RESUMO
Introduction: The COVID-19 pandemic led to the transition to remote work, triggering variations in stress and physical activity (PA), associated with context-specific instability. Objective: To identify the association between perceived stress (PS) and the level of physical activity (PA) and explore its relationship with the sociodemographic, family, work and individual characteristics of professors working remotely during the COVID-19 pandemic. Material and methods: Cross-sectional analytical study based on a virtual survey of professors. PS was assessed using the Perceived Stress Scale (PSS-14), and PA using an International Physical Activity Questionnaire. The prevalence of high PS and the association with PA were estimated using a Poisson regression analysis with robust variance that estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with a 95% confidence interval (CI). Five models were developed to assess associations of PS and PA with sociodemographic, family, work, and individual variables. Results: The information of 191 professors was analyzed; 39.27% were women, aged 52 (41-60). The prevalence of high stress was 47.12%. The age and being head of household did not show significant individual associations with PS. However, the regression analysis assessing the association of PS and other factors showed that compared to the moderate PA group, a statistically significant association was found between stress and high PA (aPR = 0.19; 0.06-0.59), low PA (aPR = 1.43; 1.02-2.01), mainly influenced by age, being head of household and sleep quality. Conclusion: Stress was associated with PA level, family and individual factors. These findings allow identifying characteristics, such as being head of household, age and quality of sleep among teachers, as being associated with a higher probability of having high stress. Subsequent studies should consider the role of individuals and working conditions as part of occupational health surveillance, given the presence of hybrid education in the education sector.
Assuntos
Tuberculose Latente , Prisões , Humanos , Prevalência , Fatores de Risco , Teste TuberculínicoRESUMO
BACKGROUND: Electrical bioimpedance (BI) has been used to indirectly measure steatosis. This method has not yet been established in the clinics thus experimental studies are needed in big animals. We assessed BI to measure liver steatosis in porcine animals. METHODS: Twelve large-white × Landrace pigs weighing 35 kg were allocated to a study (n = 9) and a control group (n = 3). A special diet was used to promote steatosis among the study group: methionine deficient and choline-restricted diet that contains supplements of cholesterol, collate and excess of saturated fat. Control group animals were fed a normal diet. A new tetrapolar electrode model was used for BI measurement, which were performed during open laparotomy by inserting a probe into one of the lobes. Measurements were done in the third and fourth segments of the pig liver, placing the probe either on the surface or inserted into the parenchyma of the liver. Open biopsies were obtained at the end of the measurements. Histological samples were processed and stained with hematoxylin-eosin to estimate macrosteatosis. Pearson correlation coefficient between BI and percentage steatosis were calculated at different frequencies. RESULTS: After 4 months of the special diet all the animals in the study group developed steatosis (90% to 20%), whereas none of the control group was affected. Pearson correlation coefficients between BI and percentage of steatosis were significant (0.877-0.878) with the best correlations obtained with a probe placed on the fourth segment of the liver surface and the best frequency to perform the measurements being 50 and 75 kHz. CONCLUSIONS: BI is an accurate, fast method for steatosis measurements, that is easier and cheaper than either open or needle biopsy.
