Key Endothelial Cell Angiogenic Mechanisms Are Stimulated By The Circulating Milieu In Sickle Cell Disease And Attenuated By Hydroxyurea.

As hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from steady-state sickle cell anemia patients presented elevated concentrations of pro-angiogenic factors (Angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly augmenting endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice, compared with non-sickle cell disease mice, consistent with an upregulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy displayed a pro-angiogenic profile and had more significant effects on endothelial cell proliferation and capillary formation than plasma of patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factor profile, in association with an inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, sickle cell anemia and retinopathic hemoglobin SC individuals present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy for preventing progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.

Low Molecular Weight Protein Tyrosine Phosphatase (lmwptp) Upregulation Mediates Malignant Potential In Colorectal Cancer.

Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease.

Antitumor Activity Of Irradiated Riboflavin On Human Renal Carcinoma Cell Line 786-o.

Riboflavin (vitamin B2) is a precursor for coenzymes involved in energy production, biosynthesis, detoxification, and electron scavenging. Previously, we demonstrated that irradiated riboflavin (IR) has potential antitumoral effects against human leukemia cells (HL60), human prostate cancer cells (PC3), and mouse melanoma cells (B16F10) through a common mechanism that leads to apoptosis. Hence, we here investigated the effect of IR on 786-O cells, a known model cell line for clear cell renal cell carcinoma (CCRCC), which is characterized by high-risk metastasis and chemotherapy resistance. IR also induced cell death in 786-O cells by apoptosis, which was not prevented by antioxidant agents. IR treatment was characterized by downregulation of Fas ligand (TNF superfamily, member 6)/Fas (TNF receptor superfamily member 6) (FasL/Fas) and tumor necrosis factor receptor superfamily, member 1a (TNFR1)/TNFRSF1A-associated via death domain (TRADD)/TNF receptor-associated factor 2 (TRAF) signaling pathways (the extrinsic apoptosis pathway), while the intrinsic apoptotic pathway was upregulated, as observed by an elevated Bcl-2 associated x protein/B-cell CLL/lymphoma 2 (Bax/Bcl-2) ratio, reduced cellular inhibitor of apoptosis 1 (c-IAP1) expression, and increased expression of apoptosis-inducing factor (AIF). The observed cell death was caspase-dependent as proven by caspase 3 activation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. IR-induced cell death was also associated with downregulation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (avian)/protein serine/threonine kinase B/extracellular signal-regulated protein kinase 1/2 (Src/AKT/ERK1/2) pathway and activation of p38 MAP kinase (p38) and Jun-amino-terminal kinase (JNK). Interestingly, IR treatment leads to inhibition of matrix metalloproteinase-2 (MMP-2) activity and reduced expression of renal cancer aggressiveness markers caveolin-1, low molecular weight phosphotyrosine protein phosphatase (LMWPTP), and kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR-2). Together, these results show the potential of IR for treating cancer.

Effects of detachment and repositioning of the medial pterygoid muscle on the growth of the maxilla and mandible of young rats

PURPOSE: To analyze the effects of detachment and repositioning of the medial pterygoid muscle on the growth of the maxilla and mandible of young rats through cephalometry. METHODS: Thirty one-month-old Wistar rats were used, distributed into three groups: experimental, sham-operated and control. In the experimental group, unilateral detachment and repositioning of the medial pterygoid muscle was performed. The sham-operated group only underwent surgical access, and the control group did not undergo any procedure. The animals were sacrificed at the age of three months. Their soft tissues were removed and the mandible was disarticulated. Radiographs of the skull in axial projection and the hemimandibles in lateral projection were obtained, and cephalometry was performed. The values obtained were subjected to statistical analyses among the groups and between the sides in each group. RESULTS: There were significant differences in the length of the mandible relative to the angular process in the experimental group and in the height of the mandibular body in the sham-operated group. CONCLUSION: The experimental detachment and repositioning of the medial pterygoid muscle during the growth period in rats affected the growth of the angle region, resulting in asymmetry of the mandible.

