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1.
Neuropsychobiology ; 80(3): 214-224, 2021.
Article in English | MEDLINE | ID: mdl-32726779

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. PURPOSE: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. PATIENTS AND METHODS: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. RESULTS: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. CONCLUSION: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.


Subject(s)
Cerebrovascular Circulation/physiology , Depressive Disorder, Major/blood , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/physiopathology , Endothelium, Vascular/physiopathology , Regional Blood Flow/physiology , Selective Serotonin Reuptake Inhibitors/pharmacology , Adult , Cerebrovascular Circulation/drug effects , Depressive Disorder, Major/diagnostic imaging , Endothelium, Vascular/drug effects , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Regional Blood Flow/drug effects , Tomography, Emission-Computed, Single-Photon , Young Adult
2.
PLoS One ; 15(11): e0241442, 2020.
Article in English | MEDLINE | ID: mdl-33147235

ABSTRACT

Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation site was monitored at days 2, 4, 6, and 7 post-grafting using color-Doppler ultrasonography. Ovarian grafts were recovered 7 days post-transplantation and subjected to histological analyses. The exposure of the ovarian fragments to VEGF before grafting was not beneficial to the quality of the tissue; however, the cooling process of the fragments reduced the acute hyperemia post-grafting. Cooled grafts compared with non-cooled grafts contained similar values for normal and developing preantral follicles, vessel density, and stromal cell apoptosis; lower collagen type III fibers and follicular density; and higher stromal cell density, AgNOR, and collagen type I fibers. In conclusion, VEGF exposure before autotransplantation did not improve the quality of grafted tissues. However, cooling ovarian tissue for at least 24 h before grafting can be beneficial because satisfactory rates of follicle survival and development, stromal cell survival and proliferation, as well as vessel density, were obtained.


Subject(s)
Cold Temperature , Ovarian Follicle/transplantation , Transplantation, Heterotopic , Vascular Endothelial Growth Factor A/pharmacology , Animals , Apoptosis/drug effects , Caspase 3/metabolism , Cell Count , Cell Proliferation/drug effects , Female , Fibrosis , Horses , Models, Animal , Ovarian Follicle/blood supply , Ovarian Follicle/drug effects , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Regional Blood Flow/drug effects , Stromal Cells/cytology , Stromal Cells/drug effects , Transplantation, Autologous
3.
Respir Med ; 157: 59-68, 2019 10.
Article in English | MEDLINE | ID: mdl-31522031

ABSTRACT

BACKGROUND: Hyperinflation has been associated with negative cardiocirculatory consequences in patients with chronic obstructive pulmonary disease (COPD). These abnormalities are likely to worsen when the demands for O2 increase, e.g., under the stress of exercise. Thus, pharmacologically-induced lung deflation may improve cardiopulmonary interactions and exertional cardiac output leading to higher limb muscle blood flow and oxygenation in hyperinflated patients with COPD. METHODS: 20 patients (residual volume = 201.6 ±â€¯63.6% predicted) performed endurance cardiopulmonary exercise tests (75% peak) 1 h after placebo or tiotropium/olodaterol 5/5 µg via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Cardiac output was assessed by signal-morphology impedance cardiography. Near-infrared spectroscopy determined quadriceps blood flow (indocyanine green dye) and intra-muscular oxygenation. RESULTS: Tiotropium/olodaterol was associated with marked lung deflation (p < 0.01): residual volume decreased by at least 0.4 L in 14/20 patients (70%). The downward shift in the resting static lung volumes was associated with less exertional inspiratory constraints and dyspnoea thereby increasing exercise endurance by ~50%. Contrary to our premises, however, neither central and peripheral hemodynamics nor muscle oxygenation improved after active intervention compared to placebo. These results were consistent with those found in a subgroup of patients showing the largest decrements in residual volume (p < 0.05). CONCLUSIONS: The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes are not translated into enhanced cardiocirculatory responses to exertion in hyperinflated patients with COPD. Improvement in exercise tolerance after dual bronchodilation is unlikely to be mechanistically linked to higher muscle blood flow and/or O2 delivery.


Subject(s)
Benzoxazines/adverse effects , Bronchodilator Agents/adverse effects , Cardiac Output/drug effects , Pulmonary Atelectasis/chemically induced , Pulmonary Disease, Chronic Obstructive/physiopathology , Tiotropium Bromide/adverse effects , Aged , Aged, 80 and over , Benzoxazines/administration & dosage , Benzoxazines/therapeutic use , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Case-Control Studies , Cross-Over Studies , Cross-Sectional Studies , Drug Combinations , Dyspnea/physiopathology , Exercise Test/methods , Exercise Tolerance/drug effects , Female , Hemodynamics/physiology , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Oxygen/metabolism , Physical Exertion/drug effects , Placebos/administration & dosage , Quadriceps Muscle/blood supply , Quadriceps Muscle/diagnostic imaging , Quadriceps Muscle/metabolism , Regional Blood Flow/drug effects , Residual Volume/drug effects , Spectroscopy, Near-Infrared/methods , Tiotropium Bromide/administration & dosage , Tiotropium Bromide/therapeutic use
4.
Kidney Int ; 96(2): 302-319, 2019 08.
Article in English | MEDLINE | ID: mdl-31133455

