Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ∼83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ∼56% of primary tumors and in ∼90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.

Involvement of central cholinergic mechanisms on sodium intake induced by gabaergic activation of the lateral parabrachial nucleus

Bilateral injections of the GABAA agonist muscimol into the lateral parabrachial nucleus (LPBN) disrupt satiety and induce strong ingestion of water and 0.3M NaCl in fluid-replete rats by mechanisms not completely clear. In the present study, we investigated the effects of the blockade of central muscarinic cholinergic receptors with atropine injected intracerebroventricularly (i.c.v.) on 0.3M NaCl and water intake induced by muscimol injections into the LPBN in fluid-replete rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the LPBN and unilaterally into the lateral ventricle (LV) were used. Bilateral injections of muscimol (0.5nmol/0.2μL) into the LPBN induced 0.3M NaCl (32.2±9.9mL/4h, vs. saline: 0.4±0.2mL/4h) and water intake (11.4±4.4mL/4h, vs. saline: 0.8±0.4mL/4h) in fluid-replete rats previously treated with i.c.v. injection of saline. The previous i.c.v. injection of atropine (20nmol/1μL) reduced the effects of LPBN-muscimol on 0.3M NaCl (13.5±5.0mL/4h) and water intake (2.9±1.6mL/4h). The i.c.v. injection of atropine did not affect 0.3M NaCl (26.8±6.2mL/2h, vs. saline i.c.v.: 36.5±9.8mL/2h) or water intake (14.4±2.5mL/2h, vs. saline i.c.v.: 15.6±4.8mL/2h) in rats treated with furosemide+captopril subcutaneously combined with bilateral injections of moxonidine (α2-adrenoceptor/imidazoline agonist, 0.5nmol/0.2μL) into the LPBN, suggesting that the effect of atropine was not due to non-specific inhibition of ingestive behaviors. The results show that active central cholinergic mechanisms are necessary for the hypertonic NaCl and water intake induced by the blockade of the inhibitory mechanisms with injections of muscimol into the LPBN in fluid-replete rats. The suggestion is that in fluid-replete rats the action of LPBN mechanisms inhibits facilitatory signals produced by the activity of central cholinergic mechanisms to maintain satiety. © 2012 Elsevier B.V.

Cardiac remodeling induced by 13-cis retinoic acid treatment in acne patients

Background: Currently, 13-cis-retinoic acid (13-cis-RA) is the most effective therapy for acne. Isotretinoin, a first-generation synthetic 13-cis-RA compound, is associated with numerous adverse effects. To investigate the cardiac effects of 13-cis-RA, acne patients receiving 13-cis-RA were studied. Methods: Twenty male patients with acne were enrolled in the study. Patients were treated with a dose of 0.5 mg/kg/d of isotretinoin. All participants were assessed prior to treatment and after 10 weeks of therapy with Doppler-echocardiogram. Results: Patients showed reductions in right atrium vertical diameter, left atrium longitudinal diameter, left atrium volume and left ventricular diastolic diameter over the course of treatment. Significant increases in interventricular septum diastolic thickness, posterior wall diastolic thickness, relative wall relative thickness and left ventricle (LV) mass were observed. The LV mass index showed an increase in ventricular mass and a decrease in the cavity size. Examining LV systolic function, a decrease was observed for the cardiac index. Conclusion: In this study, 10 weeks of 13-cis-RA therapy at a dose of 0.5 mg/kg/d was found to promote concentric-type heart remodeling due to the occurrence of two associated events: heart hypertrophy and hypovolemia. © 2011 Elsevier B.V. All rights reserved.