Effects of the unilateral removal and dissection of the masseter muscle on the facial growth of young rats

This study analyzed the effects of the unilateral removal and dissection of the masseter muscle on the facial growth of young rats. A total of 30 one-month-old Wistar rats were used. Unilateral complete removal of the masseter muscle was performed in the removal group, and detachment followed by repositioning of the masseter muscle was performed in the dissection group, while only surgical access was performed in the sham-operated group. The animals were sacrificed at three months of age. Axial radiographic projections of the skulls and lateral projections of the hemimandibles were taken. Cephalometric evaluations were made and the values obtained were submitted to statistical analyses. In the removal group, there were contour alterations of the angular process, and a significant homolateral difference in the length of the maxilla and a significant bilateral difference in the height of the mandibular body and the length of the mandible were observed. Comparison among groups revealed significance only in the removal group. It was concluded that the experimental removal of the masseter muscle during the growing period in rats induced atrophic changes in the angular process, as well as asymmetry of the maxilla and shortening of the whole mandible.

Association between overbite and craniofacial growth pattern

The purpose of the present study was to assess the association between overbite and craniofacial growth pattern. The sample comprised eighty-six cephalograms obtained during the orthodontic pretreatment phase and analyzed using the Radiocef program to identify the craniofacial landmarks and perform orthodontic measurements. The variables utilized were overbite, the Jarabak percentage and the Vert index, as well as classifications resulting from the interpretation of these measurements. In all the statistical tests, a significance level of 5% was considered. Measurement reliability was checked by calculating method error. Weighted Kappa analysis showed that agreement between the facial types defined by the Vert index and the direction of growth trend established by the Jarabak percentage was not satisfactory. Owing to this lack of equivalency, a potential association between overbite and craniofacial growth pattern was evaluated using the chi-square test, considering the two methods separately. No relationship of dependence between overbite and craniofacial growth pattern was revealed by the results obtained. Therefore, it can be concluded that the classification of facial growth pattern will not be the same when considering the Jarabak and the Ricketts anayses, and that increased overbite cannot be associated with a braquifacial growth pattern, nor can openbite be associated with a dolichofacial growth pattern.

Comparison of radial growth rate of the mutualistic fungus of Atta sexdens rubropilosa forel in two culture media

In vitro culture of the mutualistic fungus of leaf-cutting ants is troublesome due to its low growth rate, which leads to storage problems and contaminants accumulation. This paper aims at comparing the radial growth rate of the mutualistic fungus of Atta sexdens rubropilosa Forel in two different culture media (Pagnocca B and MEA LP). Although total MEA LP radial growth was greater all along the bioassay, no significant difference was detected between growth efficiencies of the two media. Previous evidences of low growth rate for this fungus were confirmed. Since these data cannot point greater efficiency of one culture medium over the other, MEA LP medium is indicated for in vitro studies with this mutualistic fungus due its simpler composition and translucent color, making the analysis easier.

Physiological and biochemical characterization of the assai palm (Euterpe oleracea Mart.) during seed germination and seedling growth under aerobic and anaerobic conditions

Physiological and biochemical aspects of assai palm during seed germination and early seedling growth were investigated. Seeds collected from plants growing in flooded and upland forests were used to determine the influence of normoxic (aerobic) and anoxic (anaerobic) conditions in germination and the initial and average time of development in the roots and shoots. After 75 days, seedlings germinated under normoxia were transferred to trays and submitted to flooding. Seed reserves (lipids, proteins, soluble sugars and starch) were monitored for quiescent and germinated seeds maintained under normoxic and anoxic conditions, as well as after 5, 10 and 20 days of seedling growth. Alcohol dehydrogenase (ADH) activity was quantified in roots and leaves of seedlings without or with flooding (partial and total). Seeds were not able to germinate under anoxia. Different strategies of storage mobilization of lipids, proteins, soluble sugars and starch were observed in seeds of each environment. ADH activity was induced by anoxia, with the highest level observed in the leaves. This study showed that, under normoxic conditions, the best developmental performance of assai palm seeds, from flooded or upland forest areas, during germination was associated with primary metabolites mobilization and seedling flooding tolerance with increased ADH activity. We conclude that the assai palm is well adapted to the anoxic conditions provoked by flooding.

Deleterious effect of TRIS buffer on growth rates and pigment content of Gracilaria birdiae Plastino & E.C. Oliveira (Gracilariales, Rhodophyta)

This work evaluated the effects of Tris (hydroxymethyl)-aminomethane (TRIS) buffer and its interaction with nutrient concentration on the development of Gracilaria birdie, a common species on the Brazilian coast that has been exploited for agar production. Responses to different conditions were assessed through growth rates and pigment content (chlorophyll a, phycoerythrin, phycocyanin and allophycocyanin). Provasoli's nutrient solution with and without TRIS addition was tested at concentrations of 12.5, 25 and 50%. The pH was also monitored. G. birdiae grew better in the absence of TRIS and at low nutrient concentrations, 12.5 and 25% (growth rates of 10.8-11.3%.day-1). Higher contents of phycoerythrin and chlorophyll a were observed without TRIS at 12.5 and 25% (Phycoerythrin, 649.6-698.0 μg g-1 fresh biomass; Chlorophyll a, 156.0-168.6 μg g-1 fresh biomass). These findings highlight the deleterious effect of TRIS on growth and phycoerythrin and chlorophyll a content. They also demonstrate the importance of appropriate nutrient concentration for laboratory cultures, depending on the intrinsic characteristics of each species.

