LEUCINE ATTENUATES SKELETAL MUSCLE WASTING VIA INHIBITION OF UBIQUITIN LIGASES

The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization. Muscle Nerve 41: 800-808, 2010

Relationship Between Cortisol Levels and Memory Performance may be Modulated by the Presence or Absence of Cognitive Impairment: Evidence from Healthy Elderly, Mild Cognitive Impairment and Alzheimer`s Disease Subjects

An inverted U-shape function between cortisol levels and memory performance has been reported in studies on both young animals and humans. Yet little is known about this relationship in normal aging or in older subjects with cognitive impairment. This issue is particularly significant since increased levels of cortisol have been reported in Alzheimer`s disease (AD). The present study examined the association between cortisol levels and visual memory performance in healthy subjects as well as in individuals presenting mild cognitive impairment (MCI) or AD. Salivary cortisol was measured in 40 healthy elderly subjects, 31 individuals with amnestic MCI, and 40 subjects with mild probable AD. Memory performance was evaluated using the Brief Cognitive Screening Battery. Higher cortisol levels were associated with better memory performance in healthy elderly (p = 0.005), while higher cortisol levels were correlated with poorer memory performance in MCI subjects (p = 0.011). No correlation between cortisol and memory was found in the AD group (p > 0.05). These results suggest that the relationship between cortisol levels and memory performance in the aging process could vary according to the presence or absence of cognitive impairment.

Memory with emotional content, brain amygdala and Alzheimer`s disease

Objectives - A highly adaptive aspect of human memory is the enhancement of explicit, consciously accessible memory by emotional stimuli. We studied the performance of Alzheimer`s disease (AD) patients and elderly controls using a memory battery with emotional content, and we correlated these results with the amygdala and hippocampus volume. Methods - Twenty controls and 20 early AD patients were subjected to the International Affective Picture System (IAPS) and to magnetic resonance imaging-based volumetric measurements of the medial temporal lobe structures. Results - The results show that excluding control group subjects with 5 or more years of schooling, both groups showed improvement with pleasant or unpleasant figures for the IAPS in an immediate free recall test. Likewise, in a delayed free recall test, both the controls and the AD group showed improvement for pleasant pictures, when education factor was not controlled. The AD group showed improvement in the immediate and delayed free recall test proportional to the medial temporal lobe structures, with no significant clinical correlation between affective valence and amygdala volume. Conclusion - AD patients can correctly identify emotions, at least at this early stage, but this does not improve their memory performance.

Influence of the Photostabilizer in the Photoprotective Effects of a Formulation Containing UV-Filters and Vitamin A

Vitamin A palmitate has been used in cosmetics; however, studies report that this substance shows photoreactivity that can lead to loss of safety and efficacy. On the other hand, photostabilizers have been used to increase sunscreen photostability and consequently their safety and effectiveness. Thus, this study aimed to evaluate the influence of photostabilizers on the photoprotective effects of a cosmetic formulation containing UV-filters and vitamin A palmitate. The formulation containing UV-filters was supplemented with vitamin A palmitate and the photostabilizers diethylhexyl 2,6-naphthalate (DEHN), bumetrizole and benzotriazolyl dodecyl p-cresol (BTDC). Hairless mice were treated daily by topical applications and irradiated (UVA/B). Erythema index, transepidermal water loss, histological/histometric analysis and number of sunburn cells (SBC) were evaluated. The results showed that all formulations protected from UV-induced enhancement of erythema and SBC but there was no difference among them. The formulation with no stabilizers reduced viable epidermis thickness due to atrophy induced by UV radiation. Thus, it can be concluded that the presence of photostabilizers influenced the effects of formulations containing UV-filters and vitamin A palmitate, which could be seen by histological and histometric analysis. Furthermore, the formulations containing the stabilizers DEHN and BTDC showed better protective effects on hairless mice skin.

