentage of Gr1(+)/Mac-1(+), Ter119(+), B220(+), CD3(+), and Lin(-)Sca1(+)c-Kit(+) (LSK) cells in the BM of B1KO mice compared to WT animals. Low AcSDKP levels were observed in BM cultures from B1KO in comparison to WT cultures. We conclude that ACE hyperfunction in B1KO mice resulted in faster hydrolysis of AcSDKP peptide, which in turn decreased in BM tissues allowing HSC to enter the S stage of the cell cycle.


Subject(s)
Myelopoiesis/drug effects , Oligopeptides/pharmacology , Peptidyl-Dipeptidase A/metabolism , Receptor, Bradykinin B1/metabolism , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Captopril/pharmacology , Granulocytes/cytology , Granulocytes/drug effects , Kallikrein-Kinin System , Lipopolysaccharides/toxicity , Macrophages/cytology , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Mice, Knockout , Peptidyl-Dipeptidase A/genetics , Receptor, Bradykinin B1/deficiency , Receptor, Bradykinin B1/genetics , Renin-Angiotensin System
13.
Chem Biol Interact ; 177(3): 181-9, 2009 Feb 12.
Article in English | MEDLINE | ID: mdl-19026616

ABSTRACT

Previous studies reported by our group have introduced a new antitumoural drug called Biphosphinic Palladacycle Complex (BPC). In this paper we show that BPC causes apoptosis in leukaemia cells (HL60 and Jurkat), but not in normal human lymphocytes. IC(50) values obtained for both cell lines using the MTT and trypan blue exclusion assays 5h after BPC treatment were lower than 8.0 microM. Using metachromatic fluorophore, acridine orange, we observed that BPC elicited lysosomal rupture of leukaemic cells. Furthermore, BPC triggered caspase-3 and caspase-6 activation and apoptosis in cell lines, inducing chromatin condensation, apoptotic bodies, and DNA fragmentation. Interestingly, the lysosomal cathepsin B inhibitor CA074 markedly decreased BPC-induced caspase-3 and caspase-6 activation as well as cell death. Lysosomal BPC-induced membrane destabilisation was not dependent on reactive oxygen species generation, which was consistent with the absence of cellular HL60 and Jurkat membrane lipid peroxidation. We conclude that, following BPC treatment, lysosomal membrane rupture precedes cell death and the apoptotic signalling pathway is initiated by the release of cathepsin B in the cytoplasm of leukaemia cells. As no toxic effects for human lymphocytes were observed, we suggest that BPC is more selective for transformed cells, mainly due to their exacerbated lysosome expression.


Subject(s)
Antineoplastic Agents/pharmacology , Leukemia/drug therapy , Organometallic Compounds/pharmacology , Apoptosis/drug effects , Caspases/metabolism , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Jurkat Cells , Leukemia/enzymology , Leukemia/pathology , Lipid Peroxidation , Reactive Oxygen Species/metabolism
14.
Neotrop Entomol ; 36(3): 459-64, 2007.
Article in Portuguese | MEDLINE | ID: mdl-17710330

ABSTRACT

The aim of the present study was to assess the effect of six different temperatures on the development of Acarophenax lacunatus (Cross & Krantz) using eggs of Tribolium castaneum (Herbst) and Cryptolestes ferrugineus (Stephens) as hosts. The temperature affected the development of A. lacunatus. The largest values for the progeny (19 mites in T. castaneum and 15 mites in C. ferrugineus) were obtained at about 30 degrees C, as also observed for the net reproductive rate (Ro), which revealed that the A. lacunatus population increased 18 times in T. castaneum and 14 times in C. ferrugineus in a generation. The intrinsic rate of increase (r m) gradually increased with temperature, reaching the maximum value at 35 degrees C in T. castaneum (1,608) and C. ferrugineus (1,289). The generation time was negatively correlated with temperature, ranging from 1,60 to 4,85 days in T. castaneum and from 1,96 to 5,34 days in C. ferrugineus. These results suggest that the mite A. lacunatus may be used in programs of biological control of T. castaneum and C. ferrugineus in the tropics.