ABSTRACT

Chronic kidney disease (CKD) represents a global health concern, and its prevalence is increasing. The ultimate therapeutic option for CKD is kidney transplantation. However, the use of drugs that target specific pathways to delay or halt CKD progression, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors is limited in clinical practice. Mineralocorticoid receptor activation in nonclassical tissues, such as the endothelium, smooth muscle cells, inflammatory cells, podocytes, and fibroblasts may have deleterious effects on kidney structure and function. Several preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) ameliorate or cure kidney injury and dysfunction in different models of kidney disease. In this review, we present the preclinical evidence showing a benefit of MRAs in acute kidney injury, the transition from acute kidney injury to CKD, hypertensive and diabetic nephropathy, glomerulonephritis, and kidney toxicity induced by calcineurin inhibitors. We also discuss the molecular mechanisms responsible for renoprotection related to MRAs that lead to reduced oxidative stress, inflammation, fibrosis, and hemodynamic alterations. The available clinical data support a benefit of MRA in reducing proteinuria in diabetic kidney disease and improving cardiovascular outcomes in CKD patients. Moreover, a benefit of MRAs in kidney transplantation has also been observed. The past and present clinical trials describing the effect of MRAs on kidney injury are presented, and the risk of hyperkalemia and use of other options, such as potassium binding agents or nonsteroidal MRAs, are also addressed. Altogether, the available preclinical and clinical data support a benefit of using MRAs in CKD, an approach that should be further explored in future clinical trials.


Subject(s)
Acute Kidney Injury/drug therapy , Kidney/drug effects , Mineralocorticoid Receptor Antagonists/therapeutic use , Receptors, Mineralocorticoid/metabolism , Renal Insufficiency, Chronic/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Animals , Calcineurin Inhibitors/adverse effects , Clinical Trials as Topic , Disease Models, Animal , Disease Progression , Drug Evaluation, Preclinical , Global Burden of Disease , Global Health , Humans , Kidney/blood supply , Kidney/pathology , Mineralocorticoid Receptor Antagonists/pharmacology , Oxidative Stress/drug effects , Prevalence , Regional Blood Flow/drug effects , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/pathology , Treatment Outcome
5.
Fundam Clin Pharmacol ; 33(4): 428-440, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30506745

ABSTRACT

The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary density and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS period, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium-dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteinemic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals.


Subject(s)
Creatine/pharmacology , Creatine/therapeutic use , Diet, Vegan , Endothelium, Vascular/drug effects , Hyperhomocysteinemia/drug therapy , Adult , Body Weights and Measures , Creatine/administration & dosage , Dietary Supplements , Female , Folic Acid , Humans , Iontophoresis , Laser-Doppler Flowmetry , Male , Middle Aged , Regional Blood Flow/drug effects
6.
Acta Cir Bras ; 33(4): 296-305, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29768532

ABSTRACT

PURPOSE: To evaluate the effect of the cilostazol on the evolution of partially avulsed flaps, using experimental model of cutaneous degloving in rat limbs. METHODS: A controlled and randomized experimental study was carried out in which the blood flow and the percentage of flap necrosis were evaluated. We compared the study group, which received cilostazol, and the control group, which received enteral saline solution in the postoperative period. The blood flow in the flap was evaluated through Laser Doppler flowmetry, and a planimetry using the IMAGE J® software was employed for the calculation of the area of necrosis. RESULTS: Enteral administration of cilostazol was associated with a higher mean blood flow in all regions of the flap, with a statistically significant difference in the proximal and middle regions (p<0.001) and a lower percentage of necrotic area in the flap (p<0.001). CONCLUSION: Postoperative enteral administration of cilostazol increased blood flow and decreased the total area of necrosis of avulsed cutaneous flaps of rat limbs.


