Publications by authors named "Jorge Carvalho"

73 Publications

Resveratrol promotes liver regeneration in drug-induced liver disease in mice.

Food Res Int 2021 Apr 1;142:110185. Epub 2021 Feb 1.

Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil; National Institute of Science and Technology for Regenerative Medicine, INCT-REGENERA, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Electronic address:

Studies suggest that the bioactive polyphenolic compound resveratrol (RESV, trans-isomer), found naturally in certain foods such as red grapes and peanuts, may be able to ameliorate liver damage. However, the effects and efficacy of long-term treatment with RESV remain unclear. Here, we used an acetaminophen (APAP; 400 mg/kg/d for 15 days) overdose model to induce liver damage in C56BL/6 mice. Three days after the intoxication was stopped, we observed biochemical, histological and ultrastructural alterations in the livers of these mice. The APAP-treated animals were then given RESV (10 mg/kg/d) for 60 days. Blood and tissue were analyzed at days 7, 30 and 60. Our data show that long-term RESV treatment (60 days) ameliorates the liver injury caused by APAP intoxication, restoring histological features, ultrastructural organization and serum biochemical parameters (albumin, alanine aminotransferase). Ck18- and F4/80-positive cells (indicators of hepatocyte recovery) were reestablished and the number of α-SMA positive cells was normalized after long-term RESV treatment. Additionally, downregulation of the drug transporter BCRP was observed. Electron microscopy revealed that treatment with RESV was effective in restoring the shape and size of hepatic microvilli and normalizing both the number and viability of mitochondria. Taken together, these results indicate that long-term treatment with RESV is effective in alleviating liver injury caused by APAP administration.
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http://dx.doi.org/10.1016/j.foodres.2021.110185DOI Listing
April 2021

Pancreatic steatosis in adult rats induced by nicotine exposure during breastfeeding.

Endocrine 2021 Jan 9. Epub 2021 Jan 9.

Laboratory of Endocrine Physiology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Purpose: Maternal nicotine exposure negatively impacts offspring's health and metabolism, leading to obesity and insulin resistance. Here we investigated the pancreatic islet function, glycemic homeostasis, and insulin signaling in adult rat offspring that were nicotine-exposed during breastfeeding.

Methods: For this, lactating Wistar rat dams were divided into two groups: Nicotine (implanted with osmotic minipumps containing 6 mg/Kg, NIC) and Control (saline, CON). Solutions were released from postnatal (PN) day 2-16. At PN110 and PN170, 10 offspring per litter/sex/group were submitted to the oral glucose tolerance test (OGTT). PN180 offspring were killed and glycemia, insulinemia, adiponectinemia, pancreas morphology as well as pancreatic islet protein expression (related to insulin secretion) and skeletal muscle (related to insulin action) were evaluated. Males and females were compared to their respective controls.

Results: Adult NIC offspring of both sexes showed glucose intolerance in the OGTT. Despite normoglycemia, NIC males showed hyperinsulinemia while females, although normoinsulinemic, had hyperglycemia. Both sexes showed increased IRI, reduced adiponectin/visceral fat mass ratio and higher ectopic deposition of lipids in the pancreatic tissue adipocytes. In pancreatic islets, NIC males showed lower PDX-1 expression while females had higher PDX-1 and GLUT2 expressions plus lower α2 adrenergic receptor. In the muscle, NIC offspring of both sexes showed reduction of GLUT4 expression; NIC males also had lower insulin receptor and pAKT expressions.

Conclusions: Thus, glycemic homeostasis and peripheral insulin signaling in adult offspring of both sexes are affected by nicotine exposure through the milk, increasing the risk for type 2 diabetes development.
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http://dx.doi.org/10.1007/s12020-020-02579-9DOI Listing
January 2021

Phosphodiesterase-5 inhibition improves bone regeneration at the early stages of ischemic osteonecrosis of the femoral head in rats.

J Orthop Res 2020 Dec 3. Epub 2020 Dec 3.

Departamento de Histologia e Embriologia, Laboratório de Ultraestrutura e Biologia Tecidual, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Posttraumatic osteonecrosis of the femoral head (ONFH) affects patients at different ages and may lead to functional limitation and joint replacement, with total hip arthroplasty, which is a costly procedure. Proposed methods to optimize ischemic tissue regeneration have been reported. Phosphodiesterase-5 inhibitors act by inhibiting the degradation of guanosine 3',5'-cyclic monophosphate in the nitric oxide pathway, increasing its bioavailability and promoting vascular endothelial growth factor (VEGF)-mediated neovascular recruitment and the induction of tissue regeneration in the traumatized bone. Thirty male Sprague-Dawley rats (6 months old) were subjected to an experimental model of traumatic ONFH divided into two groups, according to the administration of 5 mg/kg sildenafil or water (control group). Rats were then killed at 7, 14, and 21 days. Histological (Goldner's trichrome), histochemical (periodic acid-Schiff [PAS]), and immunohistochemical (VEGF and osteopontin [OPN]) techniques were used to quantify bone and vascular responses. Higher levels of VEGF (p < 0.01) and OPN (p < 0.01) immunostaining in the epiphysis, the greater formation of osteoid tissue (p < 0.01 on Day 7; p < 0.05 on Day 14), and higher levels of PAS staining (p < 0.01 on Day 7) were observed in the sildenafil-treated group. The present study demonstrated that sildenafil optimized bone tissue regeneration by increasing VEGF signaling and OPN expression, with increased bone formation (osteoid and carbohydrate macromolecule deposition) in the early stages following traumatic ischemic insult. Thus, sildenafil treatment may improve the prognosis of patients with osteonecrosis.
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http://dx.doi.org/10.1002/jor.24934DOI Listing
December 2020

Interrelationship between renin-angiotensin-aldosterone system and oxidative stress in chronic heart failure patients with or without renal impairment.

