Patient-reported psychosocial distress in adolescents and young adults with germ cell tumours.

PURPOSE: Germ cell tumours are the most common cancer of male adolescents and young adults (AYA, age 18-39). Men in this age group have been healthy much of their lives, and a diagnosis of cancer can cause significant psychosocial distress. We therefore sought to examine the psychosocial needs of patients with germ cell tumour and determine whether needs vary based on age (AYA vs non-AYA). We hypothesized that AYA experience more anxiety and distress in emotional, practical and physical domains. METHODS: We evaluated the responses of all patients referred to British Columbia (BC) Cancer who completed a pre-consultation health assessment form. This is a validated screening questionnaire for distress, subclinical/clinical symptoms of depression and anxiety and includes the Canadian Problem Checklist domains of emotional, informational, practical, spiritual, social/family and physical concerns. RESULTS: Data were collected for 349 patients (2011-2015). Patient population was predominantly AYA (n = 227) with median age 33 (range 18-83). The top 3 AYA concerns were financial, work/school, frustration and anger. AYA patients more commonly scored positive for symptoms of subclinical/clinical anxiety than non-AYA (39.4% vs. 27.9%, p = 0.028). Those AYA patients with subclinical/clinical anxiety symptoms experienced more fears and worries, concerns regarding work/school, lack of understanding of their disease, finances and frustration and anger. CONCLUSIONS: The results of this study indicate that AYA with testicular cancer have unique needs and experience more self-reported anxiety symptoms with emotional, informational and practical concerns. This is valuable information to stakeholders for allocation of resources to address cancer survivorship amongst these patients.

Releasing and structural/mechanical properties of nano-particle/Punica granatum (Pomegranate) in poly(lactic-co-glycolic) acid/fibrin as nano-composite scaffold.

The effect of poly(lactic­co­glycolic acid) (PLGA) on structure, degradation, drug release and mechanical properties of fibrin/pomegranate(F/POM)-based drug­eluting scaffolds have been studied comprehensively. METHODS AND MATERIAL: Nanoparticle-fibrin is prepared from thrombin and fibrinogen dissolved in NaOH and HCl. Then pomegranate powder is added to it. Nanoparticles/pom are provided by freeze drying and freeze milling. The 3-D scaffold of poly(lactide-co­glycolic acid) (PLGA) was prepared via salt­leaching solvent/casting leaching method and impregnated with nanofibrin-pom. Structural and chemical component of the scaffolds were evaluated by transmission and scanning electron microscopy and furrier transmission infrared spectroscopy, respectively. Moreover, the scaffolds were characterized from the degradation rate and drug releasing rate points of view of human Adipose Derive Stem Cells (hADSCs). Cytotoxicity effects of the scaffold were evaluated on hADSCs via MTT assay. RESULTS: The results showed that the size of nanoparticles was about 100 nm. The scaffold had a slow degradation rate and it caused a sustained release pattern of pom. MTT assay indicated that nanoparticles had no cytotoxicity and fibrin-pom nanoparticles increased compressive strength of PLGA/scaffolds dramatically and also caused a proper compressive modulus. CONCLUSIONS: By adding F/POM nanoparticle to PLGA and fabricating a three­dimensional nanocomposite scaffold (PLGA/F/POM nanoparticle), special physical and mechanical properties also suitable for drug release and cell behavior were achieved, which makes it suitable for cartilage tissue engineering applications (Tab. 1, Fig. 7, Ref. 53) Keywords: hybrid composites, drug delivery, carrier, nanoparticles, scaffold.

Induction of miR-31 causes increased sensitivity to 5-FU and decreased migration and cell invasion in gastric adenocarcinoma.

Drug resistance is the main obstacle in the treatment of gastric cancer, the third most common cause of cancer-related death in the world. Due to their small size, easy entrance to cells and multiple targets, microRNAs (miRs) are considered novel and attractive targets. In the current study, parental MKN-45, MKN-45-control vector, and MKN-45-miR-31 populations were compared in terms of cell cycle transitions, migration, cell invasion, and proliferation. In addition, downstream targets of miR-31, including E2F6, and SMUG1 were examined using Real-time RT-PCR and western blotting. MKN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups (p = 0.0001, p = 0.01 and p = 0.01, respectively). There was a significant increase in the percentage of cells in G1/pre-G1 phase in MKN-45-miR-31 relative to the control groups (p = 0.001). Induction of miR-31 expression in MKN-45 caused a significant reduction of E2F6 and SMUG1 genes. Our findings indicated that induction of miR-31 expression could increase drug sensitivity, and diminish tumor cell migration and invasion of gastric cancer cells. Therefore, miR-31 can be considered as a potential target molecule in the targeted therapy of gastric cancer (Fig. 2, Ref. 43). Keywords: gastric cancer, miR-31, drug resistance, E2F6, SMUG1.

