Dietary intake of selected nutrients and persistence of HPV infection in men

Human papillomavirus (HPV) infection is a common sexually transmitted disease. Although often transitory, persistent oncogenic HPV infection may progress to a precursor lesion and, if not treated, can further increase the risk of cancer. The purpose of this study was to investigate the relation between dietary intake and HPV persistent infection in men of a Brazilian cohort. The study population consisted of 1,248 men from the Brazilian cohort of the HIM (HPV in Men) Study, ages 18 to 70 years, who completed a quantitative food frequency questionnaire. U Mann‐Whitney test was used to assess differences in median nutrient intake of selected nutrients. The association of dietary intake and persistent HPV infection was assessed in multivariate logistic models. The prevalence of any HPV infection at baseline was 66.6%. Of 1,248 participants analyzed, 1,211 (97.0%) were HPV positive at one or more times during the 4 years of follow‐up and 781 (62.6%) were persistently HPV positive. Men with nonpersistent oncogenic HPV infections had higher median intake of retinol (p = 0.008), vitamin A (p < 0.001) and folate (DFE; p = 0.003) and lower median intake of energy (p = 0.005) and lycopene (p = 0.008) in comparison to men with persistent oncogenic infections. No significant association was found between selected nutrients and persistent oncogenic HPV infection. For nononcogenic persistent infections, only vitamin B12 intake was significantly associated (p = 0.003, test for trend). No association was observed between dietary intake and persistent oncogenic‐type HPV infection; however, vitamin B12 intake was inversely associated with nononcogenic HPV persistence.     

The fatty acid-binding protein-2 A54T polymorphism is associated with renal disease in patients with type 2 diabetes

The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of long-chain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] <20 microg/min; n = 529), microalbuminuria (UAE 20-199 microg/min; n = 217), or proteinuria (UAE >199 microg/min; n = 160). Patients with end-stage renal disease (ESRD) (n = 136) were also included. The prevalence of the TT genotype was higher in patients with renal involvement compared with those with normoalbuminuria (odds ratio [95% CI] 2.4 [1.1-5.4]) following adjustment for type 2 diabetes duration, BMI, hypertension, A1C, and cholesterol levels. The risk was similar considering different stages of renal involvement. In a second independent patient sample (483 type 2 diabetic Caucasians residing in Massachusetts), a significant association was also observed between the TT genotype and proteinuria or ESRD (2.7 [1.0-7.3]; P = 0.048). This study thus provides evidence that FABP2 confers susceptibility to renal disease in type 2 diabetic patients.     

Comparison of Beta-catenin with TGF-beta1, HIF-1alpha and Patients’ Disease-free Survival in Human Colorectal Cancer

Beta-catenin accumulation is suppressed by TGF-beta1 (transforming growth factor beta1) in intestinal epithelium suggesting negative feedback between these two factors. Besides that, beta-catenin interacts with HIF-1alpha (hypoxia-inducible factor-1alpha) at the promoter region of HIF-1 target genes. Our study was aimed at comparison of beta-catenin with HIF-1alpha, TGF-beta1, Ki67 and survival of sporadic colorectal cancer patients. Expressions of beta-catenin, TGF-beta1, HIF-1alpha, Ki67 were evaluated in triads of specimens of each primary tumor of 72 sporadic colorectal cancers with immunohistochemistry due to limited availability of tissue material. Disease-free survival was analyzed in case of all 100 beta-catenin stained tumors, in 85 cancers stained for HIF-1 and in 72 neoplasms with TGFbeta1 staining. Beta-catenin, TGF-beta1 and HIF-1alpha accumulated in 72 colorectal cancer cells. Beta-catenin correlated both with HIF-1alpha and TGF-beta1 in all colorectal cancers (p < 0.009, r = 0.307 and p = 0.003, r = 0.342, respectively) and in subgroups of different clinico-pathological profile. Beta-catenin failed to correlate with Ki67. In case of beta-catenin, TGF-beta1 and HIF-1alpha, disease-free survival curves failed to show any statistically significant differences between groups of marker negative tumors, cancers with low expression and neoplasms with higher protein expression. Positive correlations between beta-catenin and TGF-beta1 may indicate ineffective attempts of TGF-beta1 to reduce intracellular level of beta-catenin in colorectal cancer. Associations between beta-catenin and HIF-1alpha reflect previously detected interactions between HIF-1alpha with beta-catenin and are confirmative for presence of such reactions in human colorectal cancer.     

