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1.
J Matern Fetal Neonatal Med ; 33(1): 42-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29863424

RESUMO

Background: Betamethasone (BMZ) is commonly administered to patients with fetal growth restriction (FGR) and abnormal umbilical artery Doppler (UAD) velocimetry due to the increased risk of preterm delivery; however, the clinical impact of UAD changes after BMZ exposure is unknown.Objective: To test the hypothesis that lack of UAD improvement after BMZ administration is associated with shorter latency and greater neonatal morbidity in patients with FGR.Study design: This was a retrospective cohort study of pregnancies complicated by FGR and abnormal UAD between 240 and 336 weeks gestation. Abnormal UAD included the following categories of increasing severity: elevated (pulsatility index >95%), absent end diastolic flow (EDF), or reversed EDF improvement was defined as any improvement in category of UAD within two weeks of BMZ. Sustained improvement was defined as improvement until the last ultrasound before delivery, whereas transient improvement was considered as unsustained. The primary outcome was latency, defined as interval from betamethasone administration to delivery. Secondary outcomes were gestational age at delivery, umbilical artery pH, and a composite of neonatal morbidity (intubation, necrotizing enterocolitis, ionotropic support, intraventricular hemorrhage, total parenteral nutrition, neonatal death). Outcomes were compared between (a) patients with and without UAD improvement and (b) patients with sustained and unsustained improvement, using univariable, multivariable and time-to-event analyses.Results: Of the 222 FGR pregnancies with abnormal UAD, 94 received BMZ and had follow-up ultrasounds. UAD improved in 48 (51.1%), with 27 (56.3%) having sustained improvement. Patients with hypertension and drug use were less likely to have UAD improvement. Patients without UAD improvement had shorter latency (21.5 days [interquartile range (IQR) 8,45] versus 35 [IQR 22,61], p = .02) and delivered at an earlier gestational age (34 weeks [IQR 31,36] versus 37 [IQR 33,37], p < .01) than those with improvement. There were no differences in umbilical artery pH between groups. Composite neonatal morbidity was higher in patients without UAD improvement, but this was not statistically significant after adjusting for confounders (aOR 2.0; 95% CI 0.08-5.1). There were no differences in outcomes between patients with sustained versus unsustained improvement.Conclusions: UAD improved in half of patients following BMZ. Lack of UAD improvement was associated with shorter latency and earlier gestational age at delivery, but no difference in composite neonatal morbidity. UAD response to BMZ may be useful to further risk stratify FGR pregnancies.


Assuntos
Betametasona/administração & dosagem , Retardo do Crescimento Fetal/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Ultrassonografia Doppler , Artérias Umbilicais/efeitos dos fármacos , Artérias Umbilicais/diagnóstico por imagem , Adulto , Betametasona/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Recém-Nascido , Doenças do Recém-Nascido/prevenção & controle , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/irrigação sanguínea , Adulto Jovem
2.
BMJ Case Rep ; 12(9)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31537594

RESUMO

Prostaglandins are widely used in aortic coarctation to maintain ductal patency and preserve systemic perfusion until surgical intervention can be performed. Although the short-term use of prostaglandins to ameliorate aortic narrowing in neonates with a closed ductus has been reported, it has not been described as a longer term therapy in extremely preterm neonates. A 27-week gestation baby weighing 560 g presented at 40 days of age with coarctation and a closed ductus arteriosus. He was successfully treated with a 7-week course of prostaglandin E2 therapy because surgical intervention was not deemed feasible in view of his size. Treatment resulted in a relaxation of the aortic constriction and improvement in aortic blood flow velocity profile, highlighting the value of long-term prostaglandin therapy in this population and supporting the hypothesis that the presence of ductal tissue contributes to the development of juxtaductal aortic constriction in some extremely preterm infants.


