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1.
J Endocrinol Invest ; 45(10): 1875-1885, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35689728

RESUMO

PURPOSE: The use of sex steroids by trans people has been of paramount importance regarding body changes during gender transition. The objective of this study was to assess the effects of an injectable steroid combination frequently used by transwomen, namely estradiol enanthate with dihydroxyprogesterone acetophenide (E2EN/DHPA), on blood pressure and metabolic outcomes using an animal model. METHODS: Two-month-old male Wistar rats were orchiectomized or sham-operated and divided into groups: (1) Sham treated with sesame oil vehicle (SG), (2) sham treated with E2EN/DHPA (SP), (3) orchiectomized rats treated with vehicle (OG), and (4) orchiectomized rats treated with E2EN/DHPA (OP), with all groups treated every 10 days for 5 months. We evaluated systolic blood pressure (SBP), body weight (BW), abdominal circumference, nasoanal length (NAL), food and water intake (FI, WI), lipid profile (triglycerides, LDL, and HDL), serum C-reactive protein (CRP), plasma concentrations of urea (URpl) and creatinine (CRpl), 24 h urinary volume (V24 h), sodium and potassium excretion (UNa+, UK+), and proteinuria. RESULTS: E2EN/DHPA administration reduced BW (SP 324.5 ± 31.1; OP 291.7 ± 41.3 g) and NAL (SP 24.5 ± 0.4; OP 24.6 ± 1.0 cm), without changing blood pressure, but increased URpl concentration (SP 55.0 ± 4.8; OP 42.5 ± 8.8 mg/dL) and CRpl (SP 0.47 ± 0.05; OP 0.46 ± 0.04 mg/dL), sodium (SP 3.1 ± 0.8; OP 3.3 ± 0.4 µEq/min/kg), potassium (SP 0.91 ± 0.22; OP 0.94 ± 0.22 µEq/min/kg) excretions and urinary volume (SP 15.5 ± 2.1; OP 16.4 ± 2.9 mL/24 h). CONCLUSION: Cross-sex hormone therapy with E2EN/DHPA significantly modified body characteristics in male rats, producing a feminizing change without altering blood pressure or generating harmful metabolic parameters, but larger translational studies are still needed.


Assuntos
Progestinas , Roedores , Animais , Pressão Sanguínea/fisiologia , Peso Corporal , Estrogênios/farmacologia , Humanos , Masculino , Potássio/farmacologia , Progestinas/farmacologia , Ratos , Ratos Wistar , Sódio
2.
Conscious Cogn ; 101: 103332, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35453102

RESUMO

Fluctuating between external conscious processing and mind wandering is inherent to the human condition. Past research showed that in tasks requiring sustained attention, mind wandering episodes in which attention is directed internally constrain conscious processing of external stimuli. Conversely, conscious processing of internal stimuli is enhanced during mind wandering. To investigate this, we developed and administered a visuomotor tracking task in which participants were instructed to track the path of a stimulus on a screen with a mouse while responding to rare targets. Prior to reports of mind wandering we found the following: The P3 event-related potential component for targets, indicative of conscious stimulus processing, was attenuated at electrodes Cz and Pz. Moreover, alpha power, indicative of internal mental states, increased globally. Theta power increased along the centroparietal area, and beta decreased along right frontal and right centroparietal areas. Interestingly, trait mind wandering was positively correlated with delta power and gamma power, but negatively correlated with the theta-beta ratio. These results demonstrate that mind wandering is characterized by distinct neural signatures at both a state and trait level.


Assuntos
Atenção , Estado de Consciência , Eletroencefalografia , Humanos
3.
Andrology ; 7(5): 690-702, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207127

RESUMO

The primary job of the epididymis is to mature and protect the luminally transiting spermatozoa. Mounting evidence is showing that innate immune components [including Toll-like receptors (TLRs) and antimicrobial proteins, among which are ß-defensins] and inflammatory mediators, under the primary influence of androgens, participate in the cellular and molecular processes that define this tissue. Here, we present an overview of the contributions of these signaling pathway components during epididymal homeostasis and discuss the hypotheses as to their involvement in epididymitis, the most common urological inflammatory condition in men, frequently impairing their fertility. Drawing primarily from rodent models, we also focus on how the distribution and functional expression of innate immune components are differentially regulated in the prenatal developing epididymis, providing new insights into the disruption of these signaling pathways throughout the lifespan. Male infertility is caused by a variety of conditions, such as congenital malformations, genetic and endocrine disorders, exposure to environmental toxicants, and inflammatory/infectious conditions. More than one-third of infertile men with an idiopathic condition cannot currently be adequately diagnosed. Thinking about the innate immunity and inflammation context of the epididymis may provide new insights and directions as to how these systems contribute to male fertility, as well as also uncover urological and andrological outcomes that may aid clinicians in diagnosing and preventing epididymal pathologies.