Biomed Pharmacother 2021 Jan 7;133:110938. Epub 2020 Nov 7.

Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Rua Dr. Plácido da Costa, S/N, Edifício Poente, Piso 3, 4200-450 Porto, Portugal; Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto (MedInUP), Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. Electronic address:

We investigated oxidative stress and RAAS biomarkers, as well as their association, in chronic heart failure (CHF) patients on optimized medical therapy, stratified by disease severity or by renal function. Since vitamin D has been shown to attenuate RAAS activation and oxidative stress, we further evaluated the relationship between vitamin D, RAAS and oxidative stress in CHF patients with or without renal impairment. Sixty CHF outpatients were included and stratified by disease severity or by renal function. We quantified urinary hydrogen peroxide, plasma and urinary isoprostanes, plasma total antioxidant status, urinary angiotensinogen (intrarenal RAAS activation biomarker) and plasma angiotensinogen, plasma renin and aldosterone concentration, serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin peptides, and serum total 25-hydroxyvitamin D (S-total 25(OH)D). Severe CHF patients had higher urinary isoprostanes (p = 0.002) and lower S-total 25(OH)D (p = 0.006) compared to mild-to-moderate patients, but no differences were observed for other redox or RAAS biomarkers. Patients with impaired renal function (iRF) had higher urinary angiotensinogen (p = 0.003) and lower S-total 25(OH)D (p = 0.028) compared to those with normal renal function (nRF), while no differences were observed for the remaining RAAS and redox parameters. Several positive correlations between oxidative stress and RAAS biomarkers were detected in iRF patients, while in patients with nRF these correlations were primarily inverse. In CHF-iRF patients, S-25(OD)D was inversely associated with urinary isoprostanes, which in turn were positively associated with plasma angiotensinogen and serum ACE. In conclusion, CHF patients with renal function impairment have increased intrarenal RAAS activation and lower vitamin D values and might benefit from the combination of RAAS blockers with vitamin D and/or antioxidants.
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http://dx.doi.org/10.1016/j.biopha.2020.110938DOI Listing
January 2021

Aliskiren Reduces the Adrenal Zona Glomerulosa Apoptosis and Autophagy in Wistar Rats with 2K1C Hypertension.

Int J Hypertens 2020 21;2020:7684849. Epub 2020 Oct 21.

Laboratory of Ultrastructure and Tecidual Biology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Hypertension is a disease classified as primary or secondary, manifested not only by elevation of blood pressure but also involved in structural and functional changes of target organs. Renal artery stenosis is a leading factor of secondary hypertension, and its progress is associated with overactivation of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion. In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Parameters as structure and ultrastructure of the adrenal glomerular zone, cellular apoptosis, nuclear cell proliferation, and AT1 receptor expression were analyzed by immunostaining and electron microscopy. Our results showed that the hypertensive animals treated with aliskiren presented a reestablishment of AT1 receptor expression and decrease in apoptosis and autophagy. In addition, treatment with aliskiren improves the cell aspects in the adrenal glomerular zone, evidenced by ultrastructural analysis through preserved nuclei and well-developed mitochondria. Therefore, our evidence suggests that aliskiren has a beneficial effect on the adrenal glomerular zone remodeling in animals with renovascular hypertension.
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http://dx.doi.org/10.1155/2020/7684849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596424PMC
October 2020

Histomorphometric, Immunohistochemical, Ultrastructural Characterization of a Nano-Hydroxyapatite/Beta-Tricalcium Phosphate Composite and a Bone Xenograft in Sub-Critical Size Bone Defect in Rat Calvaria.

Materials (Basel) 2020 Oct 15;13(20). Epub 2020 Oct 15.

Biology Department, State University of Rio de Janeiro, 20550-900, Rio de Janeiro, Brazil.

Nowadays, we can observe a worldwide trend towards the development of synthetic biomaterials. Several studies have been conducted to better understand the cellular mechanisms involved in the processes of inflammation and bone healing related to living tissues. The aim of this study was to evaluate tissue behaviors of two different types of biomaterials: synthetic nano-hydroxyapatite/beta-tricalcium phosphate composite and bone xenograft in sub-critical bone defects in rat calvaria. Twenty-four rats underwent experimental surgery in which two 3 mm defects in each cavity were tested. Rats were divided into two groups: Group 1 used xenogen hydroxyapatite (Bio Oss™); Group 2 used synthetic nano-hydroxyapatite/beta-tricalcium phosphate (Blue Bone™). Sixty days after surgery, calvaria bone defects were filled with biomaterial, animals were euthanized, and tissues were stained with Masson's trichrome and periodic acid-Schiff (PAS) techniques, immune-labeled with anti-TNF-α and anti-MMP-9, and electron microscopy analyses were also performed. Histomorphometric analysis indicated a greater presence of protein matrix in Group 2, in addition to higher levels of TNF-α and MMP-9. Ultrastructural analysis showed that biomaterial fibroblasts were associated with the tissue regeneration stage. Paired statistical data indicated that Blue Bone™ can improve bone formation/remodeling when compared to biomaterials of xenogenous origin.
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http://dx.doi.org/10.3390/ma13204598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602735PMC
October 2020

Zika Induces Human Placental Damage and Inflammation.