Assuntos
Coartação Aórtica/tratamento farmacológico , Dinoprostona/administração & dosagem , Ocitócicos/administração & dosagem , Administração Intravenosa , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/fisiopatologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Dinoprostona/uso terapêutico , Permeabilidade do Canal Arterial/diagnóstico por imagem , Ecocardiografia , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Recém-Nascido , Masculino , Ocitócicos/uso terapêutico , Resultado do Tratamento
3.
Andrologia ; 51(8): e13297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31033009

RESUMO

The penile duplex ultrasound (PDU) has been used as a diagnostic tool in erectile dysfunction (ED) management. It is currently recommended that peak systolic velocity (PSV) and end-diastolic flow (EDF) should be recorded on both the right and left cavernosal arteries. However, the clinical utility of bilateral recordings is unknown. Our primary objective is to assess the clinical utility of bilateral recordings in ED treatment with sildenafil. A total of 77 patients were included. All patients had a standardised PDU and also completed the IIEF-5 and started on-demand treatment with sildenafil at 100 mg at baseline. The IIEF-5 and EDITS were completed at the 6-month follow-up. The Spearman test was used to assess correlation. Receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) was calculated. Improvement, cure and satisfaction were high (77.9%, 64.9% and 67.5%, respectively), and the median IIEF-5 and EDITS were 25(22; 25) and 81.81(63.63; 88.63) respectively. The lowest PSV had the highest positive correlation with IIEF-5 and EDITS (p = 0.436 and 0.379, respectively), and it could predict improvement, cure and satisfaction with a fair-to-good accuracy (AUC = 0.837, 0.750 and 0.749 respectively). The present study shows bilateral penile blood-flow assessment is important, and attention should be focused on the lowest bilateral PSV.


Assuntos
Disfunção Erétil/diagnóstico por imagem , Pênis/irrigação sanguínea , Citrato de Sildenafila/administração & dosagem , Ultrassonografia Doppler Dupla , Agentes Urológicos/administração & dosagem , Idoso , Artérias/diagnóstico por imagem , Artérias/efeitos dos fármacos , Artérias/fisiopatologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Relação Dose-Resposta a Droga , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Pênis/diagnóstico por imagem , Pênis/fisiopatologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Resultado do Tratamento
4.
Life Sci ; 222: 203-211, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825546

RESUMO

AIMS: The purpose of the present study was to investigate the potential antioxidant, anti-apoptotic and sperm function-preserving effects of estrogen, estrogen receptor (ER)α and ERß agonists in a rat model of testis torsion-detorsion (T/D). MAIN METHODS: Under anesthesia, 6-8-week-old male Sprague-Dawley rats underwent sham-operation or testicular torsion by fixing left testis rotated at 720° for 2 h. After detorsion, rats were treated with ERα agonist (1 mg/kg/day, subcutaneously, sc) or ERß agonist (1 mg/kg/day, sc) or estradiol (E2, 1 mg/kg/day, in drinking water) or vehicle on the following two days. On the third day, testicular blood-flow was recorded and then left testes were extracted for molecular and histochemical analysis. KEY FINDINGS: The findings showed that reduced testicular blood-flow following torsion was partially restored on the 3rd day of detorsion, while treatments with either of the ER agonists or E2 returned blood flow fully back to the control levels. When the testis-torsioned rats were given ERß agonist during the detorsion period, tubular injury was lessened, sperm count and motility were increased, while the production of reactive oxygen metabolites and apoptosis in the testis tissues were totally suppressed. Although a down-regulated expression of androgen receptor (AR) along with a reduction in serum testosterone level was observed in the vehicle-treated T/D group, all three treatments up-regulated the expressions of AR and its mRNA, while ERα agonist and E2 suppressed the testosterone level. SIGNIFICANCE: ERß receptor activation during the post-ischemic period may be beneficial in protection against torsion-related oxidant testicular injury and infertility.


Assuntos
Receptor beta de Estrogênio/agonistas , Estrogênios/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Torção do Cordão Espermático/tratamento farmacológico , Testículo/irrigação sanguínea , Testículo/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Estrogênios/farmacologia , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Torção do Cordão Espermático/patologia , Testículo/patologia , Resultado do Tratamento
5.
Biochem Biophys Res Commun ; 512(2): 303-309, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30890334

RESUMO

Extreme deformability of human erythrocytes is a prerequisite for their ability to squeeze through narrow capillaries of the blood microcirculation system. Various drugs can modify this deformability and consequently provoke circulation problems. We demonstrate that microfluidic assemblies are very convenient platforms for in vitro study of the associated processes. Two types of microfluidic channels were designed to quantitatively investigate modifications of erythrocyte deformability induced by hydrogen peroxide, ethanol and pentoxifylline based on transit velocity measurements. With a high sensitivity our microfluidic assemblies show that hydrogen peroxide decreases erythrocyte deformability in a dose-dependent manner. Then, results on ethanol resolve a biphasic nature of this reactant on the deformability of single erythrocyte cells. Results on pentoxifylline provide evidence that, similar to ethanol, also this medical drug has a double-sided effect on the erythrocyte deformability, i.e. increasing the deformability at low concentrations, while decreasing it at higher ones. Taken together, our microfluidic designs propose a potent measurement method for the erythrocyte deformability, as well as providing a perspective to evaluate effects of drugs on it.


