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1.
Clin Exp Rheumatol ; 41(10): 2078-2086, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37902270

RESUMO

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.


Assuntos
Síndrome de Behçet , Úlceras Orais , Criança , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/etiologia , Úlceras Orais/tratamento farmacológico , Estudos Transversais , Imunossupressores/uso terapêutico , Árvores de Decisões
2.
Surg Obes Relat Dis ; 17(1): 193-207, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33011072

RESUMO

BACKGROUND: Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before. OBJECTIVE: The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. SETTING: Physiology Research Lab at the University. METHODS: Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 ß, ER-α agonist, ER-ß agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples. RESULTS: In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss. CONCLUSIONS: SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications.


Assuntos
Gastrectomia , Coto Gástrico , Receptores de Estrogênio/fisiologia , Animais , Estrogênios , Feminino , Gastrinas , Leptina , Osteoporose , Ovariectomia , Ratos , Ratos Sprague-Dawley
3.
Life Sci ; 263: 118561, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33045213

RESUMO

AIMS: Acetaminophen-induced hepatorenal toxicity varies among sexes with controversial results among species. The aim was to compare the impact of sex and ovarian hormones on hepatorenal toxicity and to elucidate protective effects of estrogen and estrogen receptor (ER) agonists. MAIN METHODS: Under anesthesia, female rats underwent ovariectomy (OVX) or sham-OVX. Starting at postsurgical 40th day, OVX-rats received subcutaneously (each, 1 mg/kg/day) 17ß-estradiol (E2), ERß-agonist (DPN) or ERα-agonist (PPT) for 10 days, while male and sham-OVX rats received vehicle for 10 days. Then, rats received either acetaminophen (3 g/kg) or saline by orogastric gavage and were decapitated at 24th h. Blood samples were obtained to measure serum ALT, AST, BUN, creatinine levels. Liver and kidney samples were obtained for histopathologic examination and for analyzing levels of luminol- and lucigenin-chemiluminescence, glutathione and myeloperoxidase activity. KEY FINDINGS: Compared to their control groups, levels of AST, ALT, BUN, creatinine, hepatic and renal myeloperoxidase activity and chemiluminescence levels were increased, and hepatic glutathione level was decreased in acetaminophen-administered male groups, while ALT and hepatic chemiluminescence levels were not elevated in sham-OVX-rats. Both ER-agonists and E2 reduced BUN, creatinine and reversed all oxidative parameters in renal tissues of OVX-rats. Additionally, ERα-agonist reversed all hepatic injury parameters, while ERß-agonist elevated hepatic glutathione level. SIGNIFICANCE: Acetaminophen toxicity in female rats presented with a more preserved hepatic function, while renal toxicity was not influenced by sex or by the lack of ovarian hormones. Pretreatment with estrogen or ER agonists, via their antioxidant actions, provided protective effects on acetaminophen-induced hepatorenal toxicity.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estrogênios/farmacologia , Nefropatias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptores de Estrogênio/química , Analgésicos não Narcóticos/toxicidade , Animais , Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Estradiol/farmacologia , Feminino , Glutationa , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Nitrilas/farmacologia , Propionatos/farmacologia , Ratos , Ratos Sprague-Dawley
4.
J Plast Reconstr Aesthet Surg ; 73(3): 590-597, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31734236

