HJV Hemochromatosis, Iron Overload, and Hypogonadism in a Brazilian Man: Treatment with Phlebotomy and Deferasirox

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil[2008/54131-0]

B-1 cells modulate oral tolerance in mice

Although the origin and functions of B-1 cells are controversial, they are considered as a cellular element of innate immunity due to their ability to produce natural autoantibodies of the IgM type. These antibodies are encoded by a relatively limited repertoire of V genes, and their resulting diversity is smaller than that produced by conventional B cells. B-1 cells constitute the larger fraction of B cells in the peritoneal cavity and migrate to non-specific inflammation sites. In addition, they contribute to the production of IgA antibodies in the intestinal lamina propria. It has been demonstrated that they participate in the induction and maintenance of peripheral tolerance. Herein, the participation of B-1 cells in inducing oral tolerance is evaluated. Unexpectedly, BALB/Xid mice, the animals deficient in B-1 cells, are not tolerized to OVA but instead are responsive to oral immunization. Conversely, BALB/c mice respond to oral tolerance to this antigen. We used these biological characteristics of these animals to investigate whether BA cells are involved in the induction of oral tolerance to OVA. Results show that B-1 cells from BALB/c mice, treated orally with OVA and adoptively transferred to BALB/Xid mice were able to suppress local hypersensitivity reaction and lymphoproliferative cellular response observed in BALB/.Xid mice. These data demonstrate that B-1 cells have regulatory properties and are involved in the induction of oral tolerance. (C) 2009 Elsevier B.V. All rights reserved.

Atorvastatin effects on SREBF1a and SCAP gene expression in mononuclear cells and its relation with lowering-lipids response

Background: The transcription factors SREBP1 and SCAP are involved in intracellular cholesterol homeostasis. Polymorphisms of these genes have been associated with variations on serum lipid levels and response to statins that are potent cholesterol-lowering drugs. We evaluated the effects of atorvastatin on SREBF1a and SCAP mRNA expression in peripheral blood mononuclear cells (PBMC) and a possible association with gene polymorphisms and lowering-cholesterol response. Methods: Fifty-nine hypercholesterolemic patients were treated with atorvastatin (10 mg/day for 4 weeks). Serum lipid profile and mRNA expression in PBMC were assessed before and after the treatment. Gene expression was quantified by real-time PCR using GAPD as endogenous reference and mRNA expression in HepG2 cells as calibrator. SREBF1 -36delG and SCAP A2386G polymorphisms were detected by PCR-RFLP. Results: Our results showed that transcription of SREBF1a and SCAP was coordinately regulated by atorvastatin (r=0.595, p<0.001), and that reduction in SCAP transcription was associated with the 2386AA genotype (p=0.019). Individuals who responded to atorvastatin with a downregulation of SCAP had also a lower triglyceride compared to those who responded to atorvastatin with an upregulation of SCAP. Conclusion: Atorvastatin has differential effects on SREBF1a and SCAP mRNA expression in PBMC that are associated with baseline transcription levels, triglycerides response to atorvastatin and SCAP A2386G polymorphism. (c) 2008 Elsevier B.V. All rights reserved.

Biophysical techniques used to evaluate the stratum corneum

Assortments of biophysical methods are used to the study the stratum corneum morphology and dynamic with the objective to elucidate the correlation between its structure and functions. Among these methods, there are: X-ray diffraction, electron paramagnetic resonance, differential scanning calorimetry, Raman spectroscopy with Fourrier transform, infrared spectroscopy and photoacustic spectroscopy. In this manuscript, methods are presented and discussed in relation to the use indication, interpretation of results and advantages and limitations to the stratum corneum analysis.

Characterization of Brazilian lager and brown ale beers based on color, phenolic compounds, and antioxidant activity using chemometrics