Subject(s)
Degloving Injuries/drug therapy , Disease Models, Animal , Phosphodiesterase 3 Inhibitors/therapeutic use , Tetrazoles/therapeutic use , Animals , Cilostazol , Degloving Injuries/pathology , Degloving Injuries/surgery , Humans , Laser-Doppler Flowmetry , Lower Extremity/blood supply , Lower Extremity/injuries , Lower Extremity/pathology , Male , Necrosis/drug therapy , Phosphodiesterase 3 Inhibitors/pharmacology , Random Allocation , Rats, Wistar , Reference Values , Regional Blood Flow/drug effects , Reproducibility of Results , Surgical Flaps , Tetrazoles/pharmacology , Time Factors , Treatment Outcome
7.
Acta cir. bras ; Acta cir. bras;33(4): 296-305, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-886282

ABSTRACT

Abstract Purpose: To evaluate the effect of the cilostazol on the evolution of partially avulsed flaps, using experimental model of cutaneous degloving in rat limbs. Methods: A controlled and randomized experimental study was carried out in which the blood flow and the percentage of flap necrosis were evaluated. We compared the study group, which received cilostazol, and the control group, which received enteral saline solution in the postoperative period. The blood flow in the flap was evaluated through Laser Doppler flowmetry, and a planimetry using the IMAGE J® software was employed for the calculation of the area of necrosis. Results: Enteral administration of cilostazol was associated with a higher mean blood flow in all regions of the flap, with a statistically significant difference in the proximal and middle regions (p<0.001) and a lower percentage of necrotic area in the flap (p<0.001). Conclusion: Postoperative enteral administration of cilostazol increased blood flow and decreased the total area of necrosis of avulsed cutaneous flaps of rat limbs.


Subject(s)
Humans , Animals , Male , Tetrazoles/therapeutic use , Disease Models, Animal , Phosphodiesterase 3 Inhibitors/therapeutic use , Degloving Injuries/drug therapy , Reference Values , Regional Blood Flow/drug effects , Surgical Flaps , Tetrazoles/pharmacology , Time Factors , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Laser-Doppler Flowmetry , Lower Extremity/blood supply , Lower Extremity/injuries , Lower Extremity/pathology , Phosphodiesterase 3 Inhibitors/pharmacology , Degloving Injuries/surgery , Degloving Injuries/pathology , Necrosis/drug therapy
8.
Eur J Pharmacol ; 807: 174-181, 2017 Jul 15.
Article in English | MEDLINE | ID: mdl-28483456

ABSTRACT

Septic shock, which is triggered by microbial products, is mainly characterised by inadequate tissue perfusion, which can lead to multiple organ dysfunction and death. An intense release of vasoconstrictors agents occurs in the early stages of shock, which can lead to ischemic injury. In this scenario, cGMP could play a key role in counterbalancing these agents and preventing tissue damage. Sildenafil, which is a phosphodiesterase-5 inhibitor, increases cGMP in smooth muscle cells and promotes vasodilation. Thus, the purpose of this study was to investigate the effect of treatment with sildenafil in the early stages of sepsis. Male rats were submitted to either cecal ligation and puncture (CLP) or a sham procedure. Eight h after the procedure, the CLP and sham groups were randomly assigned to receive sildenafil (10mg/kg, gavage) or vehicle, and twelve or twenty-four h later the inflammatory, biochemical and haemodynamic parameters were evaluated. Sepsis significantly increased levels of plasma nitrate/nitrite (NOx), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, creatine kinase and lactate. Additionally, sepsis led to hypotension, hyporesponsiveness to vasoconstrictor, renal blood flow reduction and also increased lung and kidney myeloperoxidase. Sildenafil increased renal blood flow and reduced the plasma levels of creatinine, lactate and creatine kinase, as well as reducing lung myeloperoxidase. Thus, phosphodiesterase inhibition may be a useful therapeutic strategy if administered at the proper time.


Subject(s)
Cyclic GMP/blood , Sepsis/blood , Animals , Hematologic Tests , Kidney/blood supply , Kidney/drug effects , Male , Rats , Rats, Wistar , Regional Blood Flow/drug effects , Sepsis/physiopathology , Sildenafil Citrate/pharmacology
9.
Oxid Med Cell Longev ; 2017: 1360565, 2017.
Article in English | MEDLINE | ID: mdl-28337244

ABSTRACT

We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool." Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO) and malondialdehyde (MDA), leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of "mitochondrial" enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.


Subject(s)
Endothelium, Vascular/metabolism , Glycocalyx/metabolism , Liver/enzymology , Liver/surgery , Regional Blood Flow/physiology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Calcium/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels/chemistry , Calcium Channels/metabolism , Glutamate Dehydrogenase/blood , Liver/drug effects , Liver/injuries , Malate Dehydrogenase/blood , Male , Malondialdehyde/blood , Mechanotransduction, Cellular/drug effects , Nitric Oxide/blood , Rats , Rats, Wistar , Regional Blood Flow/drug effects , Shear Strength
10.
Biol Reprod ; 93(3): 58, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26178718