Subject(s)
Acari/growth & development , Coleoptera/parasitology , Animals , Ovum/parasitology , Temperature
15.
Neotrop Entomol ; 36(2): 247-53, 2007.
Article in Portuguese | MEDLINE | ID: mdl-17607458

ABSTRACT

The objective of this study was to evaluate the effect of different temperatures with the association of the mite Acarophenax lacunatus (Cross & Krantz) on the population suppression of Rhyzopertha dominica (Fabricius). The experimental units were petri dishes containing 40 g of whole wheat grains (13% moisture content) infested with 10 adults of R. dominica, under the temperatures of 20, 25, 30 and 35 masculineC, with or without A. lacunatus, in five replicates. Relative humidity of 60 +/- 5% and escotophase of 24h were used for all temperatures. Five days after the infestation, five mites were inoculated in each experimental unit. The evaluations were carried out at 20, 40, 60, 80, 100 and 120 days after R. dominica infestation. The interaction of the temperature with the parasite A. lacunatus was an important tool for the population suppression of R. dominica. In temperatures higher than 25 masculineC, however, despite the reduction of the immature stages of R. dominica, there was a high grain weight loss after 120 days. The maintenance of the temperature of the wheat grains stored at 20 masculineC can be used to complement the biological control of R. dominica with A. lacunatus.


Subject(s)
Coleoptera/growth & development , Coleoptera/parasitology , Mites/physiology , Temperature , Animals
16.
Neotrop. entomol ; 36(3): 459-464, May-June 2007. graf
Article in Portuguese | LILACS | ID: lil-458896

ABSTRACT

O presente trabalho teve por objetivo avaliar o efeito de seis temperaturas (20, 25, 28, 30, 32 e 35°C) sobre os parâmetros biológicos de Acarophenax lacunatus (Cross & Krantz) utilizando ovos de Tribolium castaneum (Herbst) e Cryptolestes ferrugineus (Stephens) como hospedeiros. A temperatura influenciou o desenvolvimento do ácaro A. lacunatus. Os maiores valores para a progênie (19 ácaros em T. castaneum e 15 ácaros em C. ferrugineus) foram obtidos a 30°C. O mesmo foi observado para a taxa líquida de reprodução (Ro), que revelou que a população de A. lacunatus aumentou 18 vezes em T. castaneum e 14 vezes em C. ferrugineus em uma geração. A taxa intrínseca de crescimento (r m) aumentou com a elevação da temperatura, atingindo o valor máximo a 35°C em T. castaneum (1,608) e em C. ferrugineus (1,289). O tempo de geração foi inversamente proporcional à temperatura, variando de 1,60 a 4,85 dias em T. castaneum e de 1,96 a 5,34 dias em C. ferrugineus. Esses resultados sugerem que o ácaro A. lacunatus pode ser utilizado em programas de controle biológico de T. castaneum e de C. ferrugineus em regiões tropicais.


The aim of the present study was to assess the effect of six different temperatures on the development of Acarophenax lacunatus (Cross & Krantz) using eggs of Tribolium castaneum (Herbst) and Cryptolestes ferrugineus (Stephens) as hosts. The temperature affected the development of A. lacunatus. The largest values for the progeny (19 mites in T. castaneum and 15 mites in C. ferrugineus) were obtained at about 30°C, as also observed for the net reproductive rate (Ro), which revealed that the A. lacunatus population increased 18 times in T. castaneum and 14 times in C. ferrugineus in a generation. The intrinsic rate of increase (r m) gradually increased with temperature, reaching the maximum value at 35°C in T. castaneum (1,608) and C. ferrugineus (1,289). The generation time was negatively correlated with temperature, ranging from 1,60 to 4,85 days in T. castaneum and from 1,96 to 5,34 days in C. ferrugineus. These results suggest that the mite A. lacunatus may be used in programs of biological control of T. castaneum and C. ferrugineus in the tropics.