Assuntos
Fígado Gorduroso/diagnóstico , Animais , Biópsia , Deficiência de Colina/complicações , Dieta Hiperlipídica , Modelos Animais de Doenças , Impedância Elétrica , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Metionina/deficiência , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Suínos , Fatores de TempoRESUMO
PURPOSE: The current study objective was to compare blood platelet indices in full-term small-for-gestational-age newborns (SGA) and full-term appropriate-for-gestational-age newborns (AGA). MATERIALS/METHODS: We introduced to our study 61 SGA newborns (31 females and 30 males) and 70 eutrophic infants (32 females and 38 males). The SGA newborns were divided into two groups: those weighing less than the 5th centile: 35 infants (16 females and 19 males) and those between the 5th and 10th centiles: 26 infants (15 females and 11 males). Platelet indices were estimated in blood samples collected from the umbilical artery. RESULTS: SGA demonstrated a decreased count of blood platelets (238×103/µ) as compared with AGA (286×103/µL), p=0.0001. Platelet hematocrit (PTC) also showed differences in both groups (SGA=0.19% vs. AGA=0.22%; p=0.0005). Mean platelet volume (MPV) was higher in SGA (8.25fl) as compared with AGA (7.84fl); p=0.008. Large platelet count (LPLT) was higher in AGA 6.26% vs. SGA=4.75%; p=0.01. Platelet distribution width (PDW) was found to be nearly the same (SGA=47%, AGA=46%). PDW was higher in SGA newborns < 5th centile (43%) as compared with SGA infants between the 5th and 10th centiles (52%); p=0.008. CONCLUSIONS: A decreased blood platelet count, platelet hematocrit and large metabolically active platelet count, which in addition to reduced synthesis and excessive consumption of coagulation factors in states of hiperclotting is characteristic of IUGR, enhances the possibility of bleeding complications and increases the risk of infections. From a clinical point of view, it is important to take into consideration the degree of intrauterine hypotrophy during the evaluation of hemostatic disorders.
Assuntos
Plaquetas/citologia , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Contagem de Plaquetas , Peso ao Nascer , Coagulação Sanguínea , Feminino , Hematócrito , Hemostasia , Humanos , Recém-Nascido , Masculino , Risco , Fatores SexuaisRESUMO
BACKGROUND: Multiple sclerosis (MS) has a unique geographical distribution that reflects both genetic and environmental factors. Many studies have shown a positive correlation between MS frequency and latitude across both large and small geographical regions. However, scarce data have been published on the epidemiology of MS in Latin America and no study has evaluated latitudinal variation. OBJECTIVE: To evaluate the effect of latitude on MS prevalence in Latin America. METHODS: We conducted a systematic review of MS prevalence during January 2011. Prevalence rates were collected from eligible publications. The effect of latitude on prevalence was analyzed using linear regression. RESULTS: A total of ten studies were eligible for analysis, corresponding to six countries, spanning from Panama to Argentina. The crude prevalence of MS ranged from 0.75 to 21.5 per 100,000. We found a strong and significant association between prevalence and latitude (r(2) 0.8; p < 0.001) and determined an increase in prevalence of 0.33 per 100,000 per degree latitude. CONCLUSION: Our findings suggest a latitudinal prevalence gradient of MS in Latin American countries between Panama and Argentina.
Assuntos
Esclerose Múltipla/epidemiologia , Humanos , América Latina/epidemiologia , Prevalência , Fatores de RiscoRESUMO
PURPOSE: Apoptosis of activated T lymphocytes is essential to immunoregulation and its abnormalities have been observed in immune system disorders and persistent infections. To asses Borrelia burgdorferi influence on the susceptibility of T lymphocytes to apoptosis, we have measured expression of the Fas death receptor on these cells after incubation with live B. burgdorferi. MATERIAL AND METHODS: Peripheral blood mononuclear cells from 23 LD patients (18 with Lyme arthritis, 5 with neuroborreliosis) and 13 healthy controls (C) were incubated for 48 hours with and without live B. burgdorferi spirochetes: B. afzelii, B. garinii or B. burgdorferi sensu stricto. After incubation, Fas expression on CD3+ cells was measured cytometrically with FITC-labeled monoclonal antibody. RESULTS: Median fraction of Fas-expressing T lymphocytes increased under incubation with B. burgdorferi, with more cells expressing Fas after incubation with B. burgdorferi sensu stricto than with B. garinii. There was a tendency for a higher expression of Fas on T lymphocytes from LD patients then from controls, both in unstimulated and B. burgdorferi-stimulated cultures, but it did not reach a level of statistical significance. CONCLUSIONS: B. burgdorferi seems to increase Fas expression on CD3+ T lymphocytes, which may render these cells more susceptible to apoptosis. This effect is stronger for B. burgdorferi s.s. than for B. garinii genospecies.
