RESUMO
Purpose: Limited and contradictory data on the circulating levels of glucagon-like peptide (GLP-1) and resistin in hepatitis C virus genotype-4 (HCV-4) cirrhotic patients are present. Thus, this study aimed to evaluate their concentrations and to investigate the association between total GLP-1, resistin, and insulin resistance in those patients.Materials and Methods: Non-diabetic HCV-4 cirrhotic patients (n = 80; 40 with Child-Pugh A, 20 with Child-Pugh B, and 20 with Child-Pugh C), and 25 healthy subjects were enrolled in this study. The basal circulating levels of total GLP-1 and resistin along with serum insulin, glucose, total cholesterol, and triglycerides were measured.Results: Plasma GLP-1 and serum resistin levels were significantly higher in cirrhotic patients than controls (P < . 001). Moreover, circulating GLP-1 and resistin levels increased in a stepwise fashion in line with increasing grade of liver damage. According to Spearman's rank correlation, both GLP-1 and resisitin correlated positively with each other, insulin, homeostatic model assessment of insulin resistance, alanine aminotransferase (ALT), total bilirubin, and international normalized ratio while they correlated negatively with albumin (P < .001). Multiple stepwise regression analysis showed that ALT, serum resistin and Child-Pugh score independently influenced the GLP-1 levels in cirrhotic patients.Conclusions: Circulating levels of GLP-1 and resistin were elevated in cirrhotic patients with HCV-4. Further, the severity of liver cirrhosis and serum resistin were the determinant factors explaining the variability of GLP-1 levels by about 84%. In addition, a positive relation was found between insulin resistance and both GLP-1 and resistin levels.
Assuntos
Peptídeo 1 Semelhante ao Glucagon/sangue , Hepacivirus , Hepatite C/sangue , Resistência à Insulina , Cirrose Hepática/sangue , Resistina/sangue , Adulto , Idoso , Feminino , Hepacivirus/genética , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Serum Prostate-specific antigen (PSA) has been used for screening and diagnosis of prostate cancer (PCa) but it is burdened by its low accuracy, creating a need for reliable diagnostic markers. Despite prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) being widely expressed in the tissue of PCa, no definite conclusion regarding their use as clinical biomarkers due to their lacking organ specificity. Therefore, this study aimed to evaluate the peripheral blood levels of PSMA and PSCA mRNAs and examine their diagnostic significance as non-invasive integrated markers.
Materials and Methods: 125 subjects were enrolled in this study. They were divided into 25 healthy controls, 25 BPH patients, and 75 PCa patients. The expression levels of PSMA and PSCA were determined using quantitative RT- PCR, in addition to measuring serum PSA.
Results: Levels of PSMA and PSCA were over-expressed in PCa patients compared to controls and BPH patients and were found to be associated with increased susceptibility to PCa. Moreover, the diagnostic values of PSMA and PSCA to distinguish PCa patients from BPH patients and controls were inferior to that of PSA. However, the combination of PSMA and PSCA with PSA enhanced the efficacy of the latter.
Conclusion: This study suggests that these genes were associated with malignant susceptibility. Concerning the duality of PSMA-PSA or PSCA-PSA, this implies the significance of their investigation together in peripheral blood of prostate patients.
Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Próstata/patologia , Antígenos de Neoplasias/genética , Proteínas de Neoplasias , Proteínas Ligadas por GPIRESUMO
BACKGROUND: Tay-Sachs disease (TSD), an autosomal recessively inherited neurodegenerative lysosomal storage disease, reported worldwide with a high incidence among population of Eastern European and Ashkenazi Jewish descent. Mutations in the alpha subunit of HEXA that encodes for the ß-hexosaminidase-A lead to deficient enzyme activity and TSD phenotype. This study is the first to highlight the HEXA sequence variations spectrum in a cohort of Egyptian patients with infantile TSD. RESULTS: This study involved 13 Egyptian infant/children patients presented with the infantile form of TSD, ten of the 13 patients were born to consanguineous marriages. ß-hexosaminidase-A enzyme activity was markedly reduced in the 13 patients with a mean activity of 3 µmol/L/h ± 1.56. Sanger sequencing of the HEXA' coding regions and splicing junctions enabled a detection rate of ~ 62% (8/13) in our patients revealing the molecular defects in eight patients; six homozygous-mutant children (five of them were the product of consanguineous marriages) and two patients showed their mutant alleles in heterozygous genotypes, while no disease-causing mutation was identified in the remaining patients. Regulatory intragenic mutations or del/dup may underlie the molecular defect in those patients showing no relevant pathogenic sequencing variants or in the two patients with a heterozygous genotype of the mutant allele. This research identified three novel, likely pathogenic variants in association with the TSD phenotype; two missense, c.920A > C (E307A) and c.952C > G (H318D) in exon 8, and a single base deletion c.484delG causing a frameshift E162Rfs*37 (p.Glu162ArgfsTer37) in exon 5. Three recurrent disease-causing missense mutations; c.1495C > T (R499C), c.1511G > A(R504H), and c.1510C > T(R504C) in exon 13 were identified in five of the eight patients. None of the variants was detected in 50 healthy Egyptians' DNA. Five variants, likely benign or of uncertain significance, S3T, I436V, E506E, and T2T, in exons 1, 11,13, & 1 were detected in our study. CONCLUSIONS: For the proper diagnostics, genetic counseling, and primary prevention, our study stresses the important role of Next Generation Sequencing approaches in delineating the molecular defect in TSD-candidate patients that showed negative Sanger sequencing or a heterozygous mutant allele in their genetic testing results. Interestingly, the three recurrent TSD associated mutations were clustered on chromosome 13 and accounted for 38% of the HEXA mutations detected in this study. This suggested exon 13 as the first candidate for sequencing screening in Egyptian patients with infantile TSD. Larger studies involving our regional population are recommended, hence unique disease associated pathogenic variations could be identified.