Early Effects on T lymphocyte Response to Iron Deficiency in Mice. Short Communication

Iron deficiency is a common nutritional disorder, affecting about 30% of the world population. Deficits in iron functional compartments have suppressive effects on the immune system. Environmental problems, age, and other nutrient deficiencies are some of the situations which make human studies difficult and warrant the use of animal models. This study aimed to investigate alterations in the immune system by inducing iron deficiency and promoting recuperation in a mouse model. Hemoglobin concentration, hematocrit, liver iron store, and flow cytometry analyses of cell-surface transferrin receptor (CD71) on peripheral blood and spleen CD4+ and CD8+ T lymphocyte were performed in the control (C) and the iron-deficient (ID) groups of animals at the beginning and end of the experiment. Hematological indices of C and ID mice were not different but the iron stores of ID mice were significantly reduced. Although T cell subsets were not altered, the percentage of T cells expressing CD71 was significantly increased by ID. The results suggest that iron deficiency induced by our experimental model would mimic the early events in the onset of anemia, where thymus atrophy is not enough to influence subset composition of T cells, which can still respond to iron deficiency by upregulating the expression of transferrin receptor.

Trypanosoma cruzi: Effects of adrenalectomy during the acute phase of experimental infection

Glucocorticoid hormones have been implicated as an important modulator of Trypanosoma cruzi pathogenesis. Since adrenal steroid hormones play a fundamental role in modulating the immune response, we hypothesized that adrenalectomy affect the course of the experimental T. cruzi infection. This study was undertaken to determine the effects of adrenalectomy during the acute phase of T cruzi infection. Blood and tissue parasitism, macrophages, nitric oxide (NO) production and IFN-gamma were evaluated in male Wistar rats infected with the Y strain of T. cruzi. Our results show that adrenalectomized rats displayed increased number of blood and heart parasites accompanied by decreases in the total number of peritoneal macrophages and IFN-gamma when compared to controls. Adrenalectomy also reduced the levels of NO released from peritoneal macrophages of infected animals. These results suggest that adrenal corticosteroid insufficiency due to adrenalectomy could be considered an important factor during development of acute phases of experimental Chagas` disease, enhancing pathogenesis through disturbance of the host`s immune system. (C) 2008 Published by Elsevier Inc.

Prolactin: Does it exert an up-modulation of the immune response in Trypanosoma cruzi-infected rats?

During the course of infection by Trypanosma cruzi, the host immune system is involved in distinct, complex interactions with the endocrine system, and prolactin (PRL) is one of several hormones involved in immunoregulation. Although intensive studies attempting to understand the mechanisms that underlie Chagas` disease have been undertaken, there are still some pieces missing from this complex puzzle. Because data are scarce concerning the role of PRL involvement in Chagas` disease and taking into account the existence of crosstalk between neuroendocrine hormones and the immune system, the current study evaluates a possible up-regulation of the cellular immune response triggered by PRL in T. cruzi-infected rats and the role of PRL in reversing immunosuppression caused by the parasitic infection. The data shown herein demonstrate that PRL induces the proliferation of T lymphocytes, coupled with an activation of macrophages and the production of nitric oxide (NO), leading to a reduction in the number of blood trypomastigotes during the peak of parasitemia. During the acute phase of T. cruzi infection, an enhancement of both CD3+CD4+ and CD3+CD8+ T cell populations were observed in infected groups, with the highest numbers of these T cell subsets found in the infected group treated with PRL Because NO is a signaling molecule involved in a number of cellular interactions with components of the immune system and the neuroendocrine system, PRL can be considered an alternative hormone able to up-regulate the host`s immune system, consequently lowering the pathological effects of a T. cruzi infection. (C) 2011 Elsevier B.V. All rights reserved.

DHEA and testosterone therapies in Trypanosoma cruzi-infected rats are associated with thymic changes

The ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. Testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. Dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. In this paper, it was examined the effects of DHEA and testosterone supplementation in the thymic atrophy in rats infected with Trypanosoma cruzi, by comparing blood parasitism, thymocyte proliferation, TNF-alpha and IL-12 levels. Our data point in the direction that DHEA treatment triggered enhanced thymocyte proliferation as compared to its infected counterparts and reduced production of TNF-alpha during the acute phase of infection. Oppositely, the lowest values for cells proliferation and IL-12 concentrations were reached in testosterone-supplied animals. The combined treatment testosterone and DHEA improves the effectiveness of the host`s immune response, reducing blood parasites and the immunosuppressive effects of male androgens besides increasing IL-12 concentrations and decreasing TNF-alpha levels. (C) 2010 Elsevier Ltd. All rights reserved.