Multiphase permittivity imaging using absolute value electrical capacitance tomography data and a level set algorithm.

Multiphase flow imaging is a very challenging and critical topic in industrial process tomography. In this article, simulation and experimental results of reconstructing the permittivity profile of multiphase material from data collected in electrical capacitance tomography (ECT) are presented. A multiphase narrowband level set algorithm is developed to reconstruct the interfaces between three- or four-phase permittivity values. The level set algorithm is capable of imaging multiphase permittivity by using one set of ECT measurement data, so-called absolute value ECT reconstruction, and this is tested with high-contrast and low-contrast multiphase data. Simulation and experimental results showed the superiority of this algorithm over classical pixel-based image reconstruction methods. The multiphase level set algorithm and absolute ECT reconstruction are presented for the first time, to the best of our knowledge, in this paper and critically evaluated. This article is part of the themed issue 'Supersensing through industrial process tomography'.

Modifying the mechanical properties of silk nanofiber scaffold by knitted orientation for regenerative medicine applications.

Tissue reconstruction is among the increasing applications of polymer nanofibers. Fibrous scaffolds (mats) can be easily produced using the electrospinning method with structure and biomechanical properties similar to those of a cellular matrix. Electrospinning is widely used in the production of nanofibers and the GAP-method electrospinning is one of the means of producing fully aligned nanofibers. In this research, using the GAP-method, knitted fibrous scaffolds were made of silk fibroin, which is a biocompatible and biodegradable polymer. To extract fibroin from cocoons, the sodium chloride solution as well as dialysis and freeze-drying techniques were employed. The molecular weight of the extracted fibroin was measured with the SDS-Page electrophoresis technique. Moreover, the pure fibroin structure was examined using the ATR-FTIR method, and the viscosity of the solution used for electrospinning was measured with the Brookfield rotational viscometer. The scaffolds were prepared through electrospinning of the silk fibroin in pure formic acid solution. The following three structures were electrospun: 1) a random structure; 2) a knitted structure with an interstitial angle of 60 degrees; 3) a knitted structure with an interstitial angle of 90 degrees. Morphology of the resulting fibers was studied with a SEM (scanning electron microscope). Fibroin scaffolds are degradable in water. Therefore, they were fixated through immersion in methanol to be prepared for assays. The mechanical properties of the scaffolds were also studied using a tensile strength test device. The effect of methanol on the strength properties of the samples was also assessed. The hydrophilic potential of the samples was measured via a contact angle test. To increase the hydrophilicity of the scaffold surfaces, the cold oxygen plasma technique was employed. Finally, the biocompatibility and cell adhesion of the resulting scaffolds were examined through a HEK 293 cell culture, and the results were analyzed through the MTT, DAPI staining, and SEM imaging techniques. Results revealed that the oriented knitted structure contributed to the increase in Young's modulus and the maximum strength of scaffolds as compared to the random samples. Moreover, this structure can also be a suitable alternative to the typical chemical means of increasing strength.

Inhibition of breast tumor growth and abnormal angiogenesis in mice treated with endothelial cells and their progenitor mesenchymal stem cells derived from bone marrow.

Incorporation of endothelial cells or their progenitor cells into newly sprouting blood vessels can contribute to tissue vascularization after ischemic injury. However, the interaction of the stem cells-derived endothelial cells with angiogenesis within tumors is not well understood. The aim of this study was to examine the efficiency of endothelial-like cells derived from MSCs in controlling breast tumor growth associated with abnormal angiogenesis. For this purpose, Balb/c mouse model of breast carcinoma was developed and subjected to intra tumor (I.T)/intra venous (I.V) therapy with undifferentiated MSCs or endothelial cells derived from them. The homing of the stem cells was approved by measuring different markers as well as tracing green fluorescence protein (GFP)-labeled MSCs in the tumors. Tumor growth was measured following cell therapy using a digital caliper. At the end of treatment period (30 days) the angiogenesis markers; VEGFR2 expression as well as micro-vessel density (MVD) using CD31 were estimated in tumor tissues. Stem cell transplantation to mice bearing breast tumors resulted in tumor growth suppression in all experimental groups. The endothelial markers; CD31 and VEGFR2 were down regulated following I.T delivery of the endothelial cells. Accordingly, angiogenesis was suppressed following I.T administration of endothelial cells which was associated with increased focal necrosis in the tumors. In conclusion, data show that endothelial cells directly injected into tumors is more efficient compared to undifferentiated MSCs in controlling tumor-associated angiogenesis and tumor growth.

Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: safety and possible outcome.

STUDY DESIGN: This is a clinical trial (phase 1). OBJECTIVES: The objective of this study was to asses the safety and feasibility of bone marrow mesenchymal stem cell (MSC) and Schwann cell (SC) co-injection through cerebral spinal fluid (CSF) for the treatment of patients with chronic spinal cord injury. METHODS: Six subjects with complete spinal cord injury due to trauma according to International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) developed by the American Spinal Injury Association were enrolled. They received autologous co-transplantation of MSC and SC through lumbar puncture. Neurological status of the patients was determined by ISNCSCI, as well as by assessment of functional status by Spinal Cord Independent Measure. Before and after cell transplantation, magnetic resonance imaging (MRI) was performed for all the patients. Before the procedure, all the patients underwent electromyography, urodynamic study (UDS) and MRI tractograghy. After transplantation, these assessments were performed in special cases when the patients reported any changes in motor function or any changes in urinary sensation. RESULTS: Over the mean 30 months of follow-up, the radiological findings were unchanged without any evidence of neoplastic tissue overgrowth. American Spinal Injury Association class in one patient was changed from A to B, in addition to the improvement in indexes of UDS, especially bladder compliance, which was congruous with axonal regeneration detected in MRI tractography. No motor score improvement was observed among the patients. CONCLUSION: No adverse findings were detected at a mean of 30 months after autologous transplantation of the combination of MSCs and SCs through CSF. It may suggest the safety of this combination of cells for spinal cord regeneration.

Introduction: a brief overview of iterative algorithms in X-ray computed tomography.

This paper presents a brief overview of some basic iterative algorithms, and more sophisticated methods are presented in the research papers in this issue. A range of algebraic iterative algorithms are covered here including ART, SART and OS-SART. A major limitation of the traditional iterative methods is their computational time. The Krylov subspace based methods such as the conjugate gradients (CG) algorithm and its variants can be used to solve linear systems of equations arising from large-scale CT with possible implementation using modern high-performance computing tools. The overall aim of this theme issue is to stimulate international efforts to develop the next generation of X-ray computed tomography (CT) image reconstruction software.

Motion-compensated cone beam computed tomography using a conjugate gradient least-squares algorithm and electrical impedance tomography imaging motion data.

Cone beam computed tomography (CBCT) is an imaging modality that has been used in image-guided radiation therapy (IGRT). For applications such as lung radiation therapy, CBCT images are greatly affected by the motion artefacts. This is mainly due to low temporal resolution of CBCT. Recently, a dual modality of electrical impedance tomography (EIT) and CBCT has been proposed, in which the high temporal resolution EIT imaging system provides motion data to a motion-compensated algebraic reconstruction technique (ART)-based CBCT reconstruction software. High computational time associated with ART and indeed other variations of ART make it less practical for real applications. This paper develops a motion-compensated conjugate gradient least-squares (CGLS) algorithm for CBCT. A motion-compensated CGLS offers several advantages over ART-based methods, including possibilities for explicit regularization, rapid convergence and parallel computations. This paper for the first time demonstrates motion-compensated CBCT reconstruction using CGLS and reconstruction results are shown in limited data CBCT considering only a quarter of the full dataset. The proposed algorithm is tested using simulated motion data in generic motion-compensated CBCT as well as measured EIT data in dual EIT-CBCT imaging.

Enhanced growth and osteogenic differentiation of Induced Pluripotent Stem cells by Extremely Low-Frequency Electromagnetic Field.

It is accepted that induced pluripotent stem cells (iPSCs) have a great osteogenic potential differentiation, in the present study, we tried to improve this potentials using mechanical and biological stimulation. To achieve this goal, the influence of prolonged pulsed extremely low frequency electromagnetic field (ELF—EMF) (50 Hz and 1.5 mT) was investigated on cultured iPSCs. After evaluation of iPSCs biological behavior under radiation using MTT assay, osteogenic differentiation of stem cells was investigated via common important osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition and important bone—related genes. MTT result showed that proliferation rate of iPSCs significantly increased followed by stimulate with ELF—EMF. Osteogenic differentiation characterization demonstrated that potential of stem cells also was significantly increased while these cells cultured under both ELF—EMF and osteogenic medium (OM) in comparison to cultured under ELF—EMF or OM alone. According to the results, concluded that combination of OM and ELF—EMF can be a great supplement for bone differentiation of stem cells and appropriate candidate for use in the treatment of bone defects and osteoporosis patients by accelerating healing process.