Adsorption of reactive dye on seawater-neutralised bauxite refinery residue

This investigation has demonstrated the need for thermal treatment of seawater neutralised red mud (SWRM) in order to obtain reasonable adsorption of Reactive Blue dye 19 (RB 19). Thermal treatment results in a greater surface area, which results in an increased adsorption capacity due to more available adsorption sites. Adsorption of RB 19 has been found to be best achieved in acidic conditions using SWNRM400 (heated to 400 °C) with an adsorption capacity of 416.7. mg/g compared to 250.0. mg/g for untreated SWNRM. Kinetic studies indicate a pseudosecond-order reaction mechanism is responsible for the adsorption of RB 19 using SWNRM, which indicates adsorption occurs by electrostatic interactions. © 2013 Elsevier Inc.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats

Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.68). In animals exposed to gasoline, we observed an increase in AUC0-∞ for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Chirality 25:206-210, 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

Chrysobalanaceae: Secondary metabolites, ethnopharmacology and pharmacological potential

Many Chrysobalanaceae species, in special Licania and Parinari, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activities and the secondary metabolites reported so far for Chrysobalanaceae. The chemical constituents of this family include triterpenoids, diterpenoids, steroids and phenylpropanoids like flavonoids as well as chromones derivatives. © 2012 Springer Science+Business Media Dordrecht.

Ethopharmacological evaluation of the rat exposure test: A prey-predator interaction test

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT1A/5-HT2 receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs. © 2012 Elsevier B.V.

Determination of disease biomarkers in Eucalyptus by comprehensive two-dimensional gas chromatography and multivariate data analysis

In this paper is reported the use of the chromatographic profiles of volatiles to determine disease markers in plants - in this case, leaves of Eucalyptus globulus contaminated by the necrotroph fungus Teratosphaeria nubilosa. The volatile fraction was isolated by headspace solid phase microextraction (HS-SPME) and analyzed by comprehensive two-dimensional gas chromatography-fast quadrupole mass spectrometry (GC. ×. GC-qMS). For the correlation between the metabolic profile described by the chromatograms and the presence of the infection, unfolded-partial least squares discriminant analysis (U-PLS-DA) with orthogonal signal correction (OSC) were employed. The proposed method was checked to be independent of factors such as the age of the harvested plants. The manipulation of the mathematical model obtained also resulted in graphic representations similar to real chromatograms, which allowed the tentative identification of more than 40 compounds potentially useful as disease biomarkers for this plant/pathogen pair. The proposed methodology can be considered as highly reliable, since the diagnosis is based on the whole chromatographic profile rather than in the detection of a single analyte. © 2013 Elsevier B.V..

Association between energy cost of walking, muscle activation, and biomechanical parameters in older female fallers and non-fallers

Objective: To determine the nervous activation, muscle strength, and biomechanical parameters that influence the cost of walking in older fallers and non-fallers. Methods: Maximal voluntary isokinetic torque was measured for the hip, knee and ankle of older women. Oxygen consumption was measured at rest and during 8 min of walking at self-selected speed. An additional minute of walking was performed to collect kinematic variables and the electromyographic signal of trunk, hip, knee, and ankle muscles, which was analyzed by the linear envelope. Cost of walking was calculated by subtracting resting body mass-normalized oxygen consumption from walking body mass-normalized oxygen consumption. Stride time and length, and ankle and hip range of motion were calculated from kinematic data. Findings: Older adult fallers had 28% lower knee extensor strength (p = 0.02), 47% lower internal oblique activation at heel contact (p = 0.03), and higher coactivation between tibialis anterior and gastrocnemius lateralis in each of the gait phases (p < 0.05). For fallers, a higher activation of gluteus maximus was associated with a higher cost of walking (r = 0.55, p < 0.05 and r = 0.71, p < 0.01, before and after heel contact, respectively). For non-fallers, an association between cost of walking and age (r = 0.60, p = 0.01) and cost of walking and thigh muscle coactivation (r = 0.53, p = 0.01) existed. Interpretation: This study demonstrated that there may be links between lower-extremity muscle weakness, muscle activation patterns, altered gait, and increased cost of walking in older fallers. © 2013 Elsevier Ltd. All rights reserved.

Evaluation of reusable cardboard box designs: Biomechanical and perceptual aspects

Reusable cardboard boxes can be ergonomically designed for internal transportation of dry products in industrial settings. In this study we compared the effects of handling a regular commercial box and two cardboard prototypes on upper limb postures through the evaluation of movements, myoelectrical activity, perceived grip acceptability and capacity for reuse. The ergonomic designs provided a more acceptable grip, safer wrist and elbow movements and lower wrist extensors and biceps activity. Biomechanical disadvantages were observed only for one of the prototypes when handling to high surface. The prototypes were durable and suitable for extensive reuse (more than 2000 handlings) in internal industrial transportation. Despite being slightly more expensive than regular cardboard, the prototypes showed good cost-benefit considering their high durability. Relevance to industry: Cardboard boxes can be efficiently redesigned for allowing safer upper limb movements and lower muscle workload in manual materials handling. New designs can also be extensively reused for internal industrial transportation with good cost-benefit. © 2012 Elsevier B.V.