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Doença de Tay-Sachs , Cadeia alfa da beta-Hexosaminidase , Humanos , Cadeia alfa da beta-Hexosaminidase/química , Cadeia alfa da beta-Hexosaminidase/genética , beta-N-Acetil-Hexosaminidases/genética , Egito , Hexosaminidase A/genética , Mutação , Doença de Tay-Sachs/genética , LactenteRESUMO
Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.
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Anti-Inflamatórios/farmacologia , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Cisplatino/toxicidade , Raios gama/efeitos adversos , Guaiacol/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Creatina Quinase Forma MB/sangue , Ciclo-Oxigenase 2/metabolismo , Dano ao DNA , Guaiacol/farmacologia , L-Lactato Desidrogenase/sangue , Masculino , Malondialdeído/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
BACKGROUND: Cartonectin is a potent anti-inflammatory adipokine that might be implicated in metabolism and energy storage. Our objective was to evaluate the influence of weight reduction following laparoscopic sleeve gastrectomy (LSG) on serum cartonectin and vaspin levels. SUBJECTS AND METHODS: Thirty-two individuals (29 female and 3 male) with morbid obesity underwent LSG. Anthropometric indices, lipid profile, fasting serum concentrations of glucose, insulin, vaspin, and cartonectin were measured prior and 3 months after LSG. Insulin sensitivity was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Following LSG, circulating cartonectin level increased significantly while serum vaspin was significantly decreased. The percentage change of serum cartonectin level correlated negatively with the percentage changes in body mass index, waist circumference, and waist-hip ratio and positively with percentage changes in LDL-C, triglycerides, and HOMA-IR after adjustment for age and sex. Moreover, the changes in vaspin concentration positively correlated with the changes in insulin level and HOMA-IR after adjustment for age and sex. In a multiple stepwise linear regression model, the changes in waist circumference explained 13% variability of changes in cartonectin level while the changes in HOMA-IR and LDL-C were responsible for 31% of the variability in changes of vaspin level. CONCLUSION: LSG-induced weight loss rapidly increases serum cartonectin level and decreases the serum vaspin level in morbidly obese subjects. The changes in cartonictin level seem to be influenced by the changes of waist circumference while the changes of HOMA-IR and LDL-C might be determinant factors of the changes in vaspin level.
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Gastrectomia , Laparoscopia , Obesidade Mórbida/cirurgia , Serpinas/sangue , Fatores de Necrose Tumoral/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Insulina/sangue , Resistência à Insulina , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de Tempo , Redução de Peso/fisiologia , Adulto JovemRESUMO
Doxorubicin (DOX) is a highly effective antineoplastic drug; however, the clinical use of DOX is limited by its dose dependent cardiotoxicity. This study was conducted to evaluate the cardioprotective effect of sea cucumber and valsartan against DOX-induced cardiotoxicity in rats. Also, the role of exposure to low dose γ radiation (LDR) on each of them was investigated, since LDR could suppress various reactive oxygen species-related diseases. Rats received DOX (2.5mg/kg, ip) in six equal injections over a period of 2weeks, sea cucumber (14.4mg/kg, p.o) and valsartan (30mg/kg, p.o) for 8 successive weeks. Exposure to LDR (0.5Gy) was performed one day prior to DOX. Results revealed that DOX administration elevated serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK-MB) and troponin-I as well as increased cardiac lipid peroxide content and myeloperoxidase (MPO) activity. Additionally, it increased cardiac expressions of iNOS and caspase-3, accompanied by reduction in cardiac total protein and glutathione (GSH) contents. Treatment with sea cucumber or valsartan improved the cardiotoxicity of DOX. Their adjuvant therapy with LDR offers an additional benefit to the cardioprotection of the therapeutic drugs. These results confirmed by histopathological examination. In conclusion, sea cucumber and valsartan alone or combined with LDR attenuated DOX-induced cardiotoxicity via their antioxidant and anti-apoptotic activities and thus might be useful in the treatment of human patients under doxorubicin chemotherapy.
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Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Raios gama , Pepinos-do-Mar/química , Animais , Antioxidantes/química , Apoptose/efeitos da radiação , Aspartato Aminotransferases/sangue , Caspase 3/genética , Caspase 3/metabolismo , Creatina Quinase/sangue , Doxorrubicina/toxicidade , Glutationa/metabolismo , Cardiopatias/etiologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Peroxidase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Pepinos-do-Mar/metabolismo , Troponina I/sangue , Valsartana/farmacologiaRESUMO
BACKGROUND: Adipokines provides new insights about the physiology, pathology and treatment of obesity. AIM: We investigated the association between serum vaspin and serum visfatin concentrations with obesity in Egyptian children. MATERIAL AND METHODS: Twenty two obese children with body mass index (BMI) above 95th percentile; 11 males and 11 females were included in this study. Their mean age was 9.18 ± 2.8 years. After general clinical examination, fasting blood glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol were measured in cases and controls (n=11). Fasting insulin, vaspin and visfatin were detected using ELIZA. Insulin resistance was estimated by Homeostasis model assessment method (HOMA-IR). RESULTS: Blood pressure, in both systolic and diastolic measurements was elevated significantly in obese children. Significant elevation of serum insulin and insulin resistance (HOMA/IR) were observed in obese children too. Vaspin and visfatin showed significant elevation in obese children than controls. Significant positive correlations were detected between visfatin and BMI, waist circumference, hip circumference and HOMA/IR. We found that Vaspin and visfatin are higher in obese children. CONCLUSION: Visfatin but not vaspin correlates positively with waist circumference and HOMA/IR in obese children.