Front Immunol 2020 1;11:2146. Epub 2020 Sep 1.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.

In Brazil, an epidemic of Zika virus (ZIKV) infections was declared in 2015 that coincided with alarming reports of microcephaly in newborns associated with mother infection. Although the virus has placental tropism, changes in the tissue morphology and immunity of infected patients have not yet been elucidated. Here, we investigated the histopathological and ultrastructural changes along with the immunological profile and the BDNF expression in rare placental material. Tissues were obtained in the 2015-2016 Brazilian epidemic, of ten ZIKV-infected patients during pregnancy, five resulting in cases of fetal microcephaly and five non-microcephaly, compared to five non-infected control placentae. Viral antigens were only detected in samples from the ZIKV infected patients. Infected placentae presented histopathological severe damage, while the ultrastructural evaluation showed abnormal organelles, such as clusters of virus-like particles consistent with the ZIKV dimensions. Increased infiltration of CD68 and TCD8 cells, expression of MMPs, cytokines (IFN-γ and TNF-α) and other immunological mediators (RANTES/CCL5 and VEGFR-2) confirmed excessive inflammation and vascular permeability dysfunction. An evaluation of BDNF showed a decrease that could modulate neuronal damage in the developing fetus. The placental changes caused by ZIKV are not pathognomonic, however, the data provide evidence that this infection leads to severe placental injury.
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http://dx.doi.org/10.3389/fimmu.2020.02146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490298PMC
September 2020

Açaí (Euterpe oleracea Mart.) seed extract improves aerobic exercise performance in rats.

Food Res Int 2020 10 15;136:109549. Epub 2020 Jul 15.

Department of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil. Electronic address:

The purpose of this study was to examine whether the supplementation with an açai (Euterpe oleracea Mart.) seed extract (ASE) would affect the aerobic exercise performance in rats and correlate with the vascular function, muscle oxidative stress and mitochondrial biogenesis. Male Wistar rats were divided into five groups: Sedentary, Sedentary with chronic supplementation of ASE, Training, Training with chronic (200 mg/Kg/day intragastric gavage for 5 weeks) or acute (30 min before the maximal treadmill stress test (MST) supplementation with ASE. The exercise training was performed on a treadmill (30 min/day; 5 days/week) for 4 weeks. The chronic supplementation with ASE increased the exercise time (58%) and the running distance (129%) in relation to the MST, while the Training group increased 40% and 78% and the Training with acute ASE group increased 30% and 63%, respectively. The training-induced increase of ACh vasodilation was not changed by ASE, but the norepinephrine-induced vasoconstriction was reduced by chronic and acute supplementation with ASE. The increased levels of malondialdehyde in soleus muscle homogenates from the Training group was reduced only by chronic supplementation with ASE. The muscle antioxidant defense, NO levels, and expression of the mitochondrial biogenesis-related proteins (PGC1α, SIRT-1, p-AMPK/AMPK, Nrf-2) were not different between Training and Sedentary groups, but all these parameters were increased in the Training with Chronic ASE compared with the Sedentary groups. In conclusion, chronic supplementation with ASE improves aerobic physical performance by increasing the vascular function, reducing the oxidative stress, and up-regulating the mitochondrial biogenesis key proteins.
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http://dx.doi.org/10.1016/j.foodres.2020.109549DOI Listing
October 2020

Abdominoplasty with Scarpa Fascia Preservation: Randomized Controlled Trial with Assessment of Scar Quality and Cutaneous Sensibility.

Plast Reconstr Surg 2020 08;146(2):156e-164e

From Porto University Medical School; the Department of Plastic, Aesthetic, and Reconstructive Surgery, São João University Hospital; the Department of Surgery and Physiology, Faculty of Medicine, Porto University; the Plastic Surgery Department, Portuguese Institute of Oncology of Porto; the Interdisciplinary Centre of Marine and Environmental Research; and the Department of Biology, Faculty of Sciences, University of Porto.

Background: Scarpa fascia preservation during abdominoplasty has been shown to reduce complications associated with the traditional technique. As an extension of a previously published randomized controlled trial, this study aims to clarify whether preservation of Scarpa fascia during abdominoplasty has an influence on scar quality or sensibility recovery.

Methods: This was a single-center clinical trial, involving 160 patients randomly assigned to one of two surgical procedures: classic full abdominoplasty (group A) and abdominoplasty with preservation of Scarpa fascia (group B). Patients were later convoked to assess scar quality and abdominal cutaneous sensibility. Scar quality was evaluated through the Patient and Observer Scar Assessment Scale. Cutaneous sensibility was measured on the upper and lower abdomen, using light touch, Semmes-Weinstein testing (5.07/10-g monofilament), and a 25-gauge needle.