Assuntos
Epididimo/metabolismo , Epididimite/patologia , Mediadores da Inflamação/metabolismo , Receptores Toll-Like/metabolismo , beta-Defensinas/metabolismo , Androgênios/metabolismo , Animais , Epididimo/patologia , Humanos , Imunidade Inata/imunologia , Infertilidade Masculina/patologia , Masculino , Transdução de Sinais/imunologia , Espermatozoides/metabolismo
4.
Transplant Proc ; 50(10): 3650-3655, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30586839

RESUMO

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.


Assuntos
Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cálcio/análise , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Peroxidase/sangue , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Prevalência , Estudos Prospectivos , Fatores de Risco , Proteína Amiloide A Sérica/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
5.
Transplant Proc ; 49(4): 848-851, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28457409

RESUMO

BACKGROUND: There are only 4 prior studies reporting on outcomes of liver transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation solution. Detection of negative predictors of LT using IGL-1 may help finding strategies to protect selected recipients at higher risk of graft failure and death. METHODS: Review of all consecutive adult patients who underwent a first whole-graft LT using IGL-1 at authors' institution from 2013 to 2016. Primary end point was graft failure within the first 90 postoperative days (PODs). Graft losses due to any cause (including all deaths with a functioning graft) were recorded as graft failures. RESULTS: Of all 100 patients included in this study, 37 were women; median age was 58 years (range 18-71). There were 12 graft losses during the first 90 PODs (including 3 cases of primary nonfunction of the liver allograft), and 10 of the 12 graft losses occurred on first 30 PODs. All 12 patients who experienced graft loss (including 1 patient who underwent liver retransplantation) died within the first 90 PODs. Of the total 100 patients, 14 experienced biliary complications. Univariate analysis revealed prolonged warm ischemic time (WIT) as the only predictor of 90-day graft failure (odds ratio = 23.5, confidence interval = 1.29-430.18, P = .03). The cutoff by receiver operating characteristic curve for WIT was 38 minutes (area under the curve = 0.70). Positive predictive value for WIT >38 minutes was 94.3%. CONCLUSIONS: LT using IGL-1 can be performed safely. Similar to prior reports on LT using other preservation solutions, prolonged WIT was associated with adverse outcomes.


Assuntos
Transplante de Fígado/métodos , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Adolescente , Adulto , Idoso , Doença Hepática Terminal/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Isquemia Quente , Adulto Jovem
6.
Phys Rev Lett ; 118(9): 095501, 2017 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-28306281

RESUMO

Radioactive ^{27}Mg (t_{1/2}=9.5 min) was implanted into GaN of different doping types at CERN's ISOLDE facility and its lattice site determined via ß^{-} emission channeling. Following implantations between room temperature and 800 °C, the majority of ^{27}Mg occupies the substitutional Ga sites; however, below 350 °C significant fractions were also found on interstitial positions ∼0.6 Å from ideal octahedral sites. The interstitial fraction of Mg was correlated with the GaN doping character, being highest (up to 31%) in samples doped p type with 2×10^{19} cm^{-3} stable Mg during epilayer growth, and lowest in Si-doped n-GaN, thus giving direct evidence for the amphoteric character of Mg. Implanting above 350 °C converts interstitial ^{27}Mg to substitutional Ga sites, which allows estimating the activation energy for migration of interstitial Mg as between 1.3 and 2.0 eV.

7.
Environ Int ; 88: 299-309, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26851498

RESUMO

Soil plays a central role in food safety as it determines the possible composition of food and feed at the root of the food chain. However, the quality of soil resources as defined by their potential impact on human health by propagation of harmful elements through the food chain has been poorly studied in Europe due to the lack of data of adequate detail and reliability. The European Union's first harmonized topsoil sampling and coherent analytical procedure produced trace element measurements from approximately 22,000 locations. This unique collection of information enables a reliable overview of the concentration of heavy metals, also referred to as metal(loid)s including As, Cd, Cr, Cu, Hg, Pb, Zn, Sb. Co, and Ni. In this article we propose that in some cases (e.g. Hg and Cd) the high concentrations of soil heavy metal attributed to human activity can be detected at a regional level. While the immense majority of European agricultural land can be considered adequately safe for food production, an estimated 6.24% or 137,000km(2) needs local assessment and eventual remediation action.