BACKGROUND: Epidemiological studies have shown that beer has positive effects on inhibiting atherosclerosis, decreasing the content of serum low-density lipoprotein cholesterol and triglycerides, by acting as in vivo free radical scavenger. In this research, the antioxidant activity of commercial Brazilian beers (n = 29) was determined by the oxygen radical absorbance capacity (ORAC) and 1,1 -diphenyl-2-picrylhydrazyl (DPPH(center dot)) assays and results were analyzed by chemometrics. RESULTS: The brown ale samples (n = 11) presented higher (P < 0.05) flavonoids (124.01 mg L(-1)), total phenolics (362.22 mg L(-1)), non-flavonoid phenolics (238.21 mg L(-1)), lightness (69.48), redness (35.75), yellowness (55.71), color intensity (66.86), hue angle (59.14), color saturation (0.9620), DPPH(center dot) values (30.96% inhibition), and ORAC values (3,659.36 mu mol Trolox equivalents L(-1)), compared to lager samples (n = 18). Brown ale beers presented higher antioxidant properties (P < 0.05) measured by ORAC (1.93 times higher) and DPPH (1.65 times higher) compared to lager beer. ORAC values correlated well with the content of flavonoids (r = 0.47; P = 0.01), total phenolic compounds (r = 0.44; P < 0.01) and DPPH (r = 0.67; P < 0.01). DPPH values also correlated well to the content of flavonoids (r = 0.69; P < 0.01), total phenolic compounds (r = 0.60; P < 0.01), and non-flavonoid compounds (r = 0.46; P = 0.01). CONCLUSION: The results suggest that brown ale beers, and less significantly lager beers, could be sources of bioactive compounds with suitable free radical scavenging properties. (C) 2010 Society of Chemical Industry

Monitoring the authenticity of Brazilian UHT milk: A chemometric approach

In this work, chemometric methods are reported as potential tools for monitoring the authenticity of Brazilian ultra-high temperature (UHT) milk processed in industrial plants located in different regions of the country. A total of 100 samples were submitted to the qualitative analysis of adulterants such as starch, chlorine, formal. hydrogen peroxide and urine. Except for starch, all the samples reported, at least, the presence of one adulterant. The use of chemometric methodologies such as the Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) enabled the verification of the occurrence of certain adulterations in specific regions. The proposed multivariate approaches may allow the sanitary agency authorities to optimise materials, human and financial resources, as they associate the occurrence of adulterations to the geographical location of the industrial plants. (c) 2010 Elsevier Ltd. All rights reserved.

Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: Efficacy of tributyrin, a butyric acid prodrug

Hepatocellular carcinoma (HCC) ranks in prevalence and mortality among top 10 cancers worldwide. Butyric acid (BA), a member of histone deacetylase inhibitors (HDACi) has been proposed as an anticareinogenic agent. However, its short half-life is a therapeutical limitation. This problem could be circumvented with tributyrin (TB), a proposed BA prodrug. To investigate TB effectiveness for chemoprevention, rats were treated with the compound during initial phases of ""resistant hepatocyte"" model of hepatocarcinogenesis, and cellular and molecular parameters were evaluated. TB inhibited (p < 0.05) development of hepatic preneoplastic lesions (PNL) including persistent ones considered HCC progression sites. TB increased (p < 0.05) PNL remodeling, a process whereby they tend to disappear. TB did not inhibit cell proliferation in PNL, but induced (p < 0.05) apoptosis in remodeling ones. Compared to controls, rats treated with TB presented increased (P < 0.05) hepatic levels of BA indicating its effectiveness as a prodrug. Molecular mechanisms of TB-induced hepatocarcinogenesis chemoprevention were investigated. TB increased (p < 0.05) hepatic nuclear histone H3K9 hyperacetylation specifically in PNL and p21 protein expression, which could be associated with inhibitory HDAC effects. Moreover, it reduced (p < 0.05) the frequency of persistent PNL with aberrant cytoplasmic p53 accumulation, an alteration associated with increased malignancy. Original data observed in our study support the effectiveness of TB as a prodrug of BA and as an HDACi in hepatocarcinogenesis chemoprevention. Besides histone acetylation and p21 restored expression, molecular mechanisms involved with TB anticarcinogenic actions could also be related to modulation of p53 pathways. (C) 2008 Wiley-Liss, Inc.

Experimental Chagas` disease in orchiectomized Calomys callosus infected with the CM strain of Trypanosoma cruzi

The incidence and progression of disorders associated with an unbalanced immune response has among many factors the gender as a contributory factor. The aims of this work were to evaluate the effects of orchiectomy and the immune response during the experimental Trypanosoma cruzi infection. Young adult, male Calomys callous were i.p. inoculated with 1 x 10(5) blood trypomastigotes of the CM strain of T. cruzi and divided in groups: Control, Sham and Castrated. Castrated group displayed significantly lower values for prostate and seminal vesicle weights indicating a drastic drop of testosterone plasmatic levels. Orchiectomized animals also displayed lesser number of blood parasites, enhanced lytic antibody percentage, splenocyte proliferation and NO concentration when compared to its sham and control counterparts, indicating that steroid gonadal ablation actually influences immune response triggering a more efficient cellular and humoral response which led animals to become more resistant against T cruzi infection. (C) 2009 Elsevier Inc. All rights reserved.

