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Braz. j. med. biol. res ; 50(6): e5954, 2017. tab, graf
Article in English | LILACS | ID: biblio-839306


Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250–300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Animals , Male , Benzofurans/pharmacology , Drugs, Chinese Herbal/pharmacology , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Protective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion Injury/drug therapy , Blood Urea Nitrogen , Creatinine/metabolism , Inflammation/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Peroxidase/drug effects , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Signal Transduction
Braz. j. med. biol. res ; 49(5): e5129, 2016. tab, graf
Article in English | LILACS | ID: biblio-951677


This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin.

Animals , Male , Rats , Insulin Resistance/genetics , Dietary Fats/administration & dosage , Glucose Transporter Type 4/metabolism , Lipid Metabolism/genetics , Muscle Proteins/metabolism , Physical Conditioning, Animal , Time Factors , Transcription Factors , Insulin Resistance/physiology , Dietary Fats/metabolism , Random Allocation , Gene Expression Regulation , Rats, Sprague-Dawley , Glucose Transporter Type 4/genetics , Real-Time Polymerase Chain Reaction , Muscle Proteins/genetics
Braz. j. med. biol. res ; 49(12): e5647, 2016. tab, graf
Article in English | LILACS | ID: biblio-828176


The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1β-positive cells in the NP group was increased, with higher integral optical density than the control group. Compared to the control group, the serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein in the newborn rats of the NP group were significantly increased. There was no significant difference in the serum level of high-density lipoprotein or cholesterol between the groups. Perinatal exposure to NP can interfere with the in vivo estrogen and progesterone levels of pregnant rats, resulting in threatened abortion, dystocia and other adverse delivery outcomes. High liver and serum NP levels of the newborn rats led to alteration of liver tissue structure and function. The NP-induced hepatotoxicity is probably mediated by inflammatory cytokines TNF-α and IL-1α.

Animals , Female , Rats , Chemical and Drug Induced Liver Injury/etiology , Phenols/toxicity , Animals, Newborn , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Interleukin-1/analysis , Prenatal Exposure Delayed Effects/chemically induced , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/analysis
Braz. j. med. biol. res ; 47(1): 24-34, 01/2014. graf
Article in English | LILACS | ID: lil-697676


Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Humans , Antineoplastic Agents/pharmacology , Cell Movement/genetics , Cell Proliferation/genetics , /genetics , Fanconi Anemia Complementation Group F Protein/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Resistance , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , RNA Interference , RNA, Small Interfering
West Indian med. j ; 63(1): 112-114, Jan. 2014. ilus
Article in English | LILACS | ID: biblio-1045801


Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach with dense lymphocytic infiltration. More than 80% of LELGCs are positive for the Epstein-Barr virus (EBV). Here, we report a 64-year old Chinese man with swallowing discomfort while eating food. Endoscopy and computed tomography both showed a submucosal lesion at the lesser curvature of the upper gastric body. The first diagnostic impression was a gastrointestinal stromal tumour. Subsequently, the patient received a wedge resection of the stomach. On histopathological examination, the tumour was found to consist of small nests of neoplastic cells within dense lymphocytic infiltration. Additionally, most of the neoplastic cells were positive for cytokeratin and Epstein-Barr virus-encoded RNA (EBER). Subsequently, the diagnosis of LELGC was made. We believe that physicians should be aware of the diagnosis of submucosal gastric lesions, particularly in older male patients.

El carcinoma gástrico de tipo linfoepitelioma (CGLE) es una neoplasia rara del estómago con una infiltración linfocítica densa. Más del 80% de los CGLEs son positivos al virus de Epstein-Barr (EBV). Aquí reportamos el caso de un paciente chino de 64 años, que sentía malestar al efectuar la deglución de alimentos. Tanto la endoscopia como la tomografía computarizada mostraron una lesión submucosa en la curvatura menor de la parte superior del cuerpo gástrico. La primera impresión diagnóstica fue de un tumor del estroma gastrointestinal Posteriormente, al paciente se le hizo una resección en cuña del estómago. En el examen histopatológico, se halló que el tumor consistía de pequeños nidos de células neoplásicas dentro de una infiltración linfocítica densa. Además, la mayoría de las células neoplásicas eran positivas a la citoqueratina y al ARN codificado por el virus de Epstein-Barr (EBER). Posteriormente, se realizó el diagnóstico de CGLE. Creemos que los médicos deben tomar conciencia del diagnóstico de las lesiones submucosas gástricas, especialmente en los pacientes mayores hombres.