ABSTRACT

Prenatal testosterone (T), but not dihydrotestosterone (DHT), excess disrupts ovarian cyclicity and increases follicular recruitment and persistence. We hypothesized that the disruption in the vascular endothelial growth factor (VEGF) system contributes to the enhancement of follicular recruitment and persistence in prenatal T-treated sheep. The impact of T/DHT treatments from Days 30 to 90 of gestation on VEGFA, VEGFB, and their receptor (VEGFR-1 [FLT1], VEGFR-2 [KDR], and VEGFR-3 [FLT4]) protein expression was examined by immunohistochemistry on Fetal Days 90 and 140, 22 wk, 10 mo (postpubertal), and 21 mo (adult) of age. Arterial morphometry was performed in Fetal Day 140 and postpubertal ovaries. VEGFA and VEGFB expression were found in granulosa cells at all stages of follicular development with increased expression in antral follicles. VEGFA was present in theca interna, while VEGFB was present in theca interna/externa and stromal cells. All three receptors were expressed in the granulosa, theca, and stromal cells during all stages of follicular development. VEGFR-3 increased with follicular differentiation with the highest level seen in the granulosa cells of antral follicles. None of the members of the VEGF family or their receptor expression were altered by age or prenatal T/DHT treatments. At Fetal Day 140, area, wall thickness, and wall area of arteries from the ovarian hilum were larger in prenatal T- and DHT-treated females, suggestive of early androgenic programming of arterial differentiation. This may facilitate increased delivery of endocrine factors and thus indirectly contribute to the development of the multifollicular phenotype.


Subject(s)
Fetal Development/drug effects , Ovary/metabolism , Steroids/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Animals , Dihydrotestosterone/pharmacology , Female , Immunohistochemistry , Neovascularization, Physiologic/drug effects , Ovary/blood supply , Ovary/growth & development , Pregnancy , Regional Blood Flow/drug effects , Sheep, Domestic , Testosterone/pharmacology , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
11.
J Pediatr ; 167(3): 572-8.e1-2, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26116470

ABSTRACT

OBJECTIVE: To gather information for a future confirmatory trial of dobutamine (DB) for circulatory impairment (ie, low superior vena cava [SVC] flow). STUDY DESIGN: A total of 127 infants born at < 31 weeks gestational age were serially scanned from birth to 96 hours after birth. The infants were randomly assigned to 2 groups and were treated with DB (stepwise dose increase, 5-10-15-20 µg/kg/min) or placebo if they had an SVC flow < 41 mL/kg/min within the first 24 hours after birth. The primary outcome measures were the achievement and maintenance of an SVC flow ≥ 41 mL/kg/min. Secondary outcome measures were the short-term evolution of clinical and biochemical variables, near-infrared spectroscopy, cranial Doppler ultrasound, and clinical outcomes. RESULTS: SVC flow increased throughout the first 96 hours for the entire cohort. All of the randomized infants (n = 28) except 2 achieved and maintained an SVC flow ≥ 41 mL/kg/min after intervention; however, the infants treated with DB (n = 16) showed a higher heart rate and improved base excess compared with those treated with placebo (n = 12). Low SVC flow was associated with low gestational age (P = .02) and poor condition at birth (P = .02). Low SVC flow significantly increased the risk of severe ischemic events (OR, 13; 95% CI, 2.4-69.2; P < .01). CONCLUSION: This exploratory trial demonstrates a tendency toward improved short-term clinical and biochemical perfusion variable outcomes in infants with low SVC flow treated with DB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01605279) and the European Clinical Trials Database (EurodraCT 2009-010901-35).


Subject(s)
Adrenergic beta-1 Receptor Agonists/therapeutic use , Cardiotonic Agents/therapeutic use , Dobutamine/therapeutic use , Regional Blood Flow/drug effects , Vena Cava, Superior/drug effects , Adrenergic beta-1 Receptor Agonists/administration & dosage , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Cardiotonic Agents/administration & dosage , Dobutamine/administration & dosage , Echocardiography, Doppler , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Infant, Premature , Male , Pilot Projects , Spain , Spectroscopy, Near-Infrared , Treatment Outcome , Vena Cava, Superior/physiology
12.
Molecules ; 20(3): 4109-23, 2015 Mar 04.
Article in English | MEDLINE | ID: mdl-25749680

ABSTRACT

Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 µM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 µM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL-1·min-1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL-1·min-1 and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.


Subject(s)
Acetylcysteine/analogs & derivatives , Gastric Mucosa/blood supply , Nitric Oxide/metabolism , Regional Blood Flow/drug effects , Acetylcysteine/pharmacology , Animals , Laser-Doppler Flowmetry , Luminescent Measurements , Male , Nitrates/pharmacology , Nitrogen/pharmacology , Rats , Rats, Sprague-Dawley
13.
Braz Oral Res ; 292015.
Article in English | MEDLINE | ID: mdl-25627891