RESUMO

OBJECTIVE: This study used an experimental model mimicking early postoperative enteral feeding after the transfer of free jejunal flap and tested the hypothesis that jejunal infusion with dextrose or saline is associated with improved tissue perfusion and/or less mucosal damage after ischemia/reperfusion (IR) injury. METHODS: Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham group (no IR and no intraluminal infusion); IR control group (IR but not intraluminal infusion); IR plus intraluminal 0.9% NaCl infusion or 5% dextrose or 10% dextrose infusion groups. A jejunal segment of each rat was isolated. The animals had jejunal ischemia for 40 min, reperfusion, and intestinal infusion on the basis of their allocation. Jejunal tissue perfusion was measured with laser Doppler flowmetry at one hour and two hours after reperfusion, after which the animals were sacrificed and tissue samples were obtained for the scoring of histological damage at superficial and cryptic epithelium, villus structure, and inflammatory cell infiltration and tissue nitric oxide (NO), interleukin (IL)-1, IL-6, and matrix metalloproteinase-1 (MMP) level measurements. RESULTS: At 1 h of reperfusion, IR plus 5% dextrose and 10% dextrose groups both had significantly higher perfusion rates than the IR control group (384.8 ± 26.7 and 462.4 ± 44.7 versus 270.3 ± 34.2 PU, respectively, p < 0.05 for both). These differences were maintained at 2 h of reperfusion (p < 0.05 for both). Saline infusion, however, resulted in improved tissue perfusion only at the early phase of reperfusion. Intraluminal infusion with dextrose solution, either 5% or 10%, was associated with higher tissue NO, IL-1, and IL-6 levels than that in the sham group (p < 0.05 for all). In addition, intraluminal infusion of any fluid resulted in less severe histological damage (8.1 ± 0.9 versus 5.8 ± 1.0, 5.4 ± 0.9, and 5.2 ± 1.9, for IR plus saline, 5% dextrose and 10% dextrose groups, respectively, p < 0.05 for all). CONCLUSIONS: Intraluminal infusion of fluids, particularly dextrose solutions, may be protective against IR injury as demonstrated by improved tissue perfusion and less histological damage. In addition, increases in tissue NO, IL-1, and IL-6 levels in association with dextrose infusion may be explained by the activation of pro-inflammatory and anti-inflammatory protective pathways. These support early enteral feeding after free jejunum flap transfers; however, further studies are warranted.


Assuntos
Jejuno/cirurgia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Retalhos de Tecido Biológico/cirurgia , Glucose/farmacologia , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/patologia , Jejuno/irrigação sanguínea , Jejuno/metabolismo , Jejuno/patologia , Fluxometria por Laser-Doppler , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos , Traumatismo por Reperfusão/patologia
5.
Plast Reconstr Surg ; 144(1): 124-133, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246814

RESUMO

BACKGROUND: Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities. METHODS: Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically. RESULTS: Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05). CONCLUSIONS: This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.


Assuntos
Retalhos de Tecido Biológico , Iloprosta/farmacologia , Precondicionamento Isquêmico/métodos , Jejuno/transplante , Inibidores da Agregação Plaquetária/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Modelos Animais de Doenças , Esôfago/cirurgia , Fluxometria por Laser-Doppler/métodos , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
6.
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
7.
Hypertension ; 73(4): 829-838, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739537

RESUMO

Hypertension is an established risk factor for subsequent cardiovascular diseases, with Ang II (angiotensin II) playing a major role in mediating thrombotic and inflammatory abnormalities. Although T cells and IL-6 (interleukin-6) play an important role in adaptive immune responses, little is known about their role(s) in the thromboinflammatory responses associated with Ang II. Here we show using intravital microscopy coupled with the light/dye injury model that Rag-1 deficient (Rag-1-/-) and IL-6 deficient (IL-6-/-) mice are afforded protection against Ang II-induced thrombosis. Blocking IL-6 receptors (using CD126 and gp130 antibodies) significantly diminished Ang II-mediated thrombosis and inflammatory cell recruitment in mice. Furthermore, the adoptive transfer of IL-6-/--derived T cells into Rag-1-/- mice failed to accelerate Ang II-induced thrombosis compared with Rag-1-/- mice reconstituted with wild-type-derived T cells, suggesting T cell IL-6 mediates the thrombotic abnormalities associated Ang II hypertension. Interestingly, adoptive transfer of WT T cells into Rag-1-/-/Ang II mice resulted in increased numbers of immature platelets, which constitutes a more active platelet population, that is, prothrombotic and proinflammatory. To translate our in vivo findings, we used clinical samples to demonstrate that IL-6 also predisposes platelets to an interaction with collagen receptors, thereby increasing the propensity for platelets to aggregate and cause thrombosis. In summary, we provide compelling evidence for the involvement of IL-6, IL-6R, and T-cell-dependent IL-6 signaling in Ang II-induced thromboinflammation, which may provide new therapeutic possibilities for drug discovery programs for the management of hypertension.


