Desnutrição e Caquexia na Insuficiência Cardíaca Descompensada e Cardiomiopatia Chagásica: Ocorrência e Associação com Desfechos Hospitalares

BackgroundNutritional disorders are common among patients with heart failure (HF) and associated with poor prognosis. Importantly, some populations of patients, like the ones with Chagas disease, are frequently excluded from most analyses.ObjectiveWe sought to study the occurrence of undernutrition and cachexia in patients with Chagas disease during episodes of decompensated HF (DHF) as compared to other etiologies, and to investigate the influence of these findings on hospital outcomes.MethodsWe performed a consecutive case series study with patients hospitalized with DHF. Patients underwent the Subjective Global Assessment of nutritional status (SGA), besides anthropometric and laboratorial measures, and were evaluated for the occurrence of cachexia, low muscle mass and strength. We studied the occurrence of death or urgent heart transplantation during hospitalization.ResultsAltogether, 131 patients were analyzed and 42 (32.1%) had Chagas disease. Patients with Chagas disease had lower Body Mass Index (BMI) (22.4 kg/m²[19.9-25.3] vs. 23.6 kg/m2 [20.8-27.3], p=0.03), higher frequency of undernutrition (76.2% vs 55.1%, p=0.015) and higher occurrence of death or transplant (83.3% vs. 41.6%, p<0.001). We found that, in patients with Chagas etiology, the occurrence of death or cardiac transplantation were associated with undernutrition (3 [42.9%] patients with hospital discharge vs 29 [82.9%] patients with death or heart transplant, p=0.043).ConclusionsTaken together, our results indicate that patients with Chagas disease hospitalized with DHF often present with nutritional disorders, especially undernutrition; importantly, this finding was associated with the occurrence of death and heart transplant during hospitalization.     

Modulation of cytochrome P450 1 (Cyp1) by vanadium in hepatic tissue and isolated hepatocyte of C57BL/6 mice

The objective of the current study was to investigate the effect of vanadium (V⁵⁺) on Cyp1 expression and activity in C57BL/6 mice liver and isolated hepatocytes. For this purpose, C57BL6 mice were injected intraperitoneally with V⁵⁺ (5 mg/kg) in the absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15 μg/kg) for 6 and 24 h. Furthermore, isolated hepatocytes from C57BL6 mice were treated with V⁵⁺ (5, 10, and 20 μM) in the absence and presence of TCDD (1 nM) for 3, 6, 12, and 24 h. In vivo, V⁵⁺ alone did not significantly alter Cyp1a1, Cyp1a2, or Cyp1b1 mRNA, protein, or catalytic activity levels. Upon co-exposure to V⁵⁺ and TCDD, V⁵⁺ significantly potentiated the TCDD-mediated induction of the Cyp1a1, Cyp1a2, and Cyp1b1 mRNA, protein, and catalytic activity levels at 24 h. In vitro, V⁵⁺ decreased the TCDD-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels. Furthermore, V⁵⁺ significantly inhibited the TCDD-induced AhR-dependent luciferase activity. V⁵⁺ also increased serum hemoglobin (Hb) levels in animals treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone or in the presence of TCDD, there was an increase in the AhR-dependent luciferase activity. When isolated hepatocytes were treated for 2 h with V⁵⁺ in the presence of TCDD, followed by replacement of the medium with new medium containing Hb, there was further potentiation to the TCDD-mediated effect. The present study demonstrates that there is a differential modulation of Cyp1a1 by V⁵⁺ in C57BL/6 mice livers and isolated hepatocytes and demonstrates Hb as an in vivo specific modulator.     

Prominent dysautonomia in a patient with POEMS syndrome

POEMS syndrome is a rare, multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes. Here we present an unusual case of a patient with POEMS syndrome who exhibited a prominent autonomic neuropathy.     

Age-related DNA methylation changes in normal human prostate tissues.

PURPOSE: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age. EXPERIMENTAL DESIGN: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer. RESULTS: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RARbeta2 (r = 0.4; P < 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P < 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P < 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RARbeta2 (P < 0.001), RASSF1A (P = 0.005), GSTP1 (P < 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01). CONCLUSIONS: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy.     

Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil based chemotherapy.