ABSTRACT

Laser Doppler flowmetry (LDF) is a noninvasive method capable of evaluating variations in pulp blood flow (PBF) and pulp vitality. This method has thus far not been used to assess changes in blood flow after in-office bleaching. The aim of this case series report was to measure changes in PBF by LDF in the upper central incisor of three patients submitted to in-office bleaching. The buccal surfaces of the upper arch were bleached with a single session of 35% hydrogen peroxide gel with three 15-min applications. The color was recorded using a value-oriented Vita shade guide before in-office bleaching and one week after the procedure. The tooth sensitivity (TS) in a verbal scale was reported, and PBF was assessed by LDF before, immediately, and one week after the bleaching session. The lower arch was submitted to dental bleaching but not used for data assessment. A whitening degree of 3 to 4 shade guide units was detected. All participants experienced moderate to considerable TS after the procedure. The PBF readings reduced 20% to 40% immediately after bleaching. One week post-bleaching, TS and PBF were shown to be equal to baseline values. A reversible decrease of PBF was detected immediately after bleaching, which recovered to the baseline values or showed a slight increase sooner than one week post-bleaching. The LDF method allows detection of pulp blood changes in teeth submitted to in-office bleaching, but further studies are still required.


Subject(s)
Dental Pulp/blood supply , Dentin Sensitivity/chemically induced , Hydrogen Peroxide/adverse effects , Laser-Doppler Flowmetry/methods , Tooth Bleaching Agents/adverse effects , Tooth Bleaching/adverse effects , Adult , Dental Pulp/drug effects , Humans , Reference Values , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Time Factors , Tooth Bleaching/methods , Treatment Outcome , Young Adult
14.
Anim Reprod Sci ; 153: 8-12, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25578505

ABSTRACT

This study characterizes the physiological and morphological changes related to partial luteolysis in bovine corpus luteum (CL) after challenges with sub-doses of cloprostenol sodium on Day 6 (D6) of the estrous cycle. Cows (n = 12/treatment) were treated as follows: Control (2 mL, saline, i.m.); 2XPGF (two treatments i.m. 500 µg of cloprostenol sodium 2 h apart) and 1/6PGF (83.3 µg of cloprostenol sodium, i.m., once). Plasma progesterone (P4) concentration, CL volume and blood flow were measured immediately before the treatments, then every 8 h (h) for 48 h. In the Control, P4 concentrations were higher at 48 h than at 0 h. P4 decreased 8h after 2XPGF treatment (P < 0.05), and remained low until the end of the trial. P4 decreased in 1/6PGF between 8 and 16 h (P < 0.05), then began to rebound at 24 h. Luteal volume was higher in Controls at 48 h than at 0 h. Under 1/6PGF, luteal volume decreased at 24 h (P < 0.05) and began to rebound at 32 h. Luteal volume and blood flow were reduced starting at 24 and 32 h, respectively, after 2XPGF treatment (P < 0.05). In this study, we were able to describe the partial luteolysis phenomenon, induced by a treatment of a D6CL with cloprostenol sub-dose.


Subject(s)
Cattle , Cloprostenol/pharmacology , Corpus Luteum/anatomy & histology , Corpus Luteum/drug effects , Luteolytic Agents/pharmacology , Animals , Corpus Luteum/blood supply , Corpus Luteum/diagnostic imaging , Dose-Response Relationship, Drug , Female , Luteal Phase/blood , Luteal Phase/drug effects , Luteolysis/drug effects , Organ Size/drug effects , Progesterone/blood , Regional Blood Flow/drug effects , Ultrasonography
15.
Braz. oral res. (Online) ; 29(1): 1-6, 2015. tab, ilus
Article in English | LILACS | ID: lil-777173

ABSTRACT

Laser Doppler flowmetry (LDF) is a noninvasive method capable of evaluating variations in pulp blood flow (PBF) and pulp vitality. This method has thus far not been used to assess changes in blood flow after in-office bleaching. The aim of this case series report was to measure changes in PBF by LDF in the upper central incisor of three patients submitted to in-office bleaching. The buccal surfaces of the upper arch were bleached with a single session of 35% hydrogen peroxide gel with three 15-min applications. The color was recorded using a value-oriented Vita shade guide before in-office bleaching and one week after the procedure. The tooth sensitivity (TS) in a verbal scale was reported, and PBF was assessed by LDF before, immediately, and one week after the bleaching session. The lower arch was submitted to dental bleaching but not used for data assessment. A whitening degree of 3 to 4 shade guide units was detected. All participants experienced moderate to considerable TS after the procedure. The PBF readings reduced 20% to 40% immediately after bleaching. One week post-bleaching, TS and PBF were shown to be equal to baseline values. A reversible decrease of PBF was detected immediately after bleaching, which recovered to the baseline values or showed a slight increase sooner than one week post-bleaching. The LDF method allows detection of pulp blood changes in teeth submitted to in-office bleaching, but further studies are still required.