Subject(s)
Animals , Acari/growth & development , Coleoptera/parasitology , Ovum/parasitology , Temperature
17.
Anesth Analg ; 104(6): 1561-2, table of contents, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17513658

ABSTRACT

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, hereditary, autonomic recessive disorder. The inability to perceive pain results from loss of nociceptive afferents, while anhidrosis is caused by loss of innervation to the sweat glands. Insensitivity to pain and mental retardation lead to self-inflicted injuries, corneal lacerations, painless bony fractures, joint deformities with consequent chronic osteomyelitis, and septic arthritis. There are only a few reports on the anesthetic management for patients with CIPA. We describe the anesthetic management of a young woman with CIPA receiving bilateral arthrodesis of the ankle.


Subject(s)
Anesthesia, Spinal/methods , Hereditary Sensory and Autonomic Neuropathies/therapy , Adult , Female , Hereditary Sensory and Autonomic Neuropathies/diagnosis , Humans , Pain Insensitivity, Congenital/diagnosis , Pain Insensitivity, Congenital/therapy
18.
Neotrop. entomol ; 36(2): 247-253, Mar.-Apr. 2007. tab, graf
Article in Portuguese | LILACS | ID: lil-454504

ABSTRACT

O presente trabalho teve como objetivo avaliar o efeito da interação de diferentes temperaturas com o parasita Acarophenax lacunatus (Cross & Krantz) na supressão populacional de Rhyzopertha dominica (Fabricius). Os ensaios foram realizados com e sem o parasita, em cinco repetições, às temperaturas de 20, 25, 30 e 35°C, umidade relativa de 60 ± 5 por cento e escotofase de 24h. As unidades experimentais consistiram de placas de Petri, contendo 40 g de grãos de trigo (13 por cento b.u.), infestados com 10 adultos de R. dominica. Foram realizadas três inoculações de cinco fêmeas de A. lacunatus por placa de Petri. As avaliações foram realizadas depois de 20, 40, 60, 80, 100 e 120 dias do início do experimento. A interação da temperatura com A. lacunatus mostrou ser uma importante ferramenta para a supressão populacional de R. dominica. Todavia, em temperaturas maiores que 25°C, mesmo A. lacunatus reduzindo grande proporção das fases imaturas de R. dominica, as perdas de massa dos grãos foram elevadas aos 120 dias do armazenamento. A manutenção da temperatura dos grãos armazenados a 20°C pode ser usada como complemento para o controle biológico de R. dominica com A. lacunatus.


The objective of this study was to evaluate the effect of different temperatures with the association of the mite Acarophenax lacunatus (Cross & Krantz) on the population suppression of Rhyzopertha dominica (Fabricius). The experimental units were petri dishes containing 40 g of whole wheat grains (13 percent moisture content) infested with 10 adults of R. dominica, under the temperatures of 20, 25, 30 and 35°C, with or without A. lacunatus, in five replicates. Relative humidity of 60 ± 5 percent and escotophase of 24h were used for all temperatures. Five days after the infestation, five mites were inoculated in each experimental unit. The evaluations were carried out at 20, 40, 60, 80, 100 and 120 days after R. dominica infestation. The interaction of the temperature with the parasite A. lacunatus was an important tool for the population suppression of R. dominica. In temperatures higher than 25°C, however, despite the reduction of the immature stages of R. dominica, there was a high grain weight loss after 120 days. The maintenance of the temperature of the wheat grains stored at 20°C can be used to complement the biological control of R. dominica with A. lacunatus.