In vitro evaluation of permeation,toxicity and effect of praziquantel-loaded solid lipid nanoparticles against Schistosoma mansoni as a strategy to improve efficacy of the schistosomiasis treatment

Solid lipid nanoparticles (SLN) are a promising drug delivery system for oral administration of poorly-water soluble drugs because of their capacity to increase the solubility of drug molecules when loaded in their lipid matrices, with the resulting improvement of the drug bioavailability. In the present work, we have developed praziquantel (PZQ)-loaded SLN and explored the biological applications of this system for intestinal permeation of PZQ. The effect in vitro on Schistosoma mansoni culture and the cytotoxicity in HepG2 line cell were also evaluated. The results showed a significant decrease in the intestinal absorption of PZQ loaded in SLN compared to free PZQ, suggesting that the SLN matrix could act as reservoir system. In culture of S. mansoni, we observed that PZQ-loaded SLN were more effective than free PZQ, leading the death of the parasites in less time. The result was proportional to doses of PZQ (25 and 50 μg mL⁻¹) and lipid concentration. Regarding cytotoxicity, the encapsulation of PZQ into SLN decreased the toxicity in HepG2 cells in comparison to the free PZQ. From the obtained results, PZQ-loaded SLN could be a new drug delivery system for the schistosomiasis treatment especially in marginalized communities, improving the therapeutic efficacy and reducing the toxic effects of PZQ.     

A 3D fiber model of the human brainstem

A new neuroanatomic approach to evaluate the fiber orientation in gross histological sections of the human brain was developed. Serial sections of a human brainstem were used to derive fiber orientation maps by analysis of polarized light sequences of these sections. Fiber inclination maps visualize angles of inclination, and fiber direction maps show angles of direction. These angles define vectors which can be visualized as RGB-colors. The serial sections were aligned to each other using the minimized Euclidian distance as fit criterion. In the 3D data set of the human brainstem the major fiber tracts were segmented, and three-dimensional models of these fiber tracts were generated. The presented results demonstrate that two kinds of fiber atlases are feasible: a fiber orientation atlas representing a vector in each voxel, which shows the nerve fiber orientation, and a volume-based atlas representing the major fiber tracts. These models can be used for the evaluation of diffusion tensor data as well as for neurosurgical planning.     

Application of a flowchart for the detection of lysosomal storage diseases in 105 high-risk Brazilian patients

Lysosomal storage diseases (LSD) are a group of more than 40 disorders, many of them with overlapping phenotype, in which clinical diagnosis is often difficult. Definitive diagnosis is based on enzyme assays, a large number of such assays usually being necessary during the investigation of each patient. In addition, there will frequently be a need for tissue culture in order to provide enough material for analysis. Taking into account these difficulties, we designed a flowchart for the detection of LSD that is based on 2 sets of tests requiring only random urine and heparinized blood. Here we describe this routine and report the results of its application to 105 Brazilian patients in whom a LSD was suspected. We think that the application of this rationale represents a saving of work and costs, and should be of special interest to genetic centers in developing countries.     

Anatomopathological study in BALB/c mice brains experimentally infected with Toxoplasma gondii.

Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts.     

Operative Mortality After Hepatic Resection: Are Literature-Based Rates Broadly Applicable?

Introduction Literature-based data on mortality after hepatectomy may be misleading, as poor outcomes are less likely to be published. The objective of the current study was to compare published vs public, nationally available mortality rates after hepatic resection. Materials and Methods A systematic MEDLINE review was conducted to identify reports of hepatectomy outcome between January 1998–December 2004. Data were analyzed to calculate literature-based mortality rate and then compared with population-based mortality rate for hepatectomy using the Nationwide Inpatient Sample (NIS) dataset. Results Twenty-three publications fulfilled screening criteria. The studies included 7,073 patients who had undergone hepatic resection (46.1% within USA vs 53.9% outside USA). Most patients were male (58.6%) with median age of 56 years. Indications for hepatic resection included hepatocellular carcinoma (47.7%), metastatic disease (34.3%), or other (18.1%). Cirrhosis was present in 23.2% of patients; 46.9% patients underwent either a hemi-hepatectomy or extended resection. The literature-based mortality rate was 3.6% (US centers only, 2.8%). Analysis of NIS revealed 11,429 hepatectomy cases. After controlling for gender, age, extent of hepatectomy, hepatocellular cancer diagnosis, and presence of cirrhosis, the adjusted NIS-based perioperative mortality rate for hepatectomy was 5.6% (95% CI, 5.0–6.2%). The relative mortality after hepatectomy was 1.6-fold higher based on population-based data compared with reports from the literature (P < 0.05). Conclusion Actual population-based mortality rates for major liver resections may be higher than those reported in the literature. Informed consent should reflect actual local and national mortality rates rather than selective reports from the literature. Presented at the American College of Surgeons, Surgical Forum, New Orleans, LA, USA, October 10, 2007.