Assuntos
Deformação Eritrocítica/efeitos dos fármacos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Equipamento , Etanol/administração & dosagem , Etanol/toxicidade , Humanos , Peróxido de Hidrogênio/administração & dosagem , Peróxido de Hidrogênio/toxicidade , Técnicas In Vitro , Técnicas Analíticas Microfluídicas/métodos , Pentoxifilina/administração & dosagem , Pentoxifilina/toxicidade
6.
Food Funct ; 10(3): 1726-1735, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30848260

RESUMO

Acylated anthocyanins are more stable than monomeric anthocyanins, but little is known about their physiological effects. We evaluated the hemodynamic effects of single intragastric doses of purple carrot (Daucus carota L.) anthocyanin (PCA) and two monomeric anthocyanins, cyanidin 3-O-glycoside (C3G) and delphinidin 3-O-ruthenoside (D3R). PCA, C3G, or D3R was administered orally to rat and blood flow in the cremaster artery was measured for 60 min using a laser Doppler blood flow meter. After measurements, the aorta of the animal was removed and the extent of phosphorylation of aortic epithelial nitric oxide synthase (eNOS) and Akt were determined by western blotting. PCA (10 mg kg-1) or C3G (1 mg kg-1) significantly increased rat cremaster arteriole blood flow and phosphorylation of eNOS and Akt; D3G (1 mg kg-1) only slightly altered cremaster arteriole blood flow and did not affect the phosphorylation of eNOS and Akt in the aorta. These results suggest that hemodynamic alterations depend more on the chemical structure of anthocyanins, particularly the aglycon, than on the glycoside. In addition, increase of blood flow by a single oral dose of PCA was practically reduced with treatment of carvedilol (CR), a non-specific adrenaline blocker. Blood concentrations of cyanidin or its glycoside 15, 30, or 60 min after the administration of 10 mg kg-1 PCA were below the limit of detection. These hemodynamic changes may have been associated with an indirect adrenergic action induced following a single dose of PCA.


Assuntos
Músculos Abdominais/irrigação sanguínea , Antocianinas/química , Antocianinas/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Daucus carota/química , Animais , Fator 2 de Liberação do Nucleotídeo Guanina/farmacologia , Masculino , Estrutura Molecular , Óxido Nítrico Sintase/classificação , Óxido Nítrico Sintase/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Ratos
7.
Am J Physiol Lung Cell Mol Physiol ; 316(5): L936-L945, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785346

RESUMO

Paracrine erythropoietin (EPO) signaling in the lung recruits endothelial progenitor cells, promotes cell maturation and angiogenesis, and is upregulated during canine postpneumonectomy (PNX) compensatory lung growth. To determine whether inhalational delivery of exogenous EPO augments endogenous post-PNX lung growth, adult canines underwent right PNX and received, via a permanent tracheal stoma, weekly nebulization of recombinant human EPO-containing nanoparticles or empty nanoparticles (control) for 16 wk. Lung function was assessed under anesthesia pre- and post-PNX. The remaining lobes were fixed for detailed morphometric analysis. Compared with control treatment, EPO delivery significantly increased serum EPO concentration without altering systemic hematocrit or hemoglobin concentration and abrogated post-PNX lipid oxidative stress damage. EPO delivery modestly increased post-PNX volume densities of the alveolar septum per unit of lung volume and type II epithelium and endothelium per unit of septal tissue volume in selected lobes. EPO delivery also augmented the post-PNX increase in alveolar double-capillary profiles, a marker of intussusceptive capillary formation, in all remaining lobes. EPO treatment did not significantly alter absolute resting lung volumes, lung and membrane diffusing capacities, alveolar-capillary blood volume, pulmonary blood flow, lung compliance, or extravascular alveolar tissue volumes or surface areas. Results established the feasibility of chronic inhalational delivery of growth-modifying biologics in a large animal model. Exogenous EPO selectively enhanced cytoprotection and alveolar angiogenesis in remaining lobes but not whole-lung extravascular tissue growth or resting function; the nonuniform response contributes to structure-function discrepancy, a major challenge for interventions aimed at amplifying the innate potential for compensatory lung growth.


