Structural evaluation of the effects of chronic ethanol ingestion on the testis of Calomys callosus

Chronic exposure to ethanol may results in pathophysiologic changes in cellular function. The present work was designed to investigate the morphology of testis submitted to experimental ethanol ingestion. Experimental animals were divided into two groups. The control group (n = 23) received a solid diet and tap water and the alcoholic group (n = 23) received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 120 days of treatment, all animals were anesthetized, weighed and sacrificed. Testosterone and luteinizing hormone levels in serum were lower in the alcoholic group than in the control group. Histological and ultrastructural alterations were observed in the testicular alcoholic germinative cells like enormous spaces, lipid droplets accumulation, digestive vacuoles, irregular diameter of the seminiferous tubules and interstitial dilated blood vessels. It was concluded that 20% ethanol provokes lesions on the testis germinative epithelium probably inducing gonadal dysfunction. (C) 2008 Elsevier Ltd. All rights reserved.

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa. (C) 2011 Elsevier Ltd. All rights reserved.

Chronic Acetonemia Alters Liver Oxidative Balance and Lipid Content in Rats. A Model of Nash?

Acetone is considered to be a substance that can disturb cellular oxidative status, being also associated with the production of glucose during its metabolization. The objective of the present study was to determine the effects of chronic treatment with acetone in oxidative stress and metabolic parameters in rats. Twenty male Wistar rats were divided into two groups: control (CG) and chronic acetone group (CAG). After 28 days of acetone ingestion in a 5% aqueous solution (CAG) or water (CG) the animals were euthanized and urine, plasma and liver were collected for the determination of acetone, glucose, lipemia, hepatic fat, malondialdehyde (MDA), reduced glutathione (GSH), and vitamin E. As expected, urinary and plasma acetone levels were higher in CAG. There was no difference in hepatic MDA values between groups, whereas hepatic GSH was lower in CAG than in CG and hepatic vitamin E was higher in CAG than in CG. There was also an increase in glycemia, cholesterolemia and hepatic fat in CAG compared to CG. Chronic treatment with a 5% acetone solution produced an increase in acetonemia that was able to promote changes in hepatic oxidative metabolism and in lipid content in rats similar to those observed in nonalcoholic steatohepatitis.

EFFECT OF THE TEMPERATURE AND pH ON METHANOL RELEASE IN COFFEE BREW SWEETENED WITH ASPARTAME

Methanol is an alcohol which is metabolized to folmaldehyde in humans. It is a very toxic substance, responsible for blindness in cases of methanol intoxication. This study shows the production of methanol when aspartame is used to sweeten coffee brew. The temperature versus pH binomium was also tested. When assayed at 90 degrees C coffee brew+aspartame and aspartame solution showed an increase in methanol release of 17.8 and 19.3%, respectively, as compared with coffee brew. At 180 degrees C, the increase was 32.5 and 26.3%, respectively. Our data revealed a protective effect of the pH of coffee on the degradation of aspartame and formation of methanol; an important fact, mainly for specific populations that use aspartame, like diabetics.

Frequency and prognostic relevance of cancer testis antigen 45 expression in multiple myeloma

Objective. This study aims to analyze the expression of cancer testis antigen 45 (CT45) in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in multiple myeloma (MM) patients. Materials and Methods. Expression of CT45 was studied in 20 normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain and fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon, and one pool of 10 normal bone marrow samples) and bone marrow aspirates from 3 monoclonal gammopathies of undetermined significance, 5 solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by reverse transcriptase polymerase chain reaction. Results. CT45 was positive in 3 of 20 (15%) normal tissues tested: lung, brain (both fetal and adult), and spinal cord. Among monoclonal gammopathies, CT45 was positive in 2 of 5 (40%) solitary plasmacytomas bone marrow aspirates, 10 of 61 (16%) MM bone marrow aspirates, and in the U266 MM cell line. Conclusions. We did not find associations between bone marrow histology and CT45 expression. However, we demonstrated for the first time that positive expression of CT45 was associated with poor prognostic (international Staging System) and poor outcomes in MM patients, meaning that CT45-positive cases presented seven times more chance of worse evolution than the negative ones. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Effects of changing blood viscosity and heart rate on vena contracta width as evaluated by color Doppler flow mapping. An in vitro study with a pulsatile flow model