Assuntos
Imunidade Adaptativa , Pressão Sanguínea/fisiologia , Hipertensão/complicações , Hipertensão/imunologia , Interleucina-6/metabolismo , Linfócitos T/imunologia , Trombose/imunologia , Angiotensina II/toxicidade , Animais , Modelos Animais de Doenças , Citometria de Fluxo , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microcirculação/efeitos dos fármacos , Transdução de Sinais , Trombose/induzido quimicamente , Trombose/metabolismo
8.
Peptides ; 107: 1-9, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30031042

RESUMO

Testicular torsion causes ischemia-reperfusion injury and an increased risk of infertility. Nesfatin-1 is a novel peptide with antioxidant, anti-inflammatory and anti-apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin-1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague-Dawley rats (180-230 g; n = 24) had sham-operation or they underwent testicular torsion by rotating the left testis 720° and fixing it for 2 h, followed by a 2-h detorsion. Rats in each group were treated intraperitoneally with either nesfatin-1 (0.3 µg/kg) or saline prior to the torsion or sham-torsion. At the end of the 4-h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline-treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin-1-treated torsion/detorsion group. The levels of 8-OHdG, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-3 were increased in the saline-treated torsion/detorsion group as compared to sham-operated group, while nesfatin-1 pre-treatment significantly decreased the expressions of the pro-inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin-1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)-beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin-1, by regulating AKT and CREB signaling pathways and pro-inflammatory/anti-inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion-detorsion-induced tubular degeneration.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Torção do Cordão Espermático/complicações , Espermatogênese/efeitos dos fármacos , Animais , Apoptose , Masculino , Nucleobindinas , Estresse Oxidativo , Substâncias Protetoras/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Torção do Cordão Espermático/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
9.
FASEB J ; 32(6): 3448-3456, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29452567

RESUMO

Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40-/-, and CD40L-/- mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; α5ß1) antagonist, ATN-161. Our results demonstrate that CD40-/-, CD40L-/-, and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40-/- or CD40L-/- mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.


Assuntos
Angiotensina II/metabolismo , Antígenos CD40/metabolismo , Integrina alfa5beta1/metabolismo , Transdução de Sinais , Trombose/metabolismo , Angiotensina II/genética , Animais , Antígenos CD40/genética , Ligante de CD40/genética , Ligante de CD40/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Integrina alfa5beta1/genética , Masculino , Camundongos , Camundongos Knockout , Trombose/genética , Trombose/patologia
10.
Toxicol Ind Health ; 32(8): 1438-1449, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25575685

RESUMO

In this study, the association between heavy metals in water and cyprinids sampled from the Yesilirmak River stretch, which is frequently exposed to pollutant sources (a sugar production factory (Turhal) and solid wastes dump area (Tasliçiftlik) was explored, and the oxidative effects of heavy metals on cyprinids were evaluated through analyzing some liver enzymes, namely, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and cortisol. The heavy metal concentrations of both fish and water, collected from three different locations along the river during the summer of 2011 and winter of 2010 (Turhal, Tasliçiftlik, and Gümenek), were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The water and fish liver heavy metal concentrations exhibited increasing trends from upstream (Gümenek) to downstream (Turhal). The water and liver samples collected during the summer had higher heavy metal concentrations than those obtained during the winter. The mean heavy metal concentrations increased from Gümenek to Turhal. The liver heavy metal concentrations were higher than those in the water and exhibited almost the same increasing trend from Gümenek to Turhal. Positive relationships between liver and water heavy metal concentrations, especially for cadmium (R 2 = 0.91) and lead (R 2 = 0.98), were obtained. Among the liver enzymes, only MDA followed the same increasing trend from Gümenek to Turhal as was obtained for heavy metals. On the other hand, CAT and SOD had a contrary spatial pattern of change to those of heavy metals and MDA. Although the values of heavy metals and MDA in Tasliçiftlik were between the two other locations, fish inhabiting this locality had significantly higher values of cortisol, which is an indication of the other stress-causing factors for fish.