Assuntos
Capilares/crescimento & desenvolvimento , Eritropoetina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Pneumonectomia , Alvéolos Pulmonares , Administração por Inalação , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Cães , Complacência Pulmonar/efeitos dos fármacos , Masculino , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/cirurgia
8.
Mol Cell Biochem ; 456(1-2): 85-93, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30712071

RESUMO

Chymases, a family of serine proteases with chymotryptic activity, play a significant role in cardiac angiotensin II (Ang II) formation from its substrate Ang-(1-12) in both human and rodent models. No studies, to date, have assessed the differences in enzymatic activity among these isoforms in Ang II formation, particularly in the cardiomyocyte (CM). Using PCR and DNA sequencing, we demonstrated that MCP-1, MCP-2, MCP-4, and MCP-5 mRNAs are expressed in the CM of both spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). While rMCP-1 and rMCP-5 gene transcripts were higher than that of other isoforms in both rat strains, WKY CM exhibits higher levels of rMCP-1 and rMCP-5 mRNAs compared to the SHR CM. Ovariectomy (OVX) increased the expression of rMCP-1 and rMCP-5 mRNAs in WKY. In SHR, OVX was associated with a blunted increase in rMCP-1 mRNA compared to OVX normotensive WKY. Chymase activity, measured as Ang II formation from Ang-(1-12), significantly correlated with rMCP-1 and rMCP-5 mRNA expression in both rat strains. Both rMCP-1 and rMCP-5 mRNA expressions were positively correlated with progressive diastolic dysfunction (increasing the ratio of early mitral inflow velocity-to-early mitral annular velocity, E/e') and expanding chamber dimensions or increasing left ventricular internal diameter end diastole. These data show rMCP-1 and rMCP-5 as the Ang II forming chymase isoforms participating in the loss of normal cardiac function due to OVX in rodents.


Assuntos
Quimases/biossíntese , Diástole/efeitos dos fármacos , Estrogênios/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Proteínas Musculares/biossíntese , Miócitos Cardíacos/enzimologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Feminino , Miócitos Cardíacos/citologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
9.
PLoS One ; 14(1): e0208724, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615620

RESUMO

OBJECTIVES: Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms. METHODS: Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants. RESULTS: Study participants' median age was 30 years (IQR 26-34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970). CONCLUSION: Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Velocidade do Fluxo Sanguíneo/fisiologia , Hemodinâmica/fisiologia , Adulto , Ásia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Dióxido de Carbono/toxicidade , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Feminino , Voluntários Saudáveis , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Artéria Cerebral Média/fisiologia , Fluxo Pulsátil/efeitos dos fármacos , Fluxo Pulsátil/fisiologia , Ultrassonografia Doppler Transcraniana
10.
Eur J Appl Physiol ; 119(3): 697-711, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30610443