In Vitro and In Vivo investigations on fibronectin coated and hydroxyapatite incorporated scaffolds.

Topological and biochemical aspects of the matrices are essential factors to be extensively studied for more successful tissue engineering. Other characteristics including biodegradability and biocompatibility should be also considered. Nanofibrous structure mimics topography of the natural matrix. Previous in vitro studies reported the favorable effects of nanohydroxyapatite (nHA) and fibronectin (Fn) on biodegradability and biocompatibility of scaffold. Herein, the synergistic outcome of co-application of Fn and nHA incorporation into aligned electrospun polycaprolactone (PCL) seeded by mouse mesenchymal stem cells (MSC) was investigated both in vitro and in vivo. Scanning Electron Microscopy (SEM), contact angle measurement and tensile test were applied for scaffold characterization. In vitro evaluation of the seeded cells was performed by MTT, SEM and cell-cycle analyses. In congruence with in vitro findings, in vivo assessment of four weeks fibronectin coated PCL/ nHA scaffold transplanted mice illustrated the suitable compact surrounding tissue with the most penetrated cells generation. Furthermore, Fn coating resulted in cell infiltration enhancement while nHA addition led to more scaffold biodegradation. In conclusion, fabrication of nanofiberous scaffold with this combination of biochemical composition and surface stimulation caused improved biodegradability and biocompatibility of the scaffold which are desirable in more effective tissue regeneration.

Neuromuscular Responses to 14 Weeks of Traditional and Daily Undulating Resistance Training.

This study compared traditional (TP) and daily undulating (DUP) periodization on muscle strength, EMG-estimated neural drive and muscle architecture of the quadriceps femoris (QF). 10 non-athletic females (24.4±3.2 years) performed 14 weeks of isometric training for the QF exercising 1 leg using TP and the contralateral leg using DUP. Intensities varied from 60% to 80% of MVC and the intensity zones and training volume were equated for each leg. Knee extension MVC, maximal voluntary QF-EMG activity and vastus lateralis (VL) muscle architecture were measured in both legs before, after 6 weeks and after 14 weeks of training using dynamometry, surface EMG and ultrasonography. Isometric MVC and maximal QF-EMG remained unaltered after 6 weeks of training, but were significantly (P<0.05) enhanced after 14 weeks in both legs (MVC: TP 24%, DUP 23%; QF-EMG: TP 45%, DUP 46%). VL-architecture remained unchanged following 6 weeks of training, but VL-muscle thickness (TP 17%, DUP 16%) and fascicle length (TP 16%, DUP 17%) displayed significant (P<0.05) enlargements after 14 weeks in both legs. Importantly, these temporal neuromuscular alterations displayed no significant differences between the training legs. Therefore, periodization may not act as a key trigger for neuromuscular adaptations.

Change of growth pattern, metabolism, and quality and quantity of maize plants after irrigation with magnetically treated water.

Water molecules can be affected by magnetic fields (MF) due to their bipolar characteristics. In the present study maize plants, from sowing to the end period of generative stage, were irrigated with magnetically treated water (MTW).Tap water was treated with MF by passing through a locally designed alternative magnetic field generating apparatus (110 mT). Irrigation with MTW increased the ear length and fresh weight, 100-grain fresh and dry weights, and water productivity (119.5%, 119.1%, 114.2%, 116.6% and 122.3%, respectively), compared with the control groups. Levels of photosynthetic pigments i.e. chlorophyll a and b, and the contents of anthocyanin and flavonoids of the leaves were increased compared to those of non-treated ones. Increase of the activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in leaves of the treated plants efficiently scavenged active oxygen species and resulted in the maintenance of photosynthetic membranes and reduction of malondealdehyde. Total ferritin, sugar, iron and calcium contents of kernels of MTW-irrigated plants were respectively 122.9%, 167.4%, 235% and 185% of the control ones. From the results presented here it can be concluded that the influence of MF on living plant cells, at least in part, is mediated by water. The results also suggest that irrigation of maize plant with MTW can be applied as a useful method for improvement of quantity and quality of it.