Assuntos
Borrelia burgdorferi/patogenicidade , Neuroborreliose de Lyme/imunologia , Neuroborreliose de Lyme/metabolismo , Linfócitos T/imunologia , Receptor fas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Complexo CD3/metabolismo , Células Cultivadas , Feminino , Humanos , Doença de Lyme/imunologia , Doença de Lyme/metabolismo , Neuroborreliose de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismoRESUMO
Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).
Assuntos
Dieta Mediterrânea , Saúde , Óleos de Plantas , Envelhecimento/psicologia , Doenças Cardiovasculares/epidemiologia , Doença Crônica , Cognição/fisiologia , Consenso , Diabetes Mellitus/epidemiologia , Expectativa de Vida , Síndrome Metabólica/epidemiologia , Neoplasias/epidemiologia , Obesidade/epidemiologia , Azeite de Oliva , Óleos de Plantas/química , Medição de Risco , Fatores de RiscoRESUMO
The aim of this study was to evaluate platelet activation in gastric cancer patients with regard to histopathological classification and the presence of distant metastases, by using platelet morphological parameters: MPV, L-PLT, MPC, as well as quantitative evaluation of surface receptor expression: CD41a, CD61, CD42b, CD62P, by flow cytometry at the resting state and after TRAP activation. In gastric cancer patients higher values of MPV and LP, as well as decreased MPC values were determined. Quantitative evaluation of surface antigen expression also revealed higher number of CD41a, CD61 and CD62P molecules, as compared with the platelets in the control group. Significant decrease of CD42b molecules' number after TRAP incubation, and the increased CD41a, CD61 and CD62P expression also point to the retained reactivation capacity of platelets. Good correlation between morphological parameters and the number of CD62P molecules indicates the usefulness of routine tests in evaluation of platelet activation.
Assuntos
Adenocarcinoma/metabolismo , Plaquetas/metabolismo , Ativação Plaquetária/fisiologia , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/citologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: The current study objective was to compare blood platelet indices in preterm newborns (PTN) and full term newborns (FTN). MATERIALS AND METHODS: We introduced to our study 51 PTN (25 females, 26 males) and 55 FTN (25 females, 30 males). Platelet indices were estimated in blood samples collected from the umbilical artery. RESULTS: PTN demonstrated a decreased count of blood platelets (197 x 103/microL) as compared to FTN (287 x 103/microL), p=0.0001. Platelet hematocrit (PCT) also showed substantial differences in both groups (PTN=0.16% vs. FTN=0.22%; p=0.001). Mean platelet volume (MPV) was found to be nearly the same (PTN=8.02 fl, FTN=7.79 fl). Platelet distribution width (PDW) was higher in PTN (50.64%) than in FTN (46.54%), p=0.021. Large platelet count (LPLT) was diminished in PTN (5.23%) in comparison with FTN (6.12 %). CONCLUSIONS: A decreased count of blood platelets, platelet hematocrit and increased platelet distribution width may result from a low gestational age or a dysfunction of megakaryocytes and the placenta. Blood platelet indices may be vital in the diagnosis of haemostatic disorders.
Assuntos
Plaquetas/citologia , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Tamanho Celular , Feminino , Hematócrito , Humanos , Masculino , Megacariócitos/citologia , Contagem de Plaquetas , Fatores Sexuais , Artérias UmbilicaisRESUMO
Lipopolysaccharide (LPS) is an endotoxin causing sepsis. Studies from our laboratory revealed impaired intestinal absorption of L-leucine and D-fructose in LPS-treated rabbits. The aim of this study was to examine intestinal D-galactose transport following intravenous administration of LPS in the rabbit and to identify the cellular mechanisms driving this process. Endotoxin treatment diminished the buildup of D-galactose in intestinal tissue, the mucosal to serosal transepithelial flux of the sugar and its uptake by brush border membrane vesicles (BBMVs). Intracellular signaling pathways associated with protein kinase C (PKC), protein kinase A (PKA), p38 mitogen-activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK), MAPK/extracellular signal-regulated kinases 1 and 2 (MEK1/2) and proteasome were found to be involved in this reduction in sugar uptake. Na(+)/glucose cotransporter 1 (SGLT1) protein levels in BBMVs were lower for LPS-treated animals than control animals. These findings indicate that LPS inhibits the intestinal absorption of D-galactose via a complex cellular mechanism that could involve posttranscriptional regulation of the SGLT1 transporter.