RESUMO

PURPOSE: Multiday racing causes mild left ventricular (LV) dysfunction from day 1 that persists on successive days. We evaluated ingesting casein protein hydrolysate-carbohydrate (PRO) compared with carbohydrate-only (CHO) during a 3-day mountain bike race. METHODS: Eighteen male cyclists were randomly assigned to ingest 6.7% carbohydrate without (CHO) or with 1.3% casein hydrolysate (PRO) during racing (~ 4-5 h/day; 68/71/71 km). Conventional LV echocardiography, plasma albumin content, plasma volume (PV) and blood biomarkers were measured before day 1 and post race on day 3. RESULTS: Fourteen cyclists (n = 7 per group) completed the race. PV increased in CHO (mean increase (95% CI), 10.2% (0.1 to 20.2)%, p = 0.045) but not in PRO (0.4% (- 6.1 to 6.9)%). Early diastolic transmitral blood flow (E) was unchanged but deceleration time from peak E increased post race (CHO: 46.7 (11.8 to 81.6) ms, p = 0.019; PRO: 24.2 (- 0.5 to 48.9) ms, p = 0.054), suggesting impaired LV relaxation. Tissue Doppler mitral annular velocity was unchanged in CHO, but in PRO septal early-to-late diastolic ratio decreased (p = 0.016) and was compensated by increased lateral early (p = 0.034) and late (p = 0.012) velocities. Systolic function was preserved in both groups; with increased systolic lateral wall velocity in PRO (p = 0.002). Effect size increase in serum creatine kinase (CK) activity, CK-MB and C-reactive protein concentrations was less in PRO than CHO (Cohen's d mean ± SD, PRO: 2.91 ± 2.07; CHO: 7.56 ± 4.81, p = 0.046). CONCLUSION: Ingesting casein hydrolysate with carbohydrate during a 3-day race prevented secondary hypervolemia and failed to curb impaired LV relaxation despite reducing tissue damage and inflammatory biomarkers. Without PV expansion, systolic function was preserved by lateral wall compensating for septal wall dysfunction.


Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Carboidratos/farmacologia , Caseínas/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Biomarcadores/sangue , Ecocardiografia Doppler/métodos , Feminino , Humanos , Masculino , Hidrolisados de Proteína/efeitos dos fármacos , Disfunção Ventricular Esquerda/fisiopatologia
11.
Microcirculation ; 26(3): e12518, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30481399

RESUMO

OBJECTIVES: This study sought to determine whether salt-induced ANG II suppression contributes to impaired CBF autoregulation. METHODS: Cerebral autoregulation was evaluated with LDF during graded reductions of blood pressure. Autoregulatory responses in rats fed HS (4% NaCl) diet vs LS (0.4% NaCl) diet were analyzed using linear regression analysis, model-free analysis, and a mechanistic theoretical model of blood flow through cerebral arterioles. RESULTS: Autoregulation was intact in LS-fed animals as MAP was reduced via graded hemorrhage to approximately 50 mm Hg. Short-term (3 days) and chronic (4 weeks) HS diet impaired CBF autoregulation, as evidenced by progressive reductions of laser Doppler flux with arterial pressure reduction. Chronic low dose ANG II infusion (5 mg/kg/min, i.v.) restored CBF autoregulation between the pre-hemorrhage MAP and 50 mm Hg in rats fed short-term HS diet. Mechanistic-based model analysis showed a reduced myogenic response and reduced baseline VSM tone with short-term HS diet, which was restored by ANG II infusion. CONCLUSIONS: Short-term and chronic HS diet lead to impaired autoregulation in the cerebral circulation, with salt-induced ANG II suppression as a major factor in the initiation of impaired CBF regulation.


Assuntos
Angiotensina II/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Cloreto de Sódio na Dieta/farmacologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
12.
Graefes Arch Clin Exp Ophthalmol ; 257(2): 303-311, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30474717

RESUMO

PURPOSE: To evaluate the effect of topically administrated ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head (ONH) of normal rats. METHODS: Ripasudil (0.4%) or placebo was administered in the right eye of normal Brown Norway rats in a double-blind manner. Laser speckle flowgraphy was measured in the ONH of the right eye 20 or 40 min after a single instillation and before and after 7 or 14 days of twice daily instillation. Mean blur rate was evaluated in the total area (MA), the vessel region (MV), and the tissue region (MT). Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), and heart rate were also recorded at each time point. RESULTS: After a single instillation, MV was significantly larger at 40 min than 20 min in the ripasudil group (P = 0.044) and was significantly lower in the placebo group (P = 0.023). MA and MV 40 min after instillation were significantly larger in the ripasudil group than in the placebo group (P = 0.022 and P = 0.006, respectively). After continuous instillation, MA and MV in the ripasudil group significantly increased from baseline after 7 and 14 days of treatment (both P < 0.05) and MA, MV, and MT were significantly higher than in the placebo group (MA: 7 and 14 days, P < 0.01; MV: 7 days, P = 0.003, and 14 days, P = 0.012; MT: 7 days, P = 0.046). There were no significant changes in IOP, blood pressure, or OPP after single or continuous instillation. CONCLUSIONS: Topical instillation of ripasudil increased blood flow around the ONH in the eyes of normal rats.


Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Isoquinolinas/administração & dosagem , Disco Óptico/irrigação sanguínea , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Quinases Associadas a rho/antagonistas & inibidores , Animais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Instilação de Medicamentos , Masculino , Modelos Animais , Soluções Oftálmicas , Disco Óptico/efeitos dos fármacos , Distribuição Aleatória , Ratos , Valores de Referência
13.
J Matern Fetal Neonatal Med ; 32(3): 357-361, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28889765

RESUMO

OBJECTIVE: To investigate the effect of caffeine infusion on superior mesenteric artery (SMA) blood flow velocities (BFV) in preterm infants. METHODS: Prospective observational study on 38 preterm neonates 28-33+6 weeks gestation, who developed apnea on their first day of life, and caffeine citrate infusion was initiated at a loading dose of 20 mg/kg, followed by a maintenance dose of 5-10 mg/kg/day. Duplex ultrasound measurements of SMA BFV were recorded: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI), at 15 min before, 1-, 2- and 6-h after caffeine loading dose, and 2 h after two maintenance doses. RESULTS: There was a significant reduction in PSV 1-h (p = .008), a significant decrease in EDV 1- and 2-h (p = .000 and p = .005, respectively) and a significant increase in RI 1- and 2-h (p = .003 and p = .005, respectively) following caffeine loading dose, as compared to values before caffeine infusion. No significant effect of caffeine maintenance doses on SMA BFV was observed (p > .05). CONCLUSION: Blood flow in SMA is significantly reduced after caffeine citrate infusion at a loading dose of 20 mg/kg. This effect continues for at least 2 h. Meanwhile, SMA BFV seems not affected by maintenance doses.


Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Cafeína/farmacologia , Recém-Nascido Prematuro/fisiologia , Artéria Mesentérica Superior/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Cafeína/uso terapêutico , Citratos/farmacologia , Citratos/uso terapêutico , Feminino , Idade Gestacional , Hemodinâmica/efeitos dos fármacos , Humanos , Recém-Nascido , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiologia , Gravidez , Nascimento Prematuro/tratamento farmacológico , Nascimento Prematuro/fisiopatologia , Ultrassonografia Doppler Dupla
14.
Diabetes ; 68(3): 631-636, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30409780

RESUMO

Cardiovascular (CV) disease fatality rates are higher for women compared with men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post hoc analysis to determine whether there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled type 2 diabetes and without clinical evidence of obstructive CAD. We found that women had a higher rest MBF, lower CFR, and worse diastolic function compared with men. In addition, rest MBF was positively correlated with worse diastolic function in women. We previously showed that mineralocorticoid blockade improved CFR in men and women with type 2 diabetes, implicating aldosterone in the pathophysiology of coronary microvascular dysfunction. We therefore examined aldosterone levels and found that women had larger increases in aldosterone in response to an angiotensin-II infusion than did men. In conclusion, among individuals with type 2 diabetes and good cardiometabolic control, women had worse myocardial perfusion and diastolic function compared with men. The greater aldosterone responsivity in women may be a mechanism for this sex effect.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Adolescente , Adulto , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Enalapril/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
15.
Pediatr Blood Cancer ; 66(3): e27252, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29797633

RESUMO

BACKGROUND: Elevated transcranial Doppler (TCD) velocities accurately predict stroke risk in children with sickle cell disease (SCD). Chronic blood transfusion, the gold standard for primary stroke prevention, is faced with numerous challenges in Africa. Hydroxyurea (HU) has been shown to reduce elevated TCD velocities in children with SCD. AIM: To determine the effectiveness of HU in reducing the risk of primary stroke in a cohort of Nigerian children with SCD and elevated velocities treated with HU. METHODS: Children with SCD and TCD velocities ≥170 cm/sec treated with HU were prospectively followed with 3-monthly TCD and neurological evaluations for ≥12 months to determine the incidence of primary stroke. RESULTS: One hundred and four children, 53 males, and 51 females were enrolled into the study. Their ages ranged from 2 to 16 years with a mean of 6 years. At first TCD examination, velocities ranged from 173 to 260 cm/sec with conditional and abnormal risk velocities in 60 (57.7%) and 44 (42.3%) children, respectively. Follow up ranged from 1 to 8 years with a mean of 3.6 years. Mean TCD velocities showed a significant decline from 198.2 (standard deviation [SD] = 15.6) cm/sec to 169.3 (SD = 21.4) cm/sec (P < 0.001). One stroke event occurred in the cohort, giving a stroke incidence of 0.27/100 person years. CONCLUSION: HU significantly reduces TCD velocities in Nigerian children with SCD and elevated TCD velocities, with a corresponding reduction in the incidence of primary stroke. HU may represent a potential alternative for primary stroke prevention in low and middle income countries where the burden of SCD resides.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Hidroxiureia/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Ultrassonografia Doppler Transcraniana/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Nigéria/epidemiologia , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia
16.
Amino Acids ; 51(1): 39-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29926197