Lepocreadiidae (Digenea) of Australian coastal fishes: new species of Opechona Looss, 1907, Lepotrema Ozaki, 1932 and Bianium Stunkard, 1930 and comments on other species reported for the first time or poorly known in Australian waters

Opechona austrobacillaris n, sp. is described from Pomatomus saltatrix from marine sites off Western Australia and New South Wales, Australia. It differs from O. bacillaris in its elongate outline, small ventral sucker, longer pseudoesophagus (relative to the oesophagus), relatively shorter ventral sucker to ovary distance and the relatively longer post-testicular region. Lepotrema monile n. sp. is described from Pomacentrus wardi from Heron Island, Queensland. It differs from its congeners in the sphincter around the distal metraterm and the more-or-less oval ovary. Bianium spongiosum n. sp, is described from Ostracion cubicus from Lizard Island, Queensland. It differs from its congeners in lacking lateral flaps in the forebody, but in having large, internal spongiform patches in the lateral forebody. The following species are redescribed from Australian sites: Lepocreadium oyabitcha from Abudefduf whitleyi, Lizard Island; Clavogalea trachinoti from Trachinotus botla, Heron Island and T. coppingeri, New South Wales, Stradbroke Island, Queensland and Heron Island; Myzoxenus insolens from Notolabrus parilus, Western Australia; Bulbocirrus aulostomi from Aulostomus chinensis, Heron Island; Lepocreadioides orientalis [new synonyms: Bicaudum interruptum Bilqees, 1973; Lepocreadioides interruptum (Bilqees, 1973) Madhavi, Narasimhulu & Shameem, 1986; Lepocreadioides discum Wang, 1986; Lepocreadioides sp. of Karyakarte & Yadav (1976)] from Cynoglossus bilineata, Moreton Bay, Queensland; Hypocreadium patellare from Sufflamen chrysopterus, Heron Island; Echeneidocoelium indicum from Echeneis naucrates, Heron Island; Multitestis pyriformis from Epinephelus cyanopodus, Heron Island; Pseudopisthogonoporus vitellosus from Naso brevirostris, Heron Island; and Bianium hispidum from Torquigener whitleyi and T. pleurogramma, southern Queensland. Only M. solens and M. pyriformis have been reported from Australian waters before; both are new host records.

A H-1 MRS study of probable Alzheimer's disease and normal aging: Implications for longitudinal monitoring of dementia progression

In order to evaluate the capability of H-1 MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N-acetylas-partylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mi, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mi and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel. (C) 1999 Elsevier Science Inc.

Cisplatin-based therapy: A neurological and neuropsychological review

The present paper reviews research in the area of the broad-spectrum chemotherapeutic agent cisplatin (cis-diamminedichloro-platinum II) and examines the implications for clinical neuropsychology arising from the neurological disruption associated with cisplatin-based therapy. The paper begins with a brief review of cisplatin treatment in terms other than survival alone, and examines the side-effects and the potential central nervous system (CNS) dysfunction in terms of neurological symptoms and concomitant implications for neuropsychology. Two main implications for clinical neuropsychology arising from cisplatin therapy are identified. First, cisplatin therapy impacts upon the psychological well-being of the patient, particularly during and in the months following treatment. It is suggested that during this time, a primary role for neuropsychology is to focus upon the monitoring and the active enhancement of the patient's social, psychological and spiritual resources. Second, with regard to neurocognitive changes, the review suggests that (1) neurocognitive assessment may not yield stable results within 8 months following treatment and (2) while perceptual, memory, attentional and executive dysfunction may be predicted following cisplatin treatment, little systematic research has been carried out to investigate such a possibility. Future research might profitably address this issue and also specifically examine the effects of low dosage cisplatin-based therapy and the effects of recently developed neuroprotective agents. Finally, there is some evidence to suggest that women may be more susceptible to neurotoxicity during cisplatin therapy, but no gender-related cognitive effects are reported in the cisplatin literature. Future research could usefully investigate gender differences in association with cisplatin chemotherapy. Copyright (C) 2000 John Wiley & Sons, Ltd.