Pluripotency properties of embryonic stem cells isolated from stage X blastoderm of Mazandaran native chicken.

The aim of this study was to isolate Embryonic Stem Cells (ESCs) from native chicken and to characterize their pluripotency properties through the cellular and molecular markers. Samples obtained from fertilized eggs from Mazandaran native hens. Cells were isolated from area of pellucida from stage X native hens' blastoderm. Then the cells were cultured on inactivated mouse SNL feeder cells in the presence of LIF, IGF-1, bFGF, CNTF, OSM, SCF, Il-6, and Il-11 growth factors. The native chickens' ESCs colonies were picked up and subsequently passaged. To characterize the cells, they were analyzed for their alkaline phosphatase activity, and also for the expression of SSEA-4, and TRA-1-60 as embryonic-specific markers at the protein level. Furthermore, the expression of pluripotency (cPouV, Sox2, and Nanog) and cell lineage specific (Cvh, Brachyury, and Gata6) gene markers was evaluated at the level of mRNA using quantitative RT-PCR. Isolated cells were passaged repeatedly and successfully up to ten passages. The stemness of embryonic cells has been approved by the activity of the alkaline phosphatase, presence of the SSEA-4, and TRA-1-60 protein, and expression of the molecular marker (cPouV, Nanog, and Sox-2) genes. The spontaneous differentiation of chicken ESCs confirmed the pluripotecy of the cells in differentiation into specialized cell lineages. Our observation showed that ESCs can be isolated successfully from stage X blastoderm of Mazandaran native chickens and these cells maintain their stemness properties during multi-passages in vitro.

Effects of 660- and 980-nm low-level laser therapy on neuropathic pain relief following chronic constriction injury in rat sciatic nerve.

Neuropathic pain (NP) is one of the most suffered conditions in medical disciplines. The role of reactive oxygen species (ROS) and oxidative stress in the induction of NP was studied by many researchers. Neuropathies lead to medical, social, and economic isolation of the patient, so various therapies were used to treat or reduce it. During the recent years, low-level laser therapy (LLLT) has been used in certain areas of medicine and rehabilitation. Chronic constriction injury (CCI) is a well-known model for neuropathic pain studies. In order to find the effects of different wavelengths of LLLT on the injured sciatic nerve, the present research was done. Thirty Wistar adult male rats (230-320 g) were used in this study. The animals were randomly divided into three groups (n = 10). To induce neuropathic pain for the sciatic nerve, the CCI technique was used. Low-level laser of 660 and 980 nm was used for two consecutive weeks. Thermal and mechanical hyperalgesia was done before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. CCI decreased the pain threshold, whereas both wavelengths of LLLT for 2 weeks increased mechanical and thermal threshold significantly. A comparison of the mechanical and thermal threshold showed a significant difference between the therapeutic effects of the two groups that received LLLT. Based on our findings, the laser with a 660-nm wavelength had better therapeutic effects than the laser with a 980-nm wavelength, so the former one may be used for clinical application in neuropathic cases; however, it needs more future studies.

Developing a real-time quantitative loop-mediated isothermal amplification assay as a rapid and accurate method for detection of Brucellosis.

AIM: The aim of this study was designing a LAMP method for the rapid detection of Brucella and development of a sensitive quantitative-LAMP (Q-LAMP) assay for quantification of brucellosis. METHODS AND RESULTS: In this study for the LAMP detection of the causative agent of brucellosis, we used specifically designed primers to target the omp25 conserved gene of Brucella spp. The sensitivity of the LAMP method was evaluated by preparing serial tenfold dilution of omp25 gene containing plasmid followed by performing the LAMP reaction. To improve the assay as a quantitative test, LAMP products in the serial dilution were evaluated by Loopamp real-time turbidimeter system and then standard curve was generated by plotting time threshold values against log of copy number. The assay specificity was evaluated using Brucella genomic DNA and a panel containing genomes of 11 gram-positive and gram-negative organisms. The LAMP assay was highly specific and no amplification products were observed from the non-Brucella organisms. The test sensitivity for visual detection of turbidity or fluorescent colour change and also agarose gel electrophoresis was 560 ng and 5·6 ng, respectively. The lower limit of detection was 17 copies of the gene that could be detected in 50 min. CONCLUSIONS: The results of this study indicated that the LAMP assay is a simple, rapid, sensitive and specific technique for detection of Brucella spp. that may improve diagnostic potential in clinical laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP assay because of the simplicity and low cost can be preferred to other molecular methods in the diagnosis of infectious diseases.