Assuntos
Endotoxemia/metabolismo , Galactose/metabolismo , Mucosa Intestinal/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Northern Blotting , Western Blotting , Butadienos/farmacologia , Endotoxemia/induzido quimicamente , Galactose/farmacocinética , Imidazóis/farmacologia , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Nitrilas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Piridinas/farmacologia , Coelhos , Transportador 1 de Glucose-Sódio/genética , Transportador 1 de Glucose-Sódio/metabolismoRESUMO
Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-alpha seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-alpha on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-alpha decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF-alpha inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved.
Assuntos
Galactose/antagonistas & inibidores , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Antracenos/administração & dosagem , Antracenos/farmacologia , Northern Blotting , Western Blotting , Membrana Celular/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Indóis/administração & dosagem , Indóis/farmacologia , Injeções Intravenosas , Absorção Intestinal/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Maleimidas/administração & dosagem , Maleimidas/farmacologia , Microvilosidades/efeitos dos fármacos , Microvilosidades/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Inibidores de Proteassoma , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Coelhos , Sepse/metabolismo , Transportador 1 de Glucose-Sódio/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
PURPOSE: The aim of the present study was to assess the effect of tumor advancement and surgery treatment on P-selectin expression (CD 62P), level of sP-selectin and platelet count. MATERIAL AND METHODS: The study involved 27 colorectal cancer patients (CRC). They were divided into two groups: group B1--18 patients (T2-3N0M0) and group B2--9 patients (T2-4N+M0). In CRC patients the blood was collected three times: 1) before surgery (A0), 2) 3 days after surgery and 3) 12 days after surgery. RESULTS: The results obtained showed that CD 62P expression in CRC patients was twice higher (5.36%) than in control (2.58%) (p < 0.001). The level of sP-selectin concentration in both groups (B1--74.22 ng/mL and B2--70.33 ng/mL) was significantly higher than in control (46.01 ng/mL) (p < 0.001). There was no significant differences in CD 62P expression, plasma sP-selectin concentration and in PLT count between group B1 and B2. Three days after surgery in both groups of patients we observed decreased CD 62P expression and sP-selectin level compared to the results before surgery (p < 0.05). Twelve days after surgery we found an increase in the CD 62P-positive platelets and sP-selectin in group B1 and B2. We found positive correlation between plasma sP-selectin concentration and PLT count in CRC. CONCLUSIONS: In the current study on colorectal cancer we observed platelet hyperactivation, irrespective of tumor clinical advancement. Surgical procedure, in the early period following radical tumor resection, does not totally eliminate platelet activation in vivo.
Assuntos
Plaquetas/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Selectina-P/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de PlaquetasRESUMO
Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.