RESUMO

We previously obtained evidence suggesting that physical exercise increases the release of L-carnosine (CAR) from muscles and that CAR affects autonomic neurotransmission and physiological phenomena in rats. It has also been reported that exercise elicits an increase in activity of the sympathetic nerve innervating the skeletal muscle. Therefore, in this study, we investigated the effect of CAR application, onto the surface of the right femoral muscle, on activity of the sympathetic nerve innervating the left femoral muscle, in urethane-anesthetized rats. Topical application of 10 pg (44.2 fmol) of CAR increased either skeletal muscle sympathetic nerve activity (skeletal muscle-SNA) or skeletal muscle blood flow (skeletal muscle-BF) of the contralateral skeletal muscle. Furthermore, thioperamide, a histamine H3-antagonist, inhibited the increase in skeletal muscle-SNA, and butoxamine, a ß2-antagonist, abolished the increase in skeletal muscle-BF caused by topical application of CAR. The present results suggest that CAR released from muscles during physical exercise might affect skeletal muscle-SNA and skeletal muscle-BF on the opposite side of the body via a CAR evoked effect in muscles.


Assuntos
Carnosina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Condicionamento Físico Animal , Sistema Nervoso Simpático/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo/fisiologia , Butoxamina/farmacologia , Injeções Intramusculares , Cinética , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Piperidinas/farmacologia , Ratos , Ratos Wistar , Sistema Nervoso Simpático/irrigação sanguínea , Simpatolíticos/farmacologia , Transmissão Sináptica/fisiologia
17.
Acta Anaesthesiol Scand ; 63(1): 40-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30058113

RESUMO

BACKGROUND: In free flap surgery, the maintenance of proper blood flow after anastomosis of flap pedicle vessels is important. Lipo-prostaglandin E1 (lipo-PGE1) has been empirically administered to prevent blood flow insufficiency in a free flap reconstruction. We tested our hypothesis that lipo-PGE1 administration increases the arterial inflow of free flap. We also evaluated lipo-PGE1-related haemodynamic changes and complications. METHODS: Thirty-seven patients who underwent free flap reconstruction were analysed. Lipo-PGE1 was administered 10 minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30 minutes after lipo-PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30 minutes after lipo-PGE1 administration. The arterial blood pressure, heart rate, cardiac output, stroke volume variation, and pulse pressure variation were measured simultaneously. Lipo-PGE1-related complications such as hypotension, bradycardia, hypothermia, facial flushing, diarrhoea, apnoea, and seizure were also investigated. RESULTS: The maximal blood flow velocity was significantly increased at 30 minutes after lipo-PGE1 administration compared to the level before lipo-PGE1 administration (mean (standard deviation): 26.3 (8.7) cm/s vs 22.5 (8.0) cm/s, P = 0.002). The haemodynamic variables were not significantly different before and 30 minutes after lipo-PGE1 administration. No lipo-PGE1-related complications occurred. CONCLUSIONS: Lipo-PGE1 significantly increases the maximal blood flow velocity without complications in patients undergoing free flap reconstruction and may be an effective and safe method of maintaining adequate blood flow in these cases.