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-β1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg-1·day-1 (D0.01, N = 14), 1 mg·kg-1·day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-β1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ≤ 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-β1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Richards growth model and viability indicators for populations subject to interventions

In this work we study the problem of modeling identification of a population employing a discrete dynamic model based on the Richards growth model. The population is subjected to interventions due to consumption, such as hunting or farming animals. The model identification allows us to estimate the probability or the average time for a population number to reach a certain level. The parameter inference for these models are obtained with the use of the likelihood profile technique as developed in this paper. The identification method here developed can be applied to evaluate the productivity of animal husbandry or to evaluate the risk of extinction of autochthon populations. It is applied to data of the Brazilian beef cattle herd population, and the the population number to reach a certain goal level is investigated.

Effects of nitrate and phosphate availabilities on growth, photosynthesis and pigment and protein contents in colour strains of Hypnea musciformis (Wulfen in Jacqu.) J.V. Lamour. (Gigartinales, Rhodophyta)

In Brazil, Hypnea musciformis is the main raw material for carrageenan production and the knowledge of nitrogen and phosphorus metabolism in algae is critical for the success of cultivation because these elements can limit seaweed productivity. Thus, the objective of this study was to evaluate the effects of nitrate (zero to 100 μM) and nitrate plus phosphate (zero to 25 μM) availabilities on the growth, the contents of photosynthetic pigments (phycobiliproteins and chlorophyll a) and proteins, and the photosynthesis and respiration of the brown (BR) and light green (LG) strains of H. musciformis. The results revealed metabolic differences between the colour strains of H. musciformis for nitrogen metabolism: upon nitrate addition, the LG strain stored nitrogen mainly as proteins, while the BR strain stored it as proteins and pigments. Moreover, the respiration of the LG strain and the photosynthesis of the BR strain increased with nitrate concentrations, indicating that the BR strain fixed more photosynthetic carbon than the LG strain.

Growth parameters and mortality rate of the Scomber japonicus peruanus (Jordán & Hubb, 1925) along the Peruvian coast, South Pacific

The growth parameters and the mortality rates of the Scomber japonicus peruanus (Chub mackerel) were studied based on monthly data of frequency of fork length classes obtained from commercial landings off the Peruvian coast from 1996 to 1998. The asymptotic body length and growth rate values obtained by the ELEFAN I (Electronic Length Frequency Analysis) ranged from 40.20 cm to 42.20 cm and from 0.38 to 0.39, respectively. The oscillation amplitude was 0.60; the Winter point values varied from 0.50 to 0.60 and the performance index from 2.79 to 2.84. The total mortality rate of the Chub mackerel obtained by the linearized catch curve oscillated between 1.68 and 3.35. The rate of fishing mortality varied from 1.16 to 2.78 and the exploitation rate from 0.68 to 0.84. The annual rate of natural mortality estimated by the Pauly's method ranged from 0.52 to 0.53. The results obtained allow us to conclude that the longevity of the Chub mackerel was slightly over seven years.

Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days) and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days) isogenic BALB/c mice in each experiment. Cyhalothrin i) increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05), concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05), and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05); ii) increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05), and iii) decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05) and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05) in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA) axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

Infant feeding practices, childhood growth and obesity in adult life

A saúde infantil é amplamente afetada pelo estado nutricional. Há um interesse crescente acerca da possibilidade do estado nutricional apresentado pela criança e das práticas alimentares na primeira infância estarem relacionados à obesidade em indivíduos adultos, aumentando os riscos para complicações metabólicas. Sabe-se que estudos prospectivos possibilitam a investigação e a avaliação apropriadas de determinantes do desenvolvimento infantil. Consequentemente, o presente artigo objetivou revisar as principais evidências disponíveis a partir de estudos longitudinais sobre associações entre práticas alimentares na primeira infância, padrões de crescimento infantil e estado nutricional verificados durante a vida adulta