Process optimization of electrospun polycaprolactone and nanohydroxyapatite composite nanofibers using response surface methodology.

Electrospinning is a process that produces continuous polymer fibers in the sub-micron range through the action of an external electric field imposed on a polymer solution or melt. In this study the effects of process parameters on the mean diameter of electrospun polycaprolactone and nanohydroxyapatite (nHA) composite nanofibers were investigated. The fiber morphology and mean fiber diameter of prepared nanofibers were investigated by scanning electron microscopy. Response surface methodology (RSM) was utilized to design the experiments at the settings of nHA concentration, applied voltage, spinning distance and the flow rate of polymer solution. It also used to find and evaluate a quantitative relationship between electrospinning parameters and average fiber diameters. Mean fiber diameter was correlated to these variables using a third order polynomial function. Value of R-square for the model was 0.96, which indicates that 96% of the variability in the dependent variable could be explained and only 4% of the total variations cannot be explained by the model. It was found that nHA concentration, applied voltage and spinning distance were the most effective parameters and the sole effect of flow rate was not important. The predicted fiber diameters were in good agreement with the experimental results.

NeuroProtective effects of adenosine receptor agonist coadministration with ascorbic acid on CA1 hippocampus in a mouse model of ischemia reperfusion injury.

Ischemic brain injury is a leading cause of sever neurological and neurobehavioral deficits and death. The hippocampus plays vital roles in learning and memory processes and it is impaired by ischemic insults. Cerebral ischemia/reperfusion leads to Oxidative stress damage impairing the hippocampus. Here we tested whether ascorbic acid and adenosine receptor played a neuroprotective role in a mouse brain ischemia model induced by common carotid arteries occlusion. Adult male mice were randomly assigned into nine experimental groups. The animals were subjected to ischemia by the ligation of common carotid arteries for 15 min. Drugs were injected intrapritoneally once daily for 7 days. Behavioral tests performed at day 14 and then mice were killed at day 21 and their brains were fixed for microscopic studies and some samples were prepared for western blot analysis. Western blot analysis utilized to evaluate the expression of apoptosis-related proteinsin the hippocampus. Short-term memory was assessed by shuttle-box test. Our findings revealed that administration of vitamin C and N6-cyclopentyladenosine (CPA) significantly attenuated ischemia-induced brain injury. Vitamin C and CPA administration increased the expression of anti-apoptotic protein Bcl-2 and decreased the expression of pro-apoptotic protein Bax in the ischemic mice. Ischemia caused short-term memory loss that was improved by vitamin c and CPA treatment. Our results demonstrate that treatment with vitamin C and adenosine receptor agonist attenuated cerebral ischemia/reperfusion-induced brain injury as a potential neuroprotective agent.

The protective role of carnosic acid against beta-amyloid toxicity in rats.

Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer's disease (AD). Previous studies have demonstrated the role of carnosic acid (CA), an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1-40) was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aß) groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1-40) can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aß + CA group, in comparison with the Aß group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus.

Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger.

NHE3 is one of five plasma membrane Na+/H+ exchangers and is encoded by the mouse gene Slc9a3. It is expressed on apical membranes of renal proximal tubule and intestinal epithelial cells and is thought to play a major role in NaCl and HCO3- absorption. As the distribution of NHE3 overlaps with that of the NHE2 isoform in kidney and intestine, the function and relative importance of NHE3 in vivo is unclear. To analyse its physiological functions, we generated mice lacking NHE3 function. Homozygous mutant (Slc9a3-/-) mice survive, but they have slight diarrhoea and blood analysis revealed that they are mildly acidotic. HCO3- and fluid absorption are sharply reduced in proximal convoluted tubules, blood pressure is reduced and there is a severe absorptive defect in the intestine. Thus, compensatory mechanisms must limit gross perturbations of electrolyte and acid-base balance. Plasma aldosterone is increased in NHE3-deficient mice, and expression of both renin and the AE1 (Slc4a1) Cl-/HCO3- exchanger mRNAs are induced in kidney. In the colon, epithelial Na+ channel activity is increased and colonic H+,K+-ATPase mRNA is massively induced. These data show that NHE3 is the major absorptive Na+/H+ exchanger in kidney and intestine, and that lack of the exchanger impairs acid-base balance and Na+-fluid volume homeostasis.