Assuntos
Alprostadil/farmacologia , Retalhos de Tecido Biológico/irrigação sanguínea , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adulto , Idoso , Artérias/efeitos dos fármacos , Artérias/fisiologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
18.
BMC Anesthesiol ; 18(1): 174, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458723

RESUMO

BACKGROUND: Successful resuscitation from asystole induced by bupivacaine requires the reestablishment of a sufficient coronary flow (CF) quickly. This study was designed to test whether levosimendan was superior to epinephrine in the reestablishment of crucial coronary flows after bupivacaine-induced asystole. METHODS: The isolated, perfused, nonrecirculating, Langendorff rat heart preparation was used. Bupivacaine 100 µmol/L was perfused into rat hearts to induce asystole, and then for 3 min thereafter. Three experimental groups were assessed after asystole with infusions as follow: (1) a mixture of 2% lipid emulsion and 40 µmol/L bupivacaine (control group), (2) a mixture of 0.15 µg/mL epinephrine combined with 2% lipid emulsion and 40 µmol/L bupivacaine (epinephrine group), and (3) a mixture of 5 µmol/L levosimendan combined with a 2% lipid emulsion and 40 µmol/L bupivacaine mixture (levosimendan group). Coronary flow (CF), the time to recovery (Trecovery), the number of ventricular arrhythmias, and cardiac function parameters were recorded for 40 min after heartbeat recovery. RESULTS: All hearts in the control, epinephrine and levosimendan groups had heartbeat recovery. The rank order of the mean CF from highest to lowest was the levosimendan group > the epinepgrine group > the control group (P < 0.05). The rank order of Trecovery from shortest to longest was the levosimendan group < the epinephrine group < the control group (P < 0.01). During the recovery phase, isolated rat hearts developed more ventricular arrhythmias in the epinephrine group than in the levosimendan group (P = 0.01). CONCLUSION: Levosimendan is superior to epinephrine in producing higher CFs and faster recovery when reversing bupivacaine-induced asystole in the isolated rat hearts.


Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Bupivacaína/administração & dosagem , Epinefrina/administração & dosagem , Emulsões Gordurosas Intravenosas/administração & dosagem , Parada Cardíaca/tratamento farmacológico , Simendana/administração & dosagem , Anestésicos Locais/administração & dosagem , Animais , Circulação Coronária/efeitos dos fármacos , Quimioterapia Combinada , Parada Cardíaca/fisiopatologia , Preparação de Coração Isolado/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Ressuscitação/métodos
19.
Biochem Pharmacol ; 158: 185-191, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30365948

RESUMO

Blood circulation, facilitating gas exchange and nutrient transportation, is a quintessential feature of life in vertebrates. Any disruption to blood flow, may it be by blockade or traumatic rupture, irrevocably leads to tissue infarction or death. Therefore, it is not surprising that hemostasis and vascular adaptation measures have been evolutionarily selected to mitigate the adverse consequences of altered circulation. Blood vessels can be broadly categorized as arteries, veins, or capillaries, based on their structure, hemodynamics, and gas exchange. However, all of them share one property: they are lined with an epithelial sheet called the endothelium, which typically lies on a basement membrane. This endothelium is the primary interface between the flowing blood and the rest of the body, and it has highly specialized molecular mechanisms to detect and respond to changes in blood perfusion. The purpose of this commentary will be to highlight some of the recent developments in the research on blood flow sensing, vascular remodeling, and homeostasis and to discuss the development of innovative pharmaceutical approaches targeting mechanosensing mechanisms to prolong patient survival and improve quality of life.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Homeostase/fisiologia , Resistência ao Cisalhamento/fisiologia , Doenças Vasculares/patologia , Remodelação Vascular/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Homeostase/efeitos dos fármacos , Humanos , Resistência ao Cisalhamento/efeitos dos fármacos , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Remodelação Vascular/efeitos dos fármacos , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
20.
Cell Physiol Biochem ; 50(2): 585-596, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30308492

RESUMO

BACKGROUND/AIMS: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. METHODS: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. RESULTS: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. CONCLUSION: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Neuropatias Diabéticas/prevenção & controle , Glucosídeos Iridoides/uso terapêutico , PPAR gama/metabolismo , Substâncias Protetoras/uso terapêutico , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/genética , Anilidas/farmacologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Neuropatias Diabéticas/induzido quimicamente , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/veterinária , Dislipidemias/patologia , Dislipidemias/prevenção & controle , Dislipidemias/veterinária , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/patologia , Hiperalgesia/prevenção & controle , Hiperalgesia/veterinária , Glucosídeos Iridoides/farmacologia , PPAR gama/genética , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade
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