Assuntos
Cyprinidae , Exposição Ambiental/efeitos adversos , Fígado/efeitos dos fármacos , Metais Pesados/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Rios/química , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Cádmio/análise , Cádmio/metabolismo , Cádmio/toxicidade , Cobre/análise , Cobre/metabolismo , Cobre/toxicidade , Cyprinidae/sangue , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/metabolismo , Monitoramento Ambiental , Proteínas de Peixes/metabolismo , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Ferro/análise , Ferro/metabolismo , Ferro/toxicidade , Chumbo/análise , Chumbo/metabolismo , Chumbo/toxicidade , Fígado/química , Fígado/metabolismo , Metais Pesados/análise , Metais Pesados/metabolismo , Oxirredutases/metabolismo , Estações do Ano , Análise Espaço-Temporal , Espectrofotometria Atômica , Estresse Fisiológico , Turquia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
11.
Bioorg Med Chem ; 23(10): 2598-605, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25863492

RESUMO

Sulfonamides represent a significant class of biologically active compounds that inhibit carbonic anhydrase (CA, EC.: 4.2.1.1) isoenzymes involved in different pathological and physiological events. Sulfonamide CA inhibitors are used therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents. A series of new sulfonamides were synthesized using imides and tosyl chloride as starting materials. These N-acylsulfonamides efficiently inhibited the cytosolic human carbonic anhydrase isoenzymes I, and II (hCA I, and II), with nanomolar range inhibition constants ranging between 36.4 ± 6.0-254.6 ± 18.0 and 58.3 ± 0.6-273.3 ± 2.5 nM, respectively.


Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/química , Sulfonamidas/química , Inibidores da Anidrase Carbônica/síntese química , Humanos , Imidas/química , Cinética , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Compostos de Tosil/química
12.
Kulak Burun Bogaz Ihtis Derg ; 23(2): 112-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23611325

RESUMO

Tumors of the smooth muscles are rarely seen, as the number of smooth muscles is low within the intraoral region. Leiomyosarcoma is a type of malign tumor originating from smooth muscles. The most common regions of leiomyosarcoma of the oral cavity are the maxilla and mandible. In this article, we present a leiomyosarcoma detected in a 20-year-old male patient who was admitted to the clinic with the complaint of a mass for about three months. The mass was located in the left half of the soft palate and it was resected en bloc with the mucosa. No recurrence was observed during the two-year follow-up period of the patient.


Assuntos
Leiomiossarcoma/patologia , Neoplasias Palatinas/patologia , Palato Mole/patologia , Diagnóstico Diferencial , Humanos , Leiomiossarcoma/cirurgia , Masculino , Neoplasias Palatinas/cirurgia , Adulto Jovem
13.
J Am Soc Hypertens ; 7(1): 14-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23321401

RESUMO

Although it is well known that endothelial function is compromised in the presence of either hypertension (HTN) or hypercholesterolemia (HCh), less is known about whether and how the combination of these risk factors (HTN+HCh) results in impaired endothelium-dependent dilation (EDD). The aims of this study were to evaluate the influence of HTN+HCh on vasomotor function and to identify the mechanisms that underlie the altered vascular reactivity elicited by HTN+HCh. Endothelium-dependent and -independent vasomotor responses of aortic vessels were studied in mice with diet-induced HCh and/or HTN induced by chronic administration of either angiotensin II (AngII) or deoxycorticosterone acetate-salt. HTN+HCh elicited an impairment of EDD that appeared between each risk factor alone. Incubation with catalase resulted in more severe EDD impairment. Each risk factor enhanced vascular H2O2 production, but a larger response was noted with HTN+HCh. An attenuated EDD was not observed in AngII type 1a receptor deficient (AT1r(-/-)) mice, but AT1r(-/-) bone marrow chimeras exhibited more profound impairment compared with wild-type. HTN+HCh does not exert an additive effect of vasomotor dysfunction compared with either risk factor alone, and both H2O2 and blood cell-associated AT1r contribute to the impaired EDD responses in mice with HTN+HCh.