Subject(s)
Animals , Coleoptera/growth & development , Coleoptera/parasitology , Mites/physiology , Temperature
19.
Neotrop. entomol ; 35(6): 823-827, Nov.-Dec. 2006. tab, graf
Article in Portuguese | LILACS | ID: lil-442251

ABSTRACT

A interação entre Acarophenax lacunatus (Cross & Krantz) e Anisopteromalus calandrae (Howard) pode ser uma ferramenta promissora para o manejo integrado de pragas. O objetivo deste estudo foi avaliar a compatibilidade desses dois inimigos naturais sobre Rhyzopertha dominica (Fabricius) (Coleoptera: Bostrichidae). As unidades experimentais consistiram de placas de Petri (140 x 10 mm), contendo 30 g de grãos de trigo com teor de água de 13 por cento b.u. Esses grãos foram infestados com 20 adultos de R. dominica, com idade entre três e sete dias. Os tratamentos consistiram na inoculação com A. lacunatus e A. calandrae, isoladamente e em conjunto, em oito repetições. Foram realizadas três inoculações com cinco fêmeas adultas dos inimigos naturais por placa de Petri, cinco, dez e quinze dias após a infestação de R. dominica. Todos os tratamentos foram armazenados por 60 dias em câmara climática ajustada a 30 ± 1°C, 60 ± 5 por cento UR e escotofase de 24h. Os menores números de fêmeas fisogástricas de A. lacunatus e de adultos de A. calandrae foram observados quando esses inimigos naturais estavam associados. O uso de A. calandrae sozinho ocasionou menor taxa instantânea de crescimento populacional de R. dominica e maior proteção aos grãos de trigo. Quando esse inimigo natural foi associado a A. lacunatus, além de preservar seu potencial, também apresentou os menores números de imaturos de R. dominica, demonstrando a importância dessa interação como ferramenta do manejo integrado de R. dominica em unidades armazenadoras.


The interaction between Acarophenax lacunatus (Cross & Krantz) and Anisopteromalus calandrae (Howard) may be a promising tool for the integrated pest management of stored grain insect pests. The objective of this study was to evaluate the compatibility of these two natural enemies on Rhyzopertha dominica (Fabricius). The experimental units were petri dishes (140 x 10 mm) containing 30 g of whole wheat grains (13 percent water content) infested with 20 adults of R. dominica. The treatments consisted of inoculation of A. lacunatus and A. calandrae, separately and associated, in eight replicates. Three inoculations of five adult females of the natural enemies were carried out in each petri dish at five, ten and fifteen days after the infestation of R. dominica. All treatments were stored during 60 days in environmental chamber at 30 ± 1°C, 60 ± 5 percent relative humidity and 24h scotophase. The smallest numbers of physogastric females of A. lacunatus and of adults of A. calandrae were obtained when the natural enemies were in association. The use of A. calandrae alone demonstrated a low instantaneous rate of increase (r i) of R. dominica and a high protection of the wheat grains. The association of A. calandrae with A. lacunatus led to the lowest number of immatures of R. dominica. These results demonstrate the importance of this interaction as a tool of for the integrated management of R. dominica in stored wheat grains.


Subject(s)
Animals , Coleoptera/parasitology , Hymenoptera/physiology , Mites/physiology
20.
Neotrop Entomol ; 35(4): 506-10, 2006.
Article in Portuguese | MEDLINE | ID: mdl-17061800

ABSTRACT

The ability of a natural enemy to tolerate starvation increases its chances to survive in the absence of food, what is an important factor for its success in storage grain environment. The objective of the present work was to assess the survival of Acarophenax lacunatus (Cross & Krantz) in the absence of food. The experiment used individualized physogastric females of A. lacunatus placed in petri dishes (5 cm diameter) and maintained at 20, 25, 28, 30 and 32 degrees C, 50+/-5 % R.H. and 24h scotophase. The number of live mites was recorded every 6h thus assessing the progeny survival without food at different temperatures. The mites died within 60h at the temperatures 30 degrees C and 32 degrees C, while they survived for up to 108h at 20, 25 and 28 degrees C. The mean lethal time for death was 58.6h for the lowest temperatures and 39.3h for the highest temperatures. Thus, A. lacunatus subjected to starvation lived longer under lower temperatures, what is probably due to its lower metabolism. In contrast, the mites survived for about 90h at 28 degrees C, temperature commonly observed in tropical and subtropical climates, what may favor their use as control agents of stored product insects in these regions.


Subject(s)
Acaridae , Starvation/mortality , Animals , Female , Survival Rate , Temperature
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