Muscle strength and ankle mobility for the gait parameters in diabetic neuropathies

Aims: To evaluate the spatio-temporal variables of gait and the isometric muscle strength component of the ankle in patients with peripheral diabetic neuropathy. Also, verify the relationship between these variables and gait parameters. Methods: This study involved 25 diabetic peripheral neuropathy (DPN) participants (62.4 ± 8.36 years) and 27 age-matched healthy control individuals (64.48 ± 6.21 years). The assessment of the spatio-temporal parameters of gait was performed using an electronic baropodometry treadmill. Prior to the collection data, each participant was instructed to walk on the treadmill in her/his habitual self-selected speed. Results: Diabetic neuropathy group showed impairment of gait, with a smaller stride and length speed of the cycle, and increased duration of support time. Restricted dorsiflexion mobility and increased plantarflexion mobility were found, with a decrease in muscle strength of the dorsiflexors and plantiflexors. There was a significant relationship between plantiflexor muscle strength and the length and speed of the gait cycle. Also the muscle strengths of the plantiflexors and dorsiflexors, and the range of motion of dorsiflexion were predictors of gait performance. Conclusions: The ankle, muscle strength and ankle mobility variables could explain changes in gait speed and range of motion in patients with DPN, allowing for the application of preventive strategies. © 2012 Elsevier Ltd.

Caring for heart transplant recipients: The lived experience of primary caregivers

Objective: To understand the experience of primary caregivers of heart transplant recipients. Methods: A phenomenological approach was used to understand the caregivers' experience of caring for a heart transplant patient. In-depth interviews were conducted with 11 caregivers, in a Brazilian hospital, from December 2008 to March 2009. Results: Following the transplant, caregivers' lives change drastically; their priority becomes providing care for their relative. Despite successful transplant results, the uncertainty about future remains, generating permanent distress. Anxiety is exacerbated by familial or economic problems and, consequently, many participants turn to their local communities for support. Some caregivers learn from the experience and plan return to regular activities. Others feel helpless, unable to overcome personal losses and difficulties. Conclusions: Nurses are ideally placed to lead the way by providing family-centered support and education for caregivers of heart recipients. Listening to the concerns of family caregivers seems to be an essential aspect of effective interventions. © 2013 Elsevier Inc.

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

Objective: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. Materials and methods: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p < 0.05. Results: The data showed a predominance of M2 phenotype (high percentage of IL-10+TGF-β+) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). Conclusion: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time. © 2012 Elsevier Ltd. All rights reserved.

Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats

We investigated the behavioral and molecular interactions between cocaine and nicotine, through evaluating locomotor activity, nicotine intravenous self-administration and gene expression. Locomotor sensitization was induced in male Wistar rats by repeated cocaine (20 mg/kg; i.p.) or saline injections once a day over 7 days. Three days after the last injection, rats were challenged with either saline or cocaine (15 mg/kg; i.p.) and the locomotor activity was measured. The very next day animals received either saline or nicotine (0.4 mg/kg; s.c.) and the locomotor cross-sensitization was tested. Animals were then prepared with intrajugular catheters for nicotine self-administration. Nicotine self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement and a 24-h unlimited access binge. Immediately after the binge sessions animals were decapitated, the brains were removed and the nucleus accumbens was dissected. The dynorphin (DYN), μ-opioid receptor (mu opioid), neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), tropomyosin-related tyrosine kinase B receptor (TrkB) and corticotropin- releasing factor receptor type 1 (CRF-R1) gene expression were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with cocaine caused sensitization of cocaine motor response and locomotor cross-sensitization with nicotine. In the self-administration experiments repeated cocaine administration caused an increase in the nicotine break point and nicotine intake during a 24 h binge session. © 2013 Elsevier Inc.