Humans , Male , Middle Aged , Stomach Neoplasms/diagnosis , Carcinoma/diagnosis , Herpesvirus 4, Human/genetics , Stomach Neoplasms/virology , RNA, Viral/analysis , Carcinoma/virology , Lymphocytes/pathology
Braz. j. med. biol. res ; 41(7): 589-595, July 2008. ilus, tab
Article in English | LILACS | ID: lil-489521


Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters ÄH0 and ÄS0 were 68.04 kJ/mol and 319.42 J·mol-1·K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (è) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85 percent, whereas for the NZ-105-BSA system, it is 53 percent, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine_BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.

Animals , Cattle , Dihydropyridines/chemistry , Nitrophenols/chemistry , Serum Albumin, Bovine/chemistry , Circular Dichroism , Models, Chemical , Organophosphorus Compounds/chemistry , Spectrometry, Fluorescence , Thermodynamics
Asian Pac J Allergy Immunol ; 1994 Jun; 12(1): 15-20
Article in English | IMSEAR | ID: sea-36693


Bronchial hyperresponsiveness (BHR) to methacholine were evaluated in 47 asthmatic children before and after allergen-specific immunotherapy (IT) by using the forced oscillation method. Eighty-seven percent (13/16) of BHR-negative patients had good clinical response after 1-year immunotherapy while there were only 45% (14/31) in the BHR-positive asthmatic children (p < 0.02). In the BHR-positive group, the relationship between clinical response and the change of nonspecific bronchial sensitivity was further analyzed. In those of good clinical response (IT responder), the tolerance dose of methacholine was significantly increased from 0.78 +/- 0.71 to 4.11 +/- 4.65 mg/ml (p < 0.05), and bronchial sensitivity increased from 1.14 +/- 1.42 U to 7.55 +/- 9.55 U (p < 0.02). In those with no clinical improvement (IT non-responder), there were no significant changes in either methacholine tolerance dose or bronchial sensitivity. With respect to other parameters, such as Grs, PD35, and SGrs, the differences between before and after immunotherapy were similar in both the IT responders and IT non-responders. These results suggest that asthmatic children with different bronchial sensitivity had different responses to immunotherapy and the clinical improvement after immunotherapy is significantly related to the improvement of bronchial hyperresponsiveness.

Adolescent , Animals , Antigens/immunology , Antigens, Dermatophagoides , Asthma/physiopathology , Bronchial Hyperreactivity/diagnosis , Bronchial Provocation Tests , Child , Glycoproteins/immunology , Humans , Immunotherapy , Male , Methacholine Chloride , Middle Aged , Mites/immunology , Respiratory Function Tests/statistics & numerical data
Braz. j. med. biol. res ; 27(2): 195-201, Feb. 1994. ilus
Article in English | LILACS | ID: lil-138285


The genetic lesion in paroxysmal nocturnal hemoglobinuria (PNH) cells resides in a DNA element that 1) encodes a product required for assembly of GlcNAc-inositol phospholipid and 2) is commonly affected in different patients. In this study, three alternative mRNA transcripts (1600, 1200 and 950 bp) that derive from this genetic element in normal cells were characterized. The 1200-bp transcript was found to arise from splicing out of 374 bp of exonic sequence extending from positions 407-780. The 950-bp transcript was found to arise from removal of this and 284 bp of additional exonic sequence beginning further upstream at position 123. Analyses of transcripts expressed in Epstein-Barr virus (EBV)-transformed B lymphocytes prepared from two PNH patients showed that both failed to express normal 1600-bp transcripts. One expressed truncated transcripts of 1000 and 800 bp generated by an alternate splice which utilized a downstream signal in place of the normal intronic splice signal. The other expressed a 1600 bp-transcript with multiple nucleotide changes but normal 1200- and 950- bp "spliced" transcripts

Humans , Hemoglobinuria, Paroxysmal/metabolism , Receptors, Immunologic/metabolism , Base Sequence , Cell Line , Herpesvirus 4, Human , Molecular Sequence Data
Asian Pac J Allergy Immunol ; 1987 Jun; 5(1): 25-31
Article in English | IMSEAR | ID: sea-37046


The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.

Acquired Immunodeficiency Syndrome/diagnosis , Adult , Autopsy , Brain/pathology , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , HIV/isolation & purification , Homosexuality , Humans , Immunologic Techniques , Male , Taiwan