Trypanosoma cruzi: Do different sylvatic strains trigger distinct immune responses?

Strains of Trypanosoma cruzi are multiclonal populations that can be classified in groups or genotypes, differing in pathogenicity, virulence, and histotropism. In this experiment the distinct behavior of two strains of T. cruzi, MORC-1 and MORC-2, was documented. Blood parasitemia, spleen proliferation, nitric oxide, histopathology of the spleen and heart were used as tools to evaluate parasite persistence. Groups of male mice were separated and divided in three groups: Control (C), Infected (IM-1) and Infected (IM-2). The peak of parasitemia occurred on 10 days post infection for both strains. LPS stimulated animals, infected MORC-2 group displayed significant higher concentrations of NO when compared to infected MORC-1 group (P < 0.05). For ConA stimulated lymphoproliferation, infected MORC-1 group displayed higher proliferation index as compared to infected MORC-2 group. An opposite behavior for IL-4 and TNF-alpha was observed according to the strain. For MORC-1 enhanced concentrations of IL-4 were present with concomitant reduced levels of TNF-alpha, while for MORC-2 enhanced concentrations of TNF-alpha and reduced levels of IL-4 were found. The histopathology of heart and spleen showed important differences in which MORC-1 displayed statistically enhanced number of amastigote in the heart and spleen as compared to MORC-2. Concluding, each strain triggered a distinct immune response with enhanced cytokine TH-1 profile for MORC-2 and TH-2 for MORC-1. (C) 2009 Elsevier Inc. All rights reserved.

The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and Hop is located in the dimerization domain of hsp90

Structurally related tetratricopeptide repeat motifs in steroid receptor-associated immunophilins and the STI1 homolog, Hop, mediate the interaction with a common cellular target, hsp90, We have identified the binding domain in hsp90 for cyclophilin 40 (CyP40) using a two-hybrid system screen of a mouse cDNA library. All isolated clones encoded the intact carboxyl terminus of hsp90 and overlapped with a common region corresponding to amino acids 558-724 of murine hsp84, The interaction was confirmed in vitro with bacterially expressed CyP40 and deletion mutants of hsp90 beta and was delineated further to a 124-residue COOH-terminal segment of hsp90, Deletion of the conserved MEEVD sequence at the extreme carboxyl terminus of hsp90 precludes interaction with CyP40, signifying an important role for this motif in hsp90 function. We show that CyP40 and Hop display similar interaction profiles with hsp90 truncation mutants and present evidence for the direct competition of Hop and FK506-binding protein 52 with CyP40 for binding to the hsp90 COOH-terminal region. Our results are consistent with a common tetratricopeptide repeat interaction site for Hop and steroid receptor associated immunophilins within a discrete COOH-terminal domain of hsp90. This region of hsp90 mediates ATP-independent chaperone activity, overlaps the hsp90 dimerization domain, and includes structural elements important for steroid receptor interaction.

A survey of contact with offspring and assistance with child care among parents with psychotic disorders

To help improve services for parents with psychotic disorders, patients with such disorders in three treatment agencies in Queensland, Australia, were surveyed about whether they were parents, how much contact they had with their offspring, and who provided assistance with child care. Of the 342 individuals with psychotic disorders mho participated in the study, 124 were parents. Forty-eight parents in the study had children under age 16, and 20 of these parents (42 percent) had their children living with them. Most parents relied on relatives or friends for assistance with child care. Barriers to child care services identified by parents were inability to pay, lack of local services, and fear of losing custody of children.

Hippolyte obliquimanus (Decapoda : Caridea : Hippolytidae): a gonochoric or hermaphroditic shrimp species?