PURPOSE: There are no good genomic markers of survival in patients with advanced colorectal cancer. The CpG island methylator phenotype (CIMP) marks a distinctive pathway in colorectal cancer. We sought to determine the prognostic significance of CIMP in advanced colorectal cancer patients treated with 5-fluorouracil (5-FU) in an Eastern Cooperative Oncology Group clinical trial. EXPERIMENTAL DESIGN: We studied 188 patients enrolled on protocol E2290, a five-arm trial comparing 5-FU, 5-FU in combination with N-phosphonoacetyl-l-aspartic acid, oral leucovorin, i.v. leucovorin, or IFNalpha-2a in patients with advanced colorectal cancer. Methylation of MINT1, MINT31, hMLH1, p14ARF, and p16INK4a in DNA extracted from formalin-fixed paraffin-embedded specimens was evaluated by combined bisulfite restriction analysis, and methylation of MINT2 was studied by methylation-specific PCR. RESULTS: Methylation frequencies were 21% for MINT1, 23% for MINT2, 24% for MINT31, 4% for hMLH1, 11% for p14ARF, and 17% for p16INK4a. Methylation of MINT1, MINT31, p14ARF, and p16INK4a were correlated, as expected. There was no association between methylation and clinicopathologic factors or response to therapy. Methylation of MINT1, MINT31, p14ARF, or p16INK4a was associated individually with shortened overall survival. Hazard ratios were 1.51 (P = 0.05) for MINT1, 1.70 (P = 0.006) for MINT31, 2.22 (P = 0.001) for p14ARF, and 1.51 (P = 0.05) for p16INK4a. Concurrent methylation of two or more genes of the CIMP-associated subset (MINT1, MINT31, p14ARF and p16INK4a) defined a group of cases with markedly reduced overall survival and hazard ratio was 3.22 (P < 0.0001 in multivariate analyses). CONCLUSIONS: CIMP is associated with poor survival in advanced colorectal cancer patients.     

von Willebrand factor-collagen binding activity is increased in newborns and infants

ABSTRACT. von Willebrand factor (vWF) antigen (vWF:Ag) and vWF-collagen binding activity (vWF:CBA) were measured in plasma by parallel quantitative ELISAs in normal newborns and infants ( n =71). The medians for vWF:Ag (IUjml) and vWF:CBA (Ujml), respectively, were 1.46 and 1.91 for 2-7 day-old (n = 43), 1.22 and 1.40 for 2-4 week-old (n = 14), 1.22 and 1.15 for 2-6-month-old (n = 14) infants and 0.98 and 1.08 (n = 36) in normal adults. Elevated levels of vWF:Ag, but particularly vWF:CBA were seen for up to 4 weeks of life reaching adult levels between 2 and 6 months of life. The elevated levels of the vWF parameters indicate that caution should be exercised when interpreting laboratory data and diagnosing von Willebrand disease in newborns and young infants and warrant the use of age-specific reference ranges. The efficient haemostasis observed during early neonatal life may in part be due to the increased ability of vWF to interact with collagen.     

The relationship between human papillomavirus and p53 gene in conjunctival squamous cell carcinoma

PURPOSE: The p53 tumor-suppressor gene has been documented to exist in mutated forms in many types of squamous cell carcinoma in the body. Also in conjunctival squamous cell carcinoma, human papillomavirus (HPV) is accepted as an oncogenic factor. The objective of our study was to establish a correlation between p53 overexpression and the presence of HPV infection within tumor tissues from patients with conjunctival squamous cell carcinoma. METHODS: Tissue sections obtained from paraffin-embedded conjunctival squamous cell carcinoma specimens from 23 patients were examined with light microscopy, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: Seventy-eight percent of tumors were positive for p53, whereas 22% were positive for HPV. The proportion of patients positive for both p53 and HPV was 17%, whereas another 17% of the patients were negative for both p53 and HPV. Therefore no significant disproportion was found in the distribution of patients' HPV status and p53 status (p = 1.00). No significant correlation or linear association was found between the HPV status and p53 status (r = 0.022; p = 0.920). CONCLUSION: We could not show any statistical association between abnormal p53 gene-product expression by immunohistochemistry in conjunctival squamous cell carcinomas and HPV infection by PCR detection techniques.