Assuntos
Exposição Ambiental , Contaminação de Alimentos/análise , Metais Pesados/análise , Poluentes do Solo/análise , Monitoramento Ambiental , União Europeia , Humanos
8.
Trop Biomed ; 32(2): 247-56, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26691253

RESUMO

Visceral leishmaniasis (VL) is a tropical neglected disease endemic in 98 countries and affects more than 58 000 individuals per year. Several serological tests are available for VL diagnosis, including an immunochromatographic (IC) test with the rK39 antigen and finger prick-collected blood, a rapid and low-invasive test. Here, we investigate the possibility to use saliva as a non-invasive source of biological material for the rK39 IC test. Blood samples from 84 patients with suspected VL were screened by the rK39 IC test, and 29 were confirmed as being infected by a positive rK39 IC test and the presence of amastigotes on smears slides or parasite DNA (detected using PCR-RFLP) from bone marrow aspirate. The rK39 IC test using saliva samples was positive for 17 of the 29 confirmed VL cases (58.6%). The amount of Leishmania-specific IgG or total IgG, as evaluated by an immunoenzymatic assay, was higher in the saliva of patients who had rK39 IC test positivity using saliva, whereas the amount of Leishmania-specific IgA or total IgA was similar to the healthy donors. These results suggest that saliva is not an appropriated material for diagnosing VL with this test.


Assuntos
Anticorpos Antiprotozoários/análise , Antígenos de Protozoários/imunologia , Cromatografia de Afinidade/métodos , Leishmania/imunologia , Leishmaniose Visceral/diagnóstico , Proteínas de Protozoários/imunologia , Saliva/imunologia , Adolescente , Adulto , Idoso , Sangue/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
10.
Tropical Biomedicine ; : 247-256, 2015.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-630447

RESUMO

Visceral leishmaniasis (VL) is a tropical neglected disease endemic in 98 countries and affects more than 58 000 individuals per year. Several serological tests are available for VL diagnosis, including an immunochromatographic (IC) test with the rK39 antigen and finger prick-collected blood, a rapid and low-invasive test. Here, we investigate the possibility to use saliva as a non-invasive source of biological material for the rK39 IC test. Blood samples from 84 patients with suspected VL were screened by the rK39 IC test, and 29 were confirmed as being infected by a positive rK39 IC test and the presence of amastigotes on smears slides or parasite DNA (detected using PCR-RFLP) from bone marrow aspirate. The rK39 IC test using saliva samples was positive for 17 of the 29 confirmed VL cases (58.6%). The amount of Leishmania-specific IgG or total IgG, as evaluated by an immunoenzymatic assay, was higher in the saliva of patients who had rK39 IC test positivity using saliva, whereas the amount of Leishmania-specific IgA or total IgA was similar to the healthy donors. These results suggest that saliva is not an appropriated material for diagnosing VL with this test.

11.
J Mol Neurosci ; 54(4): 748-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24969325

RESUMO

Primary familial brain calcification (PFBC) is identified by mineralization of the basal ganglia and other brain regions in the absence of known causes. The condition is often inherited in an autosomal dominant pattern and can manifest itself clinically with neuropsychiatric symptoms such as Parkinsonism, headaches, psychosis, and mood swings. Mutations in the SLC20A2 gene account for ~40% of inherited cases, and this gene encodes an inorganic phosphate transporter (PiT-2), a transmembrane protein associated with Pi homeostasis. The p.Y386X mutation in SLC20A2 was identified in a patient who presented migraines, brain calcification, and mild but chronic hypovitaminosis D. SLC20A2 c.1158C > G single-nucleotide heterozygous mutation results in a premature stop codon and a putative truncated protein of 385 amino acids. Proband parents do not present the mutation, which is also not present in major public SNP databases, suggesting a de novo sporadic trait. This study describes for the first time a de novo SLC20A2 mutation in a PFBC patient with migraine and mild hypovitaminosis D. This data further reinforces the pathogenic role of SLC20A2 mutations as causal factors in PFBC physiopathology.