Results: A total of 99 patients (group A, 54 patients; group B, 45 patients) responded to contact, with a mean follow-up time of 44 months. Concerning scar quality, Patient and Observer Scar Assessment Scale scores were similar between groups. On the upper abdomen, there was a statistically significant difference between groups on cutaneous sensibility, on the examination with the Semmes-Weinstein 5.07/10-g monofilament (group A, 79.6 percent; group B, 93.3 percent; p = 0.046) and pain (group A, 90.7 percent; group B, 100 percent; p = 0.044). No statistically significant differences were found between groups on the lower abdomen. A considerable proportion of patients (two-thirds) still presented sensibility alterations in the subumbilical area 3½ years after abdominoplasty.

Conclusion: Scarpa fascia preservation during abdominoplasty does not influence scar quality, but it improves sensibility recovery in the supraumbilical area.

Clinical Question/level Of Evidence: Therapeutic, II.
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http://dx.doi.org/10.1097/PRS.0000000000007024DOI Listing
August 2020

Use of flash glucose monitoring for post-bariatric hypoglycaemia diagnosis and management.

Sci Rep 2020 07 6;10(1):11061. Epub 2020 Jul 6.

Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Jorge Viterbo Ferreira 228, Ed.1, 3rd Floor, 4050-313, Porto, Portugal.

Our aim was to assess the potential of flash glucose monitoring (FGM) for diagnostic workup of suspected post-bariatric hypoglycaemia (PBH). Patients (N = 13) with suspected PBH underwent a food and symptoms diary (FSD) record along with FGM over 14 days. Targeted data analysis confirmed the occurrence of low glucose events in parallel to meal-triggered symptoms. Glycaemic variability, as assessed by Mean Absolute Glucose change (MAG change), was increased, while a higher risk of glycaemic excursions towards both hyper and hypoglycaemia (ADRRGT) was observed in those with more frequent and severe hypoglycaemia. The herein described hypoglycaemia risk index (LBGIGT) with a cut-off value of 4.6 showed to have 100% sensitivity and 100% specificity for PBH. This pilot proof-of-concept study highlighted that FSD coupled with FGM followed by targeted data analysis, provides relevant insights towards PBH diagnosis and grading in a user-friendly and easy to implement study protocol. Furthermore, LBGIGT demonstrated to be an excellent index for PBH diagnosis. The unexpected improvement of glucose profile noticed along the monitoring time also unravels a possible application for PBH management.
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http://dx.doi.org/10.1038/s41598-020-68029-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338422PMC
July 2020

Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes.

Cells 2020 04 16;9(4). Epub 2020 Apr 16.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.

Zika virus (ZIKV) is an emergent arthropod-borne virus whose outbreak in Brazil has brought major public health problems. Infected individuals have different symptoms, including rash and pruritus, which can be relieved by the administration of antiallergics. In the case of pregnant women, ZIKV can cross the placenta and infect the fetus leading to congenital defects. We have identified that mast cells in the placentae of patients who had Zika during pregnancy can be infected. This led to our investigation on the possible role of mast cells during a ZIKV infection, using the HMC-1 cell line. We analyzed their permissiveness to infection, release of mediators and ultrastructural changes. Flow cytometry detection of ZIKV-NS1 expression 24 h post infection in 45.3% of cells showed that HMC-1 cells are permissive to ZIKV infection. Following infection, β-hexosaminidase was measured in the supernatant of the cells with a notable release at 30 min. In addition, an increase in TNF-α, IL-6, IL-10 and VEGF levels were measured at 6 h and 24 h post infection. Lastly, different intracellular changes were observed in an ultrastructural analysis of infected cells. Our findings suggest that mast cells may represent an important source of mediators that can activate other immune cell types during a ZIKV infection, which has the potential to be a major contributor in the spread of the virus in cases of vertical transmission.
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http://dx.doi.org/10.3390/cells9040975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227014PMC
April 2020

Orphan G Protein-Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling.

Circulation 2020 04 16;141(14):1168-1183. Epub 2020 Jan 16.

Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Background: G protein-coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein-coupled receptor class C group 5 member B (GPRC5B) is unclear.

Methods: We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMCs in vitro and in iSM--KO (tamoxifen-inducible, SMC-specific knockout) mice under conditions of arterial hypertension and atherosclerosis in vivo.

Results: Mesenteric arteries from SMC-specific -KOs showed ex vivo significantly enhanced prostacyclin receptor (IP)-dependent relaxation, whereas responses to other relaxant or contractile factors were normal. In vitro, knockdown of GPRC5B in human aortic SMCs resulted in increased IP-dependent cAMP production and consecutive facilitation of SMC relaxation. In line with this facilitation of IP-mediated relaxation, iSM--KO mice were protected from arterial hypertension, and this protective effect was abrogated by IP antagonists. Mechanistically, we show that knockdown of GPRC5B increased the membrane localization of IP both in vitro and in vivo and that GPRC5B, but not other G protein-coupled receptors, physically interacts with IP. Last, we show that enhanced IP signaling in GPRC5B-deficient SMCs not only facilitates relaxation but also prevents dedifferentiation during atherosclerosis development, resulting in reduced plaque load and increased differentiation of SMCs in the fibrous cap.