Assuntos
Hipercolesterolemia/epidemiologia , Hipercolesterolemia/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Sistema Vasomotor/fisiologia , Acetilcolina/farmacologia , Angiotensina II/farmacologia , Animais , Transplante de Medula Óssea , Comorbidade , Desoxicorticosterona/farmacologia , Modelos Animais de Doenças , Humanos , Hipertensão/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mineralocorticoides/farmacologia , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores de Risco , Quimeras de Transplante , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacos
14.
Hypertension ; 60(6): 1503-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23090770

RESUMO

Angiotensin II (Ang II) contributes to the pathogenesis of hypertension and other cardiovascular diseases. Ang II induces a pro-oxidative, proinflammatory, and prothrombogenic phenotype in vascular endothelial cells. Although the peptide promotes the recruitment of leukocytes and platelets and induces oxidative stress in the microvasculature, it remains unclear whether and how the blood cell recruitment is linked to the production of reactive oxygen species. In this study, we addressed the contributions of Ang II type 1 receptors (AT(1)r) and gp91(phox) to the recruitment of leukocytes and platelets and reactive oxygen species production in venules during chronic (2-week) infusion of Ang II in wild-type (WT) and mutant mice. Intravital video microscopy was used to measure the adhesion and emigration of leukocytes, the adhesion of fluorescently labeled platelets, and dihydrorhodamine oxidation (a measure of oxidative stress) in cremaster muscle postcapillary venules. In WT mice, Ang II infusion induced a time-dependent increase in the adhesion of leukocytes and platelets and enhanced reactive oxygen species production in venules. These changes in blood cell adhesion and reactive oxygen species production were not observed in AT(1)r(-/-) mice, AT(1)r(-/-) bone marrow chimeras (blood cells deficient in AT(1)r), gp91(phox-/-) mice, gp91(phox-/-) chimeras (blood cells or endothelial cells deficient in gp91(phox)), and in WT mice rendered granulocytopenic via intraperitoneal injection of antimouse granulocyte receptor 1 antibody. Thrombocytopenic WT mice (platelets depleted by intraperitoneal injection of rabbit antimouse thrombocyte antiserum) responded similar to WT mice. These findings implicate leukocyte-associated AT(1)r and gp91(phox) in the induction of the pro-oxidative, proinflammatory, and prothrombogenic phenotype assumed by microvessels that is chronically exposed to elevated Ang II.


Assuntos
Angiotensina II/farmacologia , Leucócitos/metabolismo , Microvasos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Leucócitos/imunologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Microvasos/imunologia , Microvasos/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo/fisiologia , Adesividade Plaquetária/efeitos dos fármacos , Adesividade Plaquetária/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Vênulas/efeitos dos fármacos , Vênulas/imunologia , Vênulas/metabolismo
15.
Clin J Sport Med ; 21(3): 237-42, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21490504

RESUMO

OBJECTIVES: To investigate the levels of nitric oxide (NO) and endothelin-1 (ET-1) in soccer players with exercise-induced bronchospasm (EIB), to test whether these endogenous vasoactive molecules are involved in the development of EIB, and to examine the possible participation of reactive oxygen metabolites in these alterations. DESIGN: Observational study. SETTING: Football club. PARTICIPANTS: Forty-three soccer players (N = 43) aged 16 to 22 years performed maximal exercise test on a treadmill by using Bruce protocol. INTERVENTIONS: Respiratory function tests were evaluated before and after exercise tests. Participants were grouped as control (n = 35) or EIB (n = 8) groups according to the respiratory function test results. MAIN OUTCOME MEASURES: Endothelin-1 (ET-1), nitric oxide (NO), carbonyl, malondialdehyde, and glutathione levels were determined from the blood samples taken before and after exercise tests. RESULTS: In the control group, significant decreases in plasma ET-1 and serum NO levels were determined after exercise. On the other hand, plasma malondialdehyde and carbonyl levels were significantly decreased, whereas glutathione levels were significantly increased after exercise. In the EIB group, blood levels of NO, ET-1, carbonyl, and malondialdehyde after exercise were found to be significantly increased compared with pre-exercise levels. CONCLUSIONS: These findings demonstrate that in young soccer players, EIB is associated with elevated serum NO and plasma ET-1 levels. Moreover, significant increases in lipid peroxidation and protein oxidation and decreases in antioxidant sulfhydryl (RSH) content indicate a significant compromise in the blood antioxidant status and the presence of systemic oxidative stress in young athletes with EIB.