Assuntos
Encéfalo/patologia , Calcinose/genética , Mutação , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Adulto , Calcinose/diagnóstico , Códon de Terminação , Feminino , Humanos , Masculino
12.
J Endocrinol Invest ; 36(11): 975-81, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23723040

RESUMO

BACKGROUND: We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. The entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. METHODS: A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. The entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. RESULTS: An additional p.C634Y germline mutation in the RET gene was identified in the reported family. The double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p.Y791F) in the RET gene in four other unrelated families. The overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. CONCLUSION: Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Medular/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Brasil , Calcitonina/sangue , Carcinoma Neuroendócrino , Feminino , Estudos de Associação Genética , Genótipo , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Feocromocitoma/genética
13.
Int J Cardiol ; 164(2): 221-6, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21784542

RESUMO

The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , Hepacivirus/patogenicidade , Hepatite C/epidemiologia , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/patologia , Feminino , Hepatite C/patologia , Hepatite C/virologia , Humanos , Inflamação/epidemiologia , Inflamação/patologia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
J Nanosci Nanotechnol ; 12(3): 2691-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22755110

RESUMO

Single-phase polycrystalline mixed nickel-zinc ferrites belonging to Ni0.5Zn0.5Fe2O4 were prepared on a nanometric scale (mean crystallite size equal to 14.7 nm) by chemical synthesis named the modified poliol method. Ferrite nanopowder was then incorporated into a natural rubber matrix producing nanocomposites. The samples were investigated by means of infrared spectroscopy, X-ray diffraction, scanning electron microscopy and magnetic measurements. The obtained results suggest that the base concentration of nickel-zinc ferrite nanoparticles inside the polymer matrix volume greatly influences the magnetic properties of nanocomposites. A small quantity of nanoparticles, less than 10 phr, in the nanocomposite is sufficient to produce a small alteration in the semi-crystallinity of nanocomposites observed by X-ray diffraction analysis and it produces a flexible magnetic composite material with a saturation magnetization, a coercivity field and an initial magnetic permeability equal to 3.08 emu/g, 99.22 Oe and 9.42 x 10(-5) respectively.

15.
Clin Exp Dermatol ; 37(2): 122-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22103463

RESUMO

BACKGROUND: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission routes. About 30% of HIV-positive patients are co-infected with HCV. Of the various HCV-related extrahepatic events, those involving the skin may be the first sign of infection. AIM: To specify the skin presentations in patients co-infected with HIV and HCV (co-infected patients; CP) and compare them with those found in patients with HCV mono-infection (mono-infected patients; MP). METHODS: This was a cross-sectional study, in which the studied population consisted of MP and CP from a tertiary hospital in the South of Brazil, who underwent complete skin examination and laboratory tests. RESULTS: In total, 201 patients were assessed, of whom 108 were CP, and 93 were MP. Pruritus tended to be more common in MP. MP also had significantly more dermatological conditions (mean of 5.2) than CP (mean of 4.5). In total, 104 different skin diseases were identified. There was a higher prevalence of infectious diseases and pigmentation disorders, such as verruca vulgaris and facial melasma, in CP, whereas trunk and facial telangiectasias, palmar erythema, and varicose veins were more common in MP. CONCLUSION: We found a high prevalence of skin conditions both in MP and in CP; however, the patterns of the dermatological conditions were different. CP were found to have significantly fewer skin lesions than MP, but had a higher prevalence of infectious and pigmentation disorders. By contrast, vascular conditions were more common in MP.


Assuntos
Coinfecção/complicações , Infecções por HIV/complicações , Hepatite C/complicações , Dermatopatias/etiologia , Adulto , Idoso , Brasil/epidemiologia , Coinfecção/virologia , Estudos Transversais , Feminino , Infecções por HIV/virologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Dermatopatias/epidemiologia , Dermatopatias/patologia
16.
Transplant Proc ; 43(10): 3634-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22172818

RESUMO

BACKGROUND AND AIMS: Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis. MATERIALS AND METHODS: Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW+SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-ß1 and angiotensin II AT1 receptor. RESULTS: AST was significantly lower during cold storage with UW than with the older media (P=.001); ALT was lower in the FBP group (P=.023) and LDH was lower in the FBP and SNAC groups (P=.007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P=.008 and P=.006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P=.004). Renin levels were significantly lower in the FBP group (P=.022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-ß1 or AT1 receptor. CONCLUSION: In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.