Conclusions: Taken together, our data show that GPRC5B regulates vascular SMC tone and differentiation by negatively regulating IP signaling.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043703DOI Listing
April 2020

Nanosized hydroxyapatite and β-tricalcium phosphate composite: Physico-chemical, cytotoxicity, morphological properties and in vivo trial.

Sci Rep 2019 12 20;9(1):19602. Epub 2019 Dec 20.

Instituto Militar de Engenharia, Rio de Janeiro, Brazil.

The objective of this work was to characterize the properties of a synthetic biomaterial composite with nanoparticles size (Blue Bone). This biomaterial is a composite recommended for dental and orthopedic grafting surgery, for guided bone regeneration, including maxillary sinus lift, fresh alveolus filling, and treatment of furcation lesions. The nano biomaterials surface area is from 30% to 50% higher than those with micro dimensions. Another advantage is that the alloplastic biomaterial has homogeneous properties due to the complete manufacturing control. The analyzed biomaterial composite was characterized by XRD, cytochemistry, scanning electron microscopy, porosimetry and in vivo experiments (animals). The results showed that the analyzed biomaterial composite has 78.76% hydroxyapatite [Ca(PO)(OH)] with monoclinic structure, 21.03% β-tricalcium phosphate [β -Ca(PO)] with trigonal structure and 0.19% of CaO with cubic structure, nanoparticles with homogeneous shapes, and nanoporosity. The in vivo experiments showed that the composite has null cytotoxicity, and the site of insertion biomaterials has a high level of vascularization and bone formation. The conclusion is that the synthetic biomaterial with Blue Bone designation presents characteristics suitable for use in grafting surgery applications.
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http://dx.doi.org/10.1038/s41598-019-56124-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925105PMC
December 2019

Aliskiren improves renal morphophysiology and inflammation in Wistar rats with 2K1C renovascular hypertension.

Histol Histopathol 2020 Jun 18;35(6):609-621. Epub 2019 Oct 18.

Laboratory of Ultrastructure and Tecidual Biology, Institute of Biology, State University of Rio de Janeiro, RJ, Brazil.

Hypertension is characterized by persistent elevated blood pressure levels, one of the leading causes of death in the world. Renovascular hypertension represents the most common cause of secondary hypertension, and its progress is associated with overactivation of the renin angiotensin aldosterone system (RAAS), causing systemic and local changes. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the objective of the present study was to analyze the morphophysiology of the left kidney in Wistar rats with renovascular hypertension after treatment with Aliskiren. Parameters such as systolic blood pressure, urinary creatinine and protein excretion, renal cortex structure and ultrastructure, fibrosis and tissue inflammation were analyzed. Our results showed that the hypertensive animals treated with Aliskiren presented a reestablishment of blood pressure, expression of renin, and renal function, as well as a remodeling of morphological alterations through the reduction of fibrosis. The treatment regulated the laminin expression and decreased pro-inflammatory cytokines, restoring the integrity of the glomerular filtration barrier. Therefore, our findings suggest that Aliskiren has a renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertension.
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http://dx.doi.org/10.14670/HH-18-173DOI Listing
June 2020

Time course of cardiomyopathy induced by doxorubicin in rats.

Pharmacol Rep 2019 Aug 20;71(4):583-590. Epub 2019 Feb 20.

Laboratory of Membrane Transport, Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Background: Doxorubicin (DOX)-related cardiotoxicity may expose cancer survivors to increased risk of cardiovascular morbidity and mortality. Here, we characterized the time course of DOX-induced cardiomyopathy in rats.

Methods: Sprague-Dawley male rats (12 wk old) received doxorubicin hydrochloride (1 mg/kg/d, ip) during 10 consecutive days and they were euthanized one (DOX1), two (DOX2) or four (DOX4) weeks after the last drug injection. Control group received NaCl 0.9% (ip). Hearts were mounted on a Langendorff perfusion system, left ventricle fragments were processed for microscopy and oxidative stress-related assays, and blood was collected for cardiac troponin I assay.

Results: All DOX-treated groups showed swollen and vacuolated cardiomyocytes with myofilaments disarray and mitochondrial damage. These changes were already evident after one week and became more pronounced after four weeks. Cardiac troponin I plasma levels were significantly increased in DOX1 and further increased in DOX4 compared to control group. Increased oxidative damage to lipids was observed in DOX1, and to proteins in DOX4. Glutathione peroxidase activity increased in DOX4. The morphological changes resulted in cardiac remodeling, including interstitial fibrosis, apoptosis and significant impairment of both contractile and relaxation function in DOX 4 compared to control group. Hearts from all animals displayed an early reduction in the responsiveness to norepinephrine.

Conclusions: These findings support the view that DOX cardiotoxicity occurs in a "continuum", and as the hypothesis of an irreversible cardiac injury is being challenged, understanding the progression of morphological and functional changes caused by DOX may allow proper timing of initiation of prophylactic treatment.
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http://dx.doi.org/10.1016/j.pharep.2019.02.013DOI Listing
August 2019

A Stillborn Multiple Organs' Investigation from a Maternal DENV-4 Infection: Histopathological and Inflammatory Mediators Characterization.