Several studies have reported the occurrence of hermaphroditism in caridean shrimps of the family Hippolytidae. Here we provide the first observations of population traits from the small Western Atlantic shrimp, Hippolyte obliquimanus, to determine its sexual system using descriptive and experimental approaches. Specimens were collected at 2-month intervals from March 2005 to May 2006 in Ubatuba Bay on the northern coast of the state of Sao Paulo, Brazil. The sex of individuals was checked and morphometric dimensions (carapace length, maximum pleura of second abdominal segment width, appendix masculina length, maximum propodus width, and dactyl length of the third pereopod) were also analyzed. The gonads were dissected and examined for signs of abnormalities. The possibility of sex change was experimentally evaluated under laboratory conditions. A total of 674 specimens were collected: 211 males, 339 non-ovigerous females, and 124 ovigerous females. The carapace length ranged from 0.55 to 3.20 mm, with females being significantly larger than males. Hippolyte obliquimanus showed sexual dimorphism in the third pereopod, absence of cincinnuli in the first pleopod, and no reduction of the appendix masculina in the largest males. All males examined had only testes, and all females had only ovaries. There was no sex change observed in the experiments. Together, these data indicate a population with females reaching larger sizes than males, males with a well-developed appendix masculina, and no transitional individuals. The results presented allow characterizing H. obliquimanus as a gonochoric species.

Cost effectiveness of adding magnetic resonance imaging to the usual management of suspected scaphoid fractures

Objective: To determine the cost effectiveness of a magnetic resonance imaging scan (MRI) within 5 days of injury compared with the usual management of occult scaphoid fracture. Methods: All patients with suspected scaphoid fractures in five hospitals were invited to participate in a randomised controlled trial of usual treatment with or without an MRI scan. Healthcare costs were compared, and a cost effectiveness analysis of the use of MRI in this scenario was performed. Results: Twenty eight of the 37 patients identified were randomised: 17 in the control group, 11 in the MRI group. The groups were similar at baseline and follow up in terms of number of scaphoid fractures, other injuries, pain, and function. Of the patients without fracture, the MRI group had significantly fewer days immobilised: a median of 3.0 (interquartile range 3.0-3.0) v 10.0 (7-12) in the control group (p = 0.006). The MRI group used fewer healthcare units (median 3.0, interquartile range 2.0-4.25) than the control group (5.0, 3.0-6.5) (p = 0.03 for the difference). However, the median cost of health care in the MRI group ($594.35 AUD, $551.35-667.23) was slightly higher than in the control group ($428.15, $124.40-702.65) (p = 0.19 for the difference). The mean incremental cost effectiveness ratio derived from this simulation was that MRI costs $44.37 per day saved from unnecessary immobilisation (95% confidence interval $4.29 to $101.02). An illustrative willingness to pay was calculated using a combination of the trials measure of the subjects' individual productivity losses and the average daily earnings. Conclusions: Use of MRI in the management of occult scaphoid fracture reduces the number of days of unnecessary immobilisation and use of healthcare units. Healthcare costs increased non-significantly in relation to the use of MRI in this setting. However, when productivity losses are considered, MRI may be considered cost effective, depending on the individual case.

Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or nore-pineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. Conclusions: Our study suggests that vmPFC DES in rats maybe useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.

Thoracic aorta calcification detected by electron beam tomography predicts all-cause mortality

Background: The presence of coronary artery calcium (CAC) is an independent marker of increased risk of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally identified without further scanning during assessment of CAC, is unknown. Methods: We followed a cohort of 8401 asymptomatic individuals (mean age: 53 +/- 10 years, 69% men) undergoing cardiac risk factor evaluation and TAC and CAC testing with electron beam computed tomography. Multivariable Cox proportional hazards models were developed to predict all-cause mortality based on the presence of TAC. Results: During a median follow-up period of 5 years, 124 (1.5%) deaths were observed. Overall survival was 96.9% and 98.9% for those with and without detectable TAC, respectively (p < 0.0001). Compared to those with no TAC, the hazard ratio for mortality in the presence of TAC was 3.25 (95% CI: 2.28-4.65, p < 0.0001) in unadjusted analysis. After adjusting for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking and family history of premature coronary artery disease, and presence of CAC the relationship remained robust (HR 1.61, 95% CI: 1.10-2.27, p = 0.015). Likelihood ratio chi(2) statistics demonstrated that the addition of TAC contributed significantly in predicting mortality to traditional risk factors alone (chi(2) = 13.62, p = 0.002) as well as risk factors + CAC (chi(2) = 5.84, p = 0.02) models. Conclusion: In conclusion, the presence of TAC was associated with all-cause mortality in our study; this relationship was independent of conventional CVD risk factors as well as the presence of CAC. (C) 2009 Elsevier Ireland Ltd. All rights reserved.