Assuntos
Asma Induzida por Exercício/fisiopatologia , Endotelina-1/fisiologia , Óxido Nítrico/fisiologia , Futebol/fisiologia , Adolescente , Atletas , Endotelina-1/sangue , Teste de Esforço , Glutationa/sangue , Humanos , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Óxido Nítrico/sangue , Espécies Reativas de Oxigênio/sangue , Testes de Função Respiratória , Adulto Jovem
16.
Pulm Pharmacol Ther ; 23(3): 215-21, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19945540

RESUMO

Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of bleomycin-induced lung fibrosis. Lung fibrosis was induced by intratracheal administration of 0.1 ml of bleomycin hydrochloride (5 mg/kg in 0.9% NaCl) under anesthesia to Sprague-Dawley rats (200-250 g; n = 7-8 per group). Control rats received an equal volume of saline intratracheally. In the treatment groups, the rats were treated with either sildenafil citrate (10 mg/kg per day; subcutaneously) or saline for 14 days. Another group of rats were administered subcutaneously with N(G)-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg in 0.9% NaCl) 5 min after sildenafil injections. After decapitation, the lungs were excised and taken for microscopic evaluation or stored for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity, and for the assessment of apoptosis. Trunk blood was collected for the assessment of serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. In the group with lung fibrosis, the lung tissue was characterized by microscopic lesions, increased lipid peroxidation with a concomitant reduction in GSH content, increased MPO activity and apoptosis. Serum TNF-alpha and IL-1beta levels were higher in the lung fibrosis group compared to control values. Sildenafil reversed tissue MDA levels, MPO activity and serum pro-inflammatory cytokine levels, and preserved GSH content although its effect on the extent of tissue lesion and apoptosis was not statistically significant. Treatment with l-NAME reversed the effect of sildenafil on GSH content. In conclusion, sildenafil citrate administration to rats with bleomycin-induced lung fibrosis seems to be beneficial via prevention of lipid peroxidation, cytokine production and/or release and neutrophil accumulation.


Assuntos
Pulmão/efeitos dos fármacos , Inibidores da Fosfodiesterase 5 , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Fibrose Pulmonar/patologia , Sulfonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Bleomicina , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído , NG-Nitroarginina Metil Éster/farmacologia , Neutrófilos/metabolismo , Peroxidase/metabolismo , Fibrose Pulmonar/induzido quimicamente , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Citrato de Sildenafila , Fator de Necrose Tumoral alfa/metabolismo
17.
Neural Netw ; 22(10): 1448-62, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19556105