Viruses 2019 04 2;11(4). Epub 2019 Apr 2.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz/FIOCRUZ, Rio de Janeiro 21040-900, Brazil.

Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction.
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http://dx.doi.org/10.3390/v11040319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521294PMC
April 2019

Physicochemical, cytotoxicity and in vivo biocompatibility of a high-plasticity calcium-silicate based material.

Sci Rep 2019 03 8;9(1):3933. Epub 2019 Mar 8.

Endodontic Department, School of Dentistry, Rio de Janeiro State University, Rio de Janeiro, Brazil.

The purpose of this work was to evaluate the physicochemical properties, the cytotoxicity and in vivo biocompatibility of MTA Repair HP (MTA HP) and White MTA (WMTA). The setting time, flow, radiopacity and water solubility were assessed. To the cytotoxicity assay, primary human osteoblast cells were exposed to several dilutions of both materials eluates. MTT assay, apoptosis assay and cell adhesion assay were performed. The in vivo biocompatibility was evaluated through histological analysis using different staining techniques. No differences were observed between MTA HP and WMTA for setting time, radiopacity, solubility and water absorption (P > 0.05). However, MTA HP showed a significantly higher flow when compared to WMTA (P < 0.05). Cell viability results revealed that the extracts of WMTA and MTA HP promoted the viability of osteoblasts. After incubation of cells with the endodontic cement extracts, the percentage of apoptotic or necrotic cells was very low (<3%). Furthermore, SEM results showed a high degree of cell proliferation and adhesion on both groups. MTA HP showed similar in vivo biocompatibility to the WMTA and the control group in all time-points. The MTA HP presented adequate physicochemical and biological properties with improved flow ability when compared to WMTA. Such improved flow ability may be a result of the addition of a plasticizing agent and should be related to an improvement in the handling of MTA HP.
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http://dx.doi.org/10.1038/s41598-019-40365-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408552PMC
March 2019

l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats.

Nitric Oxide 2019 01 10;82:1-11. Epub 2018 Nov 10.

Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina, Universidade do Porto, Rua Dr. Plácido da Costa, S/N, Piso 3, 4200-450, Porto, Portugal; MedInUP - Centro de Investigação Farmacológica e de Inovação Medicamentosa, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal. Electronic address:

We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg·day) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg.min) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary HO and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary HO values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. HO and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.
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http://dx.doi.org/10.1016/j.niox.2018.10.007DOI Listing
January 2019

Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients.

BMC Res Notes 2018 Sep 3;11(1):635. Epub 2018 Sep 3.

National Institute of Cardiology, Ministry of Health, Rua das Laranjeiras No. 374, Rio de Janeiro, RJ, 22240-006, Brazil.

Background: Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purpose OBJECTIVE: To assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-β1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patients RESULTS: The present study will add information to the vascular degenerative processes occurring in diabetic patients.
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http://dx.doi.org/10.1186/s13104-018-3743-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122454PMC
September 2018

Placental Inflammation and Fetal Injury in a Rare Zika Case Associated With Guillain-Barré Syndrome and Abortion.

Front Microbiol 2018 16;9:1018. Epub 2018 May 16.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.

Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8 lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.
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http://dx.doi.org/10.3389/fmicb.2018.01018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964188PMC
May 2018

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease.

Evid Based Complement Alternat Med 2018 29;2018:4956079. Epub 2018 Apr 29.

Laboratory of Ultrastructure and Tissue Biology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.
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http://dx.doi.org/10.1155/2018/4956079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949171PMC
April 2018

Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension.

Eur J Vasc Endovasc Surg 2018 05 24;55(5):694-702. Epub 2018 Mar 24.

Laboratório de Pesquisas Clínicas e Experimentais em Biologia Vascular, Centro Biomédico, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.

Objectives: To assess protective effects of micronized purified flavonoid fraction (MPFF) on microcirculation in an original chronic model of hind limb venous hypertension with low blood flow in small animals.

Methods: Vein ligatures were performed on male hamsters, as follows: A-right femoral vein; A + B-right femoral vein and its right branch; A + C-right femoral vein and its left branch; A + B + C-right femoral and its right and left branches; D-external right iliac vein. In sham operated groups, similar vascular dissections were performed without ligatures. Superficial (epigastric) and central (jugular) venous pressure evaluations were made during a 10 week period. Hamsters subjected to A + B + C and D ligatures were selected for leukocyte rolling and sticking, functional capillary density (FCD), and venular and arteriolar diameter observations. D ligature was selected to evaluate pharmacological treatment efficacy. MPFF (100 mg/kg), concomitant active flavonoids of MPFF (diosmetin, hesperidin, linarin, and isorhoifolin) (10 mg/kg), diosmin (100 mg/kg) or drug vehicle were administered orally during 2 weeks before vein ligature and 6 weeks thereafter.