Two new species of Neolebouria Gibson, 1976 (Digenea : Opecoelidae) from temperate marine fishes of Australia

Neolebouria moretonensis n. sp. is described from Gerres subfasciatus (Gerreidae) from Moreton Bay, south-east Queensland and N. lineatus n. sp. is described from Centroberyx lineatus (Berycidae) from off Rottnest Island, south-west Western Australia. C. lineatus represents a new host family and order (Beryciformes) for the genus. The two new species are distinguished within the genus by their entire, tandem to oblique testes and cirrus-sacs that do not extend into the hind-body, by being less than 1 mm in length, and by the position of the genital pore and the relative size of the forebody and post-testicular region. N. lineatus and N. moretonensis are very similar but are distinguished by their caeca which extend further posteriorly in N. moretonensis. There is no apparent pattern in the host-specificity of this genus.

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men

The epsilon4 allele of apolipoprotem E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, arnyloid beta1-40 (Abeta40) and homocysteine, (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) mumol/L. The MTHFR genotype had no obvious impact on Hey levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hey and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95% CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hey and Alzheimer's disease.

Hyaluronidase Behavior at the Air/Liquid and Air/Lipid Interfaces and Improved Enzymatic Activity by Its Immobilization in a Biomembrane Model

Bovine testicular hyalurphidase (BT-HAase), a tetrameric enzyme responsible for randomly hyaluronic acid, catalytic hydrolysis, was successfully immobilized on Langmuir- Blodgett films prepared with the sodium salt of dihexadacylphosphoric acid, (DHP-Zn(II)) ending with dipalmitoylphosphatidylcholine, DPPC. Data of protein, adsorption at the air-liquid interface by means of pendant drop shipe analysis and interaction of the protein with Langmuir monolayers of DPPC, using a Langmuir trough, have provided information. about the conditions to be used in the protein immobilization. The dynamic surface pressure curves obtained from pendant drop experiments for the enzyme in buffer solutions indicate that, within the range of concentration investigated in this study, the enzyme exhibits the largest induction time at 5 mu g L(-1) attributed to diffusion processes. Nevertheless, it seems that, at this concentration, the most probable conformation should be the one which occupies the smallest area at pi -> 0. The surface pressure (pi) area curves obtained for BT-HAase and mixed DPPC- BT-HAase monolayers reveal the presence of the enzyme at the air-lipid interface up to 45 mN m(-1). Tests of enzymatic activity, using hyaluronic acid, HA, as the substrate, showed an increase of activity compared to the homogeneous medium. A simplified model of protein insertion into the lipid matrix is used to explain the obtained results.

Behcet`s disease associated with celiac disease: a very rare association

There are common findings between Beh double dagger et`s disease (BD) and celiac disease (CD); however, association in the same patient is a rarity. We relate the third case in the literature of this overlap in a 40-year-old woman with history of obstipation since her childhood. She also presented asymmetric polyarthralgia, loss of weight, anemia, oral recurrent aphthas (> 3/year) and genital ulcerations, inflammatory lower back pain, bowel bleeding and abdominal colic. Afterwards, she presented episodes of erythema nodosum, superficial thrombophlebitis, pseudofolliculitis and aseptic meningitis, thus fulfilling criteria for BD. Due to persistence of the digestive complaints, a gastrointestinal endoscopy was performed. The biopsy showed chronic duodenitis with intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. Endomysial antibody was positive. She fulfilled the diagnosis criteria for CD; a gluten-free diet was applied with clinical improvement. Ascertaining whether pathogenic mechanisms are common in these two conditions requires further investigation.