RESUMO

In this paper, we propose a novel technique for the automatic design of Artificial Neural Networks (ANNs) by evolving to the optimal network configuration(s) within an architecture space. It is entirely based on a multi-dimensional Particle Swarm Optimization (MD PSO) technique, which re-forms the native structure of swarm particles in such a way that they can make inter-dimensional passes with a dedicated dimensional PSO process. Therefore, in a multidimensional search space where the optimum dimension is unknown, swarm particles can seek both positional and dimensional optima. This eventually removes the necessity of setting a fixed dimension a priori, which is a common drawback for the family of swarm optimizers. With the proper encoding of the network configurations and parameters into particles, MD PSO can then seek the positional optimum in the error space and the dimensional optimum in the architecture space. The optimum dimension converged at the end of a MD PSO process corresponds to a unique ANN configuration where the network parameters (connections, weights and biases) can then be resolved from the positional optimum reached on that dimension. In addition to this, the proposed technique generates a ranked list of network configurations, from the best to the worst. This is indeed a crucial piece of information, indicating what potential configurations can be alternatives to the best one, and which configurations should not be used at all for a particular problem. In this study, the architecture space is defined over feed-forward, fully-connected ANNs so as to use the conventional techniques such as back-propagation and some other evolutionary methods in this field. The proposed technique is applied over the most challenging synthetic problems to test its optimality on evolving networks and over the benchmark problems to test its generalization capability as well as to make comparative evaluations with the several competing techniques. The experimental results show that the MD PSO evolves to optimum or near-optimum networks in general and has a superior generalization capability. Furthermore, the MD PSO naturally favors a low-dimension solution when it exhibits a competitive performance with a high dimension counterpart and such a native tendency eventually yields the evolution process to the compact network configurations in the architecture space rather than the complex ones, as long as the optimality prevails.


Assuntos
Redes Neurais de Computação , Algoritmos , Inteligência Artificial , Neoplasias da Mama/diagnóstico , Sistemas Computacionais , Diabetes Mellitus/diagnóstico , Diagnóstico por Computador , Cardiopatias/diagnóstico , Humanos , Neurônios/fisiologia , Processos Estocásticos
18.
Nutr Neurosci ; 12(2): 89-94, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19356311

RESUMO

The aim of the present study was to investigate whether high fat consumption changes the effects of stress on both motor activity performance, striatal and cortical dopamine and serotonin metabolites in rats. The animals were fed either with high fat or standard diet for 4 weeks. Restraint stress lasting for 15 min at +4 degrees C was applied daily to stress-exposed groups. Motor activity performance was measured weekly by using motor activity monitoring systems. At the end of the study, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels of the striatum and cerebral cortex were measured by HPLCEC. It was observed that restraint stress increased locomotor activity and high-fat diet prevented this effect. Stress and high-fat intake had an additive decreasing effect on striatal HVA levels. 5-HIAA levels, on the other hand, were lower in both high fat and high fat + stress groups compared to the stress group. These results suggest that high-fat intake differentially affected the stress response on striatal dopaminergic and serotonergic neurons in rat brain regions studied and this may be related to the effects observed in motor activity performance.


Assuntos
Química Encefálica/fisiologia , Gorduras na Dieta/administração & dosagem , Ácido Homovanílico/análise , Ácido Hidroxi-Indolacético/análise , Atividade Motora/fisiologia , Estresse Fisiológico/fisiologia , Animais , Córtex Cerebral/química , Temperatura Baixa , Corpo Estriado/química , Dopamina/fisiologia , Masculino , Neurônios/fisiologia , Ratos , Ratos Wistar , Restrição Física , Serotonina/fisiologia
19.
Saudi Med J ; 26(11): 1809-11, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16311672

RESUMO

In this study, we report a rare variation of the branching of the celiac trunk. During a routine abdominal dissection on a female cadaver, we found the celiac trunk to emerge from the abdominal aorta as 2 roots named hepatogastric trunk and hepatosplenic trunk. The hepatogastric trunk arises from the anterior surface of the abdominal aorta and divides into an aberrant branch to the right lobe of the liver, a branch to the right hemi diaphragm, the left hepatic and the left gastric arteries. The hepatosplenic trunk, which arises 1.5 cm below the hepatogastric trunk, gave off the common hepatic and splenic arteries. The common hepatic artery divided into the gastroduodenal, the right branch to the hepatic and the cystic arteries. It is important to know the variations of hepatogastric trunk and hepatosplenic trunk for the success of surgical operations to the liver and radiological investigations of those regions.


Assuntos
Artéria Celíaca/anormalidades , Artéria Celíaca/anatomia & histologia , Cadáver , Dissecação , Feminino , Humanos
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