Assuntos
Apolipoproteínas E/genética , Ácido Linoleico/química , Ácidos Linoleicos Conjugados/metabolismo , Proteômica/métodos , Ração Animal , Animais , Aterosclerose/patologia , Glicemia/metabolismo , Western Blotting , Composição Corporal , Peso Corporal , Citosol/metabolismo , Dieta , Ácidos Graxos/metabolismo , Ligação Genética , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Inflamação , Insulina/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Oxigênio/metabolismo , Perfusão , Análise de Componente Principal , Biologia de Sistemas , Triglicerídeos/metabolismoRESUMO
1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Neoplasias/prevenção & controle , Óleos de Plantas , Envelhecimento/efeitos dos fármacos , Gorduras Insaturadas na Dieta/farmacologia , Medicina Baseada em Evidências , Humanos , Azeite de Oliva , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/química , Óleos de Plantas/farmacologiaRESUMO
Tumor necrosis factor-alpha (TNF-alpha) is an important immunoregulatory cytokine involved in septic responses during bacterial infection. The aim of this study was to examine the effect of TNF-alpha on the transport of D-fructose across rabbit jejunum. A sepsis condition was evoked by intravenous administration of this cytokine and hematological and plasma parameters were analyzed and body temperature was recorded. D-Fructose transport was assayed in rabbit jejunum. Sugar absorption in TNF-alpha treated rabbits was lower than in control animals. TNF-alpha decreased both the mucosal-to-serosal transepithelial flux and the transport across brush border membrane vesicles of D-fructose. The number of D-fructose transporters (GLUT5) was analyzed by Western blot in an attempt to explain this inhibition. TNF-alpha treated animals had lower levels of GLUT5, indicating a reduction in the expression of GLUT5 protein and therefore in transport capacity. The inhibition could also be related with the secretagogue effect of TNF-alpha on the gut since the intracellular tissue water was affected and the absence of chloride ion in the incubation medium partly removed the cytokine inhibition on sugar intestinal transport in treated rabbits. Finally, in terms of possible mediators involved in the TNF-alpha effect, nitric oxide and prostaglandins appeared to play a role in the inhibition of D-fructose intestinal uptake.
Assuntos
Frutose/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , Enterócitos/ultraestrutura , Inibidores Enzimáticos/farmacologia , Transportador de Glucose Tipo 5 , Indometacina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Masculino , Microvilosidades/efeitos dos fármacos , Microvilosidades/metabolismo , Proteínas de Transporte de Monossacarídeos/efeitos dos fármacos , Proteínas de Transporte de Monossacarídeos/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Coelhos , Sepse/metabolismoRESUMO
PURPOSE: Previous in vitro studies have demonstrated that a potent antihypertensive agent ebelactone B inhibits cathepsin A/deamidase activity. The aim of our studies was to assess the effects of this inhibitor on cathepsin A activity in intact platelets and on platelet activation events. MATERIAL AND METHODS: PRP or washed human platelets from healthy volunteers were pre-incubated with different concentrations of ebelactone B (1-10 microM) for 10-60 min. Cathepsin A activity in platelets was assayed colorimetrically using Cbz-Phe-Ala at pH 5.5. Expression of platelet activation markers GpIIb/IIIa and P-selectin on non-activated or agonist-activated platelets (ADP, TRAP) was measured by flow cytometry. RESULTS: Pre-treatment of platelets for up to 60 minutes with 10 mumol/l ebelactone B, that effectively inhibits cathepsin A activity in platelet lysate, did not affect this activity in intact platelets. Exposure of PRP to 10 mumol/l ebelactone B alone, or before platelet activation with ADP or TRAP caused only a small but non-significant increase in P-selectin and GpIIb/IIIa expression on the platelet surface, as demonstrated by flow cytometry analysis. CONCLUSIONS: The lack of cathepsin A inhibition by ebelactone B in intact platelets indicates that this inhibitor does not enter cells. Therefore, a potential antihypertensive significance of this compound may be through the inhibition of cathepsin A/deamidase released from activated or damaged cells. In vitro ebelactone B seems to exert no effect on platelet activation. Further studies are underway to determine whether ebelactone B administration affects platelet activation events in experimental model of hypertension in rats.