Results: A, A + B and A + C models maintained venous return through collaterals. From the 2 to the 10 weeks after vein ligatures, A + B + C and D models elicited a progressive increase of superficial venous pressure (3.83 ± 0.65 vs. 8.56 ± 0.72 mmHg, p < .001 and 4.13 ± 0.65 vs. 9.35 ± 0.65 mmHg, p < .001, respectively) with significant changes to the microcirculation. As D model significantly increased superficial venous pressure without affecting central venous pressure, it was used to evaluate the long-term effects of treatment. Compared with vehicle, MPFF, concomitant active flavonoids of MPFF, and diosmin, significantly decreased leukocyte-endothelium interaction and prevented FCD reduction. Only MPFF significantly prevented venular enlargement as observed in the vehicle treated group.

Conclusion: MPFF was more effective than diosmin in improving all microvascular variables. The superiority of MPFF over diosmin alone can be explained by the synergistic beneficial effects of the association between diosmin and active flavonoids of MPFF.
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http://dx.doi.org/10.1016/j.ejvs.2018.02.009DOI Listing
May 2018

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant.

Front Immunol 2017 7;8:1704. Epub 2017 Dec 7.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.
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http://dx.doi.org/10.3389/fimmu.2017.01704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725436PMC
December 2017

Reconstruction of a near total ear amputation with a neurosensorial radial forearm free flap prelaminated with porous polyethylene implant and delay procedure.

Microsurgery 2018 Feb 5;38(2):203-208. Epub 2017 Oct 5.

Department of Plastic, Reconstructive and Maxillo-Facial Surgery, and Burn Unity, Centro Hospitalar de São João, University of Porto, Portugal.

When an auricular defect is caused by high-energy trauma that causes damage to the surrounding tissues, the patient may be not a candidate for reconstruction with local flaps and free tissue transfer may be necessary. Here we present a case of total auricular reconstruction in a 27 year-old man who had total loss of the left ear and traumatized temporal skin and fascia. A radial forearm flap prelaminated by a porous polyethylene implant was employed. A "printed" ear made of silicone, based on the patient's CT-scan of the contralateral ear, was used for intraoperative molding of the future reconstruction. Prolonged prelamination time and surgical delay (three months) were performed to reduce edema, distortion and loss of definition of the framework after revascularization. After subsequent integration and neovascularization of the added tissue, the prelaminated flap was transferred. Flap reinnervation was also performed by direct coaption of the great auricular nerve to the lateral antebrachial cutaneous nerve. The flap fully survived and there were no complications in the early postoperative period. Between 3 and 6 months, the patient returned to normal ranges in terms of warmth and cold, and recovered the discriminative facial sensibility. After one year the auricular reconstruction was intact and satisfactory aesthetic results were achieved. This method may offer a satisfactory solution for a difficult problem and may be considered for acquired total ear defects.
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http://dx.doi.org/10.1002/micr.30249DOI Listing
February 2018

Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.

JCI Insight 2017 Aug 3;2(15). Epub 2017 Aug 3.

Department of Pharmacology.

GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2 as examples, we show how this information can be used to develop new strategies for the functional modulation of Th17 cells and activated endothelial cells. Taken together, single-cell GPCR expression analysis identifies functionally relevant subpopulations with specific GPCR repertoires and provides a basis for the development of new therapeutic strategies in immune disorders.
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http://dx.doi.org/10.1172/jci.insight.95063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543912PMC
August 2017

Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-β1 Cytokine.

Dose Response 2017 Apr-Jun;15(2):1559325817705019. Epub 2017 Apr 28.

Radiological Sciences Laboratory, Department of Biophysics and Biometry, State University of Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.

Purpose: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition.

Results: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor β1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups.

Conclusion: It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment.

Advances In Knowledge: This study is important to develop strategies to prevent radiation-induced skin reactions.
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http://dx.doi.org/10.1177/1559325817705019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415163PMC
April 2017

Current uses of ground penetrating radar in groundwater-dependent ecosystems research.

Sci Total Environ 2017 Oct 18;595:868-885. Epub 2017 Apr 18.

Civil Engineering Research and Innovation for Sustainability (CERIS), Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal.

Ground penetrating radar (GPR) is a high-resolution technique widely used in shallow groundwater prospecting. This makes GPR ideal to characterize the hydrogeological functioning of groundwater-dependent ecosystems (GDE). This paper reviews current uses of GPR in GDE research through the construction of a database comprising 91 worldwide GPR case studies selected from the literature and classified according to (1) geological environments favouring GDE; (2) hydrogeological research interests; and (3) field technical and (4) hydrogeological conditions of the survey. The database analysis showed that inland alluvial, colluvial, and glacial formations were the most widely covered geological environments. Water-table depth was the most repeated research interest. By contrast, weathered-marl and crystalline-rock environments as well as the delineation of salinity interfaces in coastal and inland areas were less studied. Despite that shallow groundwater propitiated GDE in almost all the GPR case studies compiled, only one case expressly addressed GDE research. Common ranges of prospecting depth, water-table depth, and volumetric water content deduced by GPR and other techniques were identified. Antenna frequency of 100MHz and the common offset acquisition technique predominated in the database. Most of GPR case studies were in 30-50° N temperate latitudes, mainly in Europe and North America. Eight original radargrams were selected from several GPR profiles performed in 2014 and 2015 to document database classes and identified gaps, as well as to define experimental ranges of operability in GDE environments. The results contribute to the design of proper GPR surveys in GDE research.
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http://dx.doi.org/10.1016/j.scitotenv.2017.03.210DOI Listing
October 2017

Euterpe oleracea Mart. seed extract protects against renal injury in diabetic and spontaneously hypertensive rats: role of inflammation and oxidative stress.