Background: There is only limited knowledge on how the quantification of valvular regurgitation by color Doppler is affected by changing blood viscosity. This study was designed to evaluate the effect of changing blood viscosity on the vena contracta width using an in vitro model of valvular insufficiency capable of providing ample variation in the rate and stroke volume. Methods: We constructed a pulsatile flow model filled with human blood at varying hematocrit (15%, 35%, and 55%) and corresponding blood viscosity (blood/water viscosity: 2.6, 4.8, 9.1) levels in which jets were driven through a known orifice (7 mm(2)) into a 110 mL compliant receiving chamber (compliance: 2.2 mL/mmHg) by a pulsatile pump. In addition, we used variable pump stroke volumes (5, 7.5, and 10 mL) and rates (40, 60, and 80 ppm). Vena contracta region was imaged using a 3.5 MHz transducer. Pressure and volume in the flow model were kept constant during each experimental condition, as well as ultrasound settings. Results: Blood viscosity variation in the experimental range did not induce significant changes in vena contracta dimensions. Also, vena contracta width did not change from normal to low hematocrit and viscosity levels. A very modest increase only in vena contracta dimension was observed at very high level of blood viscosity when hematocrit was set to 55% . Pump rate, in the evaluated range, did not influence vena contracta width. These results in controlled experimental settings suggest that the vena contracta is an accurate quantitative method for quantifying valvular regurgitation even when this condition is associated with anemia, a frequent finding in patients with valvular heart disease.

Therapeutic Leukapheresis in Patients with Leukostasis Secondary to Acute Myelogenous Leukemia

Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French-American-British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 X 10(9)/L to 150.3 X 10(9)/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis. J. Clin. Apheresis 26:181-185, 2011. (C) 2011 Wiley-Liss, Inc.

Integration pattern of HIV-1 based lentiviral vector carrying recombinant coagulation factor VIII in Sk-Hep and 293T cells

293T and Sk-Hep-1 cells were transduced with a replication-defective self-inactivating HIV-1 derived vector carrying FVIII cDNA. The genomic DNA was sequenced to reveal LTR/human genome junctions and integration sites. One hundred and thirty-two sequences matched human sequences, with an identity of at least 98%. The integration sites in 293T-FVIIIDB and in Sk-Hep-FVIIIDB cells were preferentially located in gene regions. The integrations in both cell lines were distant from the CpG islands and from the transcription start sites. A comparison between the two cell lines showed that the lentiviral-transduced DNA had the same preferred regions in the two different cell lines.

Iron Fortification Strategies for the Control of Childhood Anemia in Brazil

This article presents data on the fortification of foods, necessary as an important public health approach for the success in reducing anemia. The use of food vehicles, iron salts and their costs, as well as recent work on iron fortification of foods in Brazil are reviewed. Recent research serves as a cornerstone for countries that attempt to implement permanent, long-lasting iron fortification programs aimed at the prevention of anemia considering cultural habits, type of iron salts and at-risk groups.

What Is the Meaning of Homocysteine in Patients on Dialysis?

Objective: To evaluate the determinants of total plasma homocysteine levels and their relations with nutritional parameters, inflammatory status, and traditional risk factors for cardiovascular disease in renal failure patients on dialysis treatment. Design: The study was conducted on 70 clinically stable patients, 50 of them on hemodialysis (70% men; 55.3 +/- 14.5 years) and 20 on peritoneal dialysis (50% men; 62 +/- 13.7 years). Patients were analyzed in terms of biochemical parameters (serum lipids, creatinine, homocysteine [Hcy], creatine-kinase [Ck], folic acid, and vitamin B(12)), anthropometric data, markers of inflammatory status (tumor necrosis factor-alpha, C-reactive protein, interleukin-6), and adapted subjective global assessment. Results: The total prevalence of hyperhomocysteinemia (>15 mu mol/L) was 85.7%. Plasma folic acid and plasma vitamin B(12) were within the normal range. Multiple regression analysis (r(2) - 0.20) revealed that the determinants of total Hcy were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Hcy was positively correlated with albumin and creatinine and negatively correlated with total cholesterol, high density lipoprotein cholesterol, folic acid, and vitamin B(12). Conclusions: The determinants of total Hcy in the study sample were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Evidently, the small sample size might have had an effect on the statistical analyses and further studies are needed. However, Hcy in patients on dialysis treatment may not have the same effect as observed in the general population. In this respect, the association between malnutrition and inflammation may be a confounding factor in the determination of the true relationship between Hcy, nutritional status, and cardiovascular risk factors in this group. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.

Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries. Vascular reactivity to ET-1 and ET(A) and ET(B) receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET(A) and ET(B) receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [(125)I]-ET-1. HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET(A) or ET(B) receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET(A) but not of ET(B) receptors abolished enhancement in HHcy tissues. ET(A) and ET(B) receptor gene expressions were not up-regulated. ET(A) receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A(2) receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO. Increased ET(A) receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET(A) receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility. British Journal of Pharmacology (2009) 157, 568-580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009 This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009.

IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy

Objectives Interleukin 33 (IL-33) is a new member of the IL-1 family of cytokines which signals via its receptor, ST2 (IL-33R), and has an important role in Th2 and mast cell responses. This study shows that IL-33 orchestrates neutrophil migration in arthritis. Methods and results Methylated bovine serum albumin (mBSA) challenge in the knee joint of mBSA-immunised mice induced local neutrophil migration accompanied by increased IL-33R and IL-33 mRNA expression. Cell migration was inhibited by systemic and local treatments with soluble (s) IL-33R, an IL-33 decoy receptor, and was not evident in IL-33R-deficient mice. IL-33 injection also induced IL-33R-dependent neutrophil migration. Antigen- and IL-33-induced neutrophil migration in the joint was dependent on CXCL1, CCL3, tumour necrosis factor a (TNF alpha) and IL-1 beta synthesis. Synovial tissue, macrophages and activated neutrophils expressed IL-33R. IL-33 induces neutrophil migration by activating macrophages to produce chemokines and cytokines and by directly acting on neutrophils. Importantly, neutrophils from patients with rheumatoid arthritis successfully treated with anti-TNF alpha antibody (infliximab) expressed significantly lower levels of IL-33R than patients treated with methotrexate alone. Only neutrophils from patients treated with methotrexate alone or from normal donors stimulated with TNF alpha responded to IL-33 in chemotaxis. Conclusions These results suggest that suppression of IL-33R expression in neutrophils, preventing IL-33-induced neutrophil migration, may be an important mechanism of anti-TNF alpha therapy of inflammation.

The A61 G EGF polymorphism is associated with development of extraaxial nervous system tumors but not with overall survival

Epidermal growth factor can activate several signaling pathways, leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. The EGF protein is involved in nervous system development, and polymorphisms in the EGF gene on chromosome band 4q25 are associated with brain cancers. The purpose of this study was to investigate the association between the single-nucleotide polymorphism of EGF + 61 G/A and extraaxial brain tumors in a population of the southeast of Brazil. We analyzed the genotype distribution of this polymorphism in 90 patients and 100 healthy subjects, using the polymerase chain reaction restriction fragment length polymorphism technique. Comparison of genotype distribution revealed a significant difference between patients and control subjects (P < 0.001). The variant genotypes of A/G and G/G were associated with a significant increase of the risk of tumor development, compared with the homozygote A/A (P < 0.0001). When the analyses were stratified, we observed that the genotype GIG was more frequent in female patients (P = 0.021). The same genotype was observed more frequently in patients with low-grade tumors (P = 0.001). Overall survival rates did not show statistically significant differences. Our data suggest that the EGF A61 G polymorphism can be associated with susceptibility to development of these tumors. (C) 2010 Elsevier Inc. All rights reserved.

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.