Assuntos
Anti-Hipertensivos/farmacologia , Plaquetas/metabolismo , Catepsina A/metabolismo , Lactonas/farmacologia , Ativação Plaquetária/fisiologia , HumanosRESUMO
BACKGROUND/AIMS: Blood platelets are cells that quite often undergo damage in chronic liver diseases. Endotoxemia and hyperkinetic circulation influence platelets in an active manner. The role of platelets in the development of hepatitis and liver fibrosis is speculative. The aim of the study was to determine the influence of chronic liver diseases on platelets morphologic parameters, their secretory activity and P-selectin expression. METHODOLOGY: The examination was completed in the group of 29 patients with chronic hepatitis and 27 with liver cirrhosis of postinflammatory etiology (HBV, HCV). Liver biopsies were carried out in all patients. Thirty-two healthy individuals were the control group. Platelets morphological parameters (number, volume, platelet crit, micro- and macrothrombocyte fraction) were estimated. beta-thromboglobulin concentration and platelet factor 4 in blood serum as well as P-selectin expression on resting platelets and after thrombin activation were also examined. RESULTS: Number, volume, and platelet crit decreased with the advancement of a liver disease. Megathrombocyte fraction increased inversely with the severity of liver damage. The concentration of beta-thromboglobulin and platelet factor 4 alpha-granule contents in blood serum was higher 2- and 7-times, respectively than in healthy controls. P-selectin expression on resting platelets was considerably higher. After stimulation with thrombin, P-selectin expression was equal (chronic hepatitis) or higher (liver cirrhosis) than in the control. CONCLUSIONS: There are changes of platelet morphological parameters, with accompanying megathrombocyte fraction increase that occur in chronic liver diseases. Thrombocytes in chronic liver diseases and liver cirrhosis are more activated. Platelet sensitivity to stimuli in these ailments is higher (liver cirrhosis) than in the healthy controls.
Assuntos
Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Cirrose Hepática/sangue , Selectina-P/sangue , Ativação Plaquetária/fisiologia , Fator Plaquetário 4/metabolismo , beta-Tromboglobulina/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Contagem de PlaquetasRESUMO
It was found that 10 microM tamoxifen induced apoptosis and a significant (approximately 50%) depletion of beta 1 integrin levels in human breast cancer cells. Estradiol-treated MCF-7 cells exhibited exceptional viability and adherence, high levels of beta 1 integrin and increased (by 100%) collagen biosynthesis. Pretreatment of MCF-7 cells with 1 nM estradiol prevented tamoxifen-induced cell death, loss of cell adherence and decrease in beta 1 integrin level. Tamoxifen and estradiol had an opposite effect on the beta 1 integrin level and adherence in breast cancer cells, suggesting that the decrease in the beta 1 integrin level may be an early event during tamoxifen-induced apoptosis in breast cancer cells.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Colágeno/biossíntese , Estradiol/farmacologia , Integrina beta1/biossíntese , Tamoxifeno/farmacologia , Neoplasias da Mama/metabolismo , Adesão Celular/efeitos dos fármacos , Humanos , Integrina beta1/análise , Necrose , Células Tumorais CultivadasRESUMO
The present study describes the effects of several high-fat low-cholesterol antiatherogenic diets on the hepatic lipid peroxidation and hepatic antioxidant systems in apolipoprotein E-deficient mice. Eighty mice were distributed into five groups and fed with regular mouse chow or chow supplemented with coconut, palm, olive and sunflower seed oils. After ten weeks, they were sacrificed and the livers were removed so that lipid peroxidation and alpha-tocopherol concentrations, and superoxide dismutase, glutathione peroxidase and glutathione reductase activities could be measured. The size of the atherosclerotic lesions in the aortas was also measured. Results showed that the diets supplemented with olive oil, palm oil or sunflower seed oil significantly decreased the size of the lesion. However, there was an association between those mice that were on diets supplemented with palm or coconut oils and a significant increase in hepatic lipid peroxidation. This association was not found in animals fed with olive or sunflower seed oils, the diets with the highest content of vitamin E. The dietary content of vitamin E was significantly correlated (r = 0.98; p < 0.05) with the hepatic concentration of this compound. Our study suggests that the high content of vitamin E in olive oil or sunflower seed oil may protect from the undesirable hepatotoxic effects of high-fat diets in apo E-deficient mice and that this should be taken into account when these diets are used to prevent atherosclerosis.