Eur J Nutr 2018 Mar 20;57(2):817-832. Epub 2017 Jan 20.

Department of Pharmacology, Institute of Biology, State University of Rio de Janeiro, Av 28 de Setembro, nº 87, Rio de Janeiro, CEP 20551-030, Brazil.

Purpose: Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kgday) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury.

Methods: Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days. The control (C) and hypertensive (H) animals received water.

Results: The elevated serum levels of urea and creatinine in D and DH, and increased albumin excretion in HD were reduced by ASE. Total glomeruli number in D and DH, were increased by ASE that also reduced renal fibrosis in both groups by decreasing collagen IV and TGF-β1 expression. ASE improved biomarkers of renal filtration barrier (podocin and nephrin) in D and DH groups and prevented the increased expression of caspase-3, IL-6, TNF-α and MCP-1 in both groups. ASE reduced oxidative damage markers (TBARS, carbonyl levels and 8-isoprostane) in D and DH associated with a decrease in Nox 4 and p47 subunit expression and increase in antioxidant enzyme activity in both groups (SOD, catalase and GPx).

Conclusion: ASE substantially reduced renal injury and prevented renal dysfunction by reducing inflammation, oxidative stress and improving the renal filtration barrier, providing a nutritional resource for prevention of diabetic and hypertensive-related nephropathy.
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http://dx.doi.org/10.1007/s00394-016-1371-1DOI Listing
March 2018

Spatiotemporal expression of extracellular matrix components during the chondrogenic and osteogenic phases of bone healing.

Rom J Morphol Embryol 2017 ;58(4):1201-1216

Laboratory of Ultrastructure and Tissue Biology, Department of Histology and Embryology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro (UERJ), Brazil;

In this study, we investigated the cascade of events involved in the early phases of bone healing in rats, especially the transition from chondrogenesis to osteogenesis, which involves cellular and extracellular matrix (ECM) components. We used a standardized closed tibial fracture model in Wistar rats, which was divided into nine groups of five animals each, and the fracture area was evaluated at 0, 12, 24, 48, 72, 96, 144, 192, and 240 hours post-injury. Histological, histochemical, immunohistochemical and morphometric techniques were used to evaluate the proliferating cell nuclear antigen (PCNA), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), type I procollagen (procoll-I), type I collagen (coll-I), and type II collagen (coll-II) expression at every time point. TGF-β expression peaked after 144 hours, in the initial chondrogenic phase. VEGF expression reached the first peak at 96-144 hours post-injury, in the initial chondrogenic phase and the second peak at 240 hours, in the osteogenic phase. Except at 48 hours, PCNA expression increased gradually from 12 hours and peaked at 96 hours in the prechondrogenic phase, and then decreased gradually until 240 hours in the osteogenic phase. Total collagen (T-coll) and coll-II reached an expression peak at 144 hours, in the chondrogenic phase. No differences were observed between their expression from 12 hours to 72 hours and at 240 hours post-injury. The results suggest that spatiotemporal expression of ECM components during the chondrogenic and osteogenic phases of bone healing depends on several combined and orchestrated factors. A better understanding of the coordinated participation of cells and ECM components in the early bone healing process may provide new insights into the etiology of abnormal or delayed fracture healing.
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September 2018

Abdominoplasty with Scarpa fascia preservation - comparative study in a bariatric population.

Surg Obes Relat Dis 2017 Mar 28;13(3):423-428. Epub 2016 Sep 28.

Surgery Department, Faculty of Medicine, Porto University, Porto, Portugal; Plastic Surgery Department, São João Hospital, Porto, Portugal. Electronic address:

Background: Abdominoplasty techniques using a more superficial plane of dissection with Scarpa fascia preservation have been shown to improve recovery and reduce complications in nonbariatric patients. Patients who have experienced massive weight loss frequently need body contour procedures and represent a high-risk group.

Objective: To evaluate the effect of this technique in patients with massive weight loss after bariatric surgery.

Setting: University hospital, Portugal.

Methods: This was a single-center retrospective study of 51 postbariatric patients who had been undergone either a classic full abdominoplasty (group A) or a similar procedure except for the preservation of Scarpa fascia below the umbilicus (group B). General characteristics of both groups were analyzed, and recorded outcomes were total and daily volume of drain output, time until drain removal, time until hospital discharge, and local and systemic complications.

Results: There were no statistically significant differences between groups regarding general characteristics or complications. The Scarpa fascia preservation group had a highly significant reduction of 79% on the total drain output, 7 days until drain removal, and 5 days' hospital stay. Long drainers (7 days or more with drains) were eliminated (reduction from 52% in group A to 3% in group B) and seroma had a 65% reduction.

Conclusion: Preserving Scarpa fascia during a full abdominoplasty in postbariatric patients improves recovery by reducing total drain output and hospital stay, allowing earlier drain removal, eliminating long periods with suction drains, and reducing seroma incidence. Clear benefits for the patient were obtained.
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http://dx.doi.org/10.1016/j.soard.2016.09.024DOI Listing
March 2017