Subject(s)
Humans , Adult , Young Adult , Dental Pulp/blood supply , Dentin Sensitivity/chemically induced , Hydrogen Peroxide/adverse effects , Laser-Doppler Flowmetry/methods , Tooth Bleaching Agents/adverse effects , Tooth Bleaching/adverse effects , Dental Pulp/drug effects , Reference Values , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Time Factors , Tooth Bleaching/methods , Treatment Outcome
16.
Toxicon ; 92: 81-9, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25449097

ABSTRACT

Integrins are involved in a number of physio-pathological processes including wound healing, chronic inflammation and neoplasias. Blocking its activity is potentially of therapeutic value in these conditions. We investigated whether DisBa-01, a recombinant His-tag RGD-disintegrin from Bothrops alternatus snake venom, could modulate key events (inflammatory cell recruitment/activation, neovascularization and extracellular matrix deposition) of the proliferative fibrovascular tissue induced by polyether polyurethane sponge implants in mice. The hemoglobin content (µg/mg wet tissue), blood flow measurements (laser Doppler perfusion imaging) and number of vessels in the implants, used as indices of vascularization, showed that the disintegrin dose-dependently reduced angiogenesis in the implants relative to the Saline-treated group. DisBa-01 inhibited neutrophil and macrophage content as determined by the myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities, respectively. Similarly, down regulation of the fibrogenic component studied (collagen deposition) was observed in DisBa-01-treated implants. VEGF, bFGF, TNF-α, CXCL1 and CCL2 levels were also decreased by the disintegrin. The inhibitory effect of this αvß3-blocking disintegrin on the angiogenic, inflammatory, and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of DisBa-01 actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.


Subject(s)
Bothrops/metabolism , Crotalid Venoms/analysis , Disintegrins/pharmacology , Extracellular Matrix/drug effects , Inflammation/prevention & control , Neovascularization, Physiologic/drug effects , Recombinant Proteins/pharmacology , Acetylglucosaminidase/metabolism , Animals , Crotalid Venoms/pharmacology , Disintegrins/analysis , Drug Evaluation, Preclinical , Laser-Doppler Flowmetry , Macrophages/drug effects , Mice , Peroxidase/metabolism , Polyurethanes , Regional Blood Flow/drug effects
17.
Rev. bras. enferm ; Rev. bras. enferm;67(5): 759-765, Sep-Oct/2014. tab
Article in Portuguese | LILACS, BDENF - Nursing | ID: lil-731225

ABSTRACT

Objetivou-se identificar o perfil sociodemográfico de idosos vítimas de trauma, caracterizar doenças preexistentes e medicamentos utilizados no domicílio; calcular índices de trauma e desfecho clínico. Estudo retrospectivo e exploratório, com a análise de dados secundários de um banco de dados de um hospital geral terciário, entre 2008 e 2010. Foram estudados 131 idosos, média de idade 69,9 anos, 73,3% homens, 55,1% casados, 54,7% aposentados; 65,6% possuíam doenças preexistentes e 48,9% usavam medicamentos no domicílio. Houve representatividade de quedas (31,3%), seguidas por atropelamento (28,2%), com cabeça/pescoço sendo a região mais acometida (59,5%). Prevaleceu o trauma moderado (44,3%), com condições de sobrevida após o evento (80,2%). Houve associação entre mecanismo do trauma e doença preexistente (p=0,01) e entre mecanismo do trauma e sexo (p=0,03). O conhecimento das variáveis envolvidas com idosos vítimas de trauma possibilita aos profissionais de saúde o planejamento de medidas preventivas, visando aprimorar sua assistência.


The objective was to identify the sociodemographic profile of the elderly victims of trauma, to characterize preexisting conditions and medications taken at home, and to calculate indices of trauma and clinical outcomes. This is a retrospective and exploratory analysis from a database of a general hospital between 2008 and 2010. There were studied 131 elderly, mean age 69.9 years, 73.3% male, 55.1% married, 54.7% retired, 65.6% had preexisting conditions and 48.9% used drugs at home. There was a representative number of falls (31.3%), followed by running over (28.2%), with the head/neck region being the most affected (59.5%). Moderate trauma prevailed (44.3%), with conditions of survival after the event (80.2%). There was an association between mechanism of trauma and preexisting disease (p=0.01) and between mechanism of trauma and sex (p=0.03). The knowledge of the variables involved with the elderly victims of trauma enables healthcare professionals to plan preventive measures aimed at improving the assistance. Key words: Aged; Wounds and Injuries; Disease; Drug Utilization.