Assuntos
Cirrose Hepática/prevenção & controle , Transplante de Fígado/efeitos adversos , Fígado/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Acetilcisteína/análogos & derivados , Acetilcisteína/farmacologia , Adenosina/farmacologia , Alanina Transaminase/sangue , Alopurinol/farmacologia , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Catalase/metabolismo , Modelos Animais de Doenças , Frutosedifosfatos/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Insulina/farmacologia , L-Lactato Desidrogenase/sangue , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Soluções para Preservação de Órgãos/química , Rafinose/farmacologia , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/sangue , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo
17.
Nitric Oxide ; 25(3): 360-5, 2011 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-21820071

RESUMO

Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100µM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFß-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFß-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.


Assuntos
Acetilcisteína/análogos & derivados , Desdiferenciação Celular/efeitos dos fármacos , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Acetilcisteína/síntese química , Acetilcisteína/química , Acetilcisteína/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Camundongos
18.
Transplant Proc ; 43(5): 1468-73, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693219

RESUMO

BACKGROUND: Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers. METHODS: Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy. RESULTS: During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP. CONCLUSION: FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury.


Assuntos
Frutosedifosfatos/administração & dosagem , Fígado , Mitocôndrias Hepáticas/efeitos dos fármacos , Preservação Biológica , Animais , Frutosedifosfatos/farmacologia , Masculino , Mitocôndrias Hepáticas/patologia , Ratos , Ratos Wistar , Soluções
19.
Transplant Proc ; 42(10): 4491-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21168722

RESUMO

BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is among the major causes of poor graft function early after liver transplantation that adversely influences patient survival. A variety of mediators have been implicated in the pathogenesis of I/R vascular injury, including nitric oxide (NO). Because of the beneficial effects of NO during preconditioning and reperfusion, strategies to prevent or ameliorate I/R injury through the stimulation of hepatic NO production are an area of significant clinical interest. We evaluated the role of S-nitroso-N-acetylcysteine (SNAC) as an NO donor in the prevention of liver I/R injury in an animal model. METHODS: Adult male Wistar rats were randomly assigned to 3 experimental groups containing 5 animals each: the University of Wisconsin (UW) solution group; SNAC solution group; and SNAC-containing UW solution (SNAC+UW) group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined in samples of the cold storage solution at 2, 4, and 6 hours of preservation. After 6 hours of cold storage, We applied a 15-minute reperfusion period. Thereafter, the reperfusion was interrupted with blood samples obtained to measure AST, ALT, LDH, and thiobarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis, and to determine of TBARS, catalase, and glutathione levels. RESULTS: During cold preservation, AST and LDH were significantly lower among the SNAC than the UW group or the SNAC+UW group (P = .004 and P = .03, respectively). ALT was comparable among the groups (P = .3). After reperfusion, serum levels of AST, ALT, and LDH, as well as of hepatic TBARS and catalase showed no differences among the groups. Glutathione concentration was lower in the SNAC and SNAC+UW group (P < .001) compared with the UW group. We did not observe histologic signs of preservation injury. CONCLUSION: The SNAC solution showed a greater protective effect to preserve rat livers during cold storage, but it was comparable with UW.


Assuntos
Acetilcisteína/análogos & derivados , Fígado/irrigação sanguínea , Doadores de Óxido Nítrico/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Acetilcisteína/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Transplant Proc ; 39(10): 3015-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18089312

RESUMO

Isolated liver perfusion has been used to evaluate the beneficial effects of several agents. In the present study, we developed a model using a recipient rat to reperfuse harvested livers in an ex situ, in vivo recirculating system. A total of 25 reperfusion procedures using adult male Wistar rats as donors and recipients were done. The preservation of the livers was performed with University of Wisconsin solution for 6 hours. Thereafter, the liver was reperfused with blood from another rat. We believe that the model presented herein offers an alternative method to evaluate early hepatocellular damage or hepatic microcirculation.


Assuntos
Circulação Hepática , Sistema Porta/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Reperfusão/métodos , Animais , Modelos Animais de Doenças , Masculino , Modelos Biológicos , Sistema Porta/patologia , Sistema Porta/fisiopatologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
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