Se objetivó identificar el perfil sociodemográfico de ancianos víctimas de trauma, caracterizar condiciones preexistentes y medicamentos tomados en casa, y calcular índices de trauma y evolución clínica. Se realizó un análisis retrospectivo y exploratorio de una base de datos de un hospital general terciario entre 2008 y 2010. Se estudiaron 131 ancianos, media of 69,9 años, 73,3% hombres, 55,1% casados, 54,7% jubilados, 65,6% tienen condiciones preexistentes y 48,9% estaban tomando medicación en casa. Hubo representación de las caídas (31,3%), seguido de atropello (28,2%). La región cabeza/cuello fue el más afectado (59,5%). Prevaleció trauma moderado (44,3%), con condiciones de supervivencia después del evento (80,2%). Se observó una asociación entre mecanismo de lo trauma y enfermedad previa (p=0,01) y entre mecanismo de lo trauma y sexo (p=0,03). El conocimiento de las variables que intervienen con ancianos víctimas de trauma permite a los profesionales de la salud planificar medidas preventivas para mejorar su asistencia.


Subject(s)
Animals , Male , Rats , Dobutamine/pharmacology , Jejunum/blood supply , Jejunum/drug effects , Solanaceous Alkaloids/pharmacology , Carbon Dioxide/metabolism , Intestinal Mucosa/blood supply , Intestinal Mucosa/drug effects , Ischemia/drug therapy , Ischemia/physiopathology , Rats, Sprague-Dawley , Regional Blood Flow/drug effects , Reperfusion Injury/drug therapy , Reperfusion Injury/physiopathology
18.
PLoS One ; 8(10): e76894, 2013.
Article in English | MEDLINE | ID: mdl-24124600

ABSTRACT

The present study aimed to show the in vivo mechanisms of action of an indole-thiazolidine molecule peroxisome-proliferator activated receptor pan-agonist (PPAR pan) and cyclooxygenase (COX) inhibitor, LYSO-7, in an ethanol/HCl-induced (Et/HCl) gastric lesion model. Swiss male mice were treated with vehicle, LYSO-7 or Bezafibrate (p.o.) 1 hour before oral administration of Et/HCl (60%/0.03M). In another set of assays, animals were injected i.p. with an anti-granulocyte antibody, GW9962 or L-NG-nitroarginine methyl ester (L-NAME) before treatment. One hour after Et/HCl administration, neutrophils were quantified in the blood and bone marrow and the gastric microcirculatory network was studied in situ. The gastric tissue was used to quantify the percentage of damaged area, as well as myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) protein and PPARγ protein and gene expression. Acid secretion was evaluated by the pylorus ligation model. LYSO-7 or Bezafibrate treatment reduced the necrotic area. LYSO-7 treatment enhanced PPARγ gene and protein expression in the stomach, and impaired local neutrophil influx and stasis of the microcirculatory network caused by Et/HCl administration. The effect seemed to be due to PPARγ agonist activity, as the LYSO-7 effect was abolished in GW9962 pre-treated mice. The reversal of microcirculatory stasis, but not neutrophil influx, was mediated by nitric oxide (NO), as L-NAME pre-treatment abolished the LYSO-7-mediated reestablishment of microcirculatory blood flow. This effect may depend on enhanced eNOS protein expression in injured gastric tissue. The pH and concentration of H(+) in the stomach were not modified by LYSO-7 treatment. In addition, LYSO-7 may induce less toxicity, as 28 days of oral treatment did not induce weight loss, as detected in pioglitazone treated mice. Thus, we show that LYSO-7 may be an effective treatment for gastric lesions by controlling neutrophil influx and microcirculatory blood flow mediated by NO.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Gastritis/metabolism , Gastritis/pathology , Indoles/pharmacology , Microcirculation/drug effects , Peroxisome Proliferator-Activated Receptors/agonists , Thiazolidinediones/pharmacology , Animals , Body Weight/drug effects , Cyclooxygenase Inhibitors/administration & dosage , Ethanol/adverse effects , Gastric Acid/metabolism , Gastritis/chemically induced , Gastritis/drug therapy , Gene Expression Regulation/drug effects , Hydrochloric Acid/adverse effects , Indoles/administration & dosage , Male , Mice , Neutrophil Infiltration/drug effects , Nitric Oxide/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Peroxisome Proliferator-Activated Receptors/genetics , Peroxisome Proliferator-Activated Receptors/metabolism , Regional Blood Flow/drug effects , Thiazolidinediones/administration & dosage
19.
Rev Bras Cir Cardiovasc ; 28(2): 224-30, 2013 Jun.
Article in English, Portuguese | MEDLINE | ID: mdl-23939319

ABSTRACT

OBJECTIVE: This work aims to study comparatively the free flow and the Doppler flowmetry of the internal thoracic artery in anesthetized dogs, with and without continuous intravenous administration of norepinephrine. METHODS: The sample was made up of ten mongrel dogs, which dissected the left and right internal thoracic arteries and evaluated your stream; first, by Doppler flowmetry and then by free flow. The mean arterial pressure and the diameter of the arteries at the beginning of the procedure were registered. The workflow checks by two methods occurred in three times: time zero, 10 and 25 minutes. After the first check in time zero, the continuous infusion of norepinephrine in the right atrium; other checks were made in the same way that the first time, to 10 and 25 minutes, in the same arteries and by two methods, each one in his artery, noting the results, as well as the corresponding average blood pressure. RESULTS: The results of the scan of the stream, between Doppler flowmetry and free flow, there were similar; being the first, zero times, ten and twenty-five minutes, respectively, 183, 230.1 and 237 ml/min compared to seconds, 168.6, 226.8 and 226.4 ml/min (P = 0.285). The mean arterial pressures of three times and the average diameter of the arteries, showed no statistically significant differences between the methods, so did not influence on the comparison of the results. CONCLUSION: The evaluations, both from Doppler flowmetry and free flow, were similar in three times checked.


Subject(s)
Laser-Doppler Flowmetry/methods , Mammary Arteries/physiology , Norepinephrine/administration & dosage , Regional Blood Flow/physiology , Vasoconstrictor Agents/administration & dosage , Administration, Intravenous , Animals , Blood Pressure/physiology , Dogs , Mammary Arteries/diagnostic imaging , Reference Values , Regional Blood Flow/drug effects , Reproducibility of Results , Time Factors , Ultrasonography
20.
Rev. bras. cir. cardiovasc ; Rev. bras. cir. cardiovasc;28(2): 224-230, abr.-jun. 2013. tab
Article in Portuguese | LILACS | ID: lil-682433

ABSTRACT

OBJETIVO: Este trabalho objetiva estudar comparativamente o fluxo livre e a dopplerfluxometria da artéria torácica interna de cães anestesiados com e sem a administração de noradrenalina endovenosa contínua. MÉTODOS: A amostra foi constituída de 10 cães mestiços, nos quais foram dissecadas as artérias torácicas internas direita e esquerda e avaliado seu fluxo; primeiramente, pela dopplerfluxometria e depois pelo fluxo livre. Foram registrados a pressão arterial média e o diâmetro das artérias no início do procedimento. As verificações do fluxo pelos dois métodos ocorreram em três tempos: tempo zero, 10 e 25 minutos. Após a primeira verificação no tempo zero, iniciou-se a infusão contínua de noradrenalina no átrio direito; as avaliações aos 10 e 25 minutos foram feitas da mesma forma que na primeira vez, nas mesmas artérias e pelos dois métodos, anotando-se os resultados, assim como a pressão arterial média correspondente. RESULTADOS: Os resultados da verificação de fluxo, entre Dopplermetria e fluxo livre, apresentaram-se similares; sendo os primeiros, nos tempos zero, 10 e 25 minutos, respectivamente, 183, 237 e 230,1 ml/min, comparados aos segundos, 168,6, 226,8 e 226,4 ml/min (P=0,285). A média das pressões arteriais dos três tempos e o diâmetro médio das artérias não apresentaram diferenças estatisticamente significativas entre os métodos, portanto, não influenciaram na comparação dos resultados. CONCLUSÃO: As avaliações, tanto da dopplerfluxometria quanto do fluxo livre, foram semelhantes nos três tempos verificados.


OBJECTIVE: This work aims to study comparatively the free flow and the Doppler flowmetry of the internal thoracic artery in anesthetized dogs, with and without continuous intravenous administration of norepinephrine. METHODS: The sample was made up of ten mongrel dogs, which dissected the left and right internal thoracic arteries and evaluated your stream; first, by Doppler flowmetry and then by free flow. The mean arterial pressure and the diameter of the arteries at the beginning of the procedure were registered. The workflow checks by two methods occurred in three times: time zero, 10 and 25 minutes. After the first check in time zero, the continuous infusion of norepinephrine in the right atrium; other checks were made in the same way that the first time, to 10 and 25 minutes, in the same arteries and by two methods, each one in his artery, noting the results, as well as the corresponding average blood pressure. RESULTS: The results of the scan of the stream, between Doppler flowmetry and free flow, there were similar; being the first, zero times, ten and twenty-five minutes, respectively, 183, 230.1 and 237 ml/min compared to seconds, 168.6, 226.8 and 226.4 ml/min (P = 0.285). The mean arterial pressures of three times and the average diameter of the arteries, showed no statistically significant differences between the methods, so did not influence on the comparison of the results. CONCLUSION: The evaluations, both from Doppler flowmetry and free flow, were similar in three times checked.


Subject(s)
Animals , Dogs , Laser-Doppler Flowmetry/methods , Mammary Arteries/physiology , Norepinephrine/administration & dosage , Regional Blood Flow/physiology , Vasoconstrictor Agents/administration & dosage , Administration, Intravenous , Blood Pressure/physiology , Mammary Arteries , Reference Values , Reproducibility of Results , Regional Blood